Principles of Clinical Medicine for Space Flight

Principles of Clinical Medicine for Space Flight

Michael R. Barratt, MD, MS

Astronaut and Physician, NASA Johnson Space Center,
Houston, TX, USA

Sam L. Pool, MD
Chief, Medical Sciences Division, NASA Johnson
Space Center (retired), Houston, TX, USA

Editors
Michael R. Barratt, MD, MS Sam L. Pool, MD
Astronaut and Physician Chief, Medical Sciences Division
NASA Johnson Space Center NASA Johnson Space Center (retired)
Houston, TX Houston, TX
USA USA

ISBN: 978-0-387-98842-9 e-ISBN: 978-0-387-68164-1

DOI: 10.1007/978-0-387-68164-1

Library of Congress Control Number: 2007939575

2008 Springer Science+Business Media, LLC

All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business
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 Dr. Patricia Hilliard Robertson (Photo courtesy of NASA)
To our cherished friend and colleague Patricia Hilliard Robertsonpilot and flight instructor, physician and flight surgeon,
adventurer and astronaut. She is greatly missed by the aerospace community and all who knew her.
Foreword
The space environment does strange things, both to the workings
of the human body and to the behavior of ordinary medical
equipment. Space medicine describes the normal person in
an abnormal environment and is an outgrowth of aviation
medicine.
Aviation medicine didnt exist when my father was born
in 1884. By the time he served in the Army during World
War I, it did, but its medical standards were still under con-
struction. The Air Service Medical Manual issued by the War
Department in 1918 discussed the publics impression that
the medical examination of an aviator was a form of refined
torture. One story was that of the needle test. This mythical
examination supposedly involved placing a needle between
the candidates forefinger and thumb, blindfolding him, then
shooting off a pistol behind his ear. The examiner would then
note whether, owing to a supposed lack of nerve, the applicant
had pushed the needle through his finger. The test sounded
plausible then.
Aviation medicine as a specialty grew quickly during
World War II and the onset of the jet age in the 1950s.
However, when the space age dawned suddenly with Sputnik
in 1957, medicine was not ready. The pages of the Jour-
nal of Aviation Medicine for the years 1959 through 1961
were filled with forecasts of the effects of zero G on the
human bodymost of them dire. For example, doubt was
expressed whether the gastrointestinal system would func-
tion when weightless; nourishment, it was reasoned, might
have to be given intravenously. The altitude and solitude, it
was opined, would cause break off phenomenon, a sort of
psychosis of loneliness. My favorite of these predictions was
that space travelers werent going to be able to urinate. This
was proven in an experiment wherein a rookie medical
technician was strapped into the back seat of a jet fighter-
trainer, helmeted, masked, and instrumented, flown to
35,000 ft, then pulled up into a zero-G parabola. At the peak
of the maneuver, the pilot cried Go! and the poor fellow
couldnt do it. Catheters were solemnly recommended for
astronauts.
It sure was fun knowing so little about the physiology of
weightlessness. Skylab was a prototype space station in which
three crews spent 1, 2, and 3 months learning how to home-
stead in space and to care for ourselves up there. A demand
that a physician be on each crew was rejected, but a small
medical kit was in place, and two members of each crew
most of whom were test pilotswere trained to sew up cuts,
extract teeth, and examine and report on their fellow crew-
men. Fortunately, the practice was slow; we never had a serious
medical problem to treat.
The U.S. Space Shuttle program, and later the joint NASA
Mir and International Space Station programs, have given the
physician-authors of this book experience with hundreds of
person-trips into space. The dreaded space motion sickness
has been conquered, end-of-mission problems with vertigo
and fluid loss have been brought under control, and confidence
in human capabilities has been engendered. But true long-
duration weightlessness is still a frontier. A Mars mission is
still a substantial challenge.
Another critical perspective on space medicine is the
recognition of its inherently interdisciplinary nature. Weight-
less humanity exists only in a special world, a space craft
crafted by engineers, a closed-loop system with a man-made
atmosphere and its own rules of up and down. This pulls doc-
tors into the world of engineers and vice versa. We must help
each other solve problems that arise not only from weightless-
ness but also from where we are and what were ina vessel
where, to get to Mars, we will have to recycle the very air we
breathe and the water we consume. Engineering equipment
medical and otherwiseis a challenge when everything floats
and nothing settles.
The details are all in this book. The nature of interplanetary
space, its effect on our bodies (and minds), the treatments and
countermeasures we currently prescribe, and the mysteries
that remain, are graphically described and illustrated. If you
are a researcher needing a fact or reference, an engineer who
wants to know how your design affects its users, or a curious
student drawn to medicine or biology but also to the adventure
vii
viii Foreword

of space flightfill your mind here, and let your imagination characteristics as human beings. The future does not exist. We
carry you to Mars. get to help write its story.
Exploration of the heavens still has a value independent
of the commercial and military arguments we use in its Joseph P. Kerwin, MD
defense. The hunger to know and to see is one of our defining Houston, Texas
Preface
In 1768, Captain James Cook was preparing his vessel, the
Whitby collier Endeavour, and her crew for an extended sea
voyage. At that time, mortality rates of 50% or more were
not uncommon for trade voyages. Scurvy, resulting from lack
of dietary ascorbic acid (vitamin C), was the great enemy.
Cook developed and, with the help of ships surgeon William
Munkhouse, administered to his crew a preventive regimen
that included required consumption of antiscorbuticsfood
supplements consisting of such items as onions, sauerkraut,
fruit, and occasionally native grasses found on islands en
route. Not a single life was lost from scurvy. Subsequent voy-
ages by Cook and countless others were spared from the curse
of scurvy, and many lives were thus saved. A new expectation
arose: that crews could safely remain at sea for the prolonged
periods required to make their voyages.
We now stand near where Cook stood more than 200 years
ago. Many bold steps have been taken into space over the
past four decades, and we now contemplate still more ambi-
tious missions of exploration and science. The mortality and
morbidity rates associated with these preliminary efforts have
been relatively low, though certainly not negligible. In tak-
ing these early steps, we have gained invaluable knowledge
of how humans live in the space environment, particularly
with regard to weightlessness. Key adverse influences and
effects have been identified, including radiation exposure and
acquired dose, bone and muscle atrophy, and cardiovascular
deconditioning. Thus far these effects have been tolerable
during the course of low-Earth orbit and preliminary lunar
explorations. However, future missions will involve greater
distances and times and will demand that these effects be
countered and other capabilities provided to sustain the human
presence and to support optimal work. Our current charge is
to expand human exploration while maintaining the safety and
health of the exploring crewmembers.
As Endeavours surgeon Munkhouse did, we too have a
standard of medical care and safety that must be taken to sea
with us. To the extent possible and practical, current standards
of medicine are expected to accompany space crews on their
There is no land uninhabitable, nor sea innavigable.
Robert Thorne, 1527
missions. Along with these standards, a more complete under-
standing of how the space environment affects the human body
is required. The application of standard medical practice in this
unique and challenging context defines space medicine as a
distinct discipline. In 1968, after the first few years of human
space flight, Dr. Douglas Busby wrote Space Clinical Medicine,
a well-referenced and highly prospective and insightful work.
Since that time, a tremendous amount of information has
accrued regarding the physiologic effects of weightlessness
as well as medical and environmental events occurring dur-
ing flight that influence crew health. In many ways, this text
is a successor to Dr. Busbys fine work. Principles of Clini-
cal Medicine for Space Flight was written by practitioners of
space medicine for practitioners of space medicine and for oth-
ers who may benefit from this knowledge in their own unique
circumstances. Neither an overall basic medical text nor a
comprehensive review of space physiology, this book focuses
on aspects of medicine that arise uniquely and are dealt with
uniquely in human space flight, and how the effects of space
flightwhether adverse or simply anomalousare addressed
to provide the best care for space crewmembers.
Principles of Clinical Medicine for Space Flight draws
heavily on the experience of the U.S. Skylab and Space
Shuttle programs as well as the Russian experience with long-
duration missions aboard the Salyut and Mir space stations
and, most recently, from our joint work on the first several
missions aboard the International Space Station (ISS). Con-
tributors have a rich and practical experience base of direct
space mission support and human life sciences research, and
this is reflected in the detailed information presented. Read-
ers will find background information on the relevant physi-
cal forces and mechanical aspects of spaceflight necessary for
complete understanding of the environment and its influence
on the human space traveler. This is followed by a comprehen-
sive review of the human response to every aspect of space-
flight, the most likely medical problems encountered, their
diagnosis, management, and prevention. Special emphasis
is given to those areas most limiting to long duration flights,
ix
x Preface
such as radiation, bone and muscle loss, cardiovascular and
neurovestibular deconditioning, nutrition and metabolism,
and psychological reactions. Flight crew medical selection
and retention standards are addressed, with discussion on
rationale and application. In addition, cutting-edge technical
issues particularly associated with provision of medical care
in space are discussed, including selection and use of medi-
cal systems, telemedicine, medical imaging, surgical care, and
medical transport. When warranted, reasonable speculations
are offered regarding principles of medical support and practice
for future exploration missions involving a return to the Moon
and interplanetary flight.
There is an expanding niche of medical practitioners who
may utilize this book as a standard of care for supporting human
space missions. This cadre is international, both civil and mil-
itary, and is now extending into the commercial sector. This
knowledge base should also greatly benefit the many groups
and academic institutions involved in space life sciences or
other environmental human research. Those participating in
aerospace program and mission support and planning which
involves or overlaps with medical decision making should
also find useful information in this book. In addition, those
involved with similar responsibilities of medical support in
environments which are analogous to spaceflight, including
submarine and surface ships, polar research stations, and other
extreme or remote settings may benefit from our findings, as
we have often benefited from such venues and exchange of
experience. Finally, for the medically curious, we offer a com-
prehensive reference on one of the very latest medical special-
ties; none is more fascinating.
The size and scope of this book attests to the technical
support and logistical efforts that were required to bring it into
being. Our thanks go to technical editors Sharon Hecht and
Luanne Jorevich and graphics wizards Sid Jones and Terry
Johnson, who went extra miles during extra hours translating
space medical jargon into plain English and clear figures; to
space life sciences librarians Janine Bolton and Kim So for
helping us to mine the worlds literature on space medicine;
and to Brooke Heathman and Ellen Prejean, who helped orga-
nize and mold the chapters into a coherent work. Special thanks
go to Chris Wogan, world expert on space life sciences techni-
cal literature, for bringing her talents to bear on this project,
and to Merry Post and her exemplary skill and patience for
guiding the transformation of our knowledge base into a user-
friendly text.
Of course our deepest gratitude goes to our families, and
especially to our spouses Michelle Barratt and Jane Pool, who
have weathered our fascinations and obsession with space
flight these many long years; we can never adequately repay
you for your dedication and support.
Finally, to all of the worlds space travelers of all flags
and professions who have undergone examination, monitoring,
and sampling for medical certification and science for over
four decades, we offer heartfelt thanks. A rising space-faring
civilization owes you a debt of gratitude for your patience,
endurance, and your great contribution to human space
flight.
Michael R. Barratt, MD, MS
Sam L. Pool, MD
Contents

Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii
Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii

Part 1. Unique Attributes of Space Medicine

Chapter 1 Physical and Bioenvironmental Aspects of Human Space Flight . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Michael R. Barratt
Chapter 2 Human Response to Space Flight . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Ellen S. Baker, Michael R. Barratt, and Mary L. Wear
Chapter 3 Medical Evaluations and Standards . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
Gary Gray and Smith L. Johnston
Chapter 4 Spaceflight Medical Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
Terrance A. Taddeo and Cheryl W. Armstrong
Chapter 5 Acute Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
Thomas H. Marshburn
Chapter 6 Surgical Capabilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
Mark R. Campbell and Roger D. Billica
Chapter 7 Medical Evacuation and Vehicles for Transport. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
Smith L. Johnston, Brian A. Arenare, and Kieran T. Smart
Chapter 8 Telemedicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163
Scott C. Simmons, Douglas R. Hamilton, and P. Vernon McDonald
Chapter 9 Medical Imaging. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
Ashot E. Sargsyan
Part 2. Spaceflight Clinical Medicine

Chapter 10 Space and Entry Motion Sickness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211

Hernando J. Ortega Jr. and Deborah L. Harm
Chapter 11 Decompression-Related Disorders: Decompression Sickness,
Arterial Gas Embolism, and Ebullism Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
William T. Norfleet

xi
xii Contents

Chapter 12 Decompression-Related Disorders: Pressurization Systems,

Barotrauma, and Altitude Sickness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247
Jonathan B. Clark
Chapter 13 Renal and Genitourinary Concerns. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273
Jeffrey A. Jones, Robert A. Pietrzyk, and Peggy A. Whitson
Chapter 14 Musculoskeletal Response to Space Flight . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293
Linda C. Shackelford
Chapter 15 Immunologic Concerns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 307
Clarence F. Sams and Duane L. Pierson
Chapter 16 Cardiovascular Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317
Douglas R. Hamilton
Chapter 17 Neurologic Concerns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361
Jonathan B. Clark and Kira Bacal
Chapter 18 Gynecologic and Reproductive Concerns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381
Richard T. Jennings and Ellen S. Baker
Chapter 19 Behavioral Health and Performance Support . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 391
Christopher F. Flynn
Chapter 20 Fatigue, Sleep, and Chronotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 413
Lakshmi Putcha and Thomas H. Marshburn
Chapter 21 Health Effects of Atmospheric Contamination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 427
John T. James
Chapter 22 Hypoxia, Hypercarbia, and Atmospheric Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 445
Kira Bacal, George Beck, and Michael R. Barratt
Chapter 23 Radiation Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 475
Jeffrey A. Jones and Fathi Karouia
Chapter 24 Acoustics Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 521
Jonathan B. Clark and Christopher S. Allen
Chapter 25 Ophthalmologic Concerns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535
F. Keith Manuel and Thomas H. Mader
Chapter 26 Dental Concerns. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 545
Michael H. Hodapp
Chapter 27 Spaceflight Metabolism and Nutritional Support . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 559
Scott M. Smith and Helen W. Lane
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 577
Contributors

Christopher S. Allen, MS, BS Christopher F. Flynn, MD

Lead, Johnson Space Center Acoustics Office, Clinical Associate Professor, Menninger Department of
ISS Acoustics Sub System Manager, NASA Johnson Psychiatry and Behavioral Sciences, Baylor College of
Space Center, Houston, TX, USA Medicine, Houston, TX, USA

Brian A. Arenare, MD, MPH, MBA Gary W. Gray, MD, PhD

Director, Cardiopulmonary Lab, Kelsey-Seybold Clinic, Senior Consultant Flight Surgeon, Canadian Space Agency,
NASA Johnson Space Center, Houston, TX, USA Toronto, Ontario, Canada

Cheryl W. Armstrong, BS Douglas R. Hamilton, MD, PhD, MSc, E Eng, PE,

Biomedical Engineer, Wyle Laboratories, Houston, TX, USA P Eng, FRCPC, ABIM
Flight Surgeon, Electrical Engineer, Wyle Laboratories,
Kira Bacal, MD, PhD, MPH, FACEP Houston, TX, USA
Research and Developmental Branch Director, Mauri Ora
Associates, Auckland, New Zealand Deborah L. Harm, PhD
Senior Scientist, Human Adaptation and Countermeasures
Ellen S. Baker, MD, MPH Division, Neurosciences Laboratory, NASA Johnson Space
Astronaut, NASA Johnson Space Center, Houston, TX, USA Center, Houston, TX, USA

Michael R. Barratt, MD, MS Michael H. Hodapp, DDS

Astronaut and Physician, NASA Johnson Space Center, University of Texas Dental Branch, Houston, TX, USA
Houston, TX, USA
John T. James, PhD
George Beck, BA, RRT, FAARC Chief Toxicologist, NASA Johnson Space Center, Houston,
Director, Engineering and Research, Impact Instrumentation, TX, USA
Inc., West Caldwell, NJ, USA
Richard T. Jennings, MD, MS
Roger D. Billica, MD, FAAFP Associate Professor, Preventive Medicine and Community
President, Tri-Life Health, Center for Integrative Medicine, Health, University of Texas Medical Branch, Galveston,
Fort Collins, CO, USA TX, USA

Mark R. Campbell, BS, MD Smith L. Johnston, MD, MS

General Surgeon, Paris Regional Medical Center, Paris,
TX, USA
Jonathan B. Clark, MD, MPH
Space Medicine Liaison, Baylor College of Medicine,
National Space Biomedical Research Institute, Houston,
TX, USA
Medical Officer, Flight Surgeon, University of Texas
Medical Branch, Preventive, Occupational, and Environmental
Medicine, NASA Johnson Space Center, Houston, TX, USA
Jeffrey A. Jones, MD, MS, FACS, FACPM
Exploration Medical Operations Lead Flight Surgeon, NASA
Johnson Space Center, Houston, TX, USA

xiii
xiv
Fathi Karouia, MS, ASD, MSS
Research Associate, Department of Biology and
Biochemistry, University of Houston, Houston, TX, USA
Joseph P. Kerwin, BA, MD
Captain, Medical Corps, United States Navy (retired),
Houston, TX, USA
Helen W. Lane, PhD, RD
NASA Chief Nutritionist, NASA Johnson Space Center,
Houston, TX, USA
Thomas H. Mader, MD
Alaska Native Medical Center, Department of
Ophthalmology, Anchorage, AK, USA
F. Keith Manuel, OD
Former Sr. Vision Consultant, Flight Medicine,
NASA Johnson Space Center, Houston, TX, USA
Thomas H. Marshburn, MD, MS
Astronaut, NASA Johnson Space Center, Houston, TX, USA
P. Vernon McDonald, PhD
Director, Commercial Human Space Flight,
Wyle Laboratories, Houston, TX, USA
William T. Norfleet, MD
Assistant Professor, Department of Anesthesiology, Yale
University School of Medicine, New Haven, CT, USA
Hernando J. Ortega, MD, MPH
Colonel, Chief Flight Surgeon, United States Air Force, San
Antonio, TX, USA
Duane L. Pierson, PhD
Senior Microbiologist, NASA Space Life Sciences
Directorate, Houston, TX, USA
Robert Pietrzyk, MS
Project Scientist, Human Adaptation and Countermeasures
Division, Wyle Laboratories Life Sciences Group, Houston,
TX, USA
Contributors
Sam Lee Pool, MD
Chief, Medical Sciences Division, NASA Johnson
Space Center (retired), Houston, TX, USA
Lakshmi Putcha, PhD, FCP
Chief Pharmacologist, NASA Johnson Space Center,
Houston, TX, USA
Clarence F. Sams, PhD
Medical Project Scientist, International Space Station,
SK/Human Adaptation and Countermeasure Division, NASA
Johnson Space Center, Houston, TX, USA
Ashot E. Sargsyan, MD
Scientist, Wyle Laboratories Life Sciences Group, Houston,
TX, USA
Linda C. Shackelford, MD
Manager, Bone and Muscle Lab, NASA Johnson Space
Center, Houston, TX, USA
Scott C. Simmons, MS
Assistant Director, The Telemedicine Center, Brody School
of Medicine, East Carolina University, Greenville, NC, USA
Kieran T. Smart, MBChB, MSc, MPH, MRCGP
Flight Surgeon, Wyle Laboratories, Houston, TX, USA
Scott A. Smith, PhD
Manager for Nutritional Biochemistry, NASA Johnson Space
Center, Houston, TX, USA
Terrance A. Taddeo, MD, MS
Medical Officer, Deputy Manager of Medical Operations,
NASA Johnson Space Center, Houston, TX, USA
Mary L. Wear, PhD
Health Care Services Manager, NASA Johnson Space
Center, Houston, TX, USA
Peggy A. Whitson, PhD
Astronaut and Research Scientist, NASA Johnson Space
Center, Houston, TX, USA
 Part 1
Unique Attributes of Space Medicine
1
Physical and Bioenvironmental
Aspects of Human Space Flight
Michael R. Barratt
Life on Earth has developed and flourished under a wide range
of diverse circumstances. These include familiar conditions
at Earths surface and in upper layers of the seas, as well as
the more exotic subterranean and deep ocean aphotic zones,
where oxidative and anaerobic life processes can flourish at
extreme limits of temperature, pressure, and exposure to what
are classically considered toxic substances. A static gravita-
tional field of 9.81 m/s2 and a protective and physiologically
supportive atmospheric gas layer comprise the major factors
that have profoundly influenced Earth as a place of human
life. We are designed to function optimally in this environ-
mentand within a fairly narrow envelope at that. Without
protective methods and devices, human beings are effectively
confined to a vertical gradient beginning at the surface of the
sea to perhaps 5,000 m in altitude, the rough practical limit
of human adaptation for prolonged acclimation. Simply put,
human performance and survivability seem optimized to near
sea level.
Nevertheless, humans have now ventured to more than 10 km
beneath the surface of the ocean, into near-Earth space, and to
the surface of the Moon. Advances in technology and politi-
cal organizations have enabled large-scale cooperative projects
that have led to the expectation that humans will travel and live
well beyond our narrow envelope. We have adapted to a larger
environment and expanded our original sphere of existence.
This expansion is a dynamic process that by all indications will
continue and probably accelerate as more nations obtain the
technology and industrial wherewithal to join this effort. As
humans continue to explore and survive in environments that
are beyond standard physiologic limits, an understanding of
human reactions to these new environments and development
of protective systems and processes becomes more critical.
Over the past century, such disciplines as aviation medicine and
diving medicine have arisen and matured, playing key roles in
expanding human performance and endurance in new environ-
ments. These disciplines have successfully fostered the neces-
sary interfaces between physical systems required to support
the human aviator or diver and the knowledge of physiology
and practice of medicine. To this same end, keeping pace with
current efforts in space exploration, the field of space medicine
is emerging as a distinct discipline.
Aviation medicine, diving medicine, and space medi-
cine all involve pressure excursions, operational changes in
body attitude and position, controlled breathing sources, and
critical dependence on supportive mechanisms and protec-
tive equipment. Many of the basic problems of space medi-
cinehypoxia, dysbarism, thermal support, moderate levels
of acceleration, response to unusual altitudeshad been stud-
ied over the course of decades of aviation and high-altitude
balloon flight and were fairly well understood before the first
human space flight ever took place. A basic working knowl-
edge of aviation medicine and physiology remains required of
the space medicine specialist. A review of these basics or of
atmospheric science is beyond the scope of this chapter; the
interested reader is referred to the sources in the Suggested
Readings section at the end of this chapter.
This book focuses on the unique medical circumstances and
clinical problems associated with excursions outside of Earths
atmosphere. These circumstances include a wide range of accel-
eration forces, adaptive processes and problems associated with
weightlessness and partial gravity fields, radiation, excursions
to other planetary bodies, and biotechnical problems associated
with life support systems in enclosed environments. This chap-
ter provides an overview of the basic physics of space flight and
physical conditions faced by human space travelers that influ-
ence their physiologic responses and adaptation.
General Physics of Human Space Flight
Leaving Earth
A singular definition of space is elusive and somewhat arbi-
trary in terms of a specific border and limit relative to the
surface of Earth; the definition varies with the particular
parameter being assessed. For example, the pressure limit for
maintaining body fluids in a liquid state (the physiologic limit)
occurs at a specific altitude (about 19 km), whereas the limit
3
4 M.R. Barratt

at which forces between aircraft or spacecraft surfaces and
the atmosphere support effective aerodynamic control (the
physical limit) is quite different (about 80 km). The common
factor for most biophysical parameters in defining a limit is
a threshold degree of removal from nominal atmospheric gas
composition and pressure, and for mechanical parameters a
threshold reduction in density leading to, for instance, absence
of aerodynamic lift and drag.
Fifty years ago Hubertus Strughold, in a classic and insight-
ful treatise on the interface between Earth and space [1],
described three major atmospheric functions that serve as
base points for understanding these limits: (1) the function of
supplying breathing air and climate; (2) the function of sup-
plying a filter against cosmic factors (e.g., ionizing radiation,
ultraviolet light, meteoroids); and (3) the function of supply-
ing mechanical support to the craft. Each of these functions
can be further stratified into specific limits and borders. Table 1.1
lists several of these limits and physiologic milestones as one
ascends vertically through the atmosphere. For astronauts fly-
ing to low Earth orbit (LEO), all of these limits and zones are
traversed in a relatively short time, on the order of several min-
utes. The flight crew is of course enclosed in a highly protec-
tive and controlled environment; however, knowledge of these
limits remains important with regard to mishaps that might
occur at any altitude during ascent or descent, and knowledge
of these limits also defines the capabilities of protective and
emergency systems.
In the process of launching to a sustainable orbit, a lofting
force must be applied that exceeds the gravitational force on
the mass to be delivered. In the history of space flight thus
far, this force has been provided by chemical rockets, which
typically combine a fuel and oxidizer at high temperatures and
pressures to create a reactive force through rapid combustion.
The hazardous aspects of these systems, with highly explosive
mixtures flowing through conduits at extremes of material
and hardware performance limits, are obvious. Engine perfor-
mance is described in terms of two basic parametersthrust
and specific impulse [2]. Thrust (F), is the amount of force
applied to a rocket based on expulsion of exhaust gases. In
simplified form:
& e
F = mV (1.1)
.
where F = force in Newtons (in N or m/kg/s2), m = mass flow
rate of propellant (in kg/s), and Ve is exit velocity of the propel-
lant (in m/s). Thrust increases with the product of combustion
chamber temperature and the ratio of combustion-chamber
pressure to nozzle-exit pressure. Thrust is usually expressed
in Newtons (N) or pounds (lbs). The five large kerosene and
liquid oxygen F1 first-stage engines of the Apollo Saturn V
vehicle each supplied 6.7 million N (1.5 million lbs) of thrust.
Each of the three Space Shuttle main engines, fueled by liq-
uid hydrogen and liquid oxygen, generates 1.67 million N
(375,000 lbs) of thrust at sea level.

Table 1.1. Physical and physiological milestones during the transition from the earth surface to space.
Altitude Event or Limit
1,5252,440 m (5,000 Cabin pressure of commercial air carriers; PAO2 = 8169 mmHg
8,000 ft)
3,048 m (10,000 ft) U.S. Air Force requires that pilots breathe supplemental oxygen. PAO2 = 60 mmHg if breathing ambient air.
4,570 m (15,000 ft) Approximate upper limit of human acclimation; PAO2 = 45 mmHg breathing ambient air. Supplemental oxygen is required if
not in pressurized cabin.
10,400 m (34,000 ft) Practical limit for breathing 100% O2 in an unpressurized cabin. Above this altitude, positive pressure breathing is required
to maintain normoxia. Ambient pressure = 187 mmHg; PAO2 on 100% O2 = 100 mmHg.
15,240 m (50,000 ft) Respiratory exchange limit; ambient pressure = 87 mmHg, equivalent to sum total of alveolar water vapor tension (47 mmHg)
and CO2 tension (40 mmHg). No respiratory exchange is possible. Pressure suit or pressurized cabin is required.
16 km (10 mi) Practical limit of atmospheric weather processes and phenomena at equator (the altitude is lower near the poles).
19,200 m (63,000 ft) Armstrongs line; Ambient pressure = 47 mmHg, equivalent to tension of water vapor at body temperature.
Above this altitude, body fluids vaporize.
2530 km (15.518.6 mi) Practical limit of ram pressurized cabin; above this altitude, fully enclosed pressurized cabins are required.
40 km (24.9 mi) Atmosphere ceases to protect objects from high-energy radiation particles.
45 km (28 mi) Little protective ozone.
80 km (50 mi) Van Karman Line; threshold of effectiveness of aerodynamic surfaces. Astronaut wings awarded.
100 km (62 mi) Minimal atmospheric light scattering, blackness of space
120 km (75 mi) The so-called atmospheric entry interface for returning spacecraft; initial onset of perceptible acceleration forces, control
surface resistance. Dysacoustic zone; insufficient atmospheric density to facilitate the effective transmission of sound.
140 km (87 mi) Meteor safe zone limit; insufficient atmospheric density to effectively stop entry of micrometeorites.
150 km (96 mi) Aerothermodynamic border; minimal aerodynamic resistance or structural heating.
200 km (124 mi) Essentially no aerodynamic support; sustainable orbital altitude.
700 km (440 mi) Border of atmosphere; collisions between atmospheric gas molecules become undetectable. Particle density gradually
diminishes over thousands of km to free space density of 110 per cc, mostly atomic hydrogen.

Note: PAO2 = alveolar oxygen tension

1. Physical and Bioenvironmental Aspects of Human Space Flight 5

Specific impulse (Isp), the other parameter of engine perfor- For initial launch to orbit, the velocity component of Earths
mance, is the ratio of the thrust F to the weight flow rate of rotation can provide a significant boost in v. Such a boost is
propellant: best afforded by launching directly into the rotational velocity
vector, or straight eastward (Figure 1.1). Practically, launch
&
I sp = F / mg (1.2) from the equator eastward would provide an additional 1,600
kilometers per hour (1,000 mph) in free v, or nearly 6%
Substituting for F in (1.1) above,
of final v required to achieve LEO, which would translate
I sp = Ve / g (1.3) into enhanced system performance and increased payload.
Thus launching from higher latitude sites, or for any given site
.
where Isp = specific impulse (in seconds), F = thrust in N, m launching to azimuth angles higher than the latitude, trans-
= propellant mass flow rate (in kg/s), Ve is the exit velocity of lates into degraded performance and diminished payload-to-
the propellant (in m/s), and g = gravitational acceleration at orbit capability. To date, all crewed launches have involved
Earths surface, 9.81 m/s2. Isp is thus a measure of the exhaust eastward or posigrade launches. The U.S. Space Shuttle,
velocity. Isp is proportional to the square root of combustion- launching from the Kennedy Space Center at about 28 degrees
chamber temperature divided by the average molecular north latitude, attains its maximum performance by launching
weight of combustion products and provides a measure of the directly eastward over the Atlantic Ocean. In doing so, the
energy content and thrust conversion efficiency of the pro- shuttle attains an orbit of 28 degrees of inclination, defined
pellant. Using a propellant with low molecular mass such as as the angle between Earths equatorial plane and the plane
hydrogen or increasing the temperature of the propellant will of the spacecrafts orbit (Figure 1.2). For a given launch site,
serve to increase Isp. Isp can also be defined as the time (in launching straight eastward attains an orbital inclination equal
seconds) required to burn one kg of propellant in an engine to the launch sites latitude. A vehicle can launch to a higher
producing one N of force. As a point of reference, the Space inclination while losing some of Earths rotational velocity
Shuttle main engines are among the most efficient chemical advantage. To date, Space Shuttle missions have ranged from
rockets yet developed, with a vacuum-rated Isp of 452.5 s. minimum inclinations of 28.35 degrees to a maximum of 62
The shuttles solid rocket boosters have a vacuum-rated Isp degrees, the latter extreme during STS-36, a Department of
of 267.3 s [3]. Defense Space Shuttle mission.
Limitations of engine performance are the most important The inclination of the desired orbit cannot be lower than the
factor currently influencing space exploration. These limita- launch site latitude without a significant performance penalty;
tions affect the amount of payload that can be delivered to in such a case, the ground site never rotates through the orbital
orbit and the payload mass and velocity that can be directed to plane, and no practical launch windows exist. Posigrade
a distant site out of LEO. For a given spacecraft, the ultimate
measure of overall performance is its capability to provide the
change in velocity, or v, required for a certain orbital maneu-
ver. This includes launch to orbit, in which the required v
is the difference between the velocity component of Earths
rotation in the desired orbital plane and the final orbital veloc-
ity. It also includes losses from drag and gravity while travers-
ing the atmosphere en route to orbit, as well as subsequent
changes in orbital altitude and plane and potentially escaping
from Earth orbit. For launching to orbit, provision of suffi-
cient v for a given payload depends greatly on the engine
efficiency and the amount of propellant. To gain an apprecia-
tion of the relationship between payload, spacecraft structure,
and propellant, it is instructive to examine the mass fractions
of a standard Earth-to-orbit spacecraft. Typical values for pro-
pellant, structural, and payload mass fractions are 0.85, 0.14,
and 0.01, respectively [4]. The Saturn V Apollo Lunar vehicle
had a total launch weight of 2,621,000 kg. Of this, 129,250 kg
(4.9%) was delivered to LEO, but only 45,350 kg or about
1.7% was accelerated to escape velocity away from Earth
toward the Moon [5]. After the lunar mission was completed,
including crew descent to the surface and subsequent shedding
of the lunar module, the final reentry weight of the command
module carrying the crew was only about 5,670 kgroughly Figure 1.1. Velocity assist from Earths rotation for eastward
0.2% of the original launch weight. (posigrade) launch
6 M.R. Barratt
Figure 1.2. Orbital inclination, the angle between the orbital plane
and earths equatorial plane. For any launch site, the minimum
achievable inclination is equal to the launch sites latitude. Higher
inclination orbits are mechanically achievable but obtain less advan-
tage from Earths rotation
launches from NASAs Kennedy Space Center site in Florida
are constrained to orbital inclinations 28 degrees and above,
whereas launches from the Russian launch site in Baikonur,
Kazakhstan are restricted to inclinations at or above the site
latitude of about 46 degrees. Geopolitical constraints prohibit
straight-east launches from Baikonur (to avoid dropping spent
stages on Chinese territory), further limiting the effective incli-
nation. A practical implication of this fact is that target orbits
for large-scale projects involving multiple launch facilities are
limited by the facility located at the highest latitude. For this
reason, the orbital inclination of 51.6 degrees for the Interna-
tional Space Station (ISS) is defined by the Russian launch,
range, and tracking capabilities and must be accommodated
by the lower-latitude U.S. and European Space Agency sites
(located in Khorou, French Guyana at 6 degrees latitude). The
most flexible launch site in terms of access to the widest range
of orbital inclinations would be located near the Equator; also,
for a given orbital altitude, higher inclination orbits, although
deriving minimal launch benefits from Earth rotation, cover
more of Earths surface in their ground track, a situation that
influences Earth observation and access to ground communi-
cation facilities.
The desired orbit to which a spacecraft is lofted is said to
be fixed in inertial space rather than relative to the ground,
although the central point of reference is the center of the Earth.
In other words, the motion of the orbiting spacecraft becomes
indifferent to the ground surface features rotating beneath it.
A reference system independent of Earth-surface features is
Figure 1.3. The J2000 Inertial Reference Frame. With Earth at the
center (geocentric), the Z axis points through the rotational North Pole,
the X axis lies in the plane of the equator and points toward the vernal
equinox (first point of Ares) for the year 2000, and the Y axis passes
through the equatorial plane to complete a right-handed coordinate
system. The inclination of a spacecrafts orbit is the angle between the
orbital plane of the spacecraft and the earths equatorial plane
needed to describe orbital motion; as such, an inertial coor-
dinate system has been adopted that characterizes the basic
elements of an objects orbit. This system is based on a geo-
centric model, which places the gravitational center of Earth
at the origin of a three-axis system (Figure 1.3). The plane
of Earths equator contains two perpendicular axes, X and Y.
The Z-axis extends through the axis of rotation, and X points
toward a fixed position in space, the vernal equinox or first
point of Ares defined for the year 2000. The Y-axis completes
a right-handed coordinate system. This so-called J2000 refer-
ence system recently replaced the M50 coordinates, for which
X was defined as the vernal equinox for the year 1950.
The most efficient insertion into a desired orbit comes about
by lofting from the launch site, which is fixed relative to the
ground, directly into the desired orbit. Missions involving ren-
dezvous and docking with another orbiting spacecraft require
synchrony between launch time and the target objects motion.
This requirement gives rise to launch windows, spans of time
during which the launch site rotates through the target orbital
plane. Thus the time of the launch depends on the latitude and
longitude of the launch site and the desired orbital plane and
inclination. Launch opportunities may exist for both ascend-
ing (northbound) and descending (southbound) legs of the
orbit. Higher inclination orbits imply steeper intersect angles
between the launch site velocity vector from Earth rotation
and launch azimuth as well as shorter launch windows. For a
Space Shuttle launching straight out from the Kennedy Space
Center at a latitude of 28 degrees with no rendezvous require-
ments, a launch window is not constrained by orbital mechan-
ics and may last several hours. By contrast, launching from
1. Physical and Bioenvironmental Aspects of Human Space Flight
that site to a high-inclination rendezvous orbit, such as to the
51.6-degree ISS, the launch window, given the current perfor-
mance limitations, effectively becomes 510 min long. Little
margin exists for steering sideways to intercept an orbital
plane if the optimal launch time is missed. Adverse weather
conditions or hardware anomalies during the period immedi-
ately before launch that require assessment and timely action
by the ground team thus can have a more profound effect on
the success of launches that attempt to reach higher inclina-
tion rendezvous targets.
Other launch-window determinants include constraints of
lighting from the angle of the Sun, the flight path over ground
sites during critical activities, the planetary geometry for trans-
planetary flights, and crew factors such as time spent in the
launch position in full launch suit and rescue gear and crew
duty day. For flights that do not involve rendezvous, lighting
and crew physical and duty limits become the primary factors
determining the duration of the launch window.
For a given orbit, the launch window changes from day
to day as Earth rotates eastward independent of the inertial
orbital plane. The node of an orbit, the point where it crosses
the equator, can be seen to track westward for a given clock
time relative to the day before. This phenomenon, known
as nodal regression, is due primarily to the oblate nature of
Earth induced by the equatorial bulge. On successive days, the
launch site rotates through the orbital plane earlier than on the
previous day. For a planned launch from Kennedy Space Cen-
ter to the 51.6-degree ISS orbit, for example, missing a launch
opportunity because of weather or mechanical factors results
in the next days opportunity being approximately 20 min ear-
lier than on the planned day. This time accumulates over a
delay of several days, and thus such a delay may require shift-
ing the crews sleep period if the crew is adapted to a certain
operational time schedule.
Earth Orbit
In attaining orbit, the influence of aerodynamics on a space-
craft and its crew becomes negligible and the influence of
the basic laws of Newtonian mechanics increases. Weight-
lessness (or free fall) is sustained when the inward force of
gravity is exactly counterbalanced by the outward centrifugal
force of the spacecraft, with sufficient velocity forward to
result in a flight path tangential to the surface of Earth. For a
circular orbit, the flight path becomes a constant altitude; for
an elliptical orbit, the altitude will vary depending on rela-
tive position on the orbital track. To be sustainable, the alti-
tude must be sufficient to escape drag-inducing atmospheric
interaction, and forward (tangential) velocity must be high
enough to keep the spacecraft falling around Earth rather
than to Earth; this is the state of free fall, which is perceived
as weightlessness. The standard orbital velocity in LEO is
8 km/s (5 mi/s). A typical Space Shuttle mission is flown at
an altitude of 320 km (200 mi) with a forward velocity of
28,160 km/h (17,500 mph).
7
Even at these altitudes, over a period of months atmo-
spheric drag is sufficient to cause eventual orbital decay. Solar
magnetic activity also is dynamic along short-term spikes and
in long-term cycles, and it may increase to cause effective
thermal expansion of the atmosphere and increase its result-
ing drag influence on an orbiting spacecraft. A large orbiting
platform thus requires periodic reboosting to remain in orbit.
As an example, in its final configuration, the Russian space
station Mir, with a mass of about 90 metric tons and a large
cross-sectional area, required several hundred kg of propellant
per year to perform altitude reboosts. A typical reboost might
loft the station from the lower levels of the operating envelope
(350 km) to the maximum levels (440 km) limited by the per-
formance of docking vehicles. Decreasing the cross-sectional
area of the craft relative to the velocity vector, which can be
done by feathering solar arrays or changing the structures
attitude, serves to decease drag and maintain orbital altitude
for longer periods.
The orbital shape of an object gravitationally held by Earth
is typically elliptical, with two major landmarks: the perigee,
the point along the elliptical path closest to Earths center, and
the apogee, the corresponding point farthest from the cen-
ter. The complete characteristics of a spacecrafts orbit can
be defined by six primary factors, or orbital elements. Also
known as the classic Keplerian elements, these elements are
based on a three-axis reference system using Earths center as
an inertial origin point.
Figure 1.4 describes the basic elements of a body in orbit.
The Z-axis is the earths axis of rotation and goes through
the north (+Z) and south poles. The X and Y-axes are in the
equatorial plane, with +X pointing to the vernal equinox and
+Y offset 90 degrees in a right-handed system. The following
elements are required to completely describe an orbit for a
two-body system [6]:
a: semi-major axis: describes the size of the ellipse (Figure 1.4A)
e: eccentricity: describes the shape of the ellipse (Figure 1.4A)
i: inclination: the angle between the angular momentum vector
and the unit vector in the Z-direction. (Figure 1.4B)
W : right ascension of the ascending node: angle from the
vernal equinox to the ascending node. The ascending node
is the point where the satellite passes through the equatorial
plane moving south to north. Right ascension is measured as a
right-handed rotation about the pole, Z. (Figure 1.4B)
w : argument of perigee: the angle from the ascending node to
the eccentricity vector measured in the direction of the space-
crafts motion. The eccentricity vector points from the center
of the earth to perigee with a magnitude equal to the eccentric-
ity of the orbit. (Figure 1.4B)
n : true anomaly: the angle from the eccentricity vector to the
satellite position vector, measured in the direction of satellite
motion. This is a time component; alternatively, time since
perigee passage could be used.
8 M.R. Barratt
Figure 1.4. A and B. The six primary elements describing a
spacecraft orbit. These are known as the classic Keplerian elements
and define the size, shape, and orientation of the orbit, as well as the
position of the spacecraft on the orbit
The precise orbit of a spacecraft may not be fully described
with these classical elements because of various perturbation
forces such as third-body effects (e.g. lunar gravitational influ-
ence), solar radiation, atmospheric drag, and the influence of
a nonspherical Earth. Although the effects of these perturba-
tion factors are smaller than those of the basic elements for a
spacecraft in LEP, the perturbation factors must nevertheless
be accounted for in mission operations. Detailed descriptions
of the classical elements and other factors is beyond the scope
of this text; however, a basic understanding of these factors is
useful for the space medicine specialists situational under-
standing of crewed space flight.
After launch and ascent, which typically lasts 79 min, a
crewed spacecraft such as the Soyuz or Space Shuttle quickly
crosses the atmosphere and realm of aerodynamics into LEO.
The path of a spacecraft over the ground (its ground track) can
be envisioned by flattening out Earths spherical shape, thus
producing the familiar sine-wave track over the Mercator pro-
jection maps used in mission control centers (Figure 1.5). The
Figure 1.5. Ground track of a spacecraft in low Earth orbit, in this case
the International Space Station with an orbital inclination of 51.6
22.5-degree westward precession of the ground track for each
90-min orbit can be seen as Earth continues to rotate eastward
independent of the inertial orbital plane.
Spacecraft can be placed into a wide variety of orbits,
including those involving retrograde launches (opposite the
direction of Earth rotation) and geostationary positions, which
maintain a constant position relative to a fixed ground point.
However, the human presence introduces limitations that are
based on environmental hazards. For human space flight, LEO
is for practical purposes bounded at the lower altitude by the
physical constraint of atmospheric interaction and at the upper
altitude by the physiologic constraint of increasing radiation
exposure from the geomagnetically held Van Allen radiation
belts. These constraints result in the standard LEO work enve-
lope for long-duration flight being between 200 km (124 mi),
below which atmospheric drag would cause rapid decay of the
spacecraft orbit, and approximately 500 km (312 mi), where
depending on orbital inclination the daily radiation dose might
exceed 5 104 sieverts (Sv) (50 millirem [mrem]). The rela-
tionship of orbital characteristics and radiation exposure is
described further in Chap. 23.
Orbital Debris
Early seafarers had to contend with uncharted reefs and occa-
sional floating debris; space vehicles in LEO are faced with
an analogous collision potential. Operations in Earth orbit can
bring spacecraft near other similarly held objects, primarily
originating from artificial sources. Given the standard orbital
velocities of such objects and assuming unlimited radical orbital
paths, the collision velocities can be formidable, with an aver-
age relative velocity between two objects of 10 kilometers per
1. Physical and Bioenvironmental Aspects of Human Space Flight
second (kps); with this relative velocity, a 100-gram fragment
possesses kinetic energy equivalent to 1 kg of TNT [7].
Most of the material in LEO is artificial, consisting of active
spacecraft, spent and inactive satellites, booster components,
and fragmentation products resulting from pyrotechnic sepa-
ration devices. More than 95% of tracked objects are consid-
ered unusable debris. The more heavily used orbits tend to be
the most cluttered with debris. In contrast, the flux of natural
material, consisting mostly of fragmentation and disintegra-
tion products of comets and asteroids, is much lower than
that of artificial material. Natural material flux is primarily
confined to particles smaller than 1 mm with velocity on the
order of 16 kps. Such particles continually rain down on Earth
and rarely slow enough to become trapped in LEO. Approxi-
mately 40 million kg of such matter is thought to reach Earths
surface annually, with the peak in the size distribution at about
200 m in diameter. This mass amount is thought to be com-
parable over very long time scales to the contribution from
bodies of much larger size (in the 1-cm to 10-km range) [8].
Orbiting objects are tracked by the U.S. Space Surveillance
Network; objects larger than 10 cm (4 in.) can be detected and
tracked with Earth-bound radar. Currently about 8,000 such
objects are being actively tracked [9]. Figure 1.6 depicts the
rise over time in the number of tracked objects in LEO, where
most spacecraft operate, showing a nearly linear and parallel
relationship with the history of spaceflight activities. These
tracking data occasionally allow avoidance maneuvers to be
made when imminent collisions or proximity are calculated,
as has been done for the Space Shuttle, Mir, and ISS. However,
most of the material, in terms of both number and total mass,
consists of small objects below the size threshold for track-
ing by radar. Shielding can be reasonably afforded against
hypervelocity collision forces with objects up to 1 cm in size;
shielding for larger objects becomes unduly heavy and car-
ries substantial costs in terms of performance and structure.
As such, the greatest danger for large crewed space platforms
stems from objects 110 cm in size, which are large enough
Figure 1.6. Population over time of orbital debris larger than 10 cm
in low Earth orbit, as cataloged by the Space Surveillance Network
9
to inflict substantial damage on spacecraft but are essentially
invisible and therefore unavoidable. Risk parameters for colli-
sion of orbital debris with crewed platforms and EVA systems
are discussed further in Chap. 12, which deals specifically with
the issue of decompression of habitable cabin atmospheres.
International efforts are currently being made to minimize the
further generation of orbital debris by limiting the use of fran-
gible bolts and actively deorbiting spent stages.
Beyond Earth Orbit
Pulling away from Earth requires an escape velocity that
depends on the radius of the orbit, according to the equation
Vesc = 2 / r (1.4)
where Vesc is escape velocity (in km/s), is Earths gravita-
tional constant (equal to Earths mass multiplied by G, the
universal gravitational constant, or 398,600.5 km3/s2), and
r is the distance from Earths center (the radius of the orbit).
The farther the distance from Earths center, the smaller the
V required. At the surface of Earth, where the distance from
Earths center to the equator is 6,378 km, a theoretical V of
11.2 km/s is needed to escape gravitational pull; an additional
V would be needed to make up for atmospheric losses. For
example, from the typical LEO altitude of the ISS (386 km
with an orbital radius of 6,764 km), the escape velocity is
10.8 km/s; for a spacecraft already established in this orbit
with a velocity of about 7.8 km/s, only a small additional V
is required.
For travel beyond near-Earth space, the factor of great-
est influence becomes sheer distance and its effect on travel
time and subsequent radiation exposure. Near-Earth destina-
tions outside of LEO such as the Moon and Lagrangian points
(points of Earth-Sun or Earth-Moon gravitational equilibrium)
can be reached relatively easily with currently available chem-
ical rockets, although the payload mass that can be delivered
to these sites remains limited. However, with conventional
chemical rocket technology, travel beyond near-Earth space
becomes much more daunting. Most Mars flight scenarios
have involved mission durations on the order of 450 to more
than 1,000 days [1012] and mission profiles at the extremes
of chemical rocket capabilities. These missions might also
involve some gravitational assist maneuver such as a plan-
etary (Venus or Earth) flyby. The bulk of the total mission
time could be taken up by interplanetary transit in weightless
conditions.
Aside from the limitations on the vehicles involved, such
mission scenarios also are well outside the current experi-
ence with human space flight. The longest space flight to
date was the laudable 438-day mission of the Russian phy-
sician-cosmonaut Dr. Valery Polyakov aboard Mir between
January 1994 and March 1995. Although this mission was
highly successful, the longer limit of flight duration must be
extended significantly to entertain thoughts of very long mis-
10
sions using current propulsive technology. Provision of some
degree of artificial gravity en route, although fraught with
medical, performance, and engineering challenges, may miti-
gate the adverse effects of prolonged exposure to microgravity
(described later in this chapter under Microgravity and Partial
Gravity). However, to consider distances to Mars and other
more distant potential targets of crewed missions such as the
larger asteroids, the development of advanced propulsion and
power systems must be a high priority to enable human explo-
ration of the solar system in earnest. Scenarios involving the
exposure of humans for many months to interplanetary transit,
with its harsh radiation environments, should be avoided by
applying technology to travel faster. Although the desirabil-
ity of faster interplanetary transit times may seem obvious,
specific operational factors may be identified that bolster this
requirement. Prominent among these factors is the absolute
radiation dose to which a human can be exposed and still meet
the annual and career limits of radiation exposure. Mainte-
nance of bone and muscle mass and cardiovascular condi-
tioning in microgravity also becomes critically dependent on
the use of countermeasures, and to date no countermeasure
regimen has proven completely effective. Unlike crewmem-
bers who return to Earth after a long-duration mission, crew-
members landing on the surface of Mars, with its gravitational
field of 0.38 G (where G is a multiple or fraction of g = unit
gravity on Earth, or 9.8 m/s2), will be alone in managing their
postflight medical treatment and rehabilitation program, with
only remote guidance from ground specialists and onboard
medical references to augment their preflight medical train-
ing. The author and others, in observing several crewmembers
freshly returned from long-duration flight, have noted a con-
siderable degree of individual variability in postflight condi-
tion and performance despite similarities in flight experience
and use of countermeasures. It would be highly advisable that
those crewmembers embarking on inaugural remote explora-
tion missions with planned surface excursions have previous
experience with long-duration space flight and well docu-
mented postflight performance and readaptation to a gravity
field. The psychological tolerance and mission performance
of such crewmembers should also be known. A problem
becomes immediately apparent in making previous long-dura-
tion flight a requirement. Such experience on a LEO station,
for instance, coupled with 14- to 36-month interplanetary
transit times would probably result in radiation exposure that
exceeds established career radiation limits.
With a few notable exceptions, standard LEO duty tours
onboard the Mir and ISS have been on the order of 120180
days; this constitutes a reasonable period for performing effec-
tive work without incurring unacceptable cumulative radiation
exposure and bone mineral loss. Perhaps the only reason to
perform longer missions would be to expand the long-dura-
tion flight envelope for characterization of human response
and development of more effective countermeasures. A clear
near-term goal, then, is to provide transit times well within
this experience base. This would ensure that radiation limits
M.R. Barratt
can be met, experienced long-duration space crewmembers
with known in-flight and postflight performance can be sent,
and reasonable microgravity countermeasures can be used.
Provision of artificial gravity may prove to be an effective
countermeasure if prolonged exposures to weightlessness are
inevitable. However, providing a constant rotational artificial-
gravity field confers substantial mechanical and engineering
problems in addition to human tolerance challenges. From a
life sciences standpoint, the most efficacious solution to ensure
mission success is to keep transit times short. Critical space
medical research objectives would thus focus on optimizing
human performance within a familiar time envelope and on
developing true clinical autonomy during space flight.
Many new propulsion technologies are currently being
examined to use propellants much more efficiently and reduce
transit times to destinations such as Mars. Figure 1.7 compares
the relative performance characteristics of several propulsion
concepts. Although expounding on the details of propulsion
is beyond the scope of this text, it is readily evident that con-
ventional chemical rocket technology is at the low end of the
scale with regard to enabling crewed solar system explora-
tion. Technical comparisons of new propulsion technologies
are factored into exploration mission planning [2,13]. Some of
these advanced technologies, such as nuclear thermal rocket
engines, are relatively mature and offer performance well
beyond that of chemical systems, although crews will need
to be shielded from artificial ionizing radiation. Other tech-
nologies, such as magnetoplasmadynamic engines, are more
exotic and require much forward work but offer tremendous
Figure 1.7. Relative performance of various propulsion concepts.
Although chemical rockets have served well for near-Earth space
exploration, exploration class missions must utilize advanced
technologies to become practical
1. Physical and Bioenvironmental Aspects of Human Space Flight
advantages in planetary transit scenarios. Given that Mars is at
an extreme limit of chemical rocket technology for round-trip
flights, it is logical to use a new technology on an evolutionary
step toward these advanced propulsion concepts, then apply
and enhance the same technology to go further and to increase
the feasibility and practicality of maintaining a presence on
the surface of Mars.
One such concept, the variable specific-impulse magneto-
plasma rocket (VASIMR), consists of a plasma engine that
can be throttled. The relative balance of thrust F and spe-
cific impulse Isp is varied under constant power, enabling
the optimal use of propellant. Greater F is used for orbital
boost and deceleration phases, whereas lower F and higher
Isp are used for efficient transplanetary flight [14]. Plans for
Mars missions involve multiple launches for vehicle assem-
bly and unmanned cargo missions, with transit times shorter
than those that can be achieved with chemical rockets. One
representative piloted scenario uses a 12-MW nuclear-electric
VASIMR rocket to deliver a payload mass of 61 metric tons
to Mars [15]. The cryogenic hydrogen propellant can also
be positioned around the crew cabin, providing an optimal
barrier against high-energy galactic cosmic rays. Along with
enabling the near-term exploration of Mars, this basic technol-
ogy could represent an evolutionary step over a greater time
scale, most likely on the order of several decades. Incorpora-
tion of advanced power systems, such as nuclear fusion, as
they become available will afford a further drastic improve-
ment in performance. With 10100 gigawatts available, for
example, accelerations involving potentially protective frac-
tions of linear unit-gravity, on the order of 0.30.5 G, become
available. Such technology could fully open up the solar sys-
tem to human exploration and exploitation.
A similar need for advanced technologies exists for onboard
power generation. Systems such as environmental control and
life support, avionics, communication, and laboratory and
investigational facilities require electrical power in abundance.
Solar energy is readily available in LEO, and solar arrays have
proven effective in supplying satellites and crewed stations.
At assembly-complete, the solar arrays of the ISS will sup-
ply the 75 kW needed for systems and laboratory operations.
However, these arrays typically provide little reserve power in
standard operations and, because of their large surface area,
are vulnerable to damage by orbital debris. Venturing further
outward in the solar system also means that diminished solar
energy flux will be available to generate power. Fuel cells,
such as those used on the Space Shuttle, function well for
short-duration missions and provide the added by-product of
potable and hygiene-grade water after reacting liquid hydro-
gen and oxygen. Power requirements on the Space Shuttle
average 14 kW, and thus water is in fact produced in surplus,
necessitating periodic overboard dumps. However, coupled
with the relatively short operational life of fuel cells, a typical
Space Shuttle mission involves the consumption of 1,590 kg
(3,500 lbs) of cryogenically stored hydrogen and oxygen to
generate the onboard electrical power needed.
11
To venture confidently and frequently beyond near-Earth
space, high-yield and reliable power systems are required to
ensure autonomy and mission success and to enhance crew
safety and comfort. A transplanetary craft carrying four to
six crewmembers might be expected to require 2060 kW for
systems operations, and the same would be true for a mod-
est surface habitat. These power requirements must be met
over periods of at least several months and must be absolutely
assured. As such, a forward step beyond solar and fuel cells is
necessary. Submarines provide a historical analog: the transi-
tion from fossil-fuel burning engines to nuclear-powered steam
turbines has afforded electrical power generally in excess of
standard propulsion requirements. Power for life support
system functions, desalinization of seawater and processing
it into potable and hygienic water, electrolytic production of
breathing oxygen from seawater, and various other support
systems has become relatively abundant.
For space flight, access to abundant power with sufficient
margins is critical for crew safety as well as for mission suc-
cess. Nuclear fission reactorsif they can be safely launched
and managedoffer an attractive and currently available
option for generating electrical power for long-duration space
flights. This approach would change the current situation
of resource and power limitation to one of resource limita-
tion only; resources could then be better managed, such as
by advanced but power-intensive regenerative life support
systems. Using nuclear reactors as a power source for an
advanced propulsion system might afford this electrical power
as a by-product and drastically increase the margin for mis-
sion success and safety. Obviously, many safety and engineer-
ing issues are associated with nuclear systems; aside from the
potential problems of further exposing the crews to ionizing
radiation, such systems may require large radiators to dissipate
heat, which would be vulnerable to debris and micrometeor-
oid impact while the craft is in LEO. However, with no other
equivalent available power source in the immediate future,
barring a breakthrough in fusion technology, the safe and
careful use of nuclear reactors for spaceflight propulsion and
planetary surface use should be vigorously explored. Whether
any sustainable crewed exploration beyond near-Earth space
can be undertaken without nuclear power is doubtful.
Acceleration Forces
Acceleration Basics
With the advent of powered vehicles, notably aircraft and space-
craft, the possibility first arose for prolonged human exposures
to significant sustained acceleration forces. As stated earlier,
ascending the gravity ladder to leave Earth implies a climb to
above the atmosphere and a v of 8 kps to attain a sustainable
LEO. The time during which the spacecraft must accelerate to
this new velocity determines the forces acting on the human
occupant. In theory, this acceleration could be slow enough to
produce minimal effects; in practice, however, the time span is
12
bounded by vehicle performancea slow ascent to final veloc-
ity and sustainable orbit involves more time fighting against
gravity and hence greater propellant consumption, whereas an
overly rapid ascent incurs greater aerodynamic and structural
loads. The acceleration of ascent is not linear, but rather shows
peaks and troughs based on engine staging and structural lim-
its. At the end of a mission, after a deorbit engine burn, the
spacecraft must reenter the atmosphere and slow to its origi-
nal velocity in a reciprocal negative acceleration (deceleration)
profile, with aerodynamic drag as the prevailing force. Return-
ing from the Moon, the Apollo capsules carried more velocity
than a spacecraft returning from LEO and thus were subject to
even higher acceleration loads for entry.
Earth launch and landing loads will probably be the great-
est acceleration forces experienced by human beings as more
remote exploration missions are considered, and these forces
have shown to be tolerable. In any case, physiologically sig-
nificant acceleration loads are a fundamental consequence of
transition between gravity fields of planetary bodies. Exten-
sive reviews of acceleration forces and their effects on the
human are available in the aviation medical literature; this
section focuses instead on the genesis of acceleration forces
in the spaceflight environment and highlights the differences
between aviation and space crewmembers.
A review of Sir Isaac Newtons three basic laws of motion
is both useful and relevant in clarifying acceleration:
1 A body at rest (in motion) will remain at rest (in motion)
unless acted upon by an outside force.
2 F = ma, where F = force in Newtons (kg/m/s2), m = mass in
kg, and a = acceleration in m/s2.
3 For every action, there is an equal and opposite reaction.
The constant acceleration caused by Earths gravity at sea level
is taken as 9.81 m/s2, and is denoted as g. Using this value
as a reference, the notation G is used to denote fractions or
multiples of g; G is thus a dimensionless quantity. The unit
G is not to be confused with G, the universal gravitational
constant, as discussed later.
Acceleration Forces in Space Flight
In many aerospace operations, components of basic accelera-
tions can be mixed. However, the loads typically involved in
spacecraft launch and entry involve linear acceleration, with
the spacecraft maintaining a more or less constant relation to
the acceleration vector. This situation allows crewmembers
and payloads to be placed in optimal positions relative to the
acceleration vector so as to best withstand those forces. An
exception is the U.S. Space Shuttle, which effectively becomes
an airplane with standard upright seating as it reenters Earths
atmosphere during landing.
For any activity involving sustained acceleration loads, the
orientation of the human crewmember to the vector of G load-
ing, along with the absolute G load incurred, can profoundly
influence crew activity and performance. In terms of aviation,
M.R. Barratt
the pilot of a high-performance aircraft is seated upright,
which is necessary for optimal control in a dominantly hori-
zontal reference plane. However, during tight turns, that posi-
tion subjects the pilot to G loads in the most physiologically
vulnerable axis (head to foot or +Gz). The major determinant
and limiting factor of performance under sustained +Gz accel-
eration is the cardiovascular system; the hydrostatic pressure
acting on the vertical blood column between the heart and
brain in particular renders cerebral perfusion vulnerable. In
the early days of human space flight, control during ascent
and descent was highly automated; the human inputs that
were required were largely independent of the familiar hori-
zontal vision reference required and maintained by the aviator.
Thus for the first 20 years of space flight, the space flyer did
not require upright orientation, thus avoiding this physiologi-
cally vulnerable position and allowing positions with the most
favorable orientation to the G vector, +Gx (chest to back), to
be assumed for launch and landing. Moreover, as spacecraft
have become less of a crewed ballistic missile and more of
the multiperson, payload-carrying, and cross-range-capable
spaceships of today, launch and landing loads have eased.
The basic types of acceleration are linear, radial, angular,
and Coriolis, all of which can occur alone or in combination,
and each of which contributes a vector component to a resultant
sum. Accelerations are characterized by the vector direction
(axis), rate of onset, magnitude, and duration of application to
the human occupant. The accelerations described also involve
reactive forces (linear and torque) determined by the mass of the
object. From the three basic laws of motion, it is understood that
mass provides inertial resistance to acceleration. These inertial
forces, resulting from changes in linear and angular velocity,
are what actually lead to the physiologic effects. In addition to
considering the basic accelerations encountered in space flight,
one must also consider the forces resulting from those accelera-
tions; Coriolis accelerations in particular will be considered in a
subsequent discussion of artificial rotational gravity.
Linear acceleration. For linear acceleration, the direction
of movement is constant, and only the velocity changes. The
equation for linear acceleration is:
a = v/t (1.5)
where a = acceleration (expressed in m/s2), v = change in
velocity (in m/s), and t = time (in s). The resultant force on a
human undergoing linear acceleration, which acts opposite the
perceived acceleration, is described by Newtons second law:
F = ma (1.6)
where F is the force acting on a body (in N [m/kg/s 2]),
m = the mass of an object (in kg), and a = acceleration (in m/s2).
The gravitational force that holds us to Earths surface implies
a reactive force based on our mass and a linear acceleration
of 9.81 m/s2, denoted as g or 1 G. Significant, sustained lin-
ear accelerations involving multiple Gs are a phenomenon
of spacecraft, associated thus far with launch and landing
activities. (For a hypothetical spacecraft capable of prolonged
1. Physical and Bioenvironmental Aspects of Human Space Flight 13

acceleration at 9.8 m/s2, the force acting downward on the
body would be perceived as natural unit gravity.)
The well-known effects of multiple-G forces on the human
body depend greatly on orientation, and thus require a coordi-
nate system to depict direction. The accepted body coordinate
system, along with resulting inertial forces and circumstances
of these linear acceleration components in space flight, is
shown in Table 1.2.
In all piloted launch vehicles leaving Earth, crewmembers
are positioned such that the major G loads incurred by the
body during ascent are taken along the body +Gx axis. Repre-
sentative G profiles of various piloted launch vehicles during
nominal ascent are shown in Figure 1.8; Figure 1.9 shows entry
G loads for the same vehicles. The vector sum of the resultant
loads on the human occupant depends on seat positioning and
orientation with respect to the vehicle and acceleration vector.

Table 1.2. Standard three-axis coordinate system describing linear accelerations and resulting inertial forces
on the human body for space flight.
Primary Spaceflight Circumstances
Axis/Direction Acceleration Resultant Inertial Force (Most involve mixed acceleration vector components)
+Gz Headward Head to Foot Space Shuttle entry (1.2 G sustained)
Shuttle landing turn (1.21.98 G)
Apollo Lunar Ascent Module
Gz Footward Foot to Head
+Gx Forward Chest to Back Launch (38 G all vehicles)
Entry (1.2 G recumbent in Shuttle to 8 G in Mercury-
type capsules)
Launch abort scenarios (1720 G)
Aerocapture maneuvers (future transplanetary flight)
Parachute opening (Apollo, Soyuz, etc.)
Landing impact (transient, 420 G)
Gx Backward Back to Chest Shuttle runway deceleration from brakes, drogue chute
+Gy To Right Right to Left Impact (land or water) on capsule from horizontal
velocity component (wind)
Gy To Left Left to Right Same
Note: Spacecraft orbital maneuvering can be applied to all axes, typically involving very low G forces.

Figure 1.9. Representative acceleration profiles and resultant G loads

Figure 1.8. Representative acceleration profiles and resultant G
loading for launch of the Gemini, Apollo, and Space Shuttle (Space
Transportation System) spacecraft. Most of the loading is received
along the crewmembers +Gx axis
on occupants of the Gemini, Apollo, and Space Shuttle (Space Trans-
portation System) spacecraft during atmospheric reentry. Gemini
and Apollo crew capsules allowed most of the load to be taken in
the crewmembers +Gx axis. Space Shuttle crewmembers land in an
upright, seated position, exposing deconditioned crewmembers to
much smaller loads but in the +Gz axis for much longer periods
14
Such positioning is also related to vehicle structure, center of
gravity, and flight characteristics.
Crewmembers returning from a U.S. Space Shuttle mission
assume an upright position, the position of greatest vulnera-
bility in the transition from being adapted to weightlessness to
being relatively deconditioned aviators. Crewmembers main-
tain a standard aircraft seating arrangement during landing,
with the entry vector in the +Gz orientation for vehicle and
occupants. Shuttle landing forces are fairly gentle and grad-
ual, with a constant acceleration of about 1.2 G over 17 min
during actual atmospheric entry, culminating in a turn to final
approach resulting in a maximum of 2.0 +Gz, with 1.41.5
+Gz being typical.
Mishaps during ascent and entry can lead to much higher
loads, primarily in the +Gx axis. Escape tower systems, such
as those currently used for the Russian Soyuz booster and
those formerly used for the U.S. Apollo and Mercury space-
craft, are designed to remove the crewmember from the launch
pad or from an early launch explosion as rapidly as possible.
This design incurs very high (1020 G) acceleration loads in
the +Gx orientation. This system has been used operationally
on one occasiona fire on the launch pad during the Soyuz
T10A launch. During that event, the escape rockets pulled the
capsule containing cosmonauts V. Titov and G. Strekalov up
and away from the fire, briefly subjecting them to about
17 +Gx while a safe altitude was attained for parachute deploy
followed by a soft landing about 4 km away from the launch
pad [16,17]. Launch abort scenarios are also possible, such as
that experienced by cosmonauts V. Lazarev and O. Makarov
in the Soyuz 18A flight bound for the Salyut 4 orbital station.
Failure of third-stage separation on ascent subjected the crew-
members to a high-load suborbital flight lasting approximately
21 min before the chute deployed and the craft landed. Maxi-
mal forces were said to be 2021 +Gx. Although some minor
injuries were sustained during the hillside landing, no persis-
tent effects from the high G loads sustained were reporteda
remarkable testament to G-load tolerance in this axis [18,19].
In both of these extreme cases, crewmembers were not
already deconditioned from weightlessness. A more rapid bal-
listic entry after a LEO mission might result from an overly
long deorbit burn time, with higher transient G loads than
normal. Loads such as these typically would not be as high
as those in a launch abort scenario, but because they would
be applied to deconditioned individuals, they may have more
significant physiologic effects.
Radial acceleration. Radial acceleration involves a
change in direction without a change in speed. In particular,
for an object traveling in a circular course, radial acceleration
describes the inward or centripetal acceleration towards the
center of the circle:
2 tional inertia (in kg-m2/radian, where the radius of the rotation
a = v /r (1.7)
where a = radial acceleration (in m/s2), v = velocity about the
circular course, and r = radius of the circle. The force that
produces the radial acceleration is balanced by a pseudoforce
M.R. Barratt
acting on the body in the opposite direction of angular accel-
eration (outward), the centrifugal force:
Fc = mv2/r (1.8)
where Fc = centrifugal force (in N), v = velocity about the
circular course, m = the mass of an object in kg, and r = radius
of the circle. From the standpoint of human exposures, sig-
nificant, multiple-G radial accelerations are experienced in
human-rated centrifuges, in which a rigid moment arm holds
a crew fixed to the center of rotation, and high-performance
aircraft, in which engine thrust applied in a constant direc-
tion and aerodynamic lift forces circularize the path. Loads of
112 G can be incurred by piloted aircraft, with the centrifugal
force applied to the pilot in the +Gz body orientation caus-
ing the well-known adverse effects on the hydrostatic blood
column. For a spacecraft that is free of the atmosphere, such
radial motion and forces are fairly untenable because of the
huge expense in propellant necessary to apply thrust to sup-
port constant directional change. The one caveat, however, is
the Space Shuttle, which effectively becomes an aircraft upon
landing. A turn around an imaginary heading alignment circle
aligns the Shuttle for final approach to land, incurring a force
of between 1.0 and 1.8 sustained +Gz on its upright-seated
occupants. Although this force is small compared with that
on occupants of high-performance aircraft, the cardiovascular
deconditioning and relative plasma-volume depletion charac-
teristic of returning space flyers renders them physiologically
equivalent to terrestrial pilots experiencing several Gs.
The major implications of radial acceleration for human
space flight relate to the provision of artificial gravity, as dis-
cussed in the next section.
Angular acceleration. Angular acceleration involves
change in rotation rate about an axis passing through the body,
as might be incurred in a rotating chair or rolling an aircraft.
Angular motion may be expressed in degrees of rotation, revo-
lutions, or radians, where one radian is one revolution (360
degrees) divided by 2, or about 57.3 degrees. Angular veloc-
ity and acceleration are given by:
w = (21)/t or d/dt (1.9)
a = (w2w1)/t or dw/dt (1.10)
where = angular velocity (in radians/s), = angular motion,
= angular acceleration (in radians/s2), and t = time (in s). In
general, angular acceleration is caused by torque, caused by a
force applied at a specific distance (the moment arm) from the
center of rotation:
M = Ja (1.11)
where M = torque applied to a rotating body (in N-m), J = rota-
is expressed in meters), and = the angular acceleration (in
radians/s2).
In space flight, angular accelerations can be incurred by
human occupants of a spacecraft undergoing orbital maneuvers
1. Physical and Bioenvironmental Aspects of Human Space Flight
or ballistic reentry vehicles undergoing spin stabilization (e.g.,
the early space capsules). These maneuvers involve some off-
set from the spin axis, so that components of both radial and
angular acceleration are involved (although the angular accel-
erations involved would be fairly small). Mishaps can provide
large and adverse components of angular accelerations; one
such event occurred on Gemini VIII as a result of a rotational
thruster that was stuck in the on position. In addition, crew-
members can themselves induce angular accelerations, both
inside and outside the spacecraft, to levels that can produce
motion sickness in the first few days of flight. Unlike linear
and radial accelerations, where the resultant forces mechani-
cally affect organs and blood columns, the angular motion
itself is provocative to the neurovestibular system at thresh-
olds greatly below those for mechanical organ effects. Angu-
lar accelerations exert these influences through their effects
on the graviceptors and the visual system, both components
of body motion perception and control (discussed further in
Chap. 17).
Acceleration Forces and Spaceflight
Deconditioning
The human response to sustained acceleration in the +Gx ori-
entation has been known for several decades. However, these
responses have been characterized and documented primar-
ily in healthy subjects in centrifuges and thus apply to nor-
mally conditioned individuals during launch. The hypokinetic
states of bed rest [20,21] and actual space flight [22] and its
attendant physiologic deconditioning are known to adversely
influence the response to sustained accelerations. In terms of
spacecraft operations, concerns focus on the pilots ability
to make manual inputs to spacecraft control during the entry
phase as well as the crews ability to perform physical tasks
immediately after landing, when the G load incurred in the
vulnerable Gz axis is fully dictated by the bodys postural
positioning. As such, more conservative limits are needed for
space flight than those in the aviation environment. The cur-
rent NASA limit for sustained linear acceleration in the +Gz
axis during landing after prolonged space flight is 0.5. This
limit would also apply to other linear acceleration loads that
may be encountered, including engine burns and aerobraking
after transplanetary flight.
The Space Shuttle returns from space unpowered and human-
piloted, placing unique performance demands on the decondi-
tioned flight crew. Protective measures such as fluid loading,
anti-G garments, active cooling, and anti-G straining maneu-
vers are used if needed (described further in Chap. 16). These
measures have been relatively effective for Space Shuttle flights
lasting up to 18 days. However, missions that last 30 days or
more (considered long-duration flights in the current system,
based on best available information and risk thresholds) engen-
der other considerations with regard to crew duty rotations and
the need for mission-specific hardware. For example, crew-
members returning on the Space Shuttle from a long-duration
15
flight assignment, such as from an ISS or Mir station tour, do so
in a recumbent seat on the Shuttle middeck that positions them
on their backs with their feet forward to meet the +Gz limit
noted above. (Such crewmembers are not involved in piloting
the Space Shuttle during entry and landing.)
Landing Loads
Landing loads associated with impact refer primarily to tran-
sient acceleration events that last 500 ms or less. Before the
advent of the Space Shuttle, which lands on a runway like a
conventional aircraft, U.S. spacecraft used parachutes to slow
themselves as they passed through the atmosphere and landed
in water. Landing loads were somewhat variable, depending
in part on wind and waves, which might induce horizontal and
angular components to the impact forces. A typical Apollo
capsule landing with an initial vertical velocity of 9 m/s (30 ft/s)
during the final parachute descent in 5-knot (2.6 m/s) winds
might experience a sharp 17-G spike, peaking in the first few
ms, in the vehicles +Gx axis. Such spikes were also incurred
in the body +Gx axis and were found to be tolerable by crew-
members returning from Apollo lunar and Skylab missions.
(The water impact was then followed by the real possibility of
seasickness.) Soviet and Russian spacecraft have used land-
based landing systems that involve a combination of para-
chutes, braking rockets, and form-fitting seat liners in couches
with independent compression struts. A typical Soyuz landing
profile induces a +Gx impact load on the crewmember of a
400-ms square-wave pulse at about 4 G in the vehicles verti-
cal axis, with the possibility of an added horizontal component
from wind velocity. Should the soft-landing engines fail, the
parachute-and-compression-strut combination affords a +Gx
transient spike of more than 20, which has been experienced
on two occasions without undue injuries. These impact profiles
have shown to be well within the tolerance of crewmembers
returning from long-duration missions, provided that the seats
and equipment are secured. During the landing of Apollo 12,
a camera broke loose from its mounting and struck the pilot in
the head, inflicting a minor laceration [23].
Microgravity and Partial Gravity
Microgravity
Probably the most pervasive physical factor associated with
orbital operations, and certainly the one most associated with
human space flight, is the absence of perceptible gravity, also
known as weightlessness. Gravitational force is described by
Newtons Law of Universal Gravitation:
F = GM1m2/r2 (1.12)
where F is the magnitude of force, G is the universal gravi-
tational constant common to all bodies and planetary sur-
faces, M1 and m2 are the two masses being described, and
r is the effective radius between gravitational centers. For
16
LEO operations, M1 is Earth and m2 represents the orbiting
spacecraft. The term zero G is often used when referring to
LEO, although from a physical standpoint this is somewhat
of a misnomer; as the above equation shows, the gravitational
force is nowhere near zero. With an equatorial Earth radius of
6,378 km (3,963 mi), a spacecraft orbiting over the equator at a
typical altitude of 370 km (230 mi) still experiences a relative
force of gravity of (6,378)2/(6,748)2, or about 90% of what
would be felt at the surface. The practical influence of gravity
on an object persists until the object is removed from a domi-
nant mass to such a distance that the force is negligible, or
until forces of gravity and inertia are in balance and the object
attains a state of free-fall. This is the dominant condition for
orbiting spacecraft. This weightless state affects all aspects of
physical activities, from liquid fuel transfer to any of a number
of standard processes relying on air-fluid separation (buoy-
ancy), such as delivering intravenous infusions free of bubbles
and handling body fluids and liquid laboratory reagents. The
presence of any remaining or unbalanced gravitational force
will influence mechanical and fluid systems. For most scien-
tific and investigational purposes, microgravity is determined
as 106 G. However, below a certain arbitrary threshold, which
probably resides near a few hundredths of a G (where fluid
shifts and body pressure on surfaces would be imperceptible),
the space flyer for all practical purposes resides in a weight-
less state.
Although humans thrive in a 1-G environment and may
be said to physiologically maintain a 1-G set point, this ter-
restrial set point itself actually implies a dynamic condition.
Humans possess adaptive mechanisms to account for changes
in body orientation with respect to the standard G vector. For
example, lying down (i.e., shifting position from standing to
recumbent) changes the effective G load on the hydrostatic
blood column between the heart and brain from one or unit
gravity to near zero. From the standpoint of cardiovascular
(as well as musculoskeletal) regulation, the weightless state
induces a much more constant loading condition that closely
resembles the recumbent state. Entering weightlessness thus
does not imply entering a completely foreign physiologic con-
dition, and of course space flyers can endure very long periods
in weightlessness.
Human response to microgravity can be adequately studied
only in space. Parabolic flight provides brief periods of free-
fall, on the order of 2025 s, and has become a useful tool
for evaluating hardware and human factors and for studying
physical processes that react quickly to the absence of grav-
ity. However, these brief periods of zero G alternate with
periods of increased G load as the aircraft pulls out of its
powered dives. The resultant oscillating G field, between zero
and 1.8 G, does not invite the same possibilities for human
adaptation and is provocative to the neurovestibular system
in a manner different from prolonged weightlessness (see
Chap. 10). Water immersion provides a suitable analog for
some task-evaluation and training activities, notably EVA
practice. Neutral buoyancy affords simulation of body motion
M.R. Barratt
and mass handling such that end-to-end tasks are timelined
with reasonable accuracy as compared with their in-flight exe-
cution. However, rapid limb movements are limited by hydro-
static drag in neutral buoyancy, which increases in proportion
to the square of velocity [24]. In addition, effects such as sinus
pooling persist, a reminder that gravity is still at work on the
body, and thus hanging upside down for prolonged periods
in a water-immersed suit is uncomfortable.
The human response to microgravity is described in more
detail in Chap. 2. Among the more quickly perceived aspects
are the novel (e.g., flying from one place to another) and the
annoying (e.g., constantly losing items that float away upon
being laid aside). Along with human factors and ergonomics
issues, microgravitys influences on some of the more funda-
mental physical forcesincluding buoyancy, sedimentation,
hydrostatic pressure, and convectionare relevant to life and
medical sciences and are noted below.
Buoyancy, the separation of substances, especially liquids
and gases, by gravity owing to differences in their densities,
is absent in weightlessness, leading to a more homogeneous
mixing of fluids and gases than on Earth. The implications of
loss of buoyancy range from difficulty in handling fluids to
loss of standard air-fluid levels in diagnostic imagery. As an
example, one cannot expect to see the familiar gastric bubble
on chest or abdominal radiography.
Sedimentation, the downward force, or physical separa-
tion of liquids and solutes caused by the linear acceleration of
gravity, is typically opposed by buoyancy and frictional forces
and is described by the expression:
Fs = mg Fb Ff (1.13)
where Fs is the sedimentation force, m is the mass of a sol-
ute, g is the linear acceleration of gravity, Fb is the buoyancy
force, and Ff is the frictional force. Sedimentation is also
absent in weightlessness, with the corresponding implications
again including homogeneous mixing, this time between liq-
uids and solutes or suspended particles. For example, a urine
sample centrifuged for microscopic analysis must be spun and
read before the physical separation induced by the centrifugal
force is undone by the lack of gravitational force. Also, con-
taminants are not easily separated and must be filtered rather
than eluted away from a supernatant unless centrifugally sepa-
rated. On a more macroscopic level, atmospheric particles do
not settle out from spacecraft cabin air and as such may be
inspired or inadvertently ingested by crewmembers.
Hydrostatic pressure is the force F of a liquid caused by its
weight standing above a certain surface area A, expressed by:
Ph = F/A (1.14)
and Ph is linearly proportional to g. The total pressure act-
ing on a fluid column consists of hydrostatic plus atmospheric
pressure. In weightlessness, hydrostatic pressure is reduced to
atmospheric pressure and any other induced forces, such as
centrifugal or pump forces. The physiologic implications are
that no changes in pressure in the hydrostatic blood column
1. Physical and Bioenvironmental Aspects of Human Space Flight 17

accompany changes in position, and blood pressure above the of cardiovascular regulatory mechanisms, endocrine changes
heart is dominated more by intrinsic cardiovascular dynamics associated with volume changes, and neurovestibular distur-
such as pumping forces and vascular constriction and dilation. bances. It should not come as a particular surprise that humans
This pressure can be added back in weightlessness by using function as well as has been observed in weightlessness. How-
centrifugal forces. ever, an awareness of the above forces and how they influence
Convection is the dynamic movement of fluids and gases human physiology is necessary for filling in the substantial
that facilitates heat transfer and affects mixing as well. Con- gaps remaining in our understanding of zero G physiology.
vection can be based on density variations and thus be driven A basic understanding of this physiology enables a practical
by buoyancy, or it can result from forced or induced flow. approach to various medical problems involving fluid han-
Standard terrestrial buoyancy-driven convection is the force dling, heat transfer, gaseous dispersion, and biomechanics.
that facilitates candle burning, involving movement of oxygen
to replenish the oxygen that is locally consumed and circula-
tion of volatilized fuel and combustion products. Without con- Fractional G
vection, a flame in weightlessness will consume the oxygen in
Partial gravitational fields, that is, fractional relative to Earth-
close proximity and if forced airflow from an outside source
normal, must be thought of on a graded scale with several prac-
or the means to propagate along a fuel source to an oxygen-
tical threshold values. From the human standpoint, threshold
ated area is not provided, the flame will extinguish itself. In
of detection stands at the far end, where in a spacecraft the
microgravity, forced convection is important to make up for
crewmember will notice objects (including himself) resting
the absence of buoyancy-driven convection for such processes
on a surface oriented opposite to the acceleration vector. This
as dispersion of metabolically produced CO2 and body cool-
probably occurs with a few hundredths of G. Other potentially
ing. The basic equation for convective heat transfer is:
relevant thresholds include effective air-fluid separation, a
C = hc(t1 t2) (1.15) force sufficient to support an active gait, and passive loads
sufficient to influence bone and muscle mass.
where C is the rate of heat transfer (typically watts/m2 of sur-
Sustained partial G is of interest for the human space flyer
face area), t1 and t2 are the temperatures of the body and fluid
in two main areas: planetary surfaces and provision of artifi-
medium, and hc is the convection coefficient, which includes
cial G as a countermeasure to the deleterious effects of pro-
consideration of fluid movement.
longed exposure to weightlessness. Planetary surface forces
Other forces and processes are not altered in weightless-
most relevant to us currently are lunar (1/6 G) and Mars grav-
ness. Heat transfer may still occur via conduction, radiation,
ity (about 1/3 G), and possibly smaller fields such as may be
and evaporation, and gases and liquids may still be mixed by
encountered during short-term flights to asteroids (or other
diffusion. Terrestrially, diffusion exerts a lesser influence on
planetary satellites). People have worked successfully on the
mixing and particulate dispersion than buoyancy, convection
lunar surface despite the changes noted in biomechanics and
and sedimentation, but this is one of the more prominent mix-
energetics [25], although none have stayed long enough to
ing forces in zero G. In a pressurized LEO module lacking
effect detectable changes in physiologic parameters, particu-
any artificial physical agitation, diffusion alone will drive the
larly bone and muscle mass losses. Given the demonstrated
dispersion of an atmospheric contaminant from a point source
feasibility of lunar surface exploration, Mars should not be
throughout the remainder of the volume. This process is slow
problematic for exploration efforts from the practical human
enough relative to physiologic CO2 production that local areas
standpoint; the major issue is that it will most likely follow
of increased concentration will build around a crewmember,
prolonged exposure to weightlessness. This implies neuroves-
who may then manifest signs of CO2 toxicity in an unventi-
tibular deconditioning, orthostatic intolerance, and bone and
lated module. Similarly, for a crewmember breathing supple-
muscle atrophy commensurate with the amount of time spent
mental oxygen in the same circumstance, the oxygen-enriched
in microgravity during the voyage.
exhalation may produce a local flammability risk. Induced air
Provision of artificial G as a countermeasure to deleteri-
movement is a fundamental requirement for human occupants
ous effects of weightlessness has been considered for many
of a weightless habitat.
decades. Shipov has written an excellent review of these
The human body is a highly active and dynamic machine,
considerations [26]. Artificial G may be afforded by rotat-
endowed with countless processes to facilitate mixing and
ing a spacecraft or a structure, which may be contained within a
transport. Circulation of blood and other fluids, active trans-
non-rotating spacecraft, to provide continuous centrifugal
port and diffusion across membranes, nerve conduction, and
force. This could be employed for a stable platform, such as
chemotactic mechanisms are basically left to function intact in
an orbiting station, or an interplanetary spacecraft. Expressed
weightlessness. It is mainly on the macro level that weightless-
in terms of angular velocity , the pseudoforce known as
ness exerts its primary effects. These effects, such as unload-
centrifugal force conveniently describes rotational artificial
ing of the hydrostatic blood column, thoracic fluid shifts, and
G and is expressed by:
unloading of otoconia and other gravitational sensors, give
rise to corresponding secondary effects such as desensitization Fc = mw2r (1.16)
18
It is apparent that altering the rotational velocity and radius
components influence two extreme ends of a practicality
continuum. At the structural end, very large formations and
masses well beyond anything built in space thus far would be
required to maintain a relatively low rotational rate while pro-
viding Earth-equivalent artificial G. For example, a structure
with a rotation radius of 900 m with an angular velocity of
one revolution per minute (about 0.1 rad/s) would be required
to provide Earth-normal gravity [27]. Various approaches have
been elaborated, from very large structures to distinct capsules
joined by a tether and spinning about a central axis. Problems
include limitations in structural mass, tether performance
and reliability, abort capabilities for interplanetary spacecraft
because of a limited number of spin/de-spin cycles, mishaps
that might require EVA repair, and interference with astro-
nomical observations. It is much more feasible to increase
rotational velocity for short-radius structures to obtain a
desired force. However, this is bounded by the biomechanical
end associated with human tolerance of rotation.
A significant implication of rotation to a human occupant
is unwanted Coriolis acceleration effects, induced with linear
motion in a rotating reference frame. Coriolis acceleration Ac
and force Fc can be expressed by:
Ac = 2(v ) (1.17)
Fc = 2m(v ) (1.18)
where v is the linear velocity of a moving object in m/s, is
the angular velocity of a rotating system in rad/s, and m is the
mass of an object in kg. Coriolis forces will affect the motion
of any object or occupant, complicating motion sensation,
motor control, and mass handling.
Humans are equipped with sensitive multiaxial accelera-
tion sensors in the form of semicircular canals and otoliths,
designed to work optimally to sense motions and changes in
body orientation in a static 1-G background field. In a rotating
structure, head movement will change the orientation of these
sensors to the direction of rotation and induce an unwanted
transient input suggesting whole body rotation. These are
so-called cross-coupled responses to angular motions in two
planes. Cross-coupled Coriolis responses are known to be
annoying and potentially provocative to humans. Effects and
symptoms are greatest when moving in a plane perpendicular
to the axis of rotation, and include neurovestibular instability,
vertigo, nausea, emesis, and disorientation.
Preliminary U.S [2830]. and Russian [31,32] studies in the
early 1960s with human subjects have proven the capacity for
sustained tolerance to angular acceleration in rotating rooms,
but this tolerance was limited by neurovestibular disturbances
and motion disorders at rotation rates well below what might
be required to produce a significant fractional G level (when
the pervasive Earth G component was subtracted). It was gen-
erally thought that rotational rates must be limited to 45 rpm
to avoid incapacitating vestibular and motor effects. Subse-
quently, it was demonstrated that gradually increasing the
M.R. Barratt
rotation rates will allow tolerance of these sustained rates [33]
up to 10 rpm [34]. With stepwise increases in rotational forces,
it may be possible for crewmembers to adapt to rates whereby
structures a few tens of meters in diameter could provide use-
ful and protective levels of G. For example, a structure with a
10-m (33-ft) rotational radius at 10 rpm would provide 1.1 G at
the rim; a 15-m (49-ft) radius at 7 rpm would provide 0.82 G.
Aside from potentially inducing cross-coupling effects and
neurovestibular dysfunction, a rotating structure implies a
gravity gradient extending from the rotational hub to the rim.
The perception of this gradient would be most pronounced
with shorter radii, of which a human subjects height is a sig-
nificant fraction. Considering a rotating crew module with
a diameter of 7.2 m (23 ft) and a rotational radius of 3.6 m
(11.8 ft), a 1.8-m (71-inch) crewmember would assume half of
this height when standing. The force at the head will be half of
the force at the level of the feet, introducing a gradient of 50%
over the crewmembers standing height. This gradient induces
significant motor control and mass handling challenges as
the crewmember bends and transitions between standing and
seated or horizontal postures. A rotational radius longer than
12.2 m (40 ft) would be required to produce gravity gradients
below a recommended 15% for a rotating spacecraft or centri-
fuge [35]. In addition, an overall additive velocity effect serves
to increase weight while ambulating in the direction of rota-
tion and to decrease weight in the opposite direction. These
anomalies, along with mass handling and motor control chal-
lenges, suggest that comprehensive adaptation to such rates
may be difficult. However ground studies have suggested that
humans can gradually adapt to these higher rotational rates
with regard to head and arm control along with tolerance of
cross-coupling effects [36].
An alternative to sustained rotation of a habitation module
is provision of short periods of artificial G more intense than
one G. Various schemes involving human-rated centrifuges,
some human-powered to couple cardiovascular countermea-
sures with this loading, have been proposed [3739]. Com-
binations of time and multiples of G could be determined to
lead to a gravitational acquired dose curve [40] specifically
oriented toward maintenance of bone and muscle mass.
The most elegant solution for interplanetary flight, most
likely relegated to the far future, is provision of a linear G
field in some significant fraction of Earth gravity. This implies
constant linear acceleration, which might be provided by a
highly advanced propulsion system. Such advanced systems
would be needed to reach and practically sustain operations
on desirable targets of interest beyond Mars, such as asteroids.
Linear G would enable a constant vertical reference with pas-
sive exposure to the acceleration load, broken only at some
midcourse point when the ships engine is powered down to
turn and begin the deceleration burn. Ironically, the ensuing
sudden exposure to microgravity might imply a mid-mission
risk of space motion sickness, albeit a transient one. Assum-
ing that large stationary platforms may someday be built at
departure and destination points that can be spun and are large
1. Physical and Bioenvironmental Aspects of Human Space Flight
enough to avoid undesirable Coriolis effects, a propulsion
concept affording linear G offers the best solution for long
transit times.
For rotational and linear G, it must be determined what
fraction of unit gravity would be required to maintain bone
and muscle. One G may be considered the gold standard, but
a lesser fraction is more in keeping with attainable structures,
future propulsion, and energy cost. During in-flight artificial
gravity studies with centrifuged rats, Yuganov et al. observed
a threshold level of 0.15 G for bioelectric activity, which
steadily increased in parallel with transverse G forces up to
a level of 0.28 G. Between 0.28 and 0.31 G, the bioelectric
activity was equivalent to what was seen in ground controls,
and no further increase was seen up to 0.7 G [41]. In an inves-
tigation to determine the minimum fractional G load that
would sustain bone in hindlimb-suspended rats, Schultheis
and colleagues determined that 0.25 G may be equivalent to
0.75 G in preserving bone formation [42]. From the standpoint
of human factors, studies in parabolic flight of progressive G
levels have demonstrated that for walking, mass handling, and
mechanical tasks such as bolt tightening, very little gain is
seen beyond 0.2 G [43]. Although much research remains to
be done, provision of a constant force of perhaps 0.3 G may
enable fairly normal biomechanical activity, and in combina-
tion with modest physical countermeasures augmented with
heavy resistive exercise, may well maintain bone and muscle
mass at near Earth-normal levels. It is hoped that this critical
focus of investigation will be addressed with the laboratory
facilities on board the ISS.
Radiation Sources
For what has been found to be such a pervasive entity in
the universe and among the more important factors limiting
human exploration beyond Earth, radioactivity was discov-
ered relatively recently. In 1895, Konrad Wilhelm Roentgen
discovered that invisible, penetrating rays (x rays) could be
produced by electrically exciting a low-pressure gas. Radio-
activity was discovered and first described a year later in
1896 by Antoine-Henry Becquerel while he was experiment-
ing with uranium salts. Becquerel observed that these salts
could blacken a photographic plate in the absence of light,
and he later determined that this was caused by the emission
of energetic particles from the element uranium. Over the
ensuing years, many other emitting substances were identi-
fied and their radioactivity characterized. As sensitive detec-
tors were developed, a background flux of radioactivity was
noted to persist in the absence of known emitters. Some of
this radioactivity was eventually attributed to naturally occur-
ring substances in the ground. However, balloon experiments
conducted between 1911 and 1913 by V.F. Hess in which
these detectors were flown to altitudes of 9,000 m showed a
tenfold increase in this background flux over surface values,
suggesting an extraterrestrial source [44]. These observations
19
were bolstered by further balloon experiments to 15,000 m in
1925, and prompted R.A. Millikan to term this background
flux cosmic radiation.
The term radiation can be broadly defined as the emission
and propagation of waves transmitting energy through space or
a medium and includes electromagnetic energy (X rays, gamma
rays, visible light, radio waves, etc.) as well as charged par-
ticles (protons, electrons, alpha particles, etc.) and uncharged
particles (neutrons). Radioactivity refers to a certain type of
radiation emitted by a specific substance, typically from decay
of unstable nuclei. These particles and waves carry a wide
spectrum of energies and may interact with a medium they
traverse. If this interaction involves collisions with atoms or
molecules such that imparted energy expels electrons and cre-
ates new charged ion species, it is termed ionizing radiation.
Radiation may induce damage directly, as by a high-energy
particle imparting energy to a cellular molecule, or indirectly,
by inducing the formation of secondary ion species through
collision events. These secondary particles may then go on to
interact with biological material. High-energy electrons tra-
versing a dense medium, such as metal structures, may interact
with the material, and, in the process of slowing and imparting
their kinetic energy to the material they induce the formation of
X rays. This phenomenon is termed bremsstrahlung (German for
braking radiation) and has obvious implications for shield-
ing considerations. Non-ionizing radiation, such as from ultra-
violet light and radiofrequency energy, may also cause tissue
damage from burns and local heating effects.
Throughout the early experiments mentioned above,
adverse health effects from radiation were observed, includ-
ing local effects such as eye irritation, skin burns, and dermal
necrosis. Over time, more sinister effects such as blood and
lymphoid malignancies and solid tumors were noted. Many of
these effects were directly related to the overzealous use of X
rays, in both diagnostic and therapeutic applications. Despite
the significant energies involved, human senses cannot detect,
and thus cannot avoid, radioactivity and most forms of elec-
tromagnetic radiation. Rather, the damaging secondary effects
consisting of physical, chemical, and biological changes are
what are eventually perceived. As such, dose-response rela-
tionships were slow to be identified, especially with regard
to malignancies arising after a prolonged latency period. The
establishment of the International Council for Radiological
Protection, along with international acceptance of common
monitoring units in 1928, led to a more systematic under-
standing of this relationship and the means for monitoring and
mitigating radiation-induced health problems [45].
We have learned that space is a radiation environment, or
more properly that Earth, thanks to its protective atmosphere
and magnetic field, is a radiation haven, a shelter from the
effects of products of the most fundamental processes in the
universe. These processes include the formation, life, and
death of stars, solar system accretion, and stellar and plan-
etary magnetism. Radiation exposures for humans in space
flight stem from three main natural sources: galactic cosmic
20
rays, solar particles and electromagnetic radiation, and geo-
magnetically bound charged particles. In addition, secondary
particles (e.g. neutrons) are known to be produced from the
interaction of primary particles with spacecraft structures.
Future artificial sources (power sources, detonation of nuclear
weapons) may also be considered. The character of radiation
sources, their biological effects, and risk mitigation strategies
are discussed in detail in Chap. 23. The present discussion
will be limited to the physical distribution of the major ion-
izing radiation sources pertaining to human space flight.
Galactic Cosmic Radiation
A background flux of high-energy-particle radiation is present
in interstellar space. This galactic cosmic radiation, or GCR,
most likely originates in supernova explosions, in which mas-
sive quantities of nuclei from hydrogen (H) and helium (He)
and a smaller proportion of heavier nuclei are ejected in the
stellar debris. Kinetic energy is imparted in the initial explo-
sion, and these charged particles may be further accelerated
by interstellar magnetic fields to near light speed (3 108 m/s).
Although supernova explosions are point events, the distribu-
tion of GCR seems to be isotropic because of galactic mag-
netic field lines that prevent travel along straight paths. It is
estimated that supernovae can maintain the observed flux of
GCR if such explosions occur, on average, every 50 years in
our galaxy [46].
GCR consists primarily of protons or H nuclei (about 90%),
and alpha particles or He nuclei (about 9%), with the remain-
ing species being heavier elements in ionized states. Com-
pared with terrestrial radiation sources, which might generate
detectable counts of many millions of particles per cm2 per
second, the flux from GCR is relatively low, at a few spe-
cies per cm2 per second. However, GCR species contain mas-
sively higher amounts of energy. These energies are typically
denoted in electron volts, or eV, which is a convenient unit of
measure for particle physics. One eV is defined as the energy
gained by an electron accelerating between two plates, 1 m
apart, with a potential difference of 1.0 volts; one eV = 1.6021
1019 joules (J). Whereas radium may emit energies on the
order of several mega eV (MeV, where mega = 106), GCR
particles must often be measured in the giga eV range (GeV,
where giga = 109). The most abundant GCR species are pro-
tons with energy of about 2 GeV, and the remainder consists
of an exponentially diminishing flux of progressively higher
energy species, up to 1011 GeV (1020 eV). To put this energy
into perspective, a single cosmic ray particle at the very high
end of the energy spectrum, with 1.5 1020 eV, carries 25
joules, sufficient to raise 1 kg a height of 2.5 m on Earth [47].
GCR is effectively attenuated by Earths atmosphere, which
has a thickness equivalent of 1,000 grams/cm2, and by pow-
erful geomagnetic fields to a relatively low flux at the sur-
face. Local solar system effects also modulate GCR. The
solar wind and interplanetary magnetic field lines distort the
paths of charged GCR particles with energies less than 1 GeV
M.R. Barratt
[46], causing them to lose significant energy and some to be
deflected away. This modulation varies with the biphasic
22-year solar cycle so that at solar maximum, the GCR bath-
ing Earth is about half of the flux at solar minimum [48].
Particles with energies exceeding 10 GeV are minimally sus-
ceptible to the influence of the solar wind and magnetic fields
and continue unimpeded.
Solar Radiation and Solar Cosmic Particles
The Sun, with a radius of 6.95 105 km, is a generator of mas-
sive energies. Fueled by the fusion of H into He and heavier
nuclei at its core, the Sun radiates energy at a rate of 3.86 1026
W, virtually all in the visible light spectrum. Along with elec-
tromagnetic radiation, which among other things affords our
planet light and warmth, a continual emission of electrically
neutral plasma known as the solar wind streams outward. Free
electrons are electrically balanced primarily by protons, as
well as alpha particles and some heavier ionic species, mov-
ing in magnetic field lines that spiral outward because of the
Suns rotation. These particles carry the Suns magnetic field
into the solar system and are thus distributed in an anisotropic
fashion. Irregularities in the solar corona alter plasma velocity
and density. The velocity of these particles as measured near
Earth ranges 300700 km/s, with particle densities of 120/
cm3 [49]. Solar wind particles are of low energy, typically
about 1,000 eV (1 keV).
In contrast to the relatively gentle flux of the solar wind are
solar cosmic rays (SCR), particles similar to those of the solar
wind but of much higher energy. These stem from solar flares,
which are associated with large magnetic disturbances on the
surface, and carry energies typically in the MeV range and
possibly up to 20 GeV. These flares also radiate in the electro-
magnetic spectrum, with such radiation ranging from gamma
rays and X rays through ultraviolet and long-wavelength
radio waves. Along with electromagnetic emission and accel-
erating atomic particles, solar flares induce a blast wave that
propagates through the solar wind at 1,500 km/s. The relative
energy distribution is such that about half is invested in the
electromagnetic emission, half in the blast wave, and only
about 1% in the actual SCR. Most of the particles detected
near Earth are protons, and a smaller fraction consists of He
nuclei. A large electron flux is stemmed by loss of energy in
exciting radiofrequency bursts in the corona, the Suns outer
atmosphere.
SCR particles at the high end of the energy range reach
Earth vicinity 2030 min after the first optical evidence of
the flare can be seen, with periods of maximal SCR flux last-
ing a few hours. Clouds of lower energy particles and solar
wind disturbance reach Earth in 624 h. A diminishing flux
of high-energy particles followed by lower-energy particles
can be detectable for several days after a large flare. The vast
majority of SCR particles is effectively stopped by the geo-
magnetic field and poses little threat to crewmembers in LEO
in typical orbital inclinations. The main hazard with regard
1. Physical and Bioenvironmental Aspects of Human Space Flight
to human space flight arises for activities outside of the geo-
magnetosphere, such as interplanetary transit, occupation of
a Lagrangian point station, or lunar surface activities, where
radiation flux could increase by a thousand-fold to a million-
fold. A minimally shielded crewmember, such as one engag-
ing in EVA operations, could receive a lethal dose of ionizing
radiation in a few hours during a major solar flare.
Solar flares correlate with the 22-year biphasic solar cycle,
the most frequent and intense being at or near the solar maxi-
mum. The resulting periods of increasing probability of solar
flare occurrence can drive some operational considerations for
long-term human space flight activities. However, although a
buildup may be detected early enough to warn a crew to take
shelter in a radiation-hardened structure, buildups cannot be
reliably forecasted. As for solar wind emissions, SCR emis-
sions are anisotropically projected into the solar system, in
part because of the regionality of their sources on the solar
surface. Most flares producing high-energy particles seem to
originate in the Suns western hemisphere [44]; this coupled
with the Suns rotational rate of 25 days at the equator (slower
at higher latitudes) means that not all flares are visible from
Earth. For a spacecraft not in Earths vicinity, e.g., one en route
to Mars, a major flare detected on Earth may not be problem-
atic for or even detected by the spacecraft; however the oppo-
site is also true. Transplanetary spacecraft should be equipped
with the means to detect sentinel electromagnetic and particle
emissions preceding high particle flux and guide appropriate
crew responses. Strategically placed solar-orbiting spacecraft
with electromagnetic and particle detection capability could
also relay such information to spacecraft and Earth, analogous
to ocean weather buoys.
Geomagnetically Bound Radiation
Magnetism and Earths magnetic field have been known and
exploited for centuries by ocean navigators. More recent is
the appreciation that Earth is endowed with a dipolar mag-
netic field, with field lines emerging at the North magnetic
pole and re-entering at the South magnetic pole. This dipolar
magnetic axis is offset by some 12 degrees from the rotational
axis. Most of the geomagnetic field originates from Earths
center, where conducting liquid iron of the outer core flows
around the solid iron inner core, with the motion probably
driven by convection resulting from heat flow from the core to
cooler outer layers. Movement of the conducting fluid around
the inner cores preexisting magnetic field, most likely a rem-
nant of core formation, induces an electric current, which in
turn induces a secondary magnetic field much stronger than
the original [50]. This is known as the geomagnetic dynamo
model. Although much remains to be learned about the intrin-
sic properties of the geomagnetic field, the first landmark
scientific discovery of the space age involved extraterrestrial
implications of these field lines.
In 1958, the first successful U.S. satellite, Explorer 1, lofted
a Geiger counter in an experiment devised by James Alfred
21
Van Allen to study GCR flux above Earths atmosphere.
Unexpectedly, this and subsequent Explorer and Pioneer
space probes led to the discovery that the external field lines
are heavily populated with highly energetic charged particles.
Two main belts of intense trapped radiation, with fluxes many
orders of magnitude over that of the background GCR, were
identified [51]. These now bear the name of their discoverer,
the Van Allen belts. The Van Allen belts are arranged as two
concentric doughnuts centered on the geomagnetic equator
(Figure 1.10). Two distinct concentration bands with a defini-
tive gap between them have been mapped, although this gap is
not totally devoid of particles. The inner belt begins at roughly
1,000 km in altitude and extends to 5,000 km; the outer belt
extends from about 15,000 km to 25,000 km at the equator.
The charged species populating the Van Allen belts are
essentially captured particles from the solar wind and solar
cosmic rays. Inner belt protons most likely originate from
interaction of GCR with atmospheric species, inducing the
formation of short-lived neutrons. Some of these neutrons
decay into protons and electrons, which are then bound by the
geomagnetic field. Eventually, they are removed by interac-
tion with atmospheric molecules; the relative rates of removal
and replenishment drive the concentrations observed. Outer
belt particles originate from interaction of the solar wind with
the magnetosphere, in which a small fraction of these parti-
cles leak into the field lines rather than being deflected away.
The outer belt is more susceptible to the dynamic effects of
the solar wind and SCR and so may vary considerably in
Figure 1.10. The Van Allen radiation belts, showing relative distribu-
tion and shape of the inner and outer bands of geomagnetically bound
charged particles. Darker shaded areas denote regions of greater par-
ticle density. The orbital track of a typical crewed spacecraft in low
Earth orbit is seen to be well below the inner belt
22 M.R. Barratt

concentration. All bound particles travel along geomagnetic
field lines, spiraling around these lines and bouncing back
and forth between northern and southern mirror points with
a period of 0.13 s.
Inner belt particles typically carry high energies, with
protons of 50 MeV and electrons of 30 MeV. The flux may
be as large as 2 105 per cm2 per second, higher than the
GCR flux by a factor of 104. These energies and quantities
would constitute a grave radiation hazard to the occupants
of spacecraft and their systems if sufficient time were spent
in zones of high concentration. Most human platforms in
LEO, such as the ISS at about 375 km altitude, operate well
below the floor of the inner belt. However, the borders are
not sharply defined, and a measurable increase in flux is
observed with increasing altitude. In addition, an offset of
the geomagnetic and rotational axes causes a defect in the
basic shape of the inner belt in which it dips down to a lower
altitude. This defect, known as the South Atlantic anomaly
(SAA), consists of a region in which the radiation flux at a
relatively low altitude is equivalent to that at a much higher
altitude. The shape and boundaries of the SAA change with
altitude. A spacecraft at 225 km altitude will experience a
100-fold increase in radiation flux while passing through the
SAA, whereas a 1,000-fold increase would be experienced
at 440 km altitude [52]. The greatest fraction of the radiation
dose delivered to LEO crewmembers results from orbital
crossings of the SAA.
Although containing large quantities of charged particles,
the geomagnetic field serves the vital role of shielding Earth
from the brunt of the solar wind and SCR as well as from
lower energy GCR. The shielding afforded depends on posi-
tion relative to the dipole; with the shape of the magnetic
fields shown in Figure 1.10, higher-inclination orbits become
progressively less protected from GCR and SCR. A polar
orbiting spacecraft is exposed to radiation flux similar to that
in free space.
considerations for humans will likely be restricted to the moon
and Mars. Table 1.3 [46,53] shows comparisons of physical
attributes of Earth, the Moon, and Mars.
Lunar exploration efforts, although brief, were highly suc-
cessful, implying that more extensive and long-term efforts
could be undertaken. However, particular medical consider-
ations are associated with surface activities, some of which
were suggested during our brief time on the moon. Two of the
major factors underlying these considerations, partial gravity
and surface dust, are discussed in the following sections. Radi-
ation sources have been noted in a previous section, and Chap.
23 will cover aspects of surface dosimetry and shielding.
Partial Gravity
Even a fraction of Earth gravity offers a tremendous conve-
nience to human occupants. Locomotion in a familiar vertical
reference frame is possible, and it is easier to adapt terrestrial
tools and processes to this environment. Fluids and gases can
separate, and items remain where they are placed. Some of
the fundamental physiologic problems associated with pro-
longed weightlessness, such as bone demineralization and
muscle atrophy, may be mitigated to some extent by even a
partial gravitational field. Along with fractional Earth grav-
ity, the activities inherent in exploration and exploitation of
resources will likely favorably augment this force with regard
to bone and muscle loading. Such activities will include use
of heavy EVA suits, carrying heavy loads, and operating tools
for construction and excavation. In addition, although partial
gravity fields should not be considered benign environments,
physical countermeasures are simplified by the existence of a
gravitational vertical and the ease of increasing resistive force
loads. However, the presence of partial gravity also restores,
to some extent, a potential for injury that is largely absent in
microgravity.

TABLE 1.3. Selected physical attributes of Earth, Earths Moon, and

Planetary Surface Factors Mars.
Earth Moon Mars
By far the greatest portion of human spaceflight activity has Solar distance, semi-major 149.6 149.6 228
occurred in the weightlessness of LEO, with a small fraction axis (106 km)
of time spent on the lunar surface during the U.S. Apollo mis- Radius, equatorial (km) 6,378 1,738 3,394
sions. However, activities such as these are a much-anticipated Surface gravity (relative to 1.0 0.16 0.39
Earth-normal)
aspect of future endeavors, without which we are limited to
Escape velocity (km/s) 11.18 2.38 5.03
microgravity investigations and Earth-observation studies. On Atmospheric pressure, 760 mmHg Essentially 0 4.8 mmHg
planetary surfaces, we trade such problems as weightlessness, surface global
attitude control, and orbital thermal cycling for a stable base mean
to support more familiar locomotion, allow construction, and Atmospheric composition, N2 78%; CO2 95.3%;
major constituents O2 21% N2 2.7%
provide raw materials for use. Inherent in this situation is a
Rotational period (sidereala) 23.93 h 27.3 days 24.62 h
greater degree of isolation, both from the standpoint of dis- Rotational period (solar) 24.00 h 29.53 days 24.65 days
tance from Earth and the additional gravity ladder that must Sidereala period (days) 365.26 686.98
be climbed to leave the new surface. Because of the extreme
Source: Data from Lodders [53] and Zeilik [46].
distances and inhospitable radiation environments associ- a
The term sidereal refers to time relative to the stars; solar is referenced to
ated with the moons of the giant planets, near-term surface Earths Sun.
1. Physical and Bioenvironmental Aspects of Human Space Flight
Terrestrially, most major trauma is associated with forces in
events such as motor vehicle accidents and falls. Surface vehi-
cles were used on the Moon and will certainly be required for
further lunar and Mars exploration. Falls were not uncommon
during the lunar EVAs, although those falls were not associ-
ated with injuries [54]. Traversing more challenging terrain
might easily lead to more serious falls, augmented by unfa-
miliar body mechanics. Carrying loads and obtaining samples
may induce muscle strain injuries, as occurred during the core
drilling operation on one lunar mission [23]. Construction
activities could also lead to penetrating trauma whereby an
EVA suit environment is compromised and injury is sustained.
These are the primary factors that drive a medical capabil-
ity involving the means to manage orthopedic and penetrating
trauma, as well as decompression disorders, beyond what is
required for LEO.
Surface Dust
The surfaces of the Moon and Mars are largely covered with
loose, unconsolidated rock material known as regolith. (This
term may also be applied to terrestrial surface rock and soils,
although the extraterrestrial implication is more common.)
Lunar regolith is fairly well known from first-hand observa-
tions and sample analysis; it consists primarily of fragments
less than 1 cm in size produced by shattering of material from
meteorite impacts. Local lunar regolith formation begins with
a nearby large impact that deposits large boulders and coarse
material excavated from bedrock. Over geologic time, smaller
impacts erode and fragment the coarse material, forming a
fine component, and given enough time, the original coarse
material disappears. Regolith can be 45 m thick in the lunar
mare and as much as 1015 m thick in the lunar highlands. In
a mature regolith, the subcentimeter component is called lunar
soil. The average grain size of analyzed soils is between 60
and 80 m [55].
During the Apollo missions, lunar dust established itself
early as a nuisance because of its physical properties and
associated difficulties in its control and cleanup. With the lack
of an atmosphere and in low-gravity conditions, lunar dust is
easily dislodged from the surface by walking, by operating
machinery, or by engine plumes. Lunar dust has a very low
electrical conductivity and is prone to building up an elec-
trostatic charge, with subsequent electrostatic deposition on
surfaces. It is hard, abrasive, and easily embedded in loose-
weave fabrics.
Although largely chemically inert, lunar dust did evoke
symptoms of respiratory irritation in some crewmembers. Dust
was introduced into the cabin atmosphere after ingress from
a surface EVA, adhering to the suits and equipment. Scientist
pilot Harrison Schmidt noted breathing irritation associated
with dust upon returning to the Lunar Module cabin after the
first EVA [56]. Some crewmembers used expectorants to facil-
itate clearance of the particles from the upper airways. Alan
Bean, during the Apollo 12 mission, observed that after lunar
23
liftoffa great quantity of dust floated free in the cabin. This
dust made breathing without the helmet difficult, and enough
particles were present in the cabin atmosphere to affect our
vision [57]. These effects seem to have been acute albeit mild
reactions to airborne dust particles deposited in and cleared
from the upper airways.
No lasting respiratory effects were seen in returning Apollo
crewmembers. However, the question arises regarding the pro-
pensity of lunar dust to cause chronic pulmonary diseases after
prolonged exposures, similar to terrestrial occupational lung
diseases. Pneumoconiosisinterstitial lung disease caused
by dust exposure and the lungs subsequent reaction to the
dustis caused by exposures to silica, coal dust, and asbestos
(fibrous silicate) dusts. Classic silicosis results from moder-
ate exposures to silica dust (SiO2) over many years, involv-
ing deposition of small particles into the alveoli and uptake
by alveolar macrophages. Subsequent activation of alveolar
macrophages causes them to release oxidants, cytokines, and
other mediators that injure surrounding tissue and stimulate
fibrosis. Typically, deposition occurs with particles in inspired
air of 5 m or smaller in size, with 1-m particles having the
best chance of deposition [58]; particles larger than 10 m in
diameter are effectively filtered by the upper and lower air-
ways. Deposition may be enhanced for particles with electro-
static charges [59].
Several factors make pneumoconiosis from lunar dust
unlikely. Silicate minerals, consisting of repeating crystal-
line structures of nonfibrous SiO4, are abundant and con-
tribute 90% of the volume of most lunar rocks. By contrast,
silica minerals, associated with terrestrial silicosis and char-
acterized by the repeating formula SiO2, are fairly rare on
the Moon [60]. In addition, the particles in the bulk of natu-
rally occurring lunar dust are large enough to preclude their
deposition in air exchange structures. More than 80% (by
weight) of dust grains from most Apollo samples are larger
than 20 m, and most of the smaller particles are still larger
than 10 m [55]. Certainly in the near future, exposures for
the periods associated with terrestrial pneumoconioses are
not anticipated.
The main health hazard associated with lunar dust will be
probably be interference with environmental and life sup-
port systems and pressure seals as well as a greater chance
of foreign bodies in the eye because of reduced gravity and
possibly local skin irritation from direct contact with this
abrasive material. However, bearing in mind that terres-
trial occupational lung diseases were largely unanticipated,
simple pulmonary monitoring for long-term lunar or Mars
inhabitants may be prudent. Periodic pulmonary spirometry
and chest x ray or an equivalent imaging modality could
be performed on site. In any case, means of dust control to
minimize levels in the habitable atmosphere will be neces-
sary both for crew health and mitigating adverse affects on
sensitive systems.
Unlike the lunar regolith, which is formed by repeated
impacts, Martian regolith is produced by physical weathering
24
and chemical activity [61]. Mars surface dust, although only
studied remotely, should be somewhat easier to control than
lunar dust, given the presence of a low pressure atmosphere
and a somewhat greater gravitational field. A particular haz-
ard condition on Mars is the known ability of dust particles to
become windborne. Wind speeds are seasonal, being lowest
during the Martian summer, at 27 m/s, and highest in autumn
and winter, at 510 m/s. Despite the rarefied atmosphere, suf-
ficient dynamic pressure periodically builds to cause large and
even global dust storms. During such storms, winds speeds
can increase to 30 m/s. Such a dust storm could potentially
halt surface activity for a period of several weeks to months
and threaten sensitive systems. However, the observation that
the solar-powered Viking Landers were able to function on the
surface for several years during the late 1970s suggests this
problem will not be insurmountable.
Conclusions
This chapter was intended as an overview of the basic body
of information required of the space medicine practitioner
to understand the adaptive and operational environment of
space flyers. An understanding of the physiologic and medi-
cal implications of this environment enables the practitioner
to provide optimal medical support. This information should
provide a foundation for discussions of physiologic and psy-
chological processes associated with space flight and allow
the response to medical events to be placed in proper con-
text. Understanding this context also prepares the spaceflight
surgeon to serve as a consultant in space program organiza-
tions, where human needs must fit into mission parameters
and priorities.
Acknowledgments The author thanks Drs. Kevin Ford, Stan-
ley Love, and Wendell Mendell for their thoughtful reviews
and constructive comments while this chapter was being
written.
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London, UK: Hodder Arnold; 2006.
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2
Human Response to Space Flight
Ellen S. Baker, Michael R. Barratt, and Mary L. Wear
Over the past 45 years of piloted space flight, we have gained
the knowledge, and indeed built the expectation, that humans
can adapt to this environment and endure long and productive
periods in space, up to and exceeding 1 year. Although the
dominant condition associated with space flight that affects
human physiology is weightlessness, other factors and phases
of flight can influence the health and performance of crewmem-
bers as well. Many of these factors have adverse consequences
and require operational considerations, countermeasures, and
protection. As such, an understanding of these factors and their
influences is necessary for optimizing human performance.
This chapter presents a comprehensive framework for
understanding the experience and clinico-physiological
response of human beings to space flight. This is purposely
not an exhaustive physiology review, but rather an overview
of consistent and predictable changes that are clinically rele-
vant. These changes include outward symptoms and effects on
health and performance as well as laboratory values and test
results deemed important for understanding the clinical norms
associated with space flight. Further physiological details
are included in the subsequent system-oriented chapters;
interested readers are also referred to the more detailed work
in the Handbook of Physiology [1] and the recent text Space
Physiology by Buckey [2].
By way of introduction, this chapter offers a brief history of
human space flight to provide a context for the current state of
knowledge of space medicine.
Historical Aspects of Space Medicine
Many questions were raised in the early 1960s as the United
States and Soviet Union were contemplating the first human
flights. However, based on the existing knowledge of aviation
and environmental medicine as well as educated speculation
at the time, the risk was considered acceptable to proceed with
the first few flights, and confidence was bolstered by the early
experience demonstrating that humans could tolerate space
flight reasonably well.
Medical and physiological data were collected from the
beginning of human space flight, consisting primarily of pre-
flight and postflight studies and passive inflight biomedical
monitoring oriented toward high-level crew safety and veri-
fication that subsequent programmatic steps could be taken.
Those steps included fundamental enabling technologies and
practices such as extravehicular activity (EVA), piloted ren-
dezvous and docking, and deployment of equipment. Early
results along with crewmember reports and experience helped
to quickly orient medical investigation and the provision
of inflight medical care. As human space flight grew more
routine, some missions specifically included assessments of
physiological responses and the gathering of medical data,
particularly with regard to systems most overtly affected.
Scores of biomedical experiments have now been conducted
during space flight, and a small number of missions dedicated
to life sciences issues have provided considerable detail about
some physiological systems.
Although much has been learned about how humans
respond to this new environment, that humans could tolerate
or even survive space flight was hardly a foregone conclu-
sion in the early days. The acceleration forces associated with
launch into orbit and reentry into Earths atmosphere, as well
as prolonged exposure to weightlessness, were seen by some
to preclude human existence, let alone performance of useful
work. The sentiments of the time preceding the first human
launches were nicely summarized by Charles Berry:
People who were concerned with the future of man in space quickly
became aligned with one of two points of view. On the one side, there
were the more cautious and conservative members of the medical
and scientific community who genuinely believed man could never
survive the rigors of the experience proposed for him. The spirit in
the other camp ranged from sanguine to certain. Some physicians,
particularly those with experience in aeronautical systems, were op-
timistic. It became the task of the medical team to work toward
bringing these divergent views toward a safe middle ground where
unfounded fears did not impede the forward progress of the space
program, and unbounded optimism did not cause us to proceed at a
pace that might compromise the health or safety of the individuals
who ventured into space. [3]
27
28
FIGURE 2.1. Summary of human spaceflight experience as of Decem-
ber 2005, tabulated as person-flight experiences of orbital launches and
depicting the relative flight durations. Suborbital flight experiences are
not included. The time category of 120 days includes independent
spacecraft and short-duration stays on orbiting stations; subsequent
categories involve long-term residence on orbiting stations
We now have decades of accumulated information and flight
experience from which to plan follow-on spaceflight activi-
ties. Figure 2.1 depicts the integrated experience of the Rus-
sian, U.S., and Chinese spaceflight activity to date, showing
the relative distribution of person-flight experiences over the
duration of flights. However, some of the sentiments echoed
above still ring true as we contemplate taking steps beyond
Earth orbit and subjecting crewmembers to additional
challenges to health and performance, such as the increased
remoteness and duration of missions, environmental exposures
such as radiation and planetary surface dust, and the physical
demands associated with lunar and Mars surface activities. In
this regard, the role of the flight surgeon and medical support
team remains much as it did in the formative years.
A Brief Chronology of Space Flight
The pioneering human steps into space, beginning with
Yuri Gagarins flight on April 12, 1961, were preceded by
directed ground experimentation with humans and animals.
This information was augmented with knowledge of human
performance in other environments analogous in their isola-
tion, crew composition, level of medical screening, and physical
demands, such as polar stations, submarines, and surface
ships. With regard to actual flight, the first terrestrial spacefar-
ers in both the U.S. and Russian programs were animals. The
Air Force Man-High and Navy Strato-Lab projects and
other balloon studies gave an understanding of and experience
with sealed cabin atmospheres in a near-spaceflight environ-
ment. The 1957 flight of Major David Simons, attaining an
altitude of 31,100 m (102,000 ft) lasted more than 32 h, with
E.S. Baker et al.
44 h actually spent in the capsule [4]. By comparison, the first
space flights were lasted several minutes to h. Life support
and medical monitoring systems, scientific observations, and
escape systems applicable to human space flight were fielded
and verified during these balloon flights, and psychological
and performance observations were made as well. The decade
of the 1960s, the briskly paced formative years of human space
flight, was begun with this information plus a fundamental
understanding of human tolerance to acceleration forces from
high-performance jet and rocket powered aircraft programs.
Most of the more overt and clinically relevant physiologi-
cal changes associated with space flight were identified early.
At the conclusion of the Gemini program in 1966, more than
2,000 man-hours had been accrued by U.S. flight crews, and
space flight was recognized to be associated with diminished
red cell mass, body calcium loss, diminished postflight exer-
cise capacity, and postflight orthostatic intolerance. By the
conclusion of the Apollo program, many of the basic obser-
vations had been made that remain at the core of the human
response to weightlessness (Table 2.1). Similar observations
and conclusions were made in the Russian program. Given the
effects of these findings on human performance, the goal of
both programs became to further characterize these findings
and to determine the mechanistic details underlying them, with
the aim of developing protective countermeasures that would
allow safe extension of human missions in space. To this end,
more directed flight programs were developed involving well-
equipped orbital laboratories and long-duration stays.
The first U.S. long-duration experience was the three Skylab
missions, flown in 1973 and 1974, each of which were crewed
by three men; these missions lasted approximately 28, 59, and
84 days. The Skylab flights were dedicated to the systematic
investigation of the physiological effects of space flight as well
as the conduct of astronomical, geological, and other experi-
ments and evaluation of equipment. Dietary issues, including
long-term food storage and provision of palatable foods, phys-
ical countermeasures including aerobic and resistive exercise,
and methods of medical and hygienic support were all tested
TABLE 2.1. Summary of significant biomedical observations in the
Apollo program [5].
Observation
Vestibular disturbances
Flight diet adequate; food consumption suboptimal
Postflight dehydration and weight loss
Decreased postflight orthostatic tolerance
Reduced postflight exercise tolerance
Cardiac arrhythmiasa
Decreased red cell mass and plasma volume
Negative inflight balance of nitrogen, calcium, other electrolytes
Increased inflight adrenal hormone secretion
No inflight diuresisb
a
Sustained bigeminy during lunar orbit and surface EVA during Apollo 15
mission.
b
An expected consequence of the thoracic fluid shift.
2. Human Response to Space Flight
and refined during this program. The biomedical findings of
these missions still stand as relevant contributions to space
medicine; among the more significant outcomes were the
development of procedures for efficiently operating a crewed
space laboratory and the practical experience of long-duration
flight. The Russian experience with the early Salyut stations
was similar to that of Skylab. By the mid 1970s, both nations
had concluded that humans could live and work effectively
in weightlessness for periods up to 3 months and that noth-
ing precluded longer missions if sufficient countermeasures
were available [6,7]. Further Russian space activities involved
a succession of orbital stations and longer duration missions;
after a lag of several years, the United States began flying the
Space Shuttle.
The U.S. Space Shuttle science program has made great strides
in working out details of human life sciences of short-duration
space flight (i.e., up to 17 days). The ability to fly sophisticated
laboratory facilities with interchangeable payloads and support-
ing sampling and analysis equipment, abundant power, additional
crew members (including trained scientists), and high-band-
width satellite communication have all been enabling aspects of
this program. Along with human life sciences, the Space Shuttle
program has benefited Earth observations, astronomy, materi-
als and physical sciences, and fundamental biology. One of the
more tangible benefits has been expansion of the basic medical
and clinical knowledge base owing to the large volume of human
flight experiences supported by this program. This knowledge
base has guided the development of successful medical opera-
tional support to ensure that crew health and performance levels
are sufficient to execute mission tasks.
By the early 1980s, the Russian flight experiences had
exceeded 6 months in duration, and the era of nearly continu-
ous Russian presence in long-duration flight had begun. The
Salyut series of space stations was succeeded by the vener-
able Mir station, which saw nearly continual crewed service
from 1986 through 2000. Mir hosted scores of crewmembers
in long-duration flights in addition to taxi and resupply flights
by the Soyuz and Shuttle. Russian specialists learned how to
maintain long-duration flyers for routine missions of 6 months
and longer, also building a systematic operational support pro-
gram emphasizing both physical and psychological counter-
measures. In addition, the Mir station provided a venue for the
United States to return to extended flight operations after a
20-year gap since the Skylab program. Seven U.S. crewmem-
bers flew long-duration missions on Mir in combination with
short-term Space Shuttle logistics flights.
The International Space Station (ISS) has seen continual
occupancy since 2000 and remains in assembly when this
chapter was written. The ISS will accommodate science and
technology development related to space flight and terrestrial
applications. Mature and validated countermeasures to adverse
effects of weightlessness and other practical products will be
produced to contribute to further exploration efforts. Among
the anticipated products will be an enhanced knowledge of
practicing medicine in space with a greater evidence base.
29
Preflight and Launch Factors
Space crews launching to Earth orbit, either for a short-term
mission or a long-duration stay aboard a station, have typi-
cally been in training for a few to several years. The demands
of this preflight training are rigorous, and usually training
requirements intensify in the few weeks to months preced-
ing launch. Health monitoring and physical countermeasures
are in place to ensure crew health, but accelerated training
requirements, travel, and sleep shifting to the inflight schedule
may lead to crew fatigue in the final days before launch. The
pressure to succeed, along with impending separation from
family and other social factors, can induce additional levels
of stress. It is important to take these factors into account in
developing prelaunch plans and schedules. Strict adherence
to schedule limitations, methodical and effective circadian
entrainment when sleep shifting is required, and limiting crew
contact with unscreened visitors to curtail transmission of
infectious disease are all part of the flight surgeons purview.
Since the beginning of human space flight and for the
foreseeable future, entry into space has involved a relatively
short chemical rocket ride into low Earth orbit, either as a final
destination or as a transitional phase for leaving Earth vicinity.
A typical transatmospheric flight for the Space Shuttle or
Soyuz lasts slightly more than 8 min, representing a best-fit
balance between ballistic factors and limitations of hardware
and crewmuch faster, and the greater acceleration loads
would exceed tolerance levels for crew and hardware; much
slower, and the vehicle stack would spend too much time in
the atmosphere, incurring excessive frictional heating and
requiring excessive propellant. Launch and landing are under-
standably the most critical phases of space flight with regard
to vehicle performance and crew safety, and history certainly
bears this out with the losses of the U.S. Space Shuttles Challenger
and Columbia and the loss of the Russian Soyuz 1 and Soyuz
T11 crews. As such, large portions of program infrastructure
and crew training are dedicated to the launch and landing
phases of space missions.
Without exception, crew positioning aboard spacecraft has
been oriented such that the major acceleration loads associated
with flight to Earth orbit are incurred in the most favorable
physiologic axis for sustained acceleration, that is, in the +Gx
(chest to back) direction. After donning pressure suits, crews
are seated and launch restraints are applied, usually between
1.5 and 2.5 h before launch, with crewmembers positioned in
a semi-recumbent, legs-elevated position. Launch loads in the
Shuttle and Soyuz programs are variable and typically peak at
about 3 G for the Shuttle and 3.7 for the Soyuz (see Chap. 1).
Vibrational forces also accompany launch into orbit and, in
combination with launch forces, may make throwing switches,
reading displays, accessing checklists, and other activities
requiring arm and head movements difficult. Background
noise can also interfere with voice communications. These
factors are accounted for in the design of hardware, displays,
communication systems, and crew restraints, and such activities
30
are routinely performed by flight crew members during ascent.
Flight crewmembers are constantly monitoring launch parameters
and vehicle performance, ready to execute abort procedures
and possibly assume full manual control if needed.
Ascent engines cut off abruptly, and the vehicle and crew
must transition quickly to the orbital flight phase. This phase
involves crew duties such as monitoring guidance and flight
parameters, additional engine burns to adjust and finalize
the orbit, loading new software into onboard computers, and
securing engines and other systems associated with ascent.
During this time, crewmembers may egress from restraints,
doff launch suits, and begin stowing items no longer needed
and deploying items needed during the orbital phase. The
immediate post-ascent phase is fairly demanding in terms
of crew activity, particularly as they are also adjusting to the
acute effects of weightlessness.
Weightlessness
Weightlessness is often misrepresented as a physiologically
challenging condition but is more accurately described as
an absence of the accustomed physiological challenges with
respect to the gravity vector, to which the body is typically
subjected daily in 1 G (one multiple of g, 9.8 m/s2, the gravi-
tational load at the Earths surface). For normally active
humans, steady state in 1 G is not steady at all with respect
to forces, but instead involves the dynamic and frequent reori-
entation of organ systems to the gravity vector during lying,
sitting, standing, and other activities. Many of these systems,
including the cardiovascular, pulmonary, neurovestibular, and
musculoskeletal systems, show specific or particular sensitivity to
force loading; their structure, function, and regulation are all
shaped by this gravitational dynamism. Stated simply, space
flight freezes the natural outside physical forces acting on
the body in a state of neutrality as compared with standard
postural and loading changes. Any tissue, receptor, or organ
system that depends on or is susceptible to hydrostatic
pressure gradients and loading will demonstrate alterations of
function and possibly morphology in weightlessness.
A few of the assumptions and conditions that bound our
understanding of microgravity physiology and human space
flight are worth highlighting and noted below.
The absolute effects of weightlessness on the human are
not known. What has been learned about human beings in
space has accumulated in the context of operational mis-
sions. We have not studied the absolute effects of weight-
lessness so much as the combined effects of weightlessness
with a multitude of other factors, such as physical activ-
ity associated with mission operations, deliberate exercise
countermeasures, psychological factors, environmental
parameters, medical investigations, medical treatments and
countermeasures, and other factors associated with space
flight. It is doubtful that we will ever have true microgravity
human control subjects.
E.S. Baker et al.
The immediate effects of weightlessness on the human are
not known. Relative to normal ambulatory conditions on the
ground, launch into space involves positional challenges,
acceleration forces, thermal loads, and psychological stress,
which all occur over an interval preceding the first exposure
to weightlessness. If the means were available to transition
immediately and cleanly from a normally active 1-G posture
into sustained weightlessness, certain physiologic details of
early adaptation could be seen that are otherwise masked in
the composite of forces and activities.
Adaptation to weightlessness occurs at different rates in
different systems. Multiple organ systems and tissue types
may react and adjust to weightlessness at different rates, pri-
marily based on the rapidity of response to loading in 1 G.
Secondary effects such as reduction in blood cell mass lag
behind primary effects such as reductions in plasma volume.
Processes requiring hormonal responses (e.g., certain fluid
regulation pathways) or cell turnover (e.g., skin desquama-
tion) will reflect their own timelines in their manifestations.
Longer-term processes are thought to include neuromotor
adaptation, which depends in part on experience, as well as
behavioral factors and exercise performance as the crew-
member settles into a balance of mission activities, nutrition,
physical countermeasures, and sleep schedule. Crewmem-
bers by and large are functional immediately upon arrival
into weightlessness, but several stages of adaptation occur
over periods of days to weeks as their physiological sys-
tems adapt to weightlessness, individually and in combina-
tion with other systems. For the sake of convenience, this
process can be considered in terms of specific systems or
performance parameters, but from the standpoint of overall
health and performance it represents a continuum. For some
systems, such as fluid regulation, an endpoint in adaptation
can be identified; for others, such as loss of bone density in
the skeletal system, the endpoint is not known.
Readaptation follows adaptation. Human space flight nec-
essarily includes two phases of physiological responsethat
of inflight adaptation, in particular to weightlessness, and
postflight readaptation after return to Earth. Both of these
phases follow predictable time curves with distinct starting
points, and both influence human performance and clinical
findings. This process applies both globally (overall health
and functionality) and on a systems level. Because certain
inflight changes can only be assessed before and after flight,
consideration must be given as to how these results could be
influenced by the multisystem readaptation process at the time
of assessment. Some flight activities will include intermediate
adaptation phases, as crewmembers are exposed to fractional
gravity fields of the moon or Mars, again followed by weight-
lessness and ultimately Earth return.
Standard investigative and diagnostic methods are often not
possible. Because of limitations in launch mass and volume,
power, sampling and sample storage, interference with other
activities, and the difficulties associated with fluid handling
and other laboratory techniques in microgravity, inflight data
2. Human Response to Space Flight
may not be collected with the same level of control and scientific
rigor as is possible during ground investigations. Investigators
and support technicians are replaced by multipurpose crew-
members, who serve as subjects and operators in addition to
performing their other flight-related duties. Life scientists
often must settle for less than optimal means of deriving
physiological and medical information during flight or simply
settle for observations made after flight.
The sample size remains small. As of the end of 2005, 971
human flight experiences (defined as reaching a sustainable
orbit) have taken place with 435 separate individuals. Spe-
cific medical parameters have been measured in standardized
fashions on only fractions of this group, and variability, both
between and within individuals, remains a strong factor.
Adaptation involves plasticity. Sustained weightlessness
provides a state in which the neutralization of forces influ-
encing physiological processes can be observed. Changes in
heart mass, baroreceptor sensitivity, and pulmonary ventila-
tion-perfusion distribution have been noted that suggest a
greater degree of plasticity in mature organ systems than was
previously thought.
Overall, the human response to weightlessness involves
adaptation without functional impairment, largely preserving
human work capacity as required by the new environment. As
noted throughout this book, the basic direction of adaptation
seems less like optimizing to weightlessness and more like
shedding physiological capabilities and functional control that
help in the 1-G world but are no longer needed in space. Most
of the impairment associated with space flight occurs when
the body must transition back to a steady-state gravitational
field. The exceptions to this are transient and occur in the
period immediately after launch.
Short-Term Responses
Given the requirement for rocket ascent into Earth orbit, it
is understandable that the transition from normal terrestrial
activity to weightlessness can be difficult. Crewmembers don
protective pressure suits several hours before launch, which
are uncomfortable and may involve a degree of heat stress.
Ingress to the tight quarters of the Space Shuttle or Soyuz is
followed by secure restraint into a launch and entry seat in a
supine position with the waist and knees flexed. Inevitably,
some of the fluid shifting from the lower extremities to the
central circulation begins in the vehicle before launch while
the crewmembers are seated in the required recumbent posi-
tion. After ascent, the transition to weightlessness is abrupt as
the engines switch off, and this transition is subjectively mag-
nified by the greater-than-normal forces experienced during
the preceding several minutes. Crewmembers experience sub-
jective feelings of floating out of the launch seat, being held
in place only by restraint straps. Whatever objects had been
resting unrestrained on the spacecraft floor now float free.
Some of the more prominent physiological effects of microgravity
appear almost immediately. The two dominant short-term
31
responses, each of which has multiple effects, are the thoracic
fluid shift resulting from loss of hydrostatic gradients and
neurovestibular disturbances, particularly in the form of space
motion sickness. Because these responses are immediate and
significant, they are described here separately from the
system-oriented discussions that follow.
Fluid Shift
Upon reaching weightlessness, a thoracic body fluid shift
beyond that induced by the launch position occurs in earnest,
and it is this fluid shift that underlies many of the immedi-
ate effects of weightlessness. A sensation of fullness in the
head is commonly reported, with onset in a few minutes to
a few hours of becoming weightless, occasionally accompa-
nied by nasal congestion. Some crewmembers equate this to
the feeling of hanging upside down on Earth. Within minutes,
objective facial edema and erythema may become apparent.
The volume of the lower extremities begins to diminish, and
the superficial vascular system of the upper body is seen to
engorge. Subjectively, crewmembers may complain of dis-
comfort associated with feelings of facial fullness, especially
behind the eyes and in the maxillary and frontal sinus areas.
The unpleasant sensation typically lasts from a few hours to
a few days, and it usually resolves to a tolerable level as new
set points for fluid regulation are established. Interestingly,
Skylab crews reported relief from these symptoms with cycle
exercise, presumably related to return of blood to the lower
extremities [8]. Fluid shifting contributes to many of the
findings noted later in this chapter regarding anthropometric
changes and fluid regulation.
Space Motion Sickness
From entry into microgravity until 34 days into flight, approx-
imately two thirds of Space Shuttle crewmembers experience
some degree of space motion sickness [9]. Space motion
sickness among U.S. astronauts was first described during
Apollo 9. The incidence was estimated to be 35% during the
Apollo program and 60% during the Skylab program. Reports
from the Russian program indicate an incidence of 4050%
among Salyut-6 and Soyuz crewmembers [10]. The syndrome
varies in symptoms and intensity and includes increased sen-
sitivity to motion, headache, diminished appetite, stomach
awareness, nausea, and vomiting. Onset of motion sickness
has occurred as early as 15 min and as late as 3 days after
reaching orbit. Symptoms generally last 23 days, but may
persist for up to 710 days in a small number of people. In the
U.S. program, the treatment of choice has been prometha-
zine, given by intramuscular injection. Promethazine has been
effective in more than 90% of cases; it is normally adminis-
tered late in the first day before sleep, and reported side effects
have been few [11]. In particular, sedation is rarely reported as
a side effect in space relative to ground use.
Increased motor activity and head movements worsen the
illusions and symptoms of motion sickness, whereas diminished
32
activity reduces the symptoms. Crewmembers are educated
before flight and also discover for themselves that slower
movements are less provocative. Consciously maintaining a
sense of a vertical in the environment also seems to be
protective for many crewmembers during the early hours of
flight. Purposely restraining the feet and bending down
to retrieve an object rather than flipping upside down with
the newfound freedom of movement, for example, is a wise
choice early on. From a mission management perspective,
EVA sorties are not scheduled within the first 72 h of launch
to accommodate neurovestibular adaptation and to allow any
symptoms of space motion sickness to clear.
Anthropometric Changes
The basic structure of the human body is a result of long-term
terrestrial development. However, certain aspects of body
size and shape are more dynamic and may be influenced by
force loading. Although variability exists between individuals,
predictable trends are seen that influence the fit of highly
customized garments and spacesuits as well as physical crew
interfaces with the spacecraft such as work station restraint
systems, medical and sleep station restraints, and landing vehicle
couches. Internal motion and redistribution of organs may
result secondarily from postural and musculoskeletal changes
or independently from effects of fluid shifting and floating, all
of which can influence findings on physical examination and
medical imagery. Both internal and external findings may be
influenced by the more long-term changes in physical activity,
metabolism, and energetics associated with space flight. An
understanding of these processes and findings is important to
space medicine practitioners and hardware designers alike.
Body weight is a fundamental clinical measure reflect-
ing immediate fluid balance and, on a more long-term scale,
metabolism. Generally some degree of weight loss has been
noted after both short- and long-duration flights. Buckey et al
reported an average loss of 1.1 kg in 14 subjects immediately
after 10- to 14-day Space Shuttle flights [12]. Measurements
obtained before and after flight can be compared but are sub-
ject to changes and fluid shifts during landing, and of course
cannot guide inflight activity such as nutritional support and
performance of countermeasures. The ability to assess body
mass during flight was recognized early as a health monitor-
ing requirement by the Russian and U.S. programs. Body
mass has for years been determined in weightlessness by
means of fixing the body to a linear spring-tension system and
inducing oscillating motion. Knowing the mechanical char-
acteristics and in particular the spring-constant of the system
allows body mass to be assessed by the timing of the oscilla-
tion cycle. Currently on the ISS, body mass is measured every
2 weeks during long-duration missions.
Losses in body mass of 45% are typical in long-duration
flights and most likely result from negative dietary and energy
balances [13,14] (see Chap. 27). A decline of a few kilograms
below preflight baseline at the end of a 6-month mission is
E.S. Baker et al.
common, although considerable variability has been noted. In
describing a series of flight experiences on the Salyut 6 station
lasting between 96 and 185 days, Kozerenko et al. reported
losses up to 5.4 kg and, less often, gains in body mass, with a
maximum gain of 4.7 kg [15]. Smith and colleagues reported
a mean body weight loss of 5% for 11 astronauts aboard the
ISS for 128- to 195-day missions [16]. Although inflight find-
ings reflect individual variability and are subject to sporadic
measurements, most of the mass loss seems to occur within
the first 48 weeks of flight, followed by a slower decline or
plateau for the duration of the mission.
Limb volume, as determined by standardized circumference
measurements, provides another more easily obtainable mea-
sure of tissue mass, reflecting body fluid shifting and muscu-
lar growth or atrophy. Typically calf circumference decreases
rapidly within the first 48 h of flight in association with acute
thoracic fluid shifting, which is not necessarily coupled to
body mass loss. Buckey et al. reported a mean leg volume loss
of 748 ml after Space Shuttle flights of up to 14 days [12]. In
longer flights, this acute drop is followed by a more gradual
decline associated with muscular atrophy, typically reaching a
plateau depending on response to countermeasures and other
individual factors. Measurements from two cosmonauts fly-
ing a year-long mission on the Mir station showed that calf
circumference declined steadily to about 20% below preflight
baseline, whereas arm and forearm circumference remained
essentially unchanged [17]. Figure 2.2 shows calculated left
upper and lower limb volume loss for three Skylab crewmembers
during that 84-day flight.
Changes in thoracic and abdominal anthropometry reflect
axial unloading and perhaps represent the greatest threat to
fitting highly customized garments and restraints. Observed
increases in seated height in weightlessness presumably result
from expansion of the unloaded intervertebral disks and loss
of the thoracolumbar curvature [18]. Most of the increase
occurs during the first 2 weeks and then stabilizes at approxi-
mately 3% above the preflight baseline [19]. A corresponding
decrease in abdom inal girth is seen as the abdominal viscera
float in a rostral direction and are pushed in by unopposed
abdominal muscle tone, with a lesser decrease in chest girth.
Figure 2.3 shows trunk measurements for two Skylab crewmem-
bers during the 84-day flight.
+0.3
Volume change, liters
0
-0.3
-0.6
-0.9
-1.2
Arm
-1.5
Leg
0 4 8 31 37 57 59 82 0 2 4 6 8 10
Launch Landing
Mission Day
FIGURE 2.2. Changes in left limb volume for three crewmembers on
the Skylab 4 mission. Combined/redrawn from [18]
2. Human Response to Space Flight 33

+6 Postural changes also follow predictable trends and are

+4 relevant to the design of inflight crew systems. The neutral
+2 body posture assumed in weightlessness (Figure 2.4) typically
Change, cm

0 includes flexion of the musculature proximal to the limbs

-2 and thoracolumbar straightening with retention of the cervi-
-4 Height Circumferences cal curvature, resulting in neck flexion. This position should
Chest (insp)
-6 Chest (exp) be accommodated by crew restraints at work and sleep sta-
-8 Waist
tions; any other shape forces the body out of this position.
-10 Crewmembers testing a conventional medical restraint system
0 10 20 30 40 50 60 70 80 R+10 +17 during the STS-40 Space Shuttle mission noted significant
Mission Day
discomfort with being restrained in an Earth-normal recum-
bent position [20].
FIGURE 2.3. Changes in trunk measurements for two Skylab crewmem-
bers during the 84-day flight. Combined/redrawn from [18]
Physical Examination Findings
Physical examination is a time-honored means of obtaining vital
information without the use of invasive techniques, electrical
recording, or imaging. As is true on Earth, physical examina-

FIGURE 2.4. The neutral body posture assumed in weightlessness. Segment angles shown are means; values in parentheses are standard
deviations. Data were developed in Skylab studies and based on measurements from three subjects [19]
34
tion has a crucial role in space flight for making initial diagnoses
and for monitoring health trends. Considered in light of medi-
cal history, findings from physical examination can hasten the
diagnosis and treatment of an ill or injured crewmember and
help to direct the use of other available investigative studies,
which must be used strategically because of resource limita-
tions. Most of the basic techniques and instruments used in
terrestrial physical examination and diagnosis have been
used during space flight. However, the known multisystemic
physiological adaptation to weightlessness suggests that nor-
mal physical findings achieve new baselines, which must be
considered for monitoring health and for interpreting new-onset
possibly abnormal findings.
Harris et al. developed a systematic method for performing
physical examinations in weightlessness [21]. The techniques
involved were verified during ground and parabolic flight ses-
sions and then performed on seven subjects during the course
of an 8-day Space Shuttle flight by a physician astronaut.
Subjects underwent preflight and postflight examination and
served as their own controls. Findings from longer flights are
expected to reflect findings that may not have been captured
by this investigation; however, the results of Harris study
constitute the most complete systematic collection of space
normal physical findings obtained by inflight physicians thus
far. Major findings are presented below in the order of their
performance during a standard physical examination, with
corroboration and supplementation from other sources as
available. Genitourinary and rectal systems were not examined.
Eyes: Mild conjunctival erythema noted in some crewmem-
bers, otherwise no changes. Normal funduscopic exam with
no papilledema [21]. Increases in intraocular pressure of 92%
during the first 16 min and then by 2025% after 44 min of
flight [22], suggesting a trend towards normal over time.
Ears: No significant changes from preflight assessment
[21].
Nose: Generally showed increased erythema and edema of
nasal mucosa [21].
Throat: Slight hyperemia of mucosal membranes [21].
Neck: Jugular venous distension extending along entire
length of neck [18,21]. Increase in jugular vein cross section
via sonography [23].
Skin: Acutely edematous and hyperemic on face and upper
body; prominent eyelid edema. Some subjects showed hyper-
emia and injection of conjunctivae and mucosal membranes
[21]. Loss of calluses on feet and normal weight-bearing skin
surfaces are noted after weeks in long-duration flight.
Chest: Barrel appearance resulting from standard anthro-
pometric changes [18,21]. Elevation of the diaphragm by one
to two intercostal spaces, with corresponding decrease in basal
lung sounds in some crewmembers.
Heart: No discernible difference in intensity or rhythm.
Substernal displacement of point of maximal impulse in four
of seven subjects, not palpable in three [21].
Abdomen: Flattened abdominal contour [18,21]. Dimin-
ished bowel sounds in five of seven subjects, increasing over
E.S. Baker et al.
time but not returning to baseline. Rostral relocation of liver
and spleen by palpation [21].
Musculoskeletal: All subjects assumed the neutral body
posture. Noticeably diminished size and thinning of large
muscle groups of lower extremities [21].
Neurological: Brisker tendon reflexes noted in five of seven
subjects [21].
The following sections address more specifically the known
clinical changes in specific physiological systems associated
with weightlessness.
Cardiovascular System and Volume Regulation
The cardiovascular system, which can be simplistically des-
cribed as a closed hydraulic circuit oriented along the bodys
longitudinal axis with a more or less centrally located pump,
is one of the systems most influenced by hydrostatic gradi-
ents. In an effort to maintain end perfusion of body tissues
and support oxidative metabolism in highly variable demand
states, a complex system of interrelated subsystems and
responses (neural, renal, endocrine) serves to compensate for
dynamic changes in these hydrostatic forces as the body reori-
ents itself relative to the gravity vector and responds to other
physiologic perturbations. Volume-sensitive stretch recep-
tors (baroreceptors) reside in the aorta and carotids in large
numbers and normally help to mediate the rapid response to
gravitational stresses to central circulation. Increasing pres-
sure induces the firing of afferent nerves from baroreceptors
to stimulate a centrally integrated and parasympathetically
mediated vasodilatation and reduction in cardiac output in
an effort to maintain normal arterial pressure. Conversely,
a reduction in sensed pressure by the baroreceptors stimu-
lates a centrally mediated sympathetic response, driving the
opposite effect to maintain pressure during acute reductions.
This baroreceptor reflex preserves pressure during postural
changes, particularly in moving from recumbent to seated to
standing positions [24].
In weightless environments, many of the non-gravitation-
ally oriented factors that could influence demand and hence
cardiac output (e.g., exercise, cold stress, volume loss, hypoxia)
remain unchanged. However the hydrostatic gradients vanish,
along with them the periodic stimulus for maintaining cardiac
output under various orientations to gravitational loading.
Venous pressure, normally under a significant gravitational
influence, essentially equalizes throughout the body and
directly reflects right atrial pressure. The changes of the car-
diovascular and fluid regulatory system largely reflect the
removal of these hydrostatic gradients and, to a lesser extent,
the hypokinesia relative to terrestrial activity.
Investigations of cardiovascular variables during space flight
has been driven largely by the early recognition of postflight
orthostatic intolerance and attempts to elucidate how adapta-
tion leads to this maladaptive condition on return to Earth.
Some of the major findings associated with the cardiovascular
system in weightlessness observed during carefully controlled
2. Human Response to Space Flight 35

studies are summarized in Table 2.2. Unless otherwise noted,
these findings are based on inflight measurements; the
exceptions are for those variables less influenced by the immediate
reverse fluid shifts and other dynamic effects of landing, such
as cardiac mass and red blood cell (erythrocyte) mass. The
major time division is artificial and tied to vehicle experience. Space
shuttle flights have included sophisticated science payloads
and allowed high-fidelity results, but of course are time-lim-
ited (up to 17 days in duration). Longer-duration flights from
space station programs are better platforms for characterizing
the long-term human response and changes over time. Gener-
ally speaking, the cardiovascular system undergoes predict-
able changes but adapts well to prolonged weightlessness,
with a few significant findings.
Cardiovascular changes such as increased cardiac output due
to increased cardiac filling and stroke volume begin very early
during flight, accompanying the immediate central fluid shift.
The observed maintenance of mean arterial pressure implies
a corresponding decrease of peripheral vascular resistance.
Unlike that in the terrestrial supine position, central venous
pressure does not increase in response to this shift in weight-
lessness [26]. This may relate to the increased thoracic diam-
eter consistent with the anthropometry changes noted above.
Parabolic flight studies have corroborated the thoracic shape
change [39] as well as the concomitant decrease of central
venous pressure immediately upon entering weightlessness
[40]. A lower thoracic pressure may result in lower central
venous pressure and increased cardiac output, but would also

TABLE 2.2. Major cardiovascular findings associated with weightlessness.

Variable
Heart rate
Heart rate variability
Systolic blood pressure
Diastolic blood pressure
Mean arterial pressure
Central venous pressure
Systemic vascular resistance
Plasma volume
Red blood cell mass
Echocardiographic findings
Left ventricular end diastolic volume
Left ventricular End systolic volume
Stroke volume
Left ventricular mass
Cardiac output
Short-term response (Max 17-day flight) Long-term response
Slightly decreased in comparative 24-h ambulatory studies, Unchanged c/w preflight, measured FW 8, 16, and
n = 12 [25]. No change early in flight c/w preflight seated 24, n = 4 [29]; unchanged at 1,3, and 5 months,
(n = 3 [26]; n = 4 [27]) or minimally decreased c/w supine n = 6 [23]; 1012 bpm n = 2, and to
(n = 6 [28]) moderate bradycardia n = 1, measured
periodically during 8-month flight [30]
Decreased in comparative 24-h ambulatory studies, n = 12 [25]
Unchanged, comparative 24 h ambulatory studies, n = 12 [25] Unchanged while awake, slightly during sleep c/w
preflight, measured FW 8, 16, and 24, n = 4 [29];
unchanged at 1, 3, and 5 months, n = 6 [23]
Decreased in comparative 24-h ambulatory studies, n = 12 [25]; slightly c/w preflight, measured FW 8, 16, and
c/w preflight supine, n = 6 [28] 24, n = 4 [29]; unchanged at 1, 3, and 5 months,
n = 6 [23]
Unchanged c/w preflight seated, FD1 and FD 7/8, n = 4 [27]; Unchanged at 1, 3, and 5 months, n = 6 [23]
c/w preflight supine, n = 6 [28]
8.42.5 cm H2O c/w seated preflight, FD1, n = 3 [26]
Unchanged to slightly decreased c/w with preflight supine, n
= 1 [31]
No change early in flight c/w preflight seated, n = 3 [26];
24% FD1 and 14% FD8, n = 4 [27]
17% in first 24 h, then stabilizing at 1015% by FD 5, 8.4%, n = 3, R + 0 of 28-day flight; 13.1%,
n = 6 [32] n = 3, R + 0 of 59-day flight; 15.9%, n = 3,
R + 0 of 84-day flight [33]
10% within 1 week, n = 6 [34] 11.1%, n = 9, R + 0 of 28-, 59-, and 84-day flights
[33]
4.604.97 cm c/w preflight supine, n = 3 [26] 824% at 1, 3, and 5 months, n = 6 [23]
No change, n = 3 [26] up to 19% n = 2, and up to 20% n = 1, measured
periodically during 8-month flight [30]
46% c/w preflight standing, n = 4 [35]; 5677 ml, 1016% at 1, 3, and 5 months, n = 6 [23];
n = 3 [26]; 55% c/w preflight standing, 9% c/w supine, 1215%, n = 2, and up to 20% n = 1, measured
n = 6 [28]; 40% early in flight (n = 2), followed by return periodically during 8-month flight [30]
to preflight values [36]
12% c/w preflight, n = 4 postflight measurement after 10-day
flight [37]
8% c/w preflight, n = 3, postflight measurement after 84-day
flight [38]
c/w prelaunch supine, FD1, n = 3 [26] 17%20% at 1, 3, and 5 months, n = 6 [23]
c/w prelaunch seated, 29% FD1 and 22% FD 7/8, n = 4 [27];
26% c/w preflight standing, unchanged c/w supine, n = 6
[28]; 18% c/w preflight standing, n = 4 [35]

Abbreviations: FD, flight day; FW, flight week; , increase; , decrease; n, subject number; c/w, compared with.
a
Measured as part of a study of the effect of thigh cuffs on cardiovascular dynamics in space flight. Cuffs were worn 10 h each day, but measurements were
taken before the cuffs were put on.
36
be expected to increase lung volumes. As described in the
next section on pulmonary findings, the opposite is seen. This
seeming paradox remains to be definitively resolved, and is
discussed in detail in Chap. 16 and by Buckey [41].
Plasma volume loss also begins early, with a predominant
mechanism being extravasation from the vascular space to the
intracellular space, apparently because of increased capillary
permeability [32]. A resulting increase in hematocrit is seen
along with other factors leading to inhibition of erythropoietin
[34]. Over the course of several days, stabilization of plasma
volume is accompanied by a reduction in red blood cell mass
to an appropriate space flight set point, with normalization
of hematocrit [34]. The decrease in erythrocyte mass seems
to involve a process of selective hemolytic removal of the
youngest erythrocytes (neocytolysis), facilitating more rapid
adaptation to the microgravity circulatory state [42]. This
state represents a basic euvolemic set point for weightless-
ness (1015% reduction in plasma volume, 10% reduction in
erythrocyte mass).
Diuresis is not observed to accompany the fluid shifting and
resetting to lower plasma volume in the first days of flight, in
part because of decreased fluid intake related to reduced thirst
and space motion sickness and possibly due to intracellular
fluid shifts. Further changes over time include a decrease in
cardiac chamber dimensions to reflect the new volume status.
New homeostatic conditions for central circulation seem to
most closely mimic those associated with the terrestrial seated
posture [26,43]. Eventual decreases in resting cardiac output,
left ventricular mass, and chamber volumes are seen, stabiliz-
ing to reflect the new balance between physical activity, diet,
and fluid volume status. Cardiopulmonary performance
is discussed in a separate section below, but in general left
ventricular contractile function is maintained as normal as
assessed by echocardiography after 3-month [38] to 8-month
periods of weightlessness [30].
Given that the baroreceptors, which normally help to medi-
ate the rapid response to gravitational stresses to central circu-
lation, are relatively unchallenged in zero G, downregulation
of this function would be expected. Although the aortic and
cardiopulmonary baroreceptors are difficult to test directly,
the carotid baroreceptors may be selectively and temporarily
deformed with a form-fitting pressure cuff. Under those con-
ditions, the normal heart-rate and blood-pressure responses
to carotid baroreflex activity are seen to be diminished both
during [44] and after short-duration Shuttle flights [45,46].
Changes in these responses to Valsalva maneuvers and respi-
ratory frequency R-R interval spectral power further suggest
decreases in parasympathetic control of blood pressure and
baroreflex gain during both short-duration [46,47] and long-
duration (9-month) flights [48]. Sympathetic neural control
seems to be maintained, as ascertained by inflight responses
to lower-body negative pressure (LBNP), which mimics the
lower-extremity volume redistribution of assuming an upright
posture on the ground. Increases in heart rate, blood pressure,
and peripheral vascular resistance accompanied decreases in
E.S. Baker et al.
stroke volume, suggesting that the inflight status reflects
primarily the relative fluid deficit with normal [49] or even
exaggerated sympathetic response to orthostatic stress [50].
No evidence exists to suggest that the cardiovascular
changes associated with normal adaptation to weightlessness
are clinically threatening or functionally limiting of inflight
mission requirements. Particular attention has been paid to
the incidence of arrhythmias arising from space flight such as
those involving ventricular bigeminy and profound bradycar-
dia during an Apollo mission [51], paroxysmal supraventricu-
lar tachycardia arising during and persisting after EVA [52,53],
and a run of ventricular tachycardia caught incidentally during
a 24-h Holter study [54]. However, other stressors that may lead
to arrhythmias are also present during space flight, including
high physical workload, fatigue, psychological stress, hydra-
tional challenges, and electrolyte changes. Attempts are made
during astronaut selection to screen out those with underlying
coronary artery disease, but the relatively high prevalence of
this condition and the difficulties involved in screening it out
with 100% accuracy cannot totally preclude the possibility
of someone with coronary artery disease flying in space. In
a few astronauts, clinical manifestations of coronary artery
disease appeared within 2 years after space flight, and the
arrhythmias noted may have reflected the presence of under-
lying disease. Closer systematic investigation into incidents
of inflight arrhythmias has revealed no increase in incidence
during Shuttle flights, either during normal activities [25] or
during EVA [55].
Acceleration and vibrational forces, along with the factors
noted above, are also known to induce cardiac arrhythmias.
Cardiac monitoring during the more dynamic phases of flight
was instituted beginning with the first space flights; crew-
members wore electrocardiographic monitors during launch
and landing in the first three major U.S. programs, and they
continue to do so in the Russian program. In parallel with
space program experience, aviation medical studies involv-
ing hundreds of subjects have demonstrated that a wide vari-
ety of arrhythmic conditions normally accompany exposure
to acceleration that are not associated with impairment and
do not reflect underlying abnormalities [56]. Those studies
involved healthy, non-deconditioned subjects exposed to +Gz
accelerations up to 9 G. A follow-on study showed no differ-
ence between men and women [57]. These findings, coupled
with observations during the early space program of a lack of
negative clinical events correlated with these findings, led to
the abandonment of cardiovascular monitoring during launch
and landing phases early in the Space Shuttle program. Heart
rate and rhythm are still monitored during EVA, where the
physiological margins are lower and the workload is particu-
larly high, as well as during inflight activities that may involve
more specific risk of arrhythmogenic responses (e.g., LBNP
and maximal exercise testing). In such cases, real-time man-
agement decisions can be made based on the cardiac findings,
such as calling for rest in the EVA cycle or terminating the
LBNP session.
2. Human Response to Space Flight
Respiratory System
As is true of the cardiovascular system, the respiratory system
is affected during the process of adaptation but is not function-
ally impaired during flight, and no reports have been made of
difficulty in breathing or other primary respiratory complaints.
However, the respiratory system is an open-loop system and
unique in its potential for interaction with the environment,
particularly in a sealed cabin with an artificial atmosphere void
of the most prominent natural forces that normally remove
particulates and heavy aerosols. Secondary effects, reactive
symptoms to dust and contaminant exposure, may overlap with
other expected effects of adaptation. Distinguishing between
headward fluid shifting and atmospheric nuisance dust causing
the often-reported nasal stuffiness can be difficult, and head-
aches early in the mission caused by a contaminant such as
CO2 can be confused with space motion sickness.
The risk of aspirating foreign particles in the weightless
environment is higher than that on Earth, and mild cough reactions
from such events are not uncommon. The risk is further
elevated with activities that could cause inadvertent release of
particulates, such as large-scale stowage transfer operations
involving movement of fabric bags, and when minute venti-
lation is high, such as during exercise. Efforts are made to
decrease the particulate levels during construction, outfitting,
and ground processing of modules and payloads by carefully
selecting materials and foods and by using standardized
processes for handling fluids and particulates. Forced air circula-
tion and use of high-efficiency particulate-absorbing filters on
ISS actively reduce the atmospheric particulate burden there.
High-risk activities such as cleanup of spills and transfer of
some materials prompt crewmembers to don protective masks.
Aerosols may be released from leaking fluid lines, as occurred
when ethylene glycol coolant leaked onboard the Mir station,
and particulates and contaminant gases can be released from
pyrolysis events such as those that occurred on the Shuttle
(STS-40) and the Mir station (further discussed in Chap. 21).
The lungs themselves, easily deformable and well known
to be sensitive to gravitational loads, are expected to undergo
changes in weightlessness. Gravitational and other accelera-
tion forces are particularly influential in a system whose func-
tion depends on regional interaction between substances of
vastly different densities, namely gas-filled lung tissue and
blood. The upright posture involves a gradient in which apical
regions are less well perfused than basal regions, contribut-
ing to alveolar dead space and creating a regional mismatch
between ventilation and perfusion. The supine posture reduces
this mismatch, limiting the vertical gradient to the antero-
posterior dimension of the lung. In a high +Gz environment,
overall compliance of the respiratory system (lungs and chest)
decreases. The diaphragm is displaced downward (caudally),
resulting in an increase in functional residual capacity and
tidal volume; reflex increases in abdominal wall tension and
abdominal pressure prevent full diaphragmatic movement
and reduce vital capacity [58]. However, functional reserves
37
exist to maintain sufficient pulmonary gas exchange dur-
ing transient high-G exposures and sustained moderate-G
exposures in rotating rooms. The known changes of thoracic
shape and upward movement of abdominal viscera seen in
weightlessness represent the opposite of this condition, and
they also influence chest wall mechanics. During a short-dura-
tion Shuttle flight as well as a long-duration flight on Mir, the
abdominal contribution to tidal volume was shown to increase
significantly [59].
A small number of Space Shuttle missions dedicated to life
sciences investigations have produced precise measurements
of pulmonary indices from crewmembers on these short-dura-
tion flights. These measurements are summarized in Table
2.3. Changes reflect the early process of adaptation, as forces
of fluid regulation, cardiovascular dynamics, abdominal and
chest shape change, and perfusion distribution strike a new
balance. Performance of standard crew duties and exercise are
not impaired. Neither oxygen uptake nor CO2 output change
in microgravity [60]. The ventilatory response to hypoxia is
attenuated in microgravity, persisting during a 16-day mission
among five subjects and resolving quickly after return; how-
ever, ventilatory response to hypercapnia was unchanged from
preflight values [61].
Decreases in tidal volume, with partially compensating
increases in respiratory frequency, have been observed; this is
TABLE 2.3. Pulmonary changes associated with space flight.
Variable Short-term response (Max 17-day flight)
Respiratory 9% c/w preflight standing, n = 8, 2 Shuttle flights of
frequency 9 & 14 days [60]
Tidal volume 15% c/w preflight standing, n = 8, 2 Shuttle flights
of 9 & 14 days [60]
Vital capacity 5% after 24 h c/w preflight standing, then resolve to
normal by 72 h, n = 7, during 9 day flight [62]
Forced vital capacity 35% on FD2 c/w preflight standing, then resolved
to normal by FD4, slightly by FD9, n = 4 [63]
Peak expiratory flow 12.5% c/w preflight standing on FD2, 11.6% on
rate FD4, and 5.0% on FD5, returned to norm by FD9,
n = 4 [63].
Functional residual 15% c/w preflight standing but higher than preflight
capacity supine, n = 7 [62].
slightly early inflight c/w preflight, n = 2, resolved
to normal later inflight, n = 4 [36]
Residual volume about18% c/w preflight standing, n = 4 [62]
Alveolar ventilation Unchanged, n = 8, 2 Shuttle flights of 9 & 14 days
[60]
Tissue volume About 24 h, n = 2 no change; At FD9 & 10, n = 4, a
25% decrease c/w preflight controls (p < 0.001).
(Concomitant reduction in stroke volume, to the
extent that it was no longer significantly different
from preflight control.)
Pulmonary diffusing DLco and the membrane component (Dm) both
capacity (DLco) increase 28% c/w preflight standing after 24 h,
unchanged over 9 days, n = 4; DLco increased 13%
about 24 h into flight, n = 2, maintained at 13%
FD9/10, n = 4 (different method)
Abbreviations: FD, flight day; c/w, compared with.
38 E.S. Baker et al.

fully compensated by an observed decrease in physiological Bone

and alveolar dead space, attributed to more uniform distribu-
Bone integrity and calcium homeostasis are issues of concern
tion of pulmonary perfusion in the weightless environment
for long-duration space flight. Conditions of immobilization
such that alveolar ventilation remains normal [60]. Decreases
such as spinal cord injury [67,68] or deliberate bed rest [69,70]
in residual volume relative to preflight standing and supine
are well known to be accompanied by loss of bone mineral
values presumably reflect the diminished regional apico-basal
density (BMD). Measurable decreases in BMD have been
gradients seen on the ground [62]. Vital capacity [62] and
reported in professional scuba divers, presumably caused by
forced vital capacity [63] each undergo slight decreases within
the decreased loading associated with water immersion [71].
24 h of arriving in weightlessness, both resolving to normal
Loss of mineral from weight-bearing bones has been well
within 34 days. This early decrease in vital capacity has been
documented since the first long-duration space flights [72],
suggested to reflect the initial increase in intrathoracic blood
in combination with loss of bone density, loss of body cal-
volume, resolving as plasma volume decreases over the same
cium and phosphate, and decreases in calcium absorption. The
time course [34,64]. Despite early concerns that pulmonary
development of advanced assessment techniques and assays
edema would result from thoracic fluid shifts, diffusing capac-
for metabolic markers over the past two decades has enabled a
ity has been seen to increase during flight [35,36], presumably
better understanding of the process, although the mechanistic
because of more uniform capillary filling and the subsequent
details have yet to be fully identified.
increase in effective surface area supporting diffusion [35].
Bone mineral is lost preferentially from the weight-bear-
Although investigations indicate that the gravitationally sensi-
ing bones, including the lower extremities, lower pelvis, and
tive apico-basal gradients are largely absent in microgravity,
lumbar spine, during space flight. Loss in BMD at the rates
cardiogenic oscillations in expired oxygen and CO2 persist
incurred by space flight or bed rest typically requires several
[60,65], suggesting some nongravitational regional inhomo-
weeks to detect via imaging studies. For Skylab crewmembers,
geneity in ventilation perfusion. This topic is further discussed
photon absorptiometry did not detect bone loss in the calca-
in an excellent review by Prisk [64].
neus in the crew on the 28-day flight, but showed a 7% loss
Little information is available on pulmonary variables
for those on the 59-day flight and an 11.2% loss for those on
during long-duration missions, although many of the acute
the 84-day flight [69], with no losses seen in the distal radius
changes in volumes seem to resolve early in the course of short-
or ulna. Crewmembers on the Mir station flying multimonth
duration flights, and observations during exercise and EVA
missions lost BMD at an average monthly rate of 0.3% from
over the course of several months indicate no perceived limi-
the total skeleton, with 97% of that loss coming from the pel-
tation to pulmonary performance. During a 6-month mission,
vis and legs as assessed by magnetic resonance imaging and
vital capacity and expiratory reserve volume, measured in two
dual X-ray absorptiometry [73]. LeBlanc and colleagues used
subjects, was seen to reflect preflight supine values on FDs 9
dual X-ray absorptiometry to define the rate and distribution
and 175 [66]. On the day after return to Earth, vital capacity
of bone loss from long-duration missions in 18 cosmonauts
had decreased by 30%, presumably because of decreases in
(Table 2.4) [74]. In another study of 14 ISS crewmembers,
expiratory reserve volume and inspiratory capacity attributed
BMD was shown to be lost at a rate of 0.9% per month at the
to weakening of respiratory muscles. Future activities on the
spine, 1.41.5% per month at the hip, and 0.4% per month
ISS should help to further characterize the effects of long-
at the calcaneus [75]. Loss in BMD in these regions in ISS
duration space flight, if any, on pulmonary function.
crewmembers (Figure 2.5) identifies these areas as targets for
countermeasures [76].
Musculoskeletal System Calcium loss from the skeletal system, which also serves as
the bodys storage pool of this mineral, begins early in flight.
The musculoskeletal system provides the framework and
During comprehensive metabolic monitoring studies on Skylab,
means of motion, locomotion, and force exertion for the
human body. Muscle and bone are vital tissues that continually
respond structurally and functionally to loads, increasing TABLE 2.4. Changes in bone mineral density after 414.4 months of
space flight [74].
in mass and strength in response to sustained exposures to
increasing loads and decreasing with diminishing loads. As Percent change Standard
Anatomical site No. of subjects per month deviation
such, the musculoskeletal system is directly shaped by the
Spine 18 1.06* 0.63
outside loads against which it must react and oppose. The
Neck 18 1.15* 0.84
skeletal system provides rigid attachment points for the skeletal Trochanter 18 1.56* 0.99
muscle that moves the body and also applies direct loads Total 17 0.35* 0.25
to the bone at these points, further influencing bone struc- Pelvis 17 1.35* 0.54
ture. Working in concert, the muscles supplying the power Arm 17 0.04 0.88
Leg 16 0.34* 0.33
and the bones supplying the framework and system of levers
for force exertion, these two systems cannot, in practice, be *
p < 0.01.
considered separately. Source: From A LeBlanc et al. [74]. Used with permission.
2. Human Response to Space Flight
FIGURE 2.5. Mean percent change ( standard error) from preflight
values in bone mineral density of 15 U.S. crewmembers after return
from ISS Expeditions 112 [76]
crewmembers exhibited negative calcium balance, with
increased urinary and fecal calcium excretion and decreased
intestinal absorption of calcium [72]. Reduced intestinal
absorption and increased urinary excretion were confirmed on
a subsequent long-duration mission [77]. Another biochemical
marker of skeletal turnover and breakdown, urinary hydroxy-
proline, was noted to be elevated in Skylab crewmembers
[72], and more recently other markers of resorption, such as
n-telopeptide and deoxypyrodinoline, have been consistently
elevated during flight [7880]. Markers of bone formation
such as bone-specific alkaline phosphatase and osteocalcin
have been either decreased [79] or unchanged [80] as a result
of weightlessness. Increased resorption and diminished intes-
tinal absorption of calcium seem to have central roles in the
loss of BMD caused by space flight. Parathyroid hormone
levels have been reported to be increased during [79] and
immediately after long-duration flight [81], unchanged dur-
ing short-duration flights [82] and after long-duration flights
[80], and increased during short-duration flight [83]. Levels of
active vitamin D (1,25-dihdroxycholecalciferol) were reduced
during flight and unchanged immediately after landing from
long-duration missions [80] and were found to increase during
shorter flights [82]. The lack of ultraviolet light in the spacecraft
environment probably contributes to the reported reductions
in vitamin D stores (25-hydroxycholecalciferol) after space
flight [80,84], and vitamin D supplements are given during
flights aboard the ISS to ensure adequate levels of this factor.
Loss of BMD seems to continue unabated in weightless-
ness and presumably would eventually lead to clinically rel-
evant losses of BMD and increases in risk of fractures. Bone
loss also carries an inherent risk of nephrolithiasis because
of hypercalciuria, which begins upon first arrival to weight-
lessness (discussed further below). Structurally, decreases
in BMD do not seem to breach the clinical threshold even in
standard long-duration missions; no increase in the incidence
of fractures attributable to bone loss has been seen during the
postflight period, at least with current flight durations. Inflight
39
physical countermeasures may have a protective role against
loss of BMD; such countermeasures are evolving, and it is
hoped that new devices providing the means for heavy resistive
exercise, soon to be available on ISS, will help to further mitigate
bone loss. One such device, the advanced resistive exercise
device, can provide axial loading of up to several hundred
pounds for exercises such as squats and dead lifts.
Muscle
Skeletal muscle atrophy and loss of strength are long-known
consequences of space flight. Like bone, skeletal muscle is
also dynamic and depends on relative balances of demand
based on loading forces and metabolic factors regulating
synthesis and breakdown. Changes in muscle manifest more
quickly than changes in bone, because bone involves more
long-term deposition of mineral salts. Practically, this pro-
cess is influenced by nutrition, exercise countermeasures, and
individual genetic disposition. Muscle atrophy is associated
with negative nitrogen balance, which was observed as early
as the Apollo program and more thoroughly characterized in
the Skylab program. Significant losses of urinary nitrogen and
phosphorus were documented during these flights and asso-
ciated with observed reduction in muscle tissue [72]. Losses
were accentuated during the first week, most likely correlating
with the relative anorexia accompanying the first several days
of the flight. In postflight evaluations, corresponding losses of
strength relative to preflight measurements, particularly in the
lower extremities, were seen, with strength loss in extensors
reaching nearly 20% and that in flexors ranging from 10% to
17% after the first two crewed Skylab missions [85]. After
the first Skylab mission, in which physical countermea-
sures consisted only of bicycle ergometry, additional exercise
capability was added to the next two missions; this additional
capability consisted of mild resistive exercise and a slippery
surface to serve as a surrogate treadmill to allow running and
jumping under loads. Additional food was also supplied with
the intent of increasing food intake. Muscle loss was much
diminished compared with the loss experienced during the
first mission, but still persisted [85].
Although coupled with comprehensive nutritional and met-
abolic studies, the Skylab data on muscle loss were influenced by
the small sample size (only nine crewmembers total) and sub-
stantial variations in nutritional states and availability of exer-
cise countermeasures among the missions. Subsequent flight
experiments on the Space Shuttle and with Russian station
crews have extended the Skylab findings and allowed better
characterization of the effects of weightlessness on skeletal
muscle, as noted briefly below.
A basic understanding of skeletal muscle structure is helpful
for interpreting space flight findings of muscle morphology.
Demands on skeletal muscle with regard to power and endur-
ance vary with required function and hence distribution
throughout the body. As such, differences in morphology and
supportive metabolism exist that serve to optimize functionality
40
in these different roles. Broadly peaking, skeletal muscle can
be distinguished by fiber type, driven by these structural and
functional differences. The diameter, velocity of contraction,
and ability to utilize different metabolic fuels are basic deter-
minants of fiber type. Individual skeletal muscles consist of a
combination of the three basic muscle fiber types, with their
proportions depending on the action of that muscle as well as
genetic influences.
Type I fibers, slow-twitch fibers with slow contraction veloci-
ties, primarily utilize oxidative metabolism as an energy source
and are resistant to fatigue. Type I fibers are relatively small in
diameter, contain large amounts of myoglobin to enable oxy-
gen utilization and delivery, and are rich in capillaries and
mitochondria. These types of fibers are distributed in greater
proportions in postural muscles, such as the lower extremities
(soleus), back, and neck, which are nearly constantly active in
maintaining posture in 1 G. Type II fibers are fast-twitch fibers
with high contraction velocities and are further divided into IIa
and IIb types. Type IIa fibers utilize oxidative and glycolytic
metabolic energy sources, and so they also contain myoglobin
and are relatively rich in capillaries and mitochondria. Type
IIa fibers are moderately resistant to fatigue and are recruited
for exertions requiring a high force output for a short amount
of time. Type IIb fibers are relatively large in diameter and
utilize primarily anaerobic energy sources such as glycogen
and creatine phosphate; they contain low levels of myoglobin
and relatively few capillaries and mitochondria. Type IIb fibers
support high-power, short-duration exertions, such as lifting,
sprinting and jumping, and they fatigue rapidly. Type IIb fibers
are distributed in greater proportions in the arms and shoulders
as well as the gastrocnemius.
Measurement of muscle volume and cross-sectional area
by imaging provides an objective means of assessing skeletal
muscle changes associated with space flight. These changes
can be augmented by strength and power assessments, along
with the occasional histologic studies requiring muscle biopsy,
to fully assess the effects of weightlessness on skeletal muscle.
As expected, the postural muscles tend to be most affected in
their relatively unloaded state in weightlessness. Calf muscle
loss after the initial fluid-shifting response to weightlessness
contributes to the bird legs appearance of crewmembers
during space flight. Less expected was the rapidity with which
these changes manifest themselves in weightlessness.
Volumes of postural muscles in four individuals after
an 8-day Shuttle flight, as assessed by magnetic resonance
imaging at 24 h after landing, showed the following changes:
posterior calf (soleus-gastrocnemius), 6.3%; anterior calf,
3.9%; hamstrings, 8.3%; quadriceps, 6.0%; and intrinsic
back 10.3% [86]. Similar muscle group assessments in four
individuals after a 17-day flight revealed a muscle volume
decreases of 310% in all muscles measured [73]. In another
study involving magnetic resonance imaging, three astronauts
flying 9-, 15-, or 16-day flights had volumes of knee exten-
sor, knee flexor, and plantar flexor muscles assessed before
and after flight. All showed volume reductions, ranging from
E.S. Baker et al.
5.5% to 15.4% for knee extensor, 5.614.1% for knee flexor,
and 8.815.9% for plantar flexor [87]. Postflight biopsies of
vastus lateralis muscle after 5-day and 11-day Shuttle flights
in eight astronauts showed 68% fewer type I fibers than pre-
flight measurements. After the 5-day flight, cross-sectional
areas were diminished by 11% for type I fibers and by 24%
for type II fibers. The number of capillaries per fiber was
diminished by 24%, although the ratio of capillaries to over-
all muscle cross-sectional area remained constant. Metabolic
changes in energy substrate utilization also differed among
fiber types; myofibrillar adenosine triphosphate activity was
increased after flight in type II but not type I fibers [88]. Long-
duration flights, in which the steady-state effects of physical
countermeasures are more influential, show similar volume
losses, suggesting a plateau effect. Cosmonauts have shown
loss of posterior calf volumes of 620% after 6-month flights
on the Mir station [89].
Very little has been published regarding losses in upper
extremity strength and mass since the early Skylab flights,
when deliberate countermeasures targeting the arms were
not available or in development. The second and third Sky-
lab crews, which made use of a dedicated resistive exercise
device, demonstrated negligible losses in strength except for
arm extensors in the third crew, mostly accounted for by a
single individual [85]. Since that time, more definitive coun-
termeasures preserving upper extremity muscle groups have
been available during long-duration missions.
Investigations of strength loss subsequent to the Skylab era
have helped to further characterize skeletal muscle behavior
in space flight. Strength data from 17 individuals after Shuttle
flights of up to 16 days are shown in Table 2.5, classified by
concentric (muscle shortening against a load) and eccentric
(muscle lengthening against a load) test contractions [90].
Again, more strength was lost in the lower extremities and
postural muscles than in the upper extremities. Lambertz et
al. found that after flights lasting 90180 days, 14 individu-
als showed a mean 17% decrease in isometric plantar flexor
torque during maximal voluntary contraction [91]. Postflight
assessments of quadriceps and hamstring for 12 individuals
after 4- to 6-month flights on the ISS are shown in Figure 2.6
[76]. Maximal power of the lower limb, as assessed by force
platform measurements and by short, intense bouts of cycling,
has been shown to decrease by 54% after 21 days of flight [92]
and by 50% after 169- to 180-day flights [93]. Some have pro-
posed that a new steady state is established after roughly 110
days in microgravity, and further losses in peak limb muscle
torque would not be expected after this time [94].
In spite of the losses in muscle strength and mass due to
atrophy, contraction velocity has consistently been elevated
after both short-duration [95] and long-duration flights
[91,96]. This phenomenon partially compensates for the
mass loss to preserve muscle power. In a thoughtful review
of muscle behavior in space flight, Fitts and colleagues noted
that although loading is the guiding determinant of muscle
size, the major mechanism for muscle protein loss and atro-
2. Human Response to Space Flight 41

TABLE 2.5. Mean percent changes (landing day vs preflight) in skel- in-depth investigation on Skylab into human performance in
etal muscle strength in 17 crewmembers after Space Shuttle missions anticipation of longer-duration missions.
up to 16 days. The constellation of factors associated with adaptation to
Test mode weightlessness includes several that might be expected to
Muscle group Concentric Eccentric decrease performance, such as blood volume loss, hypokinesia
Back 23 (4)* 14 (4)* with resultant skeletal muscle loss, and nutritional deficits.
Abdomen 10 (2)* 8 (2)* Assessment and eventual optimization of human physical
Quadriceps 12 (3)* 7 (3) performance with regard to these and other medical variables
Hamstrings 6 (3) 1 (0) broadly has a twofold aim: supporting the successful completion
Tibialis anterior 8 (4) 1 (2)
Gastrocnemius/Soleus 1 (3) 2 (4)
of mission objectives and ensuring crew health during and
Deltoids 1 (5) 2 (2) after the mission. The chief physical challenges associated
Pectorals/Latissimus 0 (5) 6 (2)* with space flight are associated with EVAs, entry, and land-
Biceps 6 (6) 1 (2) ing. Physical assessments and countermeasures are oriented
Triceps 0 (2) 8 (6) in part toward these activities. A performance decrement may
*
p < 0.05. be tolerable if the required functionality is maintained with an
Source: From Greenisen et al. [90]. adequate margin and sufficient capability returns after flight
to support long-term crew health.
Results from cardiovascular evaluations of exercise capac-
ity reflect in part the method of assessment and whether that
method accounts for the peculiarities and artifacts of weight-
lessness to make comparison with preflight findings meaning-
ful. Cycle ergometry is relatively transparent to the effects of
weightlessness, and metabolic rates associated with a given
level of cycle exercise are unchanged from preflight levels [8].
The same may not be true in assessments of activities that nor-
mally require postural muscles for stability, such as upright
locomotion and resistance-force assessments simulating
weight lifting. Both inflight findings and ground predictions
would seem to indicate a decrease in mechanical efficiency
associated with treadmill exercise in weightlessness [98].
Therefore assessments of cardiovascular fitness are typically
made by using graded cycle ergometry. Variables measured in
FIGURE 2.6. Mean percent change ( standard error) from preflight these assessments typically
. include heart rate and blood pres-
values in isokinetic strength of quadriceps (knee extension) and sure. Oxygen uptake [VO2] is a valuable integrated variable
hamstring (knee flexion) for 15 crewmembers after return from ISS measured to assess exercise capacity, which reflects global
Expeditions 112 [76] cardiovascular function. Oxygen uptake has been calculated
from heart rate and blood pressure and from preflight data,
phy seems to be a decline in synthesis without an increase or it can be measured directly by analyzing metabolic gases,
in muscle breakdown [94]. This observation underscores the typically as part of a research protocol.
importance of adequate nutritional support to augment physi- Echocardiographic findings during inflight exercise have
cal countermeasures during space flight. also contributed to our understanding of inflight cardiovascu-
lar fitness. Safety concerns preclude testing to maximum levels
during flight, although crewmembers are not prohibited from
Inflight Physical Performance exercising to max levels during personal exercise sessions. All
After reviewing the reactions of the body systems that con- assessments are monitored by inflight and ground personnel.
tribute most directly to human physical performance, it seems Skylab crewmembers did not show appreciable inflight
appropriate to consider this aspect of crew capability during decrements in mechanical efficiency during cycle ergometry,
the inflight period as well. Apollo medical testing showed a and in fact six of the
. nine crewmembers demonstrated a slight
significant postflight decrease in oxygen uptake for a given increase. Inflight VO2 decreased slightly in six crewmembers
exercise load, with heart rate significantly elevated for a given for a given. workload (determined as 75% of preflight
level of oxygen consumption on return day as compared with maximum VO . 2), and
. heart rate generally increased slightly
preflight values [97]. Of all 27 of the Apollo crewmembers, 20 for a givenVO2 [8].VO2 measured for four individuals during
showed significant decreases in exercise tolerance on return a 17-day Shuttle flight exercising at a workload correspond-
day, which largely resolved within 2436 h [8]. These find- ing to 85% of maximal capacity progressively decreased to
ings, along with other early observations, prompted further a value of 11.3% on flight day 13 [99]. The change in estimated
42
.
VO2 for 15 ISS crewmembers during long-duration flight is
depicted in Figure 2.7 [76].
Physician-cosmonaut Atkov and colleagues assessed echo-
cardiographic variables during cycle exercise of two crewmem-
bers during an 8-month space flight. Resting left-ventricular
end-diastolic volume and stroke volume were lower during
flight than before, and resting heart rate was 1012 beats
per minute faster, maintaining cardiac output at essentially
unchanged levels. Measurements during exercise at 175 watts
revealed decreases in stroke volume of 30% and 25% for the
two crewmembers, with respective increases in heart rate of
16% and 11%, compared with preflight. An increase in car-
diac output from exercise was 1315% lower than preflight
values at the same level of exercise, and was attributed to
changes in heart rate only. Myocardial contractility was not
compromised, suggesting that diminished circulating blood
volume was primarily responsible for the decreases in stroke
volume and left-ventricular end-diastolic volume [30]. These
results have been corroborated by other long-duration flight
studies aboard the Mir station [100] and aboard short-duration
flights. Shykoff et al. noted a noted a lesser increase in cardiac
output and a smaller stroke volume for a given workload in six
crewmembers during two Shuttle flights [28].
EVAs primarily require upper body strength, which is gen-
erally preserved in weightlessness. However, preflight training
during water immersion to simulate neutral buoyancy, while
crewmembers are not deconditioned and are exercising normally,
is highly demanding. Upper extremity soreness and fatigue after
EVA training as well as actual EVA is common. Because upper
body performance is crucial to the success of EVAs, physical
countermeasures to maintain arm and shoulder strength in a high
state of fitness, along with the means to monitor the effectiveness
of countermeasures, are prudent during long-duration flight.
In summary, crewmembers can maintain slightly dimin-
ished but nevertheless high levels of aerobic capacity and
FIGURE 2.7. Mean percent change (. standard error) from preflight
values in estimated oxygen uptake [ VO2] index for 15 crewmembers
after return from ISS Expeditions 112 [76]
E.S. Baker et al.
upper extremity strength during flight. An increase in car-
diac output in response to exercise primarily results from
an increase in heart rate rather than a change in stroke vol-
ume, and in general cardiac output for a given workload
does not attain the same level as before flight. Reduced
blood volume rather than cardiac impairment seems to
be the dominant effect influencing altered cardiovascular
dynamics, and these effects are expected to be accentuated
upon Earth return and upon transition from relative to abso-
lute hypovolemia.
Neurological Findings
On Earth the visual, vestibular, and somatosensory systems
use gravity as a reference for orientation. In the absence of
gravity, new strategies for positional sensing are used, most
likely involving a reweighting of visual, otolith, and per-
haps tactile and somatic signals [101]. Several sensorimo-
tor changes have been demonstrated during flight, including
slowed pointing responses [102], degraded manual tracking
performance [103], attenuation of postural responses [104],
and occasional illusory motion of the self and visual sur-
round [105]. Like the cardiovascular and respiratory systems,
the neurological system undergoes changes that by and large
are not associated with impairment. Unlike changes in other
systems, neurological changes are less likely to be manifested
in standard observations, and clinical neurological tests are not
available aboard the ISS. Sophisticated, directed investigative
methods would be required to detect and quantify changes in
neurological functioning during flight. The exception is space
motion sickness, which does breach the clinical horizon and
most likely results largely from this process of adaptation and
reorientation. Other than that, clinically relevant, functional
consequences of changes in neurological system functions are
not problematic during flight. The major manifestations are in
the form of reentry and postlanding phenomena. Chapter 17
discusses neurological findings in detail.
The typical spacecraft environment is not particularly chal-
lenging with regard to body motion control. Spacecraft are rel-
atively confined, and the stowage and placement systems rely
on an artificially defined vertical. Crewmembers occasionally
report transient disorientation, especially when moving to
different modules, but in general these perceptions diminish
with time and do not affect operations. Turning ones attention
to outside the spacecraft or station, as is needed for robotic
operations, docking, and rendezvous activities, changes the
sense of orientation and may induce greater motion control
challenges. In these activities, operative cues rely largely on
camera views and interpretation of numerical data to deter-
mine the positions of objects being manipulated in space.
These views may be supplemented with dynamic virtual
views, constructed in real time with positional data inputs and
displayed to the crewmember. Such inputs augment whatever
direct visual cues may be used, which are sensitive to lighting
and orientation.
2. Human Response to Space Flight
Adaptation mechanisms seem to serve flight crews well
during normal flight activities. Crewmembers have been
able to perform complex tasks requiring fine motor control
routinely during space flight, indicating adequate integrated
functioning of the neurovestibular and somatosensory sys-
tems. Aside from the external operations noted above, typi-
cal on-board tasks include operation and sometimes intricate
repair of equipment, animal dissection, wiring and soldering,
among others.
Beyond sensorimotor implications, the role of the neuro-
logical system in cardiovascular control and blood pressure
regulation is probably the next most important consideration.
Inflight investigations have shown exaggerated catecholamine
responses to physical stress challenges such as exercise [106]
and LBNP [50], indicating maintenance of the sympathoadre-
nal system. Vagal activity seems to be attenuated, as indicated
by diminished vagal baroreflex gain in inflight measurements
of response to the Valsalva maneuver [48,107] and diminished
heart rate variability [48].
Renal and Endocrine Systems
Renal function and hormonal regulation of body systems in
response to physical challenges are complex and interactive,
highly sensitive to outside influences, and often require spe-
cialized and rigorously controlled investigative techniques to
isolate a relevant finding from other influences. In addition,
conditions associated with space flight other than weightless-
ness can influence endocrine function, including physical and
psychological stress, confinement, heat stress, and dietary
changes. As such, much of the knowledge of endocrine sys-
tem behavior in space flight is incomplete, and reported find-
ings are at times contradictory and inconclusive. Findings that
seem to be consistent across studies or those particularly rel-
evant to understanding the clinical picture will be discussed
here. Much of what is known relates to the role of the renal
and endocrine systems in the adaptation of fluid and plasma
volume regulation to weightlessness. Beyond the general
observations seen in the acute stages of adaptation, most of
these changes are clinically transparent but are described
briefly here to be understood as possible new clinical norms.
Many of the predicted findings with regard to renal and
endocrine control of fluid regulation in weightlessness have
not been realized. Decades ago, Gauer and Henry elucidated
mechanisms whereby different process leading to an increase
in intrathoracic volume would be sensed as an overall volume
overload and elicit diuresis of water and salt, mediated in
part by volume sensitive stretch receptors [108]. Indeed,
water immersion, used as an analog for weightlessness, has
long been known to cause a brisk water diuresis resulting
from central fluid shift [109,110]. It was anticipated that
neutralization of hydrostatic forces in weightlessness would
have effects similar to those of immersion, with subsequent
cardiac distension, baroreceptor stimulation, and decreases
in antidiuretic hormone (ADH) levels and in the activity of
43
the renin/angiotensin/aldosterone axis as fluid volume is
reduced to a lower level.
Although volume does contract fairly rapidly upon enter-
ing weightlessness, other findings are somewhat paradoxical
when compared with a classical Gauer-Henry response. The
absence of diuresis and decreases in fluid intake were noted
during the Apollo [5] and Skylab [111] programs. However,
it has taken more complicated payloads supporting sophis-
ticated inflight investigations to further elucidate the events
associated with fluid regulation. The well-documented find-
ings of thoracic fluid shift, cardiac chamber expansion, and
rapid volume contraction within the first 24 h of space flight
occur against a backdrop of apparently decreased intratho-
racic pressure, decreased urine output, and decreased oral
fluid intake, as noted in the discussion on cardiovascular
response, and has been described in both the US and Russian
programs [15].
Arguably the most thorough inflight investigation to date
on fluid regulation during short-duration flight has been the
Spacelab Life Sciences (SLS)-1 and SLS-2 flight experiments
described by Leach and colleagues [112]. To summarize, the
lack of diuresis and low fluid intake were confirmed, with no
change in serum osmolality. The glomerular filtration rate
was seen to increase early and remain elevated for at least a
week. Creatinine clearance was slightly decreased on flight
day 1 (FD1) but normalized by FD2 and remained normal-
ized thereafter. Volume contraction was most marked within
the first 48 h and was characterized by a decrease in extra-
cellular fluid, increase in intracellular fluid, and total body
water remained unchanged. ADH levels increased by a fac-
tor of four on FD1, returning to preflight levels by FD2. This
elevation in ADH may seem paradoxical in lieu of decreased
thirst; however, ADH has been seen to increase in response
to physical stress [113] and in response to motion sickness
provoked via the Coriolis effect [114]. Plasma renin activity
and aldosterone levels decreased significantly by FD1, then
gradually increased toward normal levels. Atrial natriuretic
peptide, which normally increases in response to the disten-
tion of atrial stretch receptors in volume overload, tended to
decrease during the course of the flights.
The SLS-1 and SLS-2 investigations confirmed that vol-
ume contraction does occur but that it is not primarily brought
about by water or sodium diuresis. Interestingly, infusion of
saline during space flight was associated with a significantly
attenuated volume and sodium excretory response compared
with preflight values when the subjects were supine; plasma
norepinephrine and renin levels approximated preflight
seated levels, whereas aldosterone levels were between pre-
flight supine and seated levels [115]. These findings led Ger-
zer [116], Norsk [115], and others [117] to posit a previously
unrecognized large body capacity for extravascular storage
of sodium, uncoupled from normally understood water bal-
ance mechanisms. Further details on this and other investiga-
tions into fluid regulation in weightlessness are provided in
Chap. 27.
44
Another observation in the SLS studies was the inference of
decreases in sweating and insensible fluid losses [112]. These
variables were noted to be decreased in Skylab crewmembers
by 11% relative to preflight values, and the decreases were
attributed to the buildup of a sweat film during exercise owing
to the absence of gravity and convective forces, exerting a sup-
pressive effect on further sweat production [118]. These find-
ings, along with the observation of increased core temperature
for comparable levels of exercise and decreased sweating 5
days after return from long-duration space flight relative to
preflight values [119] suggests that multiple mechanisms may
affect thermoregulation during flight.
Several factors associated with space flight interact to
increase the risk of nephrolithiasis. Mobilization of calcium
and phosphate from bone begins rapidly in weightlessness.
Analyses of urine samples collected before and after Space
Shuttle flights show significant increases in the relative super-
saturation of the stone-forming salts calcium oxalate, calcium
phosphate (brushite), and uric acid as well as low urine volume,
low pH, and hypocitraturia [120]. Studies on long-duration
flights involving inflight urine collection demonstrate similar
findings of hypercalciuria and increases in urinary concentra-
tions of stone-forming salts [121]. The relative hypovolemia
associated with Earth return makes this a particularly vulner-
able period [122]. One probable event of inflight nephrolithia-
sis occurred in the Salyut program [123], and several events
have been seen clinically in the immediate postflight period
after short-duration flights. This topic is discussed in detail
in Chap. 13.
Stein and colleagues conducted studies of inflight
urinary hormone levels associated with the SLS-1 and SLS-
2 missions [124]. Norepinephrine levels were decreased
but epinephrine levels were maintained at normal levels
throughout the flights. Further analysis of the catecholamine
findings revealed a sex difference in norepinephrine, with
three female crewmembers showing essentially no change
and four male crewmembers showing significant decreases
[125]. Levels of free 3,5,3-triiodothyronine, prostaglandin
E2, and its metabolite prostaglandin EM were decreased
during flight relative to preflight levels, which could be
related to muscle atrophy. Cortisol levels were significantly
increased on FD1 only but tended to be higher than preflight
values throughout the flights. In other studies, cortisol levels
have been shown to remain unchanged [126] or to increase,
possibly related to stress [127].
Concern has been expressed over suppression of thyroid
function during flight from exposure to pharmacologic doses
of iodine, used on the Space Shuttle to disinfect potable
water. McMonigal et al. documented a transient increase of
thyroid-stimulating hormone in postflight laboratory studies
of Shuttle crewmembers suggestive of thyroid suppression,
which resolved after installation of equipment that removes
iodine before drinking the water [128]. No increase has been
detected in the incidence of clinical thyroid disease associated
with this iodine exposure.
E.S. Baker et al.
Inflight data from long-duration flights are fewer. Skylab
studies of urinary hormone levels showed increases in aldoste-
rone, cortisol, and total 17-ketosteroids, whereas epinephrine,
norepinephrine, and ADH levels tended to be lower during
flight than before. Plasma cortisol levels were also elevated,
though not always significantly [111]. The 438-day flight of
physician-cosmonaut Polyakov revealed that plasma renin
activity, ADH, and aldosterone were maintained within normal
clinical limits, but atrial natriuretic peptide levels remained
lower during flight than before [129]. Both epinephrine and
norepinephrine were significantly increased at 5 and 9 months
but within normal limits in the early and late mission stages.
Adrenocorticotropic hormone and cortisol did not show con-
sistent changes [129].
A few other hormonal responses to space flight have been
noted. Parathyroid hormone, which is relevant to calcium
homeostasis and bone metabolism, is discussed in the preced-
ing section on the musculoskeletal system. Insulin resistance
is known to develop in individuals in sedentary conditions,
and this has been observed in space flight [130,131]. Con-
sidering space flight to be a physiological stress, Strollo and
colleagues studied four individuals, expecting a decrease in
testicular androgens mediated through the pituitary gonado-
tropin luteinizing hormone. Salivary, urinary, and plasma
testosterone were found to be diminished during flight, along
with a decrease in sex drive as assessed by questionnaire.
However, luteinizing hormone levels were found to be para-
doxically increased [132]. The causes remain to be elucidated,
although salivary testosterone levels were noted to recover by
return day one.
Gastrointestinal System
That gravity has a role in digestion is evident to anyone who
has tried to eat while recumbent; there is a definite assist in
assuming the upright position for swallowing and esophageal
transit. Although the gastrointestinal (GI) tract follows a cir-
cuitous and convoluted route, the general gradient is favored
by the upright posture. Arun has speculated that a loss of
polarity of propulsion of digested material occurs in micro-
gravity as the bowel floats but that this effect is partially
compensated by movement that is driven by diaphragmatic
excursions [133]. Bowel activity seems to be diminished
during the first hours to days of flight, as assessed by electro-
gastrography [134] and by recording of bowel sounds [135].
This reduction in bowel activity seems to be related to space
motion sickness, and by and large it clears after a few days.
A study of GI function involving a lactulose-hydrogen breath
test showed a trend toward increased transit time, but these
findings, from only two individuals, were considered incon-
clusive [136]. Russian studies have documented hyperacidity
during long-duration flights that seems to arise after about 3
months in flight [137]. This observation, along with evidence
of slight hepatic and pancreatic enlargement on sonography
(apparently due to edema), slowed gastric emptying and
2. Human Response to Space Flight
gastrointestinal motility, and mild pancreatic insufficiency are
considered to reflect digestive tract adaptation to long-dura-
tion flight [131].
Nevertheless, digestion does not seem to be clinically
problematic in weightlessness. Crew reports of esophageal
reflux, abdominal distension, or other GI complaints do not
seem to be more common in space than on Earth, with the
possible exception of constipation. The weight loss typically
seen associated with long-duration space flight can be primar-
ily accounted for by decreased energy intake. Further study is
warranted, however, to better define the effects of weightless-
ness on GI function with regard to nutritional utilization and
the bioavailability of pharmacologic agents.
Inflight Clinical Laboratory Findings
Laboratory studies have been an important part of preflight
and postflight medical evaluations since the first space flights.
Postflight findings, however, are almost certainly influ-
enced by the multisystemic readaptation process associated
with return to gravity and thereby reflect a combination of
weightlessness and 1-G effects. Blood and urine samples are
occasionally collected during short flights for investigational
purposes; typically samples are stored frozen or otherwise pre-
served to allow postflight analysis in definitive ground-based
laboratories. During long-duration flight, limited inflight
analytical capability is available to support two main clinical
functionsassessment of selected blood values that are either
relevant to periodic health assessments or used for diagnosis
and monitoring of a clinical problem. The results may also be
used investigationally, but their primary worth is in determin-
ing clinical normative values for space flight and detecting
potential health anomalies that may require remediation or
further research.
The Russian medical support program has used an onboard
analyzer to periodically measure enzymes in blood samples
during long-duration flight. Preflight baseline values are
obtained for each variable to be measured inflight. In an
assessment of 17 Mir station crewmembers, increases were
seen in fasting levels of glutamic-oxaloacetic transaminase,
glutamate pyruvic transaminase, total amylase activity, glu-
cose, and total cholesterol; decreases were noted in creatinine
kinase activity, hemoglobin, high-density lipoprotein, choles-
terol, and the ratio of high-density to low-density lipoprotein.
Despite these apparent changes, values remained within normal
clinical limits [138]. The US space program has made use
of a smaller clinical analyzer to assess primarily electrolyte
values during periodic health evaluations aboard long-dura-
tion missions on the ISS [139]. The findings are inconclusive
as yet, but suggest that most values remain within clinically
normal ranges. Periodic inflight urinalysis is performed with
chemical reagent sticks. Results are generally remarkable
only for specific gravity tending to be high (between 1.025
and 1.030), reflecting a state of reduced hydration. No pro-
teinuria has been seen, consistent with the observation that
45
urinary albumin excretion is reduced in long-duration flight
compared with preflight values [140].
Entry and Landing
The cadence of entry and landing day varies considerably with
the type of flight. Free-flying spacecraft such as the Apollo
capsules and Shuttle simply reconfigure controlling software
and systems and land. The Soyuz, and at times the Shuttle,
may be returning after separation from an orbital station such
as Mir or the ISS. If a mission involves crew rotations on an
orbiting station, that implies a handover between the departing
crew and the oncoming crew, which typically takes place over
several time- and labor-intensive days. Crew rotations aboard
the Space Shuttle may also involve cargo transfer, EVAs, and
robotics activities during this period. Activity density dur-
ing such docked operations is high, and often crewmembers
depart with some degree of fatigue. The Shuttle usually loiters
on orbit for a day or two after separation, whereas the Soyuz
lands within a few hours after separating from the station. In
anticipation of descent, crewmembers don the same pressure
suits as are used for launch for protection in case of loss of
pressure.
The return from low Earth orbit is fairly brief. After a low-
thrust braking burn that serves to lower the orbit to a point
sufficient for atmospheric drag to further decelerate the space-
craft, less than 1 h remains until landing. As is the case for
launch to orbit, the crew must pass again through the velocity
barrier that sustains their orbit, decelerating from 7.8 km/s to
0 relative to the Earth surface. Acceleration loads are again
present, but for landing the prime source of these loads is the
braking effect of the atmosphere rather than engine power,
with the direction of the loading dependent on vehicle and
crew orientation to the entry velocity vector. In both launch
and landing, physical loads beyond the orbital or terrestrial
norms separate crewmembers from either endpoint. The now-
deconditioned crewmembers do not transition cleanly back
to 1 G but rather pass through a hyperloaded state, inducing
greater physiologic stress and influencing the clinical profile
and readaptation process. It is during entry that the effects of
gravity and the implications of the relative deconditioning are
first felt.
As is true for launch, landing is a dynamic and dangerous
phase of flight, with critical control inputs and event moni-
toring required of crew and ground personnel. Moreover, for
crews returning after a long-duration flight, formal high-fidel-
ity training may have taken place more than 6 months earlier.
For Soyuz crews, inflight refresher training is provided before
landing with laptop-based simulator programs and proce-
dural reviews. Shuttle flight crewmembers with piloting and
monitoring duties are constrained to short duration flights.
Crew duties during entry and landing vary, but as a minimum,
required flight crew monitor engine operation during the deor-
bit burn and the postburn maneuvering, guidance and navi-
46
gation, and vital spacecraft systems, being ready to assume
manual control if needed to respond to contingencies. This
monitoring requires vigilance and fairly intense concentration,
as well as close communication with the ground and among
other crewmembers. Control inputs and instrument scans may
require occasional head movements, which may be both pro-
vocative and adaptive with regard to motion sickness.
As noted in Chap. 1, each vehicle has a characteristic entry
G-profile to which the crew is subject. The Space Shuttle is
unique in that crewmembers are seated in the upright position,
thereby incurring body +Gz loads during entry and landing.
Crews returning from long-duration missions (for this purpose
arbitrarily defined as 30 days) are situated in a recumbent seat
system on the middeck to circumvent these loads, and thus
take the prolonged 1.2 G primarily in the body +Gx direction.
The Soyuz places all crewmembers in the recumbent posi-
tion, as did the US space capsules. In either type of spacecraft,
measures are taken to protect crewmembers from the effects
of cardiovascular adaptation, which begins to transition from
a state of relative to absolute hypovolemia at the first onset
of G loads. Crewmembers begin a program of oral fluid and
salt loading before the deorbit burn to increase their vascular
volume, and they don anti-orthostatic garments beneath their
launch and entry suits. The Shuttle suit accommodates a pneu-
matic anti-G garment with pressure bladders controlled by the
crewmembers, along with active liquid cooling. Soyuz suits
use gas cooling and accommodate a highly customized elastic
garment, primarily for postlanding anti-G protection.
Cardiovascular reactions are among the first to manifest dur-
ing entry and landing. An increase in heart rate is a sensitive
indicator of orthostatic stress and is expected during landing.
Crewmembers returning on Soyuz undergo active monitor-
ing by electrocardiography, sensed cardiac contractions, and
respiratory rate. In a comparative study of 16 crewmembers
returning on Soyuz after short (821 days, 4 subjects) or long
(186380 days, 12 subjects) Mir station flights, Kotovskaia
and colleagues noted more pronounced sinus tachycardia and
a greater frequency of arrhythmias, neurovestibular effects,
labored breathing, speech difficulties, and petechial hema-
tomas in the back in the long-duration crew as compared
with the short-duration crew during entry monitoring [141].
Arrhythmias consisted primarily of isolated monomorphic
extrasystoles for the short-duration crews, joined by polymor-
phic and occasional grouped extrasystoles for long-duration
crews. However, no changes in consciousness and no visual
disorders were noted, supporting the protective effect of crew
orientation and anti-G countermeasures. In an investigation
comparing three individuals returning in a recumbent posi-
tion from a 4-month flight on the Mir station with a larger
pool of upright Shuttle flight crewmembers returning from
short-duration missions, heart rate was seen to be 25 beats
per minutes lower in the recumbent crewmembers than their
seated counterparts on prior missions. This difference was
abolished upon standing, during which heart rate increased in
both groups to the same extent [142]. This observation again
E.S. Baker et al.
supports the efficacy of recumbent seating in returning from
weightlessness.
Although the numbers are small, observations suggest that
female crewmembers returning on the Soyuz are physiologi-
cally stressed to a greater extent than their male counterparts
if the anti-G garment is not worn; use of the garment abolishes
the sex difference [143].
Neurovestibular disturbances are also expected to begin with
the onset of entry loads, as the otoconia again assume weight
and the ability to signal independent of head movement, as
visual cues transition from a three-dimensional reference
frame to an inherent vertical, and as proprioceptors and other
positional sensors detect direct and indirect effects of body
weight and movement. Unlike monitoring for cardiac activity,
direct monitoring of vestibular function is complicated and
thus is not performed during landing. Subjective reports have
been given of vestibular disturbances provoked by head move-
ments out of the velocity vector. Cosmonauts report sensations
of positional illusions and mild vertigo during entry, which are
more frequent with longer exposures to weightlessness [141].
Crewmembers are taught to minimize provocative head move-
ments and, as is true for the aviation environment, to believe
their instruments. The Shuttle becomes a highly complex
aircraft at the end of a mission, and it is precisely guided to
a manual landing by the flight crew after flights of up to 17
days. Neurovestibular disturbances that may be occurring dur-
ing entry seem to be largely compensated by training, task
focus, and flight instruments, although continued analysis and
vigilance in this area is warranted.
Spacecraft landings are highly planned and rehearsed
operations, with recovery personnel standing by to assist crew-
members and help ensure the safety of the vehicle. However,
spacecraft can and have landed off target. In addition, emer-
gency deorbit, either from a suddenly uninhabitable station
(e.g., fire, loss of pressure) or from a major systems problem
with the primary spacecraft, could cause a landing at an
unplanned time. These possible scenarios compel the crew to
maintain some degree of self-sufficiency and possibly require
higher levels of performance in the postlanding period.
Postlanding Period
At the words contact during landing in the Soyuz, or wheel-
stop during Shuttle landing, the dynamic phase of space
flight is over and much of the psychological stress associated
with space flight is relieved. Crew duties in the immediate
postlanding period involve powering off unneeded equip-
ment and ensuring safe configurations of engines and cool-
ing systems that may be hazardous to recovery personnel. For
nominal landings, none of these duties require that the crew
stand or manipulate heavy loads before vehicle egress; for both
Soyuz and Shuttle, crewmembers are typically aided by recov-
ery and medical specialists within several minutes. Returning
long-duration flyers describe a profound sense of heaviness
2. Human Response to Space Flight
in the minutes after landing, especially noted with the first limb
movements made while unfastening the restraints. In spite of
active cooling systems, heat stress is common for landing
crews because of the pressure suit and vehicle heating during
entry and on the ground after landing. Passive readaptation to
normal gravity is occurring during this time.
Many of the processes involved in adaptation to weight-
lessness now proceed in reverse during Earth readaptation.
Returning to gravity and its resulting hydrostatic gradients
and the reintroduction to the upright posture demand a return
to the 1-G volume status and reawakening of regulatory cir-
cuits. Those systems most sensitive to loading forces, such
as cardiovascular and volume control, muscle, and bone, both
declare themselves during adaptation to weightlessness and
are particularly affected during readaptation. As expected, the
effects of this readaptation on performance are pronounced,
because the functional capacity-to-demand ratio, which was
more positive on entering weightlessness, is now decidedly
negative upon returning to gravity. In addition, a neuroves-
tibular system accustomed to weightlessness must now inter-
pret gravitational cues and guide purposeful body and eye
movements in Earths constant gravity. Although readaptation
begins immediately, systems return to preflight functional lev-
els at different rates.
The dominant clinical entities associated with immedi-
ate return from space flight are orthostatic intolerance and
neurovestibular impairment. They can occur individually or
in combination, and entry adaptation syndrome may lead to
emesis, which can further degrade volume status. These enti-
ties, which most affect human performance in the immedi-
ate postlanding period, are discussed in greater detail below.
Further information on areas most affected can be found in
systems-oriented chapters (cardiovascular, neurological, and
musculoskeletal) elsewhere in this book.
Orthostatic Intolerance
Functionally, orthostatic intolerance can be defined as an
inability to maintain adequate central perfusion when assum-
ing an upright posture in the performance of required nominal
or reasonable-risk contingency activities. Cardiovascular and
blood volume status associated with adaptation to weightless-
ness produces, upon landing, a state of acute hypovolemia and
absolute anemia, which combine with decreases in barorecep-
tor sensitivity, cardiac mass, and lower-extremity muscle mass
to diminish venous valvular function and render crewmembers
more vulnerable to orthostatic intolerance. Consistent cardio-
vascular findings in the postflight period include decreased
stroke volume and increased heart rate for crewmembers after
both long-duration [38] and short-duration missions [12,144].
Convertino [145] and others have identified orthostatic intol-
erance as the most significant operational cardiovascular risk
associated with space flight and have appropriately made
orthostatic intolerance a major focus of study, both to deter-
mine its causation and to develop countermeasures for it.
47
Investigationally, cardiovascular functionality in the post-
flight period is often equated with stand test results; how-
ever, the results require some interpretation. These tests were
designed largely to delineate mechanisms of physiological
response rather than to assess functionality, and they typically
proceed to near-syncope or voluntary cessation by subjects due
to symptoms. Orthostatic intolerance as determined by stand
testing correlates with, but is not equivalent to, postflight func-
tionality. In the hundreds of short-duration flight experiences
to date, postflight syncope is rare. Remaining motionless in the
upright position does not allow movement of the lower extrem-
ities or cycling of the venous valves to aid in augmenting the
preload. Highly fit normovolemic individuals occasionally
fail this test before flight, and some crewmembers have been
upright and ambulating for 1 or 2 h after short-duration Shut-
tle flight before performing and failing to finish a stand test.
Buckey et al. have noted that reported failure rates during
investigational stand testing vary from 10% to as much as 64%
depending on the working definition of orthostatic intolerance
and methodologic variables such as tilt angle and duration of
upright posture [12]. Thus, stand testing should be viewed as
an objective and clinically useful tool to delineate mechanisms
of orthostatic intolerance and guide the development of coun-
termeasures, but it should not be used as a singular clinical
assessment to determine postflight functionality.
Stand testing does allow controlled and detailed compari-
sons of physiological characteristics between those who finish
and those who do not. Given the hypovolemic state common
to all returning crewmembers, those who are able to com-
plete a stand test are distinguished from those who are not by
relatively greater peripheral vascular resistance [12,146]. Pre-
vious findings suggest impairment of the baroreflex response
associated with space flight [45,46], possibly most prominent
in those crewmembers who cannot finish the test. Release of
norepinephrine has been shown to be lower in those who do
not finish relative to those who do [146]. More recent stud-
ies show that most of the baroreflex response to orthostatic
stress remains functional following space flight [12,146,147].
The observation that sympathetic tone was maintained in six
individuals who completed a stand test after a 16-day Shuttle
flight [148] and that norepinephrine release induced by tyra-
mine was not impaired after flight [146] suggests that the
efferent limb of the baroreflex remains intact and that those
who can finish the stand test are in part distinguished by their
sympathetic response. Noting an increase in ADH and epi-
nephrine in non-finishers, Meck and colleagues suggested
that the afferent limb of the baroreflex also remains intact,
pointing toward an impairment in central integration of this
reflex resulting from space flight [146]. Although the exact
mechanism limiting the vasoconstrictive response remains
to be delineated, reduced blood volume and impaired ability
to vasoconstrict appear to be the dominant factors associated
with post-flight orthostatoic intolerance. Sex differences have
also been observed during stand testing, with men faring bet-
ter than women in completing stand test protocols [149].
48
Further investigations may better delineate the mechanisms
that maintain blood pressure after flight. However, crewmem-
bers freshly returned from weightlessness are above all treated
as clinically hypovolemic. Crewmembers are typically thirsty
in the few hours after landing, and vigorous oral volume reple-
tion is provided. Urine and sodium output are decreased on
landing day, and a three-fold increase in ADH has been mea-
sured [112]. Maintaining cooling to prevent undue peripheral
vascular dilatation is crucial. Use of a liquid-cooling garment
during entry and landing has been associated with signifi-
cantly lower heart rates upon standing after Shuttle flights,
independent of use of the anti-G suit [150]. Doffing the entry
suit as early as possible after landing is recommended to avoid
further heat stress. Long-duration crewmembers are main-
tained in the recumbent position and are brought upright only
as needed and tolerated for the first few hours. Showers, one
of the first desires of returning crewmembers, are kept warm
but not hot to avoid undue vasodilation.
Recovery of function is rapid after short-duration flights,
with improvements in heart rate responses observable over
several hours. After the crew is recovered from the Shuttle
and changes into normal clothing, short-duration crewmem-
bers often perform a walk-around to inspect the vehicle
within the first 90 min or so of landing. The vast majority are
able to do this without difficulty.
As plasma volume is replenished, the hematologic deficit is
manifested by decreases in hematocrit and hemoglobin con-
centration. This drop induces erythropoietin release, which has
been seen to increase the day after return for crewmembers
returning after both short-duration [34] and long-duration
missions [151], which in turn stimulates erythropoiesis and
gradual complete replenishment of erythrocyte mass back
to preflight baseline. Reticulocyte counts are low on landing
day and begin to increase within a few days to a week [33].
Replenishment is complete by about 3 months after return, and
some recovery may actually start during flight, after the first
12 months in weightlessness [152]. After the 84-day Skylab
flight, observed decreases in left ventricular end-diastolic vol-
ume had completely recovered by 30 days after return [38].
Regulation of body fluid compartments after short-duration
flight returns to normal within a week [112]. After a 430-day
flight, the hormonal response to controlled LBNP stress had
returned to normal by 3 months [153].
Neurovestibular Symptoms
Essentially no significant subjective neurovestibular symp-
toms were noted during or after Mercury and Gemini flights,
presumably because of the tight volume constraints of the
spacecraft, which limited adaptation to weightlessness,
and objective postflight findings were minimal [154]. The
larger volume of the Apollo spacecraft, allowing freedom of
movement and full adaptation to weightlessness, is thought to
underlie the greater incidence of space motion sickness and
more pronounced postflight symptoms seen in this program.
E.S. Baker et al.
Only limited studies were performed in the last few crews
returning from the moon, but mild postural instability was
noted for subjects standing with eyes closed for 3 days after
landing, suggesting a shift toward reliance on visual cues for
orientation and a lessening of vestibular and proprioceptive
control [154].
The Skylab flight experience involved both longer flight
durations and a significant increase in habitable volume, which
allowed unhindered adaptation to weightlessness. During
return, as was true for the Apollo crews, Skylab crewmembers
had the added motion challenge of a sea landing followed by
a helicopter transfer onto a recovery ship. Postflight changes
in locomotion and other purposeful movements were noted
in all returning crewmembers. Investigators noted that all
crewmembers were able to walk immediately after exiting the
spacecraft, albeit with a wide-stance shuffling gait and bent-
forward posture now very familiar to space crew recovery per-
sonnel. The crewmembers themselves reported that walking
required conscious effort and that cornering was difficult and
accompanied by the tendency to lean to the outside. Improve-
ment was rapid, and few noticeable signs of ataxia or postural
instability were noted by the second return day. Objective test-
ing showed degradation in postural stability while standing
upright and motionless, particularly with eyes closed, high-
lighting the increased reliance on visual cues. Vertigo induced
by rapid head movement was also reported by all crewmem-
bers; this improved gradually and completely resolved within
34 days after landing, except for one crewmember on the
84-day flight, who had persistent sensations of vertigo for up
to 11 days after return [155].
In addition to the formal investigations the mechanisms
of neurological adaptation accommodated by the U.S. Space
Shuttle, this program has also allowed a relatively high vol-
ume of flight experiences, which has bolstered understanding
of the degree of impairment after exposure to weightlessness.
During the postflight walk-around noted above, flight sur-
geons can readily observe rapid improvements in locomotion
and posture control over the course of this 20- to 30-min activ-
ity. Cornering and gait in particular improve to the extent that
many returning crewmembers show minimal outward differ-
ences in normal ambulation within a few hours of landing.
Flight surgeons conduct formal debriefings with members
of Space Shuttle crews in addition to postlanding medical
examinations. Both are considered clinical tools to assess
function and landing experience rather than investigative
activities. Debriefs and medical examinations are performed
within a few hours of landing and again 3 days later, and both
include queries about the presence of certain symptoms dur-
ing the postflight period. They do not capture the duration of
symptoms, nor are they tied to formal testing; as such, both
are prone to subjectivity and the potential for reporting bias.
However, debrief comments capture a broad spectrum of infor-
mation and help to guide postflight activities. Bacal and col-
leagues retrospectively examined medical debrief comments
from Space Shuttle missions over a period of 18 years with
2. Human Response to Space Flight
regard to neurovestibular symptoms. The number of responses
to specific questions varied from 128 to 389. Symptoms were
classified as absent, mild, moderate, or severe, with the classi-
fication generated by both the reporting crewmember and the
recording flight surgeon. Three symptoms were noted in more
than half the respondentsclumsiness in movements (69%),
difficulty walking a straight line (66%), and persistent sensa-
tion aftereffects (60%). Most of these symptoms were noted as
mild. Some degree of walking or standing vertigo was noted
in about 30% of respondents, with the great majority again
being in the mild category. Although not formally queried,
the period of resolution for most of these symptoms was 1
day (the first return day), although minimal sensations may
persist for a week. The incidence of postflight nausea (15%)
and emesis (8%) of any degree is considerably lower than its
counterpart syndrome after launch [156]. In such cases, read-
aptation sickness occasionally persists for a few days but typi-
cally resolves within 24 h.
Postural assessments of 23 individuals after short-duration
Space Shuttle flights revealed instability and confirmed an
increased reliance on visual and somatosensory cues for main-
taining orientation, which resolved in 48 days after landing
[157]. Another investigation showed significant decreases in
head rotation velocity on landing day as compared to before
flight after short-duration flights [158].
Crewmembers on flights lasting 6 months or more show
similar symptoms that essentially require more time to
resolve. Two cosmonauts returning from a 1-year mission on
Mir were noted to have hypogravitational ataxia for more
than 2 weeks, along with anomalies in control of voluntary
movements and gaze fixation [17]. Crewmembers flying stan-
dard 4- to 6-month tours on Mir or the ISS are usually able to
ambulate unassisted on the day of or after landing, but they
typically require deliberate concentration to do so and are
appropriately conservative, avoiding sharp corners and abrupt
stops and starts.
Other Postflight Findings
The timeline for complete recovery of all affected systems
after exposure to weightlessness has not been well charac-
terized. For crews on short-duration missions, this is largely
because the crewmembers can perform most of their required
duties without undue limitations and along a known trend of
improvement after landing. Fluid volume, bone, and muscle
are replenished and regulatory mechanisms are restored, and
these systems are not directly monitored in the postflight
period. Gradual return to accustomed preflight activities is
done largely at the discretion of the crewmembers themselves,
with participation of the medical team and further assessments
only as clinically indicated after the 3-day postflight assess-
ment. For long-duration flyers, a more rigorous and regulated
program of rehabilitation incorporates assessments of muscle
strength and bone density. Muscle strength returns within
several weeks, although due to intensive training the imme-
49
diate prelaunch level may not be reflective of the usual long
term level. The time required to return to a normative curve
of bone density is known to exceed the time of exposure to
weightlessness by a factor of 2 or 3, and complete recovery
may require between 1 and 3 years [159,160].
Functional fitness assessments consisting of a variety of
strength and endurance activities are done with U.S. crew-
members after long-duration missions to provide an over-
all gauge of functional ability. Selected results are shown
in Figure 2.8. These assessments are not conducted before
flight day five to avoid overexertion injuries in the immedi-
ate postflight period, but they should still reflect end-of-mis-
sion musculoskeletal capability. Some decrements remain at
5days after return, but substantial functional ability remains
and the variables measured typically return to or exceed pre-
flight baseline levels within 30 days of landing. Further data
from ISS crewmembers will help to better characterize the
readaptation process to guide postlanding activity require-
ments and rehabilitation efforts and in anticipation of plan-
etary exploration after prolonged transit in weightlessness.
Clinical Laboratory Values
An integral part of ascertaining the effects of space flight on
crew health has been clinical laboratory monitoring, and a broad
program was initiated at the outset of the Space Shuttle pro-
gram. Results are used by space medical personnel to identify
health impacts and guide further examination of individuals as
needed, in addition to determining health effects on the overall
flying population. Results from this program have helped in
establishing the clinical norms associated with short-duration
flight. In examining preflight and postflight operational data
for Shuttle flyers, Barratt and colleagues looked at differences
between lab values taken 3 days before launch and those taken
FIGURE 2.8. Selected functional fitness variables for ISS crewmem-
bers after space flights lasting 130197 days. Data are shown as
means standard error for 15 subjects. *Mean preflight value, num-
ber of repetitions; **Mean preflight value, force in pounds for a single
maximum exertion
50 E.S. Baker et al.

within a couple of hours after landing [161]. Operational data were all within normal limits. The very small, albeit statisti-
collected over 50 sequential Shuttle missions were analyzed, cally significant, changes do not seem to be physiologically
with consideration limited to first-time flyers to avoid any or clinically significant, and none of the averaged values fall
reflight bias. Selected results are shown in Table 2.6, which outside of established clinical norms.
emphasizes those modules that manifest significant changes.
Globally, these values reflect physiological reaction to Postflight Clinical Disposition
microgravity, a mild physiological stress reaction to entry and
The responses to weightlessness and landing involve multi-
landing, and relative hypovolemia in the immediate postflight
systemic physiologic changes and an acknowledged degree of
period. They were obtained during a period of transition in
impairment in comparison with preflight functionality. How-
fluid regulation and volume status, and as such they do not
ever any such impairments are typically mild and recover rap-
indicate frank pathology. Preflight and landing-day variables
idly. On landing day after short-duration (up to 17-day) Space
Shuttle flights, crewmembers are examined by flight sur-
geons, participate in limited debrief and investigational activi-
TABLE 2.6. Landing day vs preflight differences in blood chemistry,
ties, and then almost without exception are discharged into the
hematology, and endocrine variables in Space Shuttle crewmembers.
care of their families. A medical team is available continually
Mean
for consultation and further clinical care as needed. Physical
N difference SD p value
and laboratory examinations are repeated 3 days after landing,
Biochemistry module
after which crewmembers return to their normal activities and
Glucose (mg/dl) 93 8.65 18.77 0.0001
Uric acid (mg/dl) 89 0.91 0.86 0.0001
duty, including driving, light exercise, and flight in high-per-
Creatinine (mg/dl) 93 0.03 0.15 0.0434 formance aircraft, at their own discretion.
Alkaline phosphatase (U/L) 89 1.48 6.87 0.0448 After long-duration flights, dispositioning varies accord-
Lactate dehydrogenase(U/L) 89 7.19 21.44 0.0021 ing to program. After initial medical assessments on land-
Amylase (U/L) 89 8.93 17.68 0.0001 ing day, crewmembers are usually kept in special facilities
Sodium (mmol/L) 93 0.85 2.69 0.003
Potassium (mmol/L) 93 0.27 0.44 0.0001 for observation and assistance. In the United States, crew-
Phosphate (mg/dl) 89 0.43 0.76 0.0001 members are transported home from the landing site on
Magnesium (mg/dl) 89 0.15 0.18 0.0001 the day after landing, and if they show no evidence of
Carbon dioxide (mmol/L) 88 1.26 3.44 0.0009 complications such as debilitating orthostatic intolerance
Cholesterol (mg/dl) 88 5.64 20.33 0.0109
or neurovestibular impairment, they are typically released
Triglycerides (mg/dl) 89 9.79 30.67 0.0034
High-density lipoprotein (mg/dl) 84 6.86 8.78 0.0001 to their families on that day. For Soyuz landings, crew-
Very low-density lipoprotein 84 1.88 6.55 0.0101 members are transported from the landing site in Kazakh-
(mg/dl) stan back to the Gagarin Cosmonaut Training Center near
Apolipoprotein A1 (mg/dl) 62 16.27 25.25 0.0001 Moscow and live in a rehabilitation facility for as long
Hematology module
as needed. In both the US and Russian programs, a pro-
Red blood cells (1,000/mm3) 89 0.08 0.32 0.0166
Reticulocytes (%) 80 0.16 0.38 0.0003 tracted period of physical rehabilitation begins after return
Hematocrit (%) 89 0.27 3.16 0.4155a and forms the core of all postflight activities. The three
Hemoglobin (g/dl) 89 0.6 0.84 0.0001 main elements of rehabilitation in the immediate postflight
Mean corpuscular volume (FL) 89 1.04 3.23 0.003 period are rest, passive exposure to normal gravity loads,
Mean corpuscular hemoglobin (pg) 89 0.69 1.6 0.0001
and return to familiar surroundings. Activities and load-
Mean corpuscular hemoglobin 89 0.93 2.03 0.0001
concentration (g/dl) ing challenges are presented slowly and progressively as
Platelets (1,000/mm3) 88 14.52 37.8 0.0005 tolerated. A multidisciplinary team consisting of medi-
White blood cells (1,000/mm3) 89 1.31 1.66 0.0001 cal, physical training, psychological, and other specialists
Neutrophils (%) 89 17.81 11 0.0001 guide the process of full readaptation to gravity and nor-
Lymphocytes (%) 89 16.23 9.08 0.0001
Monocytes (%) 90 0.46 3.3 0.193a
mal life. Families are educated as to the expected effects of
Eosinophils (%) 88 1.41 2.22 0.0001 space flight and the progress of rehabilitation, and medical
Basophils (%) 87 0.07 0.33 0.573a personnel are continually available for response to clinical
Band cells (%) 87 0.38 1.44 0.0161 events. Typically crewmembers are cleared for return to
Endocrinology module normal activities and duties by 30 days after return from
Triiodothyronine (ng/dl) 78 17.2 28 0.0001
Thyroxine uptake (binding ratio) 61 0.03 0.1 0.004
long-duration flight.
Thyroxine (g/dl) 78 0.45 0.8 0.0001
Angiotensin (ng/ml/h) 76 3.07 5 0.0001
Cortisol (g/dl) 78 3.19 7.8 0.0005 Lunar Surface
Abbreviation: SD, standard deviation.
Preflight samples were taken under fasting conditions. p values are from To date, human experience operating in the fractional gravity
paired t tests, of another surface remains limited to the six Apollo missions
a
not significant but included for context. to the moon. In all, 29 astronauts flew in the Apollo program,
2. Human Response to Space Flight
with 12 landing to spend a total of 4 man-weeks on the lunar
surface. This experience allowed comparison of conditions of
otherwise similar vehicles and flight profiles in attempts to
isolate effects attributable to the stay in the one-sixth G lunar
gravity. Cardiovascular deconditioning and reduced exer-
cise capacity were known from earlier flight programs and
neurovestibular disorders from the Apollo flights preceding
the first moon landing. Thus, concern was high about these
and other lesser known effects that might influence landing
and surface performance. EVA experience and knowledge of
crew performance in the EVA environment was still in a very
early phase. However, with the first surface mission of Apollo
11, much of the concern in these areas was alleviated.
Cardiovascular Issues
After launch, the Apollo crews typically spent 34 days in
weightlessness during a period of Earth orbit, translunar
coasting, and lunar orbit before landing on the lunar surface.
Descent in the lunar excursion module took place with the
crewmembers in a vertical standing position involving +Gz
acceleration forces, during which the commander integrated
information from flight instruments and outside visual cues
while making piloting control inputs. Launching from the
lunar surface in the modules ascent stage after a period of
one-sixth G exposure involved a transient phase of nearly
1+Gz. There were no crew reports of lightheadedness or
visual disorders to suggest symptoms of orthostatic intoler-
ance during these phases. Postflight response to cardiovascu-
lar challenges were expected to be different for moonwalkers
than for other Apollo flyers who remained weightless, includ-
ing orthostatic response to LBNP. However, no difference was
found in resting and stressed heart rate between these two
groups [162]. Interestingly, the cardiothoracic ratio, a radio-
graphic index reflective of the heart size and position, was
significantly decreased in those who remained weightless but
was preserved in the moon-walking group [162]. Whether this
was related to actual work effects on the heart, anthropomet-
ric changes influencing the heart shadow, or other influences
remains unknown and a subject for further investigation.
A crewmember on the Apollo 15 mission did manifest a
period of bigeminal rhythm during surface activities, correlated
with symptoms of extreme fatigue. A self-induced period of
rest was taken before continuing with activities. This experi-
ence prompted the inclusion of anti-arrhythmic medications on
subsequent flights; potassium supplements were also included
to address the possibility that hypokalemia may have been
involved. The affected crewmember was later found to have had
undetected coronary disease at the time of the flight and experi-
enced a myocardial infarct 18 months after the mission [51].
Neurovestibular Issues
After the weightless period of translunar coast and lunar
orbit, pilots of the lunar excursion modules were able to fly
51
the spacecraft close to the lunar surface and effect landings,
changing the coordinates of flight to accommodate terrain
characteristics as needed [3]. There were no reports of vestibu-
lar illusions or disorientation during any of the dynamic lunar
flight phases. Surface activities proceeded as crewmembers
naturally adopted new, energy-efficient loping gaits more
suitable to the reduced gravity. Severe constraints on time and
spacecraft volume precluded any standard investigations of
vestibular function during the Apollo lunar flights, although
limited assessment of postural stability and purposeful move-
ment by video imagery could be done as crewmembers dis-
covered and tried new methods of locomotion. No incidents
of vestibular illusions or disorientation were reported during
surface activities among the 12 moon-walkers. Lunar gravity
seems to be an adequate stimulus for otolith organs to define a
gravitational vertical and guide posture control [154].
Other Aspects of Lunar Gravity
Apollo surface activities were associated with clinical effects
that probably resulted less from direct effects of reduced
gravity and more from the increase in workload and physical
exertion. Thermal stress, overuse injuries, and fatigue were
seen in many of the missions during exploration activities that
included equipment moving, sample collection, and surface
drilling [51]. Indirect effects of reduced gravity, such as dust
irritation because of lesser settling as compared with Earth,
were noted. Thus the clinical response to fractional gravity
may be viewed in terms of the activities required, rather like a
construction workplace.
Although Apollo crewmembers did not spend enough
time on the lunar surface to show cumulative musculoskel-
etal changes, muscle and bone loss can be expected given
sufficient time there. Adaptation must be viewed differently
from adaptation to the weightless environment, in which the
vast majority of crew time is spent operating normally in
an unloaded state. Lunar crews will be expected to under-
take heavy exertions and load manipulations during surface
activities, donning heavy suits and life support systems while
manipulating lunar material and equipment. The optimal bal-
ance among effects of lunar gravity, surface EVAs, and delib-
erate countermeasures during long-duration stays remains to
be delineated.
Conclusions
The past four decades have amply demonstrated that humans
can tolerate space flight well for long periods in orbiting
spacecraft. Historically, the direct causes of mortality have
been accidents occurring during dynamic phases of flight.
The vast majority of flight time has been spent in Earth orbit,
but both in orbit and on the lunar surface, humans have dem-
onstrated the ability to maintain adequate health and to work
productively.
52
The dominant condition associated with Earth orbit affect-
ing human physiology and health is weightlessness, which
induces predictable changes in crewmembers during adapta-
tion. Acutely, these changes can induce adverse symptoms
such as space motion sickness from neurovestibular adap-
tation and facial congestion associated with a rostral fluid
shift. Typically these symptoms do not limit crew activity and
resolve within a few days. Significant but clinically asymp-
tomatic early changes include regulation to a lower plasma
volume with a concomitant decrease in red blood cell mass,
changes in cardiac and respiratory dynamics, and changes in
anthropometry. Food intake is volitionally reduced and weight
loss is common. Changes in skeletal muscle morphology are
seen, and mass and strength in postural regions are reduced
after several days. Aerobic fitness is reduced but does not
limit inflight performance. Although bone demineralization
begins almost immediately upon gravitational unloading, it is
not detected following short-duration flights. Over periods of
weeks to months, loss of postural bone mass accumulates to
detectable thresholds, prompting the need for physical coun-
termeasures to apply loads to these selected areas.
Upon Earth return, readaptation to gravity involves a
reverse of these processes. Some degree of clinical impair-
ment in the immediate postflight period owing to orthostatic
intolerance or neurovestibular symptoms is common. Such
impairments resolve rapidly after short-duration flight but
require more recovery time after longer exposures to weight-
lessness. Bone requires the longest recovery period, exceeding
the time equivalent in weightlessness by probably a factor of
two or three. Carefully guided rehabilitation activities are
required to safely return crewmembers to preflight levels of
health and fitness.
Notably, the knowledge base of space medicine and physi-
ology has been constructed from the flight experiences of
healthy, highly screened professional flight crewmembers
and a small but growing number of scientists and paying
space flight participants. As the fledgling space tourist indus-
try expands, individuals with a wider variety of health back-
grounds will present themselves for possible space flight.
Direct application of space medicine knowledge to a broader
population should be done with caution; however, no specific
contraindications to space flight have been found for the gen-
eral population. Formal analysis of certifying and operational
medical information as well as conducting deliberate studies
should be considered in these new venues to expand clinical
space medicine accordingly.
Debate remains as to whether prolonged stays in weight-
lessness and further expeditions to the moon are safe enough
for continuing operations or for taking the next steps out-
ward without more detailed research findings. Historically, as
humans have ventured into new environments, such as under-
sea and at high altitudes, steps were taken based on existing
experience, information on analogous activities, and, when
appropriate, targeted preliminary investigation. As operational
milestones are established and reasonable safety assured,
E.S. Baker et al.
engineering and medical details are worked out in these envi-
ronments to characterize human response and to further opti-
mize human health and performance. The few explorers of the
beginning stages are then joined by larger numbers to increase
activity and productivity in these new environments.
Human space flight is no exception. The transition in space
from the few to the many is well underway. Currently we oper-
ate in a middle phase of this process, where the risk of adverse
events associated with weightlessness is considered accept-
able yet the maladaptive responses to weightlessness cannot
be ignored. From a safety standpoint, current knowledge does
not restrict us from continuing missions in weightlessness up
to a year. However, investigating and documenting details of
weightless physiology will inevitably reduce the overall risk
of human occupancy. This effort will guide the development
of effective strategies to mitigate health hazards and provide
a more scholarly basis on which to practice modern medicine
in this environment.
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3
Medical Evaluations and Standards
Gary Gray and Smith L. Johnston
Rationale
Candidates for space flight are medically screened to ensure
the success of each mission by providing healthy crews who
are able to perform operational objectives. Screening is
carried out according to a framework of medical standards
based on operational requirements. Consistent applica-
tion of medical standards helps to establish an informa-
tion database against which the assumptions underlying
the standards can be objectively reviewed. These standards
are revised over time as additional findings are collected.
The ultimate goal is to produce rational, evidence-based,
refined standards that reflect the operational requirements
and the medical risks involved in space flight. By doing so,
potentially larger subsets of the population that are today
excluded from space flight may be able to participate in
future space exploration.
Objectives
Selecting Healthy Candidates
Well-considered standards are expected to ensure selection of
spaceflight candidates who are healthy and likely to remain so
throughout their careers, and who will meet defined medical
requirements of their mission or missions. Medical testing is
geared to three objectives: to identify those individuals with
overt symptomatic disease, to identify asymptomatic disease
in individuals with no apparent manifestations, and to identify
individuals with a high probability of developing a flight-lim-
iting disorder during their careers. In meeting this third objec-
tive defining and applying standards becomes most difficult.
Estimating the probability of future disease is generally based
on risk factors (typically related to biochemical, genetic,
or lifestyle factors) that apply to entire populations, but for
which extrapolation from population data to individual risk is
imprecise. The lack of precision in applying population data
on disease probability to individuals may lead to different
outcomes in different countries and agencies based on differ-
ences in the distribution of disease and risk factors.
Health Maintenance After Selection
Medical screening after crew selection is based on the prin-
ciples of preventive medicine. The objectives are to main-
tain health, detect disease early, and ensure medical fitness
for ongoing training and operations. Screening programs are
designed in the interests of the individual (to maintain health)
and of the mission (to detect any medical problems that could
affect the mission). Hickman points out that in aerospace
medicine one generally encounters three types of individu-
als: (1) those with overt disease; (2) those with documented
asymptomatic disease; and (3) those who have no symptoms
but have abnormal test results [1].
The first type is the one most often encountered in clinical
medicinethe patient with an overt disease. The latter two
cases are more common to aerospace medicine.
For the second case, the patient with documented but
asymptomatic disease, aerospace medical flight disposition
is based on both the natural history of the disorder and the
pathophysiologic effects of that disorder in the often ill-
defined or poorly understood space environment. The rela-
tively small number of spaceflight crewmembers means that
it may take decades to derive sufficient epidemiologic data
for evidence-based decisions. Aeromedical decisions made in
the context of the space environment often rely on analogue
data derived from military aviator populations. This gener-
ally results in conservative decisions about flight disposition
for asymptomatic disease.
The third case, a patient with no symptoms but abnormal
test results, often requires further investigations. The prob-
ability of finding an abnormal test result during screening is
directly proportional to the number of tests performed. This
Type I, or alpha, error is seen when the null hypothesis is
true and n independent statistical tests are performed. The
probability that at least one test will appear to be statistically
significant (p 0.05) is [1.0(0.95)n]. If 10 tests are per-
59
60
formed, there is a [1.0(0.95)10] = 0.40 probability of a Type
I error. If 20 tests are performed, there is a [1.0(0.95)20] =
0.65 probability of a false-positive test result. Further, the
spaceflight crew population represents a highly select group
with a generally low prevalence of disease. Hence, apply-
ing clinical tests that have sensitivity and specificity char-
acteristics typical for a clinical environment will result in
frequent false-positive findings. In other words, the positive
predictive value of a screening test decreases with decreas-
ing prevalence of disease. Therefore we must understand the
operating characteristics of medical screening procedures in
the spaceflight crew population and the potential for false-
positive findings.
Operational Considerations
An important goal for medical selection and subsequent
medical evaluations is to certify that the crew is healthy.
Conditions with the potential to compromise flight safety,
such as a seizure disorder, are disqualifying. The disposition
of other medical conditions is based on a risk-assessment,
evidence-based model. NASAs selection and retention
standards should be related to bona fide mission require-
ments. For example, visual standards should be based on
actual vision requirements for operational tasks (e.g., fly-
ing, performing extravehicular activities, controlling remote
manipulators, or escaping in a contingency situation). Such
data can be acquired from simulator environments or from
actual operational settings. In many cases, however, stan-
dards are based on best estimates of operational require-
ments as made by physicians on space medicine boards.
Every effort should be made in drafting and reviewing stan-
dards to objectively relate those standards to actual opera-
tional requirements.
For spaceflight crewmembers, standards for selection and
periodic evaluation reflect the operational role of the indi-
vidual crewmember. In Space Shuttle operations, standards
for pilot astronauts differ from those of mission specialists
for mission-specific variables such as visual acuity. In the
past, less-restrictive standards have been defined for crew-
members designated as payload specialists (i.e., non-career
crewmembers who manage a specific Shuttle payload rather
than Shuttle systems).
Medical standards must further reflect the incremental
risk associated with extended, long-duration, and, ulti-
mately, exploration-class missions. The statistical risk of
a medical event occurring increases with mission duration;
this increase in risk must be reflected in medical standards
and screening procedures. For example, experiencing an
episode of renal colic would disqualify a trained mission
specialist for extended or long-duration missions but per-
haps not for short-duration Shuttle missions, since preflight
sonographic screening can rule out significant retained
calculi and the probability of developing a calculus during
a brief Shuttle mission is very low.
G. Gray and S.L. Johnston
Establishing Normative Data
A less obvious but important reason to define medical stan-
dards is the need for data to be obtained and pooled accord-
ing to standards that have been consistently applied with a
standardized, systematic approach. NASAs Life Sciences
effort has recognized the importance of this aspect of medical
screening since the initial astronaut screening for Project Mer-
cury in 1959, when medical screening data at the Lovelace
Foundation were recorded on IBM color-coded punch cards
[2]. This concept evolved into a standardized battery of medi-
cal tests to be performed on all Shuttle missions (the so-called
baseline data collection), the goal of which was to establish
an epidemiologic normative medical database in the space
environment.
This process, now known as medical assessment testing,
continues in the International Space Station (ISS) era. Medical
assessment testing is a vital aspect of medical screening that
helps to address the quintessential occupational medicine
questionnamely, does an abnormal finding in an individual
reflect an abnormal (pathologic) individual response or a nor-
mal physiologic response to an abnormal environment? Medi-
cal assessment testing, by developing longitudinal normative
data, plays an important part in providing data to address
this question in the environment of space. By establishing
new population norms, medical assessment testing provides
important space medicine information for current and future
spaceflight crews and, eventually, space travelers. (Collating
medical assessment test data has demonstrated, for example,
that the microgravity environment is conducive to renal stone
formation; medical screening procedures have been modi-
fied accordingly to identify crewmembers who are at risk of
forming stones during flight.)
In some respects, medical assessment testing seems to over-
lap with Life Sciences experimentation. However, medical
assessment testing provides a longitudinal view of health that
facilitates the definition of abnormality and new population
norms in spaceflight crews. Medical assessment testing does
not seek to study basic physiologic mechanisms in the space
environment (Life Sciences) but rather to clarify the definition
of normal vs. abnormal responses in the environment (Opera-
tional Space Medicine) for the greater good.
Select-In Versus Select-Out Concepts
in Medical Screening
Selection and retention standards are generally directed
toward identifying and excluding persons who do not meet
defined standards (e.g., those for vision or hearing). A greater
challenge is the ability to identify those physical and psycho-
logical attributes that might be considered advantageous in the
space environment. These concepts have been applied in the
area of psychological assessment to identify individuals who
have the right stuff, i.e., those who are not only technically
3. Medical Evaluations and Standards 61

competent but who can sustain the rigors of long-term space
flight while maintaining their equanimity, demonstrating
leadership when required, and remaining team players [3].
Select-in concepts can also be applied to physical attributes.
Since its inception, the Russian selection system has included
functional loading tests such as those that assess tolerance
of hypoxia in an altitude chamber, tolerance of acceleration
and high-g forces in the human centrifuge, and performance
under conditions of high thermal loading and sleep depriva-
tion. The results of these tests are included in the overall medi-
cal selection process for cosmonauts but are rarely used to
exclude candidates.
Although medical standards are generally based on the
select-out principle, this is likely to change in the future
as tests are developed with high individual specificity. For
example, the multinational Human Genome Project currently
under way will, within the next decade, facilitate identifica-
tion of individuals with disease-causing genes (select-out).
However, it may also allow us to identify individuals with
a genetic makeup that is resistant to the health problems of
expeditionary space missions, including radiation damage and
bone mineral loss.
Evolution of Medical Standards
Early in the human spaceflight program, selection standards
for astronauts and cosmonauts were not defined. Because the
risks of the space environment were largely unknown, the
approach to medical screening in both the U.S. and the Rus-
sian programs was, by necessity, conservative and involved
essentially testing everything that was possible to test. The first
Mercury astronauts were medically selected in four phases
[2]: an initial records review; an extremely thorough medical
evaluation held at the Lovelace Foundation in Albuquerque,
New Mexico; an evaluation to assess responses to environ-
mental stressors such as acceleration and hypoxia at Wright-
Patterson Air Force Base in Dayton, Ohio; and psychological
and psychiatric evaluations. The importance of maintaining
a database of such information was recognized and imple-
mented from the outset.
The medical screening battery for the initial Mercury astro-
nauts took 1 week to complete. Of the 100 military test pilots
who were initially screened, 31 very outstanding men were
selected to proceed in the program and to undergo the medi-
cal screening detailed in Table 3.1. (Findings from these 31
candidates are shown in Table 3.2.) Of the final 7 astronauts
selected from that group of 31, 1 had visual acuity of less than
20/25, 5 had hearing loss of more than 15 dB, 1 had a vocal
cord tumor (removed), and 1 had an abnormal lumbosacral
spine. In the absence of defined standards, the 7 Mercury
astronauts were chosen by a panel of both technical and medi-
cal representatives.
In 1977, using medical standards from the U.S. Air Force,
the U.S. Navy, the U.S. Department of Defense, and the
Federal Aviation Authority, NASA developed specific astro-
naut medical standards that were incorporated into a work-
ing set of medical evaluation requirements. These standards
continue to evolve; they were revised in 1991 to include the
potential effects of space station missions and the long-dura-
tion nature of such missions. The ISS Multilateral Medical
Operations Panel, which includes all ISS partners, adopted
a further revision of these standards as the basis for ISS
medical standards.
Although the ultimate goal is to define common stan-
dards for all crewmembers who are involved in ISS opera-
tions, the process is challenging because of cultural, ethnic,
and philosophical differences in the approach to medical
screening among the countries and agencies that are partici-
pating in the ISS. Examples of such nuances in the Russian

Table 3.1. Medical screening tests conducted with mercury astronaut candidates at the Lovelace foundation.
Test type Details
Detailed history, including Attitude of family members to hazardous flying
Aviation history
Physical examination Proctosigmoidoscopy
Ophthalmology, including dark adaptation studies, retinal photography
Otolaryngology, including calorimetric stimulation tests
Audiometry, including voice discrimination
Cardiology, including ECG, vectorcardiography, ballistocardography, tilt table testing and a special screen
for ASD and PFO based on measurement of arterial O2 saturation during Valsalva maneuvers
Neurology, including nerve conduction studies, EMG, EEG
Radiography Chest x ray (PA and lateral views), inspiration and expiration, cardiac fluoroscopy, barium enema,
lumbosacral spine, teeth, sinuses
Laboratory analyses Hematology, fasting blood sugar, cholesterol, blood group and type, serology, electrolytes, urea clearance,
catecholamines, protein-bound iodine, protein electrophoresis, blood volume, carbon monoxide, total body water
(tritiated water), liver function tests, urinalysis, 24-h urine ketogenic steroids and ketosteroids, throat cultures,
stool examination and culture, total sperm counts, total body radiation count and body potassium, pulmonary
function testing, maximum O2 uptake, body density
Abbreviations: ECG, electrocardiography; ASD, atrial septal defect; EEG, electroencephalography; EMG, electromyography; PA, posteroanterior; PFO, patent
foramen ovale.
62
Table 3.2. Summary of clinical findings in the initial 31 mercury
astronaut candidates.
Physical system Finding
Eyes Visual acuity <20/25
Convergence weakness
Exophoria
Borderline night vision
Ears, nose, and throat Sinusitis and sinus cyst
Hearing loss >15 dB
Allergic rhinitis
Chronic pharyngitis
Cervical adenitis
Deviated septum with obstruction
Hyperactive caloric response
Small Eustachian tube openings
Vocal cord tumor
Beta hemolytic strep carrier
Cardiovascular Hypertensive vascular disease
Vasomotor instability on tilt table
Increased carotid sinus sensitivity
Gastrointestinal Retrocecal appendix
Inverted cecum
Dilated external inguinal rings
Diverticulosis
Fissure and pruritus ani
Hemorrhoids
Abnormal stool examination
Genitourinary Abnormal urethral meatus
Varicocele
Orchitis (inactive)
Testicular atrophy
Prostatitis
Glycosuria
Orthopedic Abnormal dorsal spine
Abnormal lumbosacral spine
Tight hamstrings
Osteochondrosis dessicans
Neurological Borderline EEG
Dermatological Acne
Epidermophytosis
Seborrhea
Abbreviation: EEG, electroencephalography.
and U.S. cardiovascular standards are shown in Tables 3.3 and
3.4. The outcome of addressing these differences has been to
define a set of evolving standards that reflects the need to meet
mission objectives while providing flexibility for individual
agencies to use equivalent methods for testing and to conduct
additional screening depending on ethnic and cultural differ-
ences in disease prevalence. For example, upper gastrointesti-
nal endoscopy is included in medical screening in Russia and
Japan, where the incidence of gastric erosions and ulcers (in
Russia) and gastric cancer (in Japan) is significantly higher
than in the United States. Such variances in test methods and
agency-specific requirements for testing that go beyond those
defined in the basic medical requirements document are mani-
fested in a matrix document that is reviewed and agreed upon
by all involved agencies. These equivalence matrices, specific
to each agency, revolve around a core of common medical
standards that apply to all spaceflight crews.
G. Gray and S.L. Johnston
Medical requirements are subject to a regular review pro-
cess during which the standards are revised on the basis of
factors such as new epidemiologic data derived from analysis
5 of current standards procedures, normative population data
2 derived from medical assessment testing, information derived
2 from risk assessment of space flight, changes in operational
2 requirements for a particular mission, and changes in medical
7
19
support facilities available to crews during space flight. The
6 development of new medical technologies may also result in
1 revisions to medical standards; for example, successful radio-
1 frequency ablation of a Wolff-Parkinson-White bypass tract
8 allows medical qualification of candidates who would have
1
2
been disqualified in the past.
1
3
1
2 Medical Procedures for Selection
1 and Periodic Evaluation
1
1
3 The following sections outline the procedures for selection
2 and annual evaluation of ISS crews.
1
5
2 Outcomes of Medical Selection
2
2 It is interesting to compare the first Mercury screening, in
3 which seven astronauts were selected, with the results of the
2
process carried out at the Canadian Space Agency in 1992 to
1
1 select four astronaut finalists from an application pool of more
3 than 5,000 men and women [4]. After initial aptitude/qualifi-
5 cation screening by rsum review, 337 candidates underwent
1 medical screening in three phases. NASA medical standards
1
for mission specialists were used. Phase 1 screening involved
1
1 the use of a detailed medical questionnaire. Of the 337 appli-
1 cants given the questionnaire, 145 (43%) were disqualified
2 (Table 3.5). Additional screening carried out on this group led
to 51 candidates undergoing Phase 2 screening, which involved
a baseline medical examination carried out by a flight surgeon
at a Canadian military base. Of the 51 candidates who under-
went Phase 2 medical examination, 10 (20%) were screened
out. The final phase, Phase 3, of selection involved 1 week of
psychiatric, and medical screening carried out at a hospital on
an outpatient basis. Of the 20 finalists who underwent Phase
3 medical screening, which included all aspects of the NASA
mission specialist screening battery, 4 (20%) were medically
disqualified.
The results of this screening are similar to the Mercury
astronaut screening as well as the much larger NASA astro-
naut selections in the decades that followed (Table 3.6) [5].
Of 826 applicants to the NASA astronaut program, selected
for interview, and medically screened from 1977 through
1991 using NASA standards, 190 (23%) were disqualified for
medical reasons, the most common being inadequate vision
(78, or 9.4%). The most common medical causes for rejec-
tion of NASA astronaut candidates in recent years are listed
in Table 3.7.
3. Medical Evaluations and Standards 63

Table 3.3. Cardiovascular system disqualification standards for U.S. astronauts and Russian cosmonauts.
United States
1. Clinically significant hypertrophy/dilation
2. Ejection fraction <50%
3. Elevated blood pressure (140/90)
4. Recurrent symptomatic orthostatic hypotension
5. Case-by-case history of pericarditis
6. Case-by-case history of myocarditis
7. Case-by-case history of endocarditis
8. Clinical evidence of coronary artery disease, with myocardial infarction
and angina pectoris
9. History or findings of major congenital abnormalities of the
heart or vessels
History of atrial or ventricular septal defects or patent ductus,
successfully repaired after 1 year, case-by-case
10. Persistent tachycardia with supine resting pulse rate >100 beats per
minute
Clinical evidence of cardiac arrhythmia or conduction defect on resting
electrocardiography or Holter monitor abnormalities
11. Failure to meet NASA exercise stress test loads (maximum exercise,
ergometer, heat load, LBNP, and orthostatic/antiorthostatic stress tests)
12. Peripheral vascular disease
13. Cardiac tumors of any type
Cardiac tumors, unless benign and successfully resected without residual
cardiac disease after 6 months are reviewed on a case-by-case basis
14. All valvular disorders of the heart, including mitral valve prolapse
15. History of recurrent thrombophlebitis or thrombophlebitis with
persistent thrombus, evidence of circulatory obstruction, or deep
venous incompetence
16. Varicose veins if more than mild in degree, or if associated with edema,
skin ulceration, or scars from previous ulceration
Russia
Organic diseases of the cardiac muscle
Intracardiac hemodynamic disturbances
Hypertonic diseaseall stages and forms
Low tolerance of changes in body position
Pericarditis
Myocarditis
Not specified
Atherosclerosis, all cardiovascular system disease, cardiac rhythm
disturbances all forms of cardiac failure
Not specified
All cardiovascular diseases with cardiac rhythm disturbances
Decreased tolerance of physical loads
Diseases of the peripheral vessels obliterating endarteritis
Malignant tumors
Benign tumors causing functional disruption of organs
Numerous, benign, small-neoplasms (histologically confirmed lipomatosis)
that do not disturb organ function, impede movement, or interfere with
wearing special equipment are acceptable.
Single benign tumors must be surgically removed with re-examination
Organic disease of the cardiac valvular systemprolapsed mitral
or tricuspid valves with pronounced regurgitation
Disease of and consequences of trauma to peripheral vessels
Disease of and consequences of trauma to peripheral vessels

Abbreviation: LBNP, lower body negative pressure.

Table 3.5. Reasons for medical disqualification among 337

candidates for Canadian astronaut selection.
Table 3.4. Cardiovascular system screening procedures for U.S. No. (% of subgroup)
astronauts and Russian cosmonauts. Reason for disqualification disqualified
Times performed in each Phase 1. Medical Questionnaire (n = 337)
countrys program Vision 105 (31)
Procedures United States Russia Migraine history 12 (3.6)
Thyroid disorders 5 (1.5)
Chest x ray S S, A Ears/Hearing 4 (1.2)
Electrocardiography S, A S, A, MS Lungs/asthma 3 (0.8)
Echocardiography S S, A, MS Misc. (1 each); including Hodgkins disease, multiple 16 (4.7)
24-h Holter monitoring S S, A, MS sclerosis, Crohns, epilepsy, obesity, vertigo, others
Treadmill test S, A S, A, MS Totals 145 (43)
Orthostatic and MS S, A, MS Phase 2. Initial Medical Assessment (n = 51)
antiorthostatic tests Uncorrected visual acuity of <20/100 3 (5.8)
Lower-body negative pressure tests MS S, A, MS Cardiac 3 (5.8)
Cycle ergometry S, A, MS Asthma 2 (3.9)
stress test Neurologic 1 (1.9)
Heat load stress test S, A, MS Obesity 1 (1.9)
Neuroendocrine/dynamic S, A, MS Totals 10 (20)
electrocardiography Phase 3. Hospital-based Assessment (n = 20)
Capillaroscopy S, A, MS Chronic sinusitis (evident on computed tomography) 2 (10)
Phono/mechanocardiography S, A, MS Ophthalmologic (retinal disease) 1 (5)
Abnormal electroencephalogram 1 (5)
Abbreviation: S, selection examination; A, annual examinations; MS, mis-
Totals 4 (20)
sion-specific examinations.
64 G. Gray and S.L. Johnston

Table 3.6. Requirements for astronaut selection and annual requalification examinations.
Procedure Selection Annual
Medical history Yes Yes
Physical examination Full Full
Otolaryngology
Specialist examination Yes If indicated
Audiogram Yes Yes
Tympanogram If indicated
Sinus imaging If indicated
Ophthalmology Full examination, including: Full examination, including:
Visual acuity Visual acuity
Color vision Color vision
Depth perception Depth perception
Phorias Phorias
Tonometry Tonometry
Perimetry Perimetry
Fundoscopy Fundoscopy
Retinal photos
Corneal topography
Dental examination Clinical examination and imaging, to include Clinical examination with bite-wing
panorex and complete periapical dental x rays within x rays when clinically indicated
the previous 2 years
Cardiopulmonary
Exercise stress test Yes Periodica
Pulmonary function tests Yes Yes
Resting ECG Yes Yes
24-h ECG monitor Yes
Echocardiogram Yes
Imaging
Chest x ray Yes If indicated
Mammogram Women Women over 40: every 2 years until
age 50 then yearly
Bone densitometry No First annual and every 3 years
Abdominal sonography Yes
Panorex Within the previous 2 years If clinically indicated
Pelvic sonography Women
Gastrointestinal
Proctosigmoidoscopy Yes Periodicb
Stool
Culture Yes If indicated
Occult blood Yes Yes
Ova and parasites If indicated If indicated
Laboratory
Blood work, including hematology, Yes Yes
clinical biochemistry,
immunology, endocrinology
Urinalysis Yes Yes
Tuberculin test (PPD) Yes Yes
Screening for sexually Yes Yes
transmitted diseases
Musculoskeletal
Aggregate joint movement Yes
Anthropometry Yes
Muscle mass Yes
Selected strength measurements Yes
Radiation exposure evaluation Yes Annual
a
At ages 30, 35, and 40, then biannually to age 50, then annually, or as otherwise indicated.
b
Beginning at age 40, every 5 years to age 50, then every 3 years.

Military pilot screening also yields similar results, with
a 21% rejection rate of finalist candidates in the Israeli Air
Force [6] and a 1418% rejection rate (general and academy
candidates) among Royal Australian Air Force applicants [7].
Interestingly, the Israeli study followed selected candidates
through 1 year of flight training, during which time 7.4% were
rejected for medical reasons that were not discovered during
selection. Of these, 17% resulted from nondisclosure during
the initial selection process. Many aspects of medical screen-
ing continue to rely on accurate historical information that is
3. Medical Evaluations and Standards
Table 3.7. Most frequent causes for disqualification in U.S. astro-
naut selection.
Physical system Findings
Ophthalmologic Distant visual acuity, depth perception, color vision,
esotropia, refractive error, astigmatism, corneal
distortion
Cardiovascular Dysrhythmias (supraventricular or ventricular
tachycardias), hypertension, left bundle-branch
block, pulmonary stenosis
Otolaryngologic Sinusitis, allergic rhinitis, hearing loss
Genitourinary Kidney stones, renal anomalies
Endocrine Abnormal thyroid
Psychological Personality disorder, drug abuse, physical abuse
Other Positive tuberculin test, chronic liver enzyme
abnormalities, chronic headaches, irritable bowel
syndrome, carbohydrate intolerance
not always entirely reliable, since candidates may be reluctant
to divulge information that they perceive may be disqualify-
ing. The Israelis found that a way to improve this accuracy
was to concurrently obtain a history of the applicant from the
applicants parents [6].
Mission-Specific Medical Screening
In addition to the selection and annual health screening aspects
of astronaut medical evaluations, which are similar to evalua-
tions in aviation medicine, space medicine has the significant
additional requirement for further screening leading up to and
during missions of short duration (days), extended duration
(weeks), and long duration (months to years). Long-duration
missions (those lasting more than 30 days) include medical
assessments at 180 days before launch (L 180), L 30 or
L 45, L 7 or L 10, L 2, landing (or return) day (R + 0),
R + 2, R + 3, R + 5-7, R + 10, R + 15, R + 20, and R + 30. Medical
screening is also planned during long-duration missions every
30 days as well as before and after extravehicular activities and
before landing. The rationale for these assessments is twofold:
first to confirm a crewmembers medical fitness to carry out
the mission, and second to gather normative medical data with
which to compare apparent excursions from the norm. Indi-
vidual preflight data and population normative data are used to
guide postflight rehabilitation activities and to evaluate return
to preflight health and fitness to return to duty.
Selection vs. Retention Standards:
The Waiver Process
The goal of medical selection standards is to identify can-
didates with the requisite physical and mental attributes to
accomplish mission objectives and to identify candidates
who have no apparent evidence of potential career-limiting
medical problems. For trained crews, training and mission
65
experience become significant factors in determining medical
suitability for continuing crew duties. Although standards
based on factors that might affect mission and flight safety
are the same for selection and retention, standards that reflect
mission objectives or personal crew health may differ for
retention. This difference reflects both the expenditure of
training resources as well as the operational mission expe-
rience of the crewmember. For example, hearing standards
for selection are stricter than those for retention; this differ-
ence acknowledges the degradation in hearing thresholds that
takes place with age and noise exposure and recognizes that
these thresholds, while still within acceptable limits for mis-
sion requirements, are likely to be lower in older, experienced
crewmembers.
Trained crewmembers who fail to meet retention medi-
cal standards may still be considered for continuing duties
through a waiver process, during which the crewmembers
medical condition is reviewed. Considerations include the
crewmembers ability to carry out training requirements,
any potential risk to mission safety, possible risk to mission
objectives, and risk to the individual from further deteriora-
tion of the condition with continued duties. A panel of flight
surgeons develops and periodically assesses a risk-assess-
ment model based on known variables related to the crew-
members medical condition and operational experience as
well as mission objectives. If the risk assessment is favor-
able, a waiver of a particular standard may be recommended
to allow the crewmember to continue with limited or full
duties, with monitoring and follow-up of the medical con-
dition. Astronauts have been granted waivers for continuing
duties for hearing loss that falls below standard, for certain
cardiac arrhythmias (such as self-limited supraventricular
tachycardia), and for nonmetastatic testicular cancer that has
been removed with no sequelae. The waiver process has been
carefully and successfully applied throughout the U.S. space
program. Military and civilian aviation regulatory authorities
use similar procedures.
Population Bias in Astronaut
Medical Screening
One outcome of the intensive medical screening and ongoing
periodic health assessments that are in use for astronauts is the
generation of a population base that differs greatly from the
general population in terms of disease prevalence. Population
studies in analogous population cohorts, such as airline pilots
[8,9] and U.S. Air Force pilots [10], have identified a much
lower incidence of cardiovascular and respiratory diseases,
but a small excess risk of cancer (colon and brain cancer,
malignant melanoma, and Hodgkins disease in commercial
pilots and testicular and urinary bladder cancer in Air Force
pilots) when compared to the general age, sex-matched, U.S.
population. The prevalence of death from all accidental causes
is higher in fliers, but the excess in cancer mortality is of
66
concern. Airline pilots, like astronauts, are exposed to greater
amounts of cosmic radiation and electromagnetic forces than
are Earth-bound individuals, and the potential link between
such exposure and long-term astronaut health continues to be
a focus of study.
Because of the difference between the highly select popula-
tion resulting from astronaut medical selection and the general
population, extrapolation of disease incidence and prevalence
from other large studies are not likely to be valid. In the Fram-
ingham Study, a prospective, longitudinal population study
of the residents of Framingham, Massachusetts, investigators
defined the risk of a cardiovascular event on the basis of clas-
sic risk factors, including age, total and high-density lipopro-
tein cholesterol, blood pressure, and covariables (smoking,
diabetes, and left ventricular hypertrophy) in the population
[11]. Since the distribution and prevalence of standard risk
factors in the astronaut population are often different from
those in the Framingham population [12], extrapolation of the
Framingham predictive equations to the astronaut population
may not be valid.
A further complication in terms of standard medical screen-
ing procedures is that the low prevalence of disease, such as
cardiovascular disease in the highly select astronaut popula-
tion, makes the predictive value of screening tests, such as
exercise stress testing, extremely low (Bayes theorem). This
low disease prevalence makes the probability of false-posi-
tive findings more likely than true-positive findings for many
standard clinical testssuch as exercise stress testingthat
have specificity in the 7080% range. The implications of this
are that in both initial and periodic screening, standard testing
must be applied with a careful understanding of the probable
meaning of positive (abnormal) findings, and tests with the
highest possible specificity are preferable.
These and other concerns about astronaut health are cur-
rently being addressed in an important initiative, the NASA
Longitudinal Study of Astronaut Health. This long-term
study, begun in 1994, is designed to follow current and for-
mer astronauts; its goals are to examine the incidence of acute
and chronic morbidity and mortality of this group and to com-
pare the risks of morbidity and mortality associated with the
astronauts occupational exposures to the corresponding risks
for a control population of civil service employees at Johnson
Space Center in Houston. This prospective, longitudinal epi-
demiologic study will provide much-needed data on the health
implications of occupational exposure in the environment of
space, from short-duration flights through extended and long-
term, low Earth orbit missions and, ultimately, expedition-
ary space exposures. The study will also provide ongoing
prevalence data from which predictive equations for disease
probability can be derived that are relevant to the astronaut
population. A somewhat reassuring negative finding is that to
date, no statistical difference in the incidence of cancer has
been found between the control and astronaut populations,
although an apparent trend toward a higher incidence in astro-
nauts has been noted.
G. Gray and S.L. Johnston
Medical Standards for Future
Space Exploration
A return to Earth from low Earth orbit because of a medi-
cal event or an emergency is an expensive proposition that
would seriously affect mission objectives. Nevertheless,
such a return is possible and, in fact, has been done on
at least three occasions from Russian space stations. One
of these returns to Earth involved chronic prostatitis and
sepsis; another involved a potentially serious cardiac dys-
rhythmia that had not been noted before flight [13]. The
most likely scenarios prompting medical return, would
involve subacute or escalating processes that allow some
time for planning. However, if the need for return is urgent,
Shuttle contingency plans allow an emergency landing to
be made within several hours. Contingency plans for the
ISS include the possibility of emergency evacuation and
return to Earth within 24 h using a Soyuz or crew return
vehicle (see Chap. 7). The choice of medical support pro-
vided on orbit is also based on the premise of a potential
emergency return to Earth.
In the realm of expeditionary missions to Mars, return-
ing to Earth for a medical emergency will not be possible.
Communication from an expeditionary spacecraft will be
increasingly delayed the further the craft is from Earth; for
example, a maximum round-trip communication delay of
44 min can be expected between Mars and Earth. Even a Mars
fly-past with direct return to Earth may represent a 9-month
round-trip, and most Mars mission scenarios involve mission
durations of 1836 months. Analysis of spaceflight data sug-
gests that the risk of a serious medical eventwhich in near-
Earth orbit would affect the mission by possibly requiring a
medical evacuation to Earthis approximately 0.06 per per-
son-year of flight. This translates to 1 event per 2.8 years of
spaceflight operations for a crew of six (see Chap. 7).
Medical selection and provision of medical services for
space expeditions thus takes on a new dimension. Onboard
medical facilities for early expeditionary missions are likely
to be more comprehensive than they are for Shuttle missions,
for example, weight and space constraints will impose sig-
nificant limits on the ability to provide medical care. Priority
must be given to providing for contingency situations such as
trauma or fire, and more emphasis should be placed on provid-
ing primary prevention of medical diseases through stringent
preflight screening and treatment.
The first crew to depart for Mars is likely to be the most
intensely medically studied crew in the history of space
flight. Medical technology has advanced at a pace exceed-
ing even that of space technology in the past several decades.
Medical technology will allow us to identify not only indi-
viduals with disease potential (screen-out procedures) but
also individuals with characteristics that may make them
resilient to the hazards of long-term space flight (screen-
in attributes). Within the next decade, the Human Genome
3. Medical Evaluations and Standards
Project is likely to have completed human genetic mapping,
thereby providing tools with which to identify genetic
markers for a host of human diseases. Noninvasive medical
imaging will allow us to define organ structure, including
vascular anatomy, and will facilitate our identification of
individuals with lesions such as central arteriovenous mal-
formations. Developments in radiation biotechnology may
allow us to identify individuals whose cellular makeup is
more resistant to radiation damage.
This intensive medical evaluation, including genetic test-
ing, that will be incorporated into future medical standards
may create significant ethical dilemmas with respect to the
selection process. For example, identifying a previously
unidentified genetic marker of serious disease in a trained
astronaut undergoing screening for an exploration mission
may have not only serious career consequences, but it may
also affect other life issues such as insurability. Before such
testing is introduced, the issues associated with it must be
scrutinized by medical ethicists as well as by flight surgeons
who are involved in developing medical standards for flight.
Ethical considerations should include the greater good of
the mission, as well as the relative risks and benefits to the
individual.
Perhaps the biggest challenge in medical screening is the
ability to develop tools with which to identify crewmem-
bers with desirable psychological attributes to minimize the
risk of individual dysfunction or interpersonal conflicts that
might jeopardize mission safety or effectiveness. Although
we have learned a great deal from human behavior in ana-
logue environments (e.g., polar expeditions and nuclear sub-
marines) as well as from isolation experiments, there clearly
is a great deal left to learn about selecting individuals with
the right stuff for long-term expeditionary space missions.
The psychological aspects of space flight are discussed
further in Chap. 19.
67
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[1]. Hickman JR. The clinical basis for aeromedical decision mak-
ing. AGARD Conference Proceedings 553, K112; 1994;
Neuilly-Sur-Seine, France.
[2]. Lovelace WR, Schwichtenberg AH, Luft UC, Secrest RR. Selection
and maintenance program for astronauts for the National Aeronau-
tics and Space Administration. Aerospace Med 1962; 33:667684.
[3]. Santy PA, Jones DR. An overview of international issues in
astronaut psychologic selection. Aviat Space Environ Med
1994; 65:900903.
[4]. Gray GW. Selection of astronauts/medical issues: The 1992 Cana-
dian astronaut selection. Can Aeronaut Space J 1996; 42:139142.
[5]. Pool SL, Nicogossian AE, Moseley EC, Uri JJ, Pepper LJ. Medi-
cal evaluations for astronaut selection and longitudinal studies. In:
Nicogossian AE, Huntoon CL, Pool SL (eds.), Space Physiology and
Medicine. 3rd edn. Philadelphia, PA: Lea & Febiger; 1993:375393.
[6]. Froom P, Cyjon A, Lotem M, Ribak J, Gross M. Aircrew selection:
A prospective study. Aviat Space Environ Med 1988; 59:165167.
[7]. DeHart RL, Stephenson EE, Kramer EF. Aircrew medical stan-
dards and their application in the Royal Australian Air Force.
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[8]. Band PR, Spinelli JJ, Ng VTY, Moody J, Gallagher RP. Mor-
tality and cancer incidence in a cohort of commercial airline
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[9]. Irvine D, Davies DM. The mortality of British Airways pilots,
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[10]. Grayson JK, Lyons TJ. Cancer incidence in the United States
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[11]. Anderson KM, Wilson PWF, Odell PM, Kannel WB. An
updated coronary risk profile. Circulation 1991; 83:356362.
[12]. Berry MA, Squires WG, Jackson AS. Fitness variables and the
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[13]. Newkirk D. Almanac of Soviet Manned Space Flight. Houston,
TX: Gulf Publishing Company; 1990.
4
Spaceflight Medical Systems
Terrance A. Taddeo and Cheryl W. Armstrong
Providing adequate medical care for spaceflight crews requires
that appropriate diagnostic tools and treatment modalities be
available to them throughout their mission. The challenge
for mission planners is deciding what medical capability to
provide and then packaging it in a way that meets the many
unique constraints of space flight. Crews also must receive
adequate training that will help them to make correct diag-
noses and administer the appropriate level of care to an ill or
injured crewmember.
As discussed in Chap. 7, identification of appropriate levels
of medical care is driven by the risks that have been iden-
tified in space flight. One practical way of identifying such
risks is by studying risks among analogous populations, such
as military pilots, submarine crews, and Antarctic winter-over
research teams. From these groups, which undergo medical
screening processes similar to those of spaceflight crews, the
probabilities and risks of illness occurring during a mission
can be estimated. Review of reported illnesses in U.S. and Rus-
sian spaceflight crews also can be useful, although such data
were not available to medical mission planners in the earliest
days of space flight. The duration of a space mission and the
number of high-risk activities associated with it (e.g., extrave-
hicular activities) will also influence decisions concerning the
content of onboard medical systems. Mission planners must
also consider environmental factors that are unique to the
space environmentfactors that include microgravity, radia-
tion, toxicology, microbiology, and purity of reclaimed water.
Finally, the unique physiological responses to space flight
must also be examinedspace adaptation syndrome, cardio-
vascular deconditioning, and bone demineralization, among
others. Only by accounting for all of these factors can the best
possible care and facilities be provided to spaceflight crews.
Space Medical Practitioners
Two groups are charged with providing real-time care
for spaceflight crews: the onboard crew medical officers
(CMOs) and the ground medical support personnel. Although
communications resources may enable a ground-based flight
surgeon to guide a CMO through a technical procedure, the
extent of the CMOs training will correlate strongly with
medical success. The CMOs skill level must therefore be
taken into account in the selection of medical hardware.
Medical hardware flown should be appropriate to the skill
level and training of the crew. There is no sense in selecting
medical hardware that a CMO has not been trained to use.
Although including a physician in every spaceflight crew
would greatly enhance mission safety [1], there are too few
NASA astronaut-physicians for this to be possible. Flight
rules now designate that each Space Shuttle crew of five to
seven individuals must include two CMOs who, whether
they are physicians or not, must complete a training sylla-
bus designed to provide them with the basic knowledge and
skills necessary to provide first-line care on orbit. Similarly,
two CMOs are designated from the crew complement of three
to six long-duration crewmembers on the International Space
Station (ISS). These individuals are trained by flight surgeons
and other operational personnel.
The medical kits provided on various spacecraft (including
the ISS, the Space Shuttle, and the Russian space station Mir)
were and are designed to meet identified mission-specific
risks and to account for any limitations in the medical back-
ground of the crew. CMOs are trained to a basic degree of
competence through a series of structured classes and field
exercises. Onboard refresher training for medical emergency
procedures is included for long duration flights.
Medical Hardware Considerations
The desired medical capability must be weighed against the
limited resources available on board a spacecraft. Electrical
power, potable water, and other consumables are valuable and
limited commodities and are not always available for routine
medical purposes. The most expensive and scarce commod-
ity is crew time. Vehicle operations and maintenance tasks,
payload operations, and other important activities compete
69
70
with medical requirements for time in the crew schedule. To
ensure that medical tasks are completed, the procedures must
be simple and intuitive and must involve a minimal number
of personnel. A medical evaluation procedure that is either
awkward to perform or requires an inordinate amount of time
to complete may not be completed. Also, an injured or ill
crewmember will reduce the workforce for onboard activity
significantly.
Providing terrestrial standards of care to space crews requires
careful planning and forethought. Mass, volume and power
are extremely valuable on a spacecraft, and the medical sys-
tems flown must minimize their consumption of these assets.
Priority must also be given to items with a long shelf life,
stability at ambient temperature and humidity, and minimal
maintenance requirements. Simple and intuitive designs for
equipment will aid in its effective use, particularly by the non-
medical user who may handle the items very infrequently.
This is especially important for resuscitation hardware.
Microgravity itself presents many design challenges. For
example, any process that includes gas-fluid separation will
require centrifugal force or gas-fluid filter systems to act
in place of gravity. Procedures that generate particulate or
fluid contamination of the spacecraft, such as dental drilling,
specimen handling, or surgical procedures, must be performed
in specialized enclosures. Finally, restraint of operator, sub-
ject, and support items is a fundamental requirement in
microgravity.
In microgravity, most examination techniques are
unchanged, and most of the standard diagnostic and therapeu-
tic instruments need not be modified. Stethoscopes, otoscopes,
venipuncture kits, and many other familiar items have been
used successfully for years in space flight, once crews have
become accustomed to moving and managing these items in
weightlessness and adjusting for other factors such as high
ambient noise and low light levels.
The following subsections provide a discussion of selected
medical equipment and capabilities and some of these unique
considerations. Astronauts with spaceflight experience must
be included in the design of new medical systems, as they
have insight not available to ground engineers. Each new
generation of hardware must reflect the hard won lessons of
space medical operations.
Medical Restraint Systems
Experience has shown that medical examinations, intrave-
nous (IV) techniques, and other procedures can be accom-
plished in the microgravity environment without specialized
restraint systems. However, more complicated medical proce-
dures cannot be performed without the use of proper restraint
systems to bring CMO, patient, and medical support items
into close proximity. To support contingency events in which
acute care would be required, the best solution is a dedicated
medical restraint table that either can be deployed quickly
or is always deployed and at the ready. Prototypes of such
T.A. Taddeo and C.W. Armstrong
systems have been tested during parabolic flight [2] and space
flight [3]. The ideal medical restraint would accommodate
the neutral body posture assumed in microgravity (by both
patient and CMO) and would support basic procedures, such
as simple wound repair, as well as more complex operations.
This restraint also would incorporate interfaces for medical
equipment and medical waste management, such as body-
fluid-saturated pads and discarded sterile packaging.
For the near future, dedicated constantly deployed medical
restraints are unlikely to be included in spacecraft because of
volume constraints. Other available surfaces have been and
will be used, however, such as cabin walls and galley tables.
However, a smaller hybrid system consisting of a rapidly
deployable surface attached to dedicated structural mounts
offers a viable alternative. In an acute, life-threatening situation,
the time to deploy a restraint is a critical factor that could well
affect patient survival. These considerations contributed to the
development of the current ISS crew medical restraint sys-
tem. That system consists of a rapidly deployable rigid plat-
form that quickly restrains both patient and operator in close
proximity to the onboard medical system. This restraint sys-
tem also affords electrical isolation from the station systems
and rescuers should defibrillation be required.
Automated Ventilation
Advanced airway handling methods have been developed for
use in the weightless environment and have been taught to
CMOs. Equipment for endotracheal intubation has been on
hand on Skylab, Space Shuttle, Mir space station, and ISS
missions. Some type of manual respirator has always been
available during these programs, and a small automated
ventilator also is now part of the ISS medical inventory.
Because of electrical power constraints in spacecraft, the
best option for automated ventilation is a compact pressure-
driven ventilator that uses the storage pressure of respirable
gas. On Earth, such ventilators are typically used for short-term
acute care. For a patient who is incapable of adequate spon-
taneous respiration, the compact pressure-driven ventilator is
a potentially lifesaving device that replaces a crewmember
who would otherwise be required to give manual respirations
with a bag device. As noted above, ample assistance may
not be available should a medical crisis occur in flight. In
the ground-based transport and acute roles, pressure-driven
ventilators are generally powered by 100% oxygen. This
immediately creates a problem in the enclosed environment
of a spacecraft in that the patient-ventilator exhaust is nearly
90% oxygen, with the remaining 10% being expired CO2 and
water vapor. In an enclosed cabin, ambient concentrations of
oxygen can rise quickly and exceed flammability limits.
A short-term option in such a contingency would be to add a
diluent gas such as nitrogen to the cabin atmosphere to main-
tain safe concentrations. However, this option comes at a cost
in consumables as overall atmospheric pressure bleeds off to
maintain cabin pressure limits.
4. Spaceflight Medical Systems
Two potential solutions exist that could lessen that cost in
consumables. The first would be to provide an overboard dump
in which only the expired ventilator gas is vented overboard
into space or into some vessel from which the gas may be
reclaimed later. The second solution is to provide a dual-gas
system (oxygen/nitrogen) and a gas blender that would allow
the CMO to use only the oxygen concentration required to
address a clinical need. This solution also would mitigate the
potential problems of pulmonary oxygen toxicity, usually
seen after 18 or more hours of breathing 100% oxygen, should
ventilation be required for that length of time. However, since
high concentrations of oxygen may still be needed to meet
medical requirements, some combination of these 2 solutions
may be optimal.
Any future contingency respiratory capability should use a
closed system that will minimize loss of consumables. Also,
the use of an advanced technology such as molecular sieve beds
would enable a gas delivery system to obtain and concentrate
oxygen from the ambient cabin atmosphere before venting the
exhaust directly back into the cabin, with a minimal effect on
atmospheric composition.
Intravenous Fluid Therapy
Administration of small doses of IV medications is not
problematic in weightlessness. However, large volumes of flu-
ids for hydration cannot be administered in the same manner
as on Earth, by using gravity-driven free-flow devices or
pumps that automatically separate air and fluid. The simplest
means of providing IV fluids in weightlessness combines a
soft fluid packaging with a surrounding pneumatic pressure
device, such as a blood pressure cuff. Regulating the pressure
and the size of the flow orifice provides a rough means of
controlling the rate of fluid administration. Injection fluids
must be specially packaged with a minimum amount of air,
and care must be taken while preparing the infusion system to
avoid introducing further air into the line. Additional air-fluid
separation may be facilitated with an in-line filter system, or
a bubble trap. More precisely regulated infusion rates, such
as those required to administer continuous or controlled-dose
medications, will require an automated pump. Prototypes of
powered infusion pumps have been tested during space flight
[1,4], and a small commercially available device has been
adapted and included in the ISS inventory.
Although prudence dictates maintaining at least a small
stock of prepackaged IV fluids, storing large quantities of
IV fluids would represent a significant overhead in launch
mass and stowage. Moreover, most IV fluids have 1-year
shelf lives. A more efficient use of resources would be to
produce sterile injection-grade fluid as needed during flight
from potable water. Exploration-class missions should have
this capability. Technology to produce sterile injection-
grade fluid for space flight using ion exchange columns
and premeasured electrolyte and drug aliquots has been
extensively examined [5,6].
71
Cardiac Defibrillation
Contemporary advanced life support methods require the
capability for cardiac monitoring and defibrillation. A monitor/
defibrillator may consist of an off-the-shelf item that has
been modified for space flight, with capabilities for monitor-
ing, defibrillation over a range of selected energy levels, and
external cardiac pacing. Some unique considerations arise in
microgravity. A notable example is the application of charged
paddles to a patients chest, an act that normally requires a
force of 11 kg (25 lbs) to ensure adequate electrical contact.
Since the rescuer has no weight in microgravity, self-adhesive
defibrillator pads (which are becoming more common in
ground use) must be used. Insulation and electromagnetic
interference shielding must also be considered to protect those
delivering care from inadvertent electrical shock as well as
to protect sensitive avionics from damaging electromagnetic
interference pulses.
As an acute response item, the monitor/defibrillator must
be maintained in a state of readiness. Batteries must be
charged to energize the capacitor, which delivers the direct
current counter-shock, and the unit must be rapidly and
easily accessible. Since much of the patient positioning and
insulating requirements will be met by a medical restraint
system, restraint deployment may be a rate-limiting step in
delivering lifesaving defibrillation. The CMO must be well
trained in the safe and effective use of the defibrillator, since
situations requiring cardiac defibrillation, although rare, will
very likely arise and require treatment well before ground
consultation can be obtained.
Cardiopulmonary Resuscitation
Common methods of closed-chest cardiac massage depend on
the weight of the rescuers upper torso to drive the force of
compression; however, this weight, and hence this force, are
absent in microgravity. A restrained rescuers muscular power
alone may provide adequate compressive force for a short time.
Such methods have been tested during parabolic flight [7] and
during space flight [8]. However, delivering compressions of
adequate force can quickly become exhausting, particularly
for crewmembers who have experienced musculoskeletal
deconditioning during space flight. Effective compressions
can be delivered more easily by the rescuer if he or she is
reacting against an opposite surface with the feet rather than
by being restrained in a more terrestrial-standard position at
the patients side. This position requires no dedicated rescuer
restraint, it uses combinations of extensor muscles throughout
the body, and it keeps the area near the patients chest and
head clear for airway and IV procedures.
Alternatively, mechanical devices may be used, such as
pneumatically powered thumpers, or simpler lever devices,
such as those tested during the STS-40 (June 5 to June 14,
1991) Space Shuttle mission [8]. Such devices would be best
integrated into an advanced medical restraint system.
72
The On-Site Medical Checklist
Like the medical support hardware, written medical procedures
carried on board spacecraft for the use of crewmembers must be
as user-friendly and as intuitive as possible. Preflight training
with the hardware must use the same procedures as those to
be used in space flight. Moreover, since training sessions with
the hardware may have taken place months or even a year
before use, documentation of the supporting procedures must
be clearly and concisely written. Diagrams, photos, simple cue
cards, logical grouping of items, and effective labeling can
increase crew efficiency and effectiveness. These design prin-
ciples are even more important as multinational crews, whose
members are reading and writing in nonnative languages,
work together on the ISS. Notably, the ISS Medical Checklist
is a bilingual guide that is printed on facing pages in the two
main operative languages of the ISSEnglish and Russian.
Medical Systems of Spacecraft
and Space Stations
Projects Mercury and Gemini
Spaceflight medical systems have evolved from a few medi-
cations and monitoring devices to advanced life support
hardware. The medical kit (see Figures 4.1 and 4.2) for the
six piloted Project Mercury flights (May 5, 1961 to May 15,
1963) included an anti-motion-sickness drug, a stimulant,
and a vasoconstrictor to treat shock. The astronauts electro-
cardiograph, blood pressure, respiratory rate, galvanic skin
resistance, and rectal temperature were monitored by physi-
cians on the ground [9].
FIGURE 4.1. Mercury medical kits containing items such as antibiot-
ics, decongestants, stimulants, electrode paste, and medications to
treat nausea and diarrhea. (Photo courtesy of NASA)
T.A. Taddeo and C.W. Armstrong
The number of medications flown increased slightly dur-
ing the 10 crewed Project Gemini space flights (March 23,
1965 to November 15, 1966). The contents of the Gemini VII
(December 4 to December 18, 1965) medical kit reflect this
change (see Table 4.1 and Figure 4.3). In addition to the medi-
cal kit, medications were also carried in a separate survival
package. The contents of the Gemini VI-A (December 15 to
December 16, 1965) survival package medical kit included a
stimulant, motion sickness medication (oral and injectable),
pain medication (oral and injectable), an antibiotic, and aspi-
rin [11].
The Apollo Program
During the crewed Apollo Program flights (October 11, 1968
to December 19, 1972, consisting of two Earth orbit flights,
two lunar orbit flights, one lunar swingby flight [Apollo 13,
April 11 to April 17, 1970], and six lunar landing flights),
separate medical kits were required for the command mod-
ule and the lunar module (see Figures 4.44.6). These kits
included primarily medications and bandage items. An aux-
iliary kit was added to the command module kits for Apollo
16 (April 16 to April 27, 1972) and Apollo 17 (December 7 to
December 19, 1972). The contents of the Apollo command-
module medical kit are listed in Table 4.2, and the contents
of the lunar-module medical kit are listed in Table 4.3.
The Skylab Missions
The 3 crewed Skylab missions lasted 28 days (May 25 to June
22, 1973), 59 days (July 28 to September 25, 1973), and 84
days (November 16, 1973 to February 8, 1974) and provided
new challenges for medical support teams. Onboard medical
FIGURE 4.2. Mercury medical kit containing items such as saline
solution, bandages, stimulants, and decongestants (Photo courtesy
of NASA)
4. Spaceflight Medical Systems 73

TABLE 4.1. Contents of the Gemini VII medical kit [10].

Medication Indication Dose Amount
D-Amphetamine sulfate Stimulant 5-mg tablets 8
Aspirin-phenacetin- Pain Tablets 16
caffeine
Cyclizine HCl Motion sickness 50-mg tablets 8
Diphenoxylate HCl Diarrhea 2.5-mg tablets 16
Meperidine HCl Pain 100-mg tablets 4
Methyl cellulose solution Eye lubricant 15-ml bottle 1
Parenteral cyclizine Motion sickness 45 mg (0.9-ml 2
injector)
Parenteral meperidine HCl Pain 90 mg (0.9-ml 2
injector)
Pseudoephedrine HCl Decongestant 60-mg tablets 16
Tetracycline HCl Antibiotic 250-mg coated 16
tablets
Triprolidine HCl Decongestant 2.5-mg tablets 16

FIGURE 4.5. Apollo clinical physiological monitoring kit and emer-

gency medical kit (Photo courtesy of NASA)

FIGURE 4.3. Apollo medical kit containing items such as skin cream,
antibiotic ointment, nasal spray, band-aids, and stimulants (Photo
courtesy of NASA)

FIGURE 4.6. Apollo emergency medical kit (Photo courtesy of NASA)

The Space Shuttle

FIGURE 4.4. Apollo Command Module medical kit (Photo courtesy
of NASA)
systems were upgraded to provide an enhanced drug formulary
and capabilities including wound care, dental care, minor sur-
gery, urinary catheterization, and microbiology assessment.
Skylab astronauts received 80 h of paramedic-level training
before launch. The contents of the Skylab medical kits are
listed in Table 4.4.
The Shuttle Orbiter medical system (SOMS) has flown on all
Space Shuttle flights and is designed to support a crew of five
to seven for up to 20 days. A process exists to make necessary
changes and upgrades to the SOMS, and over the course of
more than 100 Space Shuttle flights, the SOMS has evolved to
meet mission needs and to keep up with advances in medical
therapy and pharmacology. This process of change and review
also permits some degree of customization for each mission.
The current SOMS comprises several subpacks, namely the
emergency medical kit (EMK), the medications and bandages
kit (MBK), the medical accessory kit (MAK), the airway
medical accessory kit (AMAK), the contaminant cleanup
74 T.A. Taddeo and C.W. Armstrong

TABLE 4.2. Contents of the Apollo Command-Module medical kit [12].

Items Indication Formulation Amounta
Actifed (triprolidine/pseudoephedrine) Decongestant Tablets 60
Afrin (oxymetazoline) Decongestant Nose drops 3
Ampicillin Antibiotic Tablets 60
Aspirin Analgesic Tablets 72
Atropineb Cardiac arrhythmias Injectable solution 12
Bacitracin Antibiotic Eye ointment 1
Benadryl (diphenhydramine)c Antihistamine Tablets 8
Darvon (propoxyphene) Analgesic Tablets 18
Demerol (meperidine)b Analgesic Injectable solution 6
Dexedrine (d-amphetamine) Stimulant Tablets 12
Lidocaineb Cardiac arrhythmias Injectable solution 12
Lomotil (diphenoxylate) Diarrhea Tablets 24
Marezine (cyclizine) Antihistamine Injectable solution 3
Marezine (cyclizine)d Antihistamine Tablets 24
Methylcellulose Laxative Capsules 2
Multivitamins Tablets 20
Mylanta (simethicone) Antiflatulent Tablets 40
Nasal emolient 1
Neosporin (polymixin B) Antibiotic Ointment 1 or 2
Ophthaine (proparacaine preparation) Topical anesthetic Eye drops 1
Pronestyl (procainamide)b Cardiac arrhythmias Tablets 80
Scopolamine-dexedrine Motion sickness Tablets 12
Seconal (secobarbital) Sleeping aid Tablets (100 mg) 21
Seconal (secobarbital)c Sleeping aid Tablets (50 mg) 12
Skin cream 1
Tetracycline Antibiotic Tablets Varied
Tetrahydrozoline HCle Eye drops 1
Tylenol (acetaminophen)c Analgesic Tablets 14
Band-aids 12
Compress bandages 2
a
Not all medications were carried in the amounts noted on all flights.
b
Carried on Apollo-16 and -17 only.
c
Carried on Apollo-8 only.
d
Carried on the first 4 missions only.
e
Carried on Apollo-17 only.

TABLE 4.3. Contents of the Apollo Lunar Module medical kit [12].
Items Indication Formulation Amounta
Actifed (triprolidine/pseudoephedrine) Decongestant Tablets 8
Afrin (oxymetazoline) Decongestant Nose drops 1
Aspirin Analgesic Tablets 12
Atropine Cardiac arrhythmias Injectable solution 4
Darvon (propoxyphene) Analgesic Tablets 4
Demerol (meperidine) Analgesic Injectable solution 2
Dexedrine (d-amphetamine) Stimulant Tablets 4
Lidocaine Cardiac arrhythmias Injectable solution 8
Lomotil (diphenoxylate) Diarrhea Tablets 12
Methylcellulose Eye drops 1
Neosporin (polymixin B) Antibiotic Ointment 1
Pronestyl (procainamide) Cardiac arrhythmias Tablets 12
Seconal (secobarbital) Sleeping aid Tablets 6
Band-aids 6
Compress bandages 2
Urine collection and transfer devices 6
a
Not all medications were carried in the amounts noted on all flights.
4. Spaceflight Medical Systems 75

TABLE 4.4. Contents of the Skylab In-Flight Medical Support System [13].
Equipment Kit Usage requirement
Accumulator assembly Microbiology No restriction
Adhesive tape, Dermicel Bandage No restriction
Adhesive tape, Micropore Bandage No restriction
Air sampler Bandage Not applicable
Airway, pharyngeal Therapeutic No restriction
Aneroid sphygmomanometer Diagnostic No restriction
Applicator, dental Bandage No restriction
Applicators, silver nitrate (12) Bandage No restriction
Antibiotic lubricant Catheterization No restriction
Band-Aids (100) Bandage No restriction
Barrier, sterile field (2) Minor Surgery Physician use/approval required
Batteries (8 AAA), (8 AA), (8 C) Diagnostic No restriction
Betadine squares (4) Minor Surgery No restriction
Bili-Labstix/Urobilistix Hematology/Urinalysis No restriction
Binocular loupe Diagnostic No restriction
Blood lancets (75) Hematology/Urinalysis No restriction
Calcium alginate balls (50) Hematology/Urinalysis No restriction
Can opener Not applicable Not applicable
Cannula Therapeutic Physician use/approval required
Capillary pipettes (50) Hematology/Urinalysis No restriction
Catheter, urinary Catheterization Physician use/approval required
Coagulase plasma Command Module Resupply No restriction
CO2 accumulator assembly Microbiology No restriction
CO2 generators (24) Microbiology No restriction
Collection bag (3) Catheterization No restriction
Container, injectables Therapeutic Physician use/approval required
Demerol injectors (5) Therapeutic No restriction
Dermicel surgical tape Hematology/Urinalysis No restriction
Digital hand counter Hematology/Urinalysis No restriction
Disinfectant pads (60) Not applicable No restriction
Disposable bags (20) Microbiology No restriction
Dressing boot (Unnas) Bandage No restriction
Dressing, abdominal (6) Bandage No restriction
Drug modules (2) Drug Supply Module Not applicable
Elastic wraps (3) Bandage No restriction
Elevator Dental No restriction
Endotracheal tube Therapeutic Physician use/approval required
Eye patch, cotton (8) Bandage No restriction
Eye patch, plastic (2) Bandage No restriction
File Dental No restriction
Filter strips (10) Microbiology No restriction
Fluorescein strips (12) Bandage No restriction
Forceps, 6-in (3) Microbiology No restriction
Forceps, mandibular anterior Dental No restriction
Forceps, mandibular posterior Dental No restriction
Forceps, maxillary anterior Dental No restriction
Forceps, maxillary posterior Dental No restriction
Forceps, mosquito Minor Surgery Physician use/approval required
Forceps, splinter Bandage No restriction
Forceps, tissue Minor Surgery Physician use/approval required
Gauze, dental Dental No restriction
Gauze, roller (6) Bandage No restriction
Gauze squares No restriction
4 in. 4 in. (24) Bandage
2 in. 2 in. (12) Bandage
2 in. 2 in. (20) Minor Surgery
Gauze squares, Betadine Bandage No restriction
Minor Surgery Physician use/approval required
Gauze, Vaseline (6) Bandage No restriction
Glass marking pencil (2) Microbiology No restriction
Gloves, examination (2 pair) Hematology/Urinalysis No restriction
Gloves, surgical (2 pair) Catheterization No restriction
(continued)
76 T.A. Taddeo and C.W. Armstrong

TABLE 4.4. (continued)

Equipment Kit Usage requirement
Glucose (2) Therapeutic Physician use/approval required
Heat sink Command Module Resupply No restriction
Hemacheck assembly Hematology/Urinalysis No restriction
Hemoglobin meter Hematology/Urinalysis No restriction
Hemolysis applicators (50) Hematology/Urinalysis No restriction
Hemostat Catheterization No restriction
Hemostat, Crile, curved Minor Surgery Physician use/approval required
Hemostat, Crile, straight Minor Surgery Physician use/approval required
Hemostat, Kocher Minor Surgery Physician use/approval required
Hemostat Therapeutic No restriction
Hydrogen peroxide Command Module Resupply No restriction
Immersion oil bottles (3) Microscope No restriction
Incubator Not applicable Not applicable
Injectables container Therapeutic No restriction
Lancets (75) Hematology/Urinalysis No restriction
Laryngoscope Therapeutic Physician use/approval required
Lens (100) Drug Supply Module No restriction
Lens tissue Microscope No restriction
Light bulbs (14) Diagnostic No restriction
Loop holders (2) Microbiology No restriction
Light source, head-mounted Diagnostic No restriction
Microscope Microscope No restriction
Microscope stage Drug Supply Module No restriction
Mirror/light Dental No restriction
Myringotomy knife Diagnostic Physician use/approval required
Nasogastric tube Catheterization No restriction
Needle holder Minor Surgery Physician use/approval required
Needles, hypodermic
16-Gauge (2) Therapeutic No restriction
18-Gauge (2) Therapeutic No restriction
20-Gauge, 4 in. (1) Command Module Medical Kit Physician use/approval required
20-Gauge (2) Therapeutic No restriction
25-Gauge (4) Therapeutic No restriction
27-Gauge, 13/16 (3) Dental No restriction
Neurologic exam instruments Diagnostic Physician use/approval required
Nozzle Catheterization Physician use/approval required
Ophthalmoscope Diagnostic No restriction
Otoscope Diagnostic No restriction
Otoscope specula (33) Diagnostic No restriction
Oxidase strips (25) Command Module Resupply No restriction
Petri dish, large (20) Command Module Resupply No restriction
Petri dish, small (20) Command Module Resupply No restriction
Pressure infusor assembly Not applicable Physician use/approval required
Probe Minor Surgery Physician use/approval required
Resupply container (2) Command Module Resupply No restriction
Retractors, skin/muscle (ALMS) Minor Surgery Physician use/approval required
Scalers, curette Dental No restriction
Scalpel, #10 (2) Minor Surgery Physician use/approval required
Scalpel, #11 (2) Minor Surgery Physician use/approval required
Scissors Bandage No restriction
Scissors, sharp/sharp Minor Surgery Physician use/approval required
Sedative restorative material (8) Dental No restriction
Sensitivity discs Command Module Resupply No restriction
Ampicillin (50)
Cephalothin (50)
Erythromycin (50)
Sulfasoxazole (Gantrisin) (50)
Penicillin G (50)
Tetracycline (50)
Sensitivity disc dispenser (3) Microbiology No restriction
Silver nitrate applicators (12) Bandage No restriction

(continued)
4. Spaceflight Medical Systems 77

TABLE 4.4. (continued)

Equipment Kit Usage requirement
Slide dispenser (75 slides) Microscope No restriction
Slide stainer Not applicable No restriction
Slide streaker (2) Drug Supply Module No restriction
Slide stainer expendables Not applicable No restriction
Specific gravity refractometer Hematology/Urinalysis No restriction
Specula, disposable Diagnostic No restriction
Sphygmomanometer Diagnostic No restriction
Splint assembly (4) Not applicable No restriction
Sterile water (2) Command Module Resupply No restriction
Steri-Strips (20) Bandage No restriction
Stethoscope Diagnostic No restriction
Stewarts transport media (58) Command Module Resupply No restriction
Streaking loops Microbiology No restriction
Suture material, chromic catgut; 000 with fingerstick Minor Surgery Physician use/approval required
(2 needle)
Suture material, dermal #5-0 with fingerstick (2 needle) Minor Surgery Physician use/approval required
Suture material, silk, 00 Minor Surgery Physician use/approval required
Swabs, cotton (24) Bandage No restriction
Swabs, dry (20) Therapeutic No restriction
Swabs, dry, crew nasal and throat samples (18) Microbiology No restriction
Swabs, dry, crew illness (12) Microbiology No restriction
Swabs, dry, cultural transport (48) Microbiology No restriction
Swabs, wet, antibiotic Sensitive (48) Microbiology No restriction
Swabs, wet, crew body sample (18) Microbiology No restriction
Swabs, wet, environ. surface sample (90) Microbiology No restriction
Syringe, dental Dental No restriction
Syringe, epinephrine Therapeutic No restriction
Syringe, plastic, 2.5-cc (2) Therapeutic No restriction
Syringe, plastic, 50-cc with needle (2) Therapeutic No restriction
Syringe, 1-cc tubex holder Therapeutic No restriction
Syringe, plastic with needle, 50-cc (3) Therapeutic Physician use/approval required
Syringe, 2-cc tubex holder Therapeutic No restriction
Syringe, 5-cc Therapeutic No restriction
Syringe, with needle, 1-cc (6) Microbiology No restriction
Syringe Catheterization No restriction
Taxos A discs (50) Command Module Resupply No restriction
Taxos P discs (50) Command Module Resupply No restriction
Thermometer, oral (2) Diagnostic No restriction
Three-way valve Command Module Medical Accessory Kit Physician use/approval required
Tissue forceps Minor Surgery Physician use/approval required
Tongue depressor Diagnostic No restriction
Tourniquet Hematology/Urinalysis No restriction
Towel Catheterization No restriction
Tracheostomy equipment Therapeutic No restriction
(Unnas) Boot dressing Bandage No restriction
Urinary catheter Catheterization Physician use/approval required
Urine sample bag (6) Microbiology No restriction
Valve, three-way Command Module Medical Accessory Kit Physician use/approval required
Vaseline gauze (6) Bandage No restriction
Velcro, sticky-back (6) Hematology/Urinalysis No restriction
Vials (58) Command Module Resupply No restriction
Water, sterile (2) Command Module Resupply No restriction
Work table Minor Surgery No restriction
Zephiran (benzalkonium chloride) wipes (81) Hematology/Urinalysis Catheterization No restriction

kit (CCK), the operational bioinstrumentation system, the
electrode attachment kit, patient and rescuer restraints, and a
resuscitator (see Figure 4.7).
Only the EMK and the MBK flew on STS-1 (April 12 to
April 14, 1981). The EMK contains injectable medications,
dental items, IV fluid administration equipment, and other
diagnostic and therapeutic instruments. The MBK contains
oral medications, topical medications, and bandages for
treating most in-flight problems. Oral medications are
in shrink-wrapped plastic bottles with attached tops and
78
FIGURE 4.7. Shuttle Orbiter Medical System. Following redesign in
2000, components include Saline Supply Bag, EENT Subpack, IV
Administration Subpack, Trauma Subpack, Sharps Container, Drug
Subpack, and Airway Subpack (Photo courtesy of NASA)
push-up dispensers for easy management in microgravity.
Crewmembers record medication use in data logs stowed
in the MBK. At the recommendation of an experienced
Space Shuttle CMO, a space motion sickness kit was also
developed. This kit, which is stowed in the pocket of the
MBK, includes, in one convenient location, all of the items
necessary for giving an intramuscular injection of prometha-
zine, thus saving crew time early in the mission, when space
motion sickness is most prevalent.
The operational bioinstrumentation system and the electrode
attachment kit were added to the SOMS in 1982. These two
items can be used during a medical contingency to downlink
a crewmembers electrocardiogram waveform to the Mission
Control Center.
The SOMS was reevaluated in the wake of the STS-51-L
Challenger accident (January 28, 1986), and the MAK, the
CCK, patient and rescuer restraints, and a resuscitator were
added for the return-to-flight mission, STS-26 (September
29 to October 3, 1988). The MAK, which contains additional
IV fluid and urinary catheterization supplies, is used to stow
additional mission-specific medical items. The CCK pro-
vides protective equipment, including gloves, goggles, masks,
containment bags, and hazard identification labelsitems
used to protect the crew in the event of a hazardous spill or
another contamination event. The restraints and resuscita-
tor enhance the crews ability to perform cardiopulmonary
resuscitation on board the Space Shuttle.
After a review of the system by emergency medicine consul-
tants in 1990, the AMAK was added. The AMAK allowed all
of the airway management equipment to be located in a single
place and added the capability for advanced airway procedures.
In 1992, the CCK was redesigned, and a supplemental
medical extended-duration Orbiter pack (MEDOP) was
T.A. Taddeo and C.W. Armstrong
developed. The CCK redesign reduced the overall size of
the kit and added an eyewash capability to decontaminate
the eyes. This Shuttle emergency eyewash was designed to
interface with the Space Shuttle galley (as the water supply
source) and the waste collection system (for disposing of the
contaminated water). The Shuttle emergency eyewash design
includes a pair of swim goggles and tubing with special
interfaces for the galley and waste collection system. The
MEDOP was designed specifically for extended-duration
Orbiter missions (that is, for Space Shuttle missions last-
ing longer than 12 days). The MEDOP contains additional
supplies located in the EMK or MBK as well as a skin sta-
pler and a rapid test for oropharyngeal group A -hemolytic
streptococcal infection, among other unique items [15].
An IV accessory kit was developed in 1998. IV supplies are
kept in the IV accessory kit, which is similar to the AMAK,
for quick access. Although the IV accessory kit is not currently
part of the Space Shuttles standard medical complement, it
flew on four missions at crew surgeon request.
Because of hazards posed by particular payloads and medical
experiments, a defibrillator has been flown on two Space Shuttle
missions. This commercial-off-the-shelf device was modified
to meet flight certification specifications. In addition to the defi-
brillator, a cardiac drug kit and crew medical restraint system
were developed. The cardiac drug kit contains primarily ACLS
cardiac medications to be used with the defibrillator. The crew
medical restraint system attaches to the middeck lockers and
restrains a crewmember while rescuers provide that crewmem-
ber with appropriate medical care. The crew medical restraint
system also ensures that the patient is electrically isolated, so
that the defibrillator can be used without risk of damage to
Space Shuttle systems from extraneous electrical current.
The contents of the standard SOMS, excluding the MEDOP,
are listed in Table 4.5. The SOMS package was redesigned
after a review by a panel that included extramural experts
in pharmacology and wilderness medicine. This redesign,
finalized in 2000, improves the layout and user-friendliness
of the system and mirrors the structure of the ISS medical
kits. A key element is the use of dedicated subpacks, with
each subpack serving a specific function or classification of
care. The subpacks include an airway subpack, an IV admin-
istration subpack, a saline supply bag, a trauma subpack, an
otolaryngologic (eye, ear, nose, and throat) subpack, and a
drug subpack. No changes were recommended for the CCK.
The MEDOP will continue to be manifested for missions
lasting longer than 12 days. The new SOMS was first flown
on the STS-98 mission in early 2001.
The Russian Space Station Mir
The medical capability on the Mir space station (19862001)
was a product of many years experience in long-duration
space flight. Medical items carried on Mir were oriented
toward supporting two or three crewmembers; these items
were replenished continuously to support the permanent
4. Spaceflight Medical Systems 79

TABLE 4.5. Contents of the Shuttle Orbiter Medical System.

Name Description Amounta
Absorbant wipes 72
Ace bandage 3 in. wide 2
Adaptic bandages 3 in. 3 in. 3
Afrin (nasal spray) 3-ml bottles 6
Air temperature monitors 90120 F 2
5888 F 2
Airway Oral 1
Alcaine (Proparacaine eye drops)b 15-ml bottle 1
Alcohol wipes 36
Ambien (zolpidem) 10 mg 75 tablets
Ambulatory leg bag 600-ml bag 1
Amikin (amikacin)b 250 mg/cc, 2-cc unit 1
Amoxil (amoxicillin)b 500 mg 24 capsules
Anusol-HC suppositories 6
Ascriptin (aspirin) 325-mg aspirin w/Maalox 25 tablets
Atropineb 1 mg/cc, 2-cc unit 2
Bactrim DS (trimethoprim/sulfamethoxasole)b 28 tablets
Bags
Chemical resistant 16 in. H 12 in. W 8
Double stick tape closure
Mess-up mitts 12 in. 11.5 in. 2
Tape closure
Red bio-wipe 12 in. 11.5 in. 2
Tape closure
Ziploc 12 in. 12 in. 9
Ziploc closure
Band-aids 1 in. 3 in. 15
Sheer spot 16
Benadryl (diphenhydramine)b, injectable 50 mg/cc, 1-cc unit 2
Benadryl (diphenhydramine), oral 25 mg 20 capsules
Biohazard identification labels 20
Blistex lip balm 1
Blood pressure cuff with aneroid sphyg 1
Butterfly infusion sets 2
Catheter, Foley 16 Fr, 30-cc balloon, silastic 2
Chemstrip 10 13
Ciloxan (ciprofloxacin) ophthalmic solutionb 0.3%, 2.5-ml bottle 3
Cipro (ciprofloxacin)b 500 mg 22 tablets
Claritin (loratadine) 10 mg 20 tablets
Cotton balls 10
Cotton swabs 6
Cough lozenges 5 mg dextromethorphan 15
Cyclogyl (cyclopentolate)b 1%, 15-ml bottle 1
Demerol (meperidine)b 50 mg/cc, 1-cc unit 4
Dental kit
Carver/file 1
Mirror 1
Needles Long: 27 G, 1.25 in. 6
Short: 27 G, 0.75 in. 6
Orangewood sticks 2
Syringe 1
Temporary filling 1
Toothache kit 1
Eugenol anesthetic drops
Tweezers
Cotton pellets
Marcaine (bupivacaine)b 0.5% w/epinephrine 1:200,000 6 dental carpules
Dexamethasoneb 10 mg/cc, 1-cc unit 2
Dexedrine (dextroamphetamine)b 5 mg 30 tablets
Diamox (acetazolamide)b 250 mg 30 capsules
Drape, sterile 1
(continued)
80 T.A. Taddeo and C.W. Armstrong

TABLE 4.5. (continued)

Name Description Amounta
Dulcolax (bisacodyl) 5 mg 30 tablets
Suppository, 10 mg 6
Duricef (cefadroxil)b 500 mg 20 capsules
Elastoplast tape 4 in. wide 1 roll
Electrode attachment kit 1
End-tidal CO2 detector 1
Entex LA (long-acting) (phenylpropanolamine/guaifenesin) 75 mg phenylpropanolamine hydrochloride, 400 mg 40 tablets
guaifenesin
Epinephrineb 1:1000, 1-cc unit 5
Eye pads 6
Finger splint 1
Flagyl (metronidazole)b 250 mg 28 tablets
Fluorescein strips 8
Forceps Blunt 1
Fox shield Metallic eye patch 1
Gauze pads 4 in. 4 in. 27
Genoptic (gentamicin) ophthalmic ointmentb 3.5-g tube 1
Gloves Chemical resistant 7 pair
Gloves Nonsterile, surgical 9 pair
Gloves Sterile, surgical 2 pair
Goggles Eye protection 7
Haldol (haloperidol)b 5 mg/cc, 1-cc unit 2
Hazard identification labels Decals (6 each level) 30
Hemostat Small 1
Curved 1
Imodium (loperamide HCl) 2 mg 32 capsules
Isoptin (verapamil)b 2.5 mg/cc, 2-cc unit 2
IV administration set 2
IV intracatheters 18 G 2
20 G 2
Kenalog (triamcinolone) cream 15-g tube 1
Kerlix dressing 4.5-in. wide 1 roll
Kling 3-in.-wide gauze dressing 5 rolls
Laryngoscope Handle with med blade 1
Lever lock cannula 2
Lidocaine/cardiac 20 mg/cc, 5-cc unit 2
Lidocaine/cardiac injector 2
Lotrimin (clotrimazole) cream 15-g tube 1
Lubricant (water-soluble) 3g 7
Magnifying glass 4 magnification 1
Masks, surgical 7
Medical data logs Crew size + generic variable
Merocel Pope (posterior nasal packing) 10 cm 3
Morphine sulfateb 10 mg/cc, 1-cc unit 3
Motrin (ibuprofen) 400 mg 30 tablets
Mycelex-7 (clotrimazole)b 100-mg suppositories 7
Mylanta Double Strength 24 tablets
Narcan (naloxone)b 0.4 mg/cc, 1-cc unit 2
Nasostat balloons 2
Needles 22 G, 1.5 in. 2
18 G, 1.5 in. 2
Neosporin Plus cream with lidocaine 0.5-oz tube, 40-mg lidocaine 1
Nitroglycerin patchb 15 mg 1
Nitrostat (nitroglycerin tablets)b 0.4 mg (1/150) 25
Op Site Transparent dressing 6
Operational Bioinstrumentation System Electrocardiograph monitor
Electrode attachment kit 1
Operational Bioinstrumentation System belt 1 each
w/signal conditioner 1
Sternal harness 2
Intravehicular activity cable 2
Biomed cable
Ophthalmoscope head 1
(continued)
4. Spaceflight Medical Systems 81

TABLE 4.5. (continued)

Name Description Amounta
Ophthalmoscope spare bulb 1
Otoscope 1
Otoscope spare bulb 1
Otoscope speculum 1
Ovral-21 (norgestrel/ethinyl estradiol)b 21 tablets
Patient/rescuer restraints 2 sets
Penrose tubing (tourniquet) 2
Pepto Bismol 24 tablets
PH strips 10 strips
Phazyme-125 (simethicone) 20 soft gel cap-
sules
Phenergan (promethazine) 50 mg/cc, 1-cc unit 11
Phenergan (promethazine) Oral, 25 mg 30 tablets
Suppository, 25 mg 14
Polysporin (polymyxin/bacitracin) 1-oz tube 1
Pope otowicks 6
Povidone-iodine swabs 20
Proventil (albuterol) inhalerb 17-g container 2
Pyridium (phenazopyridine) 200 mg 20 tablets
Radiation dosimeters
Refresh (artificial tears, eye drops) 0.3 cc 12
Restoril (temazepam) 15 mg 40 capsules
Resuscitator
Rimantadine 100 mg 42 tablets
Roller clamp irrigation assembly 1
Ruler, plastic measurement
Saline 100 ml 3
250 ml 1
500 ml 2
0.9% NaCl
Salt tablets 1 g NaCl 128 tablets
Scalpels No. 10 2
No. 11 1
Scissors, curved w/in surgical instrument assembly 1 pair
Shuttle emergency eyewash Irrigation goggles 1
Silvadene (silver sulfadiazine) cream 20-g tube 1
Silver nitrate sticks 5
Skin temperature monitors 84106F 15
Space Motion Sickness Kit 1
Alcohol wipes (10)
Band-aids (10)
Phenergan injectables (10)b
Tubex injector (1)
Splint Finger 1
Steri-Strip skin closures 3
Stethoscope 1
Suction device Toomey syringe 1
Sudafed (pseudoephedrine) 30 mg 100 tablets
Surgical Instrument Assembly 1 each
Forceps, small point
Needle holder
Hemostat, small
Tweezers, fine point
Scissors, curved
Suture 4-0 Dexon w/needle 1
5-0 Ethilon w/needle 1
4-0 Ethilon w/needle 2
3-0 Ethilon w/needle 2
2-0 Vicryl w/CT-1 needle 1
Syringes 10 cc 3
3 cc 6
Tape, Dermicel 1 in. wide 2 rolls
(continued)
82 T.A. Taddeo and C.W. Armstrong

TABLE 4.5. (continued)

Name Description Amounta
0.5 in. wide 2 rolls
Telfa pads 3 in. 4 in. nonstick bandages 5
Thermometers, disposable (Tempadot) 96104F 18
Tongue depressors 5
Tracheal tube with stylet 1
Tracheostomy Kit 1
Alcohol wipes
Dissecting scissors
Curved hemostats
Tracheal hook
Silk ties
Tracheostomy tube
Tracheostomy tube holder
Scalpel
Transparent dressing (Tegaderm) 5
Tubex injector 2
Tylenol (acetaminophen) 325 mg 60
Tylenol #3 (acetaminophen with Codeine)b 300 mg acetaminophen with 30 mg codeine 20 tablets
Urine Test Package 1
Chemstrip 10 13 strips
Color chart
Valium injectable (diazepam)b 5 mg/cc, 2-cc unit 2
Valium, oral (diazepam)b 5 mg 30 tablets
VIRA-A (vidarabine) ophthalmic ointmentb 3%, 3.5-g tube 1
VoSol HC otic solution 10-ml bottle 1
Xylocaine (lidocaine)b 2% w/epinephrine, 1:100,000, 2-cc unit 1
Xylocaine (lidocaine) Plainb 2% without epinephrine, 2-cc unit 1
Y-Type catheter extension 2
Zithromax (azithromycin)b 250 mg 18 tablets
a
Not all medications were carried in the amounts noted on all flights.
b
Indicates item to be used only after surgeon approval or as directed in medical checklist.

human presence on the station. Therapeutic items were distrib-
uted among several small, problem-oriented kits, an approach
that provided convenient access for the crew and decreased
the time required for resupply because the needed items were
conveniently added to the next launch opportunity on either
a Soyuz crew transport or a Progress freighter vehicle. Mir
medical kits contained primarily medications, bandaging sup-
plies, and splints (Table 4.6).
Other diagnostic and medical monitoring equipment that
were available on board the Mir included both a manual and
an automatic blood pressure monitor; a 12-lead electrocardio-
graph; a rheoencephalograph; and devices to measure labo-
ratory analysis values in blood (Reflotron) and urine (Urilux
analyzer).
Throughout the joint U.S.-Russian NASA-Mir Program
(March 14, 1995 to June 12, 1998), the Mir space station was
sequentially home to seven NASA astronauts and witnessed
nine visiting US Space Shuttle missions (June 27, 1995 to
June 12, 1998). To augment the Russian on-orbit medical
capability and to add a small degree of advanced life sup-
port capabilities to the medical capabilities already extant on
Mir, the Mir supplemental medical kit (MSMK) was devel-
oped. Minimal redundancy was present between the MSMK,
which was derived from the SOMS, and the Mir medical
kits. Developed jointly by the U.S. and Russian medical
communities, the MSMK was composed of reconfigured
U.S. EMK, MBK, and MEDOP kits. Airway management
items were included in the MEDOP, and astronauts and
cosmonauts were trained accordingly in life support and
airway handling.
After the NASA-1 (March 14 to July 7, 1995)/Mir-18
mission, the Mir resupply kit was added to the MSMK
system. The Mir resupply kit included a pulse oximeter, a
portable clinical blood analyzer, and additional IV fluid. The
Mir defibrillator, the cardiac drug kit, and the crew medical
restraint system were added for the NASA-5 (May 15 to Octo-
ber 6, 1997), NASA-6 (September 25, 1997 to January 31,
1998), and NASA-7 (January 22 to June 12, 1998) increments.
Items found in the MSMK are listed in Table 4.7.
The International Space Station
NASA and the Russian Aviation and Space Agency each pro-
vide medical equipment for the ISS. The NASA-provided
medical equipment is the crew health care system (CHeCS).
As well as supplying traditional medical kits to the ISS,
4. Spaceflight Medical Systems 83

TABLE 4.6. Contents of the Mir medical kits. TABLE 4.6. (continued)
Onboard Medications/Supplies Sydnocarb
Adhesive bandages, bactericidal Tolfisopam (Grandaxin)
Ammonia spirit (inhalant) Valerian extract
Aspirin Vitamin/mineral preparation (Pantogem)
Atropine sulfate Aseptic Medicine Kit
Bandage Brilliant green tincture
Belalgin (Analgin [dipyrone], belladonna, ethyl aminobenzoate, Ethyl alcohol
sodium hydrocarbinate) Iodine tincture
Caffeine Medicine for Burns and Injuries
Chloramphenicol (Levomycetin) Brilliant green tincture
Clemastine (Tavegil) Flucinar ointment (corticosteroid)
Dressing pack Ethyl alcohol
Furosemide (Lasix) Iodine tincture
Metapyrin (Analgin [dipryone]) Lincomycin ointment
Menthyl valerate (Validol) Lorindin C ointment (flumethasone, iodochlorhydroxyquinolone)
Methyluracil ointment Olasol spray (chloramphenicol, boric acid, ethyl aminobenzoate,
Nitrazepam (Radedorm) sea buckthorn oil)
Nitroglycerin (Nitrostat) Ophthalmic spatula
Oleandomycin/tetracycline (Oletrin) Sulfacetamide solution (Sulamyd)
Ophthalmic spatula Dressing Kit
Papaverine (Papazol) Bandage, 5 cm 7 cm
Perphenazine (Aethaperazine) Bandage, adhesive
Phenibut (beta-phenyl-gamma-aminobutyric acid) Bandage, adhesive, bactericidal
Potassium/magnesium asparaginase (Panangin, Asparcam) Bandage, elastic
Promedol (trimeperidine) Dressing pack
Scissors Gauze, 14 cm 16 cm
Senadexin (Senokot, Senade) Gauze, 45 cm 29 cm
Sulfadimethoxine (Madribon) Scissors
Tetracycline ointment Tampons, cotton
Tusuprex (Libexin, prenoxdiazine hydrochloride) Waxed paper
Verapamil (Isoptin) Antiphlogystic Medicine Kit #1
Splint Kit Aspirin
Splints (12) Clemastine (Tavegil)
Bandage (4) Diclofenac (Voltaren)
Tourniquet Dipyrone (Analgin)
Cardiovascular Medicine Kit Erythromycin
Ammonia spirit (inhalant) Pyrabutol (phenylbutazone, amidopyrine, dimethylaminoantipyrine)
Atropine sulfate injection Sulfadimethoxine (Madribon)
Menthyl valerate (Validol) Tetracycline/oleandomycin (Oletetrin)
Moricizine HCl (Ethmozine) Tusuprex (Libexin, prenoxdiazine hydrochloride)
Nitroglycerin (Sustac Forte) Antiphlogystic Medicine Kit #2
Nitroglycerin (Trinitrolong) Ascorbic acid
Papaverine (Papazol) Camphomen aerosol
Potassium/magnesium asparaginase (Panangin) Capsicum plaster
Propranolol (Anaprilin) Cefecon suppositories (salicylamide, caffeine, amidopyrine, phenacetin)
Trimeperidine (Promedol) Ethyl alcohol
Gastrointestinal and Urologic Kit Nozzle
Atropine sulfate 1% injection Sulfacetamide solution (Sulamyd)
Baralgin (Analgin plus antispamodics) Xylometazoline (Xilomesolin)
Charcoal, activated (Carbolen) Antiphlogystic Medicine Kit #3
Nifuroxazide (Ercefuryl) Ascorbic acid
Nitroxoline Ampicillin/oxacillin (Ampiox)
Senadexin (Senokot, Senade) Bromehexine expectorant
Sodium carbonate Doxycycline (Vibramycin)
Triamterene (Triampur) Nystatin
Trimeperidine (Promedol) Rimantadine
Trimethoprim/sulfamethoxazole (Bactrim) Antiphlogystic Medicine Kit #4
Vitamin K (Vicasol) Ethyl alcohol
Psychotropic Medications Faringosept
Glutaminic acid Fluoroquinolone (Taravid)
Nitrazepam (Radedorm) Gauze pads
Phenibut (beta-phenyl-gamma-aminobutyric acid) Sofradex drops (Neomycin B, gramicidin, dexamethasone)
Phenazepam Syringes
Pyritinol (Encephabol) Syringe needles
(continued) (continued)
84 T.A. Taddeo and C.W. Armstrong

TABLE 4.6. (continued) TABLE 4.6. (continued)

Tampons, cotton Aural probe with thread
Prophylactic Medicine #1 Aural speculum, large
Potassium/magnesium asparaginase (Asparcam) Brilliant green tincture
Potassium orotate (Orotas) Catheter
Riboxine (Inosin-F) Camphomen aerosol
Prophylactic Medicine #2 Ethyl alcohol
Lactobacillus acidophilus/colibacillus (Bifidobacterium) Faringosept
Levamisole (Decaris) Forceps, bayonette
Prophylactic Medicine #3 Forceps, nasopharyngeal extraction
Piracetam (Nootropil) Forceps, ophthalmic
Ointment Kit Gauze pads
Bandage Gentamycin sulfate (Garamycin)
Clostridil peptidase/chloramphenicol (Iruxol) Illuminator/protective cover, spare bulb
Nonivamide/nicoboxil (Finalgon) Laryngeal mirror
Solcoseryl ointment Light guide, nasal
Spatula, plastic Lorindin C ointment (fulmethasone iodochlorhydroxyquinolone)
Troxevasin gel Metapyrin (Analgin)
Aspro Kit Ophthalmic extraction instrument
Aspirin Ophthalmic loop
Aspirin dissolvable tablets Ophthalmic spatula
Aspirin/caffeine (Aspro S Forte) Scissors, blunt
Scissors Slit lamp (nozzle)
Emergency Kit #1 Sulfacetamide solution (Sulamyd)
Atropine sulfate injection Sulfadimethoxine (Madribon)
Ethyl alcohol Tampons, cotton
Gauze pads Tetracycline ophthalmic ointment
Lincomycin ointment (Linocin) Turunda, anterior nasal tamponage
Scissors Turunda, posterior nasal tamponage
Trimeperidine HCl (Promedol) Turunda, ear
Emergency Kit #2 Vitamin K (Vicasol)
Adrenaline 0.1% (epinephrine) Xylometazoline (Xilomesolin)
Ampule saw Stomatologic (Dental) Kit
Atropine sulfate Aspirin
Baralgin (Analgin plus antispasmodics) Cement spatula
Bendazol HCl (Dibasol) Cutters
Caffeine Dental drill
Dexamethasone (Dexacon) Dentine paste
Diazepam 0.5% (Relanium, Valium) Drills, hand-operated
Drofaverine 2% (Nospa) Ethyl alcohol
Enclosure bag for manipulations Excavator, double-ended
Ethyl alcohol Extractor, type 33
Fentanyl 0.005% (Duragesic) Extractor, type 51A
Furosemide (Lasix) Flask, sterilized instruments
Gauze pads Forceps, curved dental
Lidocaine 2% (Xylocaine) Fuse
Lidocaine 10% (Xylocaine) Gauze pads
Metapyrin (Analgin) Indomethacin (Indocin)
Needles for injection Metapyrin (Analgin)
Nikethamide (Cordiamine) Nozzle, angled
Scissors Plugger
Sectioned pack Pulp extractors
Sulfocamphocaine (sulfocamphoric acid, procaine) Promecon (Emete-Con, benzquinamide)
Syringes Pyrcophen (dimethylaminoantipyrine, caffeine, analgin)
Syringes with needles Scraper, double-ended
Triplenamine (Suprastatin, chloropyramine) Smoother, double-ended
Vitamin K (Vicasol) Speculum, dental
Waste product pack Scalpel, dental
Otorhinologic and Ophthalmologic Kit Tampons, cotton
Adapter Tampons, small ball
Atropine sulfate Tooth probe, angled
Aural extraction instrument Triplenamine (Suprastatin, chloropyramine)
(continued) Source: Data courtesy of the Institute of Biomedical Problems, Moscow.
4. Spaceflight Medical Systems 85

TABLE 4.7. Contents of the Mir supplemental medical kits [15].

Name Description Amounta
Ace bandage 3 in. wide 2
Adaptic bandages 3-in. 3-in. nonadherent dressing 6
Afrin (nasal spray) 3-ml bottle 6
Air temperature monitors 3249C (90120F) 2
1331C (5888F) 2
Airway Oral 1
Alcohol wipes Ethyl alcohol 114
Alupent (metaproterenol)b 20 mg 30 tablets
Ambien (zolpidem tartrate) 10 mg 75 tablets
Ambu bag, O2 reservoir 1
Ambu mask 1
Ambu O2 tubing 1
Ambulatory leg bag 600-ml bag 1
Amikin (amikacin)b 250 mg/cc, 2-cc unit 2
Amoxil (amoxicillin)b 500 mg 24 capsules
60 tablets
Anusol-HC suppositories 6
Ascriptin (aspirin) 5 grain 50 tablets
Atropineb 1 mg/cc, 2-cc unit 3
AYR (saline nasal mist) 8-ml bottle 3
Bactrim DSb (trimethoprim/sulfamethoxazole) 56 tablets
Bactroban (mypirocin) ointment 2%, 30-g tube 1
Bags
Ziploc 12 in. 12 in. 2
Biohazard 6 in. 6 in. 10
Band-Aids 1 in. 3 in. 51
Bar-code index card 3
Batteries AA 2
Alkaline, 9 V 4
DC, 10 V (defibrillator) 3
Benadryl (diphenhydramine)b, injectable 50 mg/cc, 1-cc unit 5
Benadryl (diphenhydramine), oral 25 mg 50 capsules
Benzoin swabs 11
Blistex lip balm 1
Blood Analysis Items
Alcohol wipes Ethyl alcohol 20
Band-Aids 1 in. 3 in. 26
Battery Alkaline, 9 V 4
Biohazard bags 6 in. 6 in. 10
Capillary Tube Kit 1 kit
Capillary bulb 3
Capillary tube 26
Cartridges
EC6+ 27
EC8+ 9
Gauze pads 2 in. 2 in. 15
Gloves Nonsterile 10 pair
Lancet Finger 26
Portable clinical blood analyzer 1
Portable clinical blood analyzer control solutions
Level I Blue 3
Level II Red 3
Tubex injector 1 ml 2
Blood pressure cuff 1
Butterfly INT sets 19 G 2
21 G 4
Cardiac Drug Kit 1
Alcohol wipes Ethyl alcohol 4
Atropineb 1 mg/cc, 2-cc unit 1
Butterfly INT set 21 G 1
Dermicel tape 0.5 in. wide 1 roll
Epinephrineb 1:10,000, 10-cc unit 5
(continued)
86 T.A. Taddeo and C.W. Armstrong

TABLE 4.7. (continued)

Name Description Amounta
Heparinb 100 units/cc, 1-cc unit 1
Tubex injector 2 ml 1
Verapamil (Isoptin)b 2.5 mg/cc, 2-cc unit 1
with plunger 1
Xylocaine (lidocaine)b, cardiac 20 mg/cc, 5-cc unit 2
with plunger 1
Catheters
Intravenous intracatheters 14 G 2
18 G 5
20 G 8
Foley (bladder) 16 Fr, 5-ml balloon 2
Chemstrip 10-SG Urine test package 13 strips
Ciloxan (ciprofloxacin)b ophthalmic solution 0.3%, 2.5-ml bottle 3
0.3%, 5-ml bottle 1
Cipro (ciprofloxacin)b, oral 500 mg 48 tablets
Cotton balls 5 per pack 15
Cotton swabs 2 per pack 12
Cough lozenges 39 tablets
Cyclogyl (cyclopentolate)b 1%, 15-ml bottle 1
Dalmane (flurazepam) 15 mg 30 capsules
Debrox (urea hydrogen peroxide) 15-ml bottle 1
Defibrillator Resupply Kit
Batteries DC, 10 V 3
Electrocardiogram electrodes for electrocardiogram monitoring 4 sets
Multifunction electrodes 3 sets
Deltasone (prednisone)b 10 mg 100 tablets
Demerol (meperidine)b 50 mg/cc, 1-cc unit 5
Dental items
Carver file 1
Mirror 1
Needles Long, 27 G 6
Short, 27 G 6
Orangewood sticks 2
Syringe 1
Temporary filling 1
Toothache kit 1 kit
Eugenol anesthetic drops
Tweezers
Cotton pellets
Marcaine (bupivacaine)b 0.5% w/epinephrine 6 dental carpules
Dental floss Single-use packet 1
Dycal (base) 13-g tube 1
Dycal (catalyst) 11-g tube 1
Dermicel tape 1 in. wide 1 roll
0.5 in. wide 4 rolls
Dexedrine (dextroamphetamine)b 5 mg 30 tablets
Diamox (acetazolamide)b 500 mg 15 capsules
Dilantin (phenytoin sodium)b, injectable 50 mg/cc, 2-cc unit 10
Dilantin (phenytoin sodium)b, oral 100 mg 35 capsules
Drapes, sterile 40 cm 40 cm 2
Dulcolax (bisacodyl), oral 5 mg 30 tablets
Dulcolax (bisacodyl), suppository 10 mg 6
Duricef (cefadroxil)b 500 mg 20 capsules
Ear loop for earwax removal 1
Elastoplast tape 4 in. wide 1 roll
Entex LA (phenylpropanolamine/guafenesin) 75 mg of phenylpropanolamine hydrochloride, 400 mg of guafenesin 80 tablets
Epinephrineb 1:1000, 1-cc unit 8
1:10,000, 10-cc unit 5
Erythromycinb 250 mg 48 tablets
Eye pads 6
Flagyl (metronidazole)b 250 mg 28 tablets
Fluorescein strips 8

(continued)
4. Spaceflight Medical Systems 87

TABLE 4.7. (continued)

Name Description Amounta
Forceps
Small point Surgical Instrument Assembly 1
Blunt 2
Fox Shield Metallic eye patch 1
Gauze pads 4 in. 4 in. 27
2 in. 2 in. 15
Gloves Sterile, surgical 4 pair
Nonsterile 16 pair
Haldol (haloperidol)b 5 mg/cc, 1-cc unit 2
Hemostats
Small Surgical Instrument Assembly 1
Curved 1
Heparinb 100 units/cc, 1-cc unit 11
Hexadrol (dexamethasone)b 10 mg/cc, 1-cc unit 2
with plunger 2
Imodium (loperamide HCl) 2 mg 64 capsules
Injector (Tubex) 2 ml 4
1 ml 2
Irrigation assembly, roller clamp 1
Isoptin (verapamil)b with plunger 2.5 mg/cc, 2-cc unit 3
2
Intravenous administration set 3
Kenalog cream 15-g tube 2
Kling 3 in. wide 4 rolls
Laryngoscope Handle w/Miller blade 1
Lasix (furosemide)b 10 mg/cc, 2-cc unit 5
Lotrimin cream (clotrimazole) 15-g tube 2
Lubricant (water-soluble) 3g 9
Magill forceps 1
Magnifying glass Magnification 4 1
Medical data logs 6 expanded
Merocel Pope (posterior nasal packing) 10 cm 3
Milk of Magnesia 60 tablets
Morphine sulfateb 10 mg/cc, 1-cc unit 6
Motrin (ibuprofen) 400 mg 100 tablets
Mylanta Double Strength 24 tablets
Narcan (naloxone)b 0.4 mg/cc, 1-cc unit 2
Nasostats 2
Needles 22 G, 1.5 in. 4
18 G, 1.5 in. 4
16 G, 1.5 in. 2
Needle holder Surgical Instrument Assembly 1
Neosporin Plus cream with lidocaine 0.5-oz tube with 1
40 mg lidocaine
Nitroglycerin patchb 15 mg/24 h 1
Nitrostat, sublingualb (nitroglycerin) 0.4 mg (1/150) 25 tablets
One-way valve and connecting tube 1
Ophthalmoscope head 1
Otoscope 1
Otoscope speculum Disposable 10
Penrose tubing (tourniquet) 2
Pepto Bismol 48 tablets
Phazyme-125 (simethicone) 125 mg 20 capsules
Phenerganb, injectable (promethazine) 50 mg/cc, 1-cc unit 4
Phenergan, oral (promethazine) 25 mg 30 tablets
Phenergan, suppository (promethazine) 25 mg 14
Polysporin (polymyxin/bacitracin) 1-oz tube 2
Pope Otowicks 6
Povidone-iodine (Betadine) swabs 35
Pred Forte (prednisone acetate)b ophthalmic solution 1%, 5-ml bottle 2
Prilosec (omeprazole)b 20 mg 60 tablets
Proparacaine eye dropsb 5%, 15-ml bottle 1
Proventil (albuterol) inhaler 17-g container 1
(continued)
88 T.A. Taddeo and C.W. Armstrong

TABLE 4.7. (continued)

Name Description Amounta
Pulse Oximetry Kit 1 kit
Adhesive finger sensor 2
POx instruction card 1
POx data card 1
Reusable finger sensor 1
Pulse oximeter 1
Pyridium (phenazopyridine) 200 mg 35 tablets
Refresh (artificial tears, eye drops) 0.3 ml 20
Restoril (temazepam) 15 mg 40 capsules
Saline 100 ml 1
250 ml 2
500 ml 3
Salt tablets (NaCl) 1g 20 tablets
Scalpels #10 3
#11 2
Scissors (curved) Surgical Instrument Assembly 2 pair
1 pair
Seldane (terfenadine) 60 mg 56 tablets
Silvadene cream (silver sulfadiazine) 20-g tube 2
Silver nitrate sticks 5
Skin temperature monitors 2941C (84106F) 15
Soma (carisoprodol)b 350 mg 25 tablets
Steri-Strip skin closures 4
Stethoscope 1
Suction Items
Suction cartridge 1
Suction collection bag 7 in. 6 in. 2
70-cc syringe 1
Suction tip 2
Sudafed (pseudoephedrine) 30 mg 180 tablets
Surgical Instrument Assembly 1 kit
Forceps (small point)
Needle holder
Hemostat (small)
Tweezers (fine point)
Scissors (curved)
Suture 4-0 Dexon, with needle 1
5-0 Ethilon, with needle 1
4-0 Ethilon, with needle 2
3-0 Ethilon, with needle 2
2-0 Vicryl with CT-1 needle 1
Syringes 10 cc 3
3 cc 1
70 cc 1
Tears Naturale (eye drops) 30-ml dropper bottle 1
Tegaderm (transparent dressing) 10 cm 12 cm 5
6 cm 7 cm 5
Telfa pads 3 in. 4 in. 8
Thermometers, disposable, oral 35.540.4C (96104F) 18
Tobrex (tobramycin)b ophthalmic solution 0.3%, 5-ml bottle 1
Tongue depressors Sterile 10
Toradol (ketorolac tromethamine)b 30 mg/cc, 2-cc unit 2
Tracheal tube 7.5 mm with stylet 1
8.0 mm with stylet 1
Tracheostomy tube 5.5 mm cuffed 1
Tweezers (fine point) Surgical Instrument Assembly 1
Tylenol (acetaminophen) 325 mg 90 tablets
Tylenol #3 (acetaminophen with codeine)b 30 mg of codeine and 40 tablets
300 mg of acetaminophen
Urine Test Package 1 kit
Chemstrip 10-SG 13 strips
Color chart 1

(continued)
4. Spaceflight Medical Systems
TABLE 4.7. (continued)
Name
Valium (diazepam)b, injectable
Valium (diazepam)b, oral
Vancocin (vancomycin)b
VIRA-A (vidarabine ophthalmic ointment)b
Voltaren (diclofenac sodium)
VoSol HC otic solution
Xylocaine (lidocaine)b with epinephrine
Xylocaine (lidocaine)b
Xylocaine (lidocaine)/cardiac with plungerb
Zithromax (azithromycin)b
Zovirax (acyclovir)b ointment
a
Not all medications were carried in the amounts noted on all flights.
b
Indicates item to be used only after surgeon approval or as directed in checklist.
CHeCS incorporates exercise and monitoring equipment
and environmental monitoring hardware. CHeCS consists
of three subsystems: the countermeasures system (CMS),
the environmental health system (EHS), and the health
maintenance system (HMS).
The CHeCS CMS consists of exercise hardware and
monitoring devices. Exercise hardware includes a treadmill,
a resistive exercise device, and a cycle ergometer. A portable
computer, a heart rate monitor, and a blood pressure/electro-
cardiogram monitor make up the monitoring devices. In addi-
tion to daily exercise, crewmembers using the countermeasures
system perform a fitness evaluation periodically to monitor
their fitness levels, determine what degree of deconditioning
has occurred, and modify their daily exercise prescription as
needed.
The EHS provides hardware with which to monitor the
water, surfaces, and atmosphere of the ISS, aspects of the
ISS environment that are essential to crew health. The EHS
is subdivided into water quality, microbiology, radiation, toxi-
cology, and acoustic monitoring.
The water quality hardware includes the total organic car-
bon analyzer and the water sampler and archiver kit. These
items provide in-flight and archival analysis of ISS potable
water.
Microbiology hardware includes the water microbiology
kit, the surface sampler kit, and the microbial air sampler.
The microbiology kits enable in-flight analysis of total colony
count in potable water as well as counting bacteria and fungi
on surfaces and in the atmosphere.
Radiation hardware includes the tissue equivalent propor-
tional counter, the intravehicular-charged particle directional
spectrometer, the extravehicular-charged particle directional
spectrometer, high rate dosimeters, radiation area monitors,
and crew passive dosimeters. These devices provide the means
for active and passive radiation monitoring.
89
Description Amounta
5 mg/cc, 2-cc unit 2
5 mg 30 tablets
250 mg 28 capsules
3%, 3.5-g tube 1
50 mg 60 tablets
10-ml bottle 1
2% with epinephrine 1:100,000, 2-cc unit 2
2%, 2-cc unit 2
20 mg/cc, 5-cc unit 6
250 mg 18 caplets
15-g tube 1
Toxicology hardware includes the formaldehyde moni-
tor kit, grab sample containers, the solid sorbent air sampler,
the carbon dioxide monitor kit, compound specific analyzer-
combustion products, and the volatile organic analyzer. In-
flight and archival sampling capabilities are also provided.
Acoustic hardware includes an audio dosimeter, a sound
level meter, and an acoustics countermeasures kit. ISS
crewmembers are provided with custom-molded filtering and
non-filtering ear plugs, as well as with noise-conditioning
headsets. Noise levels on the ISS are monitored as needed.
The HMS is designed to support routine minor medical
needs, similar to ground first-aid, as well as basic and advanced
life support for a crew of three for up to 180 days. Six compo-
nents make up the HMS. The first component, the ambulatory
medical pack, provides for daily needs and periodic health
examinations. The second component, the crew contamina-
tion protection kit, protects the crew in the event of a toxic
spill or contamination. The remaining four componentsthe
advanced life support pack, the crew medical restraint system,
a defibrillator, and the respiratory support pack (Figure 4.8)
provide for advanced life support and transport. The contents
of the ambulatory medical pack and the advanced life support
pack are listed in Table 4.8.
The Russian medical support system is provided by the
Russian Aviation and Space Agency. This assemblage is
very similar to the Mir medical system, and consists of mul-
tiple problem-oriented medical kits, medical monitoring
equipment, and countermeasures hardware. The overall system
can be divided into six major subsystems: first-aid equipment,
medical monitoring and observation hardware, microgravity
countermeasures equipment, an individual dosimetric moni-
toring system, station cleaning and atmospheric monitoring
equipment, and sanitary-hygiene support equipment.
The contents of the first-aid equipment subsystem are listed
in Table 4.9.
90 T.A. Taddeo and C.W. Armstrong

Biomedical Crew Training

FIGURE 4.8. ISS Health Maintenance System. Components include
(from left) defibrillator, Advanced Life Support Pack, Respiratory
Support Pack, and Crew Medical Restraint System (Photo courtesy
of NASA).
As a means of preparing for early crewed space flight, bio-
medical crew training was a product of military aviation
medicine, focused primarily on the physiological aspects of
high-speed and high-altitude flight. Flight training involved
exposing crewmembers to extreme conditions such as jungle
and desert environments (as part of survival training), centri-
fuges, altitude chambers, and a motion-based simulator [9].
As crew size, mission duration, and onboard medical capa-
bilities increased, biomedical training began to focus more on
medical treatment. For the three crewed Skylab missions, two
CMOs were assigned to each crew. The prime and backup
CMOs received 80 h of medical training at military and civil-
ian medical facilities. Training ranged from basic physical
examination and blood drawing techniques to supervised
medical care in a local emergency department [17].
All Space Shuttle crewmembers receive between 8 and
11 h of medical instruction as part of mission-specific train-
ing, including space physiology, CO2 exposure training,

TABLE 4.8. Contents of the Ambulatory Medical Pack and Advanced Life Support Pack [16].
Name Description Amounta
16-G catheter 16 g 1.25 in. 2
18-G catheter 18 g 1.25 in. 2
20-G catheter 20 g 1.25 in. 2
3-cc syringe with 22-g needle 2
10-cc syringe 1
20-cc syringe 1
Ace bandage 3 in. 2
Adaptic dressing 3 in. 3 in. 6
Adenocard (adenosine)b 2 ml @ 3 mg/ml 3
Afrin nasal spray 3-ml bottle 20
Air Temperature Monitors OMNI Air Temp Monitor
90120F 2
5888F 2
Alcohol pads 106
Ambien (zolpidem)b 10 mg 50 tablets
AMBU bag 1
Amikacinb 2 ml @ 250 mg/ml 4
Amoxil (amoxicillin)b 500 mg 84 tablets
Anusol HC (hydrocortisone) 25-mg suppositories 6
Articulating paper 1 pkg
Ascriptin (aspirin) 325 mg 150 tablets
Atropineb 2 ml @ 1 mg/ml 2
Automatic blood pressure cuff Lumiscope model #1085-M 1
Ayr Saline Mist 8-ml bottle 10
Bactrim DS (cotrimoxazole)b Double strength 56 tablets
Bactroban cream 30-g tube 1
Bandage scissors 2
Band-aids 3 in. 1 in. 100
Band-aids Sheer Spot 26
Benadryl (diphenhydramine) 25 mg 50 capsules
Benzoin swabs 20
(continued)
4. Spaceflight Medical Systems 91

TABLE 4.8. (continued)

Name Description Amounta
Blistex lip balm 0.14-oz tube 1
Blood pressure cuff Cuff w/aneroid sphygmomanometer 2
Bretyliumb 10 ml @ 50 mg/ml 2
Butterfly needles 21 g 2
23 g 2
Capillary bulbs 3
Capillary tubes with protective sheath 32
Carver/file 1
Catheters 14 G, 2 in. 2
Chemstrip 10 with specific gravity (SG) and color chart Dipstick 3 pkg
Chest drain valve Heimlich 1
Ciloxan ophthalmic solution (ciprofloxacin)b 0.3%, 2.5 ml 3
Cipro (ciprofloxacin)b 500 mg 48 tablets
Claritin (loratadine) 10 mg 28 tablets
Compazineb 25-mg suppositories 14
Cotton balls 40
Cotton swabs 13 packages
Cough lozenges (dextromethorphan) 0.5 mg 54
Cyclogyl (cyclopentolate)b ophthalmic solution 2%, 15-ml bottle 1
D5W solution dextrose solution, 500 ml 1
Debrox otic drops 15-ml bottle 1
Deltasone (prednisone)b 10 mg 100 tablets
Dental elevator size 301 1
size 34 1
Dental floss single-use package 1
Dental forceps size 17 1
size 151A 1
size 10S 1
Dental mirror 1
Dental syringe Technitouch syringe 1
Dexamethasoneb 1 ml @ 10 mg/ml 2
2 ml @ 0.4 mg/ml 2
Dexedrine (dextroamphetamine)b 5 mg 10 tablets
Diamox (acetazolamide)b 250 mg 50 tablets
Diazepamb 2 ml @ 5 mg/ml 3
Diflucan (flurazepam) 150 mg 3
Dilantin (phenytoin) 100 mg 35 tablets
Diphenhydramineb 1 ml @ 50 mg/ml 3
Dopamineb 400 mg/500 cc D5W 1
Dulcolax (bisacodyl) 10-mg suppositories 6
Dulcolax (bisacodyl) 5 mg 30 tablets
Duricef (cefadroxil)b 500 mg 40 capsules
Dycal Base 13 g 1
Dycal catalyst 11 g 1
Ear curettes 2
Elastoplast tape 2.5 yards 1
Electronic simulator for portable clinical blood analyzer 1
Entex LA (phenylpropanolamine/guafenesin) 400 mg 80 tablets
Epinephrineb 1 ml @ 1:1000 3
Epinephrine, cardiacb 10 ml @ 0.1 mg/ml 5
Endotreacheal tubes 7.0 mm with stylet 1
8.0 mm with stylet 1
Explorer/probe size 23/11 1
Eye pads 6
Eye shield Fox metallic shield 1
Fingersplint 1
Fingerstix single-use, sterile 30
Flagyl (metronidazole)b 250 mg 28 tablets
Fluorescein strips FUL-GLO Fluorescein sodium 8
Foley catheters 16 Fr, 30-ml balloon 2
Furosemideb 2 ml @ 10 mg/ml 10

(continued)
92 T.A. Taddeo and C.W. Armstrong

TABLE 4.8. (continued)

Name Description Amounta
Gauze pads 4 in. 4 in. 57
Haldol (haloperidol)b, injectable 2 ml @ 5 mg/ml 2
Haloperidolb, oral 5 mg 400 tablets
Hemostat size 5.5 in., curved, Kelly 1
Imodium (loperamide) 2 mg 64 capsules
Inderal (propanolol)b 20 mg 24 tablets
Intubation bulb esophageal detector device 1
Iodine pads 1% 10
Intravenous administration sets (powered) IMED 2
Intravenous administration sets (not powered) 2
Intravenous flowmeter 0250 ml/h 1
Intravenous infusion device 11,000 ml/h 1
Intravenous Kit 1 kit
Intravenous administration set (nonpowered)
Y-type catheter
Lever lock cannula
18 g catheter
Cue card
Intravenous pressure infusor 1L 1
Kenalog cream (triamcinolone) 0.1%, 15-g tube 2
Kenalog in Orabase 0.1%, 5-g tube 1
Kerlix dressing 4.5 in. 2
Kling dressing 3 in. 7
Laryngoscope blade Macintosh, Size 3 1
Laryngoscope handle Pediatric 1
Leg bag 600 ml 1
Lever lock cannulas Interlink 5
Lidocaineb 5 ml @ 20 mg/ml 3
Long needles 27 g, 1.25 in. 6
Lotrimin (clotrimazole) cream 15-g tube 2
Lubricant sterile, Surgi-Lube 4
Magill forceps Adult 1
Magnifying glass 5 magnification 1
Meperidineb 1 ml @ 50 mg/ml 6
2 ml @ 50 mg/ml 4
Milk of magnesia 80 tablets
Morphineb 1 ml @ 10 mg/ml 6
2 ml @ 10 mg/ml 3
Motrin (ibuprofen) 400 mg 70 tablets
Mouth/throat mirrors laryngeal mirror, size 3 2
Mylanta DS double-strength 100 tablets
Narcan (Naloxone)b 2 ml @ 0.4 mg/ml 2
Nasal airway 7 mm 1
Nasogastric tube 14 Fr 1
Needles 18 G, 1.5 in. 2
Neosporin Plus cream with lidocaine 1
0.5-oz tube
Nitroglycerin patchesb 15 mg/24 h (0.6 mg/h) 3
Nitrostat (nitroglycerin tablets)b 0.4 mg 25 tablets
Nonsterile gloves Latex, large 8 pair
Nortriptylineb 50 mg 400 capsules
Ophthalmoscope head 1
Ophthalmoscope spare bulb 1
Oral airway 90 mm 1
Otoscope 1
Otoscope spare bulb 1
Otoscope specula plastic 20
Ovral-21 (norgestrel/ethinyl estradiol) 42 tablets
Portable Clinical Blood Analyzer
Control ranges card 1
Control solution kit 1 kit
Control solutions
BK wipes

(continued)
4. Spaceflight Medical Systems 93

TABLE 4.8. (continued)

Name Description Amounta
Band-aids
Tubex injector
Gauze pads
Peak flow meter Spir-O-Flow pocket monitor 1
Penlight model #1000186 2
Pepto Bismol 48 tablets
Phazyme (simethicone) 125 mg 80 gel caps
Phenergan (promethazine)b 25 mg 30 tablets
1 ml @ 50 mg/ml 6
Phenytoinb 2 ml @ 50 mg/ml 10
Polysporin (polymyxin/bacitracin) ointment 1-oz tube 2
Polytrim ophthalmic solution 10-ml bottle 1
Pope otowicks 6
Pope posterior nasal packing 10 cm, Merocel 3
Portable clinical blood analyzer i-STAT 1
Povidone-iodine (Betadine) swabs single-use swabs 32
Pred Forte ophthalmic solution (prednisone acetate)b 1%, 1-ml bottle 1
Prilosec (omeprazole)b 20 mg 30 capsules
Proparacaine ophthalmic solutionb 0.5%, 15-ml bottle 1
Proventil inhalerb 17 g albuterol 2
Prozac (fluoxetine Hydrochloride)b 20 mg 400 capsules
Pulse oximeter transducers Oxisensor II, D-25 2
Pulse oximeter with finger sensor Nellcor 1
Pyridium (phenazopyridine) 200 mg 20 tablets
Reflex hammer 1
Refresh ophthalmic solution (artificial tears) single-use vials 20
Restoril (temazepam)b 15 mg 80 capsules
Resuscitation mask Respironics 1
Romazicon (flumazenil)b 2 ml @ 0.1 mg/ml 4
Saline solution 0.9% NaCl
100-ml bag 1
500-ml bag 2
1-L bag 3
SAM splint 36-in. 4.5-in. splint, instruction pamphlet 1
Scalpel #10 3
#11 2
Sharps container Lexan box 1
Short needles 27 g, 0.75 in. 6
Silvadene cream (silver sulfadiazine) 1%, 20-g tube 2
Silver nitrate sticks package of 5 2 pkg
Skin staple remover 6.0 in. 2.5 in. 1
Skin stapler Precise 15 shot 2
Skin temperature monitor crystalline temperature trend indicator 84106F 15
Sponges 5-in. 9-in. hermitage dressing 4
Sodium chloride 1g 128 tablets
Soma (carisoprodol)b 350 mg 25 tablets
Sterile drape 40 cm 40 cm 4
Sterile gloves size 8 5 pair
Steri-strips (skin closure) 0.25 in. 4 in. 6 pkg
0.5 in. 4 in. 2 pkg
Stethoscope 2
Stethoscope earpieces spare earpieces 2
Suction curette tip 1
Suction device 1
Suction device collection bags 2
Suction device ET catheter with Tygon tubing 1
Suction device syringe 70 cc 1
Sudafed (pseudoephedrine)b 30 mg 180 tablets
Surgical Instrument Assembly 1 kit
Forceps (2)
Hemostats (2)
Needle driver (1)

(continued)
94 T.A. Taddeo and C.W. Armstrong

TABLE 4.8. (continued)

Name Description Amounta
Iris scissors (1)
Surgical Instrument Assembly 1 kit
Forceps (2)
Hemostats (2)
Needle Driver (1)
Sutures w/needle
4-0 Dexon 1
5-0 Ethilon 1
4-0 Ethilon 4
3-0 Ethilon 2
2-0 Vicryl 1
Syringe 10 cc, with Luer lock 2
Tape 0.5-in. roll 1
1-in. roll 5
Tears Naturale 30-ml bottle 1
Tegaderm dressing occlusive dressing 16
Telfa pads 3 in. 4 in. 13
Tempadot disposable thermometers 35.540.4C, oral, disposable 36
Temporary filling (Cavit) tube 1
Tobrex ophthalmic solutionb 0.3%, 5-ml bottle 1
Tongue depressors wooden, sterile 20
Tonopen tip covers Latex 18
Tonopen tonometer model #23 1
Toothache Kit 1 kit
Eugenol
Cotton pellets
Tweezers
Toprol XL (metoprolol succinate)b 50 mg 20
Toradol (ketorolac tromethamine)b 2 ml @ 30 mg/ml 2
Tourniquet Penrose tubing 1
Tracheostomy tube cuffed, 5.5 mm 1
Tubex injector plastic 3
Tylenol (acetaminophen) 325 mg 300 tablets
Urinary straight catheters 16 Fr 2
Urine human chorionic gonadotropin detector 2
Urocit-K (potassium chloride)b 10 meq 45
Valium (diazepam)b, oral 5 mg 30 tablets
Vancocin (vancomycin)b 250 mg 28 tablets
Vaseline gauze 3 in. 18 in., sterile 2
Vasocidin ophthalmic ointmentb 3.5-g tube 1
Verapamilb 2 ml @ 2.5 mg/ml 3
Vicodin (hydrocodone)b 5 mg 36 tablets
VIRA-A (vidarabine)b ophthalmic ointment 3%, 3.5-g tube 1
Visual acuity card 1
Voltaren (diclophenac) 50 mg 60 tablets
VoSol HC otic solution 10-ml bottle 1
Xylocaine (lidocaine) jellyb 5 ml @ 20 mg/ml (2%) 1
Xylocaine with epinephrineb carpules, 2%, 1:100,000, 1.8 ml 10
Y-type catheters Interlink system Y-type catheter extension sets 2
Ziplock bags 8 in. 8 in. 7
12 in. 12 in. 8
Zithromax (azithromycin)b 250 mg 20 tablets
Zovirax ointment (acyclovir)b 5%, 15-g tube 1
a
Not all medications were carried in the amounts noted on all flights.
b
Indicates item to be used only after surgeon approval or as directed in medical checklist.
4. Spaceflight Medical Systems 95

TABLE 4.9. Medical support system first aid equipment.

Name Description Amount
Anti-Inflammatory Agents-1 Kit
Aspirin
Oletetrin [tetracycline/oleandomycin, Sigmamycin] 125,000 units 120 tablets
Analgin [dipyrone, Novaldin] 0.5 g 56 tablets
Artrotek 16
Tavegil [Suprastin, clemastine fumarate, chloropyramine] 30 tablets
Voltaren (diclofenac)/indomethacin/ortophen TBD
Erythromycin 0.1 g 68 tablets
Tusuprex [Oxeladin, Libexin, prenoxdiazine hydrochloride] 0.01 g 48 tablets
Sulfadimethoxine (Madribon) 0.5 g 56 tablets
Anti-Inflammatory Agents-2 Kit
Cametonum arosolum 1
Pepper plaster 3 packs
Cefeconum suppositories 15 units
Ethyl alcohol 6 test tubes
Sulfacetamide sodium solution [Albucid-natricum] 20% 2 squeezable droppers
Halazolin [Otrivin] 0.05% 2 units
Tsiprolet 80
Anti-Inflammatory Agents-3 Kit
Ampiox [ampicillin/oxacillin] 0.25 g 81 capsules
Doxycycline hydrochloride [Vibramycin] 0.05 g 18 capsules
Nystatin 500,000 units 36 tablets
Ascorbic acid 0.5 g ~48 tablets
Rimantadine 0.05 g 33 tablets
Bromhexine [Bisolvon] 0.008 g or 0.004 g 33 tablets
Anti-Inflammatory Agents-4 Kit
Falimint (5-nitro-2-propoxyacetanilide) 80 tablets
Sofradex (Neomycin B, gramicidin, dexamethasone) 2 bottles
Ethyl alcohol 2 test tubes
Disposable injection needles 2 units
Disposable injection syringes 2 units
Wipes 14 cm 16 cm 2 units
Cotton balls 3 packs
Tarivid [ofloxacin] 200 mg 27 tablets
Pharyngosept [ambazone] 0.1 g 63 tablets
Antiseptic Remedies Kit
Iodine solution 5%, 0.8 ml 14 test tubes
Viride nitens solution 1% 14 test tubes
Ethyl alcohol 28 test tubes
Aspro (Aspirin) Medical Kit
Aspirin (tablets) 45
Aspirin (water-soluble tablets) 24
Aspirin, Cardio 100 mg, 300 mg 90
Scissors 1 pair
Burns and Wounds Kit
Olasol (chloramphenicol, boric acid, ethyl aminobenzoate, sea buckthorn oil) 3 aerosols
Lorinden C ointment 15.0 g 1 tube
Methyluracil ointment 10% (10 g) 1 tube
Flutsinar ointment 0.025% (15 g) 1 tube
Viride nitens solution 1% 3 test tubes
Iodine solution 5% (0.8 ml) 14 test tubes
Ethyl alcohol 3 test tubes
Spatula for applying ointment to the eyes 1 unit
Lincomycin/erythromycin ointment 15 g 1 tube
Sulfacetamide sodium solution [Albucid-natricum] 20% 2 squeezable droppers
Gentamicin sulfate solution [Garamycin] 2
Cardiovascular Remedies Kit
Kardiket 20
Validol [menthyl valerate] 0.06 g 18 tablets
Sustac forte [Nitro-Mac retard] 6.4 mg 16 tablets
Aetmozinum 0.1 g 80 tablets
Papazol (papaverine) 34 tablets

(continued)
96 T.A. Taddeo and C.W. Armstrong

TABLE 4.9. (continued)

Name Description Amount
Anaprilin [inderal] Obsidan 0.04 g 48 tablets
Isoptin [verapamil, Finoptin] 40 mg 66 tablets
Athenolol 40
Trinitrolong [nitroglycerin] 0.0010.002 g 10 patches
Ammonium hydroxide [spirit of ammonia] 10% 3 test tubes
Aethacizinum 0.05 g 48 tablets
Atropine 0.1% (1.0 ml) 6 squeezable syringes
Enapren [enalapril] 0.01/0.02 (g) ~20
Dressing Pack
Bandages 5 in. 7 in. 2 units
Bandages 5 in. 5 in. 2 units
Adhesive plaster 1 unit
Wipes 14 in. 16 in. 6 units
Wipes 45 in. 29 in. 2 units
Pack of dressings 3 units
Bactericidal adhesive plaster 20 units
Ace bandage (#1 and #2) 3 units
Cotton balls 2 packs
Scissors 1 unit
Compress paper 1 sheet
Emergency First-Aid Medical Kit
Lidocaine 2% (2 ml) 5 ampoules
Adrenaline 0.1% (1 ml) 2 ampoules
Nospa [Drofaverine] 2% (2 ml) 6 ampoules
Relanium (diazepam) 0.5% (2 ml) 4 ampoules
Sulfocamphocainum (sulfocamphoric acid, procaine) 10% (2 ml) 2 ampoules
Cordiamine [nikethamide] 2 ml 2 ampoules
Lasix 6 ampoules
Lidocaine 10% (2 ml) 4 ampoules
Caffeine 2 ampoules
Baralgin 5 ml 6 ampoules
Dibazolum [bendazole hydrochloride] 1% (2 ml) 3 ampoules
Analgin [Novaldin] 50% (2 ml) 3 ampoules
Vicasol (vitamin K) 1% (1 ml) 4 ampoules
Platyphyllin [papaverin] 0.2% (1 ml) 3 ampoules
Suprastin [chloropyramine] 2% (1 ml) 3 ampoules
Dexamethasone/prednisolone [Dacortin] 5 ampoules
Ethyl alcohol 30 test tubes
Gauze pads x 30 units
Atropine 0.1% (1 ml) 8 squeezable syringes
Scissors 1 unit
Bag for handling 2 units
Syringes with needle 2 ml 42 units
Syringes with needle 5 ml 6 units
Needles 90 units
Waste packet 48 units
Appliance for opening ampoules (file) 48 units
Package with section dividers 15 units
Gastrointestinal And Urologic Remedies Kit
Soda 0.5 g 24 tablets
Senadexin (Senokot, Senade) 48 tablets
Carbolen [activated charcoal] 0.25 g 32 tablets
Biseptolum [Bactrim] 480 70 tablets
Ercefuril [Imodium, loperamide HCl) 27 capsules
Baralgin 56 tablets
Nitroxoline 0.05 g 48 tablets
Triampur (triamterene) 33 tablets
Vicasol (vitamin K) 0.015 g 16 tablets
Atropine 0.1% (1 ml) 6 squeezable syringes
Ointment Kit
Solcoseryl ointment 20 g 2 tubes
Troxerutin gel [Venoruton] 2% (40 g) 2 tubes
(continued)
4. Spaceflight Medical Systems 97

TABLE 4.9. (continued)

Name Description Amount
Finalgon ointment [nonivamide and butoxyethyl nicotinate] 15.0 g 2 tubes
Plastic plates 2 units
Bandages 2 units
Heparin ointment [Liquaemin] 1 tube
Zovirax (eye ointment) 1 tube
Zovirax cream 1 tube
Kelestoderm (cream/ointment) 1
Onboard Pharmacy Kit
Radedorm [nitrezepam] 0.01 g or 0.005 g 9 tablets
Tavegil [clemastine fumarate, Suprastin, chloropyramine] 9 tablets
Fenibut [beta-phenyl-gamma-aminobutyric acid] 0.25 g 16 tablets
Tusuprex [Oxeladin, Libexin, prenoxdiazine hydrochloride] 0.01 g 24 tablets
Panangin [Asparkam] [a preparation containing potassium and magnesium asparaginase] 16 tablets
Senadexin (Senokot, Senade) 24 tablets
Validol [menthyl valerate] 0.06 g 9 tablets
Analgin [Novaldin] 0.5 g 14 tablets
Aspirin 0.5 g 14 tablets
Madribon (sulfadimethoxine) 0.5 g 14 tablets
Levomycetin [chloramphenicol] 0.25 g 8 tablets
Oletetrin [Sigmamycin] 125,000 units 16 tablets
Caffeine 0.2 g 17 tablets
Isoptin [verapamil, Finoptin) 40 mg 16 tablets
Nitroglycerin [Anginine] 0.0005 g 25 tablets
Belalgin 16 tablets
Ammonium hydroxide [spirit of ammonia] 10% 1 test tube
Papazol 10 tablets
Tetracycline ointment 3g 1 tube
Methyluracil ointment 3g 1 tube
Bactericidal adhesive plaster 3.8 3.8 20 units
Bandages 1.5 6 5 units
Dressings 1 package
Scissors 1 pair
Spatulum for applying ointment to the eyes 1 unit
Atropine 0.1% (1 g) 4 squeezable syringes
Furosemide [Lasix] 6 tablets
Camphomen inhaler 1 unit
Preventive Remedies-1 Kit
Riboxine [Inosie F] 0.2 g 216 tablets
Panangin 112 tablets
Potassium orotate [Dioron] 0.5 g 112 tablets
Preventive Remedies-2 Kit
Vetoron TBD
Decaris [Ascaridil] 150 mg 24 tablets
Vitrum TBD
Essentiale TBD
Preventive Remedies-3 Kit
Nootropil (piracetam) 0.4 g 180 capsules
Preventive Remedies-4 Kit
Vitamins
Psychotropic Remedies Kit
Phenazepam 0.001 g 66 tablets
Fenibut [beta-phenyl-gamma-aminobutyric acid] 0.25 g 80 tablets
Persen 33
Radedorm [nitrazepam] 68 tablets
Pyritinol [Encephabol] 0.1 g 48 tablets
Rudotel (medazepam) 48
Glutamic acid 0.25 g 40 tablets
Grandaxin [tolfisopam] 50 mg 68 tablets
Pantogam [hopantenic acid] 0.25 g 16 tablets
Xanax [alprazolam] 40
Splint Kit
Splints 12 units

(continued)
98 T.A. Taddeo and C.W. Armstrong

TABLE 4.9. (continued)

Name Description Amount
Bandages 5 cm 10 cm 4 units
Tourniquet 1 unit
First Aid Kit [in the Portable Survival Kit]
Analgin (tablets) Item 1 10
Tetracycline (lozenges) Item 2 16
Sulfadimethoxine (tablets) Item 3 10
Sydnocarb (tablets) Item 4 55*
Phenazepam (tablets) Item 5 6
Diazoline (lozenges) Item 6 10
Pantocide (tablets) Item 7 40
Potassium permanganate (powder) Item 8 1 package
Promedol (syringe tubes) Item 9 6 units
Tetracycline ointment Item 10 1 package
Lip balm Item 11 1 package
Deet cream Item 12 3 packages
Gauze bandages Item 13.1 3 packages
Dressings Item 13.2 2 packages
Bactericidal adhesive plaster Item 13.3 3 packages
Razor blades 3 packages
Safety pins 3 units

decompression sickness evaluation and treatment, cardiopul-
monary resuscitation, and first aid. Two CMOs are selected
from each crew by the mission commander. (As noted ear-
lier in this chapter, these crewmembers typically do not have
a medical background.) The CMOs receive an additional
710 h of training in diagnostics and therapeutics. CMO
training is hands-on, using lifelike training mannequins to
practice procedures such as injections, airway management,
and wound care. Additional IV proficiency training is also
offered, including training in a virtual-reality simulator and
with human test subject volunteers. The overall emphasis of
preflight training is on procedures, how to use the medical
checklist, and how to make cogent medical observations so as
to make the best use of ground consultation.
When the defibrillator was flown on the two Space Shuttle
missions (STS-90 and STS-95), advanced cardiac life support
refresher training was conducted for the CMOs. The CMOs
on both of these missions were physicians so the additional
training requirements were minimal.
MSMK training was based on the Space Shuttle CMO
training flow, with additions to include the pulse oximeter
and portable clinical blood analyzer. Training duration was
increased from the standard Space Shuttle duration to accom-
modate the use of interpreters. All three Mir crewmembers
received 21 h of MSMK training. The training template
increased by 15 h when the Mir defibrillator and associated
hardware were added, including training in advanced cardiac
life support protocols.
NASA provides crew training on all CHeCS equipment and
associated in-flight activities for ISS crewmembers. Two or
all three crewmembers are trained in the use of the EHS and
countermeasures system hardware and procedures, depending
on crew tasking. As was true in the Skylab and Space Shuttle
programs, two crewmembers are trained as CMOs. These
crewmembers receive training in the HMS and associated
medical procedures. Before HMS training, the CMOs are
encouraged to participate in a field medical training course that
consists of 20 h of classroom instruction and 50 h of clinical
training in an emergency room, in an operating room, on an
ambulance, and in an animal laboratory. As has been done in
the Space Shuttle training program, CMOs are also given the
opportunity to train with the IV virtual-reality simulator and
with human test subject volunteers.
In addition to preflight training, ISS crewmembers receive
refresher training on board the ISS. Computer-based training
on all CHeCS hardware is provided. CMOs are allowed 1 h per
month for such training on the HMS; computer-based training
for the EHS and countermeasures system is made available
to the crew for refresher training, although this is optional
and is not scheduled at a specific time. The multimedia com-
puter-based training sessions allow crewmembers to work
at their own pace and review the items they feel are neces-
sary. At least once per increment, an HMS contingency drill
will take place. The drill is one of several emergency drills
in which the crew participates every other week. Other drills
include those for response to fire/smoke, toxic spill, and rapid
decompression. Crewmembers will not know which type of
drill is planned, only that a drill is scheduled. The specific
medical contingency scenario may change each time an
HMS drill is scheduled. Finally, the monthly performance of
medical evaluations by the CMO, involving simple physical
examination and laboratory analysis, ensures that the CMO
maintains some degree of proficiency in basic examination
and specimen collection skills.
The Gagarin Cosmonaut Training Center in Star City,
Russia, provides crew training on all Russian medical support
4. Spaceflight Medical Systems
system equipment and associated in-flight activities. This
includes training in medical response, countermeasures
performance and physical evaluation, and some environmen-
tal monitoring. Baseline data are collected before flight to
determine cosmonaut fitness for training and space flight and
to aid in achieving the required level of functional reserves
and psychological abilities corresponding to the tasks to be
performed during the spaceflight phase.
Future Systems
Next-generation CHeCS hardware is already in development.
It is sometimes difficult to use cutting-edge medical technolo-
gies for spaceflight operations because of flight certification
requirements and programmatic delays, as well as liabil-
ity and regulatory challenges faced by the medical industry
[18]. However, continual evaluation of mission needs and
performance of flown medical systems will ensure a process
of steady upgrades and improvements.
The new CHeCS devices will expand onboard diagnos-
tic and therapeutic capabilities, provide additional exercise
countermeasures for a crew of six to seven, and enhance
onboard environmental monitoring and analysis. Hardware
currently under investigation is listed in Table 4.10.
Space-faring nations are now examining the requirements
for human missions beyond low-Earth orbit. These missions
will test the limits of technical and human experience in
maintaining crew mental and physical health. Future space-
flight medical systems must permit a well-trained medical
officer to autonomously provide care for the crew while en
route and on the lunar or Martian surface. New challenges to
be met on these ambitious missions include acute radiation
exposure, dust-related health problems, prolonged weight-
lessness, injury-causing gravitational loads, and other events
associated with planetary surfaces.
TABLE 4.10. Hardware considered for inclusion in future crew health
care systems.
Total-organic-carbon analyzer (upgrade)
Ion-selective electrode assembly (for water analysis)
Long-term resistive exercise device
Treadmill with vibration-isolation system (upgrade)
Enhanced respiratory support system
Medical bio-hazardous waste management system
Portable gas analyzer
Intravenous fluid system
Digital spirometer
Hand-grip dynamometer / Pinch-force dynamometer
Critical care physiological monitoring system
Microbiology diagnostics kit
Enhanced microbial air sampler
Incubator
Neutron monitor
Diagnostic sonography
99
References
1. Polyakov VV. The physician-cosmonaut tasks in stabilizing the
crew members health and increasing an effectiveness of their
preparation for returning to Earth. Acta Astronautica 1991;
23:149151.
2. Houtchens BA. Minor Surgery and Anesthesia Capabili-
ties for Space Station Health Maintenance Facility (HMF).
Unpublished document prepared under NASA-JSC Contract
T-1419M; 1987.
3. Billica RD, Barratt MR. Inflight evaluation of apparatus and
techniques for performance of medical and surgical procedures
in microgravity: STS-40/SLS-1, SMIDEX Medical Restraint
System. In: Spacelab Life Sciences-1 Final Report. Houston, TX:
NASAJohnson Space Center; 1994: 5-675-82. JSC-26786.
4. Lloyd C, Creager GJ. SMIDEX IV pump experiment. In:
Spacelab Life Sciences-1 Final Report, Vol. 1. Houston, TX:
NASAJohnson Space Center; 1994: 5-835-88. JSC-26786.
5. Creager GJ. Formulation, preparation, and delivery of paren-
teral fluids for the Space Station Freedom Health Maintenance
Facility. Paper presented at the 20th Intersociety Conference on
Environmental Systems; July 912, 1990; Williamsburg, VA.
SAE Technical Paper Series No. 901325.
6. McKinley BA. Sterile water for injection system for on-site
production of IV fluids at Space Station Freedom HMF. Paper
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Systems; July 912, 1990; Williamsburg, VA. SAE Technical
Paper Series No. 901324.
7. Barratt M, Billica R. Delivery of cardiopulmonary resuscitation
in the microgravity environment. Presented at the 63rd Annual
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1014, 1992; Miami Beach, FL.
8. Billica RD, Pool SL, Nicogossian AE. Crew health-care programs. In:
Nicogossian AE, Huntoon CL, Pool SL (eds.), Space Physiology and
Medicine. 3rd edn. Philadelphia, PA: Lea & Febiger; 1994: 402423.
9. Billica RD, Jennings RT. Biomedical training of U.S. space
crews. In: Nicogossian AE, Huntoon CL, Pool SL (eds.), Space
Physiology and Medicine. 3rd edn. Philadelphia, PA: Lea &
Febiger; 1994: 394400.
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equipment, and prophylaxis). In: Talbot JM, Genin AM (eds.),
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flight Medical Support System Checklist, All Skylab Missions,
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5
Acute Care
Thomas H. Marshburn
After more than 40 years of human spaceflight operations, the
U.S. and Russian spaceflight programs now have sufficient
experience to identify the most common medical problems that
occur in space. This experience base allows the development of
means to diagnose and treat the medical problems anticipated to
occur during flightthat is, to provide spaceflight crews with
acute care. Acute care, in this sense, refers to the treatment of the
common minor medical problems that can occur during crewed
spaceflight missions. Acute care also refers to the assessment
and stabilization of the more serious illnesses and injuries that
can affect missions or cause significant crewmember morbidity.
The high cost of space travel demands maximum perfor-
mance from each crewmember during a mission both to
maintain health and to accomplish mission objectives. Conse-
quently, the common, relatively minor medical problems dis-
cussed in this chapter can significantly affect a mission. For
instance, an ankle injury sustained by a crewmember during a
long-duration space flight can result in an inability to perform
the strenuous treadmill exercises that maintain muscle mass,
lower-extremity proprioception, and aerobic capacity. This
would further lead to diminished performance upon return to
gravity (e.g., upon arrival to Mars or rapid egress from the
Space Shuttle after landing). Likewise, an extravehicular
activity (EVA) (i.e., a spacewalk) could be cancelled because
of contact dermatitis or some minor hand injury that is not
aggressively treated.
Experience with human space flight has taught us that seri-
ous illnesses can occur during missions. The crew medical
officer (CMO) who is assessing the seriously ill or injured
crewmember faces several challenges. The CMO not only
must correctly diagnose the problem so as to prevent either a
premature end to the mission or an increase in crewmember
morbidity from delaying return, but also must work with lim-
ited resources in an extreme environment, the effects of which
on humans are poorly understood.
This chapter summarizes the experience gained in diagnos-
ing and treating acute medical problems in space and provides
recommendations for treating expected problems in future
space flights.
On-Orbit Medical Resources
Ground-based flight surgeons provide each crewmember with
medical care training and equipment appropriate for the
mission, within the constraints of available payload weight and
volume and crewmember training time. A medical kit, medical
references, computer-based training, and consultation with
members of the ground support team are all means by which
flight surgeons deliver medical experience and knowledge to
each spaceflight crew.
All crewmembers can access and use nonprescription phar-
maceuticals in the medical kit without reporting to either
a CMO or the ground team, although they are requested to
record in a personal file the type, dose, and frequency of
medication used. Two members of each Space Shuttle crew
are designated CMOs; CMOs are rarely physicians, but they
have enough autonomy and training to assess and treat minor
trauma and illnesses without calling the ground-based flight
surgeon for immediate consultation. CMOs who are not phy-
sicians may use prescription medications only at the direction
of the flight surgeon or after satisfying the circumstances cited
in the medical procedures manual. The controlled-substance
category and side effects of all medications supplied in the
medical kits are listed in the procedures manual.
The CMO has access to 2 on-orbit medical resources
the procedures manual and the private medical conference
(PMC). The procedures manual is written and updated by
ground-based flight surgeons. This manual has several unique
characteristics. It contains a minimum of medical terminol-
ogy, step-by-step procedures that reference only the limited
hardware and pharmaceuticals available in the on-board medi-
cal kit, and a listing of possible side effects of the prescription
drugs in the kit. Since human performance decrements would
be detrimental to a mission, adverse side effects from medica-
tions are of primary concern in the pharmaceutical treatment
of crewmembers.
The on-orbit CMO also can confer with the ground-based
flight surgeon through daily PMCs, which are considered an
integral part of Space Shuttle operations. During the PMC,
101
102
the Mission Control Center establishes a completely private
link between the Space Shuttle crew and the flight surgeon.
PMCs are held to enhance the medical capability of the
crew and to allow the flight surgeon to communicate to the
ground team any need for mission or timeline changes that
have been driven by an onboard medical problem. PMCs
are scheduled and conducted daily during a Space Shuttle
flight, eliminating the need for the crew to use open air-
to-ground communications to request a private conference
with the flight surgeon, thereby helping to maintain medical
privacy as well as to facilitate proactive and anticipatory
medical advice from the flight surgeon. PMCs typically last
from 515 min.
A PMC is also held daily during the first few days of a long-
duration mission to the International Space Station (ISS), dur-
ing the period of acute adaptation to the new environment.
On a long-duration ISS mission (or any other long-duration
mission), after the first few flight days, PMCs are held weekly
and at the request of the flight surgeon or the crew.
The flight surgeon must provide to the ground control team
a summary of the state of the health of the crew after each
PMC. Although the flight surgeon and CMO make the medical
diagnosis and treatment decisions for an affected crewmem-
ber, the mission commander is best able to assess the effect
of the treatment plan on the mission as a whole. Before the
conclusion of the PMC, the CMO, commander and the flight
surgeon agree on the content of the PMC report to the ground
team. In cases in which a medical problem on orbit does not
result in timeline or mission changes, individual problems are
not discussed or reported by the flight surgeon. In such cases,
the PMC report typically states no mission impact. Medi-
cal privacy is paramount, both to maintain the trust between
flight surgeon and each crewmember, which may take years to
develop, and to prevent distraction from the mission by inor-
dinate media attention.
If the CMO and commander determine that the diagnosis
or treatment of a crewmembers medical problem will affect
the mission, which will necessarily involve the flight control
team in some fashion, the flight surgeons report will con-
tain only the information needed to implement changes to
the crew timeline and tasking or to modify plans for use of
consumables (e.g., O2). All attempts are made to preserve the
physician-patient relationship while also acting to best serve
the interests of the mission. In such cases, a public statement
is made noting the diagnosis, prognosis, and likely effect on
the mission.
This scheduled PMC is one of the most important components
of medical care in space flight. By facilitating communica-
tion between the crew and ground-based medical support, the
CMOs greatly expand their resources in knowledge and
expertise while being assured of complete privacy; the flight
surgeon can work with the ground team under established rules
of communication to support the medical treatment of an ill or
injured crewmember (as necessary); and the Medical Opera-
tions team at the NASAJohnson Space Center can develop
T.H. Marshburn
a non-attributable database (in which incidents cannot be
attributed to any identifiable individual) to better prepare for
future medical contingencies.
Common Disorders Requiring
Care in Space
Space Motion Sickness
Space motion sickness (SMS) is very common among astro-
nauts and cosmonauts. Although it bears some resemblance
to the motion sickness that is experienced on Earth, SMS
is nonetheless part of a symptom complex that is unique to
microgravitythat is, the space adaptation syndrome. The
nausea and vomiting associated with SMS, one of the more
deleterious symptoms of space adaptation syndrome, are very
common during the first few days of entering a microgravity
environment. SMS has been estimated to affect 67% of crew-
members on their first space flight [1]. Investigations into the
etiology, prevention, and recovery from space adaptation syn-
drome are discussed more fully in Chap. 10. In this section,
only the on-orbit treatment options available to crewmembers
are discussed.
Astronauts and cosmonauts experience SMS at different
symptom intensities. Davis and colleagues used a symptom
intensity score to evaluate symptoms experienced during
the first 24 Space Shuttle flights [1]. Of the astronauts who
experienced any symptoms, 47% had mild symptoms only,
with no more than one episode of emesis and complete res-
olution in 3648 h; 35% experienced moderate symptoms,
with waxing and waning malaise, fewer than three episodes
of emesis, and symptom resolution in 72 h; and 19% expe-
rienced severe symptoms, consisting of persistent malaise,
three or more episodes of vomiting, and symptom persis-
tence beyond 72 h [1].
Slight differences can be expected between SMS symp-
toms and those of terrestrial motion sickness. For example,
crewmembers with SMS display less pallor and sweating,
and more flushing and headache, than do people with ter-
restrial motion sickness. Nausea, vomiting, and general mal-
aise are common to both syndromes. However, the vomiting
associated with SMS can be sudden, often without anteced-
ent nausea, can occur sporadically (one episode of emesis
every few hours), and can be exacerbated by head move-
ments and olfactory stimuli (e.g., the smell emitted from the
waste containment system) [2]. Unfortunately, no physical
sign or motion analog, other than prior spaceflight experi-
ence, has yet been discovered that can be used to predict
the occurrence or severity of symptoms a particular crew-
member will experience. In general, symptoms improve with
subsequent flights.
Despite an incomplete understanding of the etiology of
SMS, the use of promethazine for treatment has met with suc-
cess in the U.S. space program. Physician-astronaut James
5. Acute Care
Bagian performed the first intramuscular (IM) injection in
space, using promethazine to treat SMS [3]. Approximately
60% of astronauts receiving IM promethazine since that time
have reported a significant improvement in SMS symptoms
in postflight debriefs [4]. Early in the Space Shuttle Program,
the crewmembers occasionally took scopolamine with dex-
troamphetamine as prophylaxis for SMS [5]. This strategy
was largely unsuccessful in reducing the symptoms associ-
ated with SMS and is no longer used. The antiemetic agent
granisetron has been investigated in a ground-based study for
its efficacy in preventing motion sickness, but it was no more
effective than a placebo in that study [6].
During preflight training, flight surgeons teach CMOs how
to give a dorsogluteal IM injection (see the section on Proce-
dures later in this chapter). Although the injection is gener-
ally well tolerated in space flight, the occasional experience
of local soreness at the injection site has led to attempts to
use other routes of administration. The combination of opera-
tional demands in the intense workload of the first hours on
orbit and limited flight opportunities have prevented the con-
duct of controlled trials to evaluate the efficacy of each route;
however, the following observations have been made.
Crewmembers have taken promethazine, 25 mg with 2.5
5.0 mg of dextroamphetamine, orally while on the launch pad
for SMS prophylaxis with variable success. (Commanders and
pilots are prohibited from this practice.) Oral consumption of
the same dose during flight is not generally successful, per-
haps because of the reduced GI absorption associated with the
ileus common upon introduction to microgravity [7]. Some
crewmembers prefer the autonomy of self-administration that
the rectal route provides, and have therefore taken a 25-mg
suppository as soon after arriving on orbit as the workload
allows. In general, however, this route of administration is not
as effective as an IM injection. IM injection is the most com-
mon route of administration. Crewmembers have the option
of receiving IM injection of promethazine from their CMO
either as prophylaxis or after the onset of symptoms; about
30% of IM promethazine injections have been used immedi-
ately before sleep [4].
Because the sedative effects of promethazine might be
expected to cause performance decrements, flight surgeons
determine the level of sedation associated with prometha-
zine for each astronaut or cosmonaut in preflight tests of oral
preparations. No problems have been reported with in flight
somnolence to date, nor has any evidence appeared of per-
formance decrements during the early in-flight period from
promethazine use [8]. Davis and colleagues speculate that the
-adrenergic effects of the excitement after arrival into the
novel environment of orbital flight may largely override seda-
tive effects [9]. Objective in-flight measures of crewmember
vigilance and performance are being developed to aid in titration
of antiemetic doses during critical phases of the mission.
One such critical phase occurs during EVAs. During an
EVA, the sedative effect of an antiemetic, considering the need
for optimal performance by spacewalkers during critical tasks,
103
must be weighed against the risk of emesis inside the space-
suit. For this reason, EVAs cannot be scheduled earlier than
72 h after arrival on orbit in the Space Shuttle Program. The
flight surgeon and the EVA crewmembers are also required to
conduct a PMC before EVAs to ascertain the extent of SMS
and its resolution and to address any other medical issues that
may have arisen. The crewmembers sedative response to pro-
methazine, established during preflight testing, is helpful in
this determination.
Antiemetics have been used before performing an EVA,
although rarely. The first use of an antiemetic agent before
EVA occurred during the Apollo Program [10]. In the Space
Shuttle Program, persistent, mild residual SMS symptoms
have similarly been treated by small doses of promethazine in
combination with oral dextroamphetamine before EVAs.
Severe or prolonged cases of SMS, although rare, can result
in significant dehydration, so intravenous (IV) normal saline
is available and can be administered on orbit. The techniques
of venous cannulation and IV hydration are discussed briefly
in the section on Procedures later in this chapter.
Trauma
Superficial Trauma
Findings from the Longitudinal Study of Astronaut Health
being conducted at NASAJohnson Space Center indicate that
superficial skin trauma is one of the most common reasons
for a Space Shuttle or Mir space station crewmember (during
the joint U.S.Russian flights of the NASA-Mir Program)
to access the resources of the medical kit once symptoms of
SMS have resolved. Superficial abrasions and minor cuts are
inevitable on board a spacecraft, because construction, repair,
and transfer operations as well as working with abrasive mate-
rials such as Velcro are a part of daily life during a mission.
Minor contusions and bruises are common as crewmembers
learn to propel and stabilize themselves in the novel micro-
gravity environment. The hands often sustain such minor inju-
ries, since astronauts or cosmonauts use them in space much
more often for stability and propulsion than on the ground.
Chafing from wearing the U.S. space suit (extravehicular
mobility unit, EMU), particularly in areas subject to inter-
trigo and on the fingertips, is also common. Since the Apollo
Program, spacewalking U.S. astronauts have often reported
blunt nail trauma from working in the EVA suit gloves.
Five of the 12 Moon-walking astronauts had at least one
subungual hemorrhage of the hands [10]. The manual dex-
terity and tactile sensitivity required to perform EVA tasks
demand that the fingertip be in close contact with the space
suit glove, especially during preflight training. The resultant
pressure often leads to nail elevation, which, with sufficient
pressure and repeated trauma, can lead to damage to the nail
matrix. This damage may be confused with onychomycosis,
which can also occur with prolonged activity in the moist
environment of the space suit glove. Placing water-resistant
104
tape over benzoin on the nails has been moderately success-
ful in preventing this problem.
Muscle Strain and Overuse Syndromes
Back pain is the most common muscular syndrome in space
flight and is one of the most common physical complaints of
spaceflight crewmembers. The pain seems to be caused by
elongation of the ligamentous components of the vertebral
spine, which is known to lengthen by 12% early in space
flight because of unloading of the axial skeleton in micro-
gravity [11]. The pain is spasmodic, is located in the para-
lumbar musculature, and can be intense enough to prevent
sleep. The pain usually subsides after the first several days
on orbit. Crewmembers have found relief from discomfort
in many cases by positional changes, such as drawing their
knees up to their chest. Restraint straps and the Soyuz reen-
try couch, which can be used to maintain a semifetal position
during the sleep period, also may afford relief. Nonsteroidal
anti-inflammatory agents are often accessed from the medi-
cal kit for relief as well.
Several muscular strain syndromes are common during mis-
sion training and during flight. Shoulder rotator cuff, forearm
lateral epicondylar, and lumbar strains are among the most
common of these syndromes. One of the first recorded cases
of in-flight shoulder strain in the U.S. space program was after
an Apollo EVA that involved drilling operations on the lunar
surface [10]. Given the compressed timelines during a space
mission, crewmembers can be expected to sustain operations
at a task without relief for hours at a time. If the work requires
an unusual posture that demands limb positioning outside of
the neutral position, muscle soreness and ligamentous strains
can be expected. Such conditions most commonly occur
during an EVA, when abduction and anterior rotation of the
shoulders is required to position the hands properly within
the space suit gloves. Work with a glove box also requires
a similar position, and prolonged operations may result in a
similar overuse syndrome. The flight surgeon can anticipate
this problem before flight by closely monitoring the crew after
sustained training sessions and by starting them on stretching
and strengthening regimens under the guidance of physical
trainers, if necessary, to eliminate pain and reduce the risk of
further injury on orbit.
Another common syndrome associated with sustained work
at a laboratory bench or glove box in microgravity is lum-
bar and anterior abdominal muscular strain. Such strain is par-
ticularly common when toe/foot loops are the only hardware
available for self-restraint. Proper body stabilization in micro-
gravity requires three points of contact with a firm surface,
which means that crewmembers can be expected to assume an
uncomfortable posture for many hours at a time. To free the
hands for delicate tasks in the glove box, for example, crew-
members may use toe loops and press their forehead against
the firm surface of the glove box. Use of T-shaped chairs
also allows crewmembers to maintain a stable posture close
to the microgravity-neutral position, which helps to prevent
T.H. Marshburn
some of the soreness in back and abdominal muscles. Since
avoidance of strain is more effective than treating a strain once
it has occurred, the flight surgeon needs to act as an advocate
for the crew by encouraging the inclusion of properly designed
restraint devices in the launch manifest.
Rarely, the back pain that occurs in space flight is associ-
ated with lancinating pain or patchy paresthesias in the lower
extremities. Mild distraction of sensory nerve roots may con-
tribute to these symptoms. Although the symptoms are usu-
ally transitory, patchy anesthesia has persisted after space
flight in some crewmembers. Postflight diagnostic imaging
and neurologic investigations have not revealed the cause or
any abnormalities after return. The CMOs clinical evaluation
is the only in-flight diagnostic modality available, and to date
symptomatic treatment with anti-inflammatory agents, benzo-
diazipines for direct muscle relaxation, and stretching tech-
niques have been sufficient to control symptoms.
Lacerations
Although no astronauts or cosmonauts have sustained lac-
erations of sufficient depth to require surgical repair during
a space flight, minor lacerations and contusions occur often,
and thus inclusion of repair hardware in an on-board medical
kit is appropriate.
For minor injuries, a variety of bandages are included; ban-
dages are one of the most commonly accessed components
in the medical kit. Handling flight checklists and Velcro are
reported to be the most common sources of minor injuries.
Recently developed Space Shuttle and ISS medical kits (see
Chap. 4) also include tissue adhesives. No difficulties have
been experienced to date using tissue adhesive terrestrial
applicators in the microgravity environment (personal com-
munication, Richard Linnehan, 1998). Even though the liquid
adhesive does not tend to leave the operative field in micro-
gravity, crewmembers currently apply it in a glove box or
while using eye protection.
The medical kits flown on the Space Shuttle and the ISS
contain synthetic absorbable and nonabsorbable suture mate-
rial with a small, sterile, minor surgery subpack for repair of
deeper lacerations. The CMO also has the option of using tis-
sue adhesives or small skin staples on orbit. Tissue adhesives
would be used for wounds less than 5 cm (2 in.) long in non-
mucosal facial lacerations and selected extremity and torso
wounds [12]except for the those on the hands, feet, and
joints, since most studies that compare tissue adhesives with
suturing have excluded hand and foot lacerations and lacera-
tions that cross a joint [13]. Staples are also included in the
medical kits to quickly close wounds in the scalp, trunk, and
extremitiesagain excluding the hands and feet. Contraindi-
cations for use of staples on orbit are the same as those on the
ground: wounds that are more than 12 h old, those that are
grossly contaminated, or those that have devitalized margins
or flaps. Because a crewmember could sustain a contaminated
wound in a spacecraft (as discussed later in this section), the
primary advantage of staples is the speed of closure, which
5. Acute Care
may reduce the frequency of infectious complications. Use of
staples on Earth, when these indications are followed, does
not seem to increase the rate of cosmetic or infectious compli-
cations, although the staples are painful to remove and may be
associated with inflammation [1416].
The components of the surgery subpack in the Space Shuttle
medical kit have been tested during parabolic flight [17,18].
To date, the greatest challenge of suturing in microgravity has
been restraining the hardware. Magnetic pads have been tested
[18], but they have been replaced by simple sterile pouches
that are smaller, lighter, and more adequately restrain suturing
tools. The elastic memory of suture helps it maintain a coil,
and thereby keeps the entire length within close proximity of
the surgical field. However, suture also floats above the surgi-
cal field, so contamination is still a possibility. Crewmembers
who have performed animal surgery in space simply cut the
suture to use the shortest length needed (personal communi-
cation, Richard Linnehan, 1998). Use of staples for wound
closure has also been investigated in parabolic flight; the only
matter of concern was maintaining control of the loose staples
after they are removed [17].
Much has also been learned about the feasibility of
hemostasis in parabolic flight and in space flight with ani-
mal models of surgery and surgical wound repair. Venous
and capillary bleeding is easier to control in microgravity
than on the ground, since surface tension forces overcome
inertial forces in the absence of a gravity field, and blood
tends to pool and form a dome around a wound. Arterial
bleeding, however, has been more difficult to control in
microgravity. Control of irrigant solutions is somewhat
more difficult because low irrigation rates are necessary to
prevent splashing. However, loose-weave absorbent gauze
held next to the surgical field easily maintains adequate
control of irrigant splash [1821].
Prevention of wound infection may be a challenge in the
microgravity environment. Superficial laceration infection
rates of 50% have subjectively been noted by U.S. astronauts
and flight surgeons [22]. Although minor infections are easily
resolved with topical bactericidal ointments, their occurrence
leads to the suspicion that infection rates in space may be
slightly higher than on the ground. Whether direct effects of
microgravity on humoral immunity, on atmospheric charac-
teristics, or both, contribute to an increased wound infection
rate remains unknown. (The function of the immune system in
space flight is addressed in Chap. 15.) For example, the Space
Shuttle atmosphere in microgravity contains more free-float-
ing particulates than are found in one-g environments, where
heavier particulates settle to the ground. The Space Shuttle
atmosphere can contain 11 times the airborne particle mass
concentration (for particles larger than 100 m) than terrestrial
indoor controls [23]. Airborne microorganisms also are associated
with these heavier particles [20].
Investigations during both Space Shuttle and Mir missions have
shown that the microbial content of spacecraft air increases
with mission duration and also increases with elevations in
105
temperature and humidity. Airborne bacterial concentrations
on the Mir were generally comparable to Space Shuttle lev-
els (120325 colony forming units (CFU)/m3) [24], bacterial
counts of up to 1,000 CFU/m3 have been noted during tem-
perature elevations [25] after failure of the cooling system.
By comparison, a conventional operating room particle count
is 133158 CFU/m3 [26]. The potential therefore exists for
greater risk of airborne contamination of wounds. The ISS
will likely experience similar temperature fluctuations, but
high-efficiency particulate air filters that have been installed
in the air revitalization system on the ISS may reduce the par-
ticle and microorganism burdens. HEPA filtering is planned
for planetary exploration vehicles and habitats.
Another potential source of infection is condensate, which
can accumulate in space stations that rely on adequate, laminar
intramodular airflow and a functioning water recovery system
to remove excess moisture from the atmosphere. Condensate
that is left to adhere to surfaces near waste collection systems
has shown a microorganismal population similar to that in
found in pond water. Bacterial mats with amoeboid species,
ciliated protozoa, and spirochetes have been recovered from
a collection of condensate. Lacerations sustained near waste
management systems (which could occur during maintenance
of those systems) or lacerations contaminated by condensate
left standing in a remote area of the spacecraft should thus be
considered dirty wounds.
Adequate irrigation of lacerations is likely to be at least
as important in preventing wound infection in space as it is
on Earth [27]. Currently, sterile solutions for irrigation are
very limited on board spacecraft. On-orbit instructions for
irrigation specify that only sterile physiological saline be used,
but potable water from the spacecraft galley can be used as
well. Ground-based studies have demonstrated that irriga-
tion of wounds with tap water can result in the same, or
lower, infection rates as irrigation with sterile solutions [28].
The highest microbial counts from the Space Shuttle galley
to date are 1,600 CFU/100 ml (measured after flight), and
generally those counts are much lower. Microbial growth in
uniodinated or inadequately iodinated Space Shuttle water is
almost universally caused by a single organism, Burkholdera
cepacia, a pseudomonad that is nonpathogenic in individuals
with normal immune function. No literature exists regard-
ing whether this microorganism has a role in wound con-
tamination. Pasteurized Space Station water has shown very
low microbial growth rates as well, although gram-positive
species such as Staphylococcus aureus have been known
to survive the pasteurization process on the Mir [25]. The
iodinated water available in the Space Shuttle contains 34
parts per million (ppm) of free iodine. This water typically
carries less than 1 CFU/100 ml of microbial growth, and it
contains less than the 1% free iodine associated with tissue
destruction [29].
Syringes and intracatheters are available in the medical kits
for high-pressure irrigation of wounds. Blood products in an
irrigant splash are more of a housekeeping concern than a
106
biohazard, because crewmembers are well-screened for the
presence of human immunodeficiency virus and for hepatitis
A, B, and C. A loose-weave absorbent gauze placed next to
the wound is therefore usually sufficient for catching splashing
irrigant [19].
Particulate matter could also pose a biohazard to space
crewmembers in terms of its possibly being retained in an
open wound. Although safety restrictions limit use of glass
or wood aboard spacecraft, sawing of coolant pipes and metal
structural components, as was required on Mir [30], could
result in retained metallic foreign bodies if a crewmember
sustains a laceration. Particulates pose more of a risk of eye
irritation or corneal abrasion than wound irritation. Diagnostic
sonography will be available on the ISS (see Chap. 9); a 7.5-
MHz probe can detect plastic and wooden foreign bodies with
9598% sensitivity and 8998% specificity [31]. Updates for
tetanus prophylaxis are also given to crewmembers before
missions to cover them for the duration of the flight.
Lidocaine and bupavicaine solutions (with and without
epinephrine) are also available in the medical kits for local
anesthesia in wound repair; pending results from actual expe-
rience on orbit, the principles of local tissue anesthesia are
expected to be the same in space than on Earth. Lidocaine
will be used for local anesthesia when return of normal sen-
sation is desirable within a few hours. Bupivacaine is flown
for situations in which longer periods of anesthesia (48 h)
may be needed.
For wound repair outside the scope of the CMOs capa-
bilities and outside the capability of the medical kit, wilder-
ness medical principles apply. Currently, neither the Space
Shuttle nor the ISS provides the capability for repairing
complex wounds such as hand tendon, eyelid, or lacrimal
sac lacerations. The hardware is not available, and the
intense training schedule for Space Shuttle and ISS crew-
members does not allow time to train CMOs in procedures
that are typically the purview of specialists in the terrestrial
setting. Delayed primary care is therefore the only treat-
ment option currently in low Earth orbit (LEO), and that
option may be appropriate for some kinds of injuries. Hart
and colleagues assert that care provided for flexor tendon
injuries, for example, can be delayed as many as 10 days
after injury with little change in outcome as compared with
immediate definitive care [32]. Irrigation, antibiotics (if
indicated), skin closure, and splinting can all be performed
on orbit. As the number of crewmembers on future missions
increases, serious consideration will be given to including
a physician as a member of the crew.
Relatively little is known about wound-healing rates in
space flight. Anecdotal evidence from flight surgeons, astro-
nauts, and cosmonauts indicates that superficial lacerations
or phlebotomy wounds may take longer to heal in space
than on Earth. No photo documentation or other objective
measure of wound repair and healing has been conducted
to date, although such a project is currently under way.
Repaired surgical wounds in animals after short-duration
T.H. Marshburn
space flight have shown increased inflammatory responses,
reduced angiogenesis, and abnormal arrangement of colla-
gen fibers, leading to decreased scar strength at the wound
margins. These findings suggest an increased risk of wound
dehiscence [3335]. Gross observations, however, have not
indicated any change in wound infection or dehiscence rates
during the 12 days after surgery (personal communication,
Linnehan, 1998). More research is needed in this area, since
delays in wound healing will affect wound management
principles such as time to suture or staple removal, which in
turn will affect mission operations.
Musculoskeletal Trauma
The Lower Extremities
More significant trauma is also possible during space flight.
The magnitude of forces involved in most terrestrial trauma
events (falls, motor vehicle accidents) are largely absent
in microgravity. However, the massive objects handled by
crewmembers during EVA or during Space Shuttle-to-ISS
transfer operations have sufficient momentum to cause
injury, particularly in the larger spacecraft interior volumes
of ISS. Moreover, the elastic restraint straps that are used to
secure stowage items and stabilize crewmembers carry sig-
nificant kinetic energy when they fail. Snapping of an exer-
cise bungee cord or a treadmill harness can, and has, resulted
in significant injury.
Risk of injury also increases when the speed of crewmem-
ber translation between modules increases, which occurs in the
activity-intense phases of a flight such as during an in-flight
emergency response or a Space Shuttle-to-ISS transfer opera-
tion. In the U.S. space program, the Space Shuttles capacity
to ferry a relatively large payload volume to the ISS demands
rapid transfer of the constituents of that payload (supplies and
experimental hardware) in a short time, increasing the risk of
soft tissue injuries and fractures.
In-flight ligamentous sprains have generally been mild
in the U.S. Space Shuttle Program to date, usually occur-
ring in the hands, the knees, and the ankles. Treatment has
required little more than symptomatic therapy with nonste-
roidal analgesics. Although crewmembers in microgravity
are essentially non-weightbearing, they are at risk of more
severe ligamentous injuries. Astronauts and cosmonauts
exercise daily on a treadmill and other devices to minimize
the muscle atrophy and bone mineral density loss known to
occur with exposure to microgravity.
For maximal training benefits, crewmembers adjust the
treadmill harness tension to exert a load equal to 7080% of
the crewmembers body weight, distributed over the crew-
members hips and shoulders. These loads increase the risk
of ankle injuries during treadmill exercise sessions. Also,
spacewalking astronauts or cosmonauts have commented that
repeated entry into and exiting from the foot restraints can
result in soreness in the ankle and knee ligamentous struc-
tures. The motion consists of foot internal and external rota-
5. Acute Care
tion with a compression or distraction force applied to the
ankle and knee joints. The problem may be exacerbated in
the crewmember with preexisting knee injuries, which is the
most common orthopedic problem in the U.S. astronaut corps
[36]. Prior meniscal or anterior cruciate ligament injuries may
remanifest during these operations. Conceivably, then, an
ankle sprain or a knee medial or lateral collateral ligament
sprain could occur or be exacerbated during flight.
Preflight injuries may place an astronaut or cosmonaut at a
higher risk of injury during a mission as well. A survey con-
ducted as part of the JSC Longitudinal Study of Astronaut
Health showed that astronauts sustain nearly three times as
many musculoskeletal injuries during the period beginning
1 year before flight to 1 year after flight than at other times.
Both ankle and knee injuries tend to occur in the period before
the mission, probably because of the high training intensity at
that time. Therefore, weaknesses in knee and ankle ligamen-
tous complexes can be expected in flight for those astronauts
who are recovering from a previous injury.
Inadvertent inversion of the foot with a sprain of the lateral
ligamentous complex is the most common ankle sprain ter-
restrially [37]. The same injury occurring on orbit would
most likely be less severe without the stronger inversion stress
driven by the weight of a person in one-g. Presentation of an
injured ankle will most likely differ in microgravity. Local
edema from a ligamentous injury may be reduced in space
flight, since diminished hydrostatic pressures in the lower
extremities would result from cephalad total body water redis-
tribution in microgravity. These shifts likely will achieve the
same effect that elevation of the injured extremity would on
Earth [38]. The examiner would then expect to see less swell-
ing than would occur in one-g and thus could underestimate
the degree of ligamentous injury. Although a CMO would
not be expected to perform an expert physical examination,
he or she could assess swelling and bruising and perform
the squeeze test to rule out syndesmotic injury. Palpation
about the ankle joint will help determine which ligaments are
affected. The anterior drawer and talar tilt tests are of limited
diagnostic accuracy, even in the hands of an experienced spe-
cialist [3941]. These studies suggest that gentle stress testing
immediately after the injury can provide useful information,
in that laxity without pain is suggestive of a third-degree tear,
and pain with minimal or no laxity is suggestive of a first-
or second-degree tear [42]. As is true in terrestrial medicine,
the examiner should rule out a fifth metatarsal or fibular head
fracture in the examination as well.
Not surprisingly, treatment options of an ankle sprain are
limited on orbit. Cryotherapy will usually not be available
because of limited refrigerator/freezer storage volume. If
available, it should be applied early [43]. As noted above, the
classic terrestrial principle of elevating the affected extremity
to limit swelling is meaningless in microgravity. An injured
crewmember should be able to continue most tasks and
remain non-weightbearing. The available medical kits have
sufficient supplies to compress the ankle with tape or elastic
107
wrap, which has been shown to be beneficial for any grade of
ankle sprain [44].
After a crewmember sustains an ankle sprain, expedient
return to treadmill exercise is essential, because aggressive
return to function is shown to hasten recovery and reduce
functional limitations after an injury [43]. This could be
accomplished by a treadmill program using lower tensions on
the harness and by an exercise program using the cycle ergom-
eter, bungee cords, and (on the Space Shuttle) rudder pedals
to strengthen the ankle everters and the muscles of plantar and
dorsiflexion. Crewmembers have found that they can simulate
ambulation in a spacecraft cabin by providing counterpressure
with their hands on an opposite wall. In this way, they can
control the pressure on the ankle.
Since estimates of healing time would be very important for
future timeline planning, an accurate determination of degree of
injury will be essential. Return to full function for ankle sprains,
for instance, depends on the grade of the sprain. For a grade 1
sprain, the expected full return to function is 7 days; that for
a grade 2 or 3 sprain can take several weeks [44]. The type of
immobilizationsuch as a simple compressive dressing or splint
for suspected syndesmotic injuries and fractures [45,46]and
the duration of treatment also depend on an accurate diagno-
sis. After assurance that no fracture or third-degree sprain is
present, aggressive rehabilitation can begin. With no roentgen-
ography capability on orbit to rule out fracture of an extremity,
CMOs and flight surgeons will need to use established decision
algorithms based on the findings from clinical and sonographic
examinations. In such cases, the Ottawa Ankle Rules can be
applied: crewmembers with ankle pain after trauma, with pain
at further attempts at ambulation on the treadmill or on palpa-
tion of the lateral malleolus and medial malleolus, or indeed
any crewmember over age 55 years, would be suspected of hav-
ing sustained a fracture. However, in some studies [47,48], the
Ottawa Ankle Rules have proven only 9498.5% sensitive for
detecting ankle fractures.
Sonography, as noted above, is available on the ISS and is
currently the only imaging modality available in spacecraft.
Fortunately, sonography has recently shown to be useful for
detecting occult ankle and foot fractures [49], and its sensitiv-
ity surpasses that of roentgenography for identifying the for-
mation of callous after injury [50].
Splints (other than finger splints) are not available in the
Space Shuttle medical kit because of volume constraints,
although crewmembers have worn air stirrup ankle splints
during flight to stabilize preflight injuries. (An ankle splint
must fit inside a boot that is worn during launch and entry, and
air bladders are opened inside of the boot to provide pressure
relief in case of cabin depressurization.) Both the U.S. and
Russian ISS medical kits carry a variety of splints, and splints
can also be constructed from available on-orbit materials.
Assessments of knee injuries would be similar to those on
Earth, although the potential for a fracture would be unlikely
without the added force applied by a one-g field. Several deci-
sion algorithms similar to the Ottawa Ankle Rules have been
108
developed for knee injuries. A review of these algorithms indi-
cates that the Pittsburgh Knee Rules allow sufficient specificity
without sacrificing much more sensitivity than the Ottawa Knee
Rules [51]. The Pittsburgh Knee Rules can be summarized
as follows: A fracture can be considered very unlikely in the
absence of blunt trauma in a person younger than 55 years if the
head of the fibula and patella are not tender; if the person can
flex the knee to 90 degrees, and if the person can bear weight
immediately or simulate ambulation for about four steps. The
Pittsburgh Knee Rules do not apply, however, if crewmembers
have a history of surgery or prior fracture.
Elements of the crewmembers history and physical that
will help the CMO determine whether an anterior cruciate
ligament injury has taken place are whether the crewmem-
ber heard or felt a pop, whether swelling is present, and
whether any mobility is lost. Pain upon simulated ambulation
indicates a meniscal tear. Once both the patient and the
CMO are sufficiently restrained, Lachmans maneuver or
the anterior drawer test can be performed. Although a com-
pression dressing and knee immobilization can be achieved
on orbit, no hardware is currently available on the ISS or
Shuttle to support knee joint aspiration.
Microgravity is less stressful than one-g on the extremi-
ties and axial skeleton, and ligamentous injuries of the lower
extremities can be worked around in the course of most
intravehicular tasks. Nevertheless, an injured crewmembers
ability to return to a gravity field remains a concern. The abil-
ity to perform safely at maximum capability upon arrival in a
gravity field makes appropriate in-flight management of these
injuries a necessity.
Perhaps most important, the flight surgeon should ensure
before launch that the assigned crewmembers are maintaining
an adequate exercise training regimen that includes aerobic
and anaerobic exercises so that the risk of on-orbit injury is
minimized. The flight surgeon should ensure that the in-flight
exercise schedule is maintained and that other mission activi-
ties do not interfere with maintaining that schedule.
Hand Injuries
Because the hands are used to provide stability and propulsion
in microgravity, the chance of injuring them may be greater
in space flight than on the ground. Standard terrestrial splint-
ing practices can easily be implemented on orbit; however,
establishing the presence or absence of a fracture will be prob-
lematic. Sonography has shown some success in delineating
tendon injuries [52] but not in delineating scaphoid fractures
[53]. The ability of sonography to detect phalangeal, metacarpal,
or other carpal injuries is not known.
Infectious tenosynovitis will also be of concern during a
long-duration mission because of its profound operational
impact owing to its morbidity when treatment is delayed.
Staphylococcus aureus and Streptococcus pyogenes cause
most hand-wound infections that are not caused by mamma-
lian bites. Although the broad-spectrum parenteral antibiot-
T.H. Marshburn
ics amikacin and imipenem are available on orbit, a complete
course of treatment will have to involve the use of oral antibi-
otics because the parenteral agents are in limited supply.
Burns
Eight instances of onboard combustion have been documented
to date, four on the U.S. Space Shuttle and four on the Russian
space stations Salyut and Mir [30,54]. Of particular note is the
fire that took place during the Shuttle-Mir increment NASA-4
in February 1997. Lithium-perchlorate canisters were used on
board Mir to supplement the Russian space stations Elektron
oxygen-generation system. One of these canisters caught fire,
producing (by some accounts) a 1-m (3.28-ft)-long flame and
releasing enough smoke to obscure visibility within seconds.
A crewmember sustained second-degree burns of the forearm
in association with this event.
Clearly spaceflight medical kits must contain hardware
and medications to support the treatment of burns. The
Space Shuttle and ISS medical kits contain silver sulfa-
diazine, sterile gauze, parenteral opioid analgesics, and
crystalloid solutions. As is usual in space flight, weight
restrictions limit the ability to replace fluid volume in severe
burns. The maximum quantity of crystalloid planned for
ISSabout 12 Lwould support a 70-kg (154-lb) crew-
member who has sustained burns over 40% of his or her
body for 24 h (following the Parkland prescription of 4 ml
per kg per percentage of surface area burned), which is the
minimum time needed to leave LEO, return to Earth, and
deliver the patient to a definitive medical care facility. Given
the high concentration of particulates present in spacecraft
atmospheres, CMOs will have to pay special attention to
secondary infection of burn wounds. With this in mind,
antiseptic cleaning, debridement, and topical antimicrobial
application can be performed with the resources provided
in both the ISS and Space Shuttle medical kits.
First-degree burns have occurred as a result of ultravio-
let (UV) light exposure through unfiltered spacecraft win-
dows. Sunlight that is not filtered by atmosphere or window
coatings carries high-intensity UV rays (180400 nm) that
can cause dermal burns in seconds. The ISS windows con-
sist of three fused silica panes, with a scratch pane that can
be removed for high-quality imaging. When this pane is
removed, the window admits a higher spectral range [55].
Skin exposure to sunlight for less than a minute through
windows without this added filter has resulted in first-degree
burns. The principles of management for first-degree burns
are the same in space flight as on the ground, and adequate
oral analgesics and topical antimicrobials are accordingly
flown in medical kits.
Headache
Headache relief is one of the most common reasons space-
flight crewmembers take oral analgesics during Space Shuttle
5. Acute Care
missions [4]. A review of 89 Space Shuttle flights involving
508 crewmembers and 4,443 flight days by the JSC Longi-
tudinal Study of Astronaut Health revealed headache in 304
(69%) of 439 men and 38 (55%) of 69 women. Headaches
can afflict crewmembers with SMS, and they seem to be
associated with the cephalad fluid shifts that occur soon after
orbital insertion; however, headaches can also occur later
during flight, even as late as several months into a mission
[56]. This section reviews the most commonly suspected
causes of headache in the unique environment of space flight
and the well-screened space crew population, and suggests
treatment options that can be used by crewmembers, CMOs,
and flight surgeons.
Headaches occurring during the first few days of space flight
are most often associated with space adaptation syndrome,
with nausea as an accompanying symptom. The headache is
self-limiting and usually resolves along with other symptoms
of space adaptation syndrome as the crewmember adapts to
microgravity, usually within 72 h.
Caffeine withdrawal, which can occur during any expedition
to a remote site, can occur early in a space flight. Although
caffeinated beverages are available to spaceflight crews, busy
work schedules often preclude their preparation. Taste prefer-
ences also change on orbit, and crewmembers may choose not
to maintain their usual caffeine intake. Therefore, caffeine-
containing oral medications should be provided for spaceflight
crewmembers who are known to be susceptible to caffeine
withdrawal symptoms. These medications can provide a sub-
stitute for colas or coffee, 8 oz (0.25 kg) of which contain
approximately 35 mg and 85 mg of caffeine, respectively.
Headaches that occur beyond the initial 72 h of microgravity
exposure should alert the flight surgeon and CMO to consider
the possibility of atmospheric contaminants. CO2 contamina-
tion, for example, is a well-known cause of headache. A con-
centration of CO2 of 2% or more in a cabin at sea level will
produce headaches in humans [57] and is the suspected cause
of some of the headaches that were experienced on board the
Mir space station and the Space Shuttle. The average CO2 lev-
els on the Space Shuttle are 0.26%. The onset of headaches in
crews aboard Mir has led at least twice to the discovery that
the CO2 removal system had failed [30].
Headaches can occur while crewmembers are working
in small, poorly ventilated volumes such as behind panels or
among tightly packed payloads. In cases such as these, archi-
val air samples have not yet revealed a causative contaminant,
perhaps because no sample has yet been collected at the spe-
cific location, and at the exact time, of symptom onset. Recent
use of a portable CO2 sensor also has not demonstrated elevated
CO2 levels in these areas. Therefore, as a cause of headache, the
accumulation of CO2 in pockets in modules that otherwise
display nominal CO2 readings has yet to be demonstrated.
A distinct odor may precede headache onset. Crewmem-
bers have identified glue or adhesive smells antecedent older than 50 years.
to their symptoms, suggesting that acetates or xylenes may be
causative agents. Again, however, archival air samples have
109
not yet demonstrated the presence of high levels of these
compounds.
Despite the inability to clearly identify a specific environ-
mental cause for headaches in space flight, exposure to freshly
scrubbed air results in symptom resolution in less than an hour
in most cases. Crewmembers with headaches that develop while
they are working in space modules that have no active air revi-
talization systems describe relief of symptoms after retreating to
a module with contaminant removal systems that contain both
activated charcoal and lithium hydroxide. (These modules are
capable of removing CO2 as well as most low molecular weight
volatile organic compounds.) Thus regardless of the cause of
the headache, symptoms usually resolve with improvement of
intramodular airflow, placement of portable fans by the work-
site, or exposure to freshly scrubbed air. The CMO and flight
surgeon can work with the ground control team to plan mission
objectives around areas of suspicious airflow and to avoid accu-
mulation of crewmembers in a single area.
Carbon monoxide has been the known cause of headache in
one case after a microimpurities filter overheated (see Chap.
21). The flight surgeon should presume that any crewmem-
ber with a headache at the time of a smoke alarm warning,
with visual identification of smoke or fire, or with olfactory
detection of smoke has been exposed to carbon monoxide.
ISS flight rules dictate that crewmembers in this scenario
should don oxygen masks and retreat to a module with uncon-
taminated air. One hundred percent oxygen is available in the
Space Shuttle and the ISS for treatment of suspected carbon
monoxide poisoning, although means of determining carboxy-
hemoglobin levels in real time are not available.
Apart from headaches associated with the aforemen-
tioned causes, the flight surgeon and CMO must also con-
sider endogenous causes of headache. During the medical
screening necessary to become an astronaut or a cosmonaut,
applicants with a history of migraine or cluster headache or
with cardiovascular disease are disqualified. Computerized
tomography or magnetic resonance imaging of the central
neuroaxis of prospective candidates is not currently per-
formed, and so subclinical central nervous system abnormali-
ties may pass undetected. However, this will be implemented
soon for long duration crewmembers. Endogenous causes of
headache that the CMO and flight surgeon must consider
include tension headaches, cluster headaches, trigeminal
neuralgia, and temporal arteritis. Tension headaches are the
most common cause of headaches in general, producing 78%
of headaches in terrestrial practice [58]. The high workload
of crewmembers during a mission makes tension headache a
likely diagnosis for in-flight headaches after the first days on
orbit. The age at first onset of cluster headaches and trigemi-
nal neuralgia can be 4050 years, a range only slightly older
than that of the average U.S. astronaut. Similarly, temporal
arteritis can become evident for the first time in individuals
Examination of a crewmember with a persistent headache
that has no apparent cause should include documentation of
110
vital signs and a directed physical examination. Signs and
symptoms that should raise suspicion of serious intracranial
abnormalities are headaches that increase in frequency and
severity; headaches associated with mental status changes,
fever, or meningeal signs; focal neurological deficits; and
headaches that occur in individuals over 55 years of age [59].
The physical examination should evaluate the affected
crewmember for otitis media and sinusitis (see the section on
Upper Respiratory Disorders later in this chapter). Variable-
applanation tonometry is available on the ISS, and glaucoma
should also be considered, particularly in crewmembers with
associated visual changes [59]. The fundoscopic examination
should include a search for flame hemorrhages, papilloedema,
and subhyaloid and retinal hemorrhages, which are diagnostic
of subarachnoid hemorrhage in the age group of spacefarers.
A focal finding on an in-flight neurologic examination (see
Chap. 17) should heighten concern regarding significant intra-
cranial abnormalities.
Although few diagnostic and treatment modalities are avail-
able on spacecraft, pain control with non-narcotic analgesics
such as acetaminophen, ibuprofen, and aspirin in addition to
air purification and provision of 100% oxygen are available if
needed. The flight surgeon must work with other members of
the ground team in adjusting the mission timeline so that the
crewmembers can avoid areas in which air contamination or
accumulation of metabolites may have occurred. The flight
surgeon should also remind crewmembers who are exhibiting
symptoms that even if the symptoms resolve spontaneously,
they should obtain an archival air sample from the area of the
spacecraft occupied by the crewmember when the headache
began. This practice may not aid in management of the medi-
cal problem for that crew, but it may enable a problem with
contaminants to be identified and addressed for the benefit of
future crews.
Sleep Disorders
The risk of chronic fatigue in spaceflight crews is signifi-
cant. The crewmembers drive to complete multiple mission
objectives and the need for spacecraft maintenance into the
period before sleep reduces the amount of sleep obtained
during flight. Also, since orbital mechanics is the main
driver of the crew mission schedule, crews must often sleep
in shifts to accommodate launch, rendezvous, and landing
times. Crewmembers can begin to experience a sleep debt
before launch. Trainers and crews typically train heavily in
the weeks before launch; and despite guidance given in the
judicious use of bright lights, dark goggles, sedative-hyp-
notics and melatonin to regulate sleep and rest cycles, sleep
debt can still accrue. Thus for ISS rendezvous missions,
a launch slip of 24 h requires a 20-min phase advance in
the sleep schedule (i.e., the crew must go to sleep 20 min
earlier for each 24-h delay that occurs.) Schedulers of the
on-orbit timeline abide by documented constraints to the
amount of sleep shifting that can be imposed on a crew;
T.H. Marshburn
nevertheless, the combination of sleep shifts, workload,
and crew motivation for high work output can result in
chronic sleep debt.
Sleep medications are therefore among the most commonly
used medications by spaceflight crews [4]. Non-benzodiazipine
hypnotics that have a short onset of action and half-life, such
as zolpidem, are being used with increasing frequency to
assist in ensuring the onset of sleep. Melatonin is preferred,
either alone or with zolpidem, by some crewmembers. Benzo-
diazipines such as temazepam are used less often. Guidelines
for use of these medications are determined before launch and
are discussed more fully in Chap. 20.
Flight surgeons can also assist in preventing crewmember
fatigue by limiting interruptions by ground control in the
crews before- and after-sleep periods. Flight surgeons also
monitor and protect the crews exercise time, which is par-
ticularly important during long-duration flights. In postflight
debriefings, long-duration crewmembers have stated unani-
mously that the daily exercise period is one of the most impor-
tant factors that promotes sleep onset and reduces the amount
of time spent awake during the sleep period.
Skin Disorders
Skin disorders are another common problem during space
flight [4]. As discussed previously, the particulate components
of spacecraft air may increase the risk of superficial infections
in crewmembers with breaks in the skin from superficial cuts
and abrasions. The relatively dry air on board Space Shuttles
typically results in only minor drying of the skin during brief
missions. More serious skin conditions such as folliculitis,
contact dermatitis, and fungal infections can occur during
longer-duration missions. Although the cause of these skin
conditions has yet to be determined, contributing factors may
include the higher humidity of space station atmospheres and
the exposure of the crews to relatively exotic compounds.
Space station maintenance operations demand close physi-
cal contact with substances such as ethylene glycol (which
was used as a coolant on Mir), cadmium and nickel (con-
stituents of anticorrosives in coolant lines), and urea (located
near waste containment systems). Problems from contact with
these materials can be prevented by using chemical-resistant
gloves and suits to protect the skin during contingency opera-
tions and in-flight maintenance.
Treatment of skin disorders depends on avoiding the source
and treating with topical steroidal, antifungal, or antibacterial
creams, alone or in combination. Since dermatologic problems
lend themselves to video downlink, the flight surgeon and
consultants can assist in the diagnosis. Cellulitis has occurred
during space flight; treatment with oral antibiotics according
to standard terrestrial protocols has been successful on orbit.
Aggressive treatment is necessary to minimize performance
degradation. EVA operations in particular cannot be effectively
conducted while the crewmember has a distracting derma-
tologic problem.
5. Acute Care
Eye Disorders
Ocular injuries, in addition to being common, are among the
most serious of ambulatory care disorders confronted dur-
ing space flight. The microgravity environment increases
the risk of eye injury and contamination from free-floating
foreign bodies that would otherwise settle onto a surface in
one-g. Failure of the elastic cords used to restrain hardware
and tether crewmembers during exercise has resulted in both
scleral and corneal injuries and abrasions. Crewmembers
have sustained potentially vision-compromising eye injuries
that have required topical antibiotic therapy, pain control, and
reevaluation over several days.
The flight surgeon should be aware of the mission phases
when foreign body injuries are most likely. Perhaps the most
hazardous time for this type of injury is during entry and
transfer operations to a station and into a new module such
as a cargo vehicle. The act of opening and entering new mod-
ules does not seem to pose a hazard, but as transfer operations
begin, metal shavings, loose debris, and dust can be released
[56]. For this reason, crews are advised to wear protective
goggles during these operations.
A magnifying lens, proparacaine drops, an ophthalmoscope
with a cobalt-blue light filter, cotton-tipped swabs, pH strips,
and fluorescein strips are available on orbit for diagnosis.
Because no slit lamp is available, subtle injuries to the anterior
chamber are difficult to detect. However, CMOs are trained to
perform a complete primary ocular examination with lid ever-
sion and examination with an ophthalmoscope.
If a foreign body is suspected of being present, an effective
initial technique for removing it is to place a bolus of drinking
water over the affected orbit. In microgravity, the fluid forms
a dome over the eye. This dome adheres via surface tension
and creates a bath in which the crewmember can blink, which
usually removes the foreign body. Water can then be absorbed
and contained with a towel. Alternatively, a drink bag can be
used to direct a low-velocity stream of potable water onto the
eye, again using a towel for water containment. To prepare for
such eventualities, Space Shuttle and ISS crewmembers are
instructed to place a drinking bag of potable galley water in
modules where activities will be performed that present a high
risk of exposure to ocular foreign bodies.
Space Shuttle and ISS medical kits also contain an emer-
gency eyewash system for removing ocular foreign bodies
and for treating ocular chemical exposure. The emergency
eyewash system consists of goggles into which galley drink-
ing water can be infused, creating a turbulent flow over the
affected eye at a rate of 1 L/min [60]. CMOs for Shuttle and
ISS are also trained to remove foreign bodies from the eye
with a moistened cotton-tipped swab or a 20-gauge needle.
Eye burrs for removing more stubborn foreign bodies or rust
rings are not available on the Space Shuttle or the ISS. Eye
patches, including a metallic eye shield, are available for use
as needed. However, CMOs are cautioned to limit the use of
patches as needed for comfort only, because patching does not
111
seem to enhance healing rates and may increase the risk of
secondary infection [61]. Cycloplegics and topical ophthalmic
antibiotic preparations such as gentamicin, erythromycin, and
ciprofloxacin are easily stowed in spacecraft medical kits and
have been included in the Space Shuttle and ISS medical kits
as well. Because the CMO can reexamine an eye injury often,
follow-up and early detection of complications or treatment
failures should not be a problem on spaceflight missions.
As the use of tissue adhesives increases in the microgravity
environment, misplaced adhesive into the eye is a potential
hazard. If a crewmembers eye is thus contaminated, the medi-
cal kit contains sufficient ophthalmic ointment to apply to the
affected eye. The eyelid should spontaneously open 14 days
after treatment as the adhesive bond releases [62].
The ISS and Space Shuttle medical kits also contain oph-
thalmic antimicrobial preparations. The relatively high con-
centration of carbonaceous particles in spacecraft air, the
frequent and potentially prolonged use of contact lenses, and
the increased risk of ocular foreign bodies all increase the
risk of bacterial keratitis and conjunctivitis. The dilation of
conjunctival vessels associated with the cephalad fluid shifts
at microgravity onset should not be confused with conjunc-
tivitis. A crewmembers eye must be carefully examined to
rule out foreign body contamination for any case of unilateral
red eye. Also, given the increasing use of soft contact lenses
among members of the U.S. Astronaut Corps, preflight train-
ing includes the caution to remove lenses before sleep.
Ciprofloxacin ointment and drops are flown in the Space
Shuttle and ISS medical kits for treatment of contact lens-
associated pseudomonas keratitis. In a contingency in
which a portion of the station is rendered uninhabitable, as
occurred after the collision between the Progress and the
Mir in 1997, ISS crewmembers can be separated from their
lens cleaning and storage system. ISS crewmembers who
wear lenses are now cautioned to carry back-up spectacles
with them at all times.
Although applying ophthalmic solutions poses little diffi-
culty in microgravity, a significant amount of solution is wasted
with each application. Titration of a dose into single drops is
difficult because of the lack of gravity-induced separation of
air and fluid in the bottle, which results in inconsistent doses
of solution with each application. For this reason, ointments
are used for serious infections such as corneal ulcers, where
prudent use of a limited supply of antibiotic is necessary to
ensure that a complete antibiotic course is available.
Judicious use of ocular antibiotics applies to the treat-
ment of the red eye on orbit as well. Conjunctivitis, for
example, is generally self-limiting, showing cure or signifi-
cant improvement by 25 days in 64% of patients, but use
of topical antibiotics is associated with an improved clinical
remission rate [63].
UV keratitis can and has also occurred on orbit [56]. Unfil-
tered sunlight, as noted above, can cause ocular injury in sec-
onds. Crews are instructed to wear UV protection at all times
when Earth-observing at any window that does not block UV
112
light, and the medical kit contains sufficient means to treat
UV keratitis should it occur. Proparacaine is used to facilitate
the examination, and a short-acting cycloplegic and antibiotic
ointment or drops is then applied. Eye patches are available as
needed for comfort. Hydrocodone and acetaminophen in oral
preparations are also available for pain control. The pain and
loss of visual acuity associated with UV keratitis is usually
resolved in 24 h.
Gastrointestinal Disorders
Upper gastrointestinal problems have not significantly affected
spaceflight operations to date, but mild complaints suggestive
of gastritis and esophageal reflux are commonly reported
by space flyers. These symptoms are generally self-limited
and are usually relieved by the over-the-counter medications
(simethicone and antacids) flown in the medical kit.
The source of these symptoms is unknown, as no attempts
have been made to document esophageal motility or changes
in lower esophageal sphincter tone during space flight.
Water dispenser malfunctions in an early Apollo mission
[10] and some Space Shuttle missions resulted in air being
entrained into the water stream, which produced mild gastritis
symptoms that were easily treated with simethicone. Gastro-
esophageal reflux symptoms have been reported after a large
meal or ingestion of a large bolus of fluid (which is required
before reentry to offset postflight orthostasis from intravas-
cular depletion).
Constipation, which can have a greater effect on operations,
is also a common problem for crewmembers upon introduc-
tion to microgravity, most likely because of the large bowel
ileus, as noted in physical examinations by astronaut physi-
cians [64,65] and in experimental investigations of gastroin-
testinal motility [66]. The decrease in bowel sounds noted on
physical examination, associated with increased transit time
of foodstuffs through the colon, is probably exacerbated by
dehydration from SMS and homeostatic hormonal responses
to fluid redistribution. Russian cosmonauts undergo bowel
preparations before launch to reduce the need for bowel move-
ments in the Soyuz spacecraft while in transit to Mir. Some
U.S. astronauts also follow this practice, whereas others use
a liquid diet for 23 days before launch. Bowel preparation is
not a preflight requirement in the U.S. space program.
Oral and rectal bowel stimulants and psyllium wafers are
available on orbit for constipation. Crewmembers also need to
maintain hydration, and aggressive resolution of SMS symp-
toms is needed in the early in-flight period to allow oral rehy-
dration. Sufficient hardware is available to perform enemas
as needed. Constipation usually resolves in the first few days
on orbit, although crewmembers have gone as long as 1 week
upon arrival on orbit without defecation.
Gastroenteritis is a less likely condition, although a few
crewmembers have experienced a combination of nausea,
vomiting, and diarrhea in the first week of space flight. Diar-
rhea and fever are not components of SMS, and thus they
T.H. Marshburn
distinguish SMS from gastric disturbances of infectious
cause. Theoretically, preflight quarantine of spaceflight crews
reduces the incidence of viral gastroenteritis during flight, but
breaches can conceivably occur. Peculiarities of the clinical
evaluation of hydration status and challenges to parenteral
fluid administration in microgravity are discussed later in this
chapter in the section on Procedures.
Evaluation of abdominal pain, particularly cases of right
lower quadrant abdominal pain, may prove to be one of the
most difficult diagnostic dilemmas on orbit. Abdominal pain,
a diagnostic dilemma on Earth, may present in a substantially
different way in microgravity. Movement of abdominal organs
in microgravity is not well described, so the positioning of the
mesentery, the stomach, and the appendix is unknown. During
laparoscopy of an insufflated abdomen of a porcine sub-
ject during parabolic flight, mesenteric retraction of viscera
towards the diaphragm was noted at the onset of simulated
microgravity [67]. Russian sonographic investigations of the
human abdomen, conducted on a Mir flight, described eleva-
tion of the diaphragm and increases in hepatic, splenic, and
renal volumes that persisted 4 months into that long-duration
mission [68] and were thought to be due to normal anatomic
changes associated with the absence of gravity. These results
raise the question of whether changes in the position of the
appendix and peritoneum in microgravity may affect the
classic presentation of appendicitis.
Given the lack of onboard imaging modalities, information
obtained from the physical examination of a crewmember
with abdominal pain will be of paramount importance to further
decision making. The differential diagnosis in the medically
screened population of astronauts and cosmonauts is less
extensive than is seen in terrestrial medicine. Vascular abnor-
malities and mesenteric ischemia are very unlikely causes of
abdominal pain. Indeed, crewmembers undergo sonographic
evaluation of the abdomen and pelvis as part of astronaut
selection and again 30 days before a long-duration flight; thus
gross abnormalities would be detected before flight. Ure-
teral colic may be difficult to distinguish from appendicitis in
space; the crew and ground flight controllers of a Salyut mission
were faced with this dilemma [56].
Even though pregnancy is contraindicated during exposure
to space radiation, a urine pregnancy test is available in the
ISS medical kit to rule out ectopic pregnancy. Any differences
in the presentation of or risks associated with pelvic pain in
microgravity vs. those on Earth are unknown at this time.
However, no abdominal symptoms or shoulder pain have been
described by female crewmembers to date that would suggest
an increased risk of endometriosis caused by microgravity
enhancement of ectopic endometrial implantation [19].
On the ISS, sonography will most likely be used to evaluate
a crewmember with abdominal pain. Sonography will be of
particular use in distinguishing ureteral colic from appen-
dicitis. Although technologic advances continue to improve
the accuracy of sonography in the evaluation of appendicitis,
the examination remains highly dependent on the skill of the
5. Acute Care
operator [69]. Because the onboard sonographer will probably
have had limited experience, training, or skill maintenance,
appropriate downlink of captured images may be necessary
to consult with experts on the ground. However, the flight
surgeon will need to compete with other consoles in the
Mission Control Center for the bandwidth required for real-
time continuous downlink of images. Also, the ISS, in certain
orientations, can shadow ground stations by antennae, trusses,
modules, and solar arrays, thereby blocking communication
with the ground. Limitations on the availability of satellites
or ground stations can lead to loss of communications for 50
70% of the time during ISS operations. For exploration-class
missions, the round-trip time of a communications signal
renders real-time consultations impractical. Therefore, maxi-
mizing the capabilities of the on-orbit CMOs is paramount,
and in-flight training and onboard mentoring programs for
this purpose are being developed by NASA and the international
space medical community.
No surgical capability exists on the Space Shuttle or the
ISS, which makes parenteral antibiotics the only treatment
option for abdominal abscesses before an ill crewmember can
be returned to Earth from a space mission in LEO. Although
the optimal antibiotic regimen for medically managing
appendicitis in adults has yet to be established, in general the
use of parenteral antibiotics that cover aerobic and anaerobic
organisms is relatively successful. Oral metronidazole has
shown some efficacy in the medical management of appen-
dicitis [70]. Imipenem and metronidazole are present in
space medical kits and would be used to attempt stabiliza-
tion of the ill crewmember before return to Earth. Gastric
decompression, essential to reduce peristalsis, can also be
accomplished on orbit [71].
Administration of morphine sulfate to a crewmember who
has acute nonbiliary abdominal pain will be considered,
because such treatment can effectively relieve pain and may
not affect the ability of CMOs to accurately evaluate the patient
[72]. Any analgesia would be administered in close consulta-
tion with the flight surgeon and other ground consultants.
Upper Respiratory Disorders
Nasopharyngeal congestion is another common problem for
astronauts and cosmonauts in the early period of exposure to
microgravity. Facial swelling from cephalad fluid shifts has
been well-documented, and nasal congestion is a frequent
associated complaint. Although nasal congestion poses mini-
mal risk to the crew, it can distract from mission tasks and
increase insensible fluid loss from mouth breathing. Intra-
nasal oxymetazolone is used most often for this condition,
followed by anti-allergenics and diphenyhydramine. It has
become increasingly apparent from crew comments and flight
surgeon observations that adequate filtering of the spacecraft
air also lessens nasal congestion. Supporting this contention
is the fact that some Space Shuttle crewmembers have noted a
rapid onset of nasal congestion immediately after accidental
113
blockage of the Orbiter cabin air-cleaner filter between the
middeck and flight deck. Removal of the blockage results in
rapid relief of symptoms.
Sinusitis, although not a prominent disorder among space-
flight crews, can be promoted by cephalad fluid shifts and
the resultant engorgement of sinus mucosal vasculature. It is
important to distinguish true bacterial sinusitis from uncom-
plicated sinus congestion; even though evidence exists to sup-
port the use of antibiotics for bacterial sinusitis for 714 days
[73], profligate use of antibiotics for presumed sinusitis will
strain on-orbit supplies as well as predispose a crewmember
to infection by resistant organisms. In one review, clinical
findings of tenderness to palpation over the sinus areas, ele-
vated body temperature, and purulent rhinorrhea were found
to be 58% sensitive and 88% specific in detecting sinusitis
that is treatable with antibiotics [74] in comparison to the
gold standard of antral aspiration [75]. Sonography, when
available to the ISS CMO, may be useful as well. A review
of five studies evaluating sonography for diagnosing maxil-
lary sinusitis showed it to be 83% sensitive and 88% specific
[74]. Although mucosal thickening is not easily visualized on
sonography, a sinus that is partially or fully filled with secre-
tions can transmit ultrasound waves. The effect of micrograv-
ity on the diagnostic accuracy of sonography is not known,
although the layering of secretions that forms a typical sign
on x-ray evaluations would not be present in microgravity.
Other upper airway inflammatory processes that can occur
commonly on the ground can also occur in space flight; the
preflight 7-day quarantine used by the U.S. and Russian
programs was established to limit viral or bacterial infections
in crewmembers. The flight surgeon and the CMO must still
consider upper airway inflammation in the differential diag-
nosis of pharyngitis, however. Since breaches in preflight
quarantine are possible, treatment of a crewmember with phar-
yngitis in the first days of a space flight is similar to that on
the ground. Carrier states are known to occur in the astronaut
or cosmonaut population, both in the quarantine period and
during flight; lateral transmission of Staphylococcus aureus
between crewmembers during missions has been documented
[76]. Changes in the crews immunity secondary to the stress
of the high workload, sleep debt, or an as yet undetermined
effect of space flight may reactivate these pathogens, resulting
in clinical disease.
Clinically based predictions of the presence of bacterial
pharyngitis are relatively poor. As noted above, headache
and rhinorrhea in spacecraft have multiple causes and are not
necessarily suggestive of upper airway infection. Sore throat,
cervical lymphadenopathy, and fever are more suggestive of
bacterial pharyngitis [77]. A rapid streptococcal immunoassay
is available in ISS medical kits that may assist in diagnosing
bacterial pharyngitis. Generally, treatment is recommended
when the clinical picture is clear, the symptoms noted above
are present, and findings on a rapid strep test are positive;
however, in giving such treatment, the CMO accepts the
possibility of unnecessary treatment of crewmembers who do
114
not have disease and that of unnecessarily depleting the on-orbit
supply of oral antibiotics [78]. An advantage in on-orbit medi-
cal care is the opportunity for close, frequent reevaluations, so
crewmembers with negative findings on a rapid strep test or
an unclear clinical picture can be easily followed without the
need for overly aggressive early treatment [75].
Several classes of oral antibiotics are available in Space
Shuttle and ISS medical kits, including penicillins, -lactamase
penicillins, macrolides, and cephalosporins. These antibiotics
can be used to reduce the incidence of suppurative complications
and perhaps shorten the duration of symptoms [77].
Because the ambient spacecraft atmospheric pressure
changes regularly in the course of mission operations, otitis
media suspected during space flight must be aggressively
treated with oral antibiotics and decongestants. Moreover,
microgravity may change the physical presentation of otitis
media with effusion, as exudate would not layer out behind
the tympanic membrane. Otherwise the principles of clinical
diagnosis of otitis media and its treatment are no different in
space flight than in terrestrial practice.
The dry air present in the Space Shuttle atmosphere in
combination with cephalad fluid shifts may predispose crew-
members to nosebleeds. The lack of gravity also prevents free
blood from descending into the nasal alae early in the nose-
bleed, so more blood may be present in the nasopharynx at
the time of presentation than in one-G. Shuttle and ISS medi-
cal kits are stocked with cotton pledgets, topical deconges-
tants and anesthetic, silver nitrate sticks, and nasal packing
as needed to treat anterior epistaxis. Foley catheters can also
be used for posterior bleeds; in that technique, the catheter is
inserted through the nasopharynx into the posterior pharynx
and its balloon is inflated and then drawn back to tamponade
the posterior nasopharynx [79].
Pulmonary Disorders
Pulmonary problems unique to space flight include exposure
to exotic atmospheric contaminants and inhalation of foreign
bodies. Hydrazine, ammonia, ethylene glycol fumes, and the
products of pyrolysis can produce disorders ranging from
minor irritation of the upper airway to disruption of pulmo-
nary capillary/alveolar integrity with resultant adult respiratory
distress syndrome.
Although pulmonary infections do not seem to occur at a
higher rate in space flight than on Earth in a standard medi-
cal practice [80], infections are a risk if breaches in infection
defense are present secondary to pulmonary injury. Inhalation
of toxic substances or aspiration of foreign bodies are two of
the most likely examples of such an injury. Since neither roent-
genographic nor bronchoscopic imaging capability will exist
on board spacecraft in the near future, accurate assessment by
the CMO will be essential. The relatively noisy environment
of spacecraft will make auscultation, the traditional chest
physical examination technique, difficult. Moreover, auscul-
tation is not sufficiently accurate to confirm the presence or
T.H. Marshburn
absence of pneumonia. Recent evaluations of the accuracy
and interobserver reliability of auscultation in detecting pneu-
monia (with the chest x-ray used as the gold standard) show
that auscultation alone has a sensitivity of less than 70% and a
specificity less than 75% [81]. Thus a high degree of suspicion
will have to be maintained when a crewmember has a produc-
tive cough and fever.
Crewmembers are always at increased risk of inhaling for-
eign bodies during space flight, particularly during activities
that increase minute ventilation (e.g., exercise). Sudden onset
of cough accompanied by a local monotonic wheeze on aus-
cultation would suggest foreign body aspiration. The CMO
must assess all anatomic lung segments in the physical exami-
nation, since the classic gravity-dependent segments may not
be at increased risk in microgravity. An affected crewmember
should be followed closely for atelectasis or pneumonia devel-
opment in lung segments distal to the occlusion.
Toxic contamination of the spacecraft atmosphere can also
lead to significant pulmonary injury. Firsthand experience
with this problem unfortunately occurred in July 1975 at the
end of the Apollo-Soyuz Test Project, when the three-member
Apollo crew was exposed to 250 ppm of nitrogen tetroxide, an
oxidizer commonly used in spacecraft propulsion systems, for
45 min during the atmospheric reentry of the Apollo com-
mand module. Initial symptoms were eye burning with tearing,
burning and itching of the skin, chest tightness with retroster-
nal burning, and nonproductive cough upon deep inhalation.
The crewmembers lungs were clear on initial examination
after splashdown and recovery, but radiologic evidence of pul-
monary edema was present a day later [82]. They recovered
fully, without sequelae.
Nitrogen tetroxide is a gas that decomposes into nitric acid
and other compounds on contact with the water in mucous
membranes. In sufficient amounts, it is highly irritating to
upper airway passages; less severe exposures may produce only
cough and coryza. Indeed, this presentation is first in a typical
triphasic progression of injury manifestation after significant
pulmonary exposure to nitrogen tetroxide. Within 330 h, one
can expect onset of pulmonary edema and adult respiratory
distress syndrome. Bronchiolitis obliterans can then affect 50%
of survivors. Intubation and respiratory support with applica-
tion of positive end-expiratory pressure (PEEP) is necessary for
patients with hypoxemia. Treatment with steroids is controver-
sial; trials with human subjects have not shown steroids to be
effective after nitrogen tetroxide exposure [83].
Hydrazine gas, a propellant used in both the Space Shuttle
and the ISS, is also extremely irritating to upper airway passages,
skin, and eyes. Similar damage to the lower pulmonary tree
can ensue with significant exposure [83].
Ammonia, which is used as a coolant on the Space Shut-
tle and the ISS, presents another pulmonary hazard. Any
contamination of the spacecraft atmosphere by ammonia
would require simultaneous breaches in several barriers
[84] or passage into the cabin via a contaminated space suit
exposed during EVA. Ammonia is very irritating to upper
5. Acute Care
airway passages, but crewmembers can adapt to exposures
of limited severity. A few seconds of ammonia gas exposure
cause inflammation of the conjunctiva and pharynx, pharyn-
geal and retrosternal pain with cough, and dyspnea, but no
abnormalities on x-rays. Hypoxemia from chemical burns to
the tracheobronchial tree may be delayed by 12 days. The
presence of rales and wheezing can predict the onset of adult
respiratory distress syndrome and progression to worsening
hypoxemia that can take weeks or longer to resolve. However,
quick removal of the affected crewmember from the source
can limit pulmonary injury, with symptomatic improvement
in a week and complete recovery in 12 months. Conversely,
some victims have developed moderate obstructive pulmo-
nary dysfunction presenting as reactive airway disease 26
months after exposure [84].
The first steps in preventing injury are to protect the crew-
members and contain the contaminant. Crews can don oxygen
masks that cover the eyes and mucous membranes of the nose
and mouth. Skin protection should be maintained with use of
gloves and chemical-resistant suits. Any contaminated cloth-
ing should be disposed of in wet trash containment systems
that entrain air through filters and dump the air overboard.
EVA-related contamination can take place if a reaction control
system jet leaks or fires inadvertently with impingement on
the space suit; the spacecraft atmosphere becomes contami-
nated when the crewmember returns to the spacecraft. The
onset of irritation, cough, and coryza in other crewmembers
immediately after an EVA should raise suspicion of such con-
tamination. The source of the contamination can be removed
by the EVA crewmember returning to the airlock and expos-
ing the space suit to the sun, which bakes out or sublimates
the contaminant from the suit [85].
Primary treatment and stabilization of crewmembers can be
accomplished with the hardware provided on the Space Shut-
tle and the ISS. After the exposed crewmember is removed
from the source of the offending contaminant and an initial
assessment is performed, -adrenergic aerosols are available
to treat reactive airway manifestations. Parabolic-flight stud-
ies showed that albuterol aerosol dispensers operate similarly
in simulated microgravity and on the ground, dispensing a
90-g dose per activation as expected [86]. Repeat examina-
tions and pulse oximetry monitoring should be continued for
at least 24 h. Carbon monoxide diffusion capacity studies of
normal crewmembers during space flight have also indicated
that thoracic fluid shifts do not produce subclinical pulmo-
nary edema, so any hypoxemia could not be attributed to a
normal physiologic response to microgravity [87]. The onset
of hypoxemia mandates consideration of return to Earth (for
missions in LEO) and provision of 100% oxygen. Increasing
levels of ventilation support up to intubation and mechanical
ventilation can be accomplished on the ISS.
Similar principles apply to crewmembers who are exposed
to toxic pyrolytic products after a spacecraft fire. Shuttle and
ISS flight rules mandate that crewmembers don oxygen masks
when a fire is detected. Real-time monitoring of spacecraft air
115
for carbon monoxide, hydrogen chloride, and hydrogen cya-
nide is possible with portable chemical and infrared sensors
available on both the Space Shuttle and the ISS.
Crewmembers experiencing symptoms after exposure to
combustion products must be monitored for 24 h for signs of
pulmonary edema and hypoxemia. This was done after the
Mir space station fire in 1997, when the onboard CMO set up
an airway station and continued reevaluation of his crewmates
over 24 h. This episode led to the design of new Space Shuttle
medical kits that allow easier access to airway equipment with
better hardware restraint.
For spaceflight crews who will return to the Moon or go
on to explore Mars, exposure of spacecraft cabin interiors to
native dust may cause cough and airway irritation to airway
passages. One Moon-walking astronaut relayed after land-
ing that the lunar soil caused breathing problems, although
no evidence of a medical problem was reported during flight
and postflight examinations were normal. Some Moon-walk-
ing astronauts reported that lunar dust caused nasopharyngeal
irritation as well [88].
Allergic Reactions
A severe allergic reaction could be disastrous during a space
mission. All crewmembers are tested before a flight for their
responses to common medications in the Space Shuttle and ISS
medical kits to determine any unexpected allergic responses or
adverse side effects. An allergic response to these medications
is not disqualifying for space flight, but it allows appropri-
ate planning of the medical kit inventory. Other antigens that
could initiate an anaphylactic response are tracers and mark-
ers used in life sciences experiments, although these markers
are evaluated carefully with the crewmembers before flight.
The clinical manifestations of vasodilatation-induced hypo-
tension in microgravity are unknown, but presumably the
presentation would be different without a gravity gradient to
exacerbate orthostatic hypotension.
Items in the Space Shuttle and ISS medical kits for treating
allergic reactions include subcutaneous epinephrine, paren-
teral and oral steroids, -agonist aerosols, and IV fluid supple-
mentation. The challenge for treatment on board spacecraft is
the need for rapid response in microgravity. The medical kits
therefore contain epinephrine autoinjectors, syringes filled
with 1:1,000 epinephrine and diphenhydramine, steroids, and
-aerosols packaged together in an easily accessible location
and restrained on Nomex fabric pallets.
Dental Disorders
Dental problems are one of the most common reasons for
evacuation from submarines and surface ships [89]. Although
dental care is of paramount importance for crewmembers who
are preparing for space flight, dental trauma or infections can
and have occurred during missions. For example, in the Russian
space program, the forces associated with the vibrations and
116
accelerations during launch have dislodged crewmembers
crowns. Dental trauma is also possible through the use of the
mouth as a convenient means of holding tools such as flashlights
when working in enclosed areas. CMOs are trained to stabilize
fractured teeth and perform temporary crown replacement, and
the Space Shuttle medical kit contains sufficient supplies to
perform these procedures. Russian and ISS medical kits also
contain tooth-extraction tools for dental trauma or for infection
that has not responded to other means of treatment. Sufficient
oral and parenteral antibiotics are also on board Russian and
U.S. spacecraft to treat apical abscesses. Lower light levels,
limited dental training for CMOs, limited supplies, and the
need to restrain tools remain the most significant challenges for
assessing and treating dental problems on orbit (see Chap. 26).
Urologic Disorders
Urologic problems during space flight can involve ureteral
stones, urinary tract infections, urinary hesitancy, and urinary
retention. Prostate infections have occurred at least twice
during space missions [10,30], and available documentation
indicates that one case led to the return of the crew from LEO.
Urologic problems in space flight are addressed in detail in
Chap. 13, and only general principles are described here.
Astronauts and cosmonauts are theoretically prone to ureteral
stone formation in the first hours of arrival on orbit and imme-
diately after return to Earth. Although no episodes of ureteral
colic have occurred during flight in the U.S. space program, it
almost caused the deorbit of a Russian Salyut crew from LEO
[30]. The on-orbit challenge, in addition to pain management,
will be diagnosis, since IV pyelography or other roentgeno-
graphic evaluation will not be available. Clinical presenta-
tion of ureteral colic is not expected to differ substantially on
orbit from that on Earth. Standard terrestrial urine dipsticks
can be used to assist in the diagnosis, but urine hemoccult
tests are only 67% accurate (for more than five red blood cells
per high-power field) for making a definitive diagnosis [90].
Sonography, available on the ISS, may be used to visualize
significant hydroureter or hydronephrosis.
Parenteral nonsteroidal anti-inflammatory agents are car-
ried in the ISS medical kits, and both the Space Shuttle and
the ISS medical kits contain parenteral opioid analgesics for
pain management of ureteral colic. The only concern is the
limited supply of analgesics. Substantial parenteral analge-
sia cannot be maintained for much longer than 24 h using the
medical kits on either spacecraft. Medical management will
focus on maintaining adequate hydration and monitoring for
fever or sonographic evidence of hydronephrosis from com-
plete ureteral obstruction. A stone visualized by sonography
that is larger than 8 mm (0.3 in.) is not likely to pass and may
require surgical removal [91].
Oral and parenteral antibiotics that cover the common
offending organisms are available in the Space Shuttle and
the ISS medical kits. E. coli is thought to be the most common
cause of urinary tract infection in space flight (as it is on Earth),
T.H. Marshburn
but this has yet to be verified because urine cultures have not
been available in flight. Broad-spectrum coverage of Pseu-
domonas spp. is necessary as well, because this was the offend-
ing organism in a case of urosepsis in the Apollo Program [10].
Urinalysis is available to assist in the diagnosis of urinary tract
infections, but measurement of blood leukocytes is not currently
possible with the ISS or Space Shuttle medical kits.
Urinary retention has occurred on a few occasions during
space flight. Urethral catheterization with leg bag drainage is
possible and has been performed in space flight. Simultane-
ously restraining hardware while maintaining sterility is the
most significant difficulty in performing catheterization in
microgravity. Wearing a leg bag in microgravity by itself does
not affect intravehicular operations, although the increased
potential for urine reflux from the catheter into the bladder
may predispose crewmembers to urinary tract infection [17].
Reasons for a possible increased rate of urinary hesitancy dur-
ing space flight missions are discussed in Chap. 13. The flight
surgeon must be aware of the amount of promethazine used
by crewmembers for treatment of SMS, as its anticholinergic
activity may add to any predisposition for urinary retention.
Cardiac Problems
As spaceflight missions increase in duration, complexity of
payloads, and number of high-risk activities (e.g., EVAs), the
need for on-site cardiac life support capability has increased
as well. The 1990s have seen acceptance of smaller, more
autonomous, and user-friendly defibrillator units outside of
traditional hospital and emergency medical service settings
in terrestrial medical care. A defibrillator is now part of the
medical inventory on some Space Shuttle and all ISS flights.
Medical care in space flight is approaching the terrestrial
ambulance-level medical care.
The first defibrillator flown in space (on the fifth NASA-
Mir mission of the joint U.S.Russian Phase I program, May
15October 6, 1997) was left on board the Mir space station.
Since that time, Space Shuttle medical payload manifests have
included defibrillators and cardiac medications on specific
missions, if required by the unique characteristics of that mis-
sion and its payload activities.
Although the astronaut and cosmonaut populations are
extensively screened for cardiovascular disease before flight,
episodes of arrhythmia and symptoms suggestive of cardiac
ischemia have nevertheless occurred during flight. During
the Apollo Program, a crewmember experienced a 14-s run
of bigeminy during flight, concomitant with a feeling of
extreme fatigue. That same crewmember experienced a myo-
cardial infarction 2 years later, from which he recovered [10].
The Russian medical community terminated one mission
early because of an episode of paroxysmal supraventricular
tachycardia [31]. In at least one other incidence, a cosmonaut
was placed on cardiac medications for symptoms suggestive
of ischemic heart disease (personal communication, V. Bogo-
molov, 2002). Moreover, long-duration space flight may
5. Acute Care
predispose crewmembers to arrhythmias. Review of electro-
cardiographic tracings during EVA [92] and the results of in-
flight Holter monitoring during Space Shuttle missions [93]
do not show a predisposition to arrhythmias during short-
duration space flight, but limited data suggest this may not
be true for long-duration space flight [94]. Also, electrocu-
tion remains a potential cause of cardiac arrhythmia during a
mission. The electrical power systems (28 Vdc on the Space
Shuttle and 120 Vdc on the ISS) represent a potential electri-
cal injury hazard. Finally, depressurization in preparation for
EVA exposes crewmembers to an increased risk of cardiopul-
monary decompression sickness (DCS), which may require
advanced cardiac life support (ACLS) capability as well.
The effects of microgravity on the symptoms and clinical
manifestations of ischemic heart disease are unknown. A
crewmember may be reluctant to assign early symptoms of
chest pain, diaphoresis, or dyspnea to cardiac causes because
of reliance on extensive medical screening performed before
the mission and because of reluctance to cause unnecessary
mission impact. Because an astronauts or cosmonauts awake
pulse rate and diastolic blood pressure are nominally about
10% lower on orbit than on Earth [38], ischemic symptoms
may not become apparent until the crewmember is partici-
pating in some vigorous activity that significantly increases
myocardial demand (e.g., exercise on the treadmill or perfor-
mance of an EVA).
Evaluation of a crewmember with ischemic heart disease
will probably rely heavily on the clinical impression of the
CMO and on consultation with the flight surgeon and ground
specialists. Some degree of jugular venous distension is present
in all crewmembers in space flight because of the cephalad
movement of intravascular volume. Signs and symptoms of
cardiac ischemiadiaphoresis, nausea, shortness of breath
are expected to be similar in space and on Earth, but this is
not certain. Auscultation will be difficult on orbit because
of high ambient noise levels, so subtle murmurs and per-
haps even rales will be difficult to detect. Dependent edema
would probably not be a prominent feature in a crewmem-
ber with significant myocardial injury and subsequent decre-
ment in ejection fraction, although edema would presumably
be present in a general distribution as well as in the face or
upper extremities. Although sonography will be available on
the ISS, the ability to determine wall motion abnormalities or
valvular damage will depend on the severity of disease, the
skill of the CMO, and the bandwidth availability for real-time
assessment of images with terrestrial consultants.
In the U.S. space program, rhythms can be monitored
on orbit with a 5-lead electrocardiograph on the ISS and a
3-lead electrocardiograph on Space Shuttle flights. Rela-
tive resting bradycardiac and decreased diastolic pressures
are known to be associated with space flight, and further
manifestations of ischemic disease on electrocardiography
in microgravity are unknown.
Treatment in space would follow standard terrestrial regi-
mens: O2 via nasal cannula or non-rebreather mask, intravas-
117
cular saline as needed, and aspirin, sublingual nitroglycerin,
morphine sulfate, and -blockers, all of which are available
to the crew as needed. ISS medical kits contain sufficient
epinephrine and lidocaine to provide two runs through the
ACLS pulseless ventricular tachycardiaventricular fibrilla-
tion algorithm [95,96]. Vasopressin and amiodarone are not
yet included in the ISS medical kits pending resolution of
packaging and storage issues.
Some aspects of ACLS, however, are unique to the space-
flight environment. In the case of the full arrest, transfer of the
affected crewmember to the ACLS location, where space must
be dedicated for restraint hardware, access to 100% oxygen,
and ACLS medications will be necessary. Fortunately, transfer
of an unconscious crewmember is much easier in micrograv-
ity than on Earth, so the time to cardioversion could be shorter
than on Earth.
Multiple simulations during parabolic flight demonstrate that
a CMO could easily perform rescue breathing while transporting
an unconscious patient [9799]. These simulations assessed the
effectiveness of a variety of cardiac compression techniques.
In general, the rescuer could deliver adequate compressions, as
measured by mannequin compression recordings, either from
the patients side by using a waist restraint or by planting
his or her feet on a surface opposite the patient and placing his
or her hands in the standard position. In the inverted position,
thrusts are delivered by knee and elbow extension. This method
has been simulated on orbit as well (Figure 5.1). Both of these
options seem to be successful because they simultaneously
allow adequate compressions and positional stability. Performing
cardiopulmonary resuscitation with one hand (while the other is
used to restrain the provider), with the provider either aside or
straddling the patient, was too fatiguing and allowed too much
movement between provider and patient [17].
External mechanical and pneumatic compression devices
have also been evaluated in Space Shuttle and parabolic
flights. Given the required deployment time and lack of sig-
nificant improvement in compression efficacy, these devices
have not been considered for use in spacecraft [17].
In general, restraining the provider and the patient is of
paramount importance throughout resuscitation. Engineering
constraints do not officially allow free-floating cardioversion
at this time [17] to avoid unintentional grounding through
wires or other floating hardware and exposing critical space-
craft-control electronics to damaging electrical pulses. Defi-
brillation units are tested to comply with electromagnetic
field limits during charging, defibrillation, and pacing. A crew
medical restraint system flown on the ISS allows electrical
isolation of the patient from the module. This restraint system
also serves as a stable platform on which the providers can
restrain the patient, themselves, and their hardware. Consistent
training of CMOs with choreographed resuscitation procedures
is one of the best safeguards against inadvertent grounding
through the providers.
Hardware restraint is a significant challenge for perform-
ing a resuscitation in microgravity. Hardware and instru-
118
FIGURE 5.1. Astronaut Dan Bursch demonstrating posture and posi-
tioning for performing cardiopulmonary resuscitation chest compres-
sions using the crew medical restraint system in the U.S. Laboratory
Module of the ISS (Photo courtesy of NASA)
ments are inevitably misplaced in the flurry of activity
surrounding a simulated-microgravity resuscitation. Blood
products, packaging, and used hardware that ordinarily fall
to the floor in a terrestrial resuscitation will float in micro-
gravity. Thus CMOs are trained to be constantly aware of
equipment placement, and straps, waste bags, and needle
containers are incorporated in the design of the medical
kits, floor layout, and restraint system to restrain critical
hardware and waste.
Microgravity allows a wide variety of unique approaches
to attaining a definitive airway in patients in respiratory
distress. Restraint of the patient is essential for adequate
direct laryngoscopy; that restraint is provided by the crew
medical restraint system. To perform direct laryngoscopy
in microgravity, the provider can use his or her knees to
grasp the head of the restraint system or even grasp the
head or shoulders of the patient so as to establish adequate
stability for excellent visualization. Microgravity also
allows the CMO to float above the patient and to more
easily perform blind digital intubation. Investigators have
evaluated intubation from the side of the patient for those
cases in which the patients head is close to a bulkhead
or another structure. Although possible, this technique
requires more time because of difficulties in restraining
the rescuer. However, the expected low success rate of
intubation via direct laryngoscopy by minimally trained
personnel has led to use of the intubating laryngeal mask
airway as the primary method of attaining a definitive air-
way during space flight [100]. A definitive airway should
be secured before the affected crewmember is transported
to the ground, either by Space Shuttle, Soyuz, or a future
dedicated return vehicle [17].
Methods of saliva containment in simulated microgravity are
different from those in terrestrial practice because of the sur-
T.H. Marshburn
face tension forces that cause secretions to adhere to oropha-
ryngeal surfaces. A manual suction device, developed to allow
one-handed operation, has been tested in parabolic flight and
is part of the current ISS medical airway kit [101].
Ensuring proper endotracheal tube placement in space flight
is expected to be the same as on the ground, with a couple of
notable exceptions. Low ambient light levels may make accu-
rate reading of colorimetric end-tidal CO2 difficult, and rela-
tively high ambient noise levels will limit auscultation. For
these reasons, an esophageal detector bulb is provided in the
ISS medical kit.
Drugs for ACLS will be given by means of an endotracheal
tube or by intravenous injection. Pulmonary function studies
in microgravity during the Apollo-Soyuz Test Project missions
[102] and those performed later by West and colleagues [87]
suggest that no significant barriers exist to using the endotra-
cheal route for drug administration in microgravity. The lack
of sedimentation of aerosolized droplets in microgravity can
result in decreased deposition of medication [103]. How this
difference would affect medications delivered by the endotra-
cheal route is unknown.
Guidelines from the American Heart Association suggest
that the recipients arms be elevated to facilitate the flow of
intravenously injected medications through the venous sys-
tem to the central circulation. Obviously, this will not help
in microgravity, and IV medications will have to be chased
with saline boluses.
Procedures
Intramuscular Injection
Promethazine is most commonly given in space flight by IM
injection; IM injection is in fact the most commonly performed
in-flight medical procedure in the U.S. Space Shuttle Program
[4]. CMOs use syringes from the SOMS kit that are filled
on the ground before flight to minimize the need to remove
bubbles from the solution. Although the injection itself differs
little from terrestrial IM injections, the CMO must ensure ade-
quate restraint of both himself or herself and the patient. The
most common technique for preventing inadvertent movement
is for patients to stabilize themselves in the corner of a cabin.
IM injections are almost always delivered into the superior
gluteal area to prevent subsequent limitation of motion of the
upper extremities from the muscle soreness that occasionally
results from the procedure.
Intravenous Catheterization
CMOs and mission specialists performing biomedical investi-
gations have inserted IV catheters on orbit in antecubital veins
with success rates similar to those in ground operations. The
greatest challenges in accomplishing venous catheterization
in microgravity are again restraint of hardware and patient.
A rapid and common means of restraint is to apply a strip of
5. Acute Care
duct tape, adhesive side facing out, near the workstation. IV
tubing, saline locks, alcohol wipes, iodine swabs, and trash
are stuck to the tape and easily kept in place and within reach.
Several kinds of sharps containers are available, including
foam blocks and metal containers with hinged lids; both have
been used successfully.
Phlebotomy and catheterization are otherwise somewhat
easier in microgravity once the CMO and patient are well
restrained. No obvious differences have been observed in
flashback or fluid flow through IV tubing, and blood control
is rendered simpler by the predominance of surface tension
in the absence of gravity. Air elimination filters that use a
hygroscopic membrane were shown to perform adequately
in removing air bubbles in the continuous microgravity con-
ditions of the Spacelab Life Sciences-1 mission (STS-40).
The filters can dry out, however, and a continuous pressure
head is required to maintain filter filling. Such pressure can
be provided by squeezing the IV bag or by placing the bag
in a blood pressure cuff and inflating it to between 50 and
75 mmHg [104].
Resconstitution of Medications
Fluid reconstitution of drug powders offers some challenges
in space flight. A bubble in a bag of normal saline or a vial,
for instance, does not float to the top. If the container is
agitated, froth forms, which makes accurate aspiration of a
desired volume difficult. Syringes cannot be thumped to
send bubbles toward the needle hub. Therefore, at present all
parenteral medications and saline bags are stored in a form in
which bubbles are removed before flight. Parenteral medica-
tions in powdered form are desirable because of their smaller
storage volume and generally longer shelf life; thus an under-
standing of how these medications can be reconstituted in
microgravity is necessary. Flight surgeons and space crews
have used several techniques to create a single airfluid level,
both in parabolic flight and on orbit. All of these techniques
involve spinning the IV bag or syringe to centripetally drive
the fluid away from the center of spin and against the outlet
port (e.g., the needle). IV doses of medications mixed on orbit
are not as consistently titrated manually as on the ground. Sev-
eral mixing devices have been developed for use on orbit, but
none has been so effective as to be worth its cost in terms of
weight and volume [105].
Other Procedures
Cricothyrotomy, tonometry, thoracostomy, laparoscopy, diag-
nostic peritoneal lavage, throacic, or abdominal sonography,
and urethral catheterization have all been performed with
animal models in parabolic flight. The general principles of
restraining hardware, patient, and operator apply for each
procedure. The investigators who performed these procedures
have established that once familiarity with self-stabilization
and locomotion in microgravity are attained, any of these
119
procedures can be performed with some modifications. Other
considerations for surgical care in the microgravity environ-
ment are addressed in Chap. 6.
Transport
Specific techniques for transporting patients from a space-
craft in LEO to a definitive care facility on the ground vary
depending on which rescue vehicle is used (i.e., Soyuz,
Space Shuttle, a U.S. crew return vehicle) and the medical
problem being experienced. The parabolic flight and Space
Shuttle investigations mentioned earlier in this chapter
revealed a series of basic principles that can be applied in
all emergency deorbit scenarios. Specifically, at least 24 h
from the moment of declaration for deorbit until delivery of
a patient to a definitive medical care facility on the ground
will be required to deorbit an injured or ill crewmember.
Stabilizing the patient before transport is as important in
space flight as in terrestrial emergency service settings. IVs,
monitors, a ventilator, and an airway need to be secured in
preparation for return [17]. Monitors available to the CMO
during reentry will be limited; such monitors currently
consist of pulse oximetry and monitoring provided by the
defibrillator. An automatic blood pressure monitor will be
available as well. Injured or ill crewmembers will not be
transported in their pressure suits, as patient access is too
limited. Returning an ill crewmember to the one-G environ-
ment in a recumbent position is both desirable and possible
in the Space Shuttle. Also, an injured or ill crewmember
returning in the Space Shuttle does so in a supine position,
with lower extremities flexed at the hip and knees, so that
the lower legs can rest in a forward middeck locker [98].
Return in a crew return vehicle or Soyuz offers other chal-
lenges; these issues are covered in Chap. 7.
Conclusions
Further refinement of these and other spaceflight medical
procedures, application of new technologies in the microgravity
environment, and better understanding of human physiology
in space flight are all areas of ongoing investigation. Two other
issues now being actively addressed are also critical to the suc-
cess of treating an acutely ill or injured spaceflight crew-
member: first, the optimal training schedule and environment
for CMOs and astronaut physicians, to ensure expertise
in medical procedures relevant to space flight; and second,
development of means to transport a critically ill patient, with
a pharmacopoeia that is necessarily limited in volume and
scope, using predefined procedures that are specifically rel-
evant to spaceflight operations. Resolution of these issues will
enhance the medical capabilities of spaceflight crews in LEO
and will be essential to medical operations during expeditionary
spaceflight missions.
120
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6
Surgical Capabilities
Mark R. Campbell and Roger D. Billica
Although no surgical procedures have been performed on
humans during space flight, the risk of a problem arising that
requires surgical intervention is nonetheless real. From a time-
weighted standpoint, until the advent of long-duration missions
in the U.S. Skylab program and the Russian Salyut and Mir
programs, the probability of an in-flight problem arising that
would require a surgical solution was small; thus clinical
experience and expertise in performing surgery on humans in
microgravity remained quite limited. The lack of on-site sur-
gical expertise was keenly felt when Russian space program
officials were faced with the possible medical evacuation
of a Salyut 7 cosmonaut who was experiencing abdominal
pain thought to be due to appendicitis. Although that episode
turned out to have been caused by probable ureterolithiasis
rather than appendicitisthe cosmonaut recovered and did
not require an early return to Earththis experience nonethe-
less underscored a pressing need in space flight.
With further increases in crew size and mission duration
projected in the near future for the International Space Sta-
tion (ISS) and the exploration-class missions that will follow,
the likelihood of events occurring in space flight that will
require surgery will also increase. Moreover, the probability of
trauma (including penetrating trauma, lacerations, crush injuries,
and thermal and electrical burns) occurring will increase as
astronauts and cosmonauts conduct ISS construction-related
extravehicular activities that involve manipulation of high-
mass hardware. A surgical need could also be precipitated
by exercise countermeasures, which may lead to minor and
major orthopedic injuries. Routine surgical diseases such
as appendicitis and cholecystitis can occur indiscriminately
at seemingly random times. The physiological changes and
deconditioning effects of prolonged weightlessness will influ-
ence surgical diseases and treatment in predictable as well as
unknown ways. Finally, the possibility of previously unknown
surgical problems in the unexplored long-duration microgravity
environment must be considered.
Analog remote medical care systems (e.g., equipment,
instruments, and personnel) have been studied to ascertain
the incidence and risk of surgical events. The authors of
these studies have suggested that illnesses or injuries that will
require major surgery will be rare.[1,2] However, as these
authors have noted, when such illnesses or injuries do occur,
the effect could be disastrouspossibly leading to a mis-
sion abort or a partial crew return. At the very least, an event
requiring that major surgery be performed on a crewmember
will greatly affect the overall mission and necessitate a large
amount of resources to be treated successfully. Although ill-
nesses and injuries that require minor surgery will probably
be more common, they will also pose challenges in the micro-
gravity environment.
The Challenges of Performing Surgery
in Space Flight
Numerous challenges will arise in performing even minor
surgical procedures in microgravity (Table 6.1). Some of the
challenges that will need to be addressed include achieving
adequate anesthesia, maintaining a sterile field and technique,
providing appropriate lighting and exposure, maintaining
hemostasis, deploying instruments, and restraining the opera-
tor and patient. The current weight and volume restrictions on
spacecraft severely limit the availability of surgical and anes-
thetic equipment to cover all but the most likely situations.
The surgical capability of any medical care system in space
flight also will be limited by the surgical capability and train-
ing of the crew medical officers (CMOs), those members of
the crew specially tasked with and trained for rendering medi-
cal aid to their crewmates.
Current limits on crew size and capabilities make it impos-
sible to provide CMOs with the intensive training needed to
handle major surgical procedures. Even if a clinically com-
petent and experienced surgeon is a crewmember, it is highly
doubtful that that individual would be able to perform suc-
cessful major surgery with minimal staff support, minimal
resources, and possibly months of surgical inactivity. The risk
that the surgeon-crewmember might actually be the patient
must also be considered.
123
124
TABLE 6.1. Issues to be considered for performing surgery in microgravity.
Restraining patient, operator(s), and equipment
Providing and maintaining sterile field
Providing appropriate lighting and exposure
Managing wastes, including sharps disposal
Maintaining hemostasis
Preventing contamination of the closed-loop spacecraft environment
Accounting for the lack of gravitational retraction during surgical procedures
Providing suction and drainage
Providing anesthesia and appropriate monitoring
Managing fluid levels and blood replacement
Providing capabilities for imaging and surgical diagnosis
Accounting for changes in endoscopic techniques
Accounting for changes in physiology
Accounting for changes in fluid dynamics that affect the behavior of
bleeding and drainage
Accounting for changes in physical landmarks (shifting of internal organs)
Providing appropriate support during recovery
TABLE 6.2. Surgical issues addressed in the NASA microgravity program.
Dental care and intervention
Wound closure techniques
Airway management and percutaneous tracheostomy
Advanced life support, including cardiopulmonary resuscitation and
defibrillation
Chest tube placement and drainage
Peritoneal lavage
Hemostasis
Prevention of cabin atmosphere contamination from bleeding and
drainage fluids
Bandaging and splinting
Sterile technique and maintenance of sterile field
Patient, operator, and equipment restraint
Surgical instrument organization, restraint and logistics
Trash management and handling of sharp disposal
Bladder drainage with Foley catheterization
Percutaneous drainage procedures
Suction techniques and drainage behavior of fluids
Monitoring technology
Sonographic imaging
Intravenous fluids and therapy
General anesthesia techniques
Endoscopy technique and technology, including laparoscopy, thorascopy,
and cystoscopy
Telemedicine direction of surgical procedures
Concerns have also been raised regarding the unknown
effects of microgravity on surgical bleeding, the need to pre-
vent contamination of the spacecraft atmosphere, and the
need to protect the operative field from the relatively high
particulate content of the spacecraft atmosphere. Physicians
who have experience in microgravity quickly raise a host of
other issues related to surgical capabilities during space flight,
including basic questions regarding diagnosis and imaging,
the positioning of tubes, techniques for suction and drainage,
the management of waste, and many other concerns. Some of
the simplest functions that we take for granted on Earthsuch
as restraint and positioning of the patient and accessibility of
instrumentscould be factors that limit the successful perfor-
mance of surgery in space. Research involving animal surgery in
M.R. Campbell and R.D. Billica
the simulated microgravity produced during parabolic flight
(Table 6.2) has explored many of these issues. These stud-
ies have led to the conclusion that after the patient, operator,
instruments, and equipment have been properly restrained,
surgical procedures may be more difficult to perform than in
1 G, but are nonetheless feasible in microgravity.
Challenges in Exploration-Class Missions
In future exploration-class missions to the Moon or Mars, the
on-board medical care system must become more capable and
autonomous as the crew size expands and the time required
to return an ill or injured crewmember to Earth to reach definitive
medical care (defined as the quality of medical care that is
available only in a hospital setting) increases. The time to
reach definitive medical care from the ISS may be as brief as
24 h but from a lunar base would be at best several days and
from a Mars expedition would be more than 9 months. This
issue is discussed further in Chap. 7.
Mortality and morbidity related to illness and injury have
accounted for more failures and delays in terrestrial expedi-
tions and new exploration than have defective transportation
systems. Historically, these failures and delays can be attrib-
uted to the long separation of the terrestrial expeditions from
definitive medical care. This has not been the case for space
travel thus far, but becomes a more serious consideration for
the exploration activities now planned.
The medical care system on a future Mars expedition,
for example, will need to be autonomous because of the
extremely long separation from definitive medical care.
Planning for exploration-class missions must include judi-
cious analysis of the limitations on mass, volume, power, and
medical training and careful balancing of those limitations
against the need for comprehensive medical and surgical
care capability, including the need for surgical interventions
(see Table 6.3). A system that includes a CMO and greater
on-board surgical capability than past space missions will
be necessary because of the increased risks inherent in an
exploration-class mission and the need to reduce the effect
of such risks on the mission and on crew health. Such a capa-
bility may be provided through a combination of traditional
resources and newer innovative technologies now in devel-
TABLE 6.3. Mission-related factors affecting surgical care.
Remoteness and correspondingly long periods to reach definitive medical care
Communication delays
Limited medical care resources (weight, power, volume, lighting)
Microgravity
Physiological changes of long-duration space flight
Limited crew training and experience
Radiation exposure
Enclosed environment
Psychological stresses
Possible delays in wound healing
Possible immunosuppression affecting healing and the incidence of disease
6. Surgical Capabilities
opment, such as smart medical systems, medical infor-
matics, telemedicine, and telerobotics.
Surgical Care System Capabilities
The capabilities of the CMO and the medical hardware available
on board will determine the surgical capabilities of any future
spaceflight medical care system; however, the CMOs training
is the factor that will most limit capability [35]. Medical and
surgical hardware is subject to strict limits in terms of weight,
volume, and electrical power required. Moreover, all of the
hardware must function accurately and reliably in the micro-
gravity environment after extended storage time with minimal
checkout and maintenance and without expert operators or
repair technicians on site. Hardware will probably be available
on future space flights to perform surgical procedures that will
be beyond the capability of the CMO, but the availability of
such hardware will also allow flexibility in handling a variety
of surgical problems on board.
Reviews of other remote medical care systems under-
score not only the importance of emphasizing CMO training
but also the need to consider the possibility of using medi-
cal treatment for diseases traditionally considered surgical,
such as appendicitis, during space flight. Assessments of
space medicine requirements and training with regard to crew
selection have emphasized the importance of surgical capabil-
ity and have proposed 23 years surgical training for future
CMOs for long-duration exploration-class space flights such
as a Mars expedition [6]. Telemedical consultation, a recent
modality with which substantial clinical experience has yet
to be accumulated, will be important to augment the clini-
cal experience necessary for spaceflight medicine. Although
clinical experience with telemedicine is limited, telemedicine
has been shown to be valuable in remote-care environments.
Nevertheless, a Mars expedition will face the problem of sig-
nificant communication delays because of the long distances
involved; two-way communication times will range from
about 856 min, depending on the orbital configuration of the
Earth and Mars, making telemedicine awkward and real-time
input impossible [7].
Surgical Capabilities During Previous Missions
Early space missions had only rudimentary medical kits on
board until the longer-duration Skylab missions [8] (see also
Chap. 4). A minor surgical kit that allowed laceration closure
was included for the first time on Skylab, as was expanded
diagnostic and medical therapeutic hardware. The Space
Shuttles medical system, which is used today, contains the
components of a minor surgical kit for laceration closure
using conventional suturing techniques, but the components
are individually wrapped, making the logistics of actually
performing a surgical procedure more difficult than if an
integrated system were used. Local anesthetics are available
125
as well as laceration closure techniques that do not require
substantial surgical skills (Steri-strips, Dermabond adhesive,
and staples). The hardware available on the Russian space
station Mir was similar to the Space Shuttle medical system
in its capabilities.
Surgical Capability for the International
Space Station
An advanced life support pack is included on board the ISS
[9] to allow advanced cardiac life support, including venti-
lation and defibrillation, and advanced trauma life support.
The invasive portions of these procedures have been evalu-
ated in parabolic flight using animal models to validate their
feasibility [10].
Because evacuating a seriously ill or injured crewmember
from the ISS to a definitive ground medical facility
would take 624 h depending on the evacuation spacecraft
available (currently a Russian Soyuz capsule), the surgi-
cal capabilities of the ISS medical care system need not
be extensive. Current ISS procedures do not require that
a physician be on board, and the CMO has only 80 h of
medical training; thus the ISS surgical hardware does not
provide the capability for major surgical procedures such
as thoracotomy, exploratory laparotomy, vascular repair, or
invasive orthopedic procedures. The emphasis instead is on
stabilization, medical transport, and initial advanced life
support capability [11].
Future Surgical Systems
As exploration-class activities such as constructing a lunar base
or an expedition to Mars become a reality, the time required
to reach definitive care will greatly increase, as will the need
for surgical capabilities in the medical care facility. The medi-
cal care facility for these programs may be similar in size and
capability to the Health Maintenance Facility that was origi-
nally planned for Space Station Freedom [12,13]. That facility
weighed 5,291 kg (2,400 lb) and displaced 30.5 m3 (100 ft3) in
volume. It consisted of a microgravity surgical workstation,
which was similar to an operating table and was designed to
restrain both the patient and the operator. It also was to have
had a digitized x-ray capability, a ventilator, a defibrillator,
monitors, an intravenous pump, a medical computer, stor-
age for medical and surgical supplies, and a microgravity
suction unit. That suction unit used centrifugal force [13,14]
to separate air/fluid mixtures and allowed the measurement
and containment of biological fluids (urine, blood, gastric
contents, and pleural fluid).
The effects of new and evolving technologies on future
surgical care systems for exploration-class space flights are
difficult to predict. Many fascinating possibilities are being
considered, and new choices will certainly emerge. The major
effect that these technologies are expected to have on surgi-
cal care will be to reduce the impact of remoteness, short-
126
ages of resources, and limited surgical skills. For example,
hemoglobin-based oxygen carriers, developed as a substitute
for blood transfusions, would greatly affect a CMOs ability
to resuscitate a trauma patient during space flight. Develop-
ments in nanorobotics, smart medical systems, computer
medical informatics, noninvasive sensors and diagnostics, and
telemedicine all have the potential to increase the autonomy of
the remote surgical team. It is hoped that the development and
validation of these technologies will allow a paradigm shift in
the requirements for traditional surgical capabilities for space
flight and will also provide feasible solutions to reducing
medical and surgical risks.
Experience from Analog Environments
The Russian experience in long-duration space flights has
been helpful in verifying that medical issues will affect the
mission in terms of lost crew work time, diminished crew per-
formance, and, in some instances, early crew return. Most of
the medical events that have taken place occurred 26 months
into the mission, well after the acute period of physiological
and psychological adaptation. Although most medical care
issues have been minor, medical evacuations have been neces-
sary during Russian space flights. These evacuations resulted
from specific medical events, but they were also enhanced by
the psychological stress of long-duration space flights.
The experiences of non-spacefarers using various remote
medical care systems have also been helpful in predicting
the incidence of specific surgical diseases and the ability
to medically treat some diseases that have classically been
considered surgical. Epidemiologic studies of analog popu-
lations, especially those on U.S. Navy submarine [1,2,15,16]
and Antarctic [17] expeditions, indicate that major surgical
events, although rare, are catastrophic to the mission, as they
often require medical evacuation. On the other hand, sus-
pected appendicitis (a so-called minor surgical disease) was,
in combination with psychiatric events, the most common
cause of medical evacuation from patrol submarines. The
incidence of minor surgical diseases in analog populations
seems to range between 1 per 8,000 to 1 per 13,000 person-
days [1,2]. This rate translates to a single event every 36
years for a six-person space station.
Analysis of other remote care medical systems reveals that
some surgical diseases can be treated medically in combination
with careful and continuous evaluation of the patient. The
successful nonsurgical treatment of acute appendicitis in the
crews of both British Royal Navy Polaris submarines and
U.S. Navy submarines is well documented [1,2,15,16]. The
U.S. Navy protocol for treating suspected acute appendicitis
consists of bowel rest, intravenous fluids, and antibiotics such
as cefoxitin and gentamycin. Patients are evacuated when
possible, and evacuation is expeditious if improvement is not
immediately evident, as was true for 5% of those cases in the
British Royal Navy and 15% of those in the U.S. Navy expe-
M.R. Campbell and R.D. Billica
riences. The incidence of appendicitis in these analog pop-
ulations has been reported as 12 per 100,000 person-days,
[1,2,1517] which would be equivalent to 12 cases every
45 years in a six-person space station.
Surgical Research in Simulated-Microgravity
Environments
Neutral Buoyancy
Research has only recently begun into surgical techniques
to be used in microgravity. Although neutral buoyancy
(underwater) evaluations of surgical techniques have been
suggested [18], such evaluations are not as feasible or as
realistic as those conducted in a true microgravity envi-
ronment, because surgical fluids interact with the water
environment far differently than they do with an air envi-
ronment. The water environment negates the predominant
effects of surface tension forces on surgical fluids such as
blood. Moreover, the water interacts with the operator to
create resistance and drag with any movements, and thus
each individual piece of hardware and tissue component
must be made neutrally buoyant so that their behavior mim-
ics that in microgravity.
Parabolic Flight Program
Parabolic flight (Figure 6.1) is the only method to investigate
surgical techniques in near-weightlessness without actually
going into space. In the NASA Microgravity Program, the
aircraft is typically flown in 40 parabolas for each mission,
with each parabola generating approximately 25 s of free fall
(weightlessness) followed by a 25-s 1.8-G pullout (Figure
6.2). The short duration of the microgravity window and its
alternation with hypergravity windows are obvious limitations
to applying parabolic flight experience to space flight; how-
ever, parabolic flight remains the best simulation of micro-
gravity available on Earth for this purpose.
Findings from Parabolic Flight Studies
Russian investigators performed limited surgical procedures
(laparotomy and celiotomy) on locally anesthetized rabbits in
parabolic flight in 1967 [19,20]. A closed, transparent surgi-
cal canopy and magnetic instrument holder were used. The
reports, which were observational and brief, stated that no
problems were encountered in controlling venous bleeding,
as the blood typically pooled at the site of injury. Arterial
bleeding, however, formed droplet streams that contaminated
the atmosphere and canopy wall. Also noted was that bowel
evisceration during the laparotomy could affect visualization
and could make abdominal wall closure difficult. Altered pro-
prioception in the short-duration microgravity environment
reportedly caused past pointing and overreaching. The overall
6. Surgical Capabilities
FIGURE 6.1. The NASA KC-135 in parabolic flight. The aircraft is
beginning another parabola that will produce about 25 s of weight-
lessness. Usually 40 parabolas are flown on a typical mission (Photo
courtesy of NASA)
FIGURE 6.2. Flight profile of the NASA KC-135. Each parabolic
maneuver gives 25 s of weightlessness followed by a 1.8 G pullout
conclusion was that surgery was possible in microgravity
without major difficulties.
U.S. parabolic flight research to examine surgical techniques
in weightlessness has also established several important
concepts. Surgical procedures in weightlessness can be per-
formed with no more difficulty than in the 1-G environment
if the principle of restraining the patient, the operating per-
sonnel, and the surgical hardware is adhered to [21]. Surgical
bleeding and free blood may be adequately controlled by local
methods such as the use of sponges and suction [22].
The experience of medical personnel in simulations aboard
Skylab and Space Shuttle as well as in neutral buoyancy
and parabolic flight indicates that many aspects of perform-
ing a surgical procedure are feasible in space flight. Simu-
lations involving prepping and draping, gloving, deploying
127
and restraining equipment, providing appropriate lighting
and exposure, and using conventional suturing techniques
have been evaluated and successfully performed in parabolic
flight [23,24]. However, these simulations have also shown
that certain basic procedures must be relearned. For instance,
glove packages must be restrained during gloving and gloves
must be removed with great care and minimal disturbance.
Because of their surface tension properties, conventional anti-
septics such as Betadine and Duraprep are easily adaptable for
use in microgravity. Finally, use of commercial sterile surgi-
cal drapes that have an adhesive surface that can be applied
directly to the surgical site greatly simplifies the otherwise
cumbersome procedure of draping in weightlessness.
Need for Restraint
Restraining the patient, the operating personnel, and all surgical hard-
ware is a critical consideration in providing effective surgical
care in microgravity. Clearly the patienteven if fully awake,
conscious, and cooperativemust be rigidly restrained. The
operating personnel also must be securely restrained and yet
be able to move their arms and hands freely. Restraint has been
shown to enable the use of standard surgical techniques and
the maintenance of sterile fields. Several options have been
examined to facilitate instrument and supply restraint, such as
procedure-oriented kits, small surgical packs deployed on an
adjacent wall, magnetic surgical trays, and a sterile surgical
restraint scrub suit that allows supplies and instruments to be
restrained in the chest area [25].
Procedure-oriented kits offer an advantage over individually
packaged instruments because all of the supplies that are
necessary for the procedure are already available and organized
on a sterile field. The disadvantage is that the entire kit is con-
taminated if only one item is needed. Velcro, elastic cords, and
magnetic areas can be used to stabilize supplies. A plastic-lined
pocket, a guarded Styrofoam block (for sharp objects), and an
adhesive pad area (for suture ends) allow trash disposal.
Sterile instruments and supplies should be restrained in
such a way as to allow efficient, organized, and conventional
procedures and to maintain sterile technique in space flight.
Conventional operating room concepts, such as a surgical tray
for immediately needed sterile items and a surgical back table
for eventually needed sterile items, should be incorporated in
the procedures. Trash items must be disposed of securely and
safely without compromising sterile technique. Indeed, the
orderly disposal of discarded supplies is critical in the small
volume of a spacecraft, particularly given the rigid constraints
on atmospheric contamination. The spacecraft atmosphere
must also be protected against the surgical debris generated,
especially if bleeding occurs, irrigation is used, or pus and
other infectious fluids are encountered.
Restraining operating personnel has been simpler than
anticipated. The initial concept of using waist belts and shoe
cleats that engage an omnigrid floor, as proposed for the Health
Maintenance Facility [13,14], has been discarded. Instead, a
128
simple, low-placed horizontal bar, which allows the operators
feet to be placed underneath, has been found to provide secure
but flexible restraint.
Currently, a floor-level, easily stored crew medical restraint
system is present on the ISS; earlier versions of this device were
flown on Mir and Space Shuttle missions (Chap. 4). Although this
restraint system is designed for transporting a critically injured
crewmember, it also allows the patient, operating personnel,
and supplies to be restrained for minor surgical procedures.
Despite the usefulness of the crew medical restraint system,
a rigid, stable, waist-level table with multiple capabilities is
still considered a more optimal configuration for a procedure-
oriented restraint system. Such a system would need to be
compact, lightweight, and flexible enough to accommodate
crewmembers of different body sizes and positions, including
the microgravity neutral body position that is characterized by
slight flexion of the knees, hips, shoulders, elbows, wrists, and
cervical spine (see Chap. 2).
The need for more complex medical restraint systems will
increase as the medical environment on board spacecraft becomes
more independent. The first surgical simulations performed in
parabolic flight demonstrated that if operating personnel and
instruments were not restrained, even simple tasks such as drap-
ing a patient became extremely awkward. With restraint, the
parabolic flight environment was not found to be much different
from the 1-G environment. Simulations of minor surgical proce-
dures on the Spacelab Life Sciences-1 (STS-40) and the Neurolab
Space Shuttle (STS-90) missions and during parabolic flight also
confirm that surgery in weightlessness may be performed with
little more difficulty than in the 1-G environment if the principle
of restraint is adhered to.
Bleeding and Hemostasis
A major concern regarding surgical procedures in microgravity has
been the behavior and control of arterial and venous bleed-
ing. A related concern regards the potential for contamina-
tion of the fragile, closed-loop spacecraft atmosphere with
surgical debris and blood, and whether such contamination
could reasonably be prevented [26]. Mutke, in a 1978 study
[27], conceptualized operating through an advanced inflat-
able, Lexan surgical bubble. Soviet investigators had actually
built several early versions of this concept and flown them
in parabolic flight simulations [19,28]. Markham and Rock,
in the United States, also tested several prototypes simulating
laceration closure on a mannequin in parabolic flight [2932].
Their prototype, which required inflation, was able to contain
floating instruments and fluids ejected from a syringe.
A NASA team evaluated a similar closed-system surgical
overhead canopy in parabolic flight (Figure 6.3) [28]. During
surgical procedures on anesthetized animals, this team exam-
ined the behavior of arterial and venous bleeding and the ability
to control bleeding and prevent atmospheric contamination.
Venous bleeding was subjectively increased over terrestrial
norms, possibly because of the lack of venous wall compression
in weightlessness. Also, both arterial and venous bleeding
M.R. Campbell and R.D. Billica
FIGURE 6.3. A prototype surgical canopy is tested with a mannequin arm
during a zero gravity maneuver in parabolic flight. Human operators
are restrained at the feet and waist, with arms inserted into sterile
glove ports. A magnetic surgical instrument tray is in the foreground;
at the opposite end is an outlet for providing laminar airflow to carry
away escaping fluids and surgical debris (Photo courtesy of NASA)
were found to form large fluid domes that adhered closely
to the bleeding tissue because of the surface tension forces
unopposed by gravity. Bleeding escaped local control methods
(e.g., suction and surgical sponges) only when an arterial
droplet streams were allowed to form. This finding was con-
sistent with results of previous experiments in which citrated
bovine blood ejected from a syringe was used inside a glove-
box during parabolic flight to simulate arterial and venous
bleeding (Figure 6.4) [26]. Those investigators concluded that
the surgical overhead canopy (Figure 6.5) would be useful if
uncontrolled arterial bleeding was present, if large amounts of
surgical debris were generated, if large amounts of irrigation
fluid were used, or if pus was encountered.
Other investigators have proposed the use of large, inflatable
environments that would surround the patient, operator, and
supplies during surgical procedures in microgravity. Although
such an arrangement may seem impractical, the prototype
hardware has surprisingly low weight and storage volume.
Laser surgical techniques have also been suggested as a means
of effecting bloodless surgical procedures in weightlessness
[33]. These techniques could be useful if the tools were min-
iaturized (handheld and battery-powered) and their safety
validated. (Electrocautery devices generate too much radiofre-
quency interference to be practical in a spacecraft, so their use
is not currently considered feasible.)
Another approach to preventing atmosphere contamination
was the concept of generating laminar airflow over the opera-
tive field to sweep up surgical debris and transport the debris
to a collecting suction apparatus. NASA has evaluated a lami-
nar airflow device in parabolic flight using mannequins and
surgery on animals. This device controlled the bleeding that
escaped local control methods and cleared the operative site of
debris that would have otherwise impaired visibility. However,
6. Surgical Capabilities
FIGURE 6.4. Blood pooling in weightlessness, which is characteristic
of most bleeding whether the source is arterial or venous. Large fluid
domes are formed due to surface tension forces at the bleeding site,
largely preventing dispersion into the enclosed cabin
FIGURE 6.5. An arterial droplet stream forming from an incision made
in the abdominal aorta of an animal model in microgravity as viewed
through an overhead surgical canopy. Operators have access to the
surgical site via arm portholes. This could easily be converted into
a non-dispersible fluid dome that remained adherent to the wound.
Some droplets have been stopped on the surface of the surgical canopy.
Instruments are well restrained on the surgical tray
that experience indicated that the use of standard surgical
techniques would be adequate to control most surgical bleeding
in weightlessness because of the formation of large, nondis-
persing fluid domes that adhere to the bleeding surface.
Advanced Cardiac and Trauma Life Support
In a series of dedicated parabolic flight experiments, NASA
space medicine experts evaluated the feasibility and practicality
of many standard techniques used for cardiac and trauma life
support. Initial basic and advanced cardiac and trauma support
procedures could be performed in parabolic flight despite lim-
itations in having only minimal equipment available and using
a nonphysician CMO. Artificial ventilation performed for the
129
first time in parabolic flight seemed to be unchanged from
such ventilation in the 1-G environment. Respiratory mechanics
and performance of artificial ventilation hardware were not
affected to a clinically significant degree. The adjunct pro-
cedures of intravenous infusion, laceration closure, and Foley
catheter drainage were also achieved without difficulty.
Although cardiopulmonary resuscitation is more difficult to
perform in weightlessness, it can be done effectively if both the
patient and the CMO are properly restrained. Although the basic
trauma support procedures of venous cutdown, cricothyroidot-
omy, peritoneal lavage, and chest tube insertion were found to
be no more difficult to perform in microgravity than in the 1-G
environment, restraint principles had to be observed, and manage-
ment of fluid infusions and drainage required minor modifications
of hardware and techniques. These modifications include degas-
sing all infusion bags and lines, using pressure pumps instead
of gravity flow, keeping drainage tubes as short and as large in
diameter as possible to negate the effects of surface tension and
capillary action, and eliminating all possible communication to
the cabin atmosphere to prevent leakage. Percutaneous peritoneal
lavage, although it required less training to perform, was found
to be dangerous in weightlessness because of the additional pres-
sure of the bowel on the anterior abdominal wall, a direct effect
of the microgravity environment that created a high risk of bowel
perforation. Although an open peritoneal lavage technique was
shown to be feasible in microgravity, it required additional
training and experience. Also, the lack of 1-G capillary fluid pull
and the increased effects of fluid surface tension forces in weight-
lessness led to decreased drainage of peritoneal lavage fluid.
A Heimlich valve and a Sorenson drainage system were used
to provide chest tube drainage and fluid collection with minimal
equipment. This combination eliminated the risk of atmospheric
contamination and also provided the capability to use autotrans-
fusion to drain blood from a hemothorax (Figure 6.6). The use
FIGURE 6.6. Chest tube placement in an animal model demonstrating
the passive drainage of a simulated hemothorax. Fluid flows up
without difficulty in weightlessness. This was performed using a
Heimlich valve and a Sorenson drainage system, which gives the
capability of immediate autotransfusion (Photo courtesy of NASA)
130
of a percutaneous dilational technique for chest tube insertion
resulted in a procedure that required minimal CMO training and
minimal equipment, was technically easier to perform, and
further decreased the risk of atmospheric contamination. Suturing
the wound tightly around the chest tube was found to be more
important in microgravity than expected to control fluid leakage
and to prevent contamination. Performance of the procedure by
a nonsurgical physician required a minimal amount of train-
ing, on the order of 1 h of ground instruction. Telemedicine was
found not only to be feasible but also of clear benefit in this
project, because it facilitated the insertion of a chest tube under
the direction of a remotely located general surgeon.
Chest tube drainage was still effective in weightlessness
when passive drainage systems (without suction) were used
because of inherent intrathoracic pressure. The Sorenson
drainage system used for these experiments had previously
been proposed for the autotransfusion of chest tube contents
from a traumatic hemothorax. Immediate autotransfusion of
blood collected from a hemothorax without further processing
or anticoagulation has been shown to be safe and effective,
especially in remote medical care situations [3436]. The
1-G disadvantage of using a short or a relatively anterior chest
tube, in which removal of thoracic fluid is limited because of
dependent pooling, should not be a factor in the micrograv-
ity environment. In microgravity, hemothorax fluid distributes
itself uniformly as an adherent sheet along the chest wall, and
neither the length of the chest tube nor its position in the chest
cavity should influence the drainage flow rate. Some locula-
tion of fluid also occurs in microgravity within the chest cav-
ity because of surface tension forces.
Patient Monitoring
Although a standard medical monitoring system (including
electrocardiography and measures of blood pressure and
ventilatory parameters) functioned normally in parabolic
flight, the hardware setup and the logistical management of
the large number of tubes and wires would be problematic if
it were the responsibility of a single CMO. A more self-
contained, centrally located, and easily deployable system
would be better. Wires and tubing should be kept as short as
possible to prevent interference with other hardware floating
in the microgravity environment.
Another form of patient monitoring that has been consid-
ered is a trauma pod that could be rapidly deployed and
transported and provide restraint for the operator and the
patient [37]. Such a trauma pod could be used for advanced
cardiac and trauma life support operative procedures as well
as for more routine medical examinations. The pod would
contain surgical hardware, instruments, and supplies for logis-
tical efficiency and rapid deployment, and it would reduce the
intense labor required to perform a procedure in weightless-
ness. By providing routing interfaces, the trauma pod concept
would also ease the difficulties caused by wires and medical
tubing in weightlessness that interfere with even a simple
M.R. Campbell and R.D. Billica
procedure. Finally, such a system would provide for disposal
of dry trash, biological waste, and any instruments with sharp
edges or points.
Atmospheric Contamination
Another theoretical concern associated with performing a
surgical procedure during space flight (as compared with a
standard operating room) is that of contamination of the
operative site by the relatively dirty spacecraft atmosphere,
which could increase the incidence of wound infection. The
amounts of particulates and colony-forming units in spacecraft
atmospheres are higher than in a conventional operating room
atmosphere by a factor of 10 [21]. In microgravity, particles
tend to be larger and are composed mostly of scurforganic
particles from skin sloughing.
Moreover, in light of preliminary evidence that the rela-
tive numbers of pathogenic bacteria on skin and surfaces may
increase during long-duration space flights and that in-flight
medical facilities may be located near waste-management
facilities or kitchen or exercise areas on future spacecraft,
concerns have been expressed that the atmosphere may
contaminate wounds in microgravity. This concern may be
mitigated through the use of surgical overhead canopy and
laminar flow devices, which have been shown to lower these
counts logarithmically [22]. The rate at which clean wounds
become infected may also be higher in space than on the
ground because of possible immunosuppression and altered
cellular responses in healing of wounds and suppression of
infections (Chap. 15) in addition to the high particulate counts
in the spacecraft atmosphere.
Surgical Endoscopy
The feasibility of performing a laparoscopy in microgravity
has been questioned, with concerns focusing on the potential
for impaired visualization from the lack of bowel retraction in
the absence of gravity and from floating debris such as blood.
In response to these concerns, parabolic flight experiments
were designed to investigate the feasibility of performing
laparoscopy and thorascopy on anesthetized animals in simu-
lated microgravity [38]. These experiments showed that use of
sophisticated endoscopic surgical tools is indeed feasible and
valuable in weightlessness but only when the CMO has the
ability, training, and experience to use them and when the nec-
essary supporting functions are in place. Cavitary endoscopy
in microgravity also has the advantage of acting as a natural
containment bubble that protects the operative site from the
high-particulate spacecraft atmosphere and contains surgical
debris and fluids.
Laparoscopic surgery has been performed successfully in
parabolic flight. Visualization was not impaired, apparently
because of the elastic mesentery tethering the bowel and the
surface tension forces present that cause any surgical debris
and blood to adhere to the abdominal wall [39]. In microgravity, the
6. Surgical Capabilities
bowel does not float within the abdomen or fall into the pelvis,
as it would in 1-G, because of this mesenteric influence, which
although minor in the presence of gravity, becomes predomi-
nant in microgravity. In 1-G, the abdominal cavity in a supine
individual forms a flattened oval because of the weight of that
persons anterior abdominal wall. The round shapes assumed
during microgravity increase the anterior-to-posterior diameter
and are better suited for laparoscopic visualization and manip-
ulation because they increase the laparoscopic domain.
Thorascopy, on the other hand, was found to be extremely
difficult in weightlessness because of the loss of the gravi-
tational retraction of the mediastinum, which is critical to
visualization. More complicated techniques such as selective
bronchial intubation and chest insufflation will probably
be required to make thorascopy a feasible procedure. The
technical difficulty of establishing a pneumoperitoneum
without the high risk of bowel perforation, the miniaturization
of laparoscopic support hardware, and the availability of
laparoscopically trained CMOs are other issues that prevent
laparoscopy from being a practical component of any present
in-flight medical care system.
Also, because large amounts of support equipment and
specialized laparoscopic instruments are required to perform
even a simple laparoscopic procedure, such a capability would
be difficult to justify in a medical care system that has strict
weight and volume limitations. More important, laparos-
copy requires considerable experience and proficiency and
is usually performed only by highly trained surgeons. This
requirement would severely limit CMO selection. The ability
to treat surgical complications that might arise would likewise
be limited in a remote medical care system. On Earth, the
incidence of laparoscopic complications depends greatly on
the experience of the operator.
Nevertheless, future development of technologies could
well make laparoscopy in weightlessness more feasible. The
most important of these developments would be miniaturiza-
tion of the large, bulky support equipment, such as the video
monitor, video camera, insufflator, and fiber-optic light source.
Minimally invasive surgery can have the substantial potential
advantage of requiring only local anesthesia. In the future,
these procedures may be performed with abdominal wall lift
devices that would eliminate the need for CO2 insufflation.
The effect of such retracting lift devices is to pull the anterior
abdominal wall anteriorly, thereby enlarging the volume of the
intra-abdominal cavity while mesenteric attachments maintain
the bowel in place. This approach would greatly simplify the
procedure and reduce the logistical support required.
Methods of controlling hemorrhage that are easier than
endoscopic suturing include the use of fibrin glue injectors,
laser technology, and advanced stapling devices. Replacing
the video display with three-dimensional stereoscopic, virtual-
reality headgear and with remote surgical telerobotics is also
actively being investigated [4044]. Telerobotics and telepres-
ence will allow a logarithmic increase in surgical precision,
because a 1-cm (0.4-in.) control input can be translated into a
131
1-mm (0.04-in.) manipulation at the surgical site. Teleprescence
surgery could also allow a surgical procedure to be performed
at a remote location. Telerobotics can enhance both images
and dexterity in a surgical procedure, but telerobotics currently
requires enormous hardware logistics and extensive training
even for the on-site personnel. These techniques also naturally
lend themselves to real-time telemedicine consultation and
telementoring if no communication delays are present [45].
Unfortunately, use of these techniques in space will be limited
by the long communication delays that make them impractical;
even the 2-s delay that occurs in low-Earth orbit (owing to
indirect satellite routing) is crippling to the performance of
remote telerobotic surgery.
Endoscopic urologic stenting to treat ureterolithiasis in
conjunction with telemedicine monitoring has been shown
to be feasible in parabolic flight [46]. On Earth laparoscopic
surgery has rapidly evolved into a system that is technically
easier, consistently more successful, and more broadly appli-
cable. In future long-duration space exploration missions, the
presence of more surgically capable CMOs will allow lapa-
roscopic procedures to be performed instead of open surgical
procedures.
Experience with Surgical Procedures
in Space
In April 1998, the crew of the Space Shuttle STS-90 Neurolab
mission performed the first survivable surgical procedure
on animals in space. In this procedure, a leg wound was
created in adult rats to inject an isotope tracer in the rats
thigh muscle. The wound was then closed with Dermabond
adhesive. Other, more complicated surgical dissections
(i.e., craniectomy, C-section, laminectomy with spinal cord
removal) were also performed on adult rats that did not survive
by experimental design.
The results of the Neurolab mission validated several
concepts of surgery in space. First, the surgical procedures
within the scope of the Neurolab experiments were no more
difficult to perform in microgravity than in 1-G. Second, the
surgical procedures that were performed in space flight were
similar to those performed in parabolic flight, thus validating
the parabolic research model. Third, space flight was not asso-
ciated with any changes in surgical dexterity, proprioception,
or fine hand-muscle motor control. Fourth, good restraint of
the patient, operator, and all of the equipment was, as expected,
of utmost importance. Fifth, surgeons must anticipate logistics
and diligently restrain all equipment, supplies, instruments,
and discarded trash. For this reason, procedures will take
longer to perform in microgravity than in 1-G. Sixth, in the
absence of gravity, fluids coalesce and do not disperse because
surface tension forces predominate; thus blood and other body
fluids were easy to control by using simple measures such as
sponging. Seventh, special care was needed in the use of sharp
objects such as scalpels and needles; simple measures, such as
132
calling out sharps on deck, increased the safety awareness
of the surgical team. Finally, no subjective gross changes in
wound healing were noted; however, no objective measures of
wound healing were used. As noted by Dr. David Williams of
the Canadian Space Agency, who served as a crewmember on
the Neurolab mission, if appropriate restraints are provided,
surgical procedures are feasible if the individual operator has
adequate 1-G surgical skills.
Limitations to Surgical Care in Space
Successful surgical care on Earth depends on many factors,
including the diagnostic capability that is available, preop-
erative preparation, intraoperative logistical support, ability
to provide postoperative care, and the availability of specialty
consultations and safe medical evacuation to a center that
can provide more definitive medical care as needed. The
presence of a surgeon who is well-trained, technically skill-
ful, and proficient is also an important determinant. Surgical
care in space will, by necessity, have limitations, including
the skill level of the surgical operator, the available medical
hardware, the altered environment of microgravity, and the
state of the physiologically compromised patient.
Regardless of the Earth-based surgical capabilities and
experience of an operator, that operators technical skills may
well be limited by changes in proprioception, a lack of experience
in operating in a microgravity environment, and the need to be
restrained in microgravity. From the experience gained thus far
from parabolic flight and space flight, the time required to
perform a given operation in low Earth orbit is estimated to
increase by a factor of 1.53 because of the need for restraint,
meticulous control of bleeding, and careful specialized han-
dling of logistics and fluids. This situation may be worse on
exploration missions, where ground resources are even more
remote. On a Mars expedition, for example, the delay in com-
munications will limit the utility of consultation. Moreover, in
that setting, evacuation to a facility that could provide a higher
level of care or more definitive care will not be an option. The
medical care system infrastructure will therefore obviously be
limited in diagnostic and therapeutic options.
Need for Specialized Equipment
Medical and surgical hardware must be accurate, reliable (as
remote repair will be difficult), simple (as expert operators
will be unavailable), and have very long lifetimes. Most hard-
ware items will not be specifically developed for flight; rather,
commercially available equipment will be only minimally
modified to withstand vibration and to function in micrograv-
ity. Hardware items also must be composed of nonflammable
materials that are not subject to prolonged off-gassing, which
would exclude many plastics. Given the complexities of the
engineering and flight certification processes, the lead time
from system design to flight is often 510 years.
M.R. Campbell and R.D. Billica
Biological fluids in weightlessness must be evacuated,
separated from air suspensions (as airfluid levels do not exist
in microgravity), collected and contained, measured, and dis-
posed of. Active suction pumps that use rotational centrifugal
force to separate gas from liquid have been studied in para-
bolic flight and were proposed for the Health Maintenance
Facility of Space Station Freedom [13]. This concept may be
revived and refined for future use on the ISS or other crewed
installations.
Resource Limitations and Trade-Offs
Medical and surgical hardware in space flight will always
be limited because of constraints on its volume, weight,
and electrical power; hence a long-duration space flight
crew may encounter medical events that will overwhelm
the onboard medical care system. The NASA space medi-
cine team has carefully analyzed what medical problems
are most likely to be encountered and will constitute the
most serious danger to the crew and mission [47]. This
research will help in designing a medical care system that
will be able to handle those medical events that are most
commonly encountered, have a substantial effect on crew-
member health, or could affect the mission.
Providing supplies and equipment for the most common
and most serious medical events will enable treatment
of other, less common or less serious medical events.
Many rare but nonetheless serious surgical events will
not be provided for, and such events could overwhelm
the systems ability to respond adequately. Many vascu-
lar injuries, for example, would be untreatable because
of lack of operator expertise even though the equipment
may be available. Logistics may prevent stocking the
equipment to treat many orthopedic injuries, for which
operator expertise may not be as critical.
Effects of Physiological Adaptation
on Surgical Care
The microgravity-adapted physiological state may well affect
the surgical patient in terms of preoperative preparation,
intraoperative response to surgical stress, and postoperative
recovery [48]. The process by which the body adapts to micro-
gravity has been relatively well described, albeit incompletely
investigated. (Specific descriptions and references are given
in Chap. 2.) The effects of such adaptation include cardiovas-
cular deconditioning (1020% loss of stroke volume), shifts
in fluid and electrolyte levels, muscular deconditioning, neu-
rovestibular deconditioning, short-term gastrointestinal distur-
bances, changes in pharmacokinetics, sustained calcium loss,
osteoporotic changes, protein catabolism, psychological stress
(which has affected medical care in previous Russian flights),
radiation exposure, changes in cellular immune function that
affect the immune response and wound healing, blunting of the
baroreceptor response to blood pressure changes, decreased
6. Surgical Capabilities
lung volumes, loss of red blood cell mass, and decreases of
about 15% in circulating blood volume.
The physiology underlying wound healing in microgravity
is unknown and requires further investigation. Cellular
immune functions seem to be altered and suppressed in
microgravity; consistent spaceflight findings have included
neutropenia; lymphocytopenia; reductions in the popula-
tions, activity, and responses of T cells; decreases in cel-
lular motility and changes in morphologic characteristics,
and decreased production of cellular mediators such as
interleukins [49]. Changes in cell-mediated immunity have
been demonstrated in the form of delayed cutaneous hyper-
sensitivity [50], which certainly would affect the initial
inflammatory stages of wound healing and increase the
incidence of postoperative infection and sepsis. Surgical
diseases with an infectious etiology, such as appendicitis,
could conceivably be more prevalent incidence during a
long-duration space flight.
Because wound healing is essentially a cellular function,
the possibility that delayed repair occurs in weightlessness
needs to be explored [51]. This need is further complicated by
a lack of understanding of the complex cellular processes that
occur during normal wound healing. Preliminary studies of
rats that have been incised on the ground before being flown
in space indicate that the inflammatory phase of wound heal-
ing might be prolonged in space flight. In those studies, cellu-
larity was decreased, collagen content was lower by 62%, and
the response to exogenous stimuli (a platelet-derived growth
factor) was blunted [52]. Tensiometric analysis showed
decreased wound strength and abnormal arrangements of col-
lagen fibers. Bone healing studies in rats sent aboard a Russian
biosatellite have shown reduced callus formation, decreased
numbers and activities of osteoblasts, and reduced angiogen-
esis [53]. Similar studies of rats flown on the Space Shuttle
have shown delayed chondrogenesis and angiogenesis [54].
Studies of wounds created in space and healed in space have
not been done. Notably, because healing is accelerated in 1-G
in the rat model, any exposure to gravitational forces during
flight, even for only a brief period, would render the results of
such a study invalid.
Resuscitation and Patient Transport
On Earth, a class I hemorrhage in a trauma patient involves
a circulating blood volume loss of about 15%, which is the
normal physiological state for space crewmembers on long-
duration flights. The combination of lower volume with
cardiovascular deconditioning, blunting of the baroreceptor
reflex, and loss of red blood cell mass and plasma volume
decreases the ability of a spaceflight trauma patient to
respond to blood loss and shock. Analogous hypovolemic
effects can be replicated by the lower-body negative pressure
device, a research tool used during space flight to simulate
orthostatic G-load and provide a cardiovascular stressor
against which to evaluate cardiovascular deconditioning (see
133
Chap. 16). The decreased ability of crewmembers to tolerate
lower-body negative pressure, as shown by increasing tachy-
cardia and hypotension, after about 2 months on Skylab [55]
suggests a decrease in the ability to tolerate blood loss or
shock in space.
A reduction in the ability to tolerate blood loss or shock
during space flight may have other repercussions as well. For
instance, the golden hour, the period immediately after
significant trauma in which intervention has the greatest effect
on outcome, may well be shorter in space. But even if the
shock responses in weightlessness are not overly fragile as
compared with Earth-normal, a medical evacuation back to
Earth for definitive care could be devastating to a patient who
is in shock.
A crewmember undergoing a medical return on the Space
Shuttle will be kept recumbent on the middeck floor and
experience 1.2 G in a chest-to-back (+Gx) axis for several
minutes. Extraction of such a crewmember after landing will
maintain the patient in the recumbent position, as orthostatic
hypotension and near-syncope are known to occur even
in uninjured crewmembers on return to Earth. The Soyuz,
which can also be used as an evacuation vehicle, lands with
the crew in a recumbent position, exposing crewmembers to
a higher peak load (4 +Gx) but for a shorter period. Research
with primates involving controlled hemorrhage followed
by centrifugation to mimic atmospheric reentry forces has
shown that exposure to reentry acceleration forces has no
adverse effects unless the hemorrhage is severe (class III
or IV, or 3050% loss of blood volume) or the forces are
excessive (8 G instead of 1.8 G) [56]. Since uninjured but
deconditioned crewmembers returning to Earth typically
display many of the hypovolemic characteristics of a class I
hemorrhage (15% loss of circulating blood volume [750 ml
blood loss] manifested as minimal tachycardia and ortho-
static hypotension), a true class I hemorrhage in space may
respond much like a class II hemorrhage on return to Earth
(i.e., 1530% blood loss, manifested as tachycardia, tachypnea,
and increased pulse pressure). Therefore, any trauma patient
in space is likely to have a decreased ability to tolerate the
return to 1-G during a medical evacuation.
Given that deconditioning, hemorrhage, and reentry accel-
eration forces will all have adverse effects on a patient in
shock, restoration of adequate blood volume while still in
space will be critical for ill or injured crewmembers before
they can be safely evacuated to Earth. The development of
hemoglobin-based oxygen carriers (artificial blood) may help
the care providers to resuscitate a traumatized crewmember
before medical evacuation [57]. In addition to the relative
hypovolemia experienced by all returning space flyers, crew-
members returning from a long-duration space flight during
a medical evacuation will have an increased risk of complicat-
ing factors such as nausea and vomiting from neurovestibular
effects, limited cardiac output, immunosuppression, delayed
wound healing, mild anemia, weakening from muscle atrophy,
and pathologic fractures.
134
Management of the Surgical Abdomen
Although blunt abdominal trauma would be fairly unlikely
in space flight, such an injury could be overwhelming to
diagnose and treat definitively [48]. Fortunately, only 10%
of all blunt traumas to the abdomen are expected to require
exploratory laparotomy. The nonsurgical treatment of blunt
abdominal injuriesincluding hepatic, splenic, and renal
injuriesin patients who are hemodynamically stable
is becoming more common. However, this nonoperative
treatment requires sophisticated diagnostic imaging and
the ability to closely monitor the patient. Moreover, it also
assumes the ability to surgically intervene if conservative
treatment is unsuccessful.
The concept of damage-control exploratory laparotomy
[58] in remote medical care situations can be applicable to
space, given adequate skills and resources. This concept
involves limited surgery to control major bleeding and
enteric spillage, but it also involves a planned subsequent
reoperation. The benefit from staging procedures in this
way would facilitate logistical planning as well as allowing
time for additional specialty consultation from the ground
and possibly time to permit medical evacuation to a higher
level of care. Therefore, laparoscopic trauma surgery or
exploratory laparotomy should be feasible during space
flight if adequate operator skills and surgical equipment are
available. [59]
Management of Chest Trauma in Space
Most chest trauma can be adequately treated with chest tube
drainage and supportive therapy alone. Injuries beyond this
level can often require extraordinary infrastructure, logis-
tics, and surgical skill to manage even in the conventional
clinical situation. Stabilization to the extent possible and
immediate transport to ground facilities would be required
for such cases.
Management of Closed Head Injuries
Closed head injuries might be worse in space than on Earth
since weightlessness is physiologically similar to being in a
continuous 6-degree head-down tilt. Intracerebral pressure has
never been measured in space (although intraocular pressure
has been shown to increase in weightlessness), but such an
increase would adversely affect any neurologic trauma. The
capability of placing burr holes in space was discussed and
equipment was manifested for such a procedure during early
preliminary planning for the Health Maintenance Facility on
Space Station Freedom, but it has not been seriously pursued
since that time.
M.R. Campbell and R.D. Billica
Management of Fractures
It is hoped that the lack of gravity will greatly decrease the
overall incidence of blunt trauma and orthopedic injuries sus-
tained by long-duration spaceflight crews. However, the lack
of gravity might also make fractures more likely because of
the osteoporotic condition induced by the chronic loss of cal-
cium in weightlessness and the muscle atrophy that occurs in
deconditioning. The diagnosis of fractures will be based on
clinical and physical examination findings alone unless an
imaging capability is present. Probably most fractures can be
diagnosed and successfully treated by clinical means, without
the use of diagnostic imaging.
Unfortunately, the treatment of orthopedic injuries requires
resources that consume large amounts of space and can nega-
tively affect the environment of a long-duration spacecraft.
Indeed, the open surgical treatment of fractures requires hard-
ware individualized to the specific procedure. Plaster cast-
ing requires mixing plaster with water and is impractical for
space flight. Fiberglass casting materials are associated with
large amounts of off-gassing, which is incompatible with the
closed-loop environments. Yet despite these drawbacks, most
fractures can be adequately splinted and treated with simple
materials such as flexible aluminized splints and elastic ban-
dages. A universal external fixation device would suffice as
an option for more complex fractures if imaging and surgical
expertise were available.
Fracture stabilization often requires gravity to effect or
maintain reduction, and manual traction of fractures will be
difficult to apply in microgravity. As is true for surgical inter-
vention, rigid restraint of the operator and the patient will be
needed, and universal external fixation devices will need to
be used to treat many fractures. Experimental evidence shows
that bone healing is delayed in space [52]. Moreover, many
lower-extremity fractures show delays in healing if no weight
is borne across the fracture site. The muscle atrophy from
deconditioning could also affect fracture healing by not pro-
viding sufficient fracture-site impaction force, which normally
influences the regenerative process. On the other hand, the
lack of gravity may make fracture reduction easier to achieve
and maintain, and injuries such as a broken leg in an astronaut
or cosmonaut who does not need to bear weight on that limb
may prove far less debilitating during the healing process.
Anesthesia
Anesthesia will be more difficult to administer during
space flight [60], especially if it is the responsibility of a
crewmember who is not the CMO. At present, inhalation
anesthetics cannot be used, as volatile gases would quickly
contaminate and overwhelm the closed-loop environment
of a long-duration space vehicle. Inhalation agents will
always be dangerous no matter how sophisticated the anesthesia
6. Surgical Capabilities
machine is in containing the inhalation agent and scavenging
the exhalation for overboard dumping.
Because spinal anesthesia depends on gravity to establish
the affected dermatome, it cannot be used in weightlessness.
Regional and epidural blocks require skill and experience
far beyond the level expected of a CMO. Intravenous anes-
thesia with ventilator support and monitoring should not
be difficult except that it requires the full attention of a
trained crewmember. Intravenous anesthesia, ventilation,
and monitoring oxygenation level, end-tidal CO2, central
venous pressure, and cardiac function have all been shown
to be feasible in parabolic flight tests with animals. Local
anesthetics present no additional difficulty in weightlessness
and have been manifested in in-flight medical kits in the
Russian space station programs and in the United States
space program since Skylab.
Future of Surgical Care in Space
Because the time to reach definitive medical care on Earth
will be extremely long and rescue or medical evacuation will
not be an option, future long-duration space flightssuch
as a Mars expeditionwill require a medical care system of
greater surgical capability [3]. Increased capabilities must be
provided in the face of the increased limitations on surgical
care expected in the long-duration weightless environment.
Such capabilities will require a surgically capable CMO and
an advanced life support system that will allow restraint of
the patient, the operators, and all of the equipment in an inte-
grated fashion.
Laparoscopy will need to be a surgical option, as it is
advantageous in terms of isolating the surgical environment
and the spacecraft environment from each other. Diagnostic
laparoscopy may need to be used because other diagnostic
options may not be available. Laparoscopic equipment for use
in space will be simpler and smaller than what is convention-
ally available. Techniques that avoid insufflation and provide
a telemedicine downlink to surgical consultants are expected
to be present on board. New technologies, such as the use of
artificial blood, will be incorporated into the medical/surgical
care system as they are developed for conventional use.
Unconventional diagnostic techniques will occasionally
be required in the spaceflight environment. Digital radiography,
with downlink of data to radiological consultants, will
eventually be available; however, because organ position
will be altered by the weightless environment, accurate sur-
gical diagnoses will require special consideration. Free air
under the diaphragm, airfluid interfaces in an obstructed
bowel, and pneumohemothorax will probably appear radically
different in space [61]. Sonographic equipment, with its
lesser weight, volume, and power requirements, could be
used instead of computed tomography scanning; sonography
can be valuable in the initial evaluation of trauma as well
135
as in determining the presence of hemoperitoneum, hemo-
thorax, and pneumothorax [6264].
Whether weightlessness will limit the usefulness of sonog-
raphy in detecting these entities is unknown and will require
further research. Sonography in conventional settings depends
on gravity to loculate fluids and air in specific portals (spleno-
renal recess, hepatorenal recess, and rectovestibular pouch)
where they can be easily detected. Such loculation will
probably be greatly diminished or absent in weightlessness,
making its detection much more difficult. Recent studies of
animals in parabolic flight have shown that relatively small
amounts of fluid can be detected in the abdominal cavity in
simulated weightlessness. Thus, fluid can be detected in the
location where it is created and does not easily drain away
posteriorly as it would in 1-G. Fluid was found in the usual
1-G sonographic portals (but only after the parabolic flight
2-G maneuver).
Fluid can also be more readily detected in bowel interloop
locations in microgravity than in 1-G [65]. Air (pneumotho-
rax) and fluid (hemothorax) in the thoracic cavity could also
be detected in weightlessness. In a conventional 1-G pneu-
mothorax, a large anterior air pocket is created that is visible
sonographically as a loss of lung sliding. [60,64] In micro-
gravity, the lung is more centrally located and the pneumotho-
rax is diffuse rather than loculated. Although this situation
reduces the sensitivity of sonography in microgravity as
compared with 1-G, sonography can still detect even a small
pneumothorax. The fluid in the chest cavity in microgravity is
more diffuse rather than being posteriorly loculated, but it can
still be detected readily. Moreover, the diffuse distribution of
air or fluids in weightlessness means that there is no need to
place a chest tube anteriorly for a pneumothorax or posteriorly
for a hemothorax.
Unconventional therapy for surgical diseases will probably
be necessary [65]. The nonsurgical treatment of hemoperi-
toneum from blunt trauma [48] and the medical (nonsur-
gical) treatment of acute appendicitis will be safe options
if the patient can be accurately evaluated and monitored.
Capability for conventional open surgical techniques will
need to be available if nonsurgical or laparoscopic treat-
ment fails. When and if a surgical procedure is performed,
the surgical skills of the operator will, in large part, determine
the success of the procedure.
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7
Medical Evacuation and Vehicles for Transport
Smith L. Johnston, Brian A. Arenare, and Kieran T. Smart

Space is a uniquely remote and hazardous environment. For Safety and performance of the transport vehicle
humans to live and work effectively in low earth orbit (LEO), Time and duration of medical transport
significant technological support must be provided to over- Safety of the transport flight profile

come the physical and psychological challenges of space Onboard medical capabilities during transport

flight. This operational environment places great demands on Medical capabilities of the receiving facility

a crew, particularly during emergency situations, where the

These factors affect the care of ill or injured patients in any
life of a crewmember may rest in the hands of a colleague or a
environment, from large urban areas to small community
Crew Medical Officer (CMO). In four decades of human space
hospitals and clinics, as well as remote isolated environments such
flight and exploration, our knowledge, activities, and capa-
as cruise ships, submarines, oil platforms, military deployments,
bilities have grown tremendously. In nearly 70 person-years
wilderness base camps, and low earth orbit (LEO) platforms like
of the worlds various agencies, medical treatment of ill or
the ISS. Shen has described clinical care in such remote environ-
injured crewmembers has been required with a low yet regular
ments as fourth-world medicine, which he defines to be clini-
frequency. Between 1971 and 2005, one evacuation, two early
cal practice in a remote, hazardous environment with advanced
returns to earth, and several emergent medical events have
technology diagnostic, therapeutic, and evacuation capabilities to
occurred during space flight. From this experience and that
augment limited medical officer training and support [2].
of analogous remote environments, it is possible to estimate
This chapter will examine key aspects of present-day
the likelihood of a serious medical event, defined as one that
terrestrial and spaceflight medical transport and evacuation,
would require emergency room care in a terrestrial setting, for
enumerate current challenges, and suggest possible solutions
a crew aboard a low earth-orbiting platform such as the Inter-
for future spaceflight activities [35]. We will discuss present
national Space Station (ISS). For a full crew complement of
and future standards of care on the ISS, and current vehicles
six or seven individuals, as is ultimately planned for the ISS,
including the Russian Soyuz and the U.S. Space Shuttle. We
such a medical contingency may be anticipated to occur, on
will also address programs such as the NASA-JSC X-38, and
average, approximately once every two and a half years. Most
the Orbital Space Plane (OSP) [69]. These concepts are appli-
of these would likely be managed using onboard medical
cable to the development of future platforms such as the CEV
capabilities. The likelihood of a critically ill or injured crew-
(Crew Exploration Vehicle). Topics addressed will include:
member requiring transport to a terrestrial definitive medical
care facility (DMCF) is estimated to be loweronce or twice
1. Likelihood and types of spaceflight medical events requiring
over the planned 15-year lifespan of the ISS.
evacuation [10]
Whether in a terrestrial, aviation, ship-borne, or space
2. Standards of spaceflight medical care and projected
environment, the priorities of triage and the principles of
capabilities for LEO space stations, lunar exploration, and
medical evacuation remain constant. These priorities are
inter-planetary missions [11]
predicated on several factors [1]:
3. Physiological de-conditioning of astronauts returning from
Severity of the illness or injury long duration microgravity exposure
Environmental conditions at the scene and during medical 4. Psychological aspects of crew performance in medical
transport emergencies after long duration space flight
Capabilities and proficiency of the first responders 5. Inherent risks associated with spaceflight medical evacua-
Available medical care, equipment and capabilities tion due to the microgravity environment and the dynamics
Telecommunications capabilities of reentry and landing [12,13]

139
140
6. Medical requirements and capabilities of an LEO transport
and return vehicle [14,15]
7. Human factors for crew work stations in vehicles such as
the crew return vehicle (CRV)
8. Ethical issues and medical standards for evacuation from
LEO and other space environments where return to defini-
tive medical care is delayed or impossible (such as a Mars
surface station).
Evidence-Based Evacuation
RiskThe Need for Transport
Longer duration missions aboard the ISS require planning for
a variety of potential adverse medical events. These events
include possible medical evacuations, both urgent and antici-
pated. As previous missions have shown, no matter how care-
fully a spaceflight crew is selected, screened, and medically
supported, illness, accidents, life support system malfunc-
tions, and logistic support problems may still occur. Though
every effort is made to limit these risks, a medical event that
exceeds onboard medical support capabilities should be antic-
ipated and programmed as far as possible. Risk analysis is the
first step in any medical contingency planning and is essential
to justify allocation of time and resources. Successful plan-
ning could determine the difference between serious inflight
morbidity or mortality and a favorable outcome with expedi-
ent and appropriate evacuation to a DMCF on earth.
Since human space exploration began with the launch of
Yuri Gagarin on Vostock 1 on April 12, 1961, more than 400
astronauts and cosmonauts have flown. Twenty-one fatalities
have occurred to date from five catastrophic events, along with
multiple other mishaps that could have potentially resulted in
fatality [16,17]. Launch aborts, aborts to lower than planned
orbits, and mishaps during reentry have each presented life-
threatening circumstances, and in several cases resulted in
fatalities. A chronology of these spaceflight events, including
flight contingencies, fatalities, near-fatalities, and significant
medical events, is detailed in Table 7.1 [18]. While this list is
not comprehensive, these events illustrate the complex human
hazards associated with the spaceflight environment and the
variety and nature of risks.
The range of events described in Table 7.1 illustrates the
medical scenarios that are addressed by three basic Design
Reference Missions (DRM) used by NASA as operational and
development guidelines for an emergency transport vehicle
[19]:
DRM-1Loss of crew return or re-supply capability, e.g.,
loss of nominal transportation vehicle (Shuttle or Soyuz
from the ISS)
DRM-2Escape from a time-critical ISS emergency, e.g.,
fire, decompression, environmental control system failure
DRM-3Full or partial crew return due to a medical
emergency
S.L. Johnston et al.
The DRM-3 or medical evacuation mission will be the pri-
mary focus of this chapter. A DRM-2 scenario also carries
the possibility of one or more crewmembers becoming ill or
injured while evacuating from a time-critical event such as
a fire, a contaminated station atmosphere, or a rapid decom-
pression. This requires a transport/evacuation vehicle to have
some stand-alone emergency medical equipment, along with
cabin purge and atmospheric scrubbing capabilities. Due to
airway reactivity from potential contaminant exposures, the
vehicles stand-alone medical kit should be heavily augmented
for respiratory problems. Such an event actually happened to
three American astronauts returning from the Apollo-Soyuz
mission in 1975. The Apollo crew was exposed to nitrogen
tetroxide (N2O4) gas when inadvertent reaction control system
(RCS) firings allowed the gas to enter the command module
through the cabin relief valve, which was open during landing.
All three crewmembers required 100% oxygen, anti-inflam-
matory medication, and bronchodilator therapy after landing,
and were hospitalized for chemical pneumonitis for three to
seven days.
Medical Event Risk Analysis
Using Analog, Mir Cosmonaut,
and Astronaut Populations
Epidemiological risk data obtained from ground-analog popu-
lations, cosmonauts in long duration space flight, analog mil-
itary and civilian populations, and data gathered by NASA
Medical Operations since 1959 on astronauts, provide a source
of representative medical events that might occur aboard a
space station. The extrapolation of ground-based data to the
space environment must be qualified for several reasons. At
best, ground-based study populations can be only rough ana-
logs to astronauts and cosmonauts. Space flight poses unique
operational and occupational risks that are not duplicated on
the ground and which are compounded by isolation from med-
ical attention and preventive measures that might be used on
earth. As a result, only approximate estimates can be made in
attempting to predict frequency and type of medical events
and their potential mission consequences in future LEO space
activities or during a voyage to the Moon or Mars.
To facilitate contingency planning, medical event incidence
rates, expressed as events per person-year, are generated to
anticipate the likelihood of a possible evacuation occurrence
for a crew of up to seven onboard the ISS. We consider three
examples of risk models derived from unique populations. The
first is a ground-based analog population representing medi-
cal evacuations from the U.S. National Science Foundations
(NSF) Polar Medicine Program at McMurdo Antarctic Sta-
tion [20]. The second involves hospitalizations among U.S.
astronauts from 1959 to the present. The third looks at actual
Russian cosmonaut inflight events and evacuation data from
1971 to 1999.
7. Medical Evacuation and Vehicles for Transport 141

TABLE 7.1. Spaceflight contingencies, morbidity and mortality, 19612003.

Date Mission Description
3/23/61 Soyuz ground test Cosmonaut Bondarenko died on March 23, 1961 in a spacecraft
simulator fire with 100% oxygen environment.
5/16/63 Mercury 9 Elevated CO2 levels and loss of power to control system, required
manual reentry.
3/18/65 3/19/65 Voskhod 2 Manual deorbit, and service module failed to separate during
reentry, landed 1,200 miles off target. Crew rescued next day.
3/16/66 Gemini 8 Docked vehicles rotated out of control near structural limits.
Crew landed earlywaited overnight before ocean recovery.
6/5/66 Gemini 9 Astronauts helmet faceplate continually fogged over during EVA,
impairing vision.
1/27/67 Apollo 1 Fire in crew module during ground test, with 100% oxygen environment.
Three crewmembers, Chaffee, Grissom, and White, perished.
4/24/67 Soyuz 1 Parachute system did not deploy after reentry; capsule destroyed on
impact, resulting in death of cosmonaut Komarov.
1/18/69 Soyuz 5 Spacecraft tumbled during entry, landing 2,000 km off target, with
hard impact. Cosmonaut had minor injuries.
4/11/70 4/17/70 Apollo 13 Mission to moon aborted after oxygen tank ruptured. Crew returned
safely. One crewmember developed urosepsis.
4/23/71 4/25/71 Soyuz 10 Failed docking with Salyut 1. During landing Soyuz air supply
became contaminated and cosmonaut lost consciousness.
6/29/71 Soyuz 11 Cabin pressure failure during reentry. Three crewmembers,
Dobrovolsky, Volkov, and Patsayev perished.
12/72 Apollo 17 Back strain from drilling core sample during walk on lunar surface.
4/5/75 Soyuz 18-A Launch vehicle malfunction, second stage abort subjecting crew to
nearly 20 +Gx. Crew landed in Eastern Russia, rescued the next day.
Crewmember suffered minor internal injuries.
7/24/75 Apollo-Soyuz Apollo crewmembers developed airway reactivity/pneumonitis from
toxic contaminants during reentry, requiring hospitalization
8/24/76 Soyuz 21/Salyut 5 Mission curtailed due to crewmember illnessrelated to
Environmental Control Systems problem
10/16/76 Soyuz 23 After failure to dock with Salyut 6, capsule landed in blizzard
conditions at night onto ice-covered Lake Tengiz; rescue team
unable to recover capsule until next morning.
11/11/82 Salyut 7 Acute abdominal pain probable kidney stone, resolved on-orbit.
9/26/83 Soyuz T-10 Launch abort due to pad fire, crew landed safely via capsule
escape system.
6/85 9/85 Soyuz T-13 Hypothermia and CO2 toxicity during reactivation of Salyut 7.
11/21/85 Salyut 7 Crewmember became ill with prostatitis and urosepsis. Return
to earth required 56 days into a 216-day mission.
1/28/86 STS-51L Solid rocket booster seal failure resulted in Shuttle destruction
73 s into flight. Seven crewmembers perished (Jarvis, McCauliffe,
McNair, Onizuka, Resnik, Scobee, Smith)
1987 Mir 2 Crewmember developed tachy-dysrhythmia during EVA, returned
early on next mission of opportunity.
6/91 STS-40 Freezer motor malfunction causing formaldehyde toxicity and
headaches, exacerbated by cabin noise
1995 Mir 18 Crewmember experienced episode of asymptomatic, sustained
ventricular tachycardia. No mission impact.
1995 Mir 18 Traumatic eye injury resolved with onboard treatment.
1996 Mir 22 One week preflight crewmember developed EKG changes and was
disqualified from the mission.
2/23/97 Mir 23 Fire due to oxygen generator; smoke and potentially toxic fumes in
station. Mild second degree burns and reactive airway changes.
Onboard treatment given.
1997 Mir 23 Three crewmembers experienced upper airway irritation and dermal
reaction following exposure to ethylene glycol.
6/25/97 Mir 23 Progress re-supply vehicle collided with Spektr module during
manual docking, resulting in station depressurization.
2/98 Mir 24 Three crewmembers exposed to elevated carbon monoxide, with
headache symptoms.
2/1/2003 STS-107 Space Shuttle Columbia was destroyed on entry, all crew were lost
(Anderson, Brown, Chawla, Clark, Husband, McCool, Ramon).

Source: Data from NASA records and Gonzales et al. [66]; Percy and Raasch [81]; Manley et al. [82]; Burluka and Dimitiadi [93].
142 S.L. Johnston et al.

Antarctic stations provide useful study analogs for TABLE 7.2. Incidence of medical evacuation events from McMurdo
space exploration programs. The Antarctic environment Station, Antarctica 19921996 (Total = 71).
is one of the most extreme on earth, with temperature and Category Number (%)
humidity at the South Pole more similar to that on Mars Trauma (by system) 34 (48%)
than to the rest of earth [21]. Like spaceflight missions, the Orthopedic 23
remoteness of Antarctic stations requires that they have Surgical 5
Dental 3
stand-alone medical care capabilities. Evacuation capa-
Ophthalmology 2
bilities are limited and may be non-existent for up to Neurology 1
eight months due to weather, seasonal lighting, and sea-ice Cardiopulmonary 8 (11%)
conditions. Additionally, their populations are medically Arrhythmia 2
screened and have epidemiological characteristics similar Angina 3
Pneumonia 1
to those of spaceflight populations [22,23].
Pulmonary embolism 1
Since 1954, the NSF Polar Program, with its three polar Lung carcinoma 1
stations, has averaged one fatality each year [24]. The larg- Dental Conditions 7 (10%)
est Antarctic station is McMurdo, typically with 1200 occu- Internal Medicine 6 (8%)
pants during the four austral summer months (November to Insulin dependent diabetes mellitus 2
Deep vein thrombosis 1
February) and 125 occupants during the eight winter-over
Other 3
months (March to October). The station has no evacuation Ob-Gyn 5 (7%)
capabilities during the winter season. In 1998, a physician at Breast disorders 4
the station was diagnosed with breast cancer and began che- Gynecology 1
motherapy treatment prior to evacuation. A dangerous winter Genito-Urological 4 (6%)
Kidney stone 1
airdrop of chemotherapy agents and ultrasound equipment
Testicular carcinoma 1
was partially successful, as only the chemotherapy agents Prostatitis 1
survived the drop to remain intact. This experience under- Urinary tract infection 1
scores the remoteness and inaccessibility of such a location Psychiatric 3 (4%)
and suggests a need for more than a single expeditionary Surgical 2 (3%)
Neurology 2 (3%)
medical officer to be trained, in the event this individual
becomes ill, injured, or otherwise incapacitated. Source: Data from: Billica et al. [28].
Medical evacuation rates at McMurdo Station have been
studied retrospectively over a five-year period from 1992
to 1996 [25]. Over five summer deployments, each of four
months duration, 71 total medical evacuations took place. than 48 h. By comparison, the approximate time required for
These are summarized by disease or pathology category in a Shuttle to be prepared on demand for a LEO emergency
Table 7.2. Each summer deployment (20 months cumulative evacuation attempt is likely to be not less than thirty days.
time) consisted of 1,200 individuals, yielding 2,000 total per- During the early design evaluations of Space Station Freedom
son-years for analysis. The incidence of medical evacuation and up to the Challenger tragedy of 1986, Shuttle evacuation
from McMurdo station is calculated as 3.55 evacuations per from the space station was considered an optimum method
operational month, equivalent to a five-year average annual of emergency crew return. However, later program reevalu-
incidence of 0.036 evacuations per person-year overall. ation assessed this option as no longer viable for emergency
With roughly comparable medical capabilities of McMurdo rescue [26,27]. It is apparent that an existing onsite return
station and ISS, the evacuation rates for the space station can capability, as with the Soyuz spacecraft on ISS, compared to
be approximated. Extrapolating from the Antarctic analog a requirement for dispatch of a rescue craft when a medical
population to a full ISS crew of seven yields an estimate event occurs, offers clear logistical advantages.
of approximately 0.25 evacuations from ISS per year. Thus, In many respects, the medical events that would necessitate
a possible evacuation event might be anticipated to occur evacuation from the Antarctic station are similar to several of
onboard ISS about once every four years for the full crew the serious medical events associated with space flight (Tables
complement in this model. 7.2 and 7.3) [28]. We can anticipate that treatment capabilities
Were a flight-ready aircraft maintained at McMurdo at required for rescue from the ISS will be roughly analogous to
all times, the ISS analogy would be more accurate. From those of McMurdo station, though there will be unique differences
McMurdo, minimal round-trip aeromedical transport time, due to microgravity. Both are isolated outposts, where rescue
from request for transfer to arrival at the referral DMCF in is difficult at best and impossible at times and where medical
Christchurch, New Zealand, is 20 h at best. Flight time by C- treatment will be required onsite. It should be noted, however,
130 Hercules aircraft is about 15 h, but due to weather, the that in the event of a medical evacuation, the Soyuz is not
need for ground preparation prior to transportation, and mar- comparable to a C-130 with dedicated medical equipment and
gin for equipment failure, actual transport time is often greater personnel onboard.
7. Medical Evacuation and Vehicles for Transport 143

TABLE 7.3. Representative non-fatal significant medical events during TABLE 7.4. ISS medical event classification.
space flight (19611999). Total = 20. (U.S. and Russian events summarized Class Description
from Table 7.1).
Class I medical event No mission impact, e.g. minor muscle strain.
Category Number of events Class II medical event Significant medical event requiring use of the
Trauma ISS HMS.
Orthopedic 1 Class II a Manageable with the HMS and not likely to
Skin exposure to glycol 1 require evacuation or affect mission dura-
Second degree burns 1 tion, e.g. prostatitis.
Other 1 Class II b Manageable with the HMS but may require
Cardiopulmonary the astronaut to return at next available
Dysrhythmias 3a opportunity for further evaluation and
Toxic inhalation/pneumonitis 3 treatment, e.g. breast mass.
Reactive airway disorders 3 Class II c Manageable with the HMS but may
Internal medicine necessitate emergent evacuation if condition
Chronic headache 1a does not improve or worsens, e.g. cardiac
Cellulitis upper extremity 1 dysrhythmia.
Other unspecified 1 Class II x An event unlikely to occur in a microgravity
GU environment or one that would be detected
Renal stone 1 in a pre-mission evaluation, e.g. herniated
Prostatitis 1a nucleus pulposis.
Urosepsis 2 Class III medical event An event requiring emergent evacuation from
the ISS, e.g. acute appendicitis, cerebral
a
Early crew return due to event in this category. hemorrhage.

Significant medical events occurring during space flight

have generally not been related to orthopedic or surgi-
cal trauma. More common, for example, are respiratory
problems due to atmospheric contamination in the closed
cabin environment. Morbidity from gravity-based events
on earth (e.g., falls) and other accidental injuries (e.g.,
motor vehicle accidents) is not represented in weightlessness.
Additionally, common metabolic conditions such as insulin-
dependent diabetes mellitus, which would have been noted
in the astronaut population by thorough pre-flight medical
screening and evaluation, are very unlikely to occur dur-
ing space flight of moderate duration. Medical screening
standards are therefore an important factor in medical risk
analysis and are discussed in Chap. 3.
An even more valuable study population than Antarctic winter-
over crew is of course the astronauts themselves, though the
astronaut population sample size is a limitation. A study con-
ducted in 1999 to estimate the occurrence, type, and severity
of injury and illness onboard the ISS used retrospective data
review of records from the NASA JSC Longitudinal Study
of Astronaut Health (LSAH) to characterize astronaut hospital-
izations [29]. The LSAH archives comprise hospitalization
data collected from 1959 to the present. A group of NASA
and Canadian Space Agency (CSA) flight surgeons evaluated
non-flight injuries and illnesses sustained by active astro-
nauts during normal activities. Classification criteria were devel-
oped according to likelihood, mission impact, and medical
management required if the disorder occurred during space
flight (Table 7.4). Each event was characterized according
to whether, if it had occurred inflight, satisfactory treatment
could have been accomplished utilizing the Health Maintenance
System (HMS), a component of the Crew Health Care System
(known as CHeCS), currently deployed on ISS.
The results, shown in Tables 7.57.7, describe the individ-
ual medical events. There were a total of 88 hospitalizations
distributed among active U.S. astronauts between 1959 and
1999. This 40-year time period represents a total of 2,715 per-
son-years. An estimate of potential evacuation events appli-
cable to the ISS setting can be made by subtracting from the
total hospitalizations the Class II x events (n = 13) that are
either unlikely to occur in a microgravity environment or that
would be detected and effectively screened out in a pre-mis-
sion evaluation. The anticipated evacuation incidence is about
0.02 events per person-year. If it is assumed that an onboard
HMS can be used to manage events that would otherwise
require evacuation (Class II c, n = 15) the anticipated evacua-
tion incidence is reduced further and may approach about 0.01
per person-year. In effect, availability of an onboard HMS can
significantly decrease the likelihood of a medically necessary
evacuation. The importance of a well-equipped and staffed
onboard medical system for risk mitigation is evident.
The most useful and directly applicable data for estimating
spaceflight medical evacuation risk stems from careful analy-
sis of actual spaceflight medical events. The Russian space
program has returned three cosmonauts prematurely for medi-
cal reasons in 41.5 person-years of space flight, resulting in
an overall rate of about one evacuation per 14 person-years.
Only one of these was from the Mir station, which operated
from February 1986 to May 2000, resulting in a Mir evacua-
tion rate of one per 31 person-years. Risk data from the popu-
lations discussed here, Antarctic station evacuations, LSAH
astronaut hospitalizations, spaceflight medical events, and the
NASA Medical Operations risk study [30,31] provide a basis
for estimating ISS evacuation event incidence rates for a seven
member crew (Table 7.8).
144
TABLE 7.5. Class IIa LSAH astronaut hospitalizations 19591999
(Total = 88).
Class IIa medical events (n = 17)
Ventricular tachycardia,
exercise-induced
Infectious colitis
Abdominal pain, right
lower quadrant
Internal hemorrhoids
Urinary tract infection
Severe epistaxis
Traumatic subluxation
of left shoulder
Neck pain
Cellulitis
Post-herpetic neuralgia
Fracture of the 4th metacarpal
Fracture of the 5th metacarpal
Fracture of the tip of terminal
phalanx
Freibergs disease (incomplete
fracture without displacement
of the fragments)
Cartilaginous loose bodies in joint
Minor superficial surgical
wound infection
Irritated compound nevus
Class IIc medical events (n = 15)
Traumatic pneumothorax
Hemopneumothorax
Pneumonia
Viral pneumonitis and pleuritis
Cardiac arrhythmia
Abdominal pain with bloody
diarrhea
Active duodenal ulcer
Cholelithiasis/chronic cholecystitis
Acute diverticulitis
Left flank pain
Hemorrhagic corpus luteum
Dysmenorrhea
Corneal ulcer
Shoulder dislocation
Septic arthritis of knee
Infectious mononucleosis
Abbreviation: HNP, herniated nucleus pulposis.
a
Class IIGround-based significant medical events requiring ISS HMS
intervention if occurring on-orbit.
Using the most conservative rates from the NASA Medical
Risk study, a Class II event (significant medical event requiring
the HMS, with potential for mission impact and or evacuation)
Class IIb medical events (n = 28)
Paroxysmal idiopathic atrial
fibrillation
Diarrhea, clostridium difficile
Menieres Disease (2)
Transient exercise-induced visual loss
Thyroid papillary carcinoma with
lymph node metastases
Thyroid nodule (2)
Asymmetric goiter
Paralysis of right vocal cord
Inguinal Hernia, left (1), right (3),
bilateral (1)
Testicular trauma with fluid collection
Impingement syndrome of shoulder
Left infrascapular Pain with paresthe-
sia of left fingers
Fracture of lateral malleolus
Fracture of 5th metatarsal
Anterior cruciate ligament tear (2)
Meniscus tear, medial (3), lateral (2)
Anterior talofibular ligament tear
Class IIx medical events (n = 14)
Near syncope
Incidental finding of anomaly of the
coronary artery
Fracture of the left 4th through 10th ribs
Cervical radiculopathy/cervical
spondylosis
Back pain/lumbar radiculopathy
Lumbar radiculopathy secondary
to HNP
C56 HNP and osteophyte
C7 radiculopathy secondary to HNP
Severe lumbosacral spasm
Comminuted fracture of left
radius & ulna
Compound fracture of left ankle &
right hand
Fracture of first 4 metatarsals
of left foot
Symptomatic buried hardware
in left foot
S.L. Johnston et al.
Table 7.6. Class IIIa LSAH astronaut hospitalizations 19591999
(Total = 15).
Class IIImedical events (n = 15)
50% total body surface area burn/30% third degree burn
Diffuse chemical pneumonitis from toxic inhalation (of nitrogen
tetroxide) (3)
Anaphylactoid reaction to intravenous tracer
Acute appendicitis
Ruptured retroperitoneal appendix
Pancreatitis/choledocholithiasis
Nephrolithiasis
Cholecystitis
Cholelithiasis
Retinal detachment
Cervical spinal stenosis with central cord syndrome
Cervical spondylosis with brown-sequard syndrome
Metastatic malignant melanoma
a
Class IIIGround-based significant medical events requiring evacuation if
occurring on-orbit.
Table 7.7. Categories of LSAH astronaut
hospitalizations 19591999.
Total hospitalizations 88
Trauma 14
Neurological 12
Gastrointestinal infections 9
Surgical 8
Pulmonary 7
Musculoskeletal 4
Other 34
can be expected to occur approximately once every 5.6 years
for a crew of three and every 2.4 years for a crew of seven
occupying ISS, while a Class III medical evacuation event
might be expected to occur one to three times during the
fifteen-year life of the ISS for a crew of seven. This latent
possibility, in fact, drove the initial development of a medi-
cal evacuation capability, as well as a requirement for an un-
suited configuration during return to allow airway access,
physiological monitoring, and intervention, where appro-
priate, none of which are currently feasible on the Soyuz.
This has resulted in NASA medical experts addressing the
requirements for more advanced treatment of ill and injured
crewmembers prior to return from the ISS on the Soyuz. It
is noteworthy that these estimates are based solely upon pri-
mary medical events and do not consider possible failures
of onboard life support systems or non-medical emergencies
such as vehicle system failures.
Standards of Medical Care in Space Flight
After examining evacuation risk, the next considerations are
the requirements and capabilities of space-based medical
care systems for long duration flight. Since NASAs Skylab
7. Medical Evacuation and Vehicles for Transport 145

Table 7.8. Evacuation estimates for ISS from ground analog and inflight populations.
Estimated yearly Estimated time
Evacuation events Estimated incidence evacuation rate between evacuations
Population (Events/person-years) (Events per person-year) (Evacuations/year) (Years/evacuation)
Analog
1. 19921996 McMurdo station
Total 71 71/2000 0.035 0.135 (3 crew) 9 years (3 crew)
0.249 (7 crew) 4 years (7 crew)
2. LSAH astronaut hospitalizations
Class IIc (15) and III (15) i.e. events requiring evacuation 30/2715 0.011 0.033 (3 crew) 30 years (3 crew)
0.077 (7 crew) 13 years (7 crew)
Inflight
3. Cosmonaut evacuations (primarily long-duration flight)
All events1959 to 2000 3/42 0.071 0.213 (3 crew) 4.5 years (3 crew)
0.500 (7 crew) 2 years (7 crew)
Medical events only 2/42 0.048 0.144 (3 crew) 7 years (3 crew)
0.333 (7 crew) 3 years (7 crew)
Mir station1987 to 5/2000 1/31 0.032 0.096 (3 crew) 12 years (3 crew)
0.226 (7 crew) 4.5 years (7 crew)
4. Astronaut evacuations (primarily short-duration flight)
1961 to 2000 0/19 0.000
5. NASA medical risk study
Likely mission impact/possible evacuation, Class II 0.059 0.177 (3 crew) 5.5 years (3 crew)
0.410 (7 crew) 2.4 years (7 crew)
Critical medical events Requiring evacuation, Class III 0.010 0.030 (3 crew) 35 years (3 crew)
0.070 (7 crew) 14 years (7 crew)

Source: Data from: Billica et al. [28].

program, this has been an ongoing process culminating in the
development of the CHeCS equipment for the ISS.
Physicians and medical support personnel have been involved
with flight since the earliest days. The French physician Jean-
Francois Piltre de Rozier was one of two crewmembers of
the first manned balloon flight in 1783. Aeromedical trans-
port as well has evolved throughout the history of flight. In
fact, the very first aeromedical evacuation took place in 1860
during the Franco-Prussian war when 160 wounded soldiers
were evacuated over enemy lines by hot air balloons. In the
United States, air evacuation began soon after the Wright
brothers flew in 1903. By World War II, the use of aircraft
to carry injured soldiers had become widespread, and flight
crews were being specifically trained for medical transport
[32]. Helicopter evacuation to Mobile Army Surgical Hospi-
tal (MASH) units began during the Korean War and contin-
ued in the Vietnam War era, with decreasing transport time
contributing to improved battlefield survival. By the 1970s,
civilian aeromedical emergency care began in earnest in the
United States. Since then, standards of care for the medi-
cal treatment, stabilization, and transportation of patients
by air have steadily evolved along with ground-based stan-
dards. Advancements in the fields of emergency medicine,
triage, and evacuation have contributed significantly to the
safety, efficiency, and acceptance of aeromedical transport.
Technical developments in medical sensors, equipment min-
iaturization, telecommunications, and emerging life support
and therapeutic modalities, along with advanced ambulance
capabilities, helicopter and fixed-wing aircraft designs, have
contributed to the utilization and success of aeromedical trans-
port. For those patients with moderate to severe non-mortal
injuries, emergency aeromedical transport is considered to
reduce risk of subsequent mortality by about 2550%, with
negligible added mortality risk from air accidents (0.006 per
transport) [21].
Terrestrial ground and air ambulance standards of care
are an appropriate starting point to develop standards for
Advanced Life Support (ALS) stabilization and transport/
evacuation capabilities for space flight. Human space flight
has always provided a means of return for crewmembers in
the event of an emergency. This may be the transport vehi-
cle itself, such as Apollo, Soyuz, or Shuttle, or in the case
of space stations, a dedicated return vehicle that is attached
and periodically rotated, remaining ready for use. The ISS,
like Mir, has used the Russian Soyuz vehicle for crew rotation
and contingency return capability. In the late 1990s, NASA
began design of a dedicated CRV, and for the long term, other
alternative vehicles such as the Orbital Space Plane were con-
sidered. The ALS standards of care for the ISS HMS and the
CRV evolved from standards of care set forth by the American
Heart Associations Cardiopulmonary Resuscitation (CPR)
and Advanced Cardiac Life Support (ACLS) programs, the
American College of Surgeons Advanced Trauma Life Sup-
port (ATLS) program, the U.S. Naval and NASA Hyper-
baric Medicine Teams, and the NASA Medical Operations
Advanced Projects Team.
146
Efforts to develop the equipment, techniques, and training
protocols for the delivery of emergent healthcare to an astro-
naut population in the unique environment of space have been
significant and ongoing at NASA JSC for many years. Ground
models, reduced gravity parabolic flights, and space-based
simulations have all been utilized in the development of ALS
capabilities [3336]. An ALS animal model for performing
parabolic-flight microgravity ACLS and ATLS research and
training has also been developed and is used to train flight
surgeons and provide supplemental training for crewmembers
of both the Shuttle and ISS [37]. These efforts have led to the
inclusion of limited ALS capabilities, including cardiac defi-
brillators, airway management items, and cardiac drugs on the
Mir station and the ISS [3840]. The ALS capabilities of the
ISS HMS are discussed further in Chaps. 4 and 5.
An inflight CMO or a ground-based flight surgeon must
address two paramount considerations in making a triage
decision:
1. The unique pathophysiologic conditions of a returning
crewmember
2. The capabilities and risks of the transport/evacuation vehicle
to be utilized
Several other elements contribute to the success of this decision.
First is the training of the designated crew medical officer
(CMO) in assessing an injured companion and the ability to
send a diagnostic evaluation to the flight surgeon. Currently
ISS crewmembers receive approximately 80 h of medical
training, enhanced where feasible with hands-on clinical
activities because the CMO is not a physician in most cases.
CMO training is a mix of basic and advanced medical topics.
Though crewmembers are trained in ACLS protocols, they do
not have the experience of a full-time practicing emergency
medical technician (EMT) or paramedic. Additionally, the
typically intensive training schedules that crewmembers fol-
low in the pre-mission phase may affect the completion of
their medical training.
A second element is readily available and secure tele-
communications. Contingencies must be addressed to man-
age medical events if these capabilities are not available at
all times to the crew, Mission Control, and the flight surgeon
[41,42]. Processes, procedures, and training are developed to
enable crewmembers to medically intervene without ground
support should this be necessary [4345].
The minimum standards for spaceflight ALS (Table 7.9) are
based upon U.S. standards for ground transport via ambulance.
These represent the desired capabilities of a first responder in
an ISS emergency care scenario. Projected medical capabilities
(Table 7.10) reflect the anticipated diagnostic and therapeutic
standards of care necessary for LEO, lunar, and planetary mis-
sion scenarios, derived from various working groups within
NASA Medical Operations. These are regularly updated to
incorporate advanced biotechnologies, medical informatics,
and enhanced CMO training and skills.
S.L. Johnston et al.
TABLE 7.9. Required medical capabilities for minimum care standards
on ISS.
Level of care Minimum capabilities required
Basic Basic CPR and first aid, including splinting and
bandaging
Intermediate Limited or modified ACLS, and ATLS capabilities:
Crew medical restraint system (CMRS)
Intravenous and intramuscular therapeutics
Electrocardiography monitoring
Defibrillation
Airway management including medical suction
Mechanical ventilation
Augmented Limited or modified hyperbaric treatment
(using the combined pressure of cabin and
EVA suit)
Advanced 24-h medical evacuation time to definitive medical
care facility with hyperbaric chamber capability.
Abbreviations: CPR, cardiopulmonary resuscitation; ACLS, advanced cardiac
life support; ATLS, advanced trauma life support; EVA, extravehicular activity.
Pathophysiology of Deconditioned
Returning Crewmembers
Another step in the delineation of spaceflight medical trans-
port and evacuation capabilities requires discussion of the
deleterious effects of microgravity exposure on the physi-
ologic state of a crewmember returning to a one-G environ-
ment. Chap. 2 addresses the known physiologic changes from
long duration exposure to microgravity [46]. This section will
summarize the pathophysiologic state encountered during the
transition from zero G to one G and greater, occurring during
the medical transport of an ill or injured crewmember to an
earth-based DMCF.
During re-adaptation to earth gravity, three physiological
systems are significantly compromised: (1) musculoskeletal,
(2) neurovestibular, and (3) cardiovascular. These physiologic
decrements produce serious functional and performance limi-
tations for returning deconditioned crewmembers [47,48].
Returning from missions of up to 14 days, such as are typical
for Shuttle and ISS Soyuz taxi flights, most crewmembers are
sufficiently readapted to be able to walk satisfactorily, though
with a slightly abnormal gait, within 3060 min following
landing. During the NASA Skylab and Shuttle-Mir programs,
involving long duration flights of one to several months,
returning crewmembers were occasionally unable to ambulate
normally for several hours, due to neurovestibular and car-
diovascular compromise, made worse by the musculoskeletal
deconditioning accompanying weightlessness.
From these limitations arise many of the human system
engineering requirements for a dedicated crew return vehicle
(CRV), which are described later in this chapter. The influence of
these effects on design can be illustrated as follows:
7. Medical Evacuation and Vehicles for Transport 147

Table 7.10. Projected Medical Capabilities for Low Earth Orbit and Beyond (Moon, Earth/Sun and
Earth/ Moon Libration Points, and Mars)
Advanced Life Support Capabilities CMO Training
Time to DMCF - 24 hours
LEO (ISS) Skill Level
Specialized Restraint Systems Emergency Medical Technician
IV/IM Medications
Oral & Endotracheal Airway /Cricothyrotomy
Automated Pneumatic Ventilator
Blood Pressure Monitoring and Pulse Oximetry
BLS protocols
Informatics/Telemedicine remote medical direction Paramedic
Defibrillator with external cardiac pacing
ECG Monitoring
IV Fluids
Modified ACLS & ATLS protocols
Hyperbaric Treatment Physician
Ultrasonography (Abdominal, Cardiac, Thoracic)
Lunar Missions / Stable Lagrangian Platforms
Time to DMCF - Days to Weeks
LEO / ISS capabilities with augmented supplies Physician and Paramedic
Radiation Shelter -or-
Paramedic and Paramedic with advanced training
Mars and Other Expeditionary Missions
Time to DMCF 9 to 30 months
Lunar capabilities with augmented supplies Physician (with surgical training) and Paramedic
Stand-Alone Capabilities: -or-
Limited Surgical Intervention Physician and Paramedic with advanced training
Banked or Synthetic Blood
Banked Bone Marrow
Informatics/Expert Systems/Clinical decision-support tools
Radiographic / MRI Diagnostic Imaging
Recuperation and Convalescence Capabilities
Abbreviations: ACLS, Advanced Cardiac Life Support; ATLS, Advanced Trauma Life Support; BLS, Basic Life Support;
CMO, Crew Medical Officer; CPR, Cardio Pulmonary Resuscitation; CMRS, Crew Medical Restraint System;
DMCF, Definitive Medical Care Facility; ECG, Electrocardiograph; EMT, Emergency Medical Technician; IM, Intra
Muscular; IV, Intra Venous; LEO, Low Earth Orbit.

Musculoskeletal System Limitations Cardiovascular System Limitations

In designing any manually actuated mechanism such as a crank
or switch for the opening of an emergency hatch on landing
that might be operated by any crewmember, the maximum
torque required has been calculated based on a 20% loss of
upper extremity muscle strength for a fifth percentile Japanese
female (NASAs anthropometric design range limits are to
accommodate a fifth percentile Japanese female up to a 95th
percentile U.S. male).
Neurovestibular System Limitations
In designing crew and piloting command capabilities for
obstacle avoidance and maneuvering during landing of a CRV,
head and eye movements, particularly rapid ones, must be
minimized due to delayed target tracking and possible inca-
pacitating Coriolis-like effects.
Returning crewmembers, due to their orthostatic intolerance,
must be placed in a recumbent position to minimize the +Gz
forces present during reentry and landing. This may preclude
steps that would nominally require the crew to assume an
upright posture.
The immediate re-adaptive state of deconditioned long
duration crewmembers (> 30 day) upon reentry and exposure
to a one-G environment is illustrated by the extent of physi-
ological decrement (Table 7.11) and their general physical
condition and overall appearance.
Of even greater concern is the return to Earth of an ill
or injured crewmember in a severely compromised physi-
ologic state. Some returning long duration crewmembers
may be unable to make any physical effort on their own
behalf, and their physiologic responses may be altered.
This is an area where more research is necessary to understand
148
Table 7.11. Typical physiologic decrements associated with long
duration space flight.
Musculoskeletal strength
Upper extremitiesaverage decrease 20%
Lower extremitiesaverage decrease 40%
Paravertebral / spinalaverage decrease 40%
Weight-bearing bone mass decreased on average 12% for
each month on orbit
Neurovestibular readaptation
Target acquisition delayed >2 s, limiting fine motor control
Neuro-kinesthetic/positional
Rapid head movement may cause incapacitation
Nausea and vomiting
Cardiovascular/orthostatic intolerance
Intravascular volume loss 612%
Syncope possible with exposure to positive Gz forces on entry and standing
Baroreceptor/autonomic nervous system dysfunction
Decreased cardiac muscle size and filling
Source: Data from: Space Biology and Medicine [46]; Bioastronautics Data
Book [47]; Nicogossian et al. [48].
basic physiologic responses of the deconditioned organism
to pathologic processes following exposure to long duration
microgravity. It is reasonable to surmise that some other-
wise healthy, returning, deconditioned crewmembers, on
exposure to reentry and landing acceleration forces, may
be unable to aid another crewmember, may be unable to
egress their seat for thirty minutes to several hours, and
possibly may be completely incapacitated. This degraded
physiologic state poses severe limitations for high G bal-
listic reentry, water landing, and unaided vehicle egress.
Some of these changes may have a significant effect on
performance in relation to crew emergency operations. There
are particular difficulties for pilots in the situation, however
unlikely, that automated control systems fail to function nor-
mally. Control of the spacecraft may require a number of
human abilities including arm-hand steadiness, finger dexter-
ity, hand-eye coordination, perception speed, and rapid reac-
tion time against a background of decreased motor function
and the effects of prolonged weightlessness and confinement
[49]. For example, the significant changes that occur in the
accuracy of psychomotor performance combined with the
postural changes that occur in response to weightlessness
result in a tendency to past point until adaptation occurs [50].
This decrease in dexterity can pose potential problems for the
manipulation of control panels, displays, and mechanical sys-
tems during an emergency return to earth [51]. However, for
standard Shuttle missions of up to 18 days, manual control of
landing has been routinely and successfully accomplished.
The decision to utilize an unscheduled or emergency return
may be problematic both medically and logistically. A crew-
member with compromised cardiac function could be placed
at increased risk by returning to earth prematurely follow-
ing a cardiac event. This must be taken into consideration
when deciding whether to recuperate in LEO before transport
to a DMCF. For example, the deconditioned crewmember
S.L. Johnston et al.
suffering a myocardial infarct several months into a LEO mis-
sion would be further compromised if returned while in the
acute injury phase. LEO evaluation and rehabilitation with
low levels of artificial gravity from a human centrifuge might
be the therapy of choice, rather than immediately subjecting
the patient to the insults and risk of reentry and landing, with
their associated acceleration forces. However, the capabil-
ity and the personnel must be onboard to provide supportive
treatment and facilitate such a course of action.
Psychological Deconditioning
of Returning Crewmembers
In an emergency situation crewmembers are called upon to act
with decisive, clear, and correct actions to prevent a crisis from
deepening and to preserve their own lives and the lives of their
colleagues. These and other aspects of functioning in space relat-
ing to the human-machine interface and the crews living and
working environment may affect their capabilities, and so present
some of the most significant challenges for an ISS crew. These
psychological effects directly relate to the problems of emer-
gency medical capabilities, particularly in light of the addi-
tional physiological stresses that such situations may place on a
crew. The adverse effects of confinement, isolation, noise, envi-
ronmental challenges, and the group dynamics associated with
these situations, have been well documented in analog situations
such as the Antarctic and on submarines [5254]. Additional
psychological stressors may arise from limited communica-
tions, on-orbit equipment failures, difficult living conditions,
and high workloads, particularly in emergencies. These may
be compounded by crew interpersonal tensions, multi-cultural
issues, lack of privacy, and deprivation of the usual sensory and
motor stimulation [55]. In space, isolation can lead to sleep dis-
turbances, headaches, irritability, anxiety, depression, boredom,
restlessness, anger, homesickness, and loneliness. These physi-
ological findings are particularly relevant to the actions and per-
formance of crews in emergency medical situations, where time
is of the essence and effective leadership and decision-making
are paramount. These issues are further discussed in Chap. 19.
Human Factors Challenges
of Crew Return Vehicle Design
For any crew return vehicle, there are substantial human fac-
tors challenges in designing the environmental systems, seat
and cockpit configurations, medical systems, restraint sys-
tems, and extraction capabilities for the transport of crewmem-
bers within NASAs required anthropometry range. The CRV
concept is used here as a generic reference design to discuss
vehicle attributes in support of medical evacuation capability.
These investigations and findings will facilitate incorporation
of desirable attributes into new vehicle programs.
7. Medical Evacuation and Vehicles for Transport
The current formal ISS program requirement is to accom-
modate the fifth percentile Japanese female to a 95th percentile
U.S. male [56]. These affect not only the design of the vehicle
as a whole but also individual activities such as flight control
and medical support. A primary driver for a crew return vehi-
cle is the requirement to accommodate a shirt-sleeve envi-
ronment if needed, due to the urgency of its mission, the need
to have access to the patient, and the time and difficulty of
donning pressure suits in a small, enclosed volume. This will
facilitate a more environmentally and user-friendly cockpit
operable without the mobility restrictions imposed on suited
crewmembers.
Unique limitations in the CRV affect how the CMO provides
medical care to the patient, including restricted motion due
to the forces of reentry. These limitations drive requirements
for medical equipment controls and supplies that are posi-
tioned to allow access to the patient and monitoring equip-
ment during different phases of flight. A returning crewmember
requiring respiratory support can serve as an example. If a
patient is being manually ventilated via bag mask, the CMO
in the CRV will encounter difficulty sustaining this once per-
ceptible acceleration forces are encountered. However, if the
patient is mechanically ventilated, the CMO could adjust the
settings with the aid of remote access to ventilator controls
and readout. This situation arises due to the seating limitations
that will place the CMO in a reclined position and therefore
unable to reach over to the patient. Additionally, human fac-
tors play an important role in the design of less complex com-
ponents. For example the patients restraints must be activated
and adjusted by another crewmember [57,58]. The design of
the CRV patient restraint system must consider these factors,
including the provision of an interface for advanced life
support equipment, such as a ventilator, defibrillator, oxygen
supply, and intravenous (IV) infusion [59,60].
The crewmembers degraded condition will also drive search
and rescue (SAR) team requirements such as response time
and medical capabilities. In particular the crew may be unable
to extract themselves from the vehicle after landing; therefore
the SAR team must be familiar with aspects of spaceflight
deconditioning and utilize appropriate crew extraction tech-
niques. The internal layout of the CRV should also facilitate crew
extraction, with the CMO and the patient situated directly
under the hatch opening. Optimally, this would mean that they
are last to enter the vehicle and first to leave it.
The NASA JSC Graphics Research and Analysis Facility
Laboratory uses three-dimensional modeling to determine the
minimum space necessary for crewmembers in various pre-
dictable activities. While there is arguably an ideal volume
required to execute a rescue mission, the designers are usually
required to work with the fixed volume and constraints of a
specific vehicle. With vehicles such as the Soyuz and X-38,
the volume available is considerably reduced due to the limita-
tions of the vehicle shell, internal equipment and supplies, and
the operator functions. For comparison, habitable volumes of
various vehicles are shown in Table 7.12.
149
Table 7.12. Habitable volumes for various spacecraft.
Habitable Volume per
Vehicle volume (m3) Crew crewmember (m3)
Space shuttle orbiter 65.8 7 9.4
Apollo command module 6.2 3 2.1
Mercury spacecraft 1.7 1 1.7
Proposed X-38/Crew 12.2 7 1.7
Return Vehicle
Soyuz descent module 4.0 3 1.3
Gemini spacecraft 2.6 2 1.3
Ground ambulance 11.0 2+ patient 3.6
box type
Designers of a crew medical rescue system should also
be aware of the requirement to implement protocols and
procedures in an international and multicultural environment
[6164]. These should be clear, intuitive, and perhaps more
visually oriented to optimize understanding by an individual
working in a second language. Finally, a crew return capa-
bility for medical emergencies requires the development of
procedures and checklists. Applying usability and human fac-
tors analysis to evaluate medical procedures will ensure that
crew performance is maximized and not affected by a poorly
designed interface. This will enable an easier, more accurate
and rapid response from the crew, thereby enhancing safety and
increasing the likelihood of a successful outcome [65,66].
Risks in Aeromedical Transport
and Evacuation
Factored into any decision to use aeromedical transport must
be the added risk inherent in evacuation and transport itself.
Sometimes, this added risk outweighs any marginal benefit of
immediate transport. EMS medevac, rescue operations, and
hospital transfers are not risk-free, and injuries occur each
year. However, the aeromedical transport fatality rate due
to air mishaps is quite low, approximately six per 100,000
transports [20]. There will be occasions, given the hazards of
the evacuation process and availability of onboard medical care,
when definitive treatment may be deferred despite evacuation
capability. For example, aboard commercial ocean freight-
ers or cruise ships, patients with acute abdominal processes,
such as acute appendicitis, are seldom evacuated by air even
when within helicopter range but are often managed
non-operatively and may be transported ship-to-ship before
definitive land-based care is reached [67].
Many aircraft have been adapted to the air ambulance role,
each with its strengths and limitations. The unique require-
ments of spaceflight medical transport present an opportunity
to design a dedicated transport vehicle with medical capabili-
ties de novo. As in design of air ambulances, factors such as
cabin space and environment, access for patient loading, use-
ful load, weight and balance, and flight performance must be
carefully balanced. Emergency medical transport and evacuation
150 S.L. Johnston et al.

from an orbiting space vehicle clearly carries additional risks
as well. While it is difficult to assess these risks given the
limited current experience base, they may be viewed as occur-
ring along an evacuation timeline, with each phase presenting
unique environmental hazards and corresponding risks. The
major risks and suggested mitigation actions are outlined in
Table 7.13.
NASAs Crew Return Vehicle Development
The need for an evacuation capability from a LEO space sta-
tion derives from basic principles underlying escape and egress
systems of the earliest manned spacecraft [6872]. In 1957
before humans were launched into orbit, Petersen [73] and
Romick [74] proposed earth-based designs for crew recovery
from disabled manned space vehicles. The following year in
1958, Elricke Krufft of NASA presented a paper concerning,
the considerations required in the use of a lifeboat for space
operations [75]. He suggested that a possible solution to the
rescue of astronauts in a stricken space vehicle could involve
the use of another vehicle already in space for the specific pur-
pose of early unplanned return. As early as 1963 the problems
of interoperability and lack of commonality were acknowl-
edged in a paper by Jack James [76], which states; Many
of the future problems involving space rendezvous may be
largely avoided by the early development of a universal, all
service, all vehicle docking/coupling mechanism. Improved
crew safety and mission reliability are by products.
From the beginnings of the space age, engineers and sci-
entists have made conscious efforts to minimize the inherent
danger to humans from the space environment. Indeed with
the launch of Gagarin in Vostok 1 on April 12 1961, the mis-
sion was planned such that in the event of a human or mechan-
ical malfunction the vehicle would automatically re-enter the

Table 7.13. Risks associated with spaceflight medical evacuation and transport.
Timeline event Risks Risk mitigation design factors
Decision to transport/evacuate Delayed or premature decision Anticipate possible scenarios
Incorrect decision (e.g., medical condition likely to Establish standing flight rules to guide decisions
worsen with evacuation)
Major mission impact Allow real-time crew decisions independent of ground support
if communication fails
Cabin environment Space-limited medical access for monitoring, proce- Cockpit configuration
dures, and resuscitation Evacuation timeline
Non-suited configuration is zero-fault-tolerant cabin Life support system consumables adequate to evacuation
environment to entire CRV crew for depressurization timeline
or toxic atmosphere event Crew time constraint of ~3 h from departing station to landing
Medical capabilities of vehicle Suited configuration limits medical access, especially Design allows unsuited transport; seat design allows CMO
for airway management and resuscitation access to patient.
Autonomous reentry Limited landing opportunities Large cross-range capability, along with deorbit opportunity
every 2 or 3 orbits
Thermal, noise, and vibration issues Low entry G profile
Acceleration profile on re-entryNominal vs. ballistic Autonomous, unpowered return
Chute deceleration effects Controlled re-entry G limits: 4 +Gx, 1 +/Gy, 0.5 +Gz
Landing Limited sight and obstruction avoidance May be autonomous
Land impact vs. water impact Inertial Navigation System, Global Positioning
System guidance
Potential impact injuries Steerable parafoil to limit landing speeds
Landing site selection & navaids
Recumbent crew seating
Landing impact attenuation system
Egress and rescue Impaired performance in one G due to deconditioning Prelanding Countermeasures
Fluid loading
Unaided egress may not be possible Pharmacologic, sympathomimetics

Land vs. water egress

Remote environment exposure anti-G-suits

Risk to Search and rescue (SAR) personnel

Evacuation to DMCF
Crew survival training
unplanned deployment, toxic propellants, unspent SAR readiness and exercises
pyrotechnics
SAR/ground force availability and response time
Additional transport event Medical Operations Contingency Support and Implementa-
tion Plan to define requirements for U.S. and international
emergency landing sites.
Medical facility capabilities at landing site may be
diminished
7. Medical Evacuation and Vehicles for Transport
Earths atmosphere after 10 days even if the retro-rockets
failed to fire. Food supplies for the same period were carried
onboard. As such, the vehicle was automated except for the
need for Gagarin to orient it for the de-orbit burn. Like other
Vostok pilots, Gagarin ejected from the craft before touch-
down to ensure a safe return.
The escape system concepts that have been developed for
earth return fall into two broad classes; lifting bodies and bal-
listic entry types [77,78].
Lifting Bodies
Lifting body spacecraft are considered to have several advantages
over other vehicle types. With expanded cross range afforded
by the wing and lifting surface, the number of available land-
ing opportunities to specific sites is increased. Acceleration loads
during entry may be limited to about 1.5 G. Both qualities are con-
sidered important when returning ill, injured, or deconditioned
space station crewmembers to Earth. Additionally, wheeled run-
way landings are possible, permitting simple, precision recovery
at many sites around the world [11,79].
NASA began with the Dynamic Soaring Vehicle (Dyna-
Soar) X-20 program, conceived in the 1940s after the capture
of research produced by Nazi Germany based on the propos-
als of E. Sanger in the 1930s. The Dyna-Soar program ran
from 1957 to its cancellation in 1963. This precursor of the
Space Shuttle, intended for a variety of peaceful missions by
the USAF and NASA, including space rescue, was designed
to land on a runway. The Soviet Union began to investigate
lifting bodies for space applications in the 1960s with the
Spiral program, in response to the USAF Dyna-Soar proj-
ect. The NASA Langley Vehicle Analysis Branch began the
development of the HL-10, M2-F3, and X-24 lifting bodies
in the 1960s and in the 1980s the HL-20 Crew Emergency
Rescue Vehicle, a proposal to backup or replace the Shuttle
after the Challenger accident in 1986. A full-size engineering
research model of the HL-20 was constructed for studying
crew seating arrangements, habitability, equipment layout,
and crew ingress and egress [80].
FIGURE 7.1. The X-24a Lifting Body (A) developed and tested during the 1960s, and the X-38 (B) under consideration at one time as a rescue
vehicle for the International Space Station (Photos courtesy of NASA).
151
In the 1980s NASA had expended considerable effort
to determine the need for escape and rescue provisions of
manned space stations [81,82], particularly for the planned
Space Station Freedom, and the Assured Crew Return Vehicle
(ACRV) program. With the transfer of NASA space station
efforts from the Freedom program to the ISS, crew return con-
cepts shifted once again. With the X-38, NASA had consid-
ered another lifting body design, based on the X-24 lifting
body shape. The X-24 was originally developed in the 1960s
as part of the USAFs Maneuverable Entry Research Vehicle
(MERV) effort, flown as a precursor to the subsequent Space
Shuttle Program. The X-38 CRV concept drew heavily on the
findings of this program (Figure 7.1).
NASAs CRV program involved an innovative new space-
craft designed to return up to seven crewmembers to earth
from ISS. The mission profile included launch to orbit in
the Space Shuttle payload bay, then docking to the ISS and
remaining in a standby condition until needed for a contin-
gency return. Following the de-orbit burn and jettison of the
engine module, the vehicle would glide unpowered from orbit
and then use a steerable parafoil parachute for its final descent
to landing. Though its primary use is as an emergency life-
boat, the CRV could be modified for other uses, such as an
international transfer spacecraft that could be launched on
other boosters like the European Ariane 5. It is envisioned that
this vehicle could provide the capability to evacuate all seven
members of a full ISS crew. The operational vehicle dimen-
sions of the CRV as planned were a length of 9.14 m and a
width of 4.42 m, which enabled it to fit into the Shuttle bay.
The internal volume as planned was 11.8 m3 with a mass of
11,340 kg [82].
Ballistic Vehicles
The earliest planned U.S. space station, the USAF Manned
Orbital Laboratory (MOL), intended to use a Gemini capsule
for primary transportation and emergency return to earth.
Although this program did not materialize, the subsequent
Skylab program utilized the three-crewmember Apollo capsule
152 S.L. Johnston et al.

in a similar fashion. A modification of the Apollo Capsule
was evaluated to accommodate six crewmembers in the event
that an Earth-originated rescue was needed. This capsule was
later considered as part of the early post-Challenger ACRV
studies [19]. In the late 1980s the European Space Agency
(ESA) developed the concept of an Apollo type capsule for
use as a potential Crew Rescue Vehicle during studies for the
free flying Columbus European Space Station (ESS). The
main mission of the permanently docked Escape Vehicle was
to allow the evacuation of and separation from ESS, followed
by safe return to earth and recovery of the entire crew by
ground teams [83,84]. Subsequent to the Challenger accident,
the Crew Emergency Return Vehicle office was established at
NASA Johnson Space Center to examine alternatives to using
the Shuttle as a main rescue vehicle [85]. One such develop-
ment by the JSC engineering team was the Simplified Crew
Rescue Alternative Module (SCRAM), conceived as a low
cost water lander configured to seat up to eight crewmembers
and to sustain them for 24 h [86]. The vehicle consisted of a
pressurized crew module to be attached to the ISS with an on
orbit life of up to 10 years once delivered. The aim was to
use compatible tried and tested technology and existing search
and rescue capabilities to minimize operational costs.
the ISS. Originally conceived to dock with a booster stage in
orbit, thereafter to be propelled around the moon, Soyuz was
later modified to fly crews to earth-orbiting Space Stations
such as Salyut and later Mir [90]. In this capacity, it has served
reliably and safely for over three decades with the exception of
the decompression event of Soyuz 11 in 1971, which prompted
re-design efforts and operational protective measures.
Russian and NASA Crew Return Vehicle
Capabilities
As of this writing, the only human-rated transport spacecraft in
current use are the U.S. Space Shuttle and the Russian Soyuz.
In 1992 the United States considered the modification of Soyuz
capsules to fit the U.S. astronaut population for use as a crew
return vehicle [91]. Designed for use as a commuter spacecraft
to shuttle to and from a large orbiting station, its habitable
volume is only 4 m3 in the descent module compartment.
Therefore, the design of the baseline Soyuz descent module has
serious limitations for medical missions (Figure 7.3).

Soyuz
The Russian Space Agency has provided escape and rescue
capability with a Soyuz spacecraft permanently available at
the Salyut and Mir Space Stations [8789]. The Soyuz is the
default return vehicle for the ISS in the assembly phase
(Figure 7.2). Designed in the 1960s, the first manned Soyuz
flight ended in tragedy with the death of Vladimir Komarov
on April 24th 1967, due to failure of the landing chute to
deploy. Despite this setback, the problem was resolved, and
the vehicle was made operational. Soyuz accumulated a sub-
stantial field history before being upgraded beginning in 1980
with the Soyuz T. From 1987 onwards, the TM series Soyuz
has been operational and has supported missions to Mir and

FIGURE 7.2. The Soyuz TM vehicles with the basic Soyuz design
have successfully ferried crews to and from orbital space stations for FIGURE 7.3. Details of the Soyuz Descent Module showing the tight
three decades. quarters, with crewmembers positioned in the launch and landing couches.
7. Medical Evacuation and Vehicles for Transport 153

Table 7.14. Selected anthropometry and mass limits for the Soyuz to a loss of pressure scenario. Each option has distinct features,
TM, Soyuz TMA, and NASA Space Shuttle. advantages, and disadvantages.
NASA limits The Soyuz and the Shuttle are flight-proven operational
Soyuz TM Soyuz TMA (Space Shuttle) transport vehicles. A crew return vehicle would be developed
Min standing 164 (64.6) 150 (59.0) 148.6 (58.5) in part as a dedicated medical evacuation spacecraft, designed
height cm (in.) with a priority on specific medical requirements and human-fac-
Min seated 80 (31.5) 80 (31.5) Not defined
tors concepts as high priority. This has a significant influence
height cm (in.)
Min weight 50 (110) 50 (110) 40 (88) on the type of medical monitoring equipment that can be used
kg (lbs) and the level of intervention possible during free flight after
Max standing 182 (71.7) 190 (74.8) 193.04 (76) undocking from the ISS. In terms of medical equipment and
height cm (in.) supplies available for patient treatment, the Soyuz and a future
Max seated 94 (37.0) 99 (37.8) Not defined
CRV or OSP are quite different. Differences in available medical
height cm (in.)
Max weight 85 (187) 95 (209) 109.32 (241) equipment and capacity to manage particular medical scenarios
kg (lbs) for each vehicles configuration are shown in Table 7.15.
With further assessment of the relative capabilities of the
suited and un-suited configurations for different types of medical
events, we can better estimate an overall relative capability
The Soyuz also accommodates a limited range of crew- of one versus the other. To this end, a panel of NASA Flight
member height and weight, compared with NASAs anthro- Surgeons estimated the relative projected medical care capa-
pometric design limits (Table 7.14) [56,92]. The data gathered bilities for specific events, by quartiles, of the suited versus
and maintained by the NASA JSC Anthropology laboratory unsuited configurations (Table 7.16). For each medical event
derived from the Astronaut population during crew selection category, an overall fractional capability of the suited configu-
assessments. Because initial astronaut selection criteria were ration relative to the unsuited configuration can then be made
based on U.S. vehicles, a significant fraction of the U.S. astro- (assuming equal event frequencies within each category). This
naut population would not fit in the standard Soyuz TM. Sev- is shown in Table 7.16 as Estimated % Relative Capability
eral studies have been performed on the spacecraft to widen for Category. When this relative capability is weighted by
the anthropometry envelope and better understand how these the incidence of each medical event category, an overall rela-
limitations might affect its role in medical transport. These tive capability of the suited configuration is estimated to be
studies have led to Soyuz modifications such as elevating the approximately 54%. In other words, the suited configuration
main instrument panel to accommodate the legs and knees of during return to earth does not provide appropriate capability
taller crewmembers, seat changes to allow better musculo- for handling about one-half of the potential events that would
skeletal support of injured crewmembers, and stowage changes prompt medical return. This overall estimate agrees well with
to accommodate medical equipment. This most recent round prior published estimates of 60%.
of upgrades has produced the Soyuz TMA, which entered ser- For critical respiratory and circulatory events, the medical
vice in 2003. NASA astronauts who fly on the Soyuz, and mission capabilities of the suited configuration are only about
initial ISS crews, who will depend upon it as an emergency 17% and 10%, respectively, of the unsuited (CRV) configura-
return vehicle, must be selected based on Soyuz anthropomet- tion. This degraded capability for respiratory and circulatory
ric requirements [93].

Table 7.15. Medical capabilities in transport and evacuation from

Patient Accessibility and Treatment the ISS: Suited vs. unsuited.
Capabilities Un-suited (Crew
Medical capability Return Vehicle) Suited (Soyuz-TM)
The differences between the Soyuz and the Shuttle are largely Patient assessment limited minimal
a result of the internal volume, equipment accessibility, and Exposure/airway access present minimal
Patient restraint device/ present with possible
crew station and seat layout. For any spaceflight medical cervicalspine restraint patient restraints
transport and evacuation vehicle, required use or non-use of Second provider assist possible minimal
a full pressure suit is one of the most fundamental crewmem- Advanced life support pack sub-packs some supplies
ber configuration decision points. This choice affects vehicle Diagnostic equipment present minimal
design, flight medical hardware, and projected medical procedure Pharmaceuticals present limited
Intravenous fluids present possible
capabilities. Clearly, a cabin environment that permits an ill or Oxygen supply100% ventilator & mask suit
injured crewmember to return to earth in an un-suited, shirt- Cardiac monitor present possible
sleeve setting allows better access for medical monitoring Defibrillator, blood pressure present minimal
and intervention. On the other hand, a pressure suit provides monitor, pulse oximeter
enhanced livable atmosphere protection and fault tolerance Survival kit (post landing) present present
154 S.L. Johnston et al.

Table 7.16. Projected relative medical capabilities of suited (unmodified any evacuation scenario. The estimated combined crew
Soyuz-TM) vs. unsuited (CRV) configurations. risk of a medical event potentially requiring evacuation is
Incidence Estimated % rela- Incidence- about 0.06 multiplied by 3, or 0.18 per person-year, that is,
Medical event requiring (per 100 tive capability for weighted suited an anticipated evacuation about once in five or six years.
transport/evacuation person-yrs) category % capability
This estimated risk is comparable with that from actual Rus-
Trauma and toxicity 1.72 66% 19%
sian spaceflight experience. Beginning with the assembly
Anaphylactic reaction
Respiratory depression complete phase, marked by crew occupancy of seven indi-
Major fracture viduals, we may anticipate a combined crew medical event
Gastrointestinal 0.87 50% 7% evacuation risk of 0.06 multiplied by 7 crewmembers, or
Severe gastroenteritis 0.42 per person-year, or about once in 30 months. For criti-
Ileus
Appendicitis
cal, life-threatening respiratory or circulatory events consid-
Pancreatitis ered independently, the combined risk estimate is about one
Cholecystitis evacuation in 14 years, or effectively once during the design
Neurologic/psychiatric 0.8 46% 6% life of the station. Thus anticipating the occurrence and type
Vertigo
Psychosis
of a significant medical event onboard a space station drives
Seizure activity the necessary implementation and design of that stations
Intracranial bleed evacuation and escape system.
Cerebral aneurysm
Cerebrovascular
accident
Respiratory 0.60 17% 2% Medical Requirements for a NASA
Pneumothorax
Pneumonia Crew Return Vehicle
Toxic pneumonitis
DCS chokes CRV type vehicles must meet well-established baseline require-
Reactive airway ments for human crew operations. Documented requirements
Airway obstruction
Respiratory arrest parameters include vehicle and system performance, envi-
Acute respiratory ronmental control specifications, human factors guidelines,
distress syndrome medical limitations, and mission support requirements [94].
Pulmonary embolus The aim of medical requirements is to ensure that a vehicle
Circulatory 0.43 10% 1%
Dysrhythmia
built to transport ill or injured crewmembers will meet the
Coronary disease/ minimum standards for patient care during a return mission
angina from the ISS. It is vital to the success of the CRV program that
Myocardial infarction these requirements are clearly defined and fulfilled. Based
Shockhypovolemic on these guidelines, the NASA Medical Operations Branch
Shockanaphylactic
Genitourinary 0.34 42% 2% has developed a specific set of minimal medical requirements
Renal calculi for a dedicated ISS Crew Return Vehicle. These requirements
Urosepsis are not intended as design solutions but merely as a guide for
Pylonephritis the vehicle designers as they develop concepts for the crew
Infectious disease 0.30 38% 2%
Sepsis
compartment of the CRV [9597]. The medical requirements
Meningitis are subdivided into those addressing patient care, crew com-
Dermatology 0.28 100% 5% partment configuration, and crew compartment environmental
Cellulitis/abscess control and life support systems (ECLSS) systems.
Urticaria
Exfoliative dermatitis
General internal 0.6 100% 10%
medicine Patient Care
Cancer
Endocrine/nutri- Equipment and Supplies
tional/others
Total ~ 6 events / 100 5.94 54 % Medical life support adequate for a minimum of one ill or
person-years injured crewmember including, but not limited to ventila-
tion, physiological monitoring with defibrillation, intra-
care is primarily due to loss of patient exposure and airway venous fluid therapy, and pharmacotherapy, are identified
access in the suited configuration. requirements. In addition, emergency medical and survival
During the assembly phase with a permanent crew of kits are essential to cover injuries and illnesses during any
three individuals, only the suited configuration (unmodified mission phase, including after landing until the arrival of
Soyuz-TM) escape vehicle will be available to accommodate search and rescue forces.
7. Medical Evacuation and Vehicles for Transport 155

Timeline Crew Medical Officer Station

To ensure that the patient transport time is minimized, the CRV Within the crew compartment area, the medical mission con-
medical mission timeline must ensure that the maximum time figuration requires specialized seats, restraints, and medical
from ISS separation to landing does not exceed three hours. This equipment interfaces and displays to accommodate the ill or
figure was derived from the projected capabilities of the vehicle injured crewmember and CMO. These must be able to sup-
and the medical requirements to minimize transport time. port an incapacitated crewmember on a mechanical ventilator,
provide electrical isolation for defibrillation, allow access to
medical equipment, patient and CMO interfaces, and allow
Crew Compartment Configuration ready access to the vehicles hatch.
The crew seat and cockpit design of the CRV should accom-
modate the full planned crew complement of the ISS, and Communications
address re-entry, chute, and impact acceleration forces and
Dedicated real-time medical communications capabilities are
crashworthiness. The following specific protective attri-
required between the CRV and Mission Control Center-Houston
butes, which must be incorporated into vehicle operations and
(MCC-H). These would include the means to support the trans-
design.
fer of medical data, including but not limited to, ECG and real-
Head-torso-lower extremity centerline axis alignment. time video, whenever possible. In addition, voice communication
Seatback angle 0 (preferred) to 12; neck < 20; hip, knee, between the CRV and SAR forces should be available.
ankle 90 relative to the local horizontal axis defined by the
prevailing velocity vector. Seating and Displays
Five-point restraint system adjustable to accommodate
The seat position for the CMO must allow access to medi-
595% of the anthropometric envelope and prevent occu-
cal equipment, controls, and displays and to dedicated air-
pant flail movements and cockpit projectiles, including for
to-ground communications. In a seven crewmember CRV
an unconscious patient.
Head restraint with lightweight communication and protec-
configuration, a rear row seat position would be designated
for an ill or injured crewmember due to proximity to the aft
tion systems that allow a fixed visual reference point.
Crew displays and controls that minimize crewmember head
egress hatch, while the parallel seat position would accom-
modate a crew medical officer (CMO). The aim is to allow the
and arm movement and effort during re-entry.
Vehicle spin and rotation limits not exceeding 5 rpm sustained
CRV pilot entry first, followed by remaining ISS crew, and
lastly the CMO and injured crewmember. This will allow the
due to crew intolerance (neurovestibular provocation).
Adequate attenuation properties to minimize G loading in
pilots to start the vehicle unhindered and will facilitate extraction
of the injured crew first after landing (Figure 7.5).
all axes of the human body with a limit on sustained (>1 s)
entry accelerations to no greater than +/4 Gx, +/ 1 Gy,
Extraction
and +/0.5 Gz in the body axis. This is designed to mini-
mize orthostatic stress and allow the crewmember a degree The entire crew returning from ISS may be incapacitated
of movement under G. A further driver to limit accelera- for several hours due to neurovestibular, cardiovascular, and
tion loads would be underlying illness or injury, that might
increase sensitivity to such forces such as blood loss or pul-
monary atelectasis.
Parachute deploy load limits (acceleration-time profiles) for

deconditioned crew are shown in Figure 7.4 [98101].

FIGURE 7.5. Mockup of the prototype X-38 CRV interior; this vehicle
would accommodate seven crewmembers and position the patient
and medical attendant just below the main overhead access hatch
FIGURE 7.4. De-conditioned crew load limits for parachute deploy. (Photo courtesy of NASA).
156 S.L. Johnston et al.

musculoskeletal deconditioning. Therefore, vehicle design should ute to orthostasis and motion sickness problems among crew-
accommodate the extraction of all incapacitated crewmembers members. The vehicle should also be capable of purging the
by search and rescue forces without help from the crewmembers interior environment of toxic products. This will also allow
themselves, with the injured crew extracted first. the CRV to act as a safe haven where astronauts could take
refuge while the ISS environmental control system scrubs a
Landing Impact Forces toxin, controls a fire, or repressurizes the station.
Pressurization. Loss of pressure is a credible ISS failure,
Impact deceleration limits should be such that risk of serious and the lowest pressure at which a crewmember can survive
or incapacitating injury as defined by the Brinkley Dynamic on 100% oxygen for a significant period of time is about
Response Model [98] in a deconditioned and ill or injured 3.0 psi (155 mmHg), or the equivalent atmospheric pressure of
crewmember is no greater than 0.5%. This is a figure that 11,600 m (38,000 ft) in altitude. In fact the earliest EVA suit
research and analysis have shown to be an acceptable level concepts and some high altitude pressure suits, such as utilized
of risk to the crewmember to prevent further injury, while for aircraft like the SR-71 Blackbird, were as low as 2.8 psi.
allowing vehicle designers a degree of latitude in develop- The re-pressurization rate limitfrom 3.0 psi to the nominal
ing a method of landing. This however is a difficult figure to 14.7 psi within 30 min, at a rate not to exceed 13.4 psi/minis
assess. Much of the data is based on Apollo capsule research, set to avoid problems with middle ear blockage and baro-
which measured peak forces higher than those more likely trauma. Although survivable, decompression from the station
to be encountered in a conventionally landed vehicle. The cabin atmosphere pressure to such a minimum pressure would
impact limits established in ACRV studies in the 1990s were likely involve some degree of decompression sickness (DCS),
10 +/Gx for 0.2 s, 5 +/ Gy for 0.2 s and 5 +/ Gz for 0.2 s so crew should remain on 100% O2 for several hours to miti-
[101,102]. gate this risk after such an event. It is important to note how-
ever, that the threshold for crew action and evacuation from
Crew Compartment Environmental Control the ISS is currently set well above 3.0 psi (see Chap. 23).
and Life Support Oxygen. Emergency and supplemental O2 is required for
use in event of toxic atmospheric contamination or a cabin
Cabin Atmosphere depressurization. This is required for a period long enough to
restore an adequate breathing environment and treat embar-
The atmosphere and environment of a CRV vehicle should
rassed respiration of exposed crewmembers. In addition the
maintain a comfortable level of temperature, humidity, and
vehicle needs to provide independent 100% breathing O2 for
ventilation for the duration of the mission to enable shirtsleeve
the ill or injured crewmember at a maximum rate of 20 liters
operation. Cabin atmosphere should be regulated according to
per minute for up to four hours. This will ensure that there is
the values in Table 7.17 [58,103].
adequate O2 for the patient from ISS separation to evacuation
This capability should extend beyond landing to include
by search and rescue after landing. This in turn necessitates a
adequate time for the removal of the deconditioned or ill or
means for dumping or recycling the exhaled O2 so that cabin
injured crewmembers. The vehicle will need an enduring
concentration limits are not exceeded with consequent flam-
ECLSS capability, as the system will need to cope with the
mability risks.
heat build-up during re-entry and landing, which may contrib-
Post-landing Recovery. Crew recovery after evacuation
from a vehicle such as the ISS does not end until the crew
Table 7.17. Crew Return Vehicle environmental control and life has reached definitive medical care. Requirements and proce-
support system design parameters. dures have been and continue to be developed to ensure that
Parameter Range an injured or ill crewmember will reach a DMCF within a
Total pressure 14.214.9 psi pre-determined period from station evacuation. This has con-
Partial pressure (pp) 0.1020.147 psi sequences for the requirements placed on the recovery vehicle
Carbon Dioxide and the SAR forces, as a result of the time required to land a
pp Oxygen 2.833.35 psi vehicle and where it will land. For example a CRV type vehi-
pp Nitrogen <11.6 psi
Relative humidity 25%70%
cle that can depart the Space Station and land within three
Atmospheric temperature 17.826.7C hours in multiple locations requires the SAR team to respond
Dew point 4.415.6C more quickly and to more locations than for a typical Soyuz
Intramodule circulation 0.0510.2 m/s landing. For a Soyuz landing, local SAR teams (augmented by
Intermodule ventilation 66 2.4 Liters/s NASA personnel where U.S. Astronauts are on board) are uti-
Fire suppression Oxygen 10.50%
concentration level
lized in locating the capsule and extracting the crewmembers.
Particulate concentration Average <0.05 mg/m3 The Soyuz Descent Module is equipped with radio and light
(0.5100 mm diameter) beacons to assist in determining its location.
Temperature of surfaces 4C <touch temperature <45C Future CRV requirements for crew recovery will be devel-
Atmospheric leakage per module Max 0.23 kg/day at 14.7 psi oped to some extent around the vehicles re-entry capabilities
7. Medical Evacuation and Vehicles for Transport
and potential landing sites. The vehicle itself will need to
be equipped with adequate survival equipment and provi-
sions in the event that SAR forces cannot reach the crew for
an extended period of time. In the Russian space program,
this has occurred on more than one occasion, with the crew
isolated for the first several to 24 h. Recovery of a crew in
an emergency return is different from the well-choreographed
and planned nominal landings of both the Soyuz and Shuttle.
Emergency recovery is not without danger to SAR forces, in
large part due to the many toxic substances carried by space-
craft for propulsion and cooling. This is compounded if the
vehicle lands in a remote and inaccessible area of the world.
Specific plans are in place for crew recovery at different
locations where a crew may land, whether the return vehicle
used is a Shuttle or Soyuz, and whether the crew is returning
from a short or long duration mission. The required capabili-
ties of recovery forces are specified in NASA documentation
and include rescue personnel, crewmember extraction capa-
bilities, and medical evacuation capability via ground or air-
craft. SAR forces at all potential landing sites are required to
be familiar with the space vehicles used for evacuation. These
plans also take into account whether there is a planned or
emergency evacuation of the space station. For a future CRV
that would land in the continental United States, comprehen-
sive vehicle-specific training is planned for SAR forces. In
addition secure communications between MCC Houston, the
SAR team, and the returning vehicle are mandated for the suc-
cess of a medical mission [104,105].
In summary, the design goals and requirements described
give an indication of the challenges faced by the design team
of a CRV to accommodate the effects of spaceflight decon-
ditioning of the crew and accommodate the pathophysiological
condition of an ill or injured crewmember.
Ethical Issues of Medical Evacuations
from LEO
While the practice of Space Medicine shares many commonalties
with terrestrial preventive medicine, it also requires exercising
unique medical experience and judgment. Like other fields of
preventive and occupational medicine, aerospace medicine
emphasizes optimizing workplace performance of essentially
healthy individuals. Medical decision making concerning
civil and military aviators and astronauts regularly involves
weighing priorities between the safety, well-being, and career
livelihood of an individual and the attainment of mission
success. Achieving and maintaining this balance permeates
every phase of space medicine practice, including mission
design, development and prescription of countermeasures,
astronaut and crew selection, training, mission preparation
and execution, inflight medical monitoring, and long-term
astronaut follow-up.
Unlike terrestrial medical practice, the potential hazards of
the space environment pose unique challenges involving the
157
safety, survival, and successful return to earth of individual
astronauts and even entire crews. Long-term space flight
itself poses additional inherent risks. Prudence dictates care-
ful deliberation of possible medical events well in advance
of their occurrence, including consideration of pre-flight
preparation, inflight management, return capabilities, poten-
tial positive or adverse outcomes, and mission impact. NASA
Medical Operations has, over several decades, adopted risk
management guidelines aimed at minimizing individual risk
while maintaining overall mission effectiveness. Longer-dura-
tion LEO and expeditionary flights to other planets present the
possibility that other limitations on certain types of missions
may be required, such as a career limit of one or two ISS type
missions for a few crewmembers based on cumulative radiation
exposure.
While every sort of inflight medical contingency cannot
be predicted, generalized onboard protocols for anticipated
medical scenarios can provide a framework for crew and
ground personnel decisions. Despite such forethought, any
medical event requiring evacuation from LEO will inevitably
involve real-time judgment. Where possible, therefore, effec-
tive communication between an ill or injured crewmember,
an onboard medical provider, ground-based medical support
(flight surgeon), and overall mission support (flight director
and mission managers) will be important to facilitate inte-
grated decision-making. However, the crew in LEO must be
prepared and equipped to make independent decisions; with
expeditionary missions, this is likely to be the norm in the
initial phases of a medical emergency.
In many ways, a vehicle capable of assuring crew return
from LEO in a medical evacuation poses more questions than
it does answers. While some scenarios may be unambiguous,
e.g., irreparable station depressurization, others are less clear.
How long should a well-trained CMO with relatively limited
onboard resources care for an acutely ill crewmember on orbit
before calling for evacuation to a DMCF? If there is a single
transport vehicle, does the entire crew evacuate, ending the
mission, or only the ill crewmember and the medical provider?
How do the risks of evacuation and landing compare to those
of administering further care on orbit? Does the occurrence
of a predictably fatal illness or injury alter medical evacua-
tion decisions? In view of other mission objectives and poten-
tial additional risks, what responsibility does a crew have to
recover and return a deceased crewmember? Though difficult
questions, these raise ethical issues worthy of advance con-
sideration. While flight rules and decision algorithms govern-
ing medical evacuation are designed to minimize real-time
deliberation, it will ultimately be a weighty responsibility
for a flight surgeon and flight director to determine, with the
onboard crew, the need for medical evacuation.
The frontier medical-legal issues raised by such questions
are numerous. The broad groundwork underlying these issues and
questions lies in the U.S. Space Act and the United Nations
Space Treaty. Therefore, as space agencies have accepted
the moral obligation to address medical emergencies from the
158
earliest days of human space flight, the agencies have a legal
duty, in the form of these international treaties, to provide for
crew rescue. The first of several treaties related to crew res-
cue was the Treaty on Principles Governing the Activities of
States in the Exploration and Uses of Outer Space, including
the Moon and other Celestial Bodies.
In a tragic coincidence, this treaty was signed on January
27, 1967, the day Grissom, White, and Chaffee died in the
capsule of Apollo 1. The treaty identifies principles related to
the rendering of all possible assistance on Earth and in space,
the prompt and safe return of crew, and the dissemination of
information about possible hazards.
The second treaty, the Agreement on the Rescue of Astro-
nauts, the Return of Astronauts, and the Return of Objects
Launched into Space was signed in December 1968, soon
after Komarov perished in the capsule of Soyuz 1 on its return
to earth. The Rescue treaty specifically requires immediate
notification of accidents, provision of rescue and assistance to
spacecraft personnel, and their prompt and safe return to the
launching authority.
More recently, these matters have been addressed specifically
with regard to crew return from the ISS by the partnering
international space medical community and their respective
agency management. Memoranda of Understanding, which
define partner roles in the ISS, have been elevated to inter-
national treaty status. Though partner nations have reached
consensus on a few specific concerns, such as standardizing
medical care inflight and for ground support, discussion of
other topics is ongoing and questions remain. What consti-
tutes a medical disability resulting from illness or accidental
injury during space flight? How is investigation of the causes
of an accident resulting in medical disability conducted? What
nation or nations maintain jurisdiction onboard an Interna-
tional Space Station? Does a hosting nation have liability for
medical consequences of a guest crewmembers injury or ill-
ness? How do we train, qualify, and certify space medicine
physicians, and ensure their competence and currency? What
differences, if any, should exist between standards for ground-
based versus inflight care providers? Addressing these questions as
well as the technical challenges is a fundamental step toward
readying ourselves for further space exploration.
Beyond Earth OrbitThe Moon and Mars
Potential medical transport and evacuation scenarios turn even
more complex in considering a mission beyond earth orbit.
Compared to a transport time of several hours from LEO, evacu-
ation from a Moon base or a space station at one of five earth-
moon fixed Lagrangian libration points would require several
days at best. For a Mars mission, the one-way communication
time may be up to 20 min duration and there may not be evacu-
ation capability at all. Clearly, injuries and illnesses that would
be potentially treatable on a LEO space station will carry more
threatening implications if they occur in remote space.
S.L. Johnston et al.
For many reasons including medical concerns, missions
beyond LEO will require levels of spacecraft and crew auton-
omy and self-sufficiency beyond what is currently realized.
Just as fault-tolerant design of vehicle components and sys-
tems will be enhanced, crewmembers will be more highly
cross-trained. The crew of a Mars or other deep space mis-
sion will likely have to anticipate how to carry their objectives
through to completion despite possible incapacitation or loss
of a crewmember. Additional onboard capability to manage
a disabling medical condition over the relatively long-time
frame of several months may be required, as well as means
to deal with a deceased crewmember. In a much greater con-
text, the expansion into the solar system will be in a staged
fashion, with decreasing capabilities expected at increasingly
remote sites. Medical evacuation from a deep space mission,
for instance to the asteroids, may well be to a fall-back posi-
tion on Mars where a greater level of care is available, rather
than by default back to very distant Earth.
Exploratory missions truly mark a change in potential risks to
both the mission and individuals. Issues such as crew selec-
tion criteria, age at mission start, optimization of physical and
mental condition, informed consent of mission risks, notifi-
cation of family of medical events, and mission-consequence
long-term health effects are just some of the concerns attend-
ing medical operations planning for future.
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8
Telemedicine
Scott C. Simmons, Douglas R. Hamilton, and P. Vernon McDonald
The delivery of medical care in space is complicated by factors
such as microgravity, extreme resource constraints, hazardous
environments, and extreme distance from definitive medical
care facilities. In addition, although the crew medical
officersthose personnel required to provide in-flight
medical careare typically not physicians, after receiving a
minimal amount of medical training (1620 h for the Space
Shuttle Program and about 80 h for the International Space
Station [ISS] Program), they are responsible for tending to
ill or injured colleagues. One method of mitigating the lack
of training and experience for crew medical officers is by
remote consultation with medical experts on Earth, or
telemedicine.
Obtaining a consensus on the definition of telemedicine is
difficult. Any definition would include at least two key com-
ponents: geographic separation between medical expertise
and the medical care provider and telecommunication or com-
puter-mediated interaction.
A simple definition of telemedicine might be the prac-
tice of medicine across a distance using telecommunication.
According to this definition, clinical space medicine has used
telemedicine since the dawn of human space exploration. To
expand on this simple definition, Grigsby and associates have
developed a useful list of functional categories of telemedi-
cine applications: (1) initial urgent evaluation of patients, tri-
age decisions, and pretransfer arrangements; (2) medical and
surgical follow-up and medication checks; (3) supervision and
consultation for primary care encounters in sites where a phy-
sician is not available; (4) routine consultations and second
opinions based on history, physical findings, and available
test data; (5) transmission of diagnostic images; (6) extended
diagnostic workups or short-term management of self-limited
conditions; (7) management of chronic diseases and condi-
tions requiring a specialist not available locally; (8) transmission
of medical data; (9) public health, preventive medicine, and
patient education [1].
Almost all of these telemedicine functions have been used
in the U.S. and Russian space programs, although most experi-
ence until recently involved remote monitoring of biomedical
and environmental parameters and voice-only consultation
via space-to-ground communication loops. When sensor and
communication technologies were first implemented, they
represented the state of the art in both terrestrial telemedi-
cine and space telemedicine. With the recent proliferation of
computers, high-speed telecommunications, and the Internet,
telemedicine is being implemented much more widely on
Earth and in space, and more robust capabilities are being
used daily in clinical practice [2].
The ISS and future planetary exploration-class missions
(e.g., to Mars) will require the incorporation of contempo-
rary telemedicine concepts and technology, tempered by the
resource restraints and operational realities of space medicine.
This chapter provides an understanding of current telemedi-
cine theory and applications, a historical perspective of space
telemedicine, and a prospective view of telemedicine for the
ISS and beyond.
Fundamental Telemedicine Concepts
The first U.S. telemedicine consultation, for telepsychiatry,
was performed in the 1950s using closed-circuit television
[3]. Telemedicine did not receive much attention within
the U.S. health care community until the 1990s, however.
The growth of telemedicine can be attributed to three major
factors. First, advances in computer, telecommunication,
and imaging technologies enabled telemedicine to become
practical and accessible. Second, the current focus on man-
aged care, health care process reengineering, and national
health care reform has stimulated industry and federal
government interest in telemedicine, which has led to a
concomitant increase in federal and state funding of tele-
medicine projects. Third, the ubiquity of the Internet has
resulted in more widespread familiarity with distributed
collaboration [2].
The application of telemedicine for space flight was born
out of necessity, since nonmedical in-flight personnel and
physical resource limitations demanded that access to medical
163
164
expertise be provided via telecommunications. Simply stated,
this was the only way for crews to gain access to medical
expertise when in space.
The practice of medicine on Earth, where many rural
and inner city communities are classified as underserved,
is fraught with similar problems of access to medical care.
Underserved communities often lack primary care physicians,
clinical care facilities, or both. To receive specialized medi-
cal care, patients in these communities often must travel to
a major university medical center or to a large hospital many
miles away. Current terrestrial telemedicine research and
development is focused on improving access to medical care
in all of these situations.
Modalities
There are three basic and distinct modalities of telemedicine
interaction: real-time, store-and-forward, and just-in-time inter-
actions. All three are classified by latency, or delay, of telecom-
munications.
Real-time (synchronous) telemedicine involves little or no
perceptible latency. Real-time interactions include full-motion
videoconferencing or a telephone conversation.
In store-and-forward telemedicine, data are collected and
stored off line and transmitted (or forwarded) to the destina-
tion site at a later time. Familiar store-and-forward interac-
tions include electronic mail, facsimile, and voice mail, all of
which are used quite effectively in contemporary home and
office environments. A store-and-forward consultation may
have a latency of more than 24 h; however, this is not much
different from referring a patient to a specialist who may not
actually see the referred patient for days or weeks.
Somewhere temporally between store-and-forward and
real-time telemedicine is the just-in-time interaction. The just-in-
time concept may be uniquely related to space medicine, and
both clinical and operational factors distinguish just-in-time
interactions from real-time or store-and-forward encounters.
Just-in-time means that data are literally received just in
time to influence the current or active patient encounter.
For example, critical-care monitoring data from an astro-
naut or a cosmonaut on a planetary exploration mission
may be transmitted to Earth continuously, in what might be
expected to constitute real time. However, because of the
great distance from Earth, the Mission Control Center (MCC)
may not receive these data until several minutes later. (Mars
communications would require 3.520 min to reach Earth for
one way travel, depending on the relative positions of Earth
and Mars.) Naturally in this situation, CMOs would have to
manage emergent problems locally; but delayed data would
be received just in time for flight surgeons on Earth to still
provide meaningful input on patient management via this type
of interaction.
Data are considered to be just in time when the feedback
after having been received, processed, and returnedarrives
just in time to influence the clinical outcome of the medical
event. The latency of data arriving from a vehicle on its way to
S.C. Simmons et al.
Mars may preclude a ground-based flight surgeon from assist-
ing crewmembers in managing an acute emergency, such as
a myocardial infarction. The ability of the flight surgeon to
influence the outcome of a medical event depends on the type
of event and the time delay (distance from Earth).
Most telemedicine programs involve real-time encounters,
using high-bandwidth (384 kbps to 5 Mbps) videoconfer-
encing systems. This real-time, videoconferencing model
of telemedicine often involves the interaction between the
primary care physician who is attending to a patient and
the medical specialist. Video cameras are used to view the
patient, and special adapters are used to affix medical video
instruments with specialized small video cameras. This
model has several limitations, including the lack of available
bandwidth in the medically underserved environments that
would benefit from telemedicine, the expense associated
with such systems, and scheduling requirements (having
two medical care providers simultaneously available, one
at each end). These systems also require technical support
personnel to install and maintain the systems and establish
communication links.
Despite these limitations, videoconferencing is often a criti-
cal part of telemedicine in clinical applications that require
real-time interaction. The assessment of neuromuscular
function, including range of motion and gait, and telepsy-
chiatry are two clinical examples that often require real-time
interaction. More recently, remote consultation for trauma
is taking advantage of such telecommunication systems.
Videoconferencing is also valuable when the remote user
is unfamiliar with operating the telemedicine equipment or
is inexperienced in conducting certain clinical studies (e.g.,
ultrasonography) that may require telementoring during a
particular medical procedure.
With the worldwide expansion and widespread use of the
Internet and continuous advancements in personal computer
(PC) technology, the utility of store-and-forward telemedicine
has grown steadily. File attachmentswhether text docu-
ments, database files, still images, or audio and video clips
can be appended to electronic mail messages.
Radiology, dermatology, and pathology are clinical special-
ties that adopted store-and-forward telemedicine very early.
Two contributing factors were that these specialties already
involved a level of abstraction from the patient and that their
mode of practice often depends on visual media for presenta-
tion of static images. The United States Armed Forces Institute
of Pathology has provided telepathology consultations since
1992 [4]. The American College of Radiology, in collabora-
tion with the National Electrical Manufacturers Association,
was one of the first of a collection of specialty societies to
develop a standard for digital imagingthe Digital Imaging
and Communications in Medicine (DICOM) standard. This
standard addresses image display requirements (e.g., spatial
and temporal resolution, levels of gray), image attributes,
clinical reporting associated with the images, and messag-
ing. Currently, DICOM is the only standard for the electronic
transmittal and storage of medical images.
8. Telemedicine
Effectiveness
Several factors can influence the effectiveness of telemedi-
cine. Bandwidth, or the data-carrying capacity of a commu-
nications system, is the most influential factor. If a plumbing
system is used as a metaphor for bandwidth, the bandwidth is
the size of the pipe. More water (representing data) can flow
through a large pipe than through a small pipe. The smallest
pipe within the system network thus influences the overall
bandwidth of the system. For example, a dial-up connection
to the Internet that uses a standard telephone line and 56-kbps
modem is limited to the bandwidth of that connection, regard-
less of whether much higher bandwidth connections are pres-
ent downstream.
System bandwidth relates to the amount of data that passes
through a connection per unit time. However, this does not
always relate to the amount of information that is transferred per
unit time. Hierarchically, data precede information and infor-
mation precedes knowledge. As such, high-bandwidth commu-
nication of data does not necessarily lead to high bandwidth
communication of information. An example of this is the band-
width of a common telephone line versus a high-fidelity stereo.
If the design requirements for a communication system that is
supporting a conversation include the ability to understand the
spoken word, the connection needs to be approximately one-
fifth the bandwidth of a standard off-the-shelf stereo.
The amount of bandwidth required to transmit medical infor-
mation is highly dependent on the medical scenario, the skill
of the medical care providers at both ends of the communica-
tions link, and the type of medical data being exchanged. In the
case of a myocardial infarction, for example, where emergency
intervention is almost always required, the medical expertise at
the patients bedside will determine the bandwidth required to
remotely support this clinical scenario. If the point-of-care pro-
vider is a skilled emergency medical technician, in most cases
only a telephone link is required since the information is pre-
processed at the remote location. Similarly in most cases, the
bandwidth required to support a medical event increases with
the difference in the level of expertise between the point-of-
care provider and the remote medical support.
Furthermore, a telecommunications network consists not
only of data pipes, but these data also must travel through
myriad bottleneckse.g., switches, routers, and gate- sub-images, or tiles, within an overall image. A rapid change
waysthat can affect latency as well. A second, major factor
is the distance the data must travel. Ordinarily, in terrestrial
applications, distance is not influential. However, because
data travel at a finite speed, distance is a major concern for
space travel beyond Earths orbit. Thus, the greater the
distance, the longer the travel time between the location of
origin and the remote expertise.
Temporal delays can grow to the extent that they preclude
fluid real-time interactions. Also, with the prospect of data
transmission over millions of kilometers (miles)as in the case
of space missions that travel beyond low Earth orbitcommu-
nication latencies can stretch into tens of minutes, thereby com-
promising the benefit of telemedicine for certain scenarios.
165
Digital Imagery
Digitally processing and storing images, video, and audio
offers several distinct advantages over traditional analog stor-
age-and-retrieval methods. Unlike analog systems that access
data serially, or temporally, digital systems can access data
randomly. Duplication of digital data is lossless between
generations; that is, no data are lost between the copies and the
originals. Data in a digital format can also be easily manipu-
lated (filtered or enhanced) by commonly available personal
computers (PCs). However, the processing and transmission
of video is problematic due to the tremendous amount of data
contained within a video stream.
The National Television Standards Committee (NTSC) video
standard is the broadcast video standard used in the United
States. In the NTSC standard, each second of video contains
30 frames, and each frame of broadcast-quality video contains
approximately 7.4 106 bits of information (640 480 pixels per
frame 24 bits color depth per pixel), or roughly 1 megabyte (8
bits per byte). Compression techniques are therefore employed
to more effectively use processing power and bandwidth and
are applied to both still images (e.g., joint photographic experts
group (JPEG) ) and video. The digital video industry standard
is the Motion Picture Experts Group (MPEG) standard, which
actually comprises two standards. MPEG-1 was developed
to play 320 240 video at 30 frames per second from a sin-
gle-speed CD-ROM (compact disk-read only memory) drive
(150 kbps). MPEG-2, which became available in its final form
in 1995, was designed for cable and satellite television and for
the video and movie production industry. MPEG4 is not cur-
rently supported by most internet based video compression sys-
tems but will most likely appear on the market soon. MPEG4
supports streaming video, multimedia, speech synthesis and
many other features including a foreground-background cod-
ing technique. MPEG4 will likely supplant MPEG2 for broad-
cast applications since it uses about one-half the bandwidth for
equivalent video and audio quality.
An important fact to consider when using videoconferenc-
ing in telemedicine is that the compression algorithms that are
used for videoconferencing are all highly sensitive to rapid
image changes. This is because rapid changes produce a
tiling effect. Tiling is the appearance of obvious rectangular
in an image, such as from movement or lighting, causes this
effect. Tiling occurs because the real-time compression algo-
rithms try to estimate the next video frame. The stochastic
nature of many video images will occasionally overwhelm the
compression algorithms ability to predict the next set of pixels
per tiles, and tiling is the result.
Clinical Efficacy of Telemedicine
Historically, telemedicine programs were supported mainly
by grant funding, and most programs were conducted as dem-
onstrations of the feasibility of telemedicine and supporting
166
technologies. The focus of the few formal evaluations that
were conducted often involved the technical performance of
systems. Clinical assessments were subjective. These early
concept demonstrations and evaluation efforts were important
for introducing telemedicine concepts and for demonstrating
the clinical applicability that telemedical care could provide.
For telemedicine to be integrated into daily clinical prac-
tice, more rigorous assessments of the efficacy of telemedi-
cine must be conducted. Although clinical evaluations such
as these have increasingly appeared in the literature since the
mid 1990s, little quantitative analysis has been done on the
efficacy of telemedicine.
The body of formal research into the clinical efficacy of tele-
medicine exists in several broad categories. These categories
include diagnostic agreement or reliability between telemedi-
cine diagnosis and conventional diagnosis; the time required
to receive specialty consultation; outcomes assessment; and
the impact of telemedicine on patient access to care.
One method of telemedicine clinical validation is to measure
the diagnostic agreement (reliability) between a gold stan-
dard diagnosis and telediagnosis. A gold standard diagnosis
is the normal method of patient assessmentusually a physi-
cians hands-on patient examination or a specialists review of
traditional diagnostic studies. Examples of gold-standard com-
parisons include radiographic plain films vs. digitized films, or
local patient auscultation vs. tele-auscultation.
Nitzkin and colleagues performed perhaps the most com-
prehensive study of the diagnostic reliability of telemedicine
when they measured the agreement between a criterion stan-
dard assessment and an alternative telemedicine assessment [5].
These investigators also examined the use of telemedicine
for cardiac and pulmonary auscultation, echocardiography,
electrocardiography, electroencephalography, obstetric ultra-
sonography, ophthalmologic examination, physical therapy
assessment, and chest radiography. They pointed out that
interobserver variability is a significant factor associated with
this sort of assessment, and they cited findings from the litera-
ture that demonstrate clinically significant variability among
observers using conventional techniques ranging from 15 to
30%. This study tried to account for interobserver variability
by also examining the agreement between conventional exam-
inations of the different physicians who reviewed the data and
comparing these to the criterion standard.
Using the results of their study (Table 8.1), Nitzkin and
colleagues made several salient observations and drew some
notable conclusions [5]. They observed that diagnostic reli-
ability correlated strongly with a physicians experience in
and knowledge of the limitations of telemedicine; the remote
operators experience affected diagnostic reliability; and
the adjustment of equipment settings greatly affected the
detection of abnormalities and the rate of false negatives.
These observations all point out the importance of training
and standardization of techniques in telemedicine.
Several studies have recently determined the efficacy of
telemedicine for dermatology (tele-dermatology) in both real-
S.C. Simmons et al.
time and store-and-forward modes. The U.S. Armys Walter
Reed Army Medical Center has, since May 1998, used a store-
and-forward, Web browser-based tele-dermatology system
[6]. An assessment of 113 randomly selected dermatology
cases demonstrated 93.8% diagnostic agreement, and only
one case (0.8%) was found to be misdiagnosed [7]. In a study
of real-time tele-dermatology, Phillips and colleagues inves-
tigated the effect of telemedicine on the assessment of skin
tumors by comparing the findings of a dermatologist who saw
patients in person with the findings of another dermatologist
who remotely examined patients using a videoconferencing
link [8]. The two dermatologists agreed absolutely on 59% of
the 107 skin tumors evaluated, and a kappa analysis showed
that telemedicine did not significantly influence the recom-
mendation to perform a skin biopsy. Roth and colleagues com-
pared the diagnostic accuracy of 35-mm photographic slides
of wounds to digitized images of the slides (spatial resolution
640 425, JPEG compression) using six physician observers
who first examined the slides and then the digitized images
[9]. The study measured 87% (p = 0.004) overall agreement
between the diagnosis and treatment from the slides and the
digitized images. From this the authors concluded that the use
of consumer-grade digital photography would be efficacious
in tele-assessment of wound healing.
An exhaustive review of the telemedicine evaluation and
validation literature is beyond the scope of this chapter. Suffice
it to say that similar results to those cited have been demon-
strated in studies of telemedicine in other clinical specialties,
including in otolaryngology, psychiatry, radiology, pathology,
cardiology, and neurology. An interesting byproduct of tele-
medicine, one that is common throughout the specialties,
is a learning effect in which the remote user at the patients
site becomes less dependent on the tele-consult as the user
becomes educated from previous interactions with special-
ists. Although more rigorous analyses will and should be con-
ducted, the findings to date coupled with anecdotal evidence
suggest the efficacy of telemedicine in terrestrial settings. The
experience required to support crewed space missions using
telemedicine will benefit greatly from the lessons learned
from the terrestrial telemedicine experience.
TABLE 8.1. Diagnostic agreement among clinical studies.
Agreement (identical or
Clinical study similar to criterion standard)
Ophthalmology, physical therapy 91.2% conventional
and cardiac auscultation 86.5% telemedicine.
Pulmonary auscultation Inconclusive; abnormalities only
and reading of chest films detected after default settings
from video were adjusted.
Tracings (ECG, EEG) and images 92% for both conventional
(echocardiography, obstetric and
telemedicine physical
therapy assessment)
Source: Nitzkin et al. [5].
8. Telemedicine
Space Telemedicine History
The U.S. and Russian space programs pioneered the use of
telemedicine in space flight. In both space programs, early
missions were limited to using small space capsules crewed
by correspondingly small crews. These missions required the
intensive efforts of skilled test pilots and technical officers.
Since members of the early astronaut and cosmonaut corps
primarily were drawn from military aviators and engineers,
few opportunities were available to include onboard medical
or life sciences expertise. Operational realities dictated that
space medicine and life science operations rely primarily on
remote support from Earth-based facilities, and scientists and
engineers had to develop innovative means for remote physi-
ological and environmental monitoring. This resulted in the
development of new systems and techniques for biomedical
signal acquisition, conditioning, and telemetrytechniques
that are the foundation of todays clinical intensive care envi-
ronment.
Telemedicine in the U.S. Space Program
Mercury and Gemini
Project Mercury (August 1959 to May 1963) marked the first
U.S. crewed presence in space. The biomedical instrumen-
tation on early Mercury flights included electrocardiogram
(ECG), blood pressure, respiration rate, galvanic skin resis-
tance, and rectal temperature [10].
Project Gemini (April 1964 to November 1966) provided
the medical knowledge and experience in human adaptation
to the space environment that enabled human lunar explora-
tion during the Apollo missions. All Gemini crewmembers
wore biomedical monitoring harnesses during the 10 crewed
missions. These harnesses provided two ECG leads and
voice, respiratory rate, body temperature, and blood pressure
monitoring [11]. The two-man Gemini crews also wore pas-
sive radiation dosimeters. Crewmembers who participated
in extravehicular activities (EVAs) were fitted with leads
for ECG and respiratory rate measurement [12]. Additional
monitoring was included in the 14-day Gemini GT-7 mission
(December 418,1965), when electroencephalogram signals
were measured during sleep by four scalp electrodes affixed to
each crewmember [11]. All biomedical data, except radiation
dosimetry data, were transmitted directly to Earth.
Apollo
Crewmembers in the Apollo Program (February 1966 to
August 1971) wore biosensor harnesses throughout all mission
phases. Biomedical monitors included a two-lead ECG, a car-
diotachometer for measuring heart rate, an impedance pneu-
mograph, and a thermistor to measure body temperature [13].
In addition to the biosensor harnesses, each crewmember wore
a personal radiation dosimeter, which measured accumulated
167
radiation dose, and three passive dosimeters [14]. The dosim-
eters were placed at different locations on the crewmembers
body to determine dosage at specific areas of interest. Radia-
tion data was not available real-time. Other parameters were
monitored and transmitted to Earth during EVAs, primarily to
determine metabolic rate during the activities. Metabolic rate
was estimated by measuring the inlet and outlet temperatures
of the cooling garment that the EVA astronaut wore and could
also be estimated from heart rate and oxygen consumption
measurements [15].
As in previous programs, biomedical data were transmitted
to the launch control centers and the MCCs and were moni-
tored continuously by the flight surgeon in the MCC. These
data were particularly important for the flight surgeon to
monitor off-nominal events such as the environmental control
system failure of Apollo 13 (April 1117, 1970) and the car-
diac dysrhythmias experienced by crewmembers during the
lunar EVAs of Apollo 15 (July 26 to August 7, 1971).
Skylab and the Apollo-Soyuz Test Project
The Skylab Program (May 1973 to February 1974), which ini-
tiated the U.S. experience with long-duration space flight, was
also the first U.S. spaceflight program in which continuous
biomedical monitoring was not performed. Instead the Skylab
Operational Bioinstrumentation System transmitted crew bio-
medical information to Earth during certain critical mission
activities, including launch, docking, EVA, suited intravehic-
ular activity, undocking, and return. In addition, biomedical
monitoring associated with specific experiments and radiation
monitoring was conducted. The Skylab program saw the first
flight of a U.S. physician in space, Dr. Joseph Kerwin.
Biomedical monitoring during the aforementioned critical
mission phases included measuring ECG, respiratory rate
(via impedance pneumogram), body temperature, and heart
rate [16]. The noninvasive automated blood pressure measuring
system measured systolic and diastolic blood pressures during
lower body negative pressure and metabolic activity experi-
ments [17]. A vectorcardiograph monitored cardiac electrical
activity during these investigations and during the in-flight
vectorcardiogram investigations [18]. Metabolic activity
experiment was supported by a metabolic analyzer that mea-
sured oxygen consumption, CO2 production, minute volume,
respiratory exchange ratio, and tidal volume during exercise
activity on the cycle ergometer [19]. Although the vectorcar-
diograph was developed for particular investigations, it could
also have been used clinically for cardiac monitoring, though
the need never arose.
In addition to biomedical monitoring, weekly audio-only
private medical conferences took place in which crewmembers
consulted with flight surgeons at the Johnson Space Center
(JSC) in Houston, Texas. Crewmembers could also request
conferences on an ad hoc basis if specific health issues arose
requiring flight surgeon consultation. Two Skylab crewmem-
bers per mission received approximately 80 h of preflight
168
medical training, and the ability of these medically trained
crewmembers to describe their findings and observations was
critical to the conduct of voice-only private medical confer-
ences. The crewmembers developed a verbal shorthand
method of describing observations, sometimes referring to
figures from the Skylab Medical Checklist.
During the nine-day Apollo-Soyuz Test Project (July 15
to July 24, 1974), ECG and respiration rate were monitored
during periods of exercise and during launch and landing pro-
cedures. As in the Apollo and Skylab Programs, each U.S.
crewmember was also assigned a personal radiation dosimeter
and a passive dosimeter to measure radiation [20].
Over the course of these early phases of U.S. human space
flight, the practice of space telemedicine underwent three
notable changes. The first was the transition from continuous
physiological monitoring and communication of medical data
to the model of intermittent and context-specific monitoring,
due in part to a growing understanding of human physiologi-
cal responses to weightlessness. The second change was the
integration of real-time communication of digital data with
store-and-forward digital data communication, thereby pre-
serving the precious communications bandwidth. The third
change was the development of techniques and procedures
for communicating medical observations and the emergence
of remote verbal consultation with a physician in the form of
a private medical conference. Such a verbal exchange rep-
resents the implementation of the most basic element of the
patient-physician encounter in space.
Space Shuttle
Both biomedical and cabin parameter monitoring continue to be
a primary component of telemedicine in the Space Shuttle Pro-
gram (April 1981present). Cabin atmosphere parameters are
continually monitored, and crewmember ECGs are monitored
during hazardous operations, such as EVAs or certain medical
experiments. Daily private medical conferences between the
crew surgeon in the MCC-Houston Flight Control Room and
the crew on board the Space Shuttle are a routine part of Space
Shuttle operations. These conferences have contributed signifi-
cantly to minimizing operational impacts of medical events.
Until recently, private medical conferences used only
air-to-ground voice communications. In the mid-1990s,
two-way videoconferencing became an option via the
Orbiter communications adapter (OCA) system. Flown ini-
tially as an operational flight experiment, OCA represented
the first mission operations communications link to use the
transmission control protocol/Internet protocol (TCP/IP) com-
munication standard. This is notable because TCP/IP is the
core standard for everyday use of the Internet.
The OCA videoconferencing system on the Space Shuttle
operates at approximately 128 kbps, which enables crewmem-
bers and the flight surgeon to see each other with low-resolution
images. In comparison, in typical terrestrial telemedicine appli-
cations with greater bandwidths (384 kbps to 1 Mbps) and mod-
ern video compression algorithms, the codeca code-decoder
used to convert analog to digital signals and back again, usually
S.C. Simmons et al.
on the same chipproduces images that are considered to be
of acceptable diagnostic quality, depending on the amount of
motion required for a particular application. Despite its low-
resolution images, the OCA videoconferencing is useful for
face-to-face interactions and is well suited for conducting private
family conferences in which, during lengthier Space Shuttle
missions, crewmembers can visit with family members.
The deployment of the OCA presented the opportunity
for space medicine experts to use commercial-off-the-shelf
(COTS) medical information system technology. However,
challenges remained, in part a result of the relatively long
round-trip satellite communication latencies of about 1.6 s.
Because of these communication latencies, many COTS soft-
ware products were found to operate poorly since they could
not tolerate such excessive communication latencies.
Telemedicine in the Russian Space Program
The first Russian spacecraft, Vostok and Voskhod, were quite
similar in design. The main differences between the spacecraft
were that Vostok carried a crew of two and ejection seats,
and Voskhod carried a crew of three, without ejection seats.
Biomedical monitoring of the cosmonauts traveling on board
these spacecraft included ECG, heart rate, electroencephalo-
gram, electromyography, and galvanic skin response [21].
Soyuz missions used essentially the same biomedical moni-
tors as were used in the Vostok and Voskhod missions. The
Soyuz vehicle, which in its current design consists of two cab-
ins separated by a hatch, typically supports crews of two to
three cosmonauts. Among the many jobs the Soyuz has per-
formed has been servicing the Salyut and Mir space stations.
A total of seven Salyut missions were launched during the
Salyut Program (April 1971 to September 1986). The Salyut
missions were as short as eight days (Salyut-6) and as long as
237 days (Salyut-7). Crewmembers conducted many medical
experiments during these missions to determine cosmonauts
responses to space flight and to select effective countermea-
sures to space deconditioning. Psychological issues were also
seriously addressed for the first time in the Salyut Program,
and the crewmembers were allowed two-way personal com-
munication with their family members [22].
The Mir station, the first element of which was launched in
1986, was the next-generation Russian space station. Mir was
outfitted with amenities, including private sleeping compart-
ments, that provided a greater degree of comfort than had been
seen in the Salyut stations. In addition, two-way communica-
tions with families, flight controllers, friends, and celebrities
provided psychological support for Mir crewmembers [23].
On board Mir, real-time detailed physiological monitoring
of exercise performance, medical experiments, and medi-
cal diagnostic evaluations during long-duration space flight
became a well-established practice. The hardware suite avail-
able on the space station included a 12-lead ECG, the means
to monitor respiratory rate and blood pressure, and several
derived central hemodynamic parameters such as central
venous pressure and cardiac output.
8. Telemedicine 169

Space-Based Telemedicine Investigations

Two major in-flight telemedicine investigations have been
conducted in the Space Shuttle Program. These have served to
prove the feasibility of new diagnostic capabilities that were
not a routine part of operational space medicine. One telemedi-
cine investigation, the video fundus camera, was originally
developed to support NASAs biomedical research program.
The portable dynamic fundus instrument, or video fundus
camera, was developed to decrease the time required to train
astronaut crews to take photographs of the retina for a flight
experiment that examined the effects of zero-gravity on the
retinal blood vessels. The device used a special adapter to
project retinal images on a video chip instead of on the usual
35-mm film. Use of the video fundus camera resulted in a
marked decrease in training time. Since the video images cap-
tured by the device were of excellent quality, the video device
was used in addition to the 35-mm film version. The instru-
ment was flown on six Space Shuttle missions. Video images
of the retina were downlinked, using the video fundus camera,
during the STS-50 mission (July 1992).
A more extensive in-flight evaluation of clinical telemedicine
capabilities was conducted in an experiment during the STS-89
mission (January 1998). Over three flight days, nonphysician
astronaut CMOs performed focused physical examinations
using the telemedicine instrumentation pack (TIP) (Figure 8.1).
TIP was developed to extend the CMOs capabilities by
allowing the CMO to perform a multimedia medical exam and Figure 8.1. Telemedicine instrumentation pack (TIP). Video, audio,
and other biomedical data were transmitted from the TIP aboard the
consult with flight surgeons at the MCC at JSC.
Shuttle Endeavour to a telemedicine workstation at the Mission Con-
During the STS-89 flight experiment, video, audio, and other
trol Center during Mission STS89. The TIP was designed to fit in
examination biomedical data were transmitted from the TIP on a standard Shuttle mid-deck locker
board the Space Shuttle Endeavour to a telemedicine worksta-
tion at the MCC-Houston. The objectives were to evaluate:
(1) the ability of the TIP to capture medical data on board the the Space Shuttle and the MCC-Houston. The Ku-band system
Orbiter and send these data to the MCC, (2) the quality of these can support data communications (2 Mbps) and video down-
data from a clinical perspective, (3) the usability of TIP in the link at the same time. The S-band system provides two bidi-
microgravity environment, (4) the operational feasibility of rectional loops for voice conferencing. Crewmembers used
using the TIP for interactive (real-time) air-to-ground medical handheld microphones to speak, via the S-band system, to the
examination, (5) and the operational utility of just-in-time and flight surgeon on the ground, and they monitored the surgeons
store-and-forward in-flight medical exams using the TIP. voice on the Space Shuttle audio system. To maintain privacy
TIP enables a user to collect, store, and transmit a variety of for crewmembers, the air-to-ground conversation between the
clinically relevant data to a remote PC workstation (a telemed- flight surgeon and the Space Shuttle was secured.
icine workstation). A flight surgeon working at this remote The physical exam the CMOs performed was a focused
workstation can receive, display, and manipulate information procedure to assess the utility of devices installed in the
transmitted from the TIP. The TIP has an embedded computer TIP. The physical exam techniques commonly taught in
at its core and uses a remote-head charge-coupled device video CMO training for Space Shuttle medical operations were
camera that can be attached to a variety of medical imaging modified to include the use of devices supported by the TIP.
instrumentsincluding an otoscope, ophthalmoscope, and a These physical exam techniques include examination of the
macro lens for live NTSC video streaming or capturing still lungs and heart with a stethoscope, the eyes with an oph-
images. The device also contains a digital electronic stetho- thalmoscope, the ears with an otoscope, and the skin with
scope for remote auscultation and is capable of monitoring a small camera using a macro lens. Other vital signs were also
ECG, blood pressure, pulse rate, and oxygen saturation. measured using automatic equipment such as blood pres-
The TIP evaluation was conducted on three consecu- sure, pulse oximetry, and electrocardiograms. Crewmembers
tive flight days in the presleep period after a private medi- were able to successfully conduct all three examination ses-
cal experiment used both the Space Shuttle Ku-band and sions, requiring an average of 51 min to complete (range:
S-band communication systems to transmit data to and from 4558 min). The ECG acquired was a standard three-lead
170
electrode system, which produces a standard rhythm strip
output on the TIP screen. The quality of the acquired rhythm
strips was comparable to that obtained by common three-lead
systems found in many commercial defibrillators. The CMO
easily read pulse oximetry using the TIP screen. Ausculta-
tion results revealed normal sounds that were easy to hear
above the Space Shuttle background noise. All biophysical
data points were downloaded from the Space Shuttle within
minutes, and the flight surgeon and clinical consultants per-
formed quality control.
Video images were acquired by a macro lens, an otoscope,
and an ophthalmoscope. The macro lens exam was conducted
to establish the clinical utility of acquiring superficial images
of the skin and other dermatological structures. Tympanic
images acquired on orbit using the otoscope clearly revealed
a nondependent distribution of intra-auricular fluid. The
ground-based consulting team visualized valsalva maneuvers.
The external auditory meatus and other external auricular
landmarks were well visualized. The ophthalmoscope was
effective for performing a foreign object survey as well as
conjunctiva, corneal, and iris exams, and it was also effec-
tive for producing images of sufficient diagnostic quality. A
retinal exam was not attempted due to the limited training
available for the crew and the need for application of topical
pharmacological agents.
The video portions of all three examination sessions were
downlinked in real time. Real-time video from the general-
view Space Shuttle camera enabled consultants to observe
the conduct of the exam, including placement of monitoring
sensors and transducers. Still images captured by the crew
were downlinked to the telemedicine workstation. It was the
unanimous consensus of the ground-based flight surgeons
that all data acquired during this evaluation could have been
used effectively for real-time or just-in-time clinical deci-
sions. During the last physical examination session, com-
munications via the Ku-band antenna (required for wide
bandwidth and video communication) were not available on
orbit and the CMO conducted the entire biomedical exam
without any observation by or direction from the flight sur-
geon. This experiment demonstrated that a non-medically
trained crew can successfully collect clinically useful bio-
medical data that prove the feasibility of store-and-forward
telemedicine [24,25].
Space Telemedicine Concepts Applied
in Terrestrial Health Settings
Space Technology Applied to Rural Papago
Advanced Health Care
In 1975, NASA applied its communications expertise to
a terrestrial telemedicine project. NASA and the Indian
Health Service performed a two-year telemedicine project
S.C. Simmons et al.
on the Papago Indian Reservation near Tuscon, Arizona.
This project, called Space Technology Applied to Rural
Papago Advanced Health Care (STARPAHC), involved
mobile health units that were linked to an Indian Health
Service hospital using a microwave communication system.
Non-physician medical personnel performed examinations
aboard the mobile health units, and video-based, audio-
based, and text-based medical data were transmitted to the
Indian Health Service hospitals staff for review. Diagnostic
imagery obtained for transmission included radiography,
microscopy, otoscopy, and ophthalmoscopy. Fuchs stated
that the projects major benefit was providing access to
health care resources not previously available in the local
area [26].
Other Telemedicine Projects
NASA has more recently provided satellite communica-
tions for several national and international telemedicine
projects. The first projects, applications technology sat-
ellite-1 (ATS-1) and its follow-on, ATS-6, were used to
provide teleconsultation services in telemedicine experi-
ments that involved 14 villages in the central Alaskan
Tanana Service unit [27]. NASA provided ATS-3 for both
the American Red Cross and the Pan American Health
Organization to support the medical relief effort after the
1985 Mexico City earthquake, in which there were as many
as 10,000 casualties [21].
In December 1988, a major earthquake devastated much
of Soviet Armenia, resulting in 150,000 casualties. NASA
quickly developed a plan for using telemedicine via satellite
and landlines to provide medical relief for victims. Because
of several technical and logistical difficulties, the system
was not operational until May 1989. Since the system could
not be used to deal with emergent health problems, the focus
was shifted to follow-up consultations. Rayman reported
that these follow-up telemedicine consultations with spe-
cialists at The Uniformed Services University of the Health
Sciences (Bethesda, Maryland), the University of Mary-
land Institute of Emergency Medical Services (Baltimore,
Maryland), The University of Texas Health Science Center
(Houston, Texas), and the Latter Day Saints Hospital/Uni-
versity of Utah (Salt Lake City, Utah) resulted in a change
from original diagnoses in 25% of cases and altered treat-
ment in 24% of the cases. [28]
One month after the Armenian earthquake relief project
began, a major gas explosion from a rail mishap occurred near
the city of Ufa, capital of the Bashkir Republic (a member of
the Russian Federation), which resulted in 1,200 casualties.
Within 3 weeks of this explosion, the NASA-led telemedicine
system was adapted to provide burn victims with consulta-
tive support. Along with providing needed medical support
to disaster stricken populations, this project, later called the
Spacebridge to Armenia and Ufa, provided NASA with a
wealth of practical knowledge in using satellite systems for
telemedicine.
8. Telemedicine
Internet Spacebridge
Because of the progress made by the U.S.Russian collabo-
ration during the Spacebridge to Armenia and Ufa project,
and to explore the telemedicine applications of emerging Inter-
net and Worldwide Web (WWW) technologies, NASA next
undertook the Spacebridge to Russia Internet telemedicine
project. The goals of the project were to: (1) Further develop
operational space telemedicine and (2) test and verify the use
of the Internet for telemedicine and (3) promote terrestrial
applications of NASAs telemedicine and telecommunica-
tions technologies [29]. The Spacebridge to Russia project
involved deploying UNIX-based computer workstations at
several United States and Russian sites, which were connected
via the Internet, using both interactive (real-time) and store-
and-forward modes of telemedicine. The multicast backbone
(MBONE)an open standard for simultaneous, multi-point
communications using the Internetwas used for interactive
consults and lectures. For store-and-forward telemedicine, a
NASA-developed hypertext multimedia medical record was
viewed and navigated using a Web browser [2]. Cases were
posted to two mirrored servers in the U.S. and Russia. Any
consultant who had proper authorization credentials could
review a case and post recommendations to the servers.
The Spacebridge to Russia project had several significant
implications for the future of both terrestrial and space tele-
medicine [2,29]. The project demonstrated the feasibility of
using the Internet for telemedicine. Open-source data repre-
sentation and protocol standards enabled physicians from dif-
ferent cultures and time zones to use disparate PC platforms
to collaborate on cases in a store-and-forward manner. Also,
contemporary Internet security features ensured that only
authorized personnel could view patient-specific information.
The significance of this project will be evident as future, mul-
tilateral space missions incorporate Internet-like technologies
for telemedicine.
Advanced Communications Technology Satellite
NASA has recently completed operation of the experimental
advanced communications technology satellite (ACTS)
program that will further advance the capabilities of satel-
lite communication. This satellite is operated in the high-
frequency Ka-band, which has a large available bandwidth.
The ACTS was available for experiments in several fields,
including telemedicine.
During the winter of 1994, JSC completed a telemedicine
experiment using ACTS and a video fundus camera. During
eight sessions conducted over four weekends, medical spe-
cialists at JSC performed telemedicine medical examinations
on 29 patients from the Fitzsimons Army Medical Center
(redesignated U.S. Army Garrison Fitzsimons since 1995),
Aurora, Colorado. A video fundus camera was used for video
fundoscopy and intravenous fluorescein angiography. B-scan
ultrasonography and three-dimensional stereo imaging were
also performed. Each consultant at JSC individually made a
171
diagnosis before group discussions took place in which a con-
sensus diagnosis was determined. These diagnoses were then
compared to the patients medical record. The kappa score for
agreement between the consensus diagnoses and the known
diagnoses (from the medical record) was 0.9378 (p < 0.001).
This study thus demonstrated the clinical utility of the fundus
camera and the ACTS for telemedicine.
Terrestrial Telemedicine Instrumentation
Pack (Tip) Evaluations
Evaluations of different TIP embodiments were conducted by
researchers throughout the design and development process.
The first terrestrial prototype was clinically evaluated during
1994 in a family medicine clinic in Dickinson, Texas. This
prototype was connected via a 1/2 T1 (768 kbps) videoconfer-
encing system to the University of Texas Medical Branch at
Galveston, Texas. Nurses at the center used the TIP to exam-
ine patients and to consult with otolaryngology, dermatol-
ogy, and ophthalmology experts at the Galveston facility. The
study provided useful technical, training, and human factors
information that was applied to the design of the TIP.
In August 1998, the JSC Medical Operations Branch deliv-
ered a TIP unit to St. Vincent Hospital and Health Center
in Billings, Montana, to be used in the Montana Partners in
Health Telemedicine Network. This network, developed to
enhance delivery of healthcare to rural Montana, is supported
by a Telemedicine Grant through the U.S. Department of
Commerce Telecommunications and Information Infrastruc-
ture Assistance Program. The original partners in this project
included St. Vincent Hospital and Health Center; the Indian
Health Service, Billings, Montana; the Crow/Northern Chey-
enne Hospital, Crow Agency; and the Northern Cheyenne
Clinic, Lame Deer, Montana. Funds for constructing the TIP
for the project were provided by the JSC Technology Transfer
and Commercialization Office, whose mission is to trans-
fer and enable commercialization of NASA technologies to
the private sector to create jobs, improve productivity, and
increase competitiveness of United States companies.
A short pilot study, which used the TIP to provide home
care to the inactive diabetic population, was conducted in
the Northern Cheyenne reservation located in southeastern
Montana. For the purpose of this study, inactive diabetics
were defined as individuals with a known diagnosis of diabetes
who had not received care in the Lame Deer clinic within a
year or more. Of the 488 diabetes patients on the reservation,
approximately 170 were considered inactive at the time the
study was initiated. This target population was chosen for
several reasons: (1) Management of diabetes and its compli-
cations are of major concern in the Native American popula-
tion. (2) The Indian Health Service has an existing standard of
care for patients with diabetes, including baseline studies and
physical examination criteria. This protocol addresses a wide
variety of potential diabetic complications, including skin
ulcers, hypertension, and ocular and cardiovascular disease.
172
Therefore, use of the TIP as an adjunct to the standard dia-
betes protocol tested all of TIPs capabilities in a head-to-toe
diabetes examination. (3) The study offered an opportunity to
reach out to the inactive diabetic patients who were not com-
ing into the clinic.
The primary goal of the project was to evaluate the TIP in
this particular environment with this target patient population
to determine improvements in the design and operation of inte-
grated, portable medical systems that can be applied in space
medicine. The secondary goal was to evaluate the utility of such
systems for terrestrial applications. On the whole, this initial
evaluation project met expectations. The TIP and telemedicine
demonstrated potential clinical benefits in this population, and
patients were satisfied and excited about their experience.
However, process and workflow issues remained problem-
atic. These must be addressed in future project phases. On
the basis of the findings from this pilot project, investigators
made recommendations to: (1) deploy TIP in satellite clinics,
(2) cluster home visits geographically, (3) improve case turn-
around, (4) provide more training and practice for TIP users,
and (5) study the clinical efficacy and effectiveness of this
approach. Investigators also recommended using Partners in
Health Telemedicine Network specialists as integral members
of the health care team since, in the delivery of telemedicine
care, such individuals become critical. Finally, as the logical
extension of successful store-and-forward telemedicine, a
recommendation was made to explore the utility of real-time
telemedicine applications.
Operation Strong Angel
NASA has formally identified the need to develop technolo-
gies and procedures to manage trauma and acute medical prob-
lems as fundamental to space operations. Increased mission
duration and the additional risk associated with construction
of the ISS have necessitated an expansion of existing on-orbit
medical care capabilities. The ability of portable critical care
monitors to provide real-time patient data from a remote envi-
ronment via a satellite communication network was evaluated
as a part of the U.S. Navys Operation Strong Angel humani-
tarian relief exercise in Hawaii [30].
Strong Angel was an experiment in combined civil and
military operations for humanitarian assistance performed as
an extension to the RIMPAC 2000 Naval exercise conducted
jointly by the Pacific Rim countries. This international exer-
cise took place in the waters off Hawaii from May 30 to
July 6, 2000, and brought together the maritime forces of
Australia, Canada, Chile, Japan, the Republic of Korea, the
United Kingdom, and the United States of America for train-
ing operations. More than 50 ships, 200 aircraft, and 22,000
sailors, airmen, marines, soldiers, and coastguardsmen were
involved. Strong Angel was based on a scenario in which
several thousand ethnic minority civilians fled to a neigh-
boring region as a result of a campaign of oppression. The
government of the neighboring region did not possess the
S.C. Simmons et al.
logistical capabilities to deal with a significant refugee crisis
and requested international humanitarian assistance. This
came in the form of Strong Angel.
Further evaluations of portable critical care monitors con-
ducted during Operation Strong Angel included the usability
of the remote interface, clinical functionality in harsh environ-
ments, and engineering design with respect to potential use
on the ISS.
During the operation, ten critical care monitors demon-
strated designs and functionality consistent with ISS per-
formance requirements, but only three of these critical care
monitors supported communication over the satellite com-
munication network. All three required a secondary network
gateway computer to translate proprietary protocols to TCP/IP.
Since proprietary communication protocols have typically
prevented critical care monitors from integrating with stan-
dard TCP/IP intranets and the Internet, adoption of medical
device communication standards by these vendors will benefit
telemedicine both terrestrially and on the ISS.
Telemedicine and Medical Data
Management in the International
Space Station Program
Space medicine operations in support of ISS crewmembers
represent a paradigm shift from Space Shuttle medical oper-
ations. The ISS medical capability is embodied in the inte-
grated medical system that comprises the U.S. crew health
care system (CHeCS) and a suite of Russian medical devices
and supporting infrastructure. Because the medical system on
board the ISS is a hybrid, new requirements were necessary to
acquire, transmit, distribute, integrate, and archive significant
amounts of private medical data.
These data, which are acquired by disparate systems, require
timely, reliable, and secure distribution to different program
participants with a vested interest in ISS medical data. Thus,
episodic telemedicine consults are now embedded in a contin-
uous effort to provide care at a distance for the ISS crew. This
effort includes providing ambulatory care, emergent care, pre-
vention and countermeasures, and environmental monitoring.
To accommodate this varied and continuously growing array of
data, the Space Medicine Division at JSC is in the process
of making a transition to a fully electronic system in support
of mission medical operations.
The first phase of this effort is seen in the installation of an
electronic patient record-keeping system at the JSC clinics.
The utility of this electronic patient record system and of its
supporting communications and data management infrastruc-
ture will be expanded to accommodate all of the participants
in ISS medical operations. Heavy emphasis is being placed
on the development of Web-enabled access to multiple data
sources using desktop integration of these data to facilitate
analysis and reporting.
8. Telemedicine
The capabilities of the space medicine data systems are
designed to be compatible with MCC and JSC information
technology standards for communication and security. The
global requirements that ISS space medicine operations must
fulfill and that motivate the need for a secure network include
the following:
1. Securely manage all crewmember health-related data/
information originating from both on-orbit (ISS, Space
Shuttle, etc.) and ground-based (preflight data entry, etc.)
data sources.
2. Provide a means by which to facilitate the secure manage-
ment and transmission of all pertinent crew health-related
data, both internal and external to the MCC-Houston.
3. Provide the flight surgeon with the ability to quickly and
securely access all pertinent crew health-related data and
information as necessary (i.e., real-time, etc.) throughout a
mission and, at the point of care, to enable rapid decision-
making and provide high quality health care to the crew.
4. Provide secure, remote access/connectivity to health-
related data and information, systems, and applications
to all pertinent remote clients (e.g., electronic medical
record) and consultants.
5. Provide a coordinated plan and resources for securely
storing and managing all crew health-related information
and data.
6. Provide an automated data transmission/distribution sys-
tem that will enable secure and reliable communication,
data translation and transformation, monitoring and alert-
ing, and routing of data and information among systems,
applications, and data stores to provide overall integra-
tion between application, system, and database functions
without the need to develop and maintain custom point-
to-point interfaces.
7. Provide the capability to process information-sharing
protocol data that are stored in the orbital data reduction
complex for inclusion in the medical data repository.
8. Provide the capability to process and display ISS telemetry.
9. Provide commanding authority to medical devices.
10. Provide the capability for private, multicast video confer-
encing.
Onboard Network Architecture
The ISS is equipped with several networks that are designed
to support a variety of operations. Relevant medical data com-
munication systems are shown in Figure 8.2. Command and
control of mission-critical systems is achieved via a 1553
busthe highly reliable communications protocol used com-
monly in high-performance aircraft. NASA medical devices
were designed to nominally communicate via one of four
CHeCS 1553 data buses to one of several centralized computers
(Figure 8.2).
The ISS is also equipped with an operational local area
network (an Ops LAN) to provide an alternative communica-
tions path to the 1553 and to provide the capability for video
173
teleconferencing. A file server computer is linked to other
laptops via the Ops LAN, a radio frequency and wired Ethernet
network of approximately 700 kbps bandwidth. The medical
equipment computer (MEC) is connected to the Ops LAN.
The payload Ethernet consists of standard 10BaseT Ether-
net lines and protocols and two payload Ethernet hub gate-
ways, located in the U.S. Laboratory module, that provide a
10 Mbps data rate. The payload fiber-optic network is used
to send high-rate payload and a limited amount of systems
data to the ground via the Ku-band and to route high-rate data
between payloads on board the ISS. This network provides a
bandwidth of 100 Mbps.
Space-to-Ground Communications
Space-to-ground communications capabilities on the U.S.
orbital segment are based on two systems: S-band and Ku-band.
The S-band communications system is used for primary com-
mand and control of the ISS. It provides air-to-ground voice
communications and is used to downlink critical system
telemetry data either in real time or in store-and-forward for-
mat. The S-band provides a forward bandwidth (to the ISS) of
72 kbps and a return bandwidth (to the ground) of 192 kbps.
When it is implemented within the command and control
architecture and with other operational factors considered,
however, the actual bandwidth available for space-to-ground
medical data transfers is approximately 60 kbps.
The Ku-band is nominally a payloads resource with one-
way data transfer supporting payload file transfer, some
payload system telemetry, and the ISS video system. The
Ku-band provides a total bandwidth of 50 Mbps to the ground
from 12 channels. Its subsystem overhead uses approximately
6.8 Mbps, leaving about 43.2 Mbps of useable capacity. One
channel of the Ku-band is dedicated to the Ops LAN network
that provides 6 Mbps downlink and 3 Mbps uplink for opera-
tions. The Ops LAN connects many operational computers to
the space-to-ground link and thus offers an Internet-like con-
nection with the ISS.
Communications with the U.S. orbital segment are nomi-
nally provided using two high-bandwidth tracking, data, and
relay system satellites (TDRSS). Signal reception is highly
directional, particularly for high bandwidth Ku coverage,
requiring precise antenna pointing and tracking. TDRSS
coverage may be compromised by impingement of the ISS
structure itself into the reception path as well as non-overlap
in TDRSS satellite coverage. Consequently, communications
with the ISS is not continuous. Indeed, expected coverage dur-
ing the assembly complete phase is estimated in the 5565%
range. A third tracking, data, and relay system satellite is
available and permits coverage to rise to over 90% during con-
tingencies such as systems failures or medical events requir-
ing ground communication. However, access to this resource
is not immediate, and the decision to call on it is made only by
the Flight Director. As a result, communication with the crew
and onboard systems is subject to regular losses of signal.
174
Figure 8.2. Medical data communication systems. The ISS is equipped with several networks designed to support a variety of mission opera-
tions. This diagram illustrates at a high level the relevant data communication pathways used to transfer medical information
The Russian Segment of the ISS can communicate with
the MCC-Moscow using direct space-to-ground links during
times when the ISS is within the range of ground tracking
stations. This communications capability can be expanded by
using Russian satellites when tracking stations are not in range.
The flow of station telemetry into the MCC-Houston and the
MCC-Moscow can be facilitated by either Russian or U.S.
space-to-ground networks. During certain high-risk activities,
such as Space Shuttle or Soyuz docking or undocking with
the ISS, the use of both networks is preferred to provide
telemetry to the MCC-Houston and the MCC-Moscow. The
ability to command the ISS using either of these space-to-
ground communication assets is also preferred during high-
risk activities. Medical data are transferred using both of
the communication systems and arrive in a timely manner to the
lead flight surgeon in the MCC-Houston.
Ground Segment
Communications from the U.S. orbital segment pass through
White Sands, New Mexico, and are routed to either JSC (oper-
ations data), or to the Marshall Space Flight Center in Hunts-
S.C. Simmons et al.
ville, Alabama (payloads data). Each of the partner control
centers is linked to the MCC-Houston through an external
interface system.
Inside the MCC-Houston are several isolated networks.
Data communicated via the S-band pass into the Ops LAN.
This network is considered mission critical and therefore is
fully redundant and highly secure. Data from the OCA/Ku-
band are passed on to the OCA LAN. Finally, flight control
disciplines have access to the JSC network for email and gen-
eral office services.
NASA space medicine has established a dedicated data cen-
ter at JSC. This center is protected by its own firewall and is
connected to users by virtual private network (VPN) technology.
Access is carefully controlled to protect the private medical
data stored on the servers in this center. The center contains
the electronic medical record with live interfaces to the clini-
cal laboratory information system at JSC and the Longitudinal
Study of Astronaut Health (LSAH) epidemiological database.
These interfaces operate on a middleware interface engine
system. The data center also supports an FTP [final transfer
protocol] server, which acts as a central repository for all ISS
medical data.
8. Telemedicine
Implications for Telemedicine
From a medical perspective, understanding the network and
communications systems infrastructure of the ISS is crucial
since these systems will provide the infrastructure by which
care is provided at a distance. Issues of latency, bandwidth,
availability, quality of service, etc., influence exactly what the
nature will be of that care at a distance.
Simply, these technical factors play a fundamental role in
defining the medical support concept of operations. Thus, if
we know that using the S-band provides a communication
bandwidth that is equivalent to a 56-kbps modem and, more-
over, that this bandwidth is only periodically available, we
know that very careful decisions must be made regarding the
resources placed on board the ISS. It also means that the med-
ical expertise of the flight surgeon on the ground can be relied
upon simply by invoking the command to Call Surgeon!
The promulgation of the Internet is another contributing
force of change that must be acknowledged when consider-
ing how to evolve the ISS medical concept of operations.
Several key Internet technology developmentsincluding
VPN, public/private key infrastructure (PKI), high-speed
commercial connectivity, interface engines, and partner col-
laboration toolshave caused us to rethink our mission sup-
port philosophy.
Traditionally, ground support of mission operations has
been largely centralized and, for the most part, wholly con-
tained within large MCCs. The development of networked
collaboration and associated technology enables a distributed
vision for mission support, in which centralized support cen-
ters are augmented by on-call mission support personnel
outside the centers. For ISS medical operations, this could
result in on-call flight surgeon and biomedical engineer sup-
port from their offices or homes. Also, this would enable peer-
to-peer collaboration between the crew surgeon or surgeons
in the MCC-Houston and medical personnel in international
control centers or agency offices. This approach may be more
practical, and potentially more cost-effective, than the tradi-
tional around-the-clock support philosophy.
Current Utilization for ISS Telemedicine
It is important for the flight surgeon to understand the sources,
accessibility, and reliability of data that will permit medical
decision-making. Medical data are transmitted from the ISS
to the flight surgeon in the MCC-Houston via a variety of
pathways.
The current operational flow of data from onboard systems
to the ground control team is depicted schematically in Figure
8.3. A central component of this system is the MEC, which is
intended to serve as the primary control, display, and down-
link interface for ISS medical data. This personal notebook
computer, which is a variant of the generic ISS notebook com-
puter or portable computing system, is dedicated to CHeCS.
CHeCS systems with communication interfaces compatible
with the MEC will initially download their data to the MEC,
where these data will be stored on the hard drive for later
175
downlink. Other CHeCS systems will store data locally on
PCMCIA cards [personal computer memory card interna-
tional association cards; now more typically known as PC
cards] that will be removed from their respective devices
and inserted into the MEC for subsequent data transfer. The
CHeCS portable clinical blood analyzer has direct data inter-
face capabilities that may be exploited in the future. Current
procedures call for portable clinical blood analyzer data to be
entered by keyboard into a database on the MEC. Using exist-
ing data transmission capabilities should eliminate transcrip-
tion errors and facilitate direct incorporation of these data into
a digital mission medical record. Another method allows users
to directly enter data into the MEC using the MEC keyboard.
The In-flight Examination Program, an electronic medical
record that is optimized for spaceflight examinations and for
CHeCS-specific diagnostic studies, is resident on the MEC
for clinical data entry. Files stored on the MEC can be trans-
ferred via the Ku-band/OCA system or 1553 data dumps.
Although most CHeCS data will be stored and forwarded,
certain devices can downlink data in a real-time mode, either
via one of the four CHeCS 1553 buses available in different
ISS locations or through the MEC. The CHeCS 1553 buses
connect directly to the payload computer for real-time down-
link from the MEC. Also, other medical devices, including the
defibrillator, blood pressure/ECG monitor, volatile organic
analyzer, and several radiation monitors (the tissue-equivalent
proportional counter and the extravehicular and intravehiclar
charged-particle directional spectrometers), have this capabil-
ity. The defibrillator can transmit a single-lead ECG rhythm
strip in real time via the 1553 bus and payload computer,
and the blood pressure/ECG monitor can telemeter three
ECG leads in via the MEC. In addition to real-time downlink,
these 1553-enabled devices can buffer their data in memory
and perform subsequent normal or extended data dumps,
depending on communications availability.
Other methods of data flow include the crew verbally
delivering data or sending e-mail. The latter two categories pose
particular problems for accurately communicating and archiving
these data, since the nature, format, and content of the message
are much less formal than the other examples we described
above. Private medical conferences, nominally intended as pri-
vate video teleconferences between a crewmember and a ground
flight surgeon, are an important element of medical care for the
ISS. One might consider this as equivalent to the history-taking
portion of any patient encounter. However, these conversations
facilitate and establish a rapport between physician and patient,
and these opportunities for one-on-one personal communication
are vital components in maintaining a healthy crew, especially
during a long-duration mission. Therefore, the psychological
aspect of these interactions should not be underestimated.
Finally, medical data may also be acquired from nominally
investigative systems such as the metabolic gas analyzer and
sonograph and communicated to JSC via the Marshall Space
Flight Center and its Telescience Center.
Consequently, the flight surgeon discipline and integrated
medical group generally face a significant challenge when it
176 S.C. Simmons et al.

Figure 8.3. Medical data are transmitted from the ISS to the Flight Surgeon in MCC-H via a variety of pathways. This schematic depicts the
current operational flow of data from onboard systems to the ground control team. A central component of this system is the Medical Equip-
ment Computer (MEC), which is intended to serve as the primary control, display and downlink interface for ISS medical data

comes to developing an integrated plan for medical data han-
dling simply due to the fact that the method, pathway, and
medium for communicating these data varies significantly.
The result is a heavy manual role in receiving, capturing,
integrating, and comprehending these data. However, efforts
are under way to semi-automate this process by using state-
of-the-art medical data management tools where possible.
Commercial-off-the-Shelf (COTS) Enhancements
Diagnostic imagery is a key component of telemedical capa-
bilities. In particular, ultrasound is increasingly becoming an
adjunct to plain film x-ray. Space-relevant applications of this
technology may include the detection of renal calculi, hemo-
peritoneum, and pneumo- and hemothoraces. The Human
Research Facility, which is currently on board the ISS, has
an ultrasound system (the HDI 5000 (Advanced Technology
Laboratories, recently bought by Phillips Medical Systems) )
as part of its life sciences research hardware complement for
echocardiographic and other ultrasound imaging. Although
the system is nominally intended for research purposes, the
HDI 5000 system is available for use as a clinical diagnostic
device. However, implementation of this clinical capabil-
ity raised several questions, including: (1) Can the Human
Research Facility ultrasound and the ISS communications
infrastructure be integrated to deliver real-time streaming
video to the flight surgeon? (2) Can this system deliver the
minimal field rate and resolution requirements to permit reli-
able and accurate diagnoses? (3) Can a minimally trained
CMO capture reliable diagnostic images? (4) Are terrestrial
sonographic diagnostic protocols appropriate and efficacious
in weightlessness?
These and other implementation issues have been addressed
in a manner that demonstrates a prototypical evolution of a
telemedicine capability (see Chap. 10, Medical Imaging).
Specifically, the solution emerged from a confluence of con-
straints. Among these constraints were communication band-
width and system integration (technology), skill level of the
local care provider and remote care provider (training), and
definition of appropriate diagnostic protocols (clinical and
anatomical). The human factors of using these devices in a
clinical scenario under the conditions of microgravity also
8. Telemedicine
Figure 8.4. This ISS crewmember is positioned in a comfortable
manner in front of the Health Research Facility. It can be seen that
the ergonomics involving the use of standard interface devices such
as the display, keyboard and mouse may not be the most optimal in
microgravity for medical situations (Photo courtesy of NASA)
must be considered. The terrestrial approach to using key-
boards and mouse pointers is complicated in microgravity.
Most COTS medical devices rely on gravity to facilitate the
patient and caregiver encounter. These ergonomic assump-
tions may need to be reengineered for microgravity environ-
ments (Figure 8.4).
Initially, as in previous space programs, ISS medical
operations will rely on the observations and diagnostic
judgment of CMOs, who are not usually physicians. Since
a CMO is required to describe an observation or a physi-
cal finding to a flight surgeon on Earth, potentially critical
crew health or mission decisions would be made on the
CMOs interpretation of a heart sound, a rash or lesion, or
an otoscopic or ophthalmoscopic exam. The capability to
transfer images, video, auscultation, and other data directly
to the flight surgeon so that he or she can virtually make
an observation can provide an increased level of diagnostic
confidence.
177
The Future: Telemedicine
for Exploration-Class Missions
Designing an exploration-class mission telemedicine system
must consider myriad factors, including mission profile,
users, intended use, information sources, and available tech-
nologies. The first Mars exploration missions may take place
with an international crew of four to six persons. Assuming
there are no major developments in propulsion technology,
the entire trip may last 9001,000 days, with a 600-day stay
on the Martian surface and 180 days required each way for
interplanetary transport. This mission will expose crewmem-
bers to hazardous, confined, and engineered environments
during the entire period.
It is likely that at least one of the Mars crewmembers will
be a physician, and one of the other crewmembers will be a
CMO with some degree of medical training. The other crew-
members should also be able to interact with the system
usually as patientsand they also may enter or browse some
of their own data. This predicates that the information system
be designed to accommodate both medically sophisticated and
unsophisticated users. On Earth, flight surgeons, mission
controllers, and medical specialty consultants should use similar
user interfaces for support continuity.
Current medical operations concepts rely on non-physician
CMOs who have minimal medical experience and who are
supported by extensive communications with Earth-based
medical personnel. This philosophy is also predicated on the
ability to return to Earth for definitive care, as these missions
are wholly conducted within low Earth orbit. Missions out-
side low Earth orbit, including crewed Mars exploration, will
require a paradigm shift in medical support. Crewmember ill-
ness or injury will have to be treated in flight, as the Mars
crew will be from 35 million to 230 million miles away, mak-
ing return to Earth for medical treatment unfeasible. Traveling
at 299,338 kilometers per second (186,000 miles per second),
radio communication will require up to 20 min to reach Mars
from Earth. Extended periods of communication blackout
may leave the Mars explorers without Earth contact for weeks.
Crews will therefore have to manage acute medical events and
recover from chronic complications without assistance. These
potential maladies, including permanent incapacitation or
injury, will require unique applications of telemedicine.
As mentioned previously, bandwidth bottlenecks and
barriers (routers, firewalls, switches, etc.) minimally affect
communications latency on Earth because the distances are
short (relative to light-seconds). However, distance will sub-
stantially affect latency during planetary exploration mis-
sions. As a result of the latency involved in planetary mission
communications, telemedicine will be primarily conducted
in a store-and-forward mode. Although real-time consulta-
tion with Earth will not be possible during emergent care, the
Mars mission telemedicine system should record and transmit
data real time from the onboard medical instrumentation and
biomedical monitoring systems. This will enable subsequent
178
review by the onboard crew physician and Earth-based medi-
cal personnel. The store-and-forward approach will be useful
for specialty consultation, patient follow-up after emergen-
cies, and preventive medicine.
However, if missions involved multiple inhabited Mars
bases or pressurized rovers, real-time or just-in-time telemedi-
cine could be practiced between sites. Medical tele-presence,
or tele-intervention, is another concept related to telemedi-
cine. This involves direct patient intervention from a distance
and includes tele-surgery. Latency makes tele-intervention
from Earth impractical for the Mars missions. The communi-
cations infrastructure for a Mars mission will be similar to low
Earth orbit. A constellation of satellites similar in function to
TDRSS will be needed in Mars orbit to facilitate communica-
tion with the surgeon console when a direct line of sight
with Earth does not exist.
The unique environments that are associated with space
travel and remote Earth settings, such as Antarctica and under-
sea habitats, may have adaptation patterns similar to those
expected to occur during Mars missions. Countermeasures to
the deleterious effects of space flight have been developed in
both the U.S. and Russian space programs and will be used
during Mars exploration missions. Each crewmember will
have a countermeasures prescription to follow. Both the
prescription and the biomedical data monitored during execu-
tion of the countermeasures program will need to be tracked
by the crewmember, the crew physician, and the Earth-based
medical personnel. Routine tests of crew physiologic metrics
will be useful to determine the efficacy of the countermeasure
prescription and to track the course of crew health.
Environmental monitors will also be linked to the system,
so environmental variables, including radiation, pressure, con-
taminants, temperature, etc., can be logged in the electronic
medical record used in medical diagnoses and treatment. Bio-
medical monitoring during EVA will likely include internal
suit parameters (air temperature, humidity, space suit pres-
sure, etc.), physiologic variables (ECG, metabolic rate, skin
temperature, etc.), and external environmental variables (radi-
ation type and dosage, external temperature, etc.), which must
be automatically entered into the system. Automated entry of
periodic physical and psychological monitoring data will help
chart the progress of the countermeasures regimen and would
include data obtained during exercise or tests of orthostatic
tolerance, motor skills, and cognitive ability.
Normal preventive health care operations will include peri-
odic multimedia wellness examinations. The Mars telemedi-
cine system will acquire inputs from an array of sensors and
devices. A variety of imaging sensors will acquire time-based
(video) and still images from specialized medical cameras,
endoscopes, and noninvasive imaging devices (i.e., sonogra-
phy or roentgenography). Biomedical sensors will measure
physical (blood pressure, heart sounds), electrical (ECG), and
chemical (blood and urine chemistry) aspects of crewmember
physiology. Examiner observations and comments will also
S.C. Simmons et al.
need to be recorded in the system. These may take the form of
progress notes via text or voice recordings.
In the event of an illness or injury, the health informatics
system must be able to collect a plethora of information and
present it to the crew physician in a manageable form. A Mars
telemedicine system will benefit from developments in several
technologies. A critical assumption is that these technologies
will be available from three to five years before Mars depar-
ture so that sufficient time is available for integration within
the Mars health care system. All Mars systems will benefit
from advances in computer, telecommunication, manufactur-
ing (microtechnology and nanotechnology), and power tech-
nology. Developments in sensor and imaging technologies
will reduce or eliminate the invasiveness of medical diagnosis.
Improvements in the way humans interact with instrumenta-
tion, computers, and data will offer perhaps the greatest effects
on an exploration telemedicine system. Advances in display
technologyincluding large, low-power, flat panels, pen and
touch-screen interfaces, heads-up displays, and holography
will benefit Mars-based and Earth-based users. Voice and
handwriting recognition will enable a more natural interface.
These technological advances can occur on Earth because of
its friendly radiation environment. Radiation can cause cata-
strophic failures in electronic equipment which uses advanced
high density microelectronic circuits, such as that commonly
found in currently manufactured medical electronics. The abil-
ity for radiation to cause equipment failures will increase with
further electronic miniaturization. The use of modern tech-
nology in medicine is usually born out of an evidenced based
requirement for it use clinically and therefore the capability
and features of future medical hardware will most likely also
be a medical requirement. Given that we will not walk on the
Moon for at least another 10 years, will we be able to use COTS
medical technology? Will we accept legacy medical hardware
for future exploration missions or build non-COTS advanced
radiation hardened medical hardware?
The unique requirements of crew health prevention and
monitoring during the past 40 years of space travel has mandated
that the space medicine discipline depends on telemedicine
as the major means of delivering health care. This paradigm
will be dominant until significant medical technology and
skill becomes resident on orbit. The cost of creating advanced
clinical care capability on-orbit prevents this from happening,
and currently deorbiting and returning a patient to a tertiary care
facility on earth is a more effective and inexpensive solution to
mitigate risk of the most serious illness and injury.
If advanced medical capability is not present, the ability to
monitor crew health and to prevent illness during missions
will require the use of telemedicine. The amount of reliance on
Earth-based medical support needed for an exploration-class
mission is not well known; however, high-fidelity, long-duration
simulations on Earth and on the ISS may help address these
issues. The role of telemedicine in exploration-class missions
will probably be similar to its present role on Earth: as a
8. Telemedicine
subset of health informatics that serves as the transport means
for the exchange of medical information.
Because no terrestrial telemedicine paradigms create a 5- to
20-min delay of real-time data streams, the unique require-
ments of space travel will again challenge our ability to
remotely deliver medical care.
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9
Medical Imaging
Ashot E. Sargsyan
It has been more than 100 years since Wilhelm Conrad Roent-
gen took the first diagnostic images using X-rays [1]. The
early applications of medical imaging sought to diagnose sim-
ple pathology such as bone fracture or foreign bodies. Today,
medical imaging has become a discrete medical discipline and
an essential part of prevention, diagnosis, and treatment stan-
dards throughout the world, revolutionizing virtually every
aspect of clinical medicine. A number of imaging modalities
are routinely employed not only to rule out overt disease or
injury but also to reveal anatomical abnormality and dysfunc-
tion of organs, often well ahead of clinical manifestations.
The advent of human space flight has brought about the
need for physicians to remotely monitor space crews for
signs of missionimpacting medical problems. Some of
these early space biomedical systems were developed before
similar technological advancements for terrestrial medicine
were even considered [2]. Presently, the technological level
of terrestrial health care has surpassed biomedical systems
originally developed for space programs, and the challenge to
space medicine is to determine which terrestrial medical tech-
nology should be adapted for space use and when that should
occur. Spaceflight medical risks have become more apparent
with long duration missions to low Earth orbit (LEO) aboard
space stations such as Skylab, Mir, and the International Space
Station (ISS) [3,4]. Under these circumstances, crewmembers
with any existing subclinical deviations from the norm are in
space for a fairly long period where the weightless environ-
ment presents a number of novel and potentially exacerbating
factors. Although the crews are trained and equipped to han-
dle minor medical conditions, a serious event could rapidly
overwhelm the modest onboard medical capability and would
almost certainly qualify as a medical emergency. Many of the
conditions that could occur in space might present significant
diagnostic and therapeutic challenges to even the most mod-
ern terrestrial health care facility. These factors conspire to
limit the ability of a flight surgeon to make difficult decisions,
such as discerning between initiating a medical evacuation
back to Earth or remaining on orbit for treatment and addi-
tional observation. Obviously, these critical decisions should
be based, if possible, on objective information and scientific,
evidence-based approaches so that the best possible outcome
is achieved with minimal impact to the mission.
History of Diagnostic Imaging in Space
Medical imaging experiments during space missions of the
1970s and 1980s were part of aggressive biomedical research
programs, which were primarily focused on physiological
changes in microgravity and on the ability of humans to live
and function in space for extended periods of time and return
to normal health upon completion of their missions. In-flight
imaging was first performed in 1982 aboard the Salyut-6 and
Soyuz-T6/Salyut-7 orbital complexes in a joint Soviet-French
research study [57]. B-mode quantitative echocardiography
with M-mode was performed with various cardiac measure-
ments, as well as continuous-wave Doppler measurements in
superficial arteries. A relatively recent technology advance at
the time, B-mode consisted of grayscale tomographic frames
updated many times a second, thus providing a live (real-time)
picture of the heart in motion. M-mode, a live recording of
cardiac motion along a selected axis vs. time, however, was
still useful in objectively quantifying the changes in chamber
size and other dimensions throughout the cardiac cycle. After
this pilot study, further investigations were performed on the
Soyuz T/Salyut-7 orbital complex, which was visited by six
long-duration (65237 days) and five short-term (812 days)
crews during 19821986. Ultrasound imaging was validated
extensively during the longest of these missions (Soyuz T10)
by physician-cosmonaut Oleg Atkov, who performed serial
sonographic examinations of 15 cosmonauts on orbit. A suc-
cessful abdominal ultrasound examination was performed
and documented for the first time during this mission, and
hemodynamic assessments were combined with research to
develop improved ultrasound techniques and equipment for
use onboard space stations [8]. A series of French and Soviet
experiments were later conducted aboard the Soyuz TM/Mir
orbital complex beginning in 1988 [911]. In addition to
181
182
echocardiography, the latter study for the first time included
complex vascular imaging tasks at higher ultrasound frequen-
cies, with concurrent Doppler measurements of blood flow in
central and peripheral vasculature. Another very important
experience in this Soviet-French program was the success-
ful performance of real-time remote guidance of the cosmo-
naut-operator with limited preflight training by experts at a
remote location; a ground communications segment was
added to link the space-based operator with an expert outside
Russia [11]. These complex procedures were undertaken to
demonstrate new in-flight training techniques and to enhance
operator performance and the resulting scientific value of the
study. However, the operational implications of the concept
of ground-based expertise and remote feedback and guidance
were significant and remain so in the era of the ISS.
The first two echocardiographic series performed in the U.S.
space program took place aboard the STS-51D (April 1985)
and STS-51G (June 1985) Space Shuttle missions, the latter in
cooperation with French scientists. The ADR-4000 (Advanced
Technology Laboratories, ATL, USA) portable mechanical
sector scanner used had undergone substantial modifications
to comply with the spaceflight requirements. Studies involved
precision cardiovascular measurements and once again dem-
onstrated feasibility of sophisticated and technically demand-
ing imaging studies in microgravity [12]. The same device
was flown on three more Shuttle missions between 1990 and
1992, later to be replaced by another modified echocardiog-
raphy system (Hewlett Packard, USA) on STS-55 in 1993.
Between 1992 and 1995, NASA flew a modified Biosound
Genesis II scanner (AERIS) with advanced Doppler capabili-
ties aboard three more Shuttle missions (STS-50, 65, and 71)
and the long duration Mir-18 mission.
Thus, by the mid 1990s, eight different imaging devices had
been flown in LEO, all of them sonographic imagers, and most
of the essential aspects of this modality were explored in space to
some extent. The success of these experiments and demonstra-
tions has justified modification and delivery of a sophisticated
multipurpose ultrasound system (HDI-5000 from ATL/Philips,
USA) for the laboratory module of the ISS as part of the Human
Research Facility (HRF) [13]. Although its primary purpose is
to support advanced biomedical and cardiovascular research in
space, this instrument has also been recognized as an important
asset for operational space medicine.
Application of Imaging Modalities in Space
Medicine
Modern diagnostic imaging methods could be considered as
promising potential additions to existing space health care sys-
tems, to enable effective mitigation of medical risks for LEO
and future exploration-class missions. As the required degree
of clinical autonomy increases with mission duration, size of
the crew, and distance from Earth, so will the demand increase
for enhanced space-based health care systems. Some aspects of
A.E. Sargsyan
such enhancements have been addressed in literature [1416].
As remote sensing of other planets provides more data and
space propulsion systems undergo dramatic improvements, it
seems more and more likely that health-related matters rather
than engineering challenges will dominate the concerns for
interplanetary missions [17,18]. Therefore, focused attention
to the medical support of future missions is warranted, cer-
tainly including the use of ISS as a test bed for technology
development.
The introduction of medical imaging into the space health
care systems seems to be an obvious requirement, yet a num-
ber of clinical questions and operational problems become
evident. Does the known and estimated medical risk in space
warrant the expense of placing diagnostic imaging hardware
aboard a spacecraft? How should diagnostic imaging proce-
dures be conducted in the space environment? How much
effort should we dedicate to pure science versus improve-
ment of the operational medical capability, and what are the
possibilities for dual-purpose systems? Can various medical
imaging modalities in space help rule out pathology in a man-
ner that minimizes mission impact and maximizes crew health
and performance? How should the terrestrial diagnostic proce-
dures and protocols be modified to work effectively in space?
Who should perform the studies, and can those individuals
be adequately trained, given the paucity of medical training
time for ISS crews? How should the data be transmitted back
to Earth for interpretation, and how effective can such inter-
actions be? To what extent would medical visualization data
change the triage, treatment, and outcome of specific illnesses
and injuries? Some of these and related questions and prob-
lems are discussed in this chapter.
Conventional Radiography and Fluoroscopy
Standard X-ray capability could play a leading role in diagnos-
ing many conditions that may occur in space. Visualization of
lung parenchyma seems to be an obvious application, which
would be sensitive for many conditions in microgravity. For-
eign body inhalation may lead to atelectasis and/or secondary
pneumonia, and a radio-opaque foreign body itself would be
possible to identify, localize, and describe with chest radiogra-
phy. Inhalation of fuel or oxidizer vapors, as happened during
the Apollo-Soyuz mission, could result in serious pneumoni-
tis. Given the limited ability to treat pulmonary injury of these
types on orbit, a means of following the effects of exposure
would provide the flight surgeon with the necessary informa-
tion to advise the flight control team regarding the need for
crew return. Although the risk of deep vein thrombosis (DVT)
in space remains controversial, some experts believe that lower
extremity hypodynamia and blood changes may be predispos-
ing factors. Pulmonary embolism with infarction would be a
condition where conventional chest X-ray would be the diag-
nostic modality of choice. For some conditions, such as pneu-
mothorax and pleural effusion, microgravity may reduce the
sensitivity of this method to an unacceptably low level, as the
9. Medical Imaging
gravity-dependent anatomy of these conditions would change
and might produce excessive false negative results. Radiog-
raphy may be applied to gastrointestinal pathology in space
to rule out foreign bodies, inflammatory conditions, or ileus.
However, many of the radiological diagnostic representations
of obstruction and perforation, such as gas-fluid levels, are
gravitationally determined and may not be present in micro-
gravity. The role of oral contrast agents must also be examined
for microgravity conditions; according to preliminary obser-
vations, these may still be helpful if used with knowledge of
their altered distribution patterns.
Intravenous (IV) administration of iodinated contrast might
be indicated in ureteral obstruction or other conditions that
normally require intravenous pyelography (IVP). However,
little is known of the behavior and effects of IV contrast agents
in conditions of space flight. With the appreciable incidence
of anaphylactic and hypersensitivity reactions to these agents,
as well as extremely limited means of response, sonography
would most likely be the method of choice for diagnosing
most renal and other urological pathology.
Radiography would probably be the most sensitive imaging
modality for ruling out, confirming, or describing fractures,
and for monitoring bone healing. These and other consid-
erations had driven radiography to be considered in the ini-
tial designs of the Space Station Freedom in the late 1980s
[19,20]. However, hardware limitations, budget cuts, and
changing medical requirements resulted in its removal.
Thus, even with the use of the latest X-ray electronics and
highly sensitive digital detector arrays [21,22], the power
consumption, potential for electromagnetic interference with
station electronics, weight, and volume have not yet justi-
fied placement of radiographic capability aboard any existing
spacecraft.
Radiography may be a medical requirement for the
space medicine clinics of exploration class planetary bases.
Although fractional lunar (1/6 g) and Martian (1/3 g) gravity
may still compromise the practical significance of some grav-
ity-dependent radiological signs, radiography will be neces-
sary, as a minimum, for evaluating bones and for suspected
pulmonary conditions, conventional as well as occupationally
or environmentally derived. For example, the effects of recur-
rent inhalation of even minute quantities of the pervasive lunar
or Martian dust may induce syndromes analogous to occu-
pational lung diseases and may require periodic imaging for
screening to complement pulmonary function tests in moni-
toring for signs of pneumoconiosis and associated pathology.
Attempts have been made to build highly portable radio-
graphic devices based on low energy pure gamma-emitters,
such as iodine 125 [23]. In spite of occasional reports of suc-
cessful experiments, such devices have not gained popularity
due to numerous inherent limitations. For space applications,
they would deserve serious consideration if relevant condi-
tions, such as metallic foreign bodies in extremity tissues or
small bone fractures, occurred with substantial prevalence.
Space medicine should closely monitor new developments
183
in technology of radiography, looking for systems with auto-
mated exposure control that would combine more effective
and electromagnetically unobtrusive X-ray sources and larger
sensor arrays or other detector systems with both high sen-
sitivity and wide dynamic range. A solid analysis of many
aspects of the future of radiography in space is given by Hart
and Campbell [24].
Computed Tomography
With only modest radiation exposures, present-day CT scan-
ners produce quality high-resolution images of any part of
the body in a standardized, easy-to-interpret format. Cur-
rently, diagnostic sonography successfully competes with
CT terrestrially in most abdominal and soft-tissue applica-
tions; however CT remains the method of choice for intra-
cranial, craniofacial, pulmonary and mediastinal, and some
retroperitoneal disorders. The technology has advanced over
recent years with the advent of high-performance helical scan-
ners with significantly increased speed and computing power
[25]. However, todays CT scanners are still too heavy, con-
sume too much power, produce too much heat, and occupy
too much volume to be considered for use aboard spacecraft.
Their maintenance is complicated, and some of their com-
ponents, such as X-ray tube cooling and power subsystems,
would require a radical and very costly redesign to operate
properly in microgravity. Of the above listed factors, power
consumption alone is prohibitive for space use and will prob-
ably remain so until drastically more effectual X-ray sources
are developed.
Space medicine is not the only area that might benefit from
CT miniaturization. A steady demand exists for intraoperative
and bedside computed tomography, which has driven develop-
ment of commercial devices that can be moved into and out of
operating rooms or intensive care units. However, these devices
employ a classical terrestrial hardware design, utilizing a mas-
sive gantry and heavy power and cooling components.
Should an effective X-ray source with low electromagnetic
interference and power consumption become available, CT
might be seriously reconsidered for use in space. In micro-
gravity, an attractive possibility exists to replace rotation
of the X-ray tube and the opposing detector array with safe
rotation of the properly positioned and constrained patient.
Taking advantage of microgravity, such an approach would
eliminate the need for the bulky gantry, with both the X-ray
source and the detector array fixed on existing structures of
the station, such as an opening between adjacent modules
(Figure 9.1). The patient rotation mechanism would require a
position sensor to provide data for CT reconstruction calcu-
lations. By substituting longitudinal translation for rotation,
radiographic images in standard projections (known and used
as topograms for CT positioning) could be acquired. Fur-
thermore, CT can be expected to be the mainstay of imaging
facilities at future extraterrestrial bases with large numbers
of inhabitants.
184
Figure 9.1. A hypothetical system for X-ray computed tomography
in microgravity: 1- X-ray source; 2- detector array; 3- fan-shaped
X-ray beam; 4- subject; 5- the axis of subject rotation; 6- fixed ISS
structure; 7- subject restraint system with position markers
Magnetic Resonance Imaging
Since the initial clinical applications devised and realized
by Raymond Damadian and colleagues in the 1970s [26,27],
MRI has revolutionized clinical medicine. MRI is of great
value to space medicine terrestrially for its unsurpassed
imaging fidelity in revealing musculoskeletal and spinal
pathology and for its capability to noninvasively screen the
central nervous system for asymptomatic conditions such
as vascular and parenchymal malformations. In space, MRI
would be of enormous scientific value in enhancing the
knowledge of space physiology and adaptation and in evalu-
ating effectiveness of bone and muscle-preserving physical
countermeasures. However, in spite of its great value, MRI
cannot be installed aboard present spacecraft. MRI scanners
are heavy, power-intensive, and prohibitively large. Further-
more, the high-density magnetic fields created by diagnostic
MRI systems will not be tolerated by the sensitive avion-
ics aboard spacecraft. Certainly, new magnet configurations,
along with advances in high-temperature superconductivity
and radio electronics, already show the possibility to dramat-
ically reduce the mass, power and volume of clinical MRI
technology. Space biomedical engineers are closely moni-
toring the developments in this advancing area of noninva-
sive diagnostic imaging.
Nuclear Imaging
Most nuclear imaging techniques, both static and dynamic,
were initially based on the detection of primary or secondary
gamma radiation emitted by radiopharmaceuticals administered
A.E. Sargsyan
orally or intravenously and eventually accumulated via metabolic
uptake in the organs or tissues of interest. The use of positron-
emitting isotopes and high-resolution dual-and single-photon
tomographic systems has established a new capability to
evaluate metabolic structural disorders. A limited number
of nuclear imaging techniques, if available, could be use-
ful for medical diagnostics or monitoring in space. These
might include bone scintigraphy for evaluating bone loss and
fractures or nuclear lung perfusion and ventilation scans for
suspected pulmonary embolism, pneumonitis, or atelectasis.
However, gamma-scintillation cameras are inherently heavy
due to the need for collimation and precise detector posi-
tioning and may require constant flow of power to maintain
multiple detectors in a calibrated state. The operational chal-
lenges associated with any single aspect of supply and/or pro-
duction, processing, and handling of radiolabeled agents in
space, radiation shielding, or even waste management would
prohibitively impact mission operations. All of these factors
have effectively precluded the use of these imaging methods
in space.
Electron Beam Computed Tomography
Since the early 1990s, electron-beam computed tomography
(EBCT) has been steadily growing in popularity and accep-
tance as a noninvasive screening tool for coronary artery dis-
ease (CAD). Although it has demonstrated the capability to
predict coronary incidents in asymptomatic populations [28],
it is only slowly becoming incorporated into medical screen-
ing standards. EBCT is also extensively studied as a clinical
evaluation tool. With the use of contrast enhancements, the
method may be accepted soon as standard for clinical situ-
ations other than CAD, primarily those associated with the
lungs and the respiratory tract [2932]. EBCT may replace
cardiac catheterization and coronary angiography in older
astronauts (cosmonauts) with risk factors for or symptoms of
CAD. EBCT would be an excellent adjunct to functional and
imaging studies such as exercise stress testing and exercise
99m
Tc or 201Tl-scintigraphy, the predictive ability of which is
doubtful for occult CAD in asymptomatic individuals. As the
age of space crewmembers increases, EBCT will probably be
used as a screening tool for astronaut selection and retention
purposes. Equipment size and complexity preclude the use of
EBCT during space flight for the foreseeable future.
Endoscopy
Gastrointestinal (GI), pulmonary, or urologic endoscopy is
often the method of choice to evaluate and treat disease or
injury in these regions. Some examples of medical scenarios
that would require endoscopic evaluation and possibly treat-
ment in space include upper-GI conditions (emesis-induced
Mallory-Weiss tears related to space motion sickness, stress
ulcers, a foreign body in the esophagus), pulmonary aspiration
of foreign bodies, conditions requiring bronchial lavage, and
9. Medical Imaging
urolithiasis. Diagnostic or therapeutic endoscopy has not been
considered a necessary on-orbit capability, since the probabil-
ity of medical events requiring this mode of imaging in space
is fairly low and the necessary degree of proficiency is cur-
rently not possible to achieve in non-physician crewmembers.
Nonetheless, many aspects of endoscopy have been studied
in conditions of simulated microgravity. In 1999, Jones and
colleagues [33] successfully performed complicated urologic
endoscopic procedures on an animal model in parabolic flight.
NASA Medical Operations has also investigated the feasibil-
ity of surgical endoscopy (thoracoscopy and laparoscopy)
using a microgravity animal model [34]. In most of these
experiments conducted on the KC-135 microgravity labora-
tory aircraft, associated gas insufflation and biohazardous
fluid containment were managed successfully. Interestingly,
a cold light source needed for these techniques had already
been spaceflight-tested on the STS-89 Space Shuttle mission
as part of the Telemedicine Instrumentation Pack experiment
[35]. Although many of the aspects of microgravity endos-
copy remain unknown or controversial, enough knowledge
and experience has been accumulated to confirm its technical
feasibility and diagnostic utility. Endoscopic manipulation is
considered invasive and inherently risky and requires extensive
training and experience to be performed safely and effectively.
In this regard, the comprehensive trials of tele-mentoring of
laparoscopy offer some optimism for the future use of endos-
copy by astronauts in low earth orbit [36,37].
Optical Imaging
To date, known injuries in space have been limited to superfi-
cial soft tissue trauma. Probable conditions requiring skin and
mucosal images include burns, frostbite, superficial infection,
orofacial pathology, local or generalized edema, and any der-
matological condition. Verbal description of a lesion would
rarely be satisfactory for clinical decision-making. Further, in
any serious condition, objective data on the patients general
habitus would greatly enhance the ground-based flight sur-
geons ability to fully perceive the essence and severity of the
condition at hand. Therefore, the capability to perform both
general and close-up photography of diagnostic quality may
be critically important. Although photographic equipment
is available on any spacecraft, the color perception in actual
lighting conditions, macro imaging capability, and timely
image transfer options should be considered with medical
applications in mind.
Full-motion or near full-motion video downlink would be
important to obtain objective data from certain types of abnor-
malities noted during physical examination, to conduct rea-
sonably detailed neurological and orthopedic exams, and to
guide the crew medical officer through complicated life sup-
port or interventional diagnostic or therapeutic procedures.
NASA has successfully tested aboard a Space Shuttle mis-
sion a special fundus camera for retinal imaging, as well as
a video system for acquisition and transmission of real-time
185
ophthalmoscopy, otoscopy, and close-up skin and mucosal
examination data as a subsystem of the Telemedicine Instru-
mentation Pack. As with photography, spacecraft video acqui-
sition and transmission modes and quality must be designed to
reasonably satisfy the needs of space medicine. Image fidelity
must be tested in advance for utility in supporting foreseeable
medical applications. For example, the ISS Video Baseband
Signal Processor (VBSP) had been tested by NASA in labora-
tory conditions for its ability to digitally convert and transmit
medical video at various frame rate and resolution settings.
Diagnostic Ultrasound
In the late 1990s, sonography became the second most widely
used imaging modality in the United States; sales of ultra-
sound equipment grew at unprecedented rates to exceed those
of any other category of medical imaging equipment [38].
Diagnostic ultrasound addresses a large and ever-growing
array of medical and surgical conditions. Ultrasound has long
been a method of choice for many specific conditions, such
as cholelithiasis or pericarditis; in others, it has been recog-
nized as a second-choice or backup modality, used especially
when the imaging technology of choice (X-ray, CT scanning,
or MRI) is not available within the appropriate clinical time-
frame. Some ultrasound applications, although used in North
America as secondary or alternative procedures, are well
established as primary evaluation steps in other parts of the
world (for example, sonography of adrenal glands, gastroin-
testinal tract, or ureters). Finally, new applications for ultra-
sound are being developed and clinically implemented at a
remarkably high rate [38].
Ultrasound imaging is an area of diagnostic medicine that
is well regulated in North America, with standards and train-
ing requirements based on routine radiological practices and
patient flow patterns in hospital and outpatient imaging depart-
ments. Typically, a trained technician captures representative
sonographic stills from numerous real-time video frames
using pre-established scanning and documenting protocols
and provides these stills to a radiologist for subsequent inter-
pretation. In other medical cultures, including some of those
represented in the ISS partnership (most European countries,
Russia, Japan), sonographic services are less standardized and
regulated. In these cultures, sonographic imagery is acquired
by a physician-radiologist rather than a technician and inter-
preted in real-time.
In the space medicine setting, elements of all the above-
mentioned diagnostic paradigms may be employed. In the
multinational operational environment of ISS, contributions
from several medical cultures are shaping many medical pro-
cedures. The cooperative experience with medical support of
international space programs has shown significant promise
[39].
Thus, ultrasound is uniformly recognized terrestrially as a
valid diagnostic tool in many conditions, some of which, such
as urolithiasis, have already been encountered in space.
186
Ocular, abdominal, and soft tissue trauma, pneumothorax,
acute localized infections, and complications of toxic inhala-
tion are a few examples of maladies that ultrasound could be
used to evaluate.
Numerous reports have confirmed the high diagnostic
value of ultrasound for clinical conditions in which it is not
considered the first choice diagnostic modality [4042]. In
the absence of other diagnostic imaging modalities in space,
ultrasonic methods and techniques must be developed specifi-
cally for space use.
Ultrasound is the most feasible imaging modality for space
medicine because of its relatively small volume and power
requirements and safe non-ionizing, noninvasive characteris-
tics. The feasibility of ultrasonic imaging in human space flight
has been demonstrated and well documented [6,8,11,4345].
This versatile clinical diagnostic tool is now deployed aboard
the ISS. On September 13, 2002, NASA astronaut and scientist
Peggy A. Whitson conducted operational testing of the hard-
ware in a series of discrete imaging procedures, employing
real-time video downlink and receiving expert guidance from
the Mission Control Center in Houston (Figure 9.2).
Portable and Specialized Sonography Systems
Recent miniaturization of sonographic hardware has facili-
tated implementation of ultrasound imaging outside the stan-
dard tertiary care imaging departments even in the United
States [46]. Ultrasound imaging is increasingly carried out in
small clinics, sometimes by private general practitioners and
specialists such as cardiologists, gynecologists, ophthalmolo-
gists, and urologists. In many of these deployments, ultra-
sound data are acquired using minimal customized protocols
with data interpreted in real time, often without formal image
archival. These focused, problem-based examinations are used
to rule out or confirm specific pathology [4750]. One of the
Figure 9.2. NASA astronaut Peggy Whitson during operational ultra-
sound imaging test on orbit (Photo courtesy of NASA)
A.E. Sargsyan
main advantages of focused, front line applications of portable
scanners is quicker availability of results in the overall evalua-
tion and initial management and triage process. In many cases,
an ultrasound examination by the imaging experts would not
be possible because of constraints on time, distance, or per-
sonnel. Portable devices are also gaining increasing attention
for potential applications in military medicine, aeromedical
transport, and other settings with limited resources, time-criti-
cal operations, and rapidly changing environments [5153].
The HRF Ultrasound on ISS is a large and complex research-
oriented system that can handle any ultrasound imaging task.
Such luxury would hardly be afforded merely for operational
purposes, and the ISS medical system takes advantage of its
presence. Smaller devices with reasonable image quality [23]
would be chosen to equip spacecraft for dedicated medical
monitoring and risk mitigation purposes. In mid 2002, the
world market of commercial devices included more than 40
different portable systems [46]. Terrestrial precedents already
exist for the use of standard computer platforms for control,
data processing, and display, thus reducing the volume of
dedicated ultrasound hardware down to that of the necessary
probes and analog components (Figure 9.3). Future space-
based medical hardware, including that for imaging, will most
likely be integrated with the centralized power, data process-
ing, and communication resources of the vehicle.
Three-Dimensional Ultrasound
Three-dimensional (3D) reconstruction in tomographic
methods such as CT, MRI, or positron emission tomogra-
phy (PET), where precise spatial coordinates of data points
are known and volume data are routinely acquired, have
long been established as valid clinical image processing
and presentation techniques. Multiplanar display and 3D
reconstruction and rendering of B-mode and color Doppler
Figure 9.3. A commercial, laptop-based, ultrasound device (Photo
courtesy of NASA)
9. Medical Imaging
ultrasound images have also been advocated for clinical
use, especially in obstetric ultrasound where congenital mal-
formations are routinely sought and described [54,55]. Three-
dimensional rendering has been explored for other areas of
ultrasonography as well, such as in ophthalmology [56] and
neonatology [57].
During the 1990s, a multi-center project (SOLUS-3D)
was conducted by the European Commission Biomedicine &
Health Research Program. Coordinated by Cambridge Uni-
versity (UK), multiple clinical and research centers through-
out Europe studied 3D-ultrasound imaging, primarily in
obstetrics and gynecology, in an attempt to standardize clini-
cal utilization. Conventional 2D ultrasound probes equipped
with six electromagnetic spatial locators were used to acquire
spatially registered series of 2D images. Volume data sets
could then be calculated in any discretional slicing plane, with
subsequent volume or surface rendering [58,59]. Several com-
mercial vendors have developed similar hardware and software
to acquire spatially tagged (3D or volume) data for analysis,
while preserving the freehand nature of conventional 2D ultra-
sound scanning. Promising clinical results with such systems
have been published by several authors [3,55,60]. Although
attractive in several respects, these techniques have not gained
wide acceptance for abdominal and vascular imaging due to
their non-real-time nature, as opposed to the traditional 2D
(B-mode) ultrasound.
Primary acquisition of volumetric data (as opposed to stor-
age of serial spatially tagged 2-D data arrays described in the
previous paragraph) has been proposed for operational use in
space. The more extensive data obtained might compensate
for the lack of training and proficiency of astronauts in explor-
atory-class missions by allowing ground teams to reconstruct
full 3-D imagery and retrospectively select the most clinically
useful views. Indeed, communication latency from a few sec-
onds to several minutes could effectively confound real-time
interaction and feedback. This alternative approach with spe-
cial 3-D-capable probes is effective for static targets but often
presents a challenge when patients are unable to hold their
breath long enough. The imaging procedure may be unduly
complicated because of the need to transmit large data arrays
before their quality and fitness for given clinical questions
are verified. Therefore, a free hand 3-D ultrasound approach
seems to offer far more promise for use in space, as it preserves
the advantages of real-time scanning with an added capabil-
ity to manipulate 3-D data sets off-line. Standard preacquired
volume blocks of exemplary ultrasound data might be used
as advanced computer-based training tools for astronaut Crew
Medical Officers (CMOs), since training and proficiency test-
ing systems using pre-acquired data blocks are effective and
available commercially [6163].
With due recognition of the potential of 3-D ultrasound, only
real-time 2-D ultrasound with remote guidance is being con-
sidered for use as a medical diagnostic capability on ISS. This
would probably satisfy the current needs for space medicine
practice in LEO where real-time remote guidance is available.
187
Three-dimensional techniques must be thoroughly considered
for future space missions, as they are further refined terrestri-
ally and adapted for commonly used computer platforms.
Diagnostic Imaging Before and After
Space Flight
The lifelong monitoring of astronaut health begins in the ini-
tial selection process. A comprehensive medical evaluation
determines whether the subject meets the medical standards to
qualify for astronaut training and future space flights. The ini-
tial medical screening program for ISS crewmembers requires
several imaging tests (Table 9.1). Medical imaging is also per-
formed at certain intervals during the career of the astronauts
and in the preflight and postflight phases of both long- and
short-duration space missions. Although the general approach
in the ISS program is to maximally follow analogous terres-
trial health screening standards (e.g., mammography, chest
X-ray, or colonoscopy), some groups advocate more rigorous
screening to include cerebral MRI angiography, gastrointes-
tinal endoscopy, or coronary angiography in older astronaut
candidates.
Diagnostic Imaging in Space
The Role of Imaging in Medical Risk Mitigation
Medical risk mitigation policies throughout the last 40 years of
human space flight have called for onboard treatment of minor
illness or injury and medical evacuation of a seriously ill or
injured crewmember to an appropriate terrestrial medical facil-
ity. However, such a determination may be extremely com-
plicated (Table 9.2). Because of the inability during flight to
properly address all medical conditions in the differential diag-
nosis of presenting symptoms, those possibilities with the most
severe impact will probably determine further decisions. Such
conservatism, although aimed at improving the chances of sur-
vival and recovery, inevitably increases the risk of unnecessary
evacuation. Decision making may be further encumbered if
two or more leading conditions call for different management,
stabilization, and transport modalities. For example, moderate
to severe chest pain and dyspnea could suggest spontaneous
pneumothorax, pulmonary embolism, myocardial ischemia,
varicella-zoster ganglionitis, acute pericarditis, or aortic dis-
section. The flight surgeon may find it difficult to weigh the
risks of further onboard management and observation against
those inherent in an emergency return, including reentry
gravitational loading, lack of advanced monitoring and life
support capability, and possible delays in rescue and transpor-
tation to a definitive care facility after landing. Furthermore,
the line between minor and serious is blurred even with a
well-established diagnosis and can be crossed rapidly during
the course of illness in both directions.
188 A.E. Sargsyan

Table 9.1. Required preflight imaging studies in the ISS program.

Imaging test At selection At annual evaluation Before flight After return Notes/acronyms
Sinus X-rays If clinically indicated No
Panorex Yes Updated every 5 years
Bite-wing X-rays Yes If clinically indicated If clinically indicated
(on long flights, at
L30/45 d)
Echocardiography Yes No; If clinically indicated
(CSA)
Chest X-ray Yes Every 5 y Posteroanterior and
lateral
Mammography Yes Every 2 y for ages 4050; Per clinical guidelines
annually for ages > 50 for age and history
No; every 5 y (CSA)
Abdominal ultrasound Yes Annually (RSA) L 180 d (for long flights) R +3, +6, +10 d
Pelvic ultrasound (women) Yes No L 180 d (for long flights)
every 5 y (CSA)
Proctosigmoidoscopy Yes Every 3 y for ages 4050;
every 2 y for ages 5056;
annually for age > 56
EGDS Yes (RSA, NASDA NASDA only Esophago-gastro-duo-
only) denoscopy
Cerebral MRI angiography CSA only No
Head and spine MRI RSA only Every 5 y
Intravenous pyelography RSA only Every 5 y
Selective coronary angiography If clinically indicated No For ages > 45
(RSA only)
Abbreviations: CSA, Canadian Space Agency; RSA, Russian [Aviation and] Space Agency; L, days before launch; R+, days after landing; NASDA, Japa-
nese Space Agency; y, year; d, days.

Table 9.2. Factors considered by flight surgeons in clinical decision-making.

Comprehensive diagnosis and prognosis
Spacecraft environment and resources
Onboard treatment options and resources
Scenarios of emergency deorbit and emergency medical
services (EMS) support
Control, confidence, and ethical aspects
Presenting complaints and their evolvement
Physical exam data (objective and subjective status) and respective trends
Objective diagnostic and monitoring information (by real-time telemetry, file transfer, and crew
call-downs), and respective trends
Predictions based on available data and trends, terrestrial and space-based evidence, and prec-
edents (if applicable)
Objective data from spacecraft systems (telemetry and crew reports)
Predictions based on calculations, trends, and precedents
Relevant onboard expertise (crew training, demonstrated and expected proficiency)
Availability of medical procedures and computer-based (written) knowledge base
Availability and supply of medications, instruments, consumables, and other items
Availability of ground-based expertise support to the provider onboard
Capability to evaluate treatment effectiveness and mitigate inherent and iatrogenic complications
Deorbit opportunities and their physiological profile
Availability of monitoring and life support aboard the rescue vehicle
Time/distance to definitive care facility
Availability of life support, monitoring, and treatment options upon landing and en-route to
definitive care facility
Availability and technical adequacy of necessary types of communications
Effectiveness of information exchange, given the pressure of the situation

A further example is two cases of nephrolithiasis with iden-
tical presentation that may require different management and
have different outcomes depending on the degree and loca-
tion of the obstruction, presence of urinary tract infection, and
other individual factors. Obstructions with higher chances of
spontaneous resolution may be treated on orbit, thus avoiding
unnecessary disruption of the mission and saving the space
program many millions of dollars. Major obstructions should
be rapidly diagnosed and medical evacuation scheduled to a
primary landing site while the patient is still stable and the
stock of adequate medications to control pain or treat infec-
tion is not yet depleted. An appropriate management plan in
this example is directly dependent on diagnostic imaging to
provide objective information on the size and location of the
obstructing calculus, the degree of obstruction, and the pres-
ence of other calculi in the urinary system.
9. Medical Imaging
Implications of Altered Gravity for Medical
Imaging
Diagnostic imaging procedures have evolved over years to take
advantage of the omnipresent force of Earths gravity. Factors
and properties such as density, buoyancy, capillary action,
and surface tension act on various combinations of gas, fluid,
solid matter, and biological tissue to determine many aspects
of normal and pathological anatomy. Fluids normally con-
centrate in dependent areas, which can be the sentinel finding
for many lifethreatening medical conditions, such as intra-
cavitary hemorrhage. Constituents with lower density, such as
air or lipid-rich matter, float above the fluid whereas those
with higher density, such as calculi or debris, sink or form
horizontal layers. As a result, gravity-based imaging tech-
niques using specific patient orientation are used extensively
in several areas of clinical imaging, and resulting images are
interpreted with gravitational effects in mind. Gravity is also
exploited to modify the mutual position of organs and tissues
to better expose the areas of interest for physical examination
and imaging. For example, echocardiography is usually per-
formed in left lateral decubitus position to gain better access
to the periapical areas of the heart and to avoid lung interfer-
ence. Vertical body or extremity positioning is often used to
enhance venous filling.
However, in the foreseeable future of low earth orbit oper-
ations, lack of gravity will remain a fact of human space
flight. In weightless conditions, the position of an object or
distribution of a fluid collection is determined by the com-
bined effect of weaker, and often random or unidentified
factors, such as viscosity and composition of the fluid and
its interaction with the given tissue surface, tissue and organ
compliance, various pressure fluctuations and gradients,
peristalsis, surface tension, and small accelerations. The result-
ing diagnostic imaging representations should therefore be
expected to differ from usual terrestrial patterns, possibly in
unpredictable ways.
These diagnostic challenges can be illustrated by the behav-
ior of pathological pleural fluid in microgravity. On Earth,
pleural fluid is distributed in a characteristic pattern within
the lowermost part of the pleural cavity with respect to grav-
ity, resulting in the classical picture of blunted costo-phrenic
angles commonly seen on standard upright X-ray images.
Table 9.3. Examples of altered anatomic appearance of disease in microgravity conditions.
Condition Terrestrial (established patterns)
Calculus in the urinary bladder Most dependent location (posterior wall/trigone in supine
position)
Pleural effusion Costopleural sinus
Ileus Horizontal levels of gas over fluid in distended bowel
loops (cups); altered peristalsis, increased diameter
Intra-abdominal hemorrhage Most dependent areas (Rectovesical/rectouterine,
Morisons, and splenorenal spaces) fill first
189
In microgravity, pleural fluids (blood or exudate) would likely
distribute relatively evenly over the whole pleural surface,
including the lung fissures and mediastinal pleura, and thus
would decrease the net opacification expected in the lower
portions of the thorax if X-ray images were taken. The some-
what increased opacification over the entire lung would prob-
ably make it difficult to distinguish between parenchymal
and pleural nature of the underlying pathology. In cases with
massive hydrothorax or hemothorax and some degree of com-
pressive atelectasis, opacification would probably be more
pronounced along the pulmonary perimeter, and the borders
of the lung fields would be blurred; however, the presence of
a well distributed but small to moderate effusion on a chest
X-ray could still be confused with an interstitial lung process.
Intraabdominal hemorrhage, sinus exudate, lung abscess, ileus
with dilated bowel loops, and bladder calculi are all conditions
where certain aspects of the disease anatomy are directly deter-
mined by the direction of the gravity vector. Several examples
of such conditions are listed in Table 9.3, with a description of
the expected or proven change in disease anatomy.
Thus, unless all aspects of an imaging technique and its
specific application are reconsidered for use in space, their
applicability in the absence of the gravity may prove to be
significantly affected. A terrestrial gold standard imaging
procedure may not provide clinically relevant information in
microgravity, whereas a less standard imaging method may
actually be the method of choice for the same condition. This
has been observed by NASA investigators using an animal
model in parabolic flight to evaluate a small quantity of pleu-
ral fluid, which in microgravity might easily be overlooked
radiographically. These experiments suggest that sonography
under the same conditions should have high diagnostic accu-
racy (Figure 9.4).
Artificial gravity may one day move from science fiction
books to the drawing boards, but it will probably be a fraction
of Earths gravity and may still remain operationally imprac-
tical for the employment of diagnostic imaging. Although
no data exist on the relative contribution of gravity vs. other
forces and factors in medical imaging, experience in normal
terrestrial and parabolic flight conditions suggests that lunar
and Martian levels of gravity would result in imaging condi-
tions close to terrestrial norms. Processes of gravity-induced
distribution, sedimentation, and separation will occur at lower
Microgravity (demonstrated or expected patterns)
Random position; may be difficult to rule out (identify) due to
atypical position
Distribution over a large surface
Insufficient data; fluid may adhere to bowel walls with the
gas forming a centrally located bubble, or multiple bubbles
Bleeding site fills first and spreads locally; blood may accu-
mulate between bowel loops and under the abdominal wall,
and spread over time to a large mesothelial surface
190
Figure 9.4. A layer of pleural fluid is clearly seen (arrows) on this
ultrasound image taken in the zero gravity phase of a KC-135
parabolic flight
rates and may be less pronounced in these circumstances and
must be considered.
Diagnostic Imaging on Transport Spacecraft
Medical imaging capability for Space Shuttle missions lasting
less than 2 weeks has been limited to real-time transmission
or recording of sonographic images or standard video and
digital photography. Pre-Shuttle NASA spacecraft (except
Skylab stations) and the Russian Soyuz capsules have had
minimal medical capabilities, and none have been equipped
with any imaging capability. Specialized medical imaging on
the Space Shuttle has been used only for experimental pur-
poses and has not been considered as part of a standard medi-
cal system. However, long-duration missions of the future to
Mars or other remote destinations of the solar system will
probably have highly portable medical imaging capabilities
and a trained crew to handle the most likely medical emer-
gencies autonomously. Upon arrival at a planetary base, the
medical hardware would be deployed as part of the bases
medical facility.
Diagnostic Imaging Aboard ISS and Future Space
Stations in Low Earth Orbit
The HRF Ultrasound is the only piece of specialized medical
imaging hardware currently available on ISS. The ISS Program
has recognized its operational value for mitigating medical
risk and considers it necessary for maintaining an acceptable
level of contingency medical care. This decision was largely
based on the results of numerous studies conducted by NASA
and affiliated medical organizations, which investigated the
role and requirements of diagnostic ultrasound and minimally
invasive surgical endoscopy in abdominal, retroperitoneal,
A.E. Sargsyan
Figure 9.5. The Human Research Facility (HRF) Ultrasound
System, delivered and installed during the ISS Expedition Two
and thoracic pathology in microgravity [18,44,47,64]. Most
of these studies have employed animal models in parabolic
flight aboard KC-135 aircraft.
The ISS Ultrasound System is a space-adapted version of
an advanced multipurpose ultrasound system widely used in
tertiary care centers throughout North America and in other
countries (HDI-5000, ATL/Philips, Bothell, WA, USA)
(Figure 9.5). Equipped with a complement of three probes
and supported by operationally and clinically valid proce-
dures, it can significantly enhance the ability to diagnose,
describe, and monitor a wide variety of medical and surgical
conditions. Upon reviewing the relevant information accumu-
lated to date, a list of medical conditions has been suggested
to include those sensitive to detection, staging, or description
in space by sonographic technology. Some of these conditions
are listed in Table 9.4 and include trauma, ocular and dental
conditions, cardiovascular pathology, urinary tract conditions,
biliary obstruction, acute and chronic infectious and inflam-
matory conditions, and soft tissue infection.
In the paradigm of a space station in LEO, the ability to
transfer data between the point of acquisition and the expert
on the ground is limited by the telecommunication system
of the spacecraft. This system is not necessarily optimal for
this specific application, is not available on demand, and
causes some deterioration of signal quality with partial loss
of potentially important information. There are frequent
interruptions in video and audio links between the space-
craft and the experts in Mission Control Center. Figure 9.6
compares two experimental images taken during ground
tests; obviously, the transmission through the ISS video baseband
signal processor causes noticeable degradation. Further,
the communications pathway for both video and voice intro-
duces a transmission delay of up to two seconds, making the
real-time interaction even more demanding. These technical
Table 9.4. Examples of conditions subject to ultrasound imaging in space.
ISS
support-
NASA KC-135 ing data
Application/condition Possible ultrasound findings Terrestrial use supporting data (human)
Abdomen/retroperitoneum/thorax
Acute appendicitis Thickened walls of appendix; non-compressibility, increased diameter, Common and A N/S; H N/S; N/S, G
increased blood flow demonstrated by Color Doppler; if compli- increasing SN
catedfree fluid; localized fluid/infiltrate, changes in bowel peristalsis.
Demonstration of normal appendix or other cause of symptoms rules out
appendicitis in most cases. Failure to identify appendix does not rule out
appendicitis.
Acute diverticulitis Non-specific findings of focal bowel wall thickening and changes in sur- Known but A- N/S; H-N/S N/S, G
rounding fat/tissues; possible identification of the diverticulum, abscess uncommon
formation, or associated fistula
Blunt abdominal trauma Free fluid at the site of injury; free fluid elsewhere in contiguous perito- Common A SN, SP; H SN, G
(includes internal bleeding) neum; organ hematoma; capsular disruption; changes in peristalsis. - SN
Retroperitoneal hematoma Detection of hematoma; possible abdominal fluid and/or signs of ileus Common, A N/S; H N/S N/S, G
secondary
Inflammatory bowel disease Thickened/infiltrated (hypoechoic) wall of terminal ileum, decreased or Common H N/S N/S, G
absent peristalsis
Hollow viscus perforation Pneumoperitoneum; changes in peristalsis, free fluid Known but A SP, SN; H-N/S N/S, G
(peptic ulcer, trauma) uncommon
Pneumothorax Absent sliding of the lung, mirror-image artifact, absent comet tails. Uncommon, A SN, SP; H SN, G
In severely symptomatic cases expect same over entire hemithorax, rapidly - SN
displacement of the mediastinal structures increasing
Pleural effusion and hemo- Demonstration of fluid separation between parietal and visceral pleura. Common A SN, SP; H SN, G
thorax Expect wide area of distribution in 0 G. Requires follow-up if negative - SN
Hepatobiliary, pancreas and spleen
Liver enlargement/diffuse Changes in shape, margins, size, relative echogeneity, echo-texture, vascu- Common A-SN, SP; H - SN SN, G
process (e.g., toxic) lar pattern
Liver or splenic hematoma Focal irregularity; Doppler signs of a space occupying lesion (S.O.L.); Common A SN; H - SN SN, G
subcapsular hematomas (Typical pattern of hypoechoic crescent-shaped
addition)
Hepatic abscess Demonstration of a gradually forming focal irregularity which assumes a Common A SN; H - SN SN, G
round shape; Doppler signs of S.O.L.
Biliary hypertension due to Dilation of intrahepatic bile ducts and extrahepatic ducts proximal to the Common A SN; H - SN SN, G
obstruction cause; possible dilation of the gallbladder; possible dilatation of the
pacreatic duct
Abnormal content of the gall- Demonstration of irregular echogenicity of gallbladder content; stones Common A SN; H - SN SN, G
bladdersludge, blood clots, readily visualized; data will differ from terrestrial
calculi, pneumobilia
Acute cholecystitis (calculous Thickened/infiltrated walls; possible peritoneal reaction; possible wall Common A SN; H - SN SN, G
or acalculous) irregularity
Splenic enlargement Changes in shape, relative position, size, relative echogenicity Common A SN; H - SN SN, G
Splenic infarct Wedge-shaped zone of irregularity/low echogenicity Common A SN; H - SN SN, G
Acute pancreatitis; pancreatic Enlargement, low echogenicity; possible irregularity; possible dilation of Common A SN; H - SN SN, G
hematoma the duct; possible free fluid and renal changes in severe cases
Genitourinary/pelvic
Renal calcifications/calculi Demonstration of calcifications and/or stones; typical pattern of obstruc- Common A SN; H - SN SN, G
tion if impacted
Ureteral obstruction/renal colic Demonstration of renal pelvic distention/ureteral dilation proximal to the Common A SN, SP; H SN, G
(stone, blood clot in trauma, stone; renal enlargement; possible demonstration of the cause - SN
urinary reflux)
Demonstration of ureteral jets or asymmetry/absence thereof contributes
to diagnosis
Acute pyelonephritis and renal Renal enlargement, shape, low relative echogenicity, possible focal lesions/ Common A SN; H - SN SN, G
abscess irregularity, possible signs of obstruction; demonstration of abscess
(Focal lesion of varying echogenicity, irregular contour of the kidney)
Renal trauma Zone of irregularity with associated perirenal changes; usually diagnostic Common A SN; H - SN SN, G
in clinical context; Power/Color Doppler essential to evaluate damage
and stage/classify
Acute diffuse pathology, renal Renal enlargement, shape, high relative echogenicity, medullo-cortical Common A SN; H - SN SN, G
enlargement (e.g., toxic contrast, change in renal vascular resistivity (pulsed Doppler)
exposure, ATN)
Renal vein thrombosis Changes in size, echogenicity, shape, arterial flow pattern (Pulsed Dop- Common A N/S; H - SN N/S, G
pler); actual thrombus may be visualized; procedure may be complicated
and time-consuming
(continued)
Table 9.4. (continued)
ISS
support-
NASA KC-135 ing data
Application/condition Possible ultrasound findings Terrestrial use supporting data (human)
Bladder calculi or blood clots Demonstration of a calculus or displaceable irregularly echogenic structure Common A SN, SP; H SN, G
in the bladder lumen; location may be atypical in 0 G - SN
Bladder infection Demonstration of turbid urine in the bladder; no layering in 0 G; thicken- Common A SP (sim) SN, G
ing of bladder walls; color Doppler interrogation causes stirring of
echogenic matter
Urinary retention Distended bladder, possibly vesico-ureteral reflux with ureteral, pelvic, Common A SP; H SN SN, G
and calyceal dilatation
Acute prostatitis/relapse and Enlarged prostate, irregularity of texture, contour irregularity, possibly Common H SN Not
prostatic abscess solitary or confluent hypoechoic focus, low echogeneity; chronic avail-
background changes, e.g., calcifications able
Testicular torsion Changes in echo-texture and asymmetry in echogeneity Common A NA; (H N/S) NA
Critical information derived from Color Doppler data (vascularity) and
Pulsed Doppler (spectral characteristics)
Normal pregnancy; incomplete Demonstration of gestational sac, thickened and echogenic endometrium; Common NA NA, G
abortion or blighted ovum typical pattern of complications
Ectopic gestation Adnexal mass, free pelvic fluid, thickened endometrium; possible demon- Common NA NA, G
stration of heartbeat
Pelvic inflammatory disease A variety of sonographic patterns; requires extensive air-to-ground interac- Common NA NA, G
(PID) tion, may require follow-up and lab support to R/O ectopic gestation
Ophthalmic
Retinal detachment Typical pattern of retinal separation of various degree and topography Common A NA; H SN NA, G
Retrovitreal and intra-vitreal Typical patterns of irregularly altered echogeneity Common A NA; H SN NA, G
hemorrhage
Lens displacement (subluxation Failure to visualize lens in normal position; Demonstration of the lens in Uncommon A NA; H SN NA, G
or dislocation) abnormal position or location
Other trauma (anterior seg- Demonstration of hyphema, distortion of the iris, and other trauma Uncommon A NA; H SN NA, G
ment) anatomy
Superficial
Sialoadenitis Hypoechoic gland, enlarged and tender, rounded, possibly dilated ductal Known but A NA; H SN NA, G
system uncommon
Subacute thyroiditis Relatively hypoechoic gland, enlargement (compare to baseline), irregular Common A NA; H SN SN, G
texture
Superficial infections (celluli- Respective patterns, typical Common A NA; H SN SN, G
tis, lymphadenitis, cutaneous
abscess, necrotizing cel-
lulitis)
Lymphadenopathy Common A NA; H SN SN, G
Cardiovascular
Pericardial effusion Demonstration of fluid separation of pericardium Common A SN; H SN SN, G
Deep venous thombosis (lower Lack of compressibility, visualization of thrombus, absent or abnormal Common NA NA
extremities) flow May be time-consuming. Technique may differ in 0 g vs. 1 g
Superficial venous thrombosis Lack of compressibility, visualization of thrombus, absent or abnormal Common N/S NA
(post-injection, post-catheter) flow.
Venous gas embolism (decom- Demonstration of VGE in B-mode and Power Doppler; pulsed-Doppler Uncommon NA NA, G
pression) may be used additionally (Duplex or Color-Duplex mode)
Musculoskeletal, dental
Superficial bone fractures (rib, Characteristic disruption of cortical bone reflection; Distortion of the bone Known but A SN; H SN SN, G
mandible, zygomatico-max- contour; soft tissue reaction/edema/hematoma Uncommon
illary complex, skull)
Long bone fractures Similar to other fractures; additional techniques (such as axial rotation) Known but H SN NA, G
may enhance study uncommon
Muscle tears/hematoma Hypoechoic zone, irregularity, local enlargement, displacement of adjacent Known but H SN N/S, G
structures uncommon
Tendon rupture Disruption of the normal pattern, asymmetry, hypoechoic zone; may dem- Known but H SN N/S, G
onstrate contracted muscle uncommon
Articular effusion/hematoma Demonstration of fluid in the articular space Uncommon NA NA, G
Periapical abscess Translabial/transbuccal demonstration of a hypoechoic periapical focus Anecdotal NA NA, G
reports
Other
Verification of endotracheal Demonstration of ET in trachea, demonstration of normal lung motion Anecdotal NA NA, G
(ET)intubation with respiration, ruling out tube in esophagus reports
Abbreviations: A, animal experiments; H, Human experiments; G, Ground simulations (human) support feasibility on ISS; SP, specific imaging protocol
demonstrated (pathology); SN, specific imaging protocol demonstrated normal data (sufficient data to rule out; condition would have been diagnosed if present);
N/S, nonspecific imaging data support feasibility; NA, data not available.
9. Medical Imaging 193

Table 9.5. Ultrasound probes for space medicine applications.

Frequency Alternative (second
Applications (MHz) Primary probe choice)
Abdominal/pelvic 25 Curved-array Phased-array (lower
(convex) resolution)
Cardiac 24 Phased-array Curved-array
(extremely limited
access due to large
probe face)
Superficial organs 7.512 (depths Linear 5- to 7.5-MHz, linear
and tissues; < 5 cm) or convex
musculoskeletal;
chest wall/ribs;
pneumothorax
evaluation;
peripheral vascu- 58 MHz
lar; ophthalmic; (depths > 3- to 5-MHz, linear
dental 5 cm) Linear or convex

Linear array probes. Linear array probes of modern ultra-

Figure 9.6. Sample echocardiography frames before (left) and after
(right) transmission to the ground
circumstances must be taken into account along with the
other more obvious factors, such as operator and ground-
based expert training, psychological aspects, and remote
guidance approaches.
Ultrasound Probe Needs for Space Medicine
A choice of ultrasound probes must be available on board to
fully realize the diagnostic potential of any ultrasound system.
The types of probes recommended for space medicine pur-
poses are listed in Table 9.5. A set of three probes is necessary
and currently available on board ISS for meeting the major-
ity of foreseeable imaging needs. Additional probes may be
advantageous in some specific imaging situations and would
also provide desirable redundancy.
Curved array probes. A curved array probe acquires
fan-shaped images through a relatively small window. These
probes with relatively low (25 MHz) frequencies are primar-
ily used for abdominal and transvesical pelvic imaging. An
important feature of broadband probes is a uniformly high
resolution throughout the field of view. If a curved array probe
is unavailable, a phased array (cardiac) probe may provide a
lower resolution alternative for the majority of abdominal
applications. It may even be preferable in large subjects, in
cases of excessive bowel gas or when its smaller flat face is
needed to minimize pressure in the area of trauma, or in cases
requiring small acoustic windows in the presence of wounds,
dressings, or other impediments. In the ISS Ultrasound sys-
tem, a broadband curved array probe operating in the 25 MHz
range (designated C5-2) is the primary choice for abdomi-
nal or pelvic application.
sound equipment usually operate at higher frequencies (7 MHz
and above) to resolve small parts and subtle tissue interfaces
with excellent clarity, tissue contrast, and detail resolution.
Within relatively shallow depths, (e.g., up to 57 cm with a
512 MHz broadband probe), these probes acquire rectangu-
lar images of very high spatial and contrast resolution.
In the ISS ultrasound system, the L12-5 probe with a
4-cm-long narrow face is the probe of choice for the most
superficial anatomical structures, such as the anterior segment
of the eye, the median nerve, thyroid and salivary glands,
breast, scrotum, or tendons of the hand and wrist. This probe
has proven to be the best choice for screening for pneumotho-
rax through visualizing the parietal-visceral pleural interface.
Pending development of respective protocols, this probe will
also support evaluation in certain dental and facial conditions,
mainly periapical abscesses and paranasal sinus exudates. Of
special interest for space medicine is its ability to provide
the finest detail of muscle, fasciae, tendons, ligaments, bur-
sae, and small joints, as well as the surfaces of superficially
positioned bones. Thanks to its excellent spectral and color
Doppler performance at shallow depths, it will also enable
evaluation for suspected testicular torsion or epididymitis,
thyroiditis, vascular aneurism or thrombosis, and a number of
ocular vascular conditions.
The ISS Ultrasound system can also be equipped with
another linear array probe (L7-4) with a longer (50 mm)
face and lower operating frequency range (47 MHz). Lower
frequencies of this probe would ensure deeper penetration
(up to 1012 cm), with a relatively reduced spatial resolu-
tion. The 47 MHz probe is ideal for evaluation of DVT,
and for examination of long bone surfaces and soft tissues
of the trunk and lower extremities. In smaller subjects, this
probe is suitable for high-definition imaging of the vermiform
appendix and other superficially located abdominal struc-
tures. In the absence of this probe, a curved array 25 MHz
probe would overcome the penetration deficiency of the
194
512 MHz probe but with severely compromised image
clarity and resolution.
Phased-array probes. Phased array probes are primarily
used for cardiac imaging. They are small and easy to handle,
have a very small footprint (face), and allow acquisition of wide
sector-shaped images through small windows such as intercos-
tals, spaces with a depth of view of up to 22 cm. Aboard the ISS,
a phased array probe is available to support echocardiography
in suspected cardiac conditions such as pericarditis and myo-
cardial or valvular dysfunction. It can also serve as a backup
probe for the majority of abdominal and pelvic applications.
Operational Issues in Space Diagnostic
Imaging
Communications Support for a Space-Based
Imaging System
For the most part, the current paradigm of medical imag-
ing in space involves a one-way space to ground pathway
for medical imaging data. Recent experience using existing
diagnostic imaging hardware on orbit and in simulations
(KC-135 and ground-based laboratory experiments) suggests
that real-time transmission of ultrasound video and reliable
two-way audio communication are essential to effective data
acquisition. The diagnosis of any medical condition in space
is challenging due to complicating factors such as micrograv-
ity, aberrant clinical presentation of disease, and the separa-
tion between the operator and the specific expertise on the
ground. Autonomous acquisition of images by CMOs on
orbit depends on the type of imaging modality employed
and the training they have received. Without making unreal-
istic assumptions regarding their training and proficiency, it
is expected that experts familiar with the specific aspects of
space medicine and space-based imaging will perform real-
time guidance and real-time or subsequent data evaluation
and clinical interpretation.
Detailed technical aspects of data transmission are outside
of the scope of this chapter and are discussed in great detail
in Chap. 11.
Operator Factors for Imaging Procedures in Space
Training and Responsibility
ISS crewmembers are likely to have little or no professional
medical background and to receive only limited CMO train-
ing. Introduction of any imaging capability would require a
carefully thought-out combination of preflight classroom and
hands-on training, appropriate use of preflight and in-flight
computer-based refresher training tools, and the use of onboard
reference tools (cue cards and written procedures) combined
with real-time guidance during data acquisition. The amount
and content of pre-flight training and practice depend directly
A.E. Sargsyan
on the target set of knowledge and skills for performing the
given set of imaging procedures.
Imaging modalities differ widely in the in requirements for
operator skills. A system with standard positioning and opera-
tion, such as a standard X-ray or CT machine or a scintilla-
tion camera, might require only modest skill and experience
if detailed written procedures were available. Realistically,
diagnostic ultrasound is very operator-dependent; application
and manipulation of the transducer with continuous real-time
adjustment of the equipment controls and scanning sequence
are vital to acquiring useful diagnostic information. Space
medicine experts agree that the expertise and confidence
necessary to independently perform an ultrasound exam in
space cannot be expected aboard the ISS. Considering the
time lag between the limited preflight ultrasound training and
the actual inflight medical event, it is indeed reasonable to
assume that the CMO does not possess the expertise to inde-
pendently acquire clinically useful ultrasound data. Limited
on-board computer-based training (CBT) tools, although very
important, cannot compensate for the lack of skill and train-
ing. Therefore, remote feedback and instruction are needed
for guidance in clinical situations.
Indeed, no matter how detailed and standardized the imag-
ing procedures and specific scanning protocols are, anatomi-
cal variability of normal and affected structures, random
factors (such as bowel gas or acoustical artifacts), and a large
variety of possible diagnostic signs still require real-time
data assessment and feedback. A standard ultrasound exam
involves continuous control over probe position and pressure
and equipment settings by the operator during the procedure,
as well as specific cooperation on the part of the subject (such
as holding breath or changing position). The procedure is
occasionally interrupted by freezing selected frames for
measurements, post-processing, annotations, transmission,
or storage for future viewing and analysis. It takes months of
training and years of practice to acquire knowledge, skills, and
eye-hand coordination for confident and efficient ultrasound
image acquisition. Wide variability exists among sonogra-
phers in their ability to think in three dimensions while con-
ducting real-time 2-D examinations. Furthermore, one must
remember that diagnostic ultrasound can be applied in nearly
any area of the human body and in a large number of condi-
tions, in which the anatomy at the site of abnormality is never
exactly the same and also tends to change over time.
A medical event on orbit would place high expectations on
the CMO to acquire useful data. Besides the imaging proce-
dure, the CMO will also be responsible for other aspects of
crew medical support, for communicating with the flight sur-
geon, and possibly for other non-medical tasks.
Preflight training and practice is critical, mainly to famil-
iarize the crewmember with the general imaging technique
and to build confidence in the end-to-end imaging system and
imaging procedures that involve provision of expert guidance.
However, allocation of large blocks of preflight training time
for any standby capability, especially one unlikely to be
9. Medical Imaging 195

realized, is difficult to justify. Even with a relatively large
amount of preflight training, the required skill set would hardly
be achieved and maintained by a CMO without prior medical
training. As a result, ultrasound training for ISS CMOs is lim-
ited to hardware use, familiarization with the basic examina-
tion technique and terminology, and limited scanning practice
in simulated flight conditions under remote guidance from an
ultrasound expert.
Computer-based training and reference tools. Several
training paradigms have been explored to overcome the inex-
perienced operator problem. Provision of computer-based
training and reference tools is certainly a tested approach
used widely by nonmedical disciplines for space flight. These
could be used by the CMO for both scheduled inflight training
and for preparation for contingency ultrasound examination
and would consist of the following:
Computer-based version of the preflight training session
(refresher)
A presentation on general scanning technique and proce-
and highly professional interaction, once performed in a real-
istic preflight simulation, allows the CMO to rely on provided
expertise and avoid frustration and doubt regarding the value
of the activity he or she had not been sufficiently trained for.
An important component of remote imaging guidance is the
convention among all participants on the exact terminology
to be used for remote instruction that includes terms denot-
ing probe positioning and movements, anatomical landmarks,
scanning directions, and instrument controls. The first version
of the ISS ultrasound cue card is shown in Figure 9.7. Identi-
cal copies of the card are available to both the onboard CMO
and the ground expert. The card identifies instrument controls,
basic probe manipulation techniques, and anatomical locations
for probe application. Cue cards of this type constitute an
essential part of the remote guidance technique developed by
NASA for the operational use of ultrasound on ISS. Before
testing on ISS, NASA conducted multiple studies in labora-
tory conditions and in parabolic flight.

dures (multimedia) Operator Positioning and Stability

Presentations on specific imaging applications (multimedia)
The lack of gravity and the spacecraft environment impose
with procedure video clips and respective sequences of typi-
challenges in terms of operator positioning and stability dur-
cal representative images to assist the CMO in recognizing
ing various manipulations of the imaging hardware and the
the target patterns. These would be essential for independent
data acquisition without remote real-time monitoring and
guidancea situation possible during communication out-
ages or in missions beyond LEO.
Sets of baseline preflight ultrasound images of all crewmem-

bers, acquired by a standardized protocol; to be used imme-

diately before or during the examination of the respective
crewmember for comparison, as well as to serve as general
reference material. Copies of these baseline data sets would
also be available to the ground-based expert during data
acquisition and interpretation.
Remote guidance. The third necessary measure to com-
pensate for the lack of onboard expertise is a system of real-
time remote guidance of a CMO by an expert on the ground.
The author believes that this component of an imaging support
system is essential to ensuring quality data acquisition and
confident interpretation. Remote guidance for this purpose
has been demonstrated during an experiment aboard a Russian
spacecraft by a group of Russian and French scientists [11].
NASA has conducted numerous ground-based simulations,
and their success has been reported to the space medicine and
telemedicine communities. These experiments have involved
operators of various backgrounds, including astronauts, and
have uniformly resulted in diagnostic information of accept-
able quality.
Having completed preflight ultrasound training and prac-
tice, the CMO is cognitively prepared to perform an imaging
study in continuous real-time communication with an expert
on the ground, who in turn is able to consistently issue distinct Figure 9.7. This ultrasound imaging reference chart (cue card) has
commands in a confident and patient manner, and to identify been successfully used during real-time remotely guided imaging
and interpret received information in real time. This unique sessions aboard ISS
196
subject. For example, for the operator to perform abdominal,
renal, or pelvic examinations with optimal performance, all
of the following conditions must be satisfied in a mutually
compatible way:
The subject must be stabilized in the immediate vicinity of the
ultrasound system, within easy reach of the probes. Unless
self-scanning is anticipated, the crew medical restraint sys-
tem (CMRS) is ideal and should be deployed to maximize
the results.
The operators position must be sufficiently comfortable to
perform the examination for at least 4560 min. Operator
restraints and other stabilization techniques must be used to
maintain a stable position with both hands available for the
imaging procedure. The operator must be able to consistently
exert a contact force of up to 5 pounds and occasionally higher
on the probe anywhere over the entire region of interest on the
subjects body. Examples of the most effective subject-opera-
tor positions are shown in Figure 9.8, as determined during
NASA KC-135 experiments conducted in 2002.
The ultrasound monitor must be easily viewable at an angle
close to 90 degrees and must be set at a distance to allow
perception of image detail and other information displayed.
Figure 9.8. Various positioning and restraining options can be used depending on circumstances. The Crew Medical Restraint System
(CMRS), shown here being tested in parabolic flight, provides the best mechanical stability (Photo courtesy of NASA)
A.E. Sargsyan
Acceptable lighting conditions must exist to ensure comfort-
able viewing and to avoid monitor glare.
Equipment controls (in case of ISS Ultrasound, the key-
board) must be within easy reach for the other hand (the one
not holding the probe) during the entire examination.
The operator must wear a voice-activated audio communica-
tions headset to receive near-real-time feedback and guid-
ance from a remote expert at the Mission Control Center.
Deployment of the operator, patient, and imaging hardware
must be globally compatible with the medical equipment
setup used for emergency medical treatment and life support
activities.
Care should be taken to avoid interference from other crew-
members during their translations within the spacecraft.
When this chapter was written, successful self-scanning had
already been demonstrated on ISS with minimal foot restraint.
However, self-scanning may not be possible for several con-
siderations, including patient distress or preflight training and
proficiency factors. The above listed conditions are believed
to be achievable using the currently deployed HRF Ultrasound
on the ISS. However, further study and demonstration of ISS-
specific positioning and scanning techniques is warranted.
9. Medical Imaging
Psychological Factors
Any potentially serious clinical situation requiring imaging,
especially if associated with subject distress and urgency,
would inevitably be psychologically challenging for all
involved: the subject, the onsite care provider (operator), and
the ground medical team. The stress of the situation and time
pressure would probably influence the baseline ability of the
CMO to perform the task, and may render him or her unable
to focus on the imaging task. The CMO would feel enormous
responsibility for performing necessary procedures efficiently
and with proper precision. Preflight training and preparation
and confident in-flight feedback and guidance are essential to
prevent operator frustration and to achieve effective and effi-
cient data acquisition. Embedding a remotely guided scanning
practice session in the preflight training flow is key to intro-
ducing a necessary degree of confidence in the CMO(s), the
ultrasound guidance expert, and the crew surgeon.
Subject Positioning for Imaging Procedures
Patient positioning techniques in medical imaging must be
standardized to stabilize the body, maintain and control spe-
cific spatial relationships between the emitting and detector
hardware and the area of interest, and to maintain a specific
spatial relationship between two or more body parts or organs.
As much as possible, subject positioning should take advan-
tage of the effects of microgravity.
Microgravity poses unique challenges regarding patient
positioning. For imaging purposes, positions such as prone
or semi-decubitus may retain some meaning only in relation
to a surface, such as the ISS Crew Medical Restraint System
(CMRS) or imaging hardware and do not imply any specific
gravitational vectors within the body. To communicate posi-
tional or directional information reliably and efficiently, a
preestablished convention is necessary for terminology and
anatomical references. Otherwise, use of such terms may be
misleading.
Stability of a subjects position relative to the imaging
system is highly desirable and often critical. In some imag-
ing techniques, such as X-ray or MRI, the patients position
is assumed to have remained unchanged throughout the data
acquisition process. On the ground, the subject is normally
able to maintain a stable position and avoid movement when
instructed to do so. In the absence of gravity, no initial posi-
tion relative to any reference, such as to the imaging system,
ensures stability, as any force inevitably leads to a momentum
directed away from the point of its application. Manipulation
of the subject and application of radiation shielding, probes,
electrodes, etc. would therefore disturb the given position.
Therefore, application of restraints, such as elastic cords or
fabric belts, will be necessary.
Furthermore, it is well known that the relaxed neutral body
posture in space (sometimes referred to as fetal), as determined
by the relatively higher flexor tone, features flexion in the spine
and extremities, thus potentially interfering with access to some
197
areas of interest. For many imaging techniques, such as echo-
cardiography, abdominal ultrasound, or spinal X-ray, a more
extended position is strongly preferred or even necessary. There-
fore, a restraining capability may be necessary to immobilize
and stabilize the patient, and to modify his or her body position.
For ultrasound imaging, CMRS deployment is highly desir-
able in all cases (except self-scanning) and essential if a time-
consuming, complicated study is expected or the subject is
in distress and may need advanced medical intervention and
care. Restraint on the CMRS is the best available means to
stabilize both the subject and the operator and ensure unhin-
dered performance of the operator during extended periods
with minimal fatigue.
Training of Remote Guidance Expert
Little information is available on the presentation and course
of disease and injury in conditions of space flight, as well as
on many aspects of underlying pathophysiology and disease
anatomy. A certain degree of familiarity of the radiologist
with human space flight and space physiology could signifi-
cantly aid data interpretation. Close interaction of the radi-
ologist with a flight surgeon is a critical factor for ensuring
overall success of imaging in space.
The remotely guiding ultrasound expert, who is not neces-
sarily the same person as the interpreting radiologist, must be
trained in advance (including space medicine familiarization
and actual remote guidance practice in the laboratory setting),
and must be familiar with mission control console techniques
and etiquette to provide effective support. The current NASA
station for remote guidance training simulates an adjustable
satellite delay for both video and audio, thus allowing the
trainee to acquire basic skills for live space-to-ground inter-
action. In the current ISS configuration, the communications
delay is approximately 2 s.
Mission Limitations on Imaging
Hardware and Use
Flight Equipment
The unique factors of space flight drive numerous require-
ments and constraints to hardware and its operating proce-
dures, beyond any terrestrial standards. Accelerations and
vibrations at launch, continuous microgravity, fluctuations
in ambient pressure, lack of effective heat exchange through
convection, and relatively high levels of radiation may damage
the equipment or cause performance decrements, errors, and
outages during its operation. Overheated plastics may produce
harmful gaseous contaminants in the sealed spacecraft cabin.
Equipment must also meet noise generation standards. Finally,
rack-mounted hardware must be made compatible with the
power, data, cooling, caution and warning, and fire suppres-
sion systems of the rack and vehicle.
198
Indeed, any household or office device nowadays under-
goes rigorous performance, availability, and safety testing.
Space hardware is usually acquired or built to a stricter set of
standards with a comprehensive scrutiny of fire and electrical
safety risks and electromagnetic emissions. Safety concerns
may render many otherwise worthwhile projects unsuitable
for space flight. Thus, however well built and reliable it may
seem, a piece of diagnostic equipment is likely to require
some, and often extensive, redesign and modification before
becoming spaceflight-certified. This modification may
include repackaging of electronic components, replacement
of housing and the power supply unit, and addition of cooling,
fire detection, and possibly fire suppression components.
Weight and Volume Limitations
The weight and volume of most modern diagnostic devices
are prohibitive for space flight. Diagnostic ultrasound is about
the only imaging modality that reasonably fits in the current
constraints, with some commercially available devices weigh-
ing as little as 2.5 kg. A partial solution to these problems is
the use of standard portable computers as control and data
display platforms for medical devices. Remaining functional
components of diagnostic systems can be combined in smaller
integrated packages. Future diagnostic devices may be further
integrated to share other components, such as power units or
display subsystems.
Power
Electric power is a precious resource on any spacecraft.
Systems and payloads are all designed to be as energy-efficient
as the current technology allows. Transport spacecraft (such as
Apollo or Soyuz capsules) would require extensive redesign
and modification work to accommodate any new piece of hard-
ware. The Space Shuttle can supply up to 5 amps of its nominal
28VDC to middeck payloads during on-orbit operations. Con-
tinuous power used by an individual middeck payload is lim-
ited to 115 W for no more than 8 h or no more than 200 W peak
for periods of 10 s or less. When outfitted with the now retired
Spacelab laboratory, the Shuttle was capable of distributing
a total of 7 kW maximum continuous (12 kW peak) power to
its subsystems and experiments during on-orbit phases. Space
laboratories like Mir or ISS, on the other hand, are designed to
power a large array of permanent and temporary experimental
equipment. For any energy user, both nominal and peak con-
sumption limits are still strictly defined and observed. Should
any device fail to fit within the limits of the given user group,
its flight certification or use would be threatened.
In the final configuration, the ISS electrical power system
is planned to have a maximal output of 110 kW, with a pay-
load power allocation of up to 30 kW. However, energy needs
of some standard imaging hardware are still notoriously high.
For example, an average computed tomography (CT) system
might consume 25 kW or higher power continuously, with
A.E. Sargsyan
peak wattage of 75 kW or more. Extensive and costly modi-
fications of the onboard electrical power system would be
required to accommodate a diagnostic device with such high
power consumption, even if it fits in the overall power capa-
bility of the station. Furthermore, the thermal control system
of the station would be seriously challenged to remove the
heat generated by such hardware, as gravity-driven convection
effects are absent in space.
Power users are prioritized in terms of their importance for
safe operation of vehicle systems. Experience with the Mir
station demonstrated how power shortage caused by electri-
cal system failures, solar panel damage, or suboptimal vehicle
orientation can affect spacecraft systems and various users. In
adverse conditions, devices with modest power needs have a
far better chance of receiving electrical power allocations than
their higher power competitors.
Diagnostic Imaging
in Exploration-Class Missions
The possible contribution of medical imaging to medical sup-
port systems for interplanetary flights and lunar or Martian bases
deserves special consideration. With clinical autonomy being
a more critical mission factor, such endeavors would require
a unique and largely self-sufficient combination of hardware,
clinically current medical expertise, and other resources nec-
essary to satisfy countermeasure and rehabilitation demands,
provide environmental monitoring, and handle any foreseeable
maladaptation, illness and injury that are likely to be the
pace-limiting variables in efforts to expand the presence of
humans into the solar system [18]. The most universal suite
of imaging hardware, chosen through analysis of existing evi-
dence, expert opinions, and most current technology, will prob-
ably have to be custom-built or heavily modified to satisfy the
specific requirements for use both en-route and upon arrival at
the destination. Of these constraints, small weight and volume,
long shelf-life and radiation stability, serviceability, and means
to upgrade, modular structure, and compatibility with shared
power, computing, and communication resources will be the
primary considerations.
Although an Earth-orbiting station can be supported almost
on demand by expertise on the ground, interplanetary missions
do not offer such luxury due to the sheer distances involved.
Unlike LEO missions, flights to remote planets such as Mars
or beyond have extremely limited, if any, mission abort options
for returning ill or injured crewmembers, any of which would
most certainly take longer than the natural course of any acute
illness. In addition, a large communication delay effectively
prevents live conversation and near-real-time data transfers,
leaving no choice but to exchange messages in a manner simi-
lar to present-day e-mail. Therefore, a considerable clinical
capability must be available aboard the interplanetary vehicle,
and the crew must possess training and skills to perform acute
medical care procedures independently.
9. Medical Imaging
Selected Medical Problems
and Imaging Solutions
Perception of medical risks in human space flight has been
published based on the information accumulated in human
space flight and several terrestrial analog populations [4].
From 20002002 NASA developed a specialized database
that lists possible medical conditions for space flight for the
purposes of determining medical capability. Ultrasound has
been identified as a key imaging modality in the diagnosis
and/or treatment of over 50% of these conditions, including
blunt and penetrating trauma, cardiovascular pathology, neph-
rolithiasis and urinary obstruction, biliary obstruction, and
acute and chronic infections. The conditions discussed in the
section that follows are considered to be possible in the set-
ting of human space flight or are known or expected to present
unique diagnostic challenges in microgravity. These selections
also illustrate the magnitude of differences that the spaceflight
environment may introduce into imaging techniques, interpre-
tation, and impact.
Pneumothorax and Other Pleural
and Pulmonary Conditions
Pneumothorax is commonly seen in patients with trauma
involving penetrating chest wounds and blast lung injuries and
those receiving positive-pressure ventilation; in many others
the precipitating event remains unclear. Radiography or CT
illustrating a classic gravitationally dependent hypodensity in
the involved hemithorax usually confirms the diagnosis. Since
the late 1980s, case reports and papers on ultrasound diagno-
sis of pneumothorax have been published [6467]. Accord-
ingly, NASA has investigated the use of ultrasound imaging
for the diagnosis of pneumothorax in space flight and remote
areas lacking radiographic capabilities. A pneumothorax
animal model was developed to test the capabilities of using
ultrasound for this condition in microgravity [68]. A case
report of ultrasound diagnosis of pneumothorax secondary to
a gunshot wound has also been published [69]. Concurrently,
in prospective human trials in cooperation with NASA [70],
thoracic sonography was shown to reliably diagnose pneumo-
thorax in the emergency room setting, with a 98% sensitivity
and a 100% specificity. Presence of the classic lung-sliding
pattern was shown to confidently exclude clinically signifi-
cant pneumothorax. Subcutaneous emphysema was the only
limiting factor and was one reason for the initial study to fall
short of 100% sensitivity. One patient had a negative chest x-
ray when the ultrasound was found to be positive; the X-ray
taken 1 h later was positive.
Largely due to these efforts, an expansion of the Focused
Assessment by Sonography in Trauma (FAST) examination
to include thoracic ultrasound is becoming a standard in many
trauma centers. NASA, in collaboration with academic medical
centers, has found that the ultrasound sign of partial lung sliding
199
can infer modest (limited) pneumothorax, which increases the
negative predictive value of this technique (Figure 9.9). It can
be hypothesized that high-quality CT would probably be diag-
nostic of pneumothorax in microgravity, but the accuracy of
chest radiography for the same purpose might be unacceptably
low because of inconsistent distribution of air and fluid in the
absence of gravity. In September 2002, for the first time in his-
tory of space flight, NASA scientist astronaut Peggy A. Whit-
son, assisted by a remote expert in the Mission Control Center,
successfully demonstrated typical patterns of normal pleural
interface in microgravity.
Free pleural fluid, either exudate or blood, would present
a diagnostic challenge in space even to a skilled physician,
primarily due to its unusual distribution. Animal studies con-
ducted by NASA in parabolic flight have clearly shown that
pleural fluid redistributes upon transition to microgravity,
partly shifting towards the mediastinum and partly forming a
uniform layer around the lung, as previously discussed. The
amount of fluid in the dependent portions (measured as the
degree of separation between parietal and visceral pleura)
markedly decreases upon insertion into microgravity, whereas
the separation elsewhere in the chest increases. Wide distri-
bution of fluid in the thorax increases the choice of sites for
probe application. The use of intercostal spaces in areas with
minimal muscle mass, such as the midaxillary line, can reveal
even small separation of pleural layers using high frequency,
high-resolution probes. Although no data exist for micrograv-
ity chest x-rays with these clinical situations, it is logical to
assume that radiography would have a high detection threshold
Figure 9.9. Partial pneumothorax with hemothorax showing pleural
separation by blood (thick white arrows) and by air (thin white
arrows). The black arrow points to a segment with a normal viscero-
parietal interface
200
and poor overall sensitivity, with the exception of large tension
pneumothoraces with apparent compressive atelectasis.
Pulmonary Parenchymal Pathology
In the absence of radiography and CT on-orbit, pulmonary paren-
chymal pathology may be easily overlooked, especially if lung
auscultation is difficult due to ambient noise. Historical medi-
cal events and known environmental hazards in past and current
space programs indicate that a potential exists for parenchymal
processes, such as pneumonitis following a toxic inhalation.
Although the normal aerated parenchyma is not easily
visualized by ultrasound, areas of lung consolidation can be
directly identified and monitored. Over the past decade, terres-
trial experience in ultrasound has advanced the ability to detect
chemical or infectious pulmonary inflammation, [71,72] sub-
pleural abscesses [73], and compressive or obstructive atelec-
tasis in previously healthy lungs. Similar procedures should
be possible with astronauts in microgravity environments.
Blunt Abdominal Trauma,
Peritoneal Fluid, and Gas
Clinicians rely heavily on CT and sonography to assist in
diagnosing intraperitoneal injury. As conventional radiogra-
phy and CT are not available aboard existing spacecraft, diag-
nostic ultrasound will remain the principal imaging modality
for abdominal trauma and peritoneal disease evaluation.
Abdominal trauma sonography, specifically the FAST
examination, has replaced diagnostic peritoneal lavage (DPL)
and CT as screening tests of choice in most trauma centers in
United States [74]. A positive FAST exam has been proven to
provide a definitive indication of intraabdominal hemorrhage
in appropriate settings. It is a rapid, safe, effective, repeatable,
and transmittable imaging tool that can screen for the pres-
ence of intracavitary hemorrhage (peritoneal, pericardial, and
pleural) or visceral leakage, and help estimate the magnitude
of the bleeding or leakage in most cases. Preliminary animal
and human trials have also shown that FAST can be expanded
to effectively diagnose or exclude traumatic pneumothorax
[68,70]. The ultrasound equipment available on ISS provides
the capability of performing FAST.
The ability to detect abnormal fluid collections relies on
the demonstration of sonolucent areas (fluid stripes) in typical
gravitationally determined anatomical locations; both CT and
sonography have traditionally relied on these fluid collections
as markers of organ injury. The behavior of intracavitary fluid
remained poorly studied in weightlessness until NASAs com-
prehensive experiments in the microgravity of parabolic flight
in 1999. These experiments resulted in a number of findings,
enriching the understanding of sonographic signs of blunt
abdominal trauma in both 1 g and microgravity. It was demon-
strated and confirmed that free fluid in the absence of gravity
does not readily localize to the predicted terrestrial anatomic
sites, and signs of its presence must be sought and interpreted
A.E. Sargsyan
differently. Erroneous interpretations of trauma sonograms in
0 g might render the study non-diagnostic or even mislead-
ing. Small quantities of fluid such as blood tend to remain in
the place of origin, initially enveloping adjacent mesothelial
surfaces, such as bowel loops, by the virtue of the dominant
forcesurface tension (Figure 9.10). As more blood accumu-
lates from a point of hemorrhage, it tends to form localized
collections and slowly spreads according to the intraperitoneal
anatomy and adjacent organ compliance. For example, blood
would reach the pelvis rather sooner from the left inframeso-
colic space or even the left subphrenic space, compared to the
right inframesocolic space, where a much larger volume of
blood would have to accumulate before it could spread over
the small bowel mesentery. Thus, although the basic FAST
exam locations remain valid in microgravity, an additional
scanning step called abdominal sweep is necessary to rule out
or detect blood collections in terrestrially atypical locations,
particularly between loops of the small bowel and in viscero-
parietal spaces.
Pneumoperitoneum may also be diagnosed by sonography
in microgravity, although the detection threshold and possible
pitfalls have not been clearly determined. In the previously
mentioned animal experiments, quantities of insufflated gas
as small as several milliliters were readily detectable. These
data confirmed previously published reports [75,76].
Acute Appendicitis
The wide variety of signs and symptoms of acute abdomen,
combined with the peculiar setting of space travel, make rul-
ing out a suspected acute appendicitis a very challenging
clinical task. Any acute right lower quadrant (RLQ) pain and
tenderness would elicit an extensive differential diagnosis,
Figure 9.10. A small hemoperitoneum in the zero gravity phase
of parabolic flight. Bowel loops in the vicinity of the bleeding are
wrapped in a thin layer of blood, seen as contouring of the bowel
sections
9. Medical Imaging
among which acute appendicitis would be considered in any
non-appendectomized crewmember. Aboard the ISS, diagnos-
tic ultrasound would be the only imaging method available
to conduct a focused study to rule out or confirm a variety of
possible conditions, including appendicitis and its complica-
tions, renal colic, diverticulitis, Crohns disease, female pel-
vic pathology, and other less frequently occurring conditions.
Imaging signs of acute appendicitis and its complications have
been thoroughly described [64,77,78]. Although these signs
are not expected to differ substantially in space, the clinical
presentation and course may be aberrant, further complicating
the flight surgeons task.
Among the abundant publications, data on the effect of
CT and diagnostic ultrasound on acute appendicitis manage-
ment vary greatly. Despite considerable skepticism expressed
by some [79,80], many radiologists assert that both methods
have a definitely positive influence on patient management, in
particular a measurable reduction of unnecessary appendec-
tomies [64]. Most experts suggest that a high index of clini-
cal suspicion should exist for appendicitis before using either
imaging technique to confirm the diagnosis [81]. A normal
appendix is visualized sonographically in 210% of healthy
individuals, although a higher success rate can be achieved
over time with consistent systematic approach and operator
training. The following statement by Puylaert clearly charac-
terizes the negative findings in suspected appendicitis: If a
normal appendix is visualized in its full length, appendicitis
can be excluded. However, this is rarely the case. In practice,
the only means to exclude appendicitis is to demonstrate an
alternative condition, which in most cases is possible by US
[ultrasound] alone. [78]
The ultrasound imaging procedure evaluating RLQ pain
must also include thorough visualization of the right kidney,
as much of the right ureter as possible, the gallbladder and
bile ducts, the pancreas, the cecal area, ileal loops with a
search for enlarged mesenteric lymph nodes, the urinary blad-
der with bilateral demonstration of ureteral jets, the uterus
with the right adnexa, and the peritoneal cavity for localized
or free fluid. In some cases, the study may also include con-
tralateral organs and tissues, or abdominal wall and psoas
muscles. Such a broad study performed by an experienced
sonographer requires 1530 min to complete. The same study
performed in LEO under real-time remote guidance would
require enormous patience and concentration and could take
considerably longer.
An inconclusive imaging report in a RLQ pain episode,
including a failure to visualize the appendix or otherwise pro-
vide a solution to the diagnostic problem, should warrant at
least another imaging session. From the authors own experi-
ence, the imaging conditions in the lower abdomen change
drastically over time because of the dynamics of intestinal
contents and peristalsis, bladder filling, abdominal guarding,
and the degree of patient and operator anxiety or concentra-
tion and cooperation with the examination. For these reasons,
imaging experts should be proactive in recommending focused
201
ultrasound exams not only in positive cases to monitor the dis-
ease anatomy and the efficacy of treatment, but also to make
repeated attempts to add confidence to previously inconclu-
sive or negative studies.
Decompression Sickness
Injury from decompression sickness (DCS), a potential result
of rapid transition to a lower ambient pressure, has been rec-
ognized and studied for over a century. Risk mitigation strate-
gies for spaceflight DCS have evolved since the first human
missions, particularly those involving extravehicular activities
(EVA) and their attendant decompression from cabin to suit
pressure. As our space activities broaden to involve construc-
tion of large and complex habitats, pressure-suited workers
must assemble, repair, and maintain these structures with pre-
cision and efficiency. The large amount of EVA time required
for assembly and maintenance of the International Space
Station, along with the stations unique EVA-related opera-
tional constraints, raise priorities for addressing likelihood,
prevention, and potentially intervention and treatment of
DCS. The mechanisms by which DCS bubbles form in body
tissues and fluids remain controversial, as does the relation-
ship between the magnitude of this gas phase and the clinical
manifestations of decompression sickness. Human hypobaric
experiments have been conducted by the Altitude Protection
Laboratory [8284] and by NASA [85,86] in collaboration
with several academic and government laboratories. The U.S.
Navy Experimental Diving Unit (NEDU) is also conducting a
large prospective study of decompression effects using trans-
thoracic echocardiography (TTE). This multiyear evaluation
of procedures for rapid decompression from shallow depth
saturation will add considerably to the body of knowledge
accumulated to date. TTE is used by many investigators to
determine the extent of gas phase formation by visual quanti-
fication of venous gas emboli (VGE) in the right and left heart
chambers. It has been demonstrated that bubble crossover and
penetration into the left circulation is associated with a higher
probability of clinically overt decompression sickness [82].
Detection of arterial gas embolism on bubble crossover during
ultrasound evaluation is thought to signify an increased risk of
type II DCS.
NASA Space Medicine and NEDU have also conducted
saturation diving experiments in a hyperbaric chamber com-
plex to determine if the ISS ultrasound equipment can be used
to detect VGE and what training would be required for space
medical care providers to acquire such information. During
these experiments, bubbles were successfully detected not only
in the cardiac chambers but also in peripheral veins of lower
extremities, such as the popliteal and anterior tibial veins. For
the first time, real-time power Doppler mapping was compared
with conventional duplex echocardiography and was shown to
have comparable and possibly better bubble detection ability.
The power Doppler technique takes advantage of shifts in the
original frequency of the ultrasonic beam due to reflection from
202
moving targets (Doppler shifts), or of ultrasonic noise emitted
by the bubbles under the influence of ultrasonic energy. Such
frequency shifts, detected along with their spatial coordinates,
are shown on the images in color, with the brightness propor-
tional to the amount (power) of the shifted ultrasound mea-
sured. It remains an open question whether ultrasound imaging
will ever be used operationally in space during or after decom-
pression events with high DCS potential; non-imaging Doppler
detection and monitoring of VGE in the course of extravehicu-
lar activity is far more feasible although the operational value
of such monitoring is debated.
Preflight screening for patent foramen ovale (PFO) is
believed by some to be a justified measure to lower the risk
of lifethreatening DCS during operational decompression
exposures, such as in diving and EVA. In conventional clinical
settings, paradoxical air embolism in neurosurgery is another
reason for PFO screening studies [8789]. The current gold
standard for identifying PFO is contrast-enhanced transesoph-
ageal echocardiography (c-TEE). Less invasive alternatives to
this method is contrast-enhanced transcranial Doppler ultra-
sonography (c-TCD) and contrast-enhanced TTE (c-TTE).
According to Stendel and colleagues [89], c-TCD is a highly
sensitive and highly specific method for detecting a PFO,
whereas C-TTE is unreliable for this purpose.
Ophthalmic Trauma
The first ophthalmic sonographic image was published in
1956 [90], and since then sonography has evolved to offer cru-
cial diagnostic information in many ophthalmic conditions,
including complications of ocular trauma. It is especially
helpful when visual inspection is impossible to perform or
does not provide a definitive diagnosis. In the past, dedicated
ophthalmic ultrasound systems were superior to multipurpose
systems for diagnosing ophthalmic injury and illness, thanks
to the use of single-crystal, high frequency probes focused at
fixed low depths, and to acceptability of low frame rates. How-
ever, this is no longer the case because modern multipurpose
systems employ sophisticated focusing and image optimiza-
tion techniques that are not feasible for the smaller systems.
Ultrasound in ophthalmology is used in three distinct clinical
applications: ultrasound biometry that pursues precise distance
measurements, ultrasound biomicroscopy (UBM) limited to
the anterior segment, and general-purpose scanning. UBM
uses extremely high frequencies (50 MHz and higher) and
provides very high resolution on the order of tens of microns
within shallow depths of about one cm [91]. Modern general-
purpose ophthalmic scanners provide excellent images of the
posterior chamber, the fundus, and orbital structures such as
orbital adipose tissue, optic nerve, vessels, and muscles. Other
imaging modalities in ophthalmology include CT and MRI to
primarily rule out facial trauma with orbital fractures, intraor-
bital masses, and suspected foreign bodies.
Astronauts undergo extensive ophthalmologic examination
at selection and during annual certifying examinations, including
A.E. Sargsyan
periodic retinal imagery and corneal topography. With actual
missions, preflight and postflight ophthalmologic examina-
tions include only visual (optical) inspection by hand held
ophthalmoscope, although any imaging modality is available if
clinically warranted. In-flight eye examinations are extremely
limited because of lack of specialized equipment and CMO
expertise. Although biometry and UBM have limited practi-
cal significance for space medicine, general scanning with a
multipurpose ultrasound device can be of great value in cer-
tain conditions. The ISS Ultrasound system is equipped with
a 12-MHz probe capable of producing ophthalmic images of
excellent quality. To prevent iatrogenic trauma in an environ-
ment devoid of gravity-stabilizing postures and fixation, safety
precautions must be strictly observed. Standard scanning pro-
tocols and real-time interaction with an expert are necessary
for efficient and dependable diagnostic evaluation. Currently,
ISS ultrasound stands as the main source of objective anatomic
information for the crew surgeon and ground-based ophthal-
mologists.
As of today, only singular cases of minor eye trauma have
been observed in space. However, the risks of serious eye
injury are present. Airborne objects, the cluttered environment
of a research laboratory, the use of elastic cords and pressur-
ized gases can all be considered risk factors for ocular and
periorbital trauma. Complications of ocular trauma, such as
recurrent hyphema or retro-vitreal hemorrhage, may evolve
over a period of 510 days; therefore, after a blunt impact,
ultrasound follow-up would be normally required, especially
with persistent or progressive symptoms. Ultrasound evalua-
tion of the eye on the ISS would be indicated in any case of
trauma with the following findings:
Disturbance of vision of any extent
Suspected globe penetration with or without a foreign body
Any abnormal finding during visual inspection of the globe
Significant pain or any other persisting symptom
Edema or bruising of periorbital tissues and eyelids
In the absence of slit lamp or other imaging options, diag-
nostic ultrasound may seek to obtain information that is nor-
mally outside the scope of standard ocular ultrasound. Some
portions of the ophthalmic ultrasound examination may be
best performed through self-examination, in order to better
coordinate probe position with the direction of gaze during
scanning and to keep the probe pressure below the discomfort
threshold.
NASA has conducted ground-based and parabolic flight sim-
ulations of remotely guided ophthalmic ultrasound in healthy
volunteers with promising preliminary results. These protocols
developed specifically for microgravity involve remote view-
ing of the ultrasound output video in near real time (2-s delay)
and verbal guidance of the subject through discrete steps of a
self-examination protocol. Volunteers with no prior experience
consistently found self-examination feasible and practical and
generated imaging sequences of diagnostic quality. The basic
protocols and scanning options are presented in Table 9.6.
9. Medical Imaging
Table 9.6. Image-guided interventional procedures.
Ultrasound guidance and control procedures
demonstrated on board the KC-135
Imaging support and verification of ureteral stent placement
Imaging support and verification of surgical thoracostomy
Image-guided aspiration and drainage of intra-abdominal fluid
Image-guided percutaneous suprapubic cystostomy
Imaging support and verification of Foley catheter placement
Imaging support of laparoscopy
Imaging support of thoracoscopy
Figure 9.11. High-resolution ultrasonic sections of the human eye.
Once acquired, these images are largely self-explanatory. 1- sagittal
section of the anterior segment; 2- coronal section through the iris
Sample images obtained by an inexperienced operator with
remote guidance on equipment identical to HRF Ultrasound
are shown in Figure 9.11.
Urolithiasis, Urinary Obstruction, and Retention
Urinary supersaturation with stone-forming salts and possible
changes in urine chemistry in microgravity may increase the
lithogenic properties of the urine, leading over time to devel-
opment of urolithiasis [9294]. Renal colic has been observed
during space flight at least once and shortly after landing in
other crewmembers. Some of these episodes might have had
a significant influence on the mission had they occurred during
203
Other possible applications for ultrasound guidance in microgravity
Soft tissue infection/abscess, to direct incision
Soft tissue or intracavitary infection/abscess, to direct puncture to aspirate
Image guidance for percutaneous pleural aspiration/thoracostomy
Image guided punctures to deliver pharmaceuticals
Image guided central venous access
Image guided removal of foreign body
flight. Although the prognosis in most cases is excellent, care-
ful diagnostic consideration, observation, and analgesia are
required. The differential diagnosis of the signs and symp-
toms of acute renal colic is quite varied, and some form of
noninvasive imaging is usually used. Associated pathology,
such as acute pyelonephritis in space would require imme-
diate attention and, if left untreated, could have devastating
consequences. At present, the space-based diagnostic experi-
ence for renal colic is minimal; therefore it is fair to assume
that diagnosis may be based on presenting complaints, scarce
physical examination data, and indirect data derived from uri-
nalysis. Among potentially useful imaging capabilities, such
as standard or helical CT, ultrasound, intravenous pyelogra-
phy (IVP), plain radiography, and urologic endoscopy, ultra-
sound is the most universal and practical to provide imaging
coverage of urolithiasis and its complications.
In case of suspected renal colic, even with mild symptoms,
ultrasound should be treated as an emergency procedure, and
30 min of net imaging time should be allocated. The patient
must be reasonably hydrated and have a full bladder. Due to
considerable variation of normal kidney anatomy, standard
sets of preflight baseline images of both kidneys should be
available to the expert on the ground.
As renal colic may be associated with both severe pain with
restlessness and transient ileus, imaging conditions may be
unfavorable. The renal ultrasound protocol includes imaging
the kidneys, the entire bladder volume (calculi may be in blind
spot locations due to microgravity), ureteral orifices, bladder
neck (with as much of the prostate and urethra as possible), and
intramural ureters. Attempts should be made to track the ureters
from the orifices backwards and upwards, from the renal pelvis
and ureteropelvic junction (UPJ) downwards, and at the iliac
vessel crossing. In case of ambiguous or negative results, the
study must proceed with a search for other causes. A follow-up
imaging session or monitoring schedule must be recommended.
The extent of renal pelvic dilatation is not always reliable
in determining the degree of ureteral obstruction, especially
when acute renal infection is present. A useful supplemen-
tary technique to assess ureteral patency or ipsilateral diuresis
is demonstration of ureteral jets (or of the lack thereof) in
color or power Doppler modes. A typical image of a
ureteral jet, acquired aboard the ISS, is shown in Figure 9.12.
Despite a usually favorable overall prognosis, it is easy to
foresee a scenario leading to evacuation of a crewmember
204
Figure 9.12. The ureteral jet (arrows) confirms patency and function
of the respective ureter. This image file was captured aboard the ISS
and downloaded during a subsequent communication session
from orbit with urolithiasis, especially if a second calculus is
detected or even suspected in the urinary system. Prevention
of unnecessary evacuation is a prime focus of imaging and
management. The following is an example of an ultrasound
report in a case of urolithiasis with good chances of a favor-
able outcome:
Imaging is complicated by bowel gas interference, restless condition of
the patient, and limited time. The right kidney is 13.5 6.0 5.0 cm;
collecting system is apparently dilated. The UPJ seems to be free from
obstruction. The right ureter is possible to track down to the lower pole
level, with a cross-section of up to 6 mm. No stones or other abnormali-
ties are identified within the kidney, UPJ, and the bladder lumen.
Through the bladder window, a small calculus (2 to 3 mm) is identified
in the intramural segment of the right ureter (at 9 mm from the orifice),
with a fluid-filled lumen proximal to the calculus. Orifices remain sym-
metrical. In the power Doppler mode, detectable ureteral jets are absent
on the right side, while strong jets are seen contralaterally. Sonography
of the left kidney is unremarkable. Conclusion: Sonographic picture is
consistent with a small calculus in the intramural segment of the right
ureter, with a significant degree of obstruction. Follow-up imaging is
recommended (full bladder is required).
Urinary retention has been observed in space. The probabil-
ity of retention is higher in the very initial phase of adapta-
tion to space microgravity, and certain medications used to
combat motion sickness, particularly those with anticholin-
ergic properties such as promethazine, may contribute to its
development. The flight surgeons decision regarding one-
time drainage with a Foley catheter or percutaneous drain-
age with temporary cystostomy would be greatly facilitated
if objective data were available on the actual volume of the
bladder and the status of the antireflux mechanisms. Gaping
ureteral orifices with distended upper urinary tract would be
easily identified by real-time ultrasound and would probably
be considered an indication for intervention, especially if the
reflux is bilateral or accompanied by symptoms of infection.
If percutaneous drainage is indicated and an appropriate ster-
ile kit is available, ultrasound would add a considerable mar-
gin of safety and confidence to the procedure. In case of Foley
catheter placement, ultrasound may be used to verify proper
A.E. Sargsyan
Figure 9.13. The cortical layer of a long bone (arrows) demonstrates
discontinuity, angulation, and possible tissue interposition. A frac-
ture can thus be diagnosed
placement and inflation and adequate resolution of the reflux.
Urinary retention and vesico-uretero-pelvic reflux have been
observed and percutaneous drainage successfully performed,
in an animal model during a KC-135 experiment. The proce-
dure, performed with proper precautions under sonographic
guidance by a physician, did not present any significant chal-
lenges in the free-fall condition.
Bone Fractures
Large mass handling in complex facilities such as the ISS
makes fractures a possibility, especially of small or superfi-
cial bones. As ultrasound may be the only available diagnos-
tic imaging capability, its clinical utility in identifying bone
fractures is of interest to space medicine. NASA investigators
in a collaborative study have sought to determine the accu-
racy of ultrasound as performed by physicians in an emer-
gency room setting in identifying fractures of the humerus
and femur. The physicians involved had been trained using a
standardized multimedia presentation. Preliminary data indi-
cate that ultrasound is very sensitive and moderately specific
for detecting acute traumatic fractures of long bones in a set-
ting with limited data acquisition and interpretation expertise.
Discontinuity of cortical bone is the primary sign of fracture
(Figure 9.13).
The Role of Imaging in Interventional
Procedures
In recent decades, Interventional Radiology has gradually
evolved into a distinct interdisciplinary branch of clinical
medicine. This trend of expanding the therapeutic and surgi-
cal role of imaging disciplines and imaging specialists, first
observed in angiography, has been followed in conventional
radiology, ultrasound, CT, and other visualization disciplines.
Interventional radiology and minimally invasive surgery
go hand-in-hand as more clinical conditions are diagnosed,
9. Medical Imaging
staged or described, and treated without major surgical trauma,
ensuring lower morbidity, cost, and personnel involvement
and shorter hospital stays. As the only imaging option aboard
the ISS, the therapeutic applications of ultrasound deserve
special attention.
Focused investigations conducted by NASA space medicine
and affiliated experts have already demonstrated feasibility of
several possible image-guided interventions for the micrograv-
ity environment; many others are expected to be possible. Some
examples of both groups are listed in Table 9.6. The degree of
clinical autonomy required; the level of medical risk accepted
by a given program, will determine the extent of sophistication
of the medical support system and the list of medical inter-
ventions available on board. As an example, peritonitis during
an interplanetary mission may require image-guided drainage
as an essential procedure to facilitate recovery [95]. Another
example of a potentially useful application is verification of
endotracheal tube placement, since in the noisy spacecraft
environment determining placement by chest auscultation may
be difficult [96,97].
The role of imaging in therapy is certainly not limited to
guided interventions. If the given pathology site or signs are
subject to ultrasound evaluation, it may be the only objective
means of monitoring progress of a disease or effectiveness of
the treatment, thus directly supporting decision-making by the
ground medical support personnel.
Conclusions
In its continuous efforts to refine the preventive and clinical
care capabilities aboard the ISS, the participating international
space medicine community has recognized medical imaging as
a required component of the stations integrated medical support
system. High-resolution optical imaging and sonography are cur-
rently available to support clinical decision-making in a poten-
tial medical event. Information has begun to accrue regarding
human anatomy in microgravity as determined by ultrasound,
and techniques and technology are being developed further to
enable this very useful imaging modality for space flight.
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 Part 2
Spaceflight Clinical Medicine
10
Space and Entry Motion Sickness
Hernando J. Ortega Jr. and Deborah L. Harm
One of the most significant clinical and operational challenges
experienced by spaceflight crews during the first few days in
microgravity is space motion sickness (SMS) [13]. SMS was
among the first adverse medical conditions encountered by
humans as they ventured outside of Earths gravity. Because of
SMS, decreased human performance is the main risk during the
critical first days of space flight. Activities typically performed
early that may be disrupted include payload activation, satellite
deployment, rendezvous, and docking. SMS symptomspar-
ticularly malaise, loss of initiative, and nauseacan range from
being mildly distracting to physically debilitating.
Physiologic systems operate effectively by maintaining
homeostasis across a broad range of physiologic functions
in Earths 1-G environment. Exposure to the microgravity
environment of space flight elicits a large collection of physi-
ologic changes and symptoms (including headward fluid
shifts, headaches, back pain, and cardiovascular, bone, and
muscle changes) that is collectively referred to as space
adaptation syndrome. SMS may be considered a component
of space adaptation syndrome. Over time, individuals adapt
to the weightless environment, and many initial physiologic
changes return to normal 1-G values. SMS is not a sickness
as such, but it is generally thought to be a natural response
to the adaptation of the neurosensory and perceptual systems
to microgravity [4]. Individuals who exhibit symptoms of
SMS should therefore not be viewed as abnormal.
Similarly, when crewmembers return to Earth, their physio-
logic systems must readapt to the 1-G environment. The collec-
tion of physiologic changes during the initial postflight period
is referred to as Earth-readaptation syndrome, and the postflight
motion sickness component is here referred to as entry motion
sickness (EMS). EMS is an operational concern for two reasons,
first because EMS may adversely affect the ability of a pilot to
control a vehicle on reentry or the ability of any crewmember to
perform an emergency egress after landing, and second because
readaptation and EMS can also become a concern for an explo-
ration-class (e.g., Mars) mission [2].
SMS can be defined as a state of diminished health charac-
terized by symptoms that occur in response to the unaccustomed
motion environment of microgravity [5]. It is typically a
self-limited and variable symptom complex that resembles
terrestrial motion sickness in onset, symptoms, and course.
EMS is a similar syndrome, one that is associated with the
readaptation process upon return to a gravitational field.
The next four subsections are a review of the signs, symp-
toms, laboratory findings, epidemiology, and neurophysiol-
ogy of SMS and EMS. Next, theories of etiology and possible
mechanisms involved in motion sickness are briefly discussed.
Finally, the last two sections describe the diagnosis and treat-
ment of SMS and EMS.
Symptoms, Signs, and Laboratory Findings
Large individual differences are apparent in the signs and
symptoms and the physiologic and biochemical correlates of
all forms of motion sickness. Moreover, no diagnostic labora-
tory tests exist for motion sickness. Next is presented a general
characterization of SMS and EMS, with a summary of the bio-
chemical correlates of terrestrial motion sickness and SMS.
Symptoms and Signs
The overt symptoms of SMS, which are similar to the symp-
toms of acute terrestrial motion sickness, typically consist of
stomach awareness, headache, drowsiness, nausea, vomiting,
pallor, sweating, and dizziness [3,6,7]. In an inflight investi-
gation during a Shuttle mission, SMS was seen to differ from
terrestrial motion sickness in the relative lack of sweating and
pallor. These manifestations were partly explained by the low
humidity of the spacecraft and possibly the facial swelling
caused by fluid shifts experienced by crewmembers in micro-
gravity [8]. Gastric motility, as measured by auscultation and
bowel sound recordings, is drastically reduced [9]. Vomiting,
should it occur, is more frequent early rather than later in the
course of SMS. It can crescendo quite suddenly, often without
prodromal symptoms, and can produce significant relief of
symptoms. Emesis episodes are typically separated by 13 h
211
212
or more. In the absence of oral intake, vomiting may not recur.
Malaise, loss of appetite, loss of initiative, and irritability are
also almost universal symptoms in SMS [10].
EMS symptoms are similar to SMS symptoms, but Russian
reports [11] (pertaining primarily to crewmembers who are
returning from space flights lasting about 6 months) suggest
that the symptoms can be more severe than those of SMS.
Other physiologic adaptations to microgravity complicate the
clinical picture. Changes in orthostatic tolerance, muscular
strength and coordination and posture and locomotion, can
affect the clinical presentation of symptoms after atmospheric
entry. The magnitude of other physiologic changes may mask
or potentiate symptoms of EMS. Orthostatic intolerance may
produce a feeling of light-headedness (commonly referred to
as dizziness), pallor, nausea, or headache. Decreases in mus-
cular strength may lead to rapid fatigue and malaise. Changes
in the control of head posture [12,13] and changes in sensory-
motor control have also been implicated in motion sickness
[13,14]. Thus, microgravity-induced changes in central mus-
cular coordination and postural control may be involved in the
generation of EMS symptoms.
Laboratory Findings
Operational constraints limit the opportunity to obtain sam-
ples of crewmembers body fluids during space flight. More-
over, the myriad physiologic changes that can affect plasma
levels and urinary excretion of electrolytes and hormones
(e.g., changes in blood volume, metabolism, renal function,
stress) complicate any interpretation of the relationships
between biochemical factors and SMS. Therefore, the find-
ings presented here should be interpreted cautiously.
Electrolytes
Motion sickness is not associated with significant changes in
serum electrolytes or glucose [15]. However, changes in elec-
trolytes might be expected if severe vomiting persists, result-
ing in a volume-contracted state with possible hypochloremic
metabolic alkalosis. In the presence of hypovolemia, sodium
will be spared, and further cation losses will lead to worsening
alkalosis, hypokalemia, or both [16,17].
In a series of 47 Space Shuttle flights, crewmembers who
did not exhibit symptoms of SMS had statistically higher pre-
flight levels of serum chloride and uric acid than preflight val-
ues of astronauts who exhibited SMS. Those astronauts without
SMS also exhibited lower urine specific gravity, osmolality,
and phosphate levels than susceptible crewmembers. However,
these sets of values were well within normal clinical ranges in
both groups [18]. Also, laboratory values from seven astronauts,
taken 2448 h into flight, showed decreases in plasma Na+ and
serum osmolality (compared with preflight values) that did not
correlate with SMS symptoms. Neither did the development of
SMS correlate with higher serum Cl and Mg2+ concentrations
during this period [18], although again, any changes observed
remained within clinical norms.
H.J. Ortega Jr. and D.L. Harm
Hormones
Thyroid-function measures, insulin levels, and most gastro-
intestinal humoral peptide levels do not change significantly
in terrestrial motion sickness. Stress-related hormones do
change, however, in the presence of motion sickness, most
notably increases in plasma cortisol, growth hormone, prolac-
tin, antidiuretic hormone (ADH), adrenal corticotropic hor-
mone (ACTH), and catecholamines [3,6,15,19]. Compared
with people who are not sick, people experiencing motion
sickness have markedly higher plasma cortisol levels. Symp-
tomatic patients also exhibit increased vasoactive intestinal
polypeptide, which decreases gastrointestinal motility [19].
Increased levels of corticotropin-releasing factor, ACTH,
and ADH seem to be associated with lesser susceptibility
to motion sickness [20]. Before flight, low-normal levels of
serum uric acid, creatinine, and thyroxine have been observed
in individuals with low tolerance to SMS, suggesting that
metabolic rate may play a role in their susceptibility to SMS.
Crewmembers who are not susceptible have higher preflight
levels of plasma cortisol than their more susceptible coun-
terparts, although the levels are not outside clinical norms
[3,21]. Increases in plasma growth hormone, cortisol, ACTH,
and ADH have been found in all space flight crews examined
during the first few days on orbit, along with a decrease in
aldosterone on flight day 1 [18,21,22]. As is the case for ter-
restrial motion sickness, higher serum levels of stress-related
hormones before and during flight seem to be associated with
lower susceptibility to SMS [18,21].
On return from space, plasma growth hormone, ACTH, and
ADH again increase in space flight crews relative to preflight
values, but serum cortisol levels are variable (some unchanged
from preflight levels, some slightly decreased). Plasma aldo-
sterone seems to increases to the high end of clinical normal
in all returning crewmembers examined [22,23]. Thus, at least
some of the stress-hormone responses seen upon return to 1-G
are also seen upon entry into microgravity. No associations
between postflight stress hormone levels and EMS symptoms
have been reported.
Epidemiology
The Russian cosmonaut Gherman Titov, on the 25-h Vostok
2 mission (the second crewed space mission in 1961), was
the first person to report experiencing SMS. He was also
the first person to spend longer than 2 h in space. The first
reported U.S. experience occurred during the Apollo 8 mission
(in December 1968), when all three crewmembers experi-
enced some degree of SMS [24].
Most of the experience in the U.S. space program has been
with short-duration flights, those lasting from several days to 2
weeks. EMS has rarely been observed after these short flights.
Although both the U.S. and Russian space programs have seen
EMS after brief missions, including as short as 4 days [11],
longer-duration space flight generally correlates with greater
10. Space and Entry Motion Sickness 213

incidence and severity of EMS. Russian investigators have
long reported a very high (> 90%) incidence of EMS and other
findings related to readaptation [11]. The difference is most
noticeable when long-duration space flight crewmembers experi-
ence the same landing event as their short-duration counterparts.
This occurred on some Soyuz crew rotation missions and in the
NASA-Mir Program, in which seven U.S. astronauts served as
crewmembers on the Mir space station during missions lasting
115188 days. In those flights, the crews returning from long
space flights clearly experienced more EMS and Earth-readap-
tation syndrome symptoms in the period immediately after land-
ing than did those returning from shorter missions.
Incidence
Table 10.1 summarizes the prevalence of SMS over the U.S.
and Russian space programs [3,4]. In the Space Shuttle Pro-
gram, the overall incidence of SMS is about 73% among those
flying for the first time [2,25]. Cases are generally classified
as mild, moderate, or severe (Table 10.2). In general, 49% of
cases are mild, 36% are moderate, and only 15% are severe
[25]. The overall incidence in the Russian experience is about
50% [11]. Since head movements are known to play an impor-
tant role in SMS, having less freedom of movement likely has
a protective function. Many crewmembers and investigators
believe that the relatively low incidence of SMS reported in
the early days of crewed space flight reflects the smaller size
of the cabins, and resulting limitation in crew movement,
in those spacecraft (Table 10.1). No SMS was reported by
astronauts in either Project Mercury or Project Gemini [26],
whereas 35% of the Project Apollo astronauts and 60% of
the astronauts aboard Skylab developed SMS [25]. Although
the Russian space capsules are slightly larger than their U.S.
counterparts, they still are much smaller than the current
Space Shuttle. In the Space Shuttle, crews are released sud-
denly into a large habitable volume after an 8-min ride to
orbit. They must doff their launch-and-entry suits, an activ-
ity that involves significant head movements. Crews on board
the Russian Soyuz craft, by comparison, spend 12 days in a
much smaller volume before reaching the much larger vol-
umes of the Mir or the International Space Station. Therefore
it is possible that the large volume of the Space Shuttle, com-
bined with the high level of activity experienced immediately
upon orbital insertion, may account for the difference in the
prevalence of SMS between astronauts and cosmonauts.
Interestingly, even though no SMS was reported during
the Gemini space flights, caloric intake was particularly low
for many crewmembers, suggesting the presence of a loss of
appetite that could have resulted from mild SMS [27]. Under-
reporting by crewmembers is a possibility, although experi-
encing SMS has absolutely no career-limiting implications
with regard to medical standards.
Male and female astronauts seem to be affected in equal
proportions by SMS, and age does not seem to affect inci-
dence. Pilots, mission specialists, and other crewmembers
also are affected equally. Those who are susceptible dur-
ing their first space flight usually have SMS on subsequent
flights. Although previous SMS is the best predictor for
future SMS, repeat exposure seems to result in the same or
less severe symptoms than those experienced during previous
flights [25]. Aerobic fitness is not related to SMS symptoms
or severity [28]. Interestingly, a preflight diet that is high in
protein and low in carbohydrates may have been associated
with SMS symptoms during the Skylab program [29].

Table 10.1. Reports of space motion sickness in the U.S. and Russian space programs.
No. crew No. reporting SMS Habitable spacecraft
Program member-flights symptoms (%) volume, m3
Mercury 6 0 (0) 1.7
Gemini 20 0 (0) 2.55
Apollo 33 11 (33)
Command Module 5.95
Lunar Module 4.5
Skylab 9 5 (56) 275
Apollo-Soyuz Test Project 3 0 (0) 5.95
Space Shuttle 71
19811986 85 57 (67)
19881998 315 252 (80)
Total (mean %), US programs 471 325 (70)
Vostok 6 1 (17) 5
Voskhod 5 3 (60) 5
Soyuz 38 21 (55) 10
Apollo-Soyuz Test Project 2 2 (100) 10
Salyut-5 6 2 (33) 70
Salyut-6 27 12 (44) 90
Mir 90a
Total (mean %), Russian programs 84 41 (49)
a 3
Plus 5090 additional m from other modules.
214
TABLE 10.2. Space motion sickness grading criteria.
Severity (score) Symptoms and signs
None (0) None except for mild, transient headache or mild
decrease in appetite.
Mild (1) One to several symptoms of a mild nature;
may be transient and only brought on as the result
of head movements; no operational impact; may
include single episode of retching or vomiting; all
symptoms resolve in 3648 h.
Moderate (2) Several symptoms of a relatively persistent nature
that may wax and wane; loss of appetite; general
malaise, lethargy, and epigastric discomfort may
be the dominant symptoms; includes no more
than two episodes of vomiting; minimal opera-
tional impact; all symptoms resolve in 72 h.
Severe (3) Several symptoms of a relatively persistent nature
that may wax and wane; in addition to loss of
appetite and stomach discomfort, malaise, leth-
argy, or both are pronounced; strong desire not to
move head; includes more than two episodes of
vomiting; significant performance decrement may
be apparent; symptoms may persist beyond 72 h.
Source: Davis et al. [25]. Used with permission.
Only one episode of what was probably EMS was reported
during the Apollo program. The Skylab 2 astronauts, who had
spent a total of 28 days in low Earth orbit in May and June 1973,
reportedly experienced seasickness on the recovery ship
immediately after splashdown. Since the seas were rough, the
contribution of EMS to these symptoms is unclear. However,
since this mission lasted almost a month, it seems likely that
EMS contributed to this postflight illness. Drug prophylaxis
with scopolamine before entry seems to have been successful
in minimizing problems on subsequent Skylab flights [30]. As
noted previously, EMS is rarely observed after short Space Shut-
tle missions. The incidence of EMS after longer Space Shuttle
missions is similar to that reported by Russian investigators after
missions lasting up to 2 weeks. In the Russian experience, EMS
reportedly afflicts 27% of the cosmonauts after short-duration
missions (414 days) and 92% after longer-duration missions
(those lasting several months to 1 year) [11]. The Russian
reports also indicate that EMS symptoms generally occur in cos-
monauts who had SMS; however, 11% of the cosmonauts who
experienced little or no SMS did experience EMS. EMS may be
complicated by the crewmembers relative state of dehydration
upon return and orthostatic intolerance after landing. Further
details of these problems are discussed in Chap. 16.
Influencing and Precipitating Factors
Anyone who has a functioning vestibular system can, under
the right conditions, experience motion sickness [3133]. The
incidence and severity of that sickness varies as a function
of the specific stimulus conditions (i.e., type of sensory con-
flict) as well as the intensity and duration of the stimulus
[34,35]. Even when stimulus conditions are of a mild to mod-
erate intensity, such as those that occur in weightlessness, the
H.J. Ortega Jr. and D.L. Harm
chronic nature of exposure to those conditions may partially
explain the high incidence of SMS. Whether an individual
experiences motion sickness in a given set of circumstances
also depends on his or her susceptibility. Individual differ-
ences in physiologic and psychological factors as well as past
experiences contribute to susceptibility [35,36].
Factors that serve to attenuate motion sickness include
concentration on performing a task [37], applying strong tac-
tile inputs (e.g., strapping oneself tightly in a seat), closing
ones eyes, and restricting activity [4,13]. Factors that seem to
worsen SMS include distasteful or unpleasant sights, noxious
odors, certain foods, excessive warmth, loss of 1-G orienta-
tion, and head movements [24].
Microgravity by itself may not induce SMS, as evidenced
by the lack of symptoms reported during the Mercury and
Gemini flights. Head movements, which were relatively mini-
mal in the close confines of those small spacecraft, are associ-
ated with the development of SMS symptoms, and they also
exacerbate existing symptoms [10,38]. Pitch head movements
(chin up or down) are the most provocative, followed by roll
and yaw [10,13,38]. Lackner and colleagues [13,39] suggested
that changes in head and limb sensory-motor control patterns
induced by altered gravitoinertial forces may be an etiologic
factor in SMS [13,14]. Restricting head motion has been shown
to reduce SMS symptoms [40]; however, those who minimize
head movementsunlike avoiding other inciting factorsseem
to have the symptoms for longer periods. Although head move-
ments worsen SMS symptoms, they are necessary to facilitate
neurovestibular adaptation to microgravity [41,42].
Similarly, EMS symptoms are induced or exacerbated by
warmth and head movements during atmospheric reentry and
in the early postflight period. The most vulnerable crewmem-
bers are those who are required to make several head move-
ments during reentry. On the Space Shuttle, for example, it
is the flight engineer (Mission Specialist 2) who must make
frequent head turns to monitor panels and throw switches.
Again, head movements likely serve a dual role, one that is
both provocative and adaptive.
Time Course
Initial symptoms of SMS can occur within minutes of expo-
sure to microgravity. Symptoms typically increase over a
period of hours until they plateau at a certain intensity. Sev-
eral instances have been reported of delays in the onset of
symptoms, some lasting as long as 48 h after arrival on orbit.
In many of these cases, the individuals had been medicated
with scopolamine, which seems to have had the desired effect
of suppressing SMS symptoms but also apparently delayed
the normal adaptation to microgravity [43].
Resolution of symptoms typically occurs after about 3048 h
of exposure to microgravity [3,4]. Some cases have resolved as
quickly as 12 h after orbital insertion, and most cases are com-
pletely resolved within 47 days [44]. Rare cases in particularly
susceptible individuals may not fully resolve at all over 14 days
10. Space and Entry Motion Sickness 215

of space flight [7]. Russian investigators report that 25% of the

cosmonauts have symptoms lasting 14 days or longer, and 17%
of cosmonauts on long-duration missions (i.e., 83365 days)
periodically develop symptoms throughout the flight [45,46].
Nevertheless, the typically rapid adaptation gives SMS a greater
relative effect on shorter-duration missions and minimizes its
importance on long-duration missions [47].
EMS follows a time course similar to that of SMS. Symp-
toms can begin quite early, within minutes of G onset (that is,
at the entry interface). Some crewmembers who have exhi-
bited no symptoms during entry and landing begin to develop
symptoms as soon as they stand for egress. EMS symptoms
tend to crescendo rapidly, then taper off over time. Symptom
severity seems to correlate with time spent on orbit; as mission
length and recovery extends past certain thresholds, symptom
severity increases. For missions 20 days in length or less, func-
tional recovery should be complete in about 7 days. For 3- to
6-month missions, those suffering from EMS symptoms should FIGURE 10.1. Artists rendering of the human vestibular system
expect a minimum of 30 days of recovery time. These represent
conservative guidelines which will be refined as further data is
A small, specialized piece of neuroepithelium, called the
analyzed.
macula, is located on the wall of both the utricle and the sac-
Some relapse phenomena have been reported during the
cule. The epithelium is covered by a gelatinous layer in which
course of recovery after landing. Exposure to some inertial
calcium carbonate crystals (otoliths or otoconia) are embedded.
environments (i.e., turning a corner in a car, lying in bed in
Hair cells, which transduce information about acceleration,
darkness, etc.) can bring on a sudden return to an early post-
project into the gelatinous layer. Acceleration forces displace
flight state of adaptation. This, in turn, can elicit mild to
the otoconia, causing a deflection of these hair cells. This
severe EMS symptoms several days to a week after return to
deflection or bending produces depolarization of the hair cells,
Earth. Recovery from such relapses generally is more rapid
transducing mechanical energy (acceleration) into neural sig-
than immediately after flight.
nals. The hair cells in the macula are oriented in different direc-
tions such that a diverse pattern of excitation occurs for various
Anatomy and Physiology head positions and acceleration forces in different directions.
Even in a resting position, nerve fibers from the hair cells trans-
Despite a large body of research concerning motion sickness, mit neural signals that indicate the gravity vector.
the specific mechanisms involved are still largely unknown. The three semicircular canals (anterior, posterior, and hori-
However, it is widely accepted that the vestibular system is zontal) are fluid-filled loops that sense angular accelerations
involved and that both the central and autonomic nervous systems of the head in the pitch, roll, and yaw planes. The three canals
play important roles in the expression of motion sickness. The are arranged at right angles to each other to represent the
following subsection provides a brief overview of the anatomy three planes in space. At the end of each is an enlarged por-
and physiology of the vestibular system and of its central con- tion known as the ampulla, which contains the neurosensory
nections that are thought to be involved in motion sickness. apparatusthe crista ampullaris. Atop the crista is a gelati-
nous mass (cupula) into which sensory hair cells project. Iner-
The Vestibular System tial movement of the endolymph produces deflection of the
cupula, and the hair cells transduce angular movement of the
The dense petrous portion of the temporal bone contains and head into neural energy.
protects the complicated, three-dimensional system compris- Animal studies have suggested the possibility that exposure
ing the human vestibular system. Within its carved-out bony to microgravity produces changes in the otolith and canal end
labyrinth lies the membranous labyrinththe tubular soft organs or changes in the neural components (hair cells, syn-
tissue of the actual sensing organs. The two vestibular sen- apses) that alter vestibular function and contribute to changes
sors are the otolith organs located within the vestibule and the in central sensory integration functions [4].
semicircular canals (Figure 10.1).
The two otolith organs, the utricle and the saccule, are
Central Neural Connections
arranged in orthogonal planes. The utricle is in the horizontal
(axial) plane, and the saccule is oriented in the sagittal plane. Vestibular afferents form part of the eighth cranial nerve,
The otolith organs sense head tilt with respect to gravity and which relays inputs from the vestibular end organs to the brains
linear acceleration along the X, Y, and Z axes. vestibular nuclei, located in the brainstem approximately at the
216
junction of the medulla and pons (superior, medial, lateral,
and inferior vestibular nuclei). Some fibers pass directly to
areas in the cerebellum. Neural pathways from the vestibular
nuclei project to areas in the medulla, the cerebellum (to
oculomotor and spinal-motor control systems), and the cere-
bral cortex. Both the vestibular nuclei and the vestibulo-
cerebellum receive inputs from other sensory systems that are
concerned with perception of the body position and movement.
The entire system operates reflexively to stabilize vision,
and to coordinate limb, trunk, and head movements so as to
maintain balance.
Because most of the signs and symptoms of motion sick-
ness are autonomically mediated, understanding the role of
the vestibular system in autonomic regulation is important.
The most direct pathway for vestibular modulation of auto-
nomic responses involved in motion sickness is via efferent
projections from the medial and inferior vestibular nuclei to
the nucleus tractus solitarius and the dorsal motor nucleus of
the vagus. Other pathways that may be involved include ves-
tibular projections to the lateral tegmental field of the reticular
formation or to the caudal ventrolateral medulla. Finally, the
cerebellum may be another route through which vestibular
inputs may modulate autonomic activity [48].
Etiology
The two major theories that have been proposed to explain
SMS are the sensory conflict theory (also known as the sen-
sory mismatch or sensory rearrangement theory) and the fluid
shift theory. Although both theories have merit and neither is
ideal, the sensory conflict theory remains the most accepted
overall explanation for motion sickness. In this subsec-
tion, these two theories are briefly described, as is an otolith
asymmetry hypothesis that has been advanced specifically to
explain SMS and hypotheses concerning sensory adaptation
to space flight.
Sensory Conflict Theory
The sensory conflict theory of Reason and Brand [49] has
withstood more than 20 years of debate and remains the
most accepted overall explanation of motion sickness etiol-
ogy. Briefly, the sensory conflict theory assumes that under
normal gravity conditions, human orientation and movement
is based on several sensory inputs to the central nervous sys-
tem. The vestibular system provides information relating to
linear and angular acceleration and position with respect
to gravity; the visual system provides information relating
to body orientation with respect to the visual world; and
the touch, the pressure, and the kinesthetic systems provide
information relating to limb and body position. When the
environment is altered in such a way that this information
does not match previously stored neural patterns, motion
sickness may occur.
H.J. Ortega Jr. and D.L. Harm
The lack of an effective gravity stimulus to some of the
sensory systems during space flight changes the relationships
among the various sensory inputs, thereby creating sensory
conflict. These altered relationships initiate adaptive processes.
Two hypotheses have been proposed to explain sensory adap-
tation to microgravity: the sensory compensation and the oto-
lith tilt-translation reinterpretation (OTTR) hypothesis. These
hypotheses are described briefly in the following paragraphs.
Sensory Compensation
Sensory compensation occurs when the input from one sensory
system is attenuated and the inputs from other sensory systems
are augmented. In the absence of an appropriate gravity signal
in weightlessness, information from other sensory modalities
can be used to maintain spatial orientation and movement
control [5053]. For example, astronauts often report increas-
ing their reliance on visual information to maintain spatial
orientation [51,52].
Otolith Tilt-Translation Reinterpretation
Because of the fundamental equivalence between linear
acceleration and gravity, signals from the otolith are ambigu-
ous by nature. The otolith organs signal both head tilt with
respect to gravity and linear acceleration, which is perceived
as translational movement. In the microgravity of space
flight, the otolith organs do not respond to head tilt, but they
still respond to linear acceleration. The OTTR hypothesis
suggests that because gravity stimulation is absent in micro-
gravity, any interpretation of otolith signals as tilt is meaning-
less. Therefore, during adaptation to weightlessness, the brain
reinterprets all otolith signals as linear translation. Until this
adaptation is complete, an altered relationship exists among
signals from the semicircular canals, otolith organs, and neck
proprioceptors that normally indicate head tilt (i.e., there is
sensory conflict). Thus, on return to Earths 1-G, the brain
must reestablish a gravity interpretation of tilt.
Sensory conflict theory explains much in general, but
little in specifics. It does not explain, for example, the spe-
cific mechanisms by which symptoms are produced in either
SMS or motion sickness, nor does it explain those cases in
which conflict exists but no symptoms occur. This theory also
does not address the observation that adaptation cannot occur
without conflict. Finally, the sensory conflict theory does
not provide any predictive power regarding who will display
symptoms under which types of sensory conflict.
Fluid Shift Theory
Since most launches require that the crew assume a supine posi-
tion with legs raised for a few hours before liftoff, a central fluid
shift begins on the launch pad and continues in microgravity.
This fluid shift has been theorized to raise intracranial pressure
and cerebrospinal fluid or endolymph pressure in the inner ear,
thus producing symptoms similar to those seen in patients with
10. Space and Entry Motion Sickness
increased intracranial pressure due to a space-occupying lesion
or obstruction (vomiting, dizziness, headache) [8].
This theory has drawbacks similar to those associated with
the sensory conflict theory, namely a lack of predictive power
and difficulty accounting for asymptomatic individuals. It also
fails to explain episodes of EMS. However, in studies inves-
tigating the possibility that fluid shifts are involved in SMS,
the time course of adaptation to the fluid shifts did match to
some extent the time course of SMS. Studies in which ana-
logs were used to mimic the fluid shift (bed rest and 6-degree
head-down tilt) failed to show that the ensuing fluid shift pro-
duced either motion sickness or an increased susceptibility to
motion sickness [53,54]. Over time, this theory has been dis-
counted because of better understanding of the nature of the
fluid shifts [55] and observations that actual central pressure
decreases in space [56]. However, the definitive studies have
yet to be completed.
Otolith Asymmetry Hypothesis
von Baumgarten and Kornilova and colleagues [5759] have
proposed a mechanism complementary to the sensory conflict
theory to explain adaptation to weightlessness, readaptation
to Earth gravity, and individual differences in SMS susceptibi-
lity. Their otolith asymmetry hypothesis states that individu-
als experience subtle differences in otolith mass between the
left and right otolith maculae that are well compensated for on
Earth. In space flight, however, the difference in mass gener-
ates asymmetrical afferent signals, leading to SMS. A similar
imbalance would occur upon return to Earth, resulting in sen-
sory-motor disturbances and EMS. Diamond and Markham
have proposed an ocular counter-rolling test that measures
this mismatch and may predict SMS [6062].
As is true for the sensory conflict and fluid shift theories,
the otolith asymmetry hypothesis is limited in its ability to
fully explain and predict SMS and EMS. For example, if the
loss of compensation for otolith asymmetry in space flight was
sufficient to produce SMS, then crewmembers should develop
symptoms without making head movements. However, as dis-
cussed earlier, movement is required for SMS symptoms to
occur. In addition, since otolith asymmetry is present during
the free-fall phase of parabolic flight, one would expect that
motion sickness during parabolic flight would predict SMS
during orbital flight. To date, however, no evidence has been
found to suggest that astronauts who become motion-sick dur-
ing parabolic flight are more likely to experience SMS than
their non-motion-sick counterparts.
Diagnosis
Clinical
The diagnosis of SMS is made by history of recent exposure
to microgravity and reported motion sickness symptoms. No
217
laboratory or other confirmatory data are needed to guide thera-
peutic decisions. Flight surgeons generally categorize the cases
as mild, moderate, or severe as shown in Table 10.2 [25].
The diagnosis of EMS is based on motion-sickness symptoms
after recent return from microgravity conditions. Although no
formal grading system has been established, categories similar
to those for SMS (Table 10.2) are used.
Differential Diagnosis
The differential diagnosis of SMS would include acute gastro-
enteritis and possible exposure to toxins. The preflight Health
Stabilization Program observed in the U.S. and Russian space
programs, which involves a 1-week period during which access
to the crew is strictly controlled and restricted to medically
screened individuals, makes an infectious etiology unlikely.
Close monitoring of onboard food and water sanitation imme-
diately before flight also minimizes infectious etiologies [63].
Cabin telemetry may provide clues regarding possible expo-
sures to toxins in flight. Flight surgeons, who are members of
the flight control team that provides real-time mission support
from the Mission Control Center, keep abreast of hazardous
payloads, possible contingency scenarios, and actual untoward
events. The most likely atmospheric contaminant that could
produce symptoms mimicking SMS is CO2. Exposure to 310%
CO2 concentrations can produce headache, malaise, dizziness,
and nausea. Indeed, local buildup of CO2 may become com-
mon in space flight because of the lack of convective currents
in microgravity and other ventilation defects in spacecraft. CO2
withdrawal can also produce similar symptoms.
If the air revitalization system on a spacecraft malfunc-
tions early in space flight, SMS vs. CO2 vs. exposure to other
toxins might be considered. Recommended actions include
avoiding certain areas or conditions (e.g., a closed sleep sta-
tion) and redirecting fans or airflow. If payload containment
is breached early during the flight, the presence of SMS symp-
toms may complicate evaluation of the toxic exposure. Many
compounds can be flown as middeck payloads; familiariza-
tion with the toxicology of all payloads is thus critical to pro-
vide proper medical support to the crew.
The Space Shuttle utility compounds that are most likely to
produce symptoms mimicking those of SMS are the propel-
lants hydrazine and monomethylhydrazine. These compounds
are not found inside the spacecraft, and exposure is not likely,
but may be inadvertently brought inside on a contaminated
suit following extravehicular activity. Exposure to these pro-
pellants can cause dizziness, nausea, vomiting, and behavioral
changes. Since exposure to both compounds generally affects
other physiologic systems as well (the eyes, respiratory tract,
skin, and central nervous system), this may be helpful in mak-
ing the differential diagnosis.
A differential diagnosis of EMS also includes acute gas-
troenteritis and possible exposure to toxins. Flight surgeons
must thus be knowledgeable concerning the medical condi-
tions that can occur in space flight. The Space Shuttle food
218
supply is carefully monitored, thereby making an infectious
etiology unlikely in the immediate postflight period; any food
or fluids consumed on board the crew transport vehicle and at
the baseline data collection facility should be considered as
possible infectious sources.
Therapy and Prognosis
Education
Flight surgeons currently discuss the natural course of SMS
and EMS with crews during routine medical training pre-
flight. Crewmembers are counseled on provocative stimuli,
such as head movements and loss of 1-G vertical orientation,
and ways of mitigating the effects of SMS. Practically, this
counseling involves instructing crewmembers to move slowly
and to bend down to access an item at knee level so as to
maintain a visual vertical reference rather than pitching upside
down during the first hours and days of space flight. Crew-
members are also advised to avoid excessive heat and noxious
odors and to maintain adequate hydration in flight during the
course of symptoms.
Flight controllers and mission planners are also educated
on the effects of SMS and EMS on crew performance. Space
Shuttle flight rules currently prohibit scheduling of critical
activities (extravehicular activities) within 3 days of reaching
orbit [1]. Mission planners also attempt to lighten crew activi-
ties during the first 1 or 2 days because of known decreases in
performance ability.
Prophylaxis
Pharmacologic interventions remain the most effective way
of preventing SMS. However, oral treatment after symptom
development is complicated by variable drug bioavailability
that may be related to changes in metabolic rate and decreased
gastrointestinal motility and absorption [1].
Early efforts at prophylaxis used a combination of 0.4 mg
scopolamine and 5 mg dextroamphetamine (ScopeDex) that
had been effective in treating seasickness and other types of
motion sickness [6466]. ScopeDex was found to prevent the
development of SMS symptoms in only a few cases, and even
then, its withdrawal led to rebound illness. ScopeDex is no
longer used by astronauts [43]. These observations are con-
sistent with ground-based research findings [67]. Numerous
other antimotion-sickness medications used to treat terrestrial
motion sickness have met with varying degrees of success
[43,68], e.g., diphenhydramine, dimenhydrinate, meclizine,
and chlorpromazine.
A review of postflight medical debriefing records from
112 astronauts who flew between 1996 and 2000 suggests
that the use of prophylactic drugs does not appreciably alter
the incidence or severity of SMS (J.B. Clark, M.D. personal
communication, 2001). However, some individuals with
H.J. Ortega Jr. and D.L. Harm
multiple flight experiences report benefits from prophylaxis.
Currently, some astronauts take an oral combination of 25 mg
promethazine with 5 mg dextroamphetamine (PhenDex)
prophylactically in the final hours before launch. Anecdotal
evidence from a few individuals suggests that this regimen
is effective and acceptable, despite earlier concerns from the
medical community about performance effects [69]. Prometh-
azine does not seem to delay adaptation [1], and it may actu-
ally hasten adaptation to provocative motion [70]. The use of
prophylactic medications is most appropriate for crewmem-
bers who are known to be susceptible to SMS. Currently no
known ground-based tests predict SMS susceptibility [3,71].
The best predictor is a history of SMS. Therefore, NASA flight
surgeons recommend that first-time flyers forego drug pro-
phylaxis to determine whether they will need medications on
future flights. In addition, because of potential adverse perfor-
mance effects, the primary Space Shuttle flight crew (i.e., the
commander, the pilot, and the flight engineer) are not allowed
to take antimotion-sickness medications before launch.
Medications are also occasionally used to prevent EMS.
Some astronauts who have histories of moderate to severe
postflight symptoms have taken PhenDex or meclizine fol-
lowing the deorbit burn to mitigate the symptoms. Because
of the global physiologic readaptation processes that start
immediately on exposure to re-entry g forces, the effective-
ness of this practice remains unknown. As noted earlier, given
the potential risk of drug side effects impairing piloting per-
formance, Space Shuttle pilots and commanders do not use
prophylactic medications.
Preflight Adaptation Training
Preflight adaptation training may hold promise as a
countermeasure for SMS. Training devices and proce-
dures designed to adapt astronauts to novel sensory and
perceptual conditions resembling those of weightlessness
continue to be developed [3,50,72]. The general concept
is that, with repeated exposure to these conditions, astro-
nauts can develop sensory-motor programs appropriate for
microgravity and can learn to rapidly switch from 1-G to
microgravity programs and vice versa (in other words, they
can become dual-adapted). This state of dual adapta-
tion is thought to facilitate adaptation to microgravity
and readaptation to Earth, thereby reducing both SMS and
EMS. This training includes education, demonstration,
and experience with a variety of perceptual illusions and
novel sensory inputs. One evaluation of this training found
a 33% improvement in SMS symptoms in participating
crewmembers as compared with those who had not partici-
pated in the training [73]. The improvement was similar in
both first-time and experienced flyers.
The Russian space program uses extensive preflight motion
training [74]. In that program, preflight vestibular training has
primarily involved Coriolis (cross-coupled angular) accelera-
tion generated by a variety of devices such as rotating chairs.
10. Space and Entry Motion Sickness
Similar preflight training was used early in the U.S. space pro-
gram but was abandoned when it failed to mitigate SMS during
flight. Moreover, the preflight training with Coriolis accelera-
tion does not duplicate the sensory conflicts encountered in
weightlessness [11,74]. Although cosmonauts continue to use
this type of training, the incidence of SMS symptoms in Rus-
sian and U.S. space flight crews is similar.
Adaptation to one sensory-conflict situation (e.g., those gen-
erated by Coriolis accelerations or parabolic flight) does not
necessarily apply to other sensory conflict situations, particu-
larly when the conflict differs considerably from one situation
to the other. The approach taken in the U.S. space program to
develop preflight adaptation training is based on duplicating,
to the extent possible, the sensory conditions encountered dur-
ing space flight. Two task-trainers and procedures are being
developed and investigated.
The first device, the device for orientation and motion envi-
ronments (DOME), was designed to allow stabilization of
graviceptors. Although gravity cannot be eliminated on Earth,
its contribution to spatial orientation in the simulated environ-
ment can be negated by keeping the gravity vector constant
with respect to the trainee as the trainee changes orientations
or makes head movements within that environment. Perceived
changes in orientation and motion are produced by changing
the visual environment around the fixed trainee, who can still
engage in simulated motion. This condition is similar to micro-
gravity in that angular head movements can be made in pitch
and roll without a changing gravity vector. The DOME is a
3.66-meter (12-foot) spherical dome with an interior virtual-
reality system designed for virtual performance of opera-
tional-type tasks. In addition, DOME training will also include
practice in navigating to various locations within a space flight
environment (Space Shuttle, Spacelab, International Space
Station) from different starting orientations to reduce spatial
disorientation on orbit.
The second device, the tilt-translation device (TTD), is
based on the OTTR hypothesis of adaptation to microgravity.
The TTD is designed to evoke reinterpretation of otolith tilt
signals as linear motion, achieved by providing an appropriate
phase relation between movement of the visual world and head
tilts (Figure 10.2). The TTD is a 1-degree-of-freedom tilting
platform on which the subject is seated in a car seat in either a
pitch or roll configuration. A visual surround mounted on the
TTD platform moves linearly, parallel to the subject. Three-
dimensional black stripes line the inside walls of the device,
and 4 successively smaller outlined black squares are attached
to its end panels. A 270-degree phase relation between tilt and
surround motion best supports reinterpretation of otolith sig-
nals as linear translation, as evidenced by perpetual reports
of linear self-motion, decreased vertical compensatory eye
movement gain (similar to those observed in crewmembers on
orbit) and decreased postural stability (similar to that observed
in crewmembers after landing). More detailed descriptions of
these devices and their underlying concepts are available else-
where [3,4,72,75].
219
Long-duration space flight missions will probably require
on-orbit countermeasures to maintain a dual-adapted state.
Many scientists believe that readaptation to gravity would
be enhanced by frequent exposure to simulated gravitational
states on board a spacecraft. This situation would require some
type of onboard human-rated centrifuge or complete space-
craft rotation to produce an inertial force similar to gravity and
would be coupled with physical countermeasures to maintain
bone and muscle mass. This solution, although potentially
effective [12], raises many operational and engineering issues
that will need to be addressed [76].
Treatment During and After Flight
The most effective in-flight treatment for SMS found to date
is parenteral (usually intramuscular) administration of pro-
methazine, in doses of 2550 mg [1,2]. A suppository form
has reportedly resolved symptoms effectively as well [1].
Although drowsiness has been reported infrequently [1,77],
promethazine is best administered just before sleep to reduce
the risk that possible drowsiness or lethargy would affect mis-
sion activities [1,2], A crewmember who is already ill will
feel better after treatment, and this improvement may help
limit negative effects on performance. The excitement of
space flight and engagement in critical tasks can also help to
counteract the soporific effects of the medication [70].
Once on orbit, some crewmembers tend to minimize head
movements and to move the head, neck, and torso as a unit,
which minimizes changes in sensory and motor control
patterns. Reducing the cabin temperature or staying close
to a fan seems to help crewmembers who are prone to or
affected by SMS. Crewmembers should carry emesis bags
in quick-access locations because of the potential for sudden
vomiting. Avoiding noxious odors and free-floating emesis in
the confined microgravity of a spacecraft are practical con-
siderations. Some crewmembers reduce their oral intake and
modify their diet to avoid fats and protein. The importance of
maintaining hydration with clear liquids and advancing diets
as tolerated is emphasized. However, those crewmembers
experiencing severe symptoms should continue to take noth-
ing by mouth, and the administration of intravenous fluid
should be considered.
Both symptoms and treatment of EMS can significantly
affect crewmember participation in postflight activities,
including life science experiments and critical debriefings,
and therefore must be monitored carefully and methodically.
Currently, NASA flight surgeons make use of medications
as needed after landing to treat moderate to severe symp-
toms. Meclizine, given in 25- to 50-mg doses, seems to be
effective provided that the crewmember can tolerate oral
medications. However, rigorous studies have yet to be done
to confirm this observation. Promethazine (2550 mg, given
intramuscularly or as a suppository) is quite effective and is
indicated for uncontrollable or large-volume emesis. Fluids
are administered as needed, either orally or intravenously, to
220
FIGURE 10.2. A and B, the NASA tilt-translation device used at NASA-Johnson Space Center for preflight vestibular-adaptation training
(Photos courtesy of NASA)
replace lost volume and to maintain hydration. Because EMS,
unlike SMS, occurs in a setting of acute relative dehydration
and cardiovascular compromise, the threshold for administer-
ing intravenous fluid supplementation should be accordingly
lower. The relative contributions of cardiovascular compro-
mise and EMS during this period can be clarified by simple
orthostatic assessment of pulse and blood pressure between
recumbent and sitting or standing positions, if tolerated, while
limiting the crewmembers head movements.
The managing flight surgeon may guide crewmembers
affected by EMS in gentle challenges to adaptation, such as
making small but progressive head movements. Avoidance of
large, rapid head movements, particularly in the pitch and roll
planes, is advisable during the early postflight period. Cau-
tion is also recommended immediately after landing while the
launch-and-entry suits are being removed.
Prognosis
SMS is a self-limited illness, and most who experience it will
overcome it quickly as they adapt to microgravity. Typically,
a single intramuscular dose of promethazine (usually 50 mg)
will resolve the acute symptoms. Rarely will moderate to
severe cases require dosing beyond flight day 2, and only a
very few cases (<1%) will have persistent symptoms [1].
EMS is also self-limited, but the recovery time tends to be
related to the time spent on orbit, lengthening with longer-dura-
tion missions. Return-to-flight status is typically accomplished
within 7 days after missions lasting less than 2 weeks. The
NASA-Mir Program protocol considered returning U.S. astro-
nauts for flying duties on an individual basis at 30 days after
return. Also, it is important to note that certain motion stimuli
H.J. Ortega Jr. and D.L. Harm
may cause relapse or toggling to an earlier stage of readap-
tation days to weeks after return from space flight [4].
Conclusions
SMS can be considered a variant of motion sickness that
occurs in microgravity. Its time course and nature make SMS
operationally significant during the first few days of space
flight [25]. The disorder is typically self-limiting, and treat-
ment is symptomatic. Intramuscular promethazine is the cur-
rent drug of choice for treatment of moderate to severe SMS;
it should be given before the sleep period on flight day one
to minimize performance effects. Other forms of prometha-
zine may also provide relief of symptoms. In a short-dura-
tion space flight, adaptation should be sufficiently complete
in approximately 3 days.
Long-duration space flight produces more problems with
EMS and readaptation to Earth gravity. EMS symptoms seem
to respond to oral meclizine (2550 mg) and to intramuscular
or rectal doses of promethazine (2550 mg). Complete recov-
ery time with no detectable findings will vary according to the
length of the mission, but 7 days can be expected for space
flights lasting 12 weeks and about 30 days for missions last-
ing several months.
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11
Decompression-Related Disorders: Decompression
Sickness, Arterial Gas Embolism, and Ebullism
Syndrome
William T. Norfleet
The three maladies to be discussed in this chapterdecom-
pression sickness, arterial gas embolism, and ebullismall
arise from changes in ambient atmospheric pressure, which
is the pressure of the gas immediately surrounding an indi-
vidual. In space flight, the largest planned change in ambient
atmospheric pressure is associated with extravehicular activi-
ties (EVAs) that take place as the crew moves back and forth
between the crew cabin and the environment outside, where
they wear pressurized suits. The cabin atmospheric pressure
in all current spacecraft typically approximates the atmo-
spheric pressure found at sea level, namely 1 atm absolute
pressure (ata) (or 101 kPa). From a strictly physiological point
of view, this design specification is probably not optimal, but
it serves other interests such as simplifying the conduct of
biomedical research. Selected space suit pressures represent
a compromise between engineering concerns, which dictate
that the internal pressure of a space suit be low to maximize
flexibility, and physiological risks. (The space suit used in
the current U.S. space program, the extravehicular mobility
unit, is pressurized to 30 kPa (4.3 psia); the Orlan suit, used
in the current Russian space program, is pressurized to 38 kPa
(5.5 psia).) Consequently, crewmembers performing EVAs
experience substantial shifts in ambient atmospheric pressure.
Unplanned crew cabin or space suit decompressions are also
possible while living and working in the hard vacuum of space.
The pathophysiological consequences of such exposures are
the subject of this chapter [1].
Nomenclature
Various schemes have been used to classify the spectrum
of disorders arising from changes in ambient pressure. The
term decompression illness has been used to refer to all of
these disorders, including such heterogeneous experiences
as arterial gas embolism (AGE) and trauma to enclosed gas
spaces, such as the thorax, sinuses, and middle ear. The subset
of diseases caused by gas bubbles that evolve from inert gas
dissolved within tissues is commonly referred to as decom-
pression sickness (DCS). DCS that occurs during diving is
termed hyperbaric DCS; the syndrome that arises from aero-
space operations is called hypobaric or altitude DCS.
Although DCS has traditionally been subdivided into two
types, differences among the definitions of subtypes by the U.S.
Navy, the U.S. Air Force, and civilian diving organizations have
made direct comparisons among databases difficult. These dif-
ferences have also hindered discussion of diagnosis, prognosis,
and ability to return to duty. In the original definition in 1960
[1], type I DCS was considered less serious than type II DCS.
The U.S. Navy later defined DCS as follows:
Type I decompression sickness includes joint pain (muscu-
loskeletal or pain-only symptoms) and symptoms involving
the skin (cutaneous symptoms), or swelling and pain in lymph
nodes. Type II, or serious symptoms, are divided into neu-
rological and cardiorespiratory symptoms. Type I symptoms
may or may not be present at the same time [2].
The U.S. Air Force modified this scheme to include the
type I peripheral nervous system case [3]. Since the pres-
ence of a diagnosis of type II DCS in the medical history of
a U.S. Air Force aviator would have career implications that
seem out of proportion to the real risk of recurrence in a future
hypobaric exposure, the motivation for this change arose more
from administrative concerns than from biomedical knowl-
edge. Medical practice within the U.S. Air Force thus evolved
such that paresthesias of limited anatomic distribution that
resolve without sequelae are labeled type I peripheral ner-
vous system DCS rather than type II DCS. This divergence
of classification methods can substantially complicate inter-
pretation of data from field experience and laboratory experi-
mentation. To confuse matters further, even the U.S. Navy
Diving Manual deviates from its own classification scheme by
creating the patchy peripheral paresthesias category, which
is treated separately in determination of return to duty [4].
Several schemes have been proposed to replace the type
I/type II classification, including those by Wirjosemito et al.
[5]. and Dutka [6]. One such scheme [6] dispenses with all
conventional subset classifications of decompression illness
and instead uses descriptions of the clinical symptoms and
223
224
course [e.g., abrupt paresthetic DCI (decompression ill-
ness)]. Bove [7] pointed out that this scheme disregards the
basic pathophysiology of the disorder; for example, a myo-
cardial infarction would be referred to in this scheme as an
abrupt painful chest illness, terminology that fails to com-
municate vital information.
No clear consensus has emerged concerning the best
nomenclature for DCS. In this chapter, we will use the type
I and II classification scheme as defined in the current U.S.
Navy Diving Manual [2].
Decompression Sickness
Although procedures for hypobaric exposures with a low risk
of DCS have been developed and effective treatments for
hypobaric DCS exist, little is known of the pathophysiology
of DCS. Nevertheless, it is clear that the disorder involves
bubbles. The remainder of this section constitutes a review of
the processes of bubble formation and resolution, the probable
sites of bubble formation within the body, the interactions of
bubbles with nearby tissue, the uptake and elimination of the
inert gas that drives bubble formation, the pathophysiology of
DCS in specific organ systems, and treatment of the disorder.
Bubble Formation
Bubbles can form when the sum of partial pressures of gases
dissolved in a liquid plus the vapor pressure of the liquid
itself exceeds the hydrostatic pressure in that liquid. When
this criterion is met, bubble formation is not instantaneous and
substantial supersaturation can occur without gas formation.
In fact, in pure water at 1 ata without existing bubbles, more
than 100 ata of gas can be held in solution before de novo gas
formation takes place [8,9]. In contrast, bubbles have been
observed in humans after modest dives [7.8 m (25 ft)] [10] and
space flight EVA simulations [3,700 m (12,000 ft)] [11]. Thus,
the process of bubble formation in humans clearly differs from
that which takes place in a beaker of still water.
Possible modifying factors for bubble formation are numer-
ous. Preexisting gas nuclei may obviate the need for de novo
gas formation. Gas may simply diffuse into and enlarge gas-
eous nuclei. Experimental evidence to support this notion can
be found from studies with rats in which dives began with
a very short duration, deep pressure spike designed to crush
preexisting nuclei. This pressure excursion protected against
DCS in subsequent decompressions [12]. Similar findings
have been obtained with shrimp [13]. However, conflicting
data have also been reporteda hydrostatic pressure spike
had no effect on bubble formation in adult crabs [14]. Thus
the role of preformed nuclei in the generation of DCS may
have been overstated, at least in lower animals [15,16].
Another factor that may influence the development of
a gas phase in humans after decompression and may also
explain the genesis of gas micronuclei is the generation of
W.T. Norfleet
negative pressures in tissues as a result of movement and
locomotion. When two closely opposed tissue surfaces are
forced to separate, fluid must flow into the widening gap
to fill that gap, but the viscous properties of the fluid tend
to oppose this flow. The resulting negative pressure in this
gap can be tremendous, large enough to cavitate the fluid.
A similar phenomenon occurs when two tissue planes slide
against each other, a process called tribonucleation [17].
Hemmingsen demonstrated the importance of locomotion in
generating bubbles in vivo during experiments in which the
development of bubbles within crabs was compared between
crabs left free to scurry around after decompression and crabs
whose legs were immobilized. More bubbles were seen in
the free-roaming crabs [18]. Studies in fish throughout their
development also established the importance of movement
in generating bubbles [15]. Hemmingsen [16] provides an
excellent review of in vivo and in vitro bubble formation.
Sites of in Vivo Bubble Formation
Where in the body do bubbles form that cause disease? The
precise location is largely unknown. For considerations of
where bubbles might form, tissue compartments can be cat-
egorized as intravascular (arterial, capillary, or venous) or
extravascular (intracellular or interstitial).
The arterial circulation seems an unlikely site for intravascu-
lar bubble formation. In most circumstances, inert gas tensions
in arterial blood are in equilibrium with alveolar gas, so arterial
blood is not supersaturated with inert gas. Moreover, arterial
blood is pressurized hydrostatically by the heart, which further
impedes any gas formation. Nevertheless, circulating bubbles
have been detected in arterial blood, and these microemboli
may be responsible for certain forms of DCS. The source of
bubbles is likely to be transpulmonary or right-to-left shunting
of the bubbles from the venous circulation [1923].
Venous blood has been shown to contain significant num-
bers of circulating microbubbles after even modest, asymp-
tomatic decompressions [10]. Bubble formation within venous
blood seems unlikely, however, at least when the vessels are
at rest. In a study in which the blood-filled venae cavae of
several species were excised, placed in saline, and decom-
pressed to altitudes well in excess of those that produce DCS,
no bubbles formed [24]. The ultimate source of venous bub-
bles is unclear. Venous bubbles may form in capillary beds
and be swept into the central venous circulation, or they may
arise in extravascular tissues and migrate into the circulation.
Regardless of their source, in most circumstances circulating
venous microbubbles do not seem to be the proximate cause
of disease since the magnitude of their numbers correlates
only very loosely with the likelihood of disease development
[25,26]. With some notable exceptions, circulating venous
microbubbles are only the fellow travelers of those bubbles
that actually cause disease.
Within the extravascular compartment, bubble formation
within cells seems to be uncommon. Cells and unicellular
11. Decompression-Related Disorders: Decompression Sickness, Arterial Gas Embolism, and Ebullism Syndrome 225

organisms are quite resistant to bubble formation [27]; the shown to adhere to bubbles [42,43]. The results can include
intracellular environment is not conducive to bubble forma- pain, edema, coagulation, reduction in local tissue perfusion,
tion, as demonstrated by the fact that microscopic particles and leukocyte chemotaxis.
that serve as a nidus for bubble formation in water fail to form Experimental observations that bridge the mechanicalnonme-
bubbles when ingested by Tetrahymena [28]. chanical paradigm include denuding of capillary endothelium by
By process of elimination, this leaves the interstitial space as a bubbles with subsequent inflammation [42,44] and peroxidation
possible site for the formation of bubbles that cause DCS symp- of myelin initiated by the release of free iron [45] when hemor-
toms. In some tissues, experimental evidence exists to support rhage occurs around autochthonous bubbles in spinal tissue [46].
this notion. For example, in situ interstitial gas formationthe The combined effects of bubbles may explain the many-faceted
so-called autochthonous bubbleshas been observed in spinal clinical presentation of DCS as well as the observation in many
cord tissue after decompression [29]. In contrast, experimental cases that symptoms may persist or even begin well beyond the
evidence suggests that bubbles cannot form in the brain and expected longevity of a bubble within a tissue.
kidney under operationally realistic pressure profiles [30]; dis-
ease in these organs is probably caused by arterial microbubbles
originating in other tissues. Attempts to document extravascular Inert Gas Uptake and Elimination
bubbles in rabbits exposed to hypobaric conditions have failed
Because bubble formation in tissues, driven by inert gas
[31,32]. It seems that bubbles formed in situ may cause some
supersaturation, is thought to be the initiating factor in DCS,
forms of DCS, whereas emboli originating in remote sites may
measurement of inert gas tension at the sites of formation of
cause other manifestations. For many forms of DCS, such as the
harmful bubbles would provide highly relevant data. How-
common, pain-only limb bends, the site of formation of the
ever, since the precise location of the microenvironments that
provocative bubbles has not been demonstrated.
produce such bubbles is unknown, these data unfortunately
cannot be acquired. As a substitute for these kinds of measure-
Interactions of Bubbles with Nearby Tissue ments, many investigators (e.g., Anderson et al.) have ana-
lyzed whole-body inert gas elimination [47], but whole-body
What is it about the presence of a bubble that causes disease?
gas elimination does not necessarily reflect gas exchange in
Broadly speaking, the effects of a bubble are both mechanical
the tissues of interest. Gas exchange has also been studied in
and nonmechanical. Mechanical effects include embolization
experimentally induced subcutaneous gas pockets [48], but
of capillary beds by circulating microbubbles, with consequent
these studies also require a leap of faith to draw conclusions
ischemia. Expanding interstitial bubbles may also compress
regarding gas exchange in clinically relevant tissues. Despite
surrounding tissue, causing ultrastructural damage and raising
this dearth of fundamental knowledge, humans have already
local tissue pressure to the point that circulation is compromised.
been exposed, with varying degrees of success, to a wide vari-
Finally, bubble accumulation in venules and veins may inhibit
ety of pressure-time profiles. Data inferred from these profiles
venous drainage, with consequent tissue edema, ischemia, and
have been used to develop mathematical models of inert gas
perhaps interstitial bubble formation as dissolved inert gas that
exchange. Such models are useful for extrapolating between
otherwise would have been swept out of the tissue in solution
known regions of the pressure-time continuum and, to a lesser
remains sequestered in the tissue and comes out of solution.
extent, for venturing into new extremes.
In many clinical situations, the nonmechanical effects of
Although describing the wide variety of mathematical
bubbles may be more important than their mechanical pres-
models that has been advanced is beyond the scope of this
ence. Indeed, the presence of bubbles in tissues is often of
text (cf. Vann & Thalmann [49]), brief consideration of one
no clinical consequence [33]. On the other hand, the onset of
method is relevantnot because it represents the state of
symptoms sometimes occurs so long after a pressure excur-
the art but rather because it has been used to govern Space
sion that when the symptoms finally begin, the continued pres-
Shuttle operations [50]. This method is used primarily for
ence of actual gas bubbles seems unlikely (e.g., Bason) [34].
modeling inert gas elimination during O2 prebreathing peri-
Apparently, the presence of bubbles in body tissues serves as
ods and step-reductions in ambient pressure. This approach
a nidus for the initiation of biochemical and cellular processes
is not new; its origins are the work of Haldane [51]. Briefly
that, once begun, can lead to morbidity and mortality, even
stated, the assumption, which is based on empirical evidence,
after the offending bubble has disappeared.
is that inert gas elimination can be modeled by dividing the
Some of the nonmechanical effects of bubbles may be initi-
body into several conceptual compartments, each of which
ated at the interface of bubbles with blood or interstitial fluid,
has its own rate constant for elimination of inert gas:
an interface that demarcates regions of vastly different phys-
iochemical properties. Proteins that interact at this interface Pt = P0 + [(Pa P0)(1 e kt)]
can undergo conformational changes [35]. The presence of
where
bubbles in blood affects many enzymatic systems, including
complement factors, coagulation factors, kinins, and fibrino- Pt = inert gas partial pressure in tissue after t minutes
lytic systems [3641]. Leukocytes and platelets have been P0 = initial inert gas partial pressure
226
Pa = inert gas partial pressure in inspired gas (although use of
alveolar or arterial gas pressure would be more correct in
physiological terms)
t = exposure time in minutes
k = compartment rate constant (k is related to the inert gas
half-time t1/2 by k = 0.693/t1/2)
In a typical operational scenario, only the compartment with
the longest gas-elimination rate (empirically determined as
having a half-time of 360 min) governs decompression.
The partial pressure of inert gas in tissue can be compared
with ambient atmospheric pressure as an indication of the
decompression stress:
TR = Pt/Pamb
where
TR = tissue ratio
Pamb = ambient atmospheric pressure
This method is useful in determining conditions under which
bubbles will form. As noted earlier in this chapter, bubbles
can form when the sum of partial pressures of gas dissolved
in a liquid exceeds the hydrostatic pressure in that liquid. The
process of bubble formation is also subject to many other
factors that make substantial supersaturation possible before
bubble formation takes place. Finally, the presence of bubbles
in tissue does not invariably lead to disease. The net result of
these deliberations is the realization that for a significant num-
ber of symptom-producing bubbles to form at all, the TR must
be greater than 1.0. Similarly, when the TR is much greater
than 1.0, DCS is likely. In other words, the risk of DCS is a
function of TR. This rather simplistic approach to quantifying
the risk of DCS has some utility, although it does not account
for many factors that are known to modify the risk. Nominal
Space Shuttle operations have avoided situations in which the
TR would exceed 1.65.
Pathophysiology
DCS manifestations are often diffuse, multifocal, and pro-
tean. Multiple organ systems can be involved simultane-
ously. Although bubbles serve as the initiating agent, the
disease can persist and probably even progress after the
bubbles have been resorbed. Since clinicians who reso-
lutely seek the one lesion are likely to be frustrated in
attempting to characterize the clinical manifestations of a
case of DCS [52,53], the following discussion of the effects
of DCS on organ systems should be read with the under-
standing that simultaneous, interacting disease can occur
in many systems.
Hyperbaric Versus Hypobaric Decompression Sickness
Much of our current understanding of the pathophysiology of
hypobaric DCS has been derived by extrapolation from expe-
rience with hyperbaric DCS. Although the two situations are
W.T. Norfleet
analogous, they are fundamentally different in terms of pres-
sure profile, the importance of gases other than inert gases,
the time course of bubble formation, the scenario at symptom
onset, and the natural history of the disease. These differences
are expanded upon below.
Pressure Profile
A typical dive begins with an individual at sea level whose
tissues contain a dissolved mass of inert gas that is in
equilibrium with the inert gas in the surrounding atmo-
sphere. The diver is said to be saturated with air at 1 ata
that contains approximately 80% inert gas (in this case,
nitrogen). During the course of the dive, the individual
descends to some depth and quickly returns to the sur-
face. The diver has accomplished a downward excursion
from saturation conditions; in other words, ambient pres-
sure increases as the diver descends. In terms of inert gas
uptake and elimination, the diver has absorbed inert gas
from the air breathed during the course of the dive and
then eliminated this gas during a process that begins upon
initiation of ascent but continues for some period after
return to the usual sea-level environment.
The typical spacewalkers pressure profile is fundamentally
different. The typical spacewalker also begins the day satu-
rated in specified conditions, but the pressure profile involves
a reduction in ambient pressure, i.e., an upward excursion
from saturation. Inert gas is eliminated during the course of
the pressure excursion, not afterwards. Most important for
the spacewalker, every exposure ends with a compression, not
a decompression. In this respect, hypobaric and hyperbaric
operations are as different as they can be.
Importance of Gases Other Than Inert Gases
In addition to inert gases such as N2, other gases are also dis-
solved in body tissues. For example, CO2 is generated by
cellular processes and is maintained by the circulatory and
ventilatory systems at a tension of approximately 5.3 kPa.
The tension of water vapor in tissues, a function of body tem-
perature, is constant at 6.3 kPa. In the diver, these tensions
are trivial compared to the tension of the inert gas, which
can reach 6,600 kPa in very deep dives [54]. Consequently,
in considering the physics of bubble formation in divers, gas
species other than inert gas can largely be ignored. The ambi-
ent atmospheric suit pressure of the spacewalker, in contrast,
is typically only about 30 kPa, so the contributions of water
vapor and CO2 (and, to a lesser extent, that of O2) to bubble
formation and resolution are very important. As an example,
under equilibrium conditions when breathing air at a depth of
10 m (33 ft), 8% of the volume of a bubble consists of species
other than N2; at an altitude of 9,100 m (30,000 ft), 56% of
the bubble volume consists of these species. This factor may
explain why some mathematical models of inert gas uptake
and elimination that work well for divers may fail when
applied to spacewalkers.
11. Decompression-Related Disorders: Decompression Sickness, Arterial Gas Embolism, and Ebullism Syndrome 227

Time Course of Bubble Formation TABLE 11.1. Manifestations of decompression sickness from
140 patients during 136,696 exposures in U.S. Navy altitude
The physical principles underlying the formation of a bubble chambers, 19811988a.
from dissolved gas are complex. For the purpose of this dis- Clinical manifestations Patients (No.) Patients (%)
cussion, it is useful to note that a bubble of a given volume
Joint and limb pain 99 70.7
will form more slowly under hypobaric conditions than it will Extremity paresthesia 46 32.9
in hyperbaric conditions. For example, Piccard [55] observed Numbness 33 23.5
that the same volume of gas was liberated from water saturated Muscular weakness 24 17.1
with air at 5 ata when the water was decompressed to 1 ata Dizziness 22 15.7
as when water at 1 ata was decompressed to 0.2 ata. Piccard Headache 12 8.6
Nausea and vomiting 11 7.8
went on to say that In the first case the bulk of dissolved air Visual disturbances 10 7.9
had escaped after 5 s, while in case 2, several minutes elapsed Fatigue and malaise 8 5.7
before the gas production even approximately ceased. Bub- Apprehension 7 5.0
ble formation may be sufficiently slowed under hypobaric Mental confusion 7 5.0
conditions to allow physiological processes to eliminate some Disorientation 7 5.0
Hyperventilation 5 3.6
inert gas from tissues before a significant gas phase has had Paralysis 4 2.9
time to evolve. Pruritis 3 2.1
Muscle spasm 3 2.1
Skin mottling 2 1.4
Scenario at Symptom Onset Ataxia 2 1.4
Chokes 1 0.7
The typical diver is at risk of developing DCS only upon
Unconsciousness 1 0.7
return to the surface, when the job is completed and the diver Slurred speech 1 0.7
is home. In contrast, symptom onset for spacewalkers most Vertical nystagmus 1 0.7
likely occurs while they are still engaged in EVAs. So if DCS Abdominal pain 1 0.7
occurs, the spacewalkers job is more likely to be disrupted by Hot and cold flashes 1 0.7
Difficulty forming words 1 0.7
it, and symptom onset is more likely to occur in the midst of
an already hazardous operation. Source: Bason [34].
a
More than a single manifestation can occur in an individual patient.

Natural History of Decompression Sickness

Typically, hypobaric DCS is less severe than hyperbaric DCS,
is less likely to cause neurologic or other sequelae, and is more
amenable to treatment. Meaningful comparisons between data-
bases from the hyperbaric and hypobaric communities therefore
require careful definition of what exactly constitutes a hit. For
example, operational managers in the hypobaric arena might be
willing to accept an overall risk of DCS that exceeds the risk
that would be considered acceptable to their colleagues in the
diving world, because the incidence of cases with serious, last-
ing injury in the hypobaric world is relatively low.
Despite these distinctions between hypobaric and hyper-
baric decompression physiology, much can be learned about
the pathophysiology of hypobaric DCS by considering experi-
ence from diving operations, especially decompression from
saturation diving. In fact, the microgravity environment may
blend elements of both flying and diving operations, involving,
for example, fluid shifts analogous to those of the immersed
diver and pressure excursions similar to those encountered
by the aviator. Consequently, the following discussion draws
heavily from diving and hyperbaric physiology.
Information regarding manifestations of hypobaric DCS
can be derived from the thousands of human exposures in
hypobaric chambers conducted as part of flight crew train-
ing by the worlds armed forces every year. Table 11.1
depicts the manifestations and incidence of DCS and related
disorders encountered by the U.S. Navy from 1981 to 1988
[34]. (A notable clinical manifestation not represented in
this table is death. Hypobaric DCS can kill, albeit rarely.)
[5658] From 1985 to 1987, the U.S. Air Force experienced
282 cases of DCS in the course of 239,343 hypobaric cham-
ber exposures; 89% of these cases were classified as type I
and 11% were classified as type II [59]. From 1984 to 1989,
the U.S. Army had 42 cases of DCS in 21,498 exposures,
but no breakdown of clinical presentation was reported
[60]. (Interestingly, military organizations outside of North
America report fewer cases of altitude DCS yearly.) [61]
Few diseases, if any, are as diverse in their manifestations
as DCS. The expressions of DCS in specific organ systems
are considered in the following discussion.
Blood
The nature of the interaction of bubbles with blood was dis-
cussed earlier in this chapter. Blood also plays many roles
in the pathophysiology of DCS by serving as a conduit for
gaseous microemboli to the pulmonic and systemic vascula-
ture, transporting leukocytes and platelets to bubble-damaged
vascular endothelium and tissues, and participating in local
inflammatory reactions. Since patients with DCS frequently
display hemoconcentration and a decline in intravascular vol-
ume [39,62,63], fluid therapy is the cornerstone of treatment
for the disease. Additional therapeutic maneuvers to counter-
act observed changes in blood, such as administering heparin
228
and low-molecular-weight dextran, have not yet been found to
be of clinical value.
Musculoskeletal System
A common form of DCS, especially in hypobaric realms, is
pain in and around extremity jointsthe bends. Symptoms
of the bends typically begin with a sense of fullness around a
joint and may progress to an aching or a throbbing pain that
can be severe. The pain is sometimes well localized, but it
can also be fleeting and migratory. In contrast to conventional
musculoskeletal injuries, the affected area is usually not ten-
der to touch and the pain is not markedly worsened by joint
movement. Alleviating factors include pressurizing the patient
in a hyperbaric chamber and, in some cases, inflating a blood
pressure cuff around the affected area. Pain in areas other than
the extremities, especially truncal pain, is thought to be a more
sinister form of DCS, reflecting involvement of spinal nerve
roots or the spinal cord itself. To date, DCS of the sternocla-
vicular joint has not been recorded, an observation that can be
useful because essentially all diving involves a good deal of
upper-extremity stress and strain that can produce non-DCS
symptoms.
Patterns of joint involvement in hypobaric DCS differ
markedly from those of the hyperbaric condition. Table 11.2
reflects the experience of the U.S. Navy [34]. In the U.S. Navy
report, 64% of cases involved the upper extremities. By con-
trast, experimentation at NASA produced DCS in the upper
extremities in only 11% of cases [64]. Patterns of exercise and
activity influence the distribution of symptoms. DCS tends to
occur in the upper extremities in individuals who do push-ups
at altitude and in the lower extremities of those who do deep
knee bends [62].
The precise etiology of bends pain is unknown, although
both mechanical and nonmechanical effects of bubbles prob-
ably contribute to it. The mere presence of moderate amounts
of gas in joint spaces and around articular cartilage, which
TABLE 11.2. Site of type I decompres-
sion sickness resulting from expo-
sures in U.S. Navy altitude chambers,
19811988.
Symptom site No. of incidents
Elbows 34
Shoulders 30
Knees 29
Arms 10
Wrists 9
Hips 5
Legs 4 nism. Microembolization of the spinal cord is probably not
Ankles 4 a significant contributor in most cases because the anatomic
Fingers 2 distribution of injury does not seem to follow a vascular pat-
Feet 2 tern [74]. A mechanism backed by considerable experimental
Hands 1
Heels 1
Source: Bason [34].
W.T. Norfleet
may arise in the course of daily activities [33], actually does
not cause pain; but expanding gas volume in a poorly com-
pliant tissue containing sensory nerves such as tendons could
cause pain. Patterns of blood flow in this tissue seem to be
conducive to poor inert gas elimination [65], and injecting lac-
tated Ringers solution into the tendons can cause pain similar
to that of DCS. Possible nonmechanical effects include the
initiation by bubbles of a cascade of humoral mediators of
the inflammatory response. The fact that the pain frequently
resolves rapidly and completely upon pressurization in a
hyperbaric chamber or upon application of a blood pressure
cuff argues against an inflammatory response being a major
contributor in such cases, however.
Long-Term Sequelae
A feared, long-term consequence of diving, especially of
saturation and experimental diving, is aseptic dysbaric osteo-
necrosis of weight-bearing bones such as of the femoral head
[66]. Fortunately, hypobaric exposures do not seem to pro-
duce this problem [67]. Since many factors can cause aseptic
osteonecrosis, a relatively small incidence of the dysbaric
form may still exist in the larger aviator population that has
yet to be detected.
Nervous System
Broadly speaking, DCS of the central nervous system mani-
fests as cerebral and spinal forms. Involvement of peripheral
nerves also seems possible. Numerous reports and oral tra-
dition have indicated that in divers spinal cord involvement
is more common than cerebral DCS and that the converse is
true in aviators. However, recent studies suggest that cerebral
involvement may occur as often as spinal disease in divers
[53,6871] and that a wide variety of central nervous system
symptoms arise from hypobaric exposures (Table 11.1).
Spinal Decompression Sickness
Spinal DCS is all too common in divers and frequently involves
the lower thoracic and upper lumbar cord [72]. DCS classically
manifests as the rapid onset of paraplegia, paraparesis, and uri-
nary retention after surfacing, sometimes preceded by prodro-
mal abdominal or girdle pain [73]. More typically, the patient
reports paresthesias of one or more limbs in a pattern that varies
with time and defies discrete neuroanatomic localization of the
lesions. Hypoesthesia and paresis may also be present.
The etiology of spinal DCS is not entirely clear and may
simultaneously involve more than one bubble-related mecha-
evidence involves bubble congestion of the epidural venous
plexus that drains the cord [20,75,76]. This valveless venous
plexus surrounds the dura-enclosed spinal cord, occupying
11. Decompression-Related Disorders: Decompression Sickness, Arterial Gas Embolism, and Ebullism Syndrome
much of the space bounded by the spinal canal [77,78]. Bub-
bles within the plexus and back pressure reflected ultimately
from pulmonary circulation are thought to cause engorgement
of this plexus, stasis of the blood, intravascular sludging, and,
ultimately, infarction of the cord. In humans, the pattern of
cord injury in DCS does not match that observed from venous
infarction of the cord from other causes [79]. This mechanism
does not now seem to be the major, proximate cause of spinal
DCS, although it may play a role in spinal DCS.
Because arterial and venous mechanisms do not seem to
be major causes of spinal DCS, phenomena within the cord
tissue have been considered [29]. Of particular interest is the
concept that autochthonous bubbles form within or adjacent
to myelin nerve sheaths and compress nearby axons [46,80].
Because myelin makes up a greater proportion of cord white
matter than gray matter, white matter would be expected to be
more involved in spinal DCS if autochthonous bubbles were a
factor. Since opportunities to examine the cord tissue of div-
ers with spinal DCS obviously are limited (although lesions
involving predominantly white matter have been reported)
[8185], animal models of spinal DCS have been developed.
In these models, the cords of stricken animals contain numer-
ous gas-filled, space-occupying lesions in white matter that
are consistent with the concept of autochthonous bubbles
[73,86]. Interpretation of these animal studies is complex,
given the need to consider the implications of the magnitude
of decompression stress, the time at which the animals were
killed in relation to that stress, and the conditions under which
the tissue was fixed and examined. Nevertheless, the weight
of the evidence seems to favor a mechanism for spinal DCS
involving expansion of short-lived autochthonous bubbles,
mechanical disruption of nearby tissue, pressure-induced
local ischemia, and perhaps peroxidation of myelin initiated
by free iron released when hemorrhage occurs around autoch-
thonous bubbles.
Bubbles in the epidural plexus may contribute to the forma-
tion of autochthonous bubbles by slowing venous drainage and
perfusion of the cord, thereby delaying inert gas elimination
from the cord. This would permit gas that otherwise would
have been washed out of the cord to participate in autoch-
thonous bubble expansion. Bubbles seem to form much more
readily in the epidural venous plexus than in other vascula-
ture [76]. Hence, both the autochthonous and epidural bubbles
may play roles in generating spinal DCS.
Although the contribution of autochthonous bubbles to
spinal DCS is fairly well established in divers, at least two
factors may diminish the formation of such bubbles in avia-
tors or spacewalkers. First, as noted above, bubble formation
is inherently slower in a hypobaric setting than in a hyper-
baric setting. If the pace of inert gas elimination from the cord
(estimated to have a time constant of about 15 min for white
matter) [87] exceeds the rate of bubble formation in the cord,
spinal DCS would be avoided. Second, a threshold decom-
pression stress for generation of autochthonous bubbles has
been identified for hyperbaric conditions. Bubble formation
229
in dogs exposed to hyperbaric air for 4 h was much more com-
mon at pressures greater than 3.6 ata than at lower pressures
[88]. How such a threshold translates to hypobaric conditions
remains unclear. In any event, spinal DCS has been reported
in aviators, albeit rarely [5]. Cord white matter injury has been
observed in humans [89] and animals [90] that were exposed
to altitude, although gray matter involvement was also seen
in these studies, perhaps implying simultaneous gas emboli-
zation of the cord. The pathophysiology of hypobaric spinal
DCS has yet to be firmly established.
Cerebral Decompression Sickness
Cerebral DCS, as discussed above, probably arises from embo-
lization of the brain by circulating bubbles rather than by bubble
formation within the brain itself. Simultaneous involvement of
many loci may occur, and the clinical manifestations of dis-
ease are diverse. These include unconsciousness, convulsions,
hemiplegia, visual disturbances, mentation difficulties, head-
aches, and subtle personality changes. More is involved in the
pathophysiology of the disorder than simple obstruction of vas-
culature by gaseous emboli. Gas that is carried to the brain in
arterial blood has been observed to pass rather quickly through
the brain [91], leaving behind damaged capillary endothelium
and a loss of the bloodbrain barrier [9294]. In the wake of
these bubbles, a chain of events is initiated that includes adhe-
sion of leukocytes to damaged tissue [95]; indeed, granulo-
cytopenic dogs are relatively resistant to neurologic damage
produced by air injected into the carotid artery. Autoregulation
of blood flow is lost along with a progressive, patchy decline in
perfusion and neurologic function [91,96]. The disturbance in
the bloodbrain barrier can be short-lived, lasting about 3 h, but
it can also recur 72 h later, perhaps because of the maturation
phenomenon in neural injury [94]. Disruption of the blood
brain barrier has also been observed in rabbits exposed to alti-
tude without detectable intracerebral intravascular bubbles or
mechanical endothelial disruption. The mechanism for these
changes remains obscure [32].
If cerebral DCS arises from embolization of the brain by
circulating microbubbles, then where do those bubbles come
from? As can be concluded from the prior discussion of
bubble formation, bubbles probably do not arise within sys-
temic arterial blood, and an extension of that argument would
suggest that bubbles do not form in pulmonary capillaries.
Thus the most likely source of the offending bubbles is venous
bubbles that have managed to either travel through the pulmo-
nary circulation or to bypass it. As discussed in more detail
below, the lungs are highly effective at filtering all but intense
bubble loads. Consequently, attention has focused recently
on determining the role in the pathophysiology of neurologic
DCS of pathways that permit venous bubbles to bypass the
lungs and reach the left atrium. Collectively, such pathways
are referred to as interatrial shunts. The archetypicalbut by
no means onlyinteratrial shunt is the patent foramen ovale.
Indirect but highly relevant (and far more abundant) findings
230
are concerned with the pathophysiology of thromboembolic
cryptogenic stroke; interatrial shunts seem to play a significant
role in this disorder [9799]. Interatrial shunts also seem to be
important in some, but not all, cases of hyperbaric cerebral
and high-spinal DCS [100,101]. Only very limited informa-
tion has been published concerning the role of shunts in alti-
tude neurologic DCS. No increased prevalence of shunts was
found in a group of military personnel who seemed to have
developed this disease [102,103], but the pressure profiles to
which they were exposed (short durations at high altitudes)
were not likely to have generated venous gas emboli. A recent
review of this topic pointed out that the size and location of
shunts are important determinants of their clinical significance
[104]. Shunts are common, but important shunts are not, so
future investigations may be more insightful if they focus on
the important shunts rather than the totality of shunts.
Decompression Sickness of Peripheral Nerves
DCS of peripheral nerves, a diagnosis recognized by some
organizations including the U.S. Air Force, is discussed in
standard textbooks of aerospace physiology [105]. When neuro-
logic involvement is confined to a portion of an extremity, it is
reasonable to postulate that a peripheral nerve is involved.
This idea is supported by some case reports [106,107]. How-
ever, since symptoms in a portion of an extremity could also
be produced by disease in a spinal nerve root, the pattern of
neurologic dysfunction in this case might follow a dermato-
mal distribution. Bubbles have been observed in epineural and
intraneural vessels of sciatic nerves of rabbits exposed with-
out prebreathe to 13,716 m (45,000 ft) [31]. In humans, the
incidence and pathophysiology of peripheral nerve DCS is not
well characterized.
Long-Term Sequelae
The relatively intense interest in neurologic DCS reflects the
fact that it can cause permanent, disabling sequelae. Fortu-
nately, in the vast majority of cases treated promptly with
hyperbaric therapy, overt disease is cured. Nevertheless, con-
cerns remain, particularly in the diving community, regarding
the possible occurrence of subtle disease that either persists
after treatment or accumulates during the course of repeated,
apparently uneventful exposures, such as inconspicuous cord
damage or the punch-drunk diver [108110]. A single case after hypobaric chamber flights and is not itself a cause for
report describes the autopsy findings of a diver who died of
unrelated trauma within days of apparently successful hyper-
baric therapy for spinal DCS; autopsy revealed extensive
damage of the lower cervical and upper thoracic cord [82].
Similarly, a dog that had apparently recovered completely
from altitude DCS was found at necropsy to have suffered
massive cord and brain stem lesions [111]. Whether hypobaric
exposures might also produce subtle, long-term neurologic
damage is unknown.
A mail survey of retired high-altitude U.S. Air Force pilots
revealed an unexpectedly high incidence of DCS in those who
W.T. Norfleet
flew U-2 operations (75% of the respondents reported devel-
oping DCS at least once in their career that was not brought
to the attention of a flight surgeon) but no unusual long-term
health problems [112]. Drawing conclusions regarding the
long-term consequences of altitude DCS from this uncon-
trolled, retrospective, survey-based study is difficult. In sum-
mary, no one has yet described long-term disease in aviators
that can be traced back to distant, resolved hypobaric DCS,
but neither has much effort has been directed to acquiring this
information.
Cardiopulmonary System
Bubbles that are carried in the venous circulation will eventu-
ally reach the pulmonary capillary vasculature and embolize
the lung. In severe cases, these gaseous microemboli produce
a syndrome known as the chokes, a syndrome characterized
by dyspnea, cough, retrosternal pain, and cardiovascular col-
lapse [113]. Although the lung is highly effective in removing
bubbles from the circulation and preventing embolization of
important systemic capillary beds in tissues such as the brain
and spinal cord, large bubble loads can overwhelm its filtering
effect [21,22,114,115].
Bubbles that lodge in the lungs remain in place for many
min, at least during air breathing [116,117], providing an ade-
quate period for the development of significant interactions
with surrounding pulmonary tissues. For example, microvas-
cular permeability has been observed to increase after gas
embolization, resulting in transient pulmonary edema [118].
Also, leukocyte counts and lysophosphatidylcholine levels
are increased in bronchoalveolar lavage fluid after decom-
pression in rats [119]. These interactions of gaseous micro-
emboli with pulmonary vasculature can impair O2 transport
by the lung [23]. Pulmonary emboli are also thought to impair
O2 transport by altering the matching of regional ventilation
and perfusion, increasing the velocity of blood flow through
non-embolized capillaries, and opening intrapulmonary arte-
riovenous shunts [120,121].
Skin and Lymphatic System
Cutaneous manifestations of DCS (skin bends) include pru-
ritis; mild, limited macular eruptions; and deep, extensive,
purple marbling. Mild pruritis is common during or shortly
concern [62,122]. Limited, mild rashes occur less frequently
but are also thought to be innocuous. Extensive marbling does
seem to be associated with more sinister pathology such as
cardiovascular instability [122] and neurologic involvement
[123]. These phenomena are thought to arise from an inflam-
matory reaction to bubbles present in cutaneous tissues or vas-
culature. Localized soft tissue edema has occurred in divers,
apparently as a result of the obstruction of lymphatic vessels
by bubbles [124,125].
Understanding of the pathophysiology of skin bends has
been enhanced by studying the formation of skin lesions in
11. Decompression-Related Disorders: Decompression Sickness, Arterial Gas Embolism, and Ebullism Syndrome
divers who breathe an N2-based gas mix while they are in a
chamber containing a He-based gas. Under these conditions,
bubbles can form in skin without any change in ambient pres-
sure, a phenomenon known as isobaric inert gas counterdif-
fusion [126]. Under more conventional conditions, however,
direct transfer of inert gas across skin from the surrounding
atmosphere may not be as important in the genesis of skin
bends as changes in regional skin blood flow. As an example,
a patch of skin that is compressed against a cold, metal surface
may be more likely to be afflicted than skin that is warm and
well perfused.
Work-Up and Differential Diagnosis
of Decompression Sickness
Despite dramatic advances in medical technology in recent
years, a history and physical examination evaluation are still
the best means of gathering diagnostic information from a
patient suspected of having DCS. Although promising results
were previously reported by Adkisson and colleagues [71],
the use of advanced methods such as computer tomography
[127], magnetic resonance imaging [128], single photon
emission tomography [129], and positron emission tomogra-
phy [130] has no proven role in the diagnosis or follow-up
of DCS. However, future developments may well change this
situation (reviewed by Hanson and Jordan) [131]. Chest radi-
ography may be useful in the future for detecting generalized
pulmonary edema arising from gas embolization of the lung
[132], wayward free gas (e.g., pneumothorax and mediastinal
emphysema), and aspiration.
Since no sensitive and specific test exists for DCS, the diag-
nosis is, to a large extent, one of exclusion. Unfortunately,
establishing a firm diagnosis of DCS can be difficult even in
hindsight. Both dysbaric and nondysbaric disease processes
must be considered. In equivocal causes, some comfort can
be found in the fact that hyperbaric therapy is a rather low-
risk therapeutic intervention. Yet in the rush to conclusions,
care must be taken to avoid withholding appropriate therapy
through misdiagnosis, such as assuming that chest pain with
respiratory distress is the chokes when, in fact, myocardial
ischemia has developed and an entirely different course of
therapy is urgently needed.
Diagnostic dilemmas become even more intense when the
patients location is geographically remote. Since the nature
of the symptoms at onset does not predict the eventual sever-
ity of the case, little solace can be derived from determining
that its only limb bends. Such circumstances call for a high
index of suspicion for DCS and a low threshold for making
the decision to transport the patient to a hyperbaric facility.
Clinical Course of Decompression Sickness
The clinical course of hypobaric DCS is influenced by several
factors, including the duration of O2 prebreathe and altitude expo-
sure; the altitude reached; the magnitude and type of exercise, if
231
any, during prebreathe and altitude exposure; the time until initi-
ation of treatment; and the type of treatment administered. (Risk
factors for altitude DCS are discussed further in Chap. 12.) Just as
all dives are not equal, all hypobaric exposures are not the same.
Most acute human exposures to hypobaric conditions occur dur-
ing physiological training courses for aviators, primarily armed
forces personnel; a wide variety of protocols are, or have been,
in use to address these (cf. Garrett and Bradshaw [133]). How-
ever, most of these exposures might be characterized as involv-
ing short prebreathes; that is, they involve short exposures to
modest altitudes, with little or no exercise performed at altitude.
Definitive diagnostic and therapeutic resources are usually avail-
able immediately.
This situation can be contrasted with current EVA opera-
tions. These activities involve relatively long prebreathe
periods (up to 4 h), long exposures (roughly 6 h), high altitudes
[9,100 m ( 30,000 ft)], modest exercise, and remote treatment
resources. By some measures, these two types of activities are
as different as they can be, and so clinical experience with
one type of operation may not be applicable to other contexts.
Since no cases of DCS have been formally reported in the
course of EVAs conducted by any country, outcomes of physi-
ological training activities are discussed here to characterize
the clinical course of altitude DCS. However, caution is urged
in extrapolating these results into different operational con-
texts such as space flight.
In the experience of U.S. Air Force physiologic training,
the onset of the signs and symptoms of DCS occurred as early
as during the altitude exposure itself to as long as 36 h after
return to ground level [59,134]. The median time of onset
was 2 h after return to ground level. From a pathophysiologic
viewpoint, it is interesting to note that most cases of hypo-
baric DCS appeared hours after termination of the hypobaric
exposure. Type I cases accounted for 89% of the total, and the
other 11% were type II. About three fourths of the patients
received hyperbaric therapy (see below). All patients seemed
to have had complete resolution of clinical disease.
The U.S. Navy observed symptom onset at altitude in 46%
of the cases and at ground level in the remaining 54% of the
cases [135]. Of those cases that began at ground level, the
median time of onset was about 1 h after flight, and 4% of
the cases began more than 20 h after exposure. The case mix
was evenly divided between type I and type II disease (see
Tables 11.1 and 11.2 for specifics). Hyperbaric therapy was
administered to 84% of the patients, and about 4% of those
patients continued to have mild symptoms after treatment.
Experience with hypobaric DCS has also been gained
through laboratory studies of human subjects exposed to
pressure profiles similar to those experienced during EVA
operations [64,136139]. It is important to understand the
limitations of these studies, however. In these investigations,
DCS was generally treated immediately and definitively at the
onset of symptoms that were, by some measures, mild. These
results contributed little to the understanding of the natural
history of DCS or its refractoriness to therapy in any other
232 W.T. Norfleet

context. Specifically, in operations of the International Space of pressurization to ground level (that is, the pressure from
Station, treatment of DCS will not be immediate and may not which the hypobaric excursion originated). In one report, 37%
be definitive. The course of DCS in spaceflight operations of altitude DCS cases with onset at altitude resolved upon
may therefore be much more malignant than that observed in descent, although 17% of these case relapsed [135]. Although
terrestrial studies of similar pressuretime profiles. no definitive study has been performed to specifically evalu-
All of these considerations indicate that altitude DCS aris- ate this intervention alone (pressurization is usually combined
ing from physiological training profiles is usually fairly mild with a period of O2 breathing as a minimal treatment for estab-
and is generally responsive to prompt therapy. Nevertheless, lished DCS), it seems likely that pressurization alone could
it must be recalled that spectacular exceptions to this benign diminish or terminate some early, mild cases of DCS [140]. In
picture of altitude DCS, including death [57], have been operational environments with limited treatment capabilities
reported. such as space flight, relatively early termination of exposures
that are producing symptoms may forestall serious disease.
(This strategy, of course, conflicts with the do nothing strat-
Treatment egy described above, and the decision of which approach to
Four fundamental therapeutic interventions are known to be take will be influenced by the specific operational context in
effective in treating altitude DCS: (1) increasing the ambi- question.)
ent pressure; (2) increasing the partial pressure of inspired
O2; (3) using fluids to maintain intravascular euvolemia; and Ground-Level Oxygen Postbreathe
(4) providing supportive care such as airway management,
In recent years, ground-level oxygen (GLO) breathing has
cardiac life support, urinary bladder catheterization, and so
been established as a treatment modality for altitude DCS
on. Although other therapies have been suggested, these four
[105,141]. This treatment seems effective for preventing
interventions represent the cornerstone of treatment. With this
recurrence of type I symptoms that resolve during descent
overall perspective in mind, we will discuss therapeutic inter-
as well as for treating mild type I symptoms that persist to
ventions in order of escalating invasiveness.
ground level. Table 11.3 shows study results of the efficacy
of GLO. A success rate of 77% has been reported in treat-
Do Nothing Approach
ing type I altitude DCS with GLO alone [142]. In one study
Even if a subject is still in a hypobaric environment, very mild [143], symptoms that resolved during descent did not recur
symptoms do not necessarily demand immediate action. To in 99.2% of cases treated with GLO; in another study [142],
date, more than 1,000 subjects have been exposed to pressure that percentage was 96.2%. Whether to treat type I symptoms
profiles similar to those used during Space Shuttle EVA oper- that begin at ground level with GLO alone is controversial.
ations [64,136,137,139]. A variety of DCS symptoms have Indeed, most investigators do not consider GLO to be appro-
been observed, ranging from mild musculoskeletal pain to, priate as the sole therapy for any type II symptoms or any
rarely, cardiovascular instability and severe central nervous recurrent symptoms.
system dysfunction. In many of these cases, subjects were not
returned to sea-level conditions unless (1) the study protocol TABLE 11.3. Efficacy of ground-level oxygen treatment for altitude
was completed, (2) type II DCS was diagnosed, or (3) type I decompression sickness.
DCS reached a severity that impaired performance of some Clinical course Total No. of cases
manual task. Some subjects developed type I symptoms that Initial onset of DCS at altitude 104
were mild or intermittent and therefore did not meet termina- Asymptomatic upon return to ground 78
tion criteria; these symptoms either did not progress or actu- Received HBO 0
Received GLO; symptoms recurred 3
ally resolved during the course of the 3- to 6-h protocol. This
Resolved with HBO 3
approach did not seem to put these subjects at an outstanding Symptomatic upon return to ground 26
risk of serious sequelae such as recurrence of symptoms at Received immediate HBO 6
ground level or progression to type II DCS. Thus, in this par- Received GLO 20
ticular context, doing nothing in the face of mild, type I DCS Successful GLO 12
Unsuccessful GLO, successful HBO 8
seems defensible. From the perspective of overall risk man-
Initial onset of DCS at ground level 117
agement, though, a hyperbaric physician was in attendance Received immediate HBO 39
and a fully staffed clinical hyperbaric treatment chamber was Received GLO 78
present down the hall, providing the option of a clear, defini- Successful GLO without recurrence 40
tive course of action if benign disease became more sinister. Successful GLO but with recurrence 5
Successful HBO 5
Unsuccessful GLO 33
Return to Ground-Level Ambient Pressure Successful HBO 33
In various hypobaric operations, complete and lasting reso- Abbreviations: GLO, ground-level O2; HBO, hyperbaric O2.
lution of symptoms has been observed during the course Source: With permission from Rudge [142].
11. Decompression-Related Disorders: Decompression Sickness, Arterial Gas Embolism, and Ebullism Syndrome
GLO has come into clinical use more by consensus among
practitioners than by science. In other words, most practitioners
have found that GLO works reasonably well, but resources and
opportunities have not been available to perform a systematic,
rigorous clinical trial to establish the efficacy of GLO relative to
conventional hyperbaric therapy. Similarly, a dose-response
curve has not been established to determine the optimal length
of GLO. A 2-h period is currently common [141].
GLO might best be thought of as a means of prevention
rather than as a means of treatment. It is effective in forestall-
ing the recurrence of symptoms that disappear during repres-
surization. For symptoms that persist to ground level, a single
session of GLO can also be used while preparations are made
for transport to a hyperbaric facility. If the patient is cured
with a 2-h course of GLO, transport can be put on hold while
the patient is carefully observed for recurrence.
The criteria that determine whether a patient is a candidate
for GLO are fairly strict. In particular, those patients with
type II DCS are not generally considered candidates. Conse-
quently, it is important for type II DCS to be actively excluded
with some confidence. For this to be accomplished, the patient
with type II DCS must be examined by a knowledgeable and
experienced practitioner who is capable of performing a good
neurologic examination. Only if a thorough neurologic exami-
nation is clean should GLO be considered appropriate as
sole therapy.
Hyperbaric Oxygen Therapy
Originally developed to treat the bends in divers, hyperbaric
oxygen (HBO) therapy has become the mainstay of therapy
for altitude DCS. HBO therapy, as the name implies, involves
both the application of increased atmospheric pressure and
the provision of high inspired partial pressures of O2. Four
salutary effects are achieved. First, HBO therapy minimizes
bubble volume by compression, according to Boyles law [the
volume of a bubble at 2.8 ata, which is equivalent to a depth of
18 m (the usual depth of a treatment dive), is about 36% of
that at sea level]. Second, HBO therapy maximizes the gradi-
ent between the partial pressure of the inert gas in the bubbles
(which is raised as the bubbles are compressed) and that of the
surrounding tissue (which approaches zero when pure O2 is
breathed), thereby accelerating resorption of gas. Third, HBO
therapy enhances delivery of O2 to tissues rendered ischemic
by DCS-induced microvascular disease. Fourth, HBO therapy
brings to bear other therapeutic effects of high partial pres-
sures of O2 such as a reduction of tissue edema and intracra-
nial pressure [144,145] and inhibition of platelet aggregation
and leukocyte adhesion to damaged capillary endothelium
[146,147].
In many cases of altitude DCS, particularly those in which
treatment has been delayed or in which clinical improvement
continues during the course of repeated treatments over many
days, HBO has been observed to be effective long after tissue
bubbles would be expected to have resolved. In these cases,
233
the third and fourth factors above may be producing a benefi-
cial effect. If, in fact, what is being treated in these cases is not
a tissue gas phase but rather the aftermath of bubbles that have
since disappeared, then the benefits of HBO depend upon the
absolute partial pressure of O2 administered. The compression
of a gas phase by the first and second factors noted above is
not involved. In such cases, O2 can be thought of as a drug
with a dose expressed in terms of partial pressure. A cham-
ber is used simply as a means of delivering O2 at a dose in
excess of 1 ata. As discussed later in this chapter, the typical
dose of O2 involved in HBO is 2.8 ata.
Unfortunately, as is true for virtually any drug, O2 has its
sinister side as well, a side that manifests itself as pulmonary
and neurologic toxicity. Since both of these side effects depend
on dose, the risk of toxicity can be managed by limiting the
dose of O2 given to the patient. These issues are considered in
more detail in the remainder of this section.
Pulmonary Oxygen Toxicity
Most clinicians are familiar with the chemical burn induced
in pulmonary tissue when intubated patients undergo ventila-
tion for many hours with a fraction of inspired O2 that exceeds
about 0.5. Detailed studies of human volunteers breathing pure
O2 without interruption in a hyperbaric chamber [148] indi-
cate that significant toxicity (defined as a 2% reduction in vital
capacity) begins to develop after about 615 min of O2 breath-
ing at 1 ata. As would be expected, this time limit decreases as
chamber pressure increases (Figure 11.1). A method has been
developed to normalize periods of O2 breathing at a variety of
partial pressures to units with which clinicians are more famil-
iar. In this method, a unit of pulmonary toxic dose (UPTD)
induces the same amount of pulmonary stress as breathing
pure O2 for 1 min at 1 ata. As mentioned previously, significant
toxicity begins to appear after about 615 min of O2 breathing
at sea level. So in terms of the UPTD method, a dose of 615
UPTDs [or in terms preferred by some authors, a cumulative
pulmonary toxicity dose (CPTD)] is the maximum dose that
can be administered without inducing clinically significant
disease. Specifically [149],
UPTD(or CPTD) = tx *(0.5/[Px 0.5]0.833)
where tx is the duration of O2 breathing in minutes and Px is the
partial pressure of O2 in ata.
According to this scheme, 615 UPTDs are reached after
pure O2 is breathed for 615 min at sea level and after pure O2
is breathed for about 173 min at 2.8 ata. During HBO treat-
ments, a guideline has been empirically established that limits
CPTD exposures to 1,425 [149]. This limit corresponds to a
decrement in vital capacity of 10%. As is true for all practice
guidelines, this limit can be exceeded when the benefits of
further hyperbaric O2 seem to exceed the risks. The CPTD
scheme is useful for estimating the magnitude of pulmonary
toxicity present during prolonged or repeated hyperbaric
treatments, especially for an unconscious patient who cannot
234
Figure 11.1. Decrements in pulmonary vital capacity induced by
oxygen breathing [148]. Used with permission.
report the development of typical symptoms such as a dry
cough and burning or substernal chest pain with inspiration.
Neurologic Oxygen Toxicity
The most dramatic manifestation of neurologic O2 toxicity is
a grand mal seizure. Such a seizure may be preceded by pro-
dromal signs and symptoms. Phenomena observed during the
course of O2-tolerance tests administered by the U.S. Navy
from 1972 to 1981 (O2 breathing at 2.8 ata in a dry chamber)
are shown in Table 11.4 [150].
Although no clear threshold dose of O2 has been established
for developing neurologic O2 toxicity, grand mal seizures are
extremely uncommon in healthy individuals who are breath-
ing pure gas from good equipment at a partial pressure of O2
of less than 1.3 ata. Conversely, exposure to O2 at 6 ata can
produce these seizures in minutes.
Several factors are thought to lower the threshold for devel-
oping neurologic O2 toxicity, among them preexisting central
nervous system disease, fever, immersion in water, hypercap-
nea, corticosteriods, thyrotoxicosis, cold exposure, and heavy
exercise [151153]. Conversely, a wide variety of interven-
tions have been found to extend tolerance to O2. The most use-
ful of these is interruption of O2 breathing with short periods
of air breathing, a method that seems to forestall both neuro-
logic and pulmonary toxicity [154,155].
An O2 seizure, although pyrotechnic in its manifestations,
does not seem to do any lasting harm to the patient. Since O2
seizures are self-limited, no treatment is generally required other
than removing the O2 mask or hood, protecting the patient from
trauma, and conventional airway management [156]. The clinical
situation is atypical in that the patient is extremely well oxygen-
ated before seizure onsetwhich is, in fact, the problemand
W.T. Norfleet
TABLE 11.4. Oxygen toxicity symptoms reported during
oxygen-tolerance tests (19721981).
Sign/symptom % of total signs/symptoms
Convulsion 34
Muscle twitching 24
Dizziness 17
Nausea 7
Visual changes 7
Unconsciousness 3
Other 7
Source: Butler & Knafelc [150]. Used with permission.
spontaneous respirations return before hypoxemia develops.
Fifteen minutes after recovery from an episode of O2 toxicity,
O2 therapy can usually be resumed without further difficulty.
Treatment Tables
With this information in mind, some general design specifi-
cations can be established for the ideal hyperbaric treatment
table. Such a table shall (1) maximize the partial pressure
of inspired O2, (2) minimize the partial pressure of inspired
inert gas, (3) maximize the duration of O2 breathing, (4)
avoid neurologic and pulmonary O2 toxicity, notwithstanding
specifications (1)(3); (5) maximize the probability of cure,
(6) minimize the time required for treatment, and (7) minimize
the risk of inducing DCS in the patients in-chamber tender.
Because some of these specifications conflict with one
another, a grand compromise will be required. If the partial
pressure of O2 exceeds something like 3 ata, the risk of neu-
rologic O2 toxicity will drastically limit the duration that O2
can be breathed. Air breaks, periods in which the patient
breathes air rather than O2, should be incorporated to fore-
stall O2 toxicity. If the dive is such that the tender picks up
a significant burden of dissolved inert gas, the tender should
breathe O2 near the end of the table to reduce the risk of devel-
oping DCS. The ascent from 3 ata to the surface should be
accomplished gradually or in stages to extend the duration of
O2 breathing and permit early detection of deterioration in the
patients condition.
Clinical experience and laboratory findings gained over
the past few decades have generated a degree of consensus
regarding the optimal partial pressure of O2 for initial treat-
ment of DCS. Tables constructed around O2 delivered at
2.8 ata have proven successful in treating both altitude [34]
and diving [157] casualties. Laboratory studies of an animal
model of hyperbaric DCS indicate that the optimum partial
pressure of O2 in this setting is 2.02.5 ata [158,159]. Most
modern clinical treatment tables center on administering
2.8 ata of O2.
The table that seems to strike the best and most effec-
tive balance among the conflicting specifications for an
ideal table is U.S. Navy Treatment Table 6 (TT6) (Figure
11.2) [160] and closely related versions published by other
branches of the U.S. armed forces and by other govern-
11. Decompression-Related Disorders: Decompression Sickness, Arterial Gas Embolism, and Ebullism Syndrome 235

Treatment Table 6
1. Descent rate - 20 ft/minute
2. Ascent rate - not to exceed 1 ft/minute. Do not compensate for slower ascent
rates. Compensate for faster rates by halting the ascent.
3. Time on oxygen begins on arrival at 60 feet.
4. If oxygen breathing must be interrupted because of CNS Oxygen Toxicity,
allow 15 minutes after the reaction has entirely subsided and resume schedule
at point of interruption (see paragraph 21-5.5.6.1.1).
5. Table 6 can be lengthened up to 2 additional 25-minute periods at 50 feet
(20 minutes on oxygen and 5 minutes on air), or up to 2 additional 75-minute
periods at 30 feet (15 minutes on air and 60 minutes on oxygen), or both.
6. Tender breathes 100 percent O2 during the last 30 minutes at 30 fsw and during
ascent to the surface for an unmodified table or where there has been only a
single extension at 30 or 60 feet. If there has been more than one extension, the
O2 breathing at 30 feet is increased to 60 minutes. If the tender has a hyperbaric
exposure within the past 12 hours an additional 60-minute O2 period is taken
at 30 feet.

Figure 11.2. U.S. Navy Treatment Table 6. From the U.S. Navy Diving Manual [160]

mental and commercial entities. Notable features of TT6
include a maximum depth of 2.8 ata, prolonged periods of
O2 breathing interspersed with short air breaks, a gradual
depressurization to 1.9 ata, a prolonged stage at 1.9 ata, and
a gradual decompression to the surface during which time
the tender also breathes O2. The total duration of the table
is 4 h and 45 min, although extensions at 2.8 ata or 1.9 ata
can be made as the patients condition dictates. This table,
as well as all of the other tables published in the U.S. Navy
Diving Manual, was developed with divers in mind, but it
has been found to be highly effective in treating altitude
DCS as well.
A closely related table to TT6 is U.S. Navy Treat-
ment Table 5 (TT5) (Figure 11.3) [160]. TT5 differs from
TT6 in that the stages at 2.8 ata and 1.9 ata are truncated,
yielding a total duration of 2 h and 15 min. This table is
intended only for type I symptoms. If all symptoms are
not resolved within 10 min of arrival at 2.8 ata, transition
to TT6 is mandatory. TT5 can also be used for follow-up
treatments of residual disease. Notably, TT5 has the repu-
tation of failing to prevent recurrence of symptoms after
an apparently successful initial treatment [161], although
good results have been reported [162]. Most practitioners
prefer to do a full TT6, if they are going to do a dive at
all, and get it over with. Nevertheless, TT5 might still
be considered in treating equivocal or very mild cases,
but the practitioner should be prepared for retreatment at
odd hours.
The ultimate in truncation of TT6 is the so-called test
of pressure, which involves compression to 2.8 ata while
breathing O2 as a means of differentiating type I symptoms
from nondysbaric forms of musculoskeletal pain such as
trauma. The approach concludes that if symptoms are alle-
viated by pressure, DCS is present and TT5 or TT6 is indi-
236
cated; but if symptoms are totally unchanged, DCS is not
present and further hyperbaric therapy is not warranted.
Unfortunately, clinical practice is rarely so straightforward.
Symptoms that may be equivocal to begin with are often
reported at depth to be maybe a little better. It therefore
usually seems prudent to give the patient the benefit of
the doubt and to proceed with more definitive treatment.
The U.S. Navy Diving Manual reflects this approachfor
divers, at leastby stating that once recompression to
60 ft is done, Treatment Table 5 will be used even if it
was decided symptoms were probably not decompression
sickness. Direct ascent to the surface is done only in emer-
gencies.
The ultimate in extension of TT6 is the Catalina table [163].
In it, the stages at 2.8 ata and 1.9 ata are greatly prolonged,
with up to 8 O2-to-air cycles at 2.8 ata and 18 cycles at 1.9 ata.
The Catalina table is used primarily for patients who continue
to have serious disease after completing the stages at 2.8 ata
or 1.9 ata in a TT6, or for patients who show decompensation
during depressurization from one of these stages. As might
be expected, considerable O2 stress is imposed on pulmonary
tissues by this exposure.
These four tables (TT6, TT5, test of pressure, and Catalina
table) constitute the core of hyperbaric treatment tables for
DCS. TT6 is used to initially treat the vast majority of cases.
Unfortunately, some patients do not respond completely to
the first HBO treatment. For these patients, additional tailing
treatments can be performed. The choice of the specific table
used for tailing treatments depends on many factors, includ-
ing the severity of symptoms, the trajectory of the clinical
course (e.g., rapid improvement, rapid decompensation, stub-
bornly stable, etc.), the pulmonary status, the fatigue of the
chamber crew, the availability of tenders, and local custom.
The range of responses extends from an immediate initiation
of a TT6 to daily TT5s or, even more simply, to a 90-min
excursion to 2.4 ata while breathing O2 on a 25 min on, 5 min
off basis. Lengthy treatment programs have been reported
in the diving literature, some including over 30 individual
daily dives [164]. Precisely when to terminate further tailing
treatments is unclear. A consensus may be developing among
practitioners, however, that further improvement is unlikely if
no change is observed over the course of two or three tailing
treatments [165].
Many other treatment tables exist, but these have little or no
applicability to altitude DCS except perhaps for the U.S. Navy
Treatment Table 7, which might, in the words of the U.S.
Navy Diving Manual, be used as a heroic measure to treat
a life-threatening disease that worsens when decompression
during treatment is attempted. These more exotic tables are
useful in treating divers who have been exposed to environmental
conditions far afield from those of the aviator or spacewalker,
such as very deep, very prolonged He/O2 dives. Tables are also
available to perform hyperbaric therapy if O2 is unavailable (air is
breathed throughout), but these are less likely to cure the patient
than TT6 and are more likely to induce DCS in the patients
tender [157]. The reader is referred to comprehensive sources
W.T. Norfleet
such as the U.S. Navy Diving Manual [160] and the National
Oceanic and Atmospheric Administration Diving Manual [166]
for additional information on these tables as well as on treatment
algorithms that can be used for table selection.
Adjunct Therapy
An important part of treating any case of DCS is providing flu-
ids to maintain intravascular euvolemia. Hemoconcentration
occurs commonly in DCS [39], as does extravasation of plasma.
Fluids should be provided by conventional clinical methods,
with recognition of the fact that catheterization of the urinary
bladder will be necessary in some cases of type II DCS. A case
could be made for excluding glucose from intravenous fluids
administered to patients with neurologic involvement [167].
In addition to pressure, O2, fluids, and supportive care, many
adjunctive therapies have been investigated [41]. A truncated
list of these therapies includes lidocaine [123,168,169], cor-
ticosteroids [170,171], perfluorocarbons [172], aspirin, and
dipyridamole [173,174]. That at least some of these interven-
tions should be effective is a reasonable hypothesis that is
backed by laboratory findings and some clinical case reports.
However, their clinical efficacy in treating DCS has yet to
be definitively established. Perhaps, in the future, as we learn
more about the pathophysiology of DCS, the beneficial effects
of hyperbaric O2 will be reproduced by other agents, and some
or all cases of DCS will be treated solely with methods that do
not involve cumbersome hyperbaric chambers.
Treatment in Space Flight
Given the substantial decompression stress involved in Space
Shuttle and International Space Station operations, some DCS
associated with EVAs seems inevitable, although the magni-
tude of this risk is unclear. Laboratory investigations indicate
that most cases will be mild [64,136,137]. Indeed, mild type
I DCS might not even be recognized by a crewmember given
the discomfort of the space suit, the focus of the crewmember
on the task at hand, and the fact that analgesic drugs are used
before and after EVAs [175]. However, serious DCS, includ-
ing cardiovascular instability and severe cognitive impair-
ment, has been observed during laboratory studies, even
though subjects were carefully monitored for the onset of such
disease and were rapidly and definitively treated when illness
was detected [176] (JM Waligora, personal communication).
Consequently, a small but real risk of serious DCS seems to
exist in current spaceflight operations.
If hyperbaric treatment of altitude DCS is delayed, the
efficacy of hyperbaric therapy is reduced [177]. To prevent
such delays, Space Station Freedom (which was cancelled in
1992) included a structure that was designed to function both
as an airlock and a multiplace, monolock hyperbaric treatment
chamber. This on-site treatment capability would have afforded
the station crew many advantages, among them the ability to
halt the progression of disease at an early stage, to effect a
cure with a single treatment, to avoid the costs of an evacu-
ation, to reduce the requirement for oxygen prebreathing
11. Decompression-Related Disorders: Decompression Sickness, Arterial Gas Embolism, and Ebullism Syndrome 237

Treatment Table 5
1. Descent rate - 20 ft/minute
2. Ascent rate - not to exceed 1 ft/minute. Do not compensate for slower ascent
rates. Compensate for faster rates by halting the ascent.
3. Time on oxygen begins on arrival at 60 feet.
4. If oxygen breathing must be interrupted because of CNS Oxygen Toxicity,
allow 15 minutes after the reaction has entirely subsided and resume schedule
at point of interruption (see paragraph 21-5.5.6.1.1).
5. Treatment Table may be extended two oxygen-breathing periods at the 30-
foot stop. No air break required between oxygen-breathing periods or prior
to ascent.
6. Tender breathes 100 percent O2 during ascent from the 30-foot stop to the sur-
face. If the tender has a previous hyperbaric exposure in the previous 12 hours,
an additional 20 minutes of oxygen breathing is required prior to ascent.

Figure 11.3. U.S. Navy Treatment Table 5. From the U.S. Navy Diving Manual [160]

until inconvenient forms of DCS appear without unduly risk-
ing the eruption of catastrophic forms of disease, and, finally,
to return the crew promptly to full duty status, operating under
a treat it and forget it philosophy. Indeed, accrual of similar
benefits is the rationale for the requirement by organizations
such as the U.S. Navy and he U.S. Occupational Safety and
Health Administration for on-site hyperbaric chambers when
stressful diving profiles are being undertaken.
The International Space Station includes no such hyper-
baric capability. The equivalent of GLO can be provided by
keeping the patient in his or her space suit. Also, delivery of
nearly 100% O2 at a pressure as great as 1.54 ata is possible
through overpressurization of the EMU with installation
of the bends-treatment apparatus in the space suit [178]. If
a crewmember requires hyperbaric therapy, however, evacua-
tion to a terrestrial facility via a highly exotic and extremely
expensive mode of transport will be the only option, a process
that may require in excess of 24 h, particularly if landing does
not take place within easy reach of a modern medical center
(as discussed in Chap. 7). Given the time required for trans-
port, the decision to evacuate a patient will need to be made
early and easily to decrease the risk of the disease progressing
into its permanently disabling or lethal forms.
Disposition and Return to Duty
Decisions about whether an individual can resume duties that
require re-exposure to decompression stresses are complex.
A host of issues, both scientific and social, are involved. Since
regulations established by the U.S. armed forces for the return
of pilots and divers to duty vary enormously, cases are often
referred to a medical certification board that considers them
on a case-by-case and therefore somewhat arbitrary basis.
NASA has developed a document that establishes its policy
for return of aircraft and spacecraft crews to duty after DCS
and AGE events [179] (Table 11.5). These criteria are not nec-
essarily the best, but they are the most contemporary attempt
to strike an effective compromise among the many conflicting
concerns at work in these situations.
Arterial Gas Embolism
Only a thumbnail sketch of the pathophysiology and treat-
ment of AGE is presented here because AGE occurs rarely in
the aerospace environment, generally in the setting of a rapid
depressurization. The problem is of much greater concern in
238 W.T. Norfleet

TABLE 11.5. Medical status after decompression-related events.

Situation Time to duty Time to reduced pressure exposure
Minor DCS (type I) 24 h after resolution of symptoms. Aircraft/Chamber Operations/
Immersion Facilities: 72 h after
resolution of symptoms.
Spaceflight: 72 h if symptoms
resolve upon repressurization,
otherwise 7 days after
symptoms resolve.
Minor DCS repetitive 24 h after resolution of symptoms. Case-by-case consideration.
event (type I)
AMB review required.
Serious DCS (type II) 48 h after resolution of symptoms. Case by case consideration.
AMB review required.
Arterial gas embolism Case-by-case consideration. Case-by-case consideration.
AMB review required.
Medical evaluation and status
Aircraft/Chamber Operations/
Immersion Facilities: MO/FS
evaluation. AMB review not required.
Space flight: CMO evaluation and PMC
as soon as practical. AMB review not
required.
Aircraft/Chamber Operations/Immersion
Facilities: MO/FS evaluation.
Space flight: CMO evaluation and PMC
as soon as practical.
All require AMB waiver for return to
reduced-pressure environments.
Aircraft/Chamber Operations/Immersion
Facilities: MO/FS evaluation.
Space flight: CMO evaluation and PMC
as soon as practical.
All require AMB waiver for return to duty
and reduced-pressure environments.
Aircraft/Chamber Operations/Immersion
Facilities: MO/FS evaluation.
Space flight: CMO evaluation and PMC
as soon as practical.
All require AMB waiver for return to duty
and reduced-pressure environments.

Repetitive EventSubject has incurred a Type I or II DCS event within the past 30 days for ground-based exposure. For spaceflight operation, repetitive
event is a more than one Type I in a given mission.
This table above summarizes JPG 1800.3 and covers all personnel for aircraft operations, immersion facilities, chamber operations, and spaceflight.
The current astronaut selection/retention policy is outlined in JSC-24834, Astronaut Medical Standards.
Mild Decompression Sickness DCS (Type I): symptoms involving joint pain, peripheral nervous system, or simple skin bends.
Mild Decompression Sickness DCS (Type I)Repetitive: symptoms involving joint pain, peripheral nervous system, or simple skin bends which have
occurred previously within the past 30 days for ground-based exposure or with in a single flight for spaceflight operation.
Serious DCS (Type II): symptoms involving the central nervous system, cardiovascular system (circulatory collapse/shock), pulmonary system (chokes), or
skin marbling.
Arterial Gas Embolism: evolved gas producing symptoms and signs consistent with passage of the gas to the arterial circulation; i.e., severe neurological
manifestations.
All medical data relating to a decompression disorder will be kept confidential and consistent with the Privacy Act.
Current definitions are clinically based on, and consistent with, commercial and military diving and aviation policies. No administrative decision on flying
duties will be based on Doppler-detectable bubbles.
All in-flight DCS events that do not resolve with available treatment options, as well as complicated type II events, may be grounds for medical return and
mission termination.
Abbreviations: DCS, decompression sickness; MO, medical officer; FS, flight surgeon; CMO, crew medical officer; PMC, private medical conference;
AMB, aerospace medicine board.

diving and in some clinical practice settings, such as in car-
diopulmonary bypass and laparoscopy. Additional informa-
tion can be found in an excellent review of AGE treatment by
Moon and Gorman [180].
Pathophysiology
If a person is exposed to a reduction in ambient pressure,
intrathoracic gas expands as described by Boyles law. If
the gas is not vented from the thorax as intrathoracic gas
enlarges (e.g., if the subject closes his or her glottis or if
the decompression is extremely rapid), lung volume will
increase. As lung volume exceeds total lung capacity (and,
in some persons, at lesser volumes) [181], structural failure
of lung tissue occurs. This releases gas from the alveoli, a
process known as volutrauma [182184]. Free gas can
track through tissue planes into the mediastinum, where it
produces mediastinal emphysema; into subcutaneous tissues,
especially those superior to the clavicles, where it generates
subcutaneous emphysema; into the pleural space, where it
results in a pneumothorax; or into the intravascular space,
where it gives rise to AGE.
Intrathoracic trauma is often described as arising from pul-
monary overpressurization, but this is not strictly true; for
example, an anesthetized, intubated, and paralyzed dog that
has its thorax splinted with thoracic and abdominal binders
(to limit lung expansion) can tolerate much higher intratho-
racic pressures than a dog without binders [185]. This makes
sense because transalveolar pressure gradients are determined
by the elastic recoil of the lungs, not by intrathoracic pressure.
11. Decompression-Related Disorders: Decompression Sickness, Arterial Gas Embolism, and Ebullism Syndrome 239

Hence, it seems that overexpansion of the lungs is what does TABLE 11.6. Signs and symptoms in
the damage, not overpressurization. scuba-related gas embolism.
The interaction of arterial gas emboli with tissue capillary Sign/symptom % of cases
beds is complex. Much experimental work has focused on the Loss of consciousness 70
effects of bubbles in the brain. These bubbles can clear from Extremity paresis 54
brain vasculature surprising quickly, but many abnormal tis- Seizure 38
Extremity numbness 31
sue responses remain [91,96,186188]. Any capillary bed is
Vertigo 31
subject to embolization, including cerebral, coronary, and spi- Mediastinal emphysema 23
nal tissues. Under the right circumstances, a combination of Nausea and vomiting 23
AGE and DCS can occur. Chest pain 15
Although AGE usually has an identifiable cause, such Subcutaneous emphysema 15
Aphasia 8
as breath-holding during decompression, not all cases are
Blindness 8
deserved. This is particularly true during submarine escape Cognitive impairment 8
training operations in which divers make carefully supervised
free ascents. Occasional cases of AGE occur despite the per- Source: Heimbach & Sheffield [105].
formance of thorough qualifying physical examinations and
the use of proper technique throughout ascent [185,189]. AGE
must therefore always be part of the differential diagnosis when Some laboratory studies indicate that TT6 may be as good as
evaluating a patient that has become ill after a decompression. or perhaps better than TT6A for AGE [196]. This thinking
is reflected in the current version of the U.S. Navy Diving
Manual [180], which calls for all patients to be compressed
Clinical Presentation initially to 2.8 ata (i.e., to begin TT6), with deeper excursion
Neurologic dysfunction occurring minutes after a decompres- on a TT6A reserved for patients who do not improve within
sion is the hallmark of AGE [190]. In 41 cases of pure AGE 20 min at 2.8 ata. Therefore, selection of TT6 for the initial
(i.e., with little coexisting inert gas burden) presenting as treatment of AGE is justifiable. As with DCS, a wide vari-
sudden loss of consciousness, collapse took place within the ety of potentially useful tables exist for AGE cases that do
first minute after surfacing in 33% of the patients and within not respond to TT6 and TT6A, especially for patients who
5 min in 100% of the patients [191]. Other associated signs decompensate during the large decompression from 6 ata to
and symptoms may include hemoptysis, respiratory distress or 2.8 ata in TT6A.
cardiovascular collapse from a pneumothorax, supraclavicular The recommendations concerning administering O2, flu-
crepitus from subcutaneous emphysema, and hoarseness from ids, and supportive care that were described above for the
mediastinal emphysema (Table 11.6) [105]. Other etiologies treatment of DCS also apply to AGE. In fact, the case for
that are associated with aerospace operations include hypox- adjunctive therapies such as corticosteroids, lidocaine, and
emia (secondary to, for example, loss of O2 supply or loss others, is much stronger in AGE than in DCS, although the
of ambient pressure), contaminated breathing gas, and DCS. use of such agents is not yet considered the standard of care
Diagnosis is based largely on history and physical examina- [180,193,195].
tion, because no single laboratory test is definitive; for exam-
ple, a chest radiograph may be normal despite clear evidence
Disposition and Return to Duty
of AGE [192].
Disposition and return to duty issues for AGE are handled
much as they are handled for DCS. Certainly, the cause of
Clinical Course and Treatment any undeserved AGE episode such as undiagnosed bron-
Some cases of AGE undergo complete clinical resolution chospastic disease or an anatomic pulmonary abnormality
without treatment. Although 21% of AGE cases reported should be sought, and the implications of any new revela-
by Leitch and Green resolved completely and permanently tions on fitness for further exposure to pressure excursions
without therapy [193], rapid administration of ground-level should be considered. Truly undeserved AGE may be cause
O2 is clearly beneficial [68]. The longstanding recommen- for disqualification from future pressure work.
dation that, during transport to a chamber, patients should
be maintained in the 30-degree Trendelenberg position
with left-lateral tilt probably does no good and may worsen Ebullism Syndrome
elevated intracranial pressure [194,195]. HBO is indicated,
although controversy exists regarding the best treatment This brief discussion of the ebullism syndrome focuses on
table for AGE. Traditionally, U.S. Navy Treatment Table three major points: (1) that the syndrome is not just a particu-
6A (TT6A) has been used. This table is similar to TT6 larly severe form of DCS but has its own unique qualities;
except that an initial excursion to 6 ata is included in it. (2) that humans may be able to survive exposure to hard vacuum
240
for a few minutes; and (3) that modest efforts to prepare treat-
ment plans for the ebullism syndrome are not entirely futile.
Pathophysiology
The ebullism syndrome arises when an individual is exposed
to an ambient pressure that is less than the vapor pressure of
body fluids at normothermic temperature, about 6 kPa [197].
Whereas DCS is primarily characterized by the formation in
tissues of the gas phase of inert gas, ebullism is character-
ized by the formation of the gas phase of water. Consequently,
O2 prebreathing, no matter how extensive, cannot prevent the
syndrome since it will arise even when the body is devoid of
dissolved inert gas.
During exposure to near-vacuum, bubbles form in all body
structures including all tissues, cavities, and potential spaces
such as the pleura. However, local tissue hydrostatic pressure
may limit or eliminate water vapor formation; for example,
for as long as blood pressure remains normal, the pressure of
arterial blood will remain above 6 kPa, thus preventing water
vapor formation. Tightly wrapping an extremity may prevent
vapor formation within that extremity. On the other hand, nor-
mal central venous pressure is only slightly above ambient
pressure, so bubble formation occurs readily within the venae
cavae, obstructing venous return to the heart [198]. Indeed,
cardiac output has been observed to virtually cease within 15 s
after animals are exposed to near-vacuum [111,199]. Since
pleural pressure is negative relative to ambient pressure,
vapor forms rapidly within this potential space. Similarly,
vapor formation readily occurs in the ocular conjunctivae and
the epithelium of the airwaysa phase transition that cools
these structures.
Bubble formation is not instantaneous, and tissues can
tolerate extreme hypobaric pressures for some time [199].
Significantly, exposure to near-vacuum was required for
90 s before substantial pulmonary damage occurred in dogs
[90]. Similarly, bubble resolution is not instantaneous upon
recompression. Once a bubble forms, gases dissolved in the
fluid surrounding the bubble will diffuse into that bubble
until all partial pressures are equalized [198]. Bubbles con-
sequently will contain water vapor, O2, CO2, and a quantity
of N2 that depends on the state of inert gas elimination from
the body at the time of extreme depressurization. Reversal
of this process upon repressurization takes time. Therefore,
an individual exposed to near-vacuum may be burdened with
substantial quantities of intravascular gas after repressuriza-
tion. The amount of inert gas dissolved in the tissues at the
time of the excursion seems to be an important determinant
of the time course of bubble resolution and the degree of tis-
sue damage that occurs. For example, pulmonary edema is
less and survival is greater in animals that are denitrogenated
before depressurization [90].
Animal studies indicate that the pulmonary system is
particularly affected in the ebullism syndrome. The formation
of water vapor within alveoli during decompression followed
W.T. Norfleet
by the collapse of this vapor upon repressurization leads
to massive atelectasis that greatly impedes pulmonary gas
exchange. Reestablishing pulmonary function is consequently
a priority in the treatment of the disorder. This type of pulmo-
nary damage is not typical of DCS, so the treatments of the
ebullism syndrome and DCS are not identical.
Additional features of the syndrome include anoxia through-
out the excursion below 6 kPa, probable coincident DCS, and
possible AGE from pulmonary volutrauma, particularly if
the decompression was explosive [200,201].
The length of time that humans can be exposed to extreme
hypobaric conditions without morbidity or mortality is
unknown. To date, published laboratory studies with animals
have limited applicability to this question because the animals
usually received little or no treatment after exposure. For what
it is worth, 14 of 15 dogs in one study survived an exposure
to near-vacuum for 2 min without an O2 prebreathe [111]. In
another study, all ten dogs survived exposure to near-vacuum
for 2 min with little O2 prebreathe [202]. In another study, 17
chimpanzees that were trained to perform complex tasks were
exposed to near-vacuum for up to 210 s after 4 h of denitroge-
nation; 16 of the chimps survived, and none of the survivors
showed performance decrements [203]. Finally, in another of
the more rigorous studies of the ebullism syndrome, Bancroft
et al. [202]. showed that exposure to hard vacuum was a much
greater physiological insult than was breathing 100% N2 at
1 ata for an equivalent time.
Two human exposures to near-vacuum have occurred. In
an accident in an industrial vacuum chamber, an individual
was rapidly decompressed without preoxygenation from sea
level to less than 4 kPa ambient pressure and was maintained
at near-vacuum for 35 min [204]. Although this person had
a stormy clinical course that required intensive care, bilateral
chest tubes, and multiple HBO treatments, he eventually
recovered completely. The other incident involved testing a
pressure suit at the Johnson Space Center during the 1960s.
The failure of a hose fitting resulted in very rapid depres-
surization (after extensive O2 prebreathing) from about
25 kPa to less than 4 kPa. The subject of this depressuriza-
tion recalled feeling the saliva on the tip of his tongue begin
to boil as he slipped into unconsciousness. Repressurization
was accomplished immediately, and the subject went home
for lunch.
Clinical Presentation, Clinical Course,
and Treatment
The clinical picture of the ebullism syndrome includes severe
cerebral anoxia, pulmonary atelectasis, cardiovascular col-
lapse, venous gas embolism, AGE, DCS, and possibly pneu-
mothorax and various forms of barotrauma. The probability
of survival seems to fall off rapidly as the duration of expo-
sure increases on a time scale measured in seconds rather
than minutes. Obviously, rapid repressurization is critical. But
beyond this, the optimum therapy for the ebullism syndrome
11. Decompression-Related Disorders: Decompression Sickness, Arterial Gas Embolism, and Ebullism Syndrome
has not yet been established. Clearly after repressurization,
reestablishing pulmonary function will be a priority with
emphasis on reversing atelectasis and decompressing any ten-
sion pneumothorax. Supportive care and fluids are to be given
as needed, and HBO may be helpful. Two humans and many
experimental animals have survived exposure to near-vacuum
for several minutes, so aggressive therapy is not necessarily a
futile gesture.
Disposition and Return to Duty
Given the rarity of the ebullism syndrome, little can be said
with confidence regarding disposition and return to duty after
exposure. The case may be as simple as the one that occurred at
the Johnson Space Center. Conversely, if the patient described
by Kolesari and Kindwall [204] had been a spaceflight crew-
member, an enormous list of issues would have needed to be
addressed. Those who first deliberate over such cases will be
writing the book on the subject.
Conclusions
Decompression illness is a risk in EVA operations. Specifi-
cally, all EVA protocols currently approved for Shuttle and
ISS operations carry a reasonable possibility of serious DCS.
The absolute magnitude of this risk is a matter of uncertainty
and debate, but the existence of a real risk seems clear. This
chapter was written in an attempt to provide guidance to prac-
titioners of space medicine confronted with a patient with
decompression illness and to aid practitioners who partici-
pate in operational planning as they address issues related to
decompression illness. The principles of operational risk man-
agement are useful in such deliberations;namely (1) identify
risk, (2) mitigate risk, (3) whenever possible, eliminate risk,
and (4) accept no unnecessary risk [205]. Consequently, this
chapter has outlined what causes the various forms of decom-
pression illness, what harm it can cause the patient, how it
can be treated, and how the occurrence of cases of it can be
reduced or, in some instances, eliminated.
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12
Decompression-Related Disorders: Pressurization
Systems, Barotrauma, and Altitude Sickness
Jonathan B. Clark
The physiological zone from sea level to 3,048 m (10,000 ft)
encompasses the pressure to which humans are well adapted,
although if appropriately acclimated they can survive
the summit of Earths highest mountain (Mt. Everest at
4,448 m/29,028 ft) without supplemental oxygen. Continuing
to altitudes above this, artificial systems are required to sup-
ply needed oxygen and, eventually, sufficient ambient pres-
sure. The most effective means of preventing physiological
problems in aircraft and spacecraft is to provide cabin pres-
surization so that occupants are never exposed to pressures
outside the physiological zone. Failure of structures, hard-
ware, or procedures may unfortunately lead to unwanted and
hazardous decompression events. This chapter will review
cabin pressurization schemes, events that might lead to loss of
pressure, and two major medical concerns of decompression:
barotrauma and altitude sickness.
Cabin Pressurization
Human aircraft and spacecraft occupants may be maintained
in rarefied atmospheres with personal support equipment such
as supplemental oxygen systems and pressure suits. However,
the risk of hypoxia and decompression-related disorders may
also be mitigated by pressurizing the habitable cabin volume.
This eliminates the need for personal supplemental oxygen,
allowing crew and passengers to move freely unencumbered
by oxygen masks and hoses or other life support equipment.
The incidence of trapped gas effects (pain in gastrointestinal
tract, middle ear, and sinuses) is reduced by smaller cabin
pressure changes that are controlled and predictable during
ascent and descent. In addition, cabin temperature, humid-
ity and ventilation can be controlled within desired comfort
levels. Prolonged passenger flights, air evacuation, and troop
movements can be accomplished with a minimum of fatigue
and discomfort.
There are structural and operational disadvantages to cabin-
wide pressurization. An increased weight of the pressure ves-
sel is typically required to maintain structural integrity, which
limits maximum performance and payload capacity. Addi-
tional maintenance, equipment, and power are required to
support the environmental control system. Finally, recircula-
tion of cabin air might foster the spread of combustion prod-
ucts, contaminants, infectious particles, and odors throughout
the cabin atmosphere.
Methods of Maintaining Cabin Pressure
The two main modalities of maintaining pressure greater than
ambient involve the conventional cabin and the sealed cabin.
The conventional method for increasing aircraft cabin
pressure is to use ambient air, forced into the cabin by
means of a compressor. Cabin pressure and ventilation are
maintained by varying the amount of air introduced into the
cabin and the amount released through adjustable outflow
valves. A high differential requires an aircraft structure
that is physically stronger and therefore heavier than that
required for a lower differential. Cabin pressurization repre-
sents an engineering and physiologic tradeoff; the increased
structural weight decreases the payload carrying capacity
of the aircraft. Pressurization requires energy expenditure
in the form of bleed air from the compressor stage of the jet
turbine engine. The larger the differential, the more power
required to provide the desired pressure and less power
available for aircraft thrust.
Conventional cabin pressurization utilizes two types of pres-
surization schedules, the isobaric and the isobaric-differential
schemes. Isobaric control refers to the condition where the cabin
pressure is maintained at a constant altitude or pressure regard-
less of the ambient pressure decrease, after a certain altitude
is reached. This pressurization system is found in most cargo
and passenger air transport aircraft, which typically maintain a
cabin pressure equivalent to 2,438 m (8,000 ft) altitude through-
out flight. Tactical jet aircraft are equipped with an isobaric-
differential pressurization system. This pressurization system
senses both cabin and ambient pressure and maintains the cabin
pressure on the basis of a fixed pressure differential. Tactical jet
aircraft typically maintain a 5 psi isobaric-differential pressur-
247
248
ization schedule. As the aircraft ascends, the cabin is depres-
surized to 2,438 m (8,000 ft) altitude. From this altitude to
approximately 7,010 m (23,000 ft), cabin pressure remains at
2,438 m equivalent altitude (isobaric range). From 7,010 m up to
the operating ceiling of the aircraft, cabin pressure is maintained
at a pressure differential of 5 psi above ambient. If an aircraft is
flying at an altitude of 12,192 m (40,000 ft), with an outside pres-
sure of 2.72 psi, the aircraft pressurization system will maintain
a pressure of 7.72 psi, or 5,029 m (16,500 ft) as the equivalent
cabin altitude.
In the increasing rarefied altitudes above 24,380 m
(80,000 ft), cabin pressurization cannot be maintained by the
conventional method delivered by a jet turbine engine. At
these very high altitudes, the ambient air is so thin the jet
engine does not receive sufficient air for compression; com-
pressor turbine blades stall, and pressurization fails. At this
point, sealed cabins must be used to maintain an adequate
habitable environment. This sealed cabin system is utilized at
extremely high altitudes and in the vacuum of space. Pressur-
ized gas is carried on the aircraft or spacecraft and metered
into the pressure vessel of the habitable space. In this closed
system, metabolic byproducts are removed and the cabin
gas is recirculated to conserve the gas supply. Before space
flight, very high altitude experimental aircraft such as the
X-15 used this scheme.
FIGURE 12.1. Schematic of the Space Shuttle pressure control system. Cryo = cryogenic, Cab = cabin, N2 = nitrogen, Emer = emergency, O2
= oxygen, LEH = launch and entry helmet, psi = pounds per square inch, EMU = extravehicular mobility unit, reg = regulator, tk = tank
J.B. Clark
Spacecraft Pressurization: The U.S. Shuttle
The Atmosphere Revitalization Pressure Control System
(ARPCS) controls the Space Shuttle crew cabin pressure to
14.7 psia, +/ 0.2 psia, with an average of 80% nitrogen and
20% oxygen mixture. Oxygen partial pressure is maintained
between 2.95 psia and 3.45 psia, with sufficient diluent nitro-
gen added to achieve a cabin total pressure of 14.7 psia. The
orbiter crew compartment provides a life-sustaining environ-
ment for a crew of up to eight. The crew cabin volume with
the airlock inside the middeck is 65.8 m3 (cubic m) (2,325 ft3);
if the airlock is located outside of the middeck in the payload
bay, a recently added modification option, the crew cabin volume
expands to 74.3 m3 (2,625 ft3). For extravehicular activity require-
ments, only the airlock is depressurized and repressurized.
The pressurization system consists of two gaseous oxygen
and two gaseous nitrogen systems, as shown in Figure 12.1.
The two oxygen systems are supplied by a cryogenic super-
critical oxygen storage system, which also supplies oxygen to
the orbiters electrical power-generating fuel cells. For normal
on-orbit operations, one of two oxygen and nitrogen supply
systems is used, while both are used for the more time-critical
launch and entry phases. The primary and secondary oxygen
and nitrogen gas supply systems have a crossover capability
to provide partial system redundancy in case of failures. These
12. Decompression-Related Disorders: Pressurization Systems, Barotrauma, and Altitude Sickness
systems provide the makeup cabin oxygen gas consumed by
the flight crew, as well as nitrogen for pressurizing the potable
supply water and waste water tanks and repressurizing the
airlock following EVA. An average of 0.8 kg (1.76 lb) of oxy-
gen is consumed per flight crewmember per day. Up to 3.5 kg
(7.7 lb) of nitrogen and 7.3 kg (15 lb) of oxygen are used per
day to make up normal loss of crew cabin atmosphere to space
and metabolic usage. The cabin atmosphere caution and warn-
ing light is illuminated for cabin pressure below 13.8 psia or
above 15.4 psia, ppO2 below 2.7 psia or above 3.6 psia, oxy-
gen flow rate above 5 lb per hour, or nitrogen flow rate above
5 lb per hour. An alarm will sound if the pressure decreases at
0.08 psi per minute or greater, indicating a dangerous cabin
leak. The normal cabin pressure loss rate (dP/dT) is 0 psi per
minute, plus or minus 0.01 psi, for nominal operations; that
is, the small leak rate is well below the detection threshold
for the caution and warning system. Two cabin relief valves
in parallel provide overpressurization protection of the crew
module above 16 psi differential (psid). The positive pressure
relief valve opens at 16 psid and re-seats at 15.5 psid. About
1 h and 30 min before lift-off, the crew module cabin is pres-
surized to approximately 16.7 psi to check for leaks in the
crew cabin and to assess relief valve function. Should the crew
cabin pressure ever become lower than the pressure outside
the crew cabin, as might occur during a rapid descent, two
negative pressure relief valves in parallel will open at a dif-
ferential of 0.20.7 psid, permitting flow of ambient pressure
into the crew cabin.
Decompression
Decompression is a serious concern in space and is one of the
three emergency (Class I) alarms on the International Space
Station (ISS); the other two are fire and toxic atmosphere.
Decompression alarms prompting emergency crew action
sound when a pressure differential of greater than 1.0 psi/hour
is detected and the pressure drops 0.4 psi (21 mmHg). Cabin
depressurization may be part of nominal procedures, such as
staged decompression of the cabin prior to an EVA, depres-
surization of the airlock to final EVA suit pressure, or cabin
equalization following atmospheric reentry. Contingency
depressurization can result from structural penetration from
a collision with orbital debris or a micrometeoroid, structural
failure of a valve, module, or seal, collision with an approach-
ing spacecraft, or procedural error. Because of the pervasive
risk of orbital debris impact and the complexity of determin-
ing risk and minimizing damage of associated hypervelocity
impacts, a detailed discussion on this topic is warranted.
Orbital Debris
Orbital debris is composed mainly of derelict spacecraft and
upper stage launch vehicles, payload carriers, debris from upper
stage explosions or collisions, solid rocket motor effluents, and
249
tiny flecks of paint released by thermal stress or small particle
impacts. Objects greater than 10 cm in diameter are referred
to as large objects and are routinely detected and tracked
from the ground and cataloged for comparison with viable
spacecraft orbits. Objects between 1 and 10 cm in diameter
may be detectable but are not large enough for tracking and
avoidance maneuvers. These are referred to as risk objects;
they carry sufficient kinetic energy to inflict major structural
damage on manned spacecraft. Over 9,000 objects larger
than 10 cm are known to exist in earth orbit, and estimates for
the number of particles between 1 and 10 cm in diameter are
greater than 100,000. Objects smaller than 1 cm in diameter
are most commonly referred to as small debris or microd-
ebris. The number of particles smaller than 1 cm probably
exceeds tens of millions.
Orbital debris fragments are typically composed of alumi-
num (density 2.78 g/cc3) with an average size of 0.5 mm in
diameter. The estimated mass of synthetic objects orbiting
within 2000 km of the Earths surface is about 2,000,000 kg.
These objects are in mostly high inclination orbits and pass
one another at an average relative velocity of 10 km/sec (about
22,000 mph). In contrast to spacecraft debris, natural meteor-
oid flux is much lower, with only about 200 kg of meteoroid
mass within 2000 km of the Earths surface at any given time.
Meteoroid mass consists mainly of particles averaging 0.1 mm
in size with a density of 0.5 gm/cc3, traveling at a greater
velocity of 20 km/s.
The trajectories of large orbital debris objects may be deter-
mined and are tracked routinely by the U.S. Space Surveil-
lance Network (SSN) using ground based radars and optical
telescopes. This allows for planned avoidance maneuvers for
propulsive spacecraft to avert collisions. Although ground-
based optical systems are intended for tracking satellites
above 5000 km, they are capable of detecting orbital debris
at lower altitudes with a resolution of about 5 cm at 500 km
altitude. The Haystack Radar is able to obtain statistical data
on debris flux for particles 1 cm and larger at 500 km altitude.
The Goldstone Deep Space Network radars are capable of
detecting 2 mm objects at 1000 km altitude, although their
primary mission is to monitor deep space probes. Optical sys-
tems have fields of view ranging from 1 to 6 degrees while the
most sensitive radars (Haystack and Goldstone) have fields of
view of a few hundredths of a degree.
The lifetimes of satellites and debris in Earth-orbit are a
function of altitude (atmospheric density) and ballistic coef-
ficients. The denser the object, the less the object will react to
atmospheric drag. An object with a large area and low mass
(e.g. aluminum foil) will decay much faster and have a shorter
orbital life than a fragment with a small area and a high mass
(e.g. ball bearing). Satellites in circular orbits at altitudes of
200400 km reenter the atmosphere within months unless
reboosted. At 400900 km orbital altitudes, orbital lifetimes
range from years to hundreds of years depending upon the
mass and area of the satellite. The combination of a vari-
able atmosphere and unknown ballistic coefficients of space
250
objects makes decay and reentry prediction inexact. Dur-
ing the peak solar cycle, occurring every 11 years, greater
atmospheric drag and enhanced natural decay rates occur as
increased solar activity heats and expands the Earths upper
atmosphere. With this heating, the upper atmosphere density
increases below 600 km, causing orbits of satellites and debris
to decay more rapidly depending on altitude and size.
Orbital debris from fragmentation may result from explo-
sion or collision between orbital objects [1]. Explosive mech-
anisms include catastrophic failure of internal components
(such as batteries), propellant-related explosions (high energy
explosions), failure of pressurized tanks (low energy explo-
sions), and intentional destruction. Low energy explosions
typically produce fewer small objects than high-energy explo-
sions. In LEO, a hypervelocity collision would typically pro-
duce many more small objects than a high-energy explosion
since the impact and resultant shock wave melts and vapor-
izes satellite materials. Spacecraft failure due to orbital debris
impact has not been definitively documented, although it is
the prime suspect in the breakup of Kosmos 1275 based on
the size and velocity distribution of the fragments following
the breakup.
A primary spacecraft design driver is the determination
of an acceptable level of risk. The specified level of risk of
manned space programs from Apollo to the present has varied
FIGURE 12.2. The relative populations of orbital debris items based on particle or fragment size, determined as cross-sectional flux per
m2 of exposed surface area per year. Orbital debris curve is determined by tracking radars and impact analysis for altitudes between 300
and 600 km. For comparison, the flux of natural material (meteoroids) is shown. The vast majority of objects larger than 1 cm are of
artificial origin
J.B. Clark
from .01 to .05 probability of penetration over the lifetime of
the space system. The actual level of risk experienced by these
spacecraft was significantly less than specified because other
design requirements made the spacecraft structurally more
robust. Earlier manned space programs only addressed the
natural meteoroid environment, while the Space Shuttle and
ISS address both the natural meteoroid and the orbital debris
environments. The ISS has been designed to protect critical
areas against the highest probability particles of 1.4 cm and
smaller, which accounts for 99.8% of the debris population.
Figure 12.2 illustrates the flux of orbital debris based on par-
ticle or fragment size. Flux is much lower as size increases,
and it is seen that objects greater than 1 cm in size are largely
of artificial origin.
The effects of orbital debris collisions depend on veloc-
ity, angle of impact, and mass of the debris. Most impact-
ing particles will be the size of grains of sand, which will
cause degradation of sensitive surfaces such as optical
lenses and solar panels. For example, Russian engineers
reported it necessary to replace window covers on the Mir
station and to shield its exterior light bulbs due to damage
from orbital debris. For debris less than 0.01 cm, surface
pitting and erosion are the primary effects. Debris of sizes
0.011 cm produce significant impact damage, depending
upon system vulnerability and defensive design provisions. For
12. Decompression-Related Disorders: Pressurization Systems, Barotrauma, and Altitude Sickness
FIGURE 12.3. Impact damage to shuttle nose cone (left) and outer window (right) resulting form orbital debris impact
debris larger than about 0.1 cm, structural damage becomes
an important consideration. Objects larger than 1 cm can
produce catastrophic damage.
It is currently practical in LEO to shield against debris par-
ticles up to 1 cm in diameter and a mass of 1.46 g (0.05 oz).
For larger debris, shielding becomes impractical due largely
to the mass of the shielding material, and the only useful
strategy is collision avoidance. Examination of Space Shut-
tle exterior surfaces has provided direct evidence of small
orbital debris impact after each mission [2]. The Shuttle win-
dows leading edges, and radiator panels on the payload bay
doors experience impacts that are observable postflight, as
evidenced by small pits and craters as seen in Figure 12.3.
The Long Duration Exposure Facility, launched and retrieved
by the Space Shuttle, remained in orbit for 69 months. On
post-landing examination, its surface was covered with more
than 32,000 impact craters visible to the unaided eye, the larg-
est being about 0.63 cm in diameter. Analysis indicates that
approximately one-half of the larger craters were of orbital
debris origin and one-half were meteoroids. Nearly all of the
smallest craters are due to orbital debris, primarily aluminum
oxide flakes.
Risk reduction plans include shielding structures such as
optical surface covers against the highest probability impact-
ing particles, and improving collision avoidance maneuvers.
For the Space Shuttle, a warning envelope is generated when
an object is forecast to enter a volume 25 km ahead or behind
and 10 km above, below or to the side of the spacecrafts pro-
jected flight path. When the object is forecast to enter a vol-
ume 5 km ahead or behind or 2 km above, below, or to the
side, a propulsive collision avoidance maneuver is initiated.
Hypervelocity impact testing is used to determine the
effects of shape, density, and velocity of impacting particles
251
on spacecraft systems and to establish impact modeling meth-
ods. Although involving velocities of only up to 7 km/sec, one
third of typical orbital impact velocities, these models allow
analysis of the response of spacecraft to internal shock-wave
propagation, material phase change, deformation, perforation,
and long-term structural effects. NASA uses a computer model
called BUMPER to determine risks of meteoroid and orbital
debris impact damage and critical penetration for spacecraft.
This applies to overall risk of collision as well as the most
likely areas impacted. The forward and side surfaces with
respect to the velocity vector (direction of travel) of ISS are
exposed to the highest concentration of orbital debris impacts.
As such, these areas are designed with the heaviest shielding
to increase the protection of crew and critical equipment.
The risk of debris impact compromising cabin atmosphere
is represented as Probability of No Penetration (PNP) and is
defined as the probability of not sustaining a critical penetra-
tion over a 10-year lifespan of ISS. The PNP changes with
vehicle attitude and its corresponding cross-sectional area
with respect to the velocity vector. As ISS is assembled and
additional research modules added, more cross-sectional area
will be exposed and vulnerable to impact debris and the PNP
will decrease. The latest predictions based on BUMPER cal-
culations show a PNP of 0.67 for the 10-year period following
first element launch. Assessed PNP calculated for the 15 year
lifetime of the ISS is 0.52, equating to a 48% risk of penetra-
tion. Most of these events would involve subacute pressure
losses that will be amenable to recovery procedures, such as
sealing off the affected module. In contrast, the chance of sta-
tion evacuation due to a more devastating meteoroid or debris
collision over the 15-year lifetime of ISS is estimated at 15%.
Penetration hazards may be divided into three major threats to
the vehicle and crew: hazards due to wall breach, fragmentation,
252
and atmospheric compromise [3]. Wall breach hazards include
depressurization, cabin atmosphere venting, and structural failure
of the pressure vessel. Fragment hazards arise from the primary
object (micrometeor or orbital debris) or more likely second-
ary fragments damaging critical vehicle components or injuring
crew. Atmospheric hazards include shock wave overpressure
(blast), temperature, and flash effects. Loss of vehicle attitude
control could occur with a new directional propulsive force
stemming from cabin atmosphere venting, depending on size of
breach (thrust) and location with respect to center of spacecraft
mass (moment arm). Decompression events in space can range
from barely detectable pressure loss to catastrophic events. Cabin
decompression occurred with the collision of a Progress cargo
vessel with the Mir space station during the Mir-24 mission in
1997. In this instance, the crew quickly isolated the leaking mod-
ule from the remainder of the station and continued the mission.
A more devastating event occurred with the decompression of the
Soyuz 11 capsule on reentry due to a procedural error, resulting
in the deaths of cosmonauts Dobrovolsky, Volkov, and Patsayev
in 1971. In this case, the crew did not have adequate access to
isolate the leak.
Survivability of the pressure vessel is crucial; closely
related to survivability is the concept of redundancy. Redun-
dant systems are physically separated on a spacecraft, allow-
ing damage to one or more systems while still allowing the
spacecraft to continue functioning. The optimum protection
system includes the best combination of shielding, mission
design, operations, and redundancy on the basis of expected
safety benefits, weight requirements, spacecraft reliability,
performance levels, and costs. Recent advances in material
science, such as composites, ceramics, fabrics, and layered
materials, have allowed new methods of constructing space-
craft pressure vessels that may be more resilient to impact
damage and catastrophic failure. These advanced materials
could also produce less secondary hazard debris and could
capture collision products.
Decompression also represents a significant threat during
Extravehicular Activity (EVA), where the margin for mishap
is extremely narrow. Suit failure, accidental puncture, or col-
lision of hypervelocity micrometeoroid debris may result in
catastrophic loss of pressure in the Extravehicular Mobility
Unit (EMU) space suit. The EMU operates at 4.3 psi using
100% oxygen. If the EMU suit pressure drops below 3.9 psi,
the EMU secondary oxygen pack switches to a purge mode
to maintain a survivable internal pressure. This pressure can
be maintained for up to 30 min with a hole less than 4 mm
diameter, allowing for translation back to the airlock. A hole
greater than 4 mm diameter is considered critical, as the abil-
ity of EMU life support systems to maintain pressure is over-
whelmed.
Orbital debris objects greater than 0.35 mm in size travel-
ing at 10 km/s will penetrate the EMU suit, and particles over
1.5 mm will likely produce a critical leak. Due to the relatively
small cross-sectional area of a suited EVA crewmember and
the limited time period for EVA sorties, the risk of a collision
J.B. Clark
resulting in a critical penetration is relatively small. Based on
orbital debris flux in LEO and the orbital altitude of ISS, the
Bumper model has predicted penetration rates during EVA
operations of 1 in 3500 for a single 6-h EVA, and 1 in 8 over
the projected 2,700 h of EVA during the life of ISS. Odds of a
critical leak scenario (>4 mm) are estimated at 1 in 16,800 for
a single 6-h EVA and 1 in 38 over the 2,700 h of EVA during
the life of ISS. In examining the possible kinetic energy of the
impacting particle (1/2 mass times velocity squared), a 1 mm
object traveling at 10 km/s would deliver 80 J and may impart
an incapacitating injury, and a 1.7 mm particle at 10 km/s
would deliver 400 J, potentially causing fatal injuries.
Physical Factors of Decompression Events
Decompression may be slow or rapid depending on the incit-
ing event. A slow decompression can occur when a leak devel-
ops in a pressure seal between modules. A slow leak may be
below the threshold for pressure sensor detection, typically
0.01 psi/min. In such a case, a slow leak would be evidenced
by a measured increase over time in consumable gas supplies
used to maintain vehicle pressure. If undetected and allowed
to progress, a slow leak could result in insidious hypoxia.
Rapid decompressions are more dangerous, resulting from a
perforation of the pressure vessel or failure of a port, valve,
or hatch. In a rapid decompression, occupants are exposed to
risk of hypoxia, decompression sickness, ebullism syndrome,
gastrointestinal gas expansion, and hypothermia. High veloc-
ity and turbulent winds create the possibility of injury by fly-
ing debris, impact with cabin structures, or extraction through
the breach in the pressure vessel. Factors that influence crew
survivability include rate of decompression (hole size), time
of useful consciousness (cabin pressure), crew injury or loss at
time of decompression, crew reaction time, and crew distribu-
tion with respect to hole and escape route.
Consequences of rapid cabin depressurization include
noise, fogging, temperature change, and flying debris. Rapid
air mass movement to a vacuum results in noise ranging from
a hiss to a loud explosive bang, hence the term explosive
decompression. Sudden decreases in temperature or pres-
sure, or both, reduce the amount of water vapor the air can
hold; during rapid decompression water vapor may instantly
condense out of the air, appearing as fog. Rapid decompres-
sion results in temperature drop, which for an aircraft in
the upper atmosphere is followed by equilibration with the
colder outside air temperature. Upon decompression, airflow
velocity increases as it approaches the hull breach, often
with such force that dislodged items are extracted through
the opening.
Inter-module hatch position may influence crew survival
in a cabin depressurization. Hatches on isolatable modules
typically remain open on the ISS to allow ease of access dur-
ing normal operations and rapid egress during a contingency.
An open hatch prolongs the decompression time for a given
platform by exposing the entire habitable volume to the leak,
12. Decompression-Related Disorders: Pressurization Systems, Barotrauma, and Altitude Sickness
allowing greater mobility in responding to the situation but
increasing the duration of venting and subsequent thrusting
of the spacecraft. Closed hatches significantly reduce crew
efficiency during normal operations and may impede rescue
efforts. With catastrophic hull breach however, closed hatches
allow improved chance for survival for those in the pressur-
ized segments. The critical issue is the time between inciting
event and subsequent decompression to a pressure that is no
longer survivable and compared with the time for the crew
to respond with emergency procedures. Crew response to a
depressurization event centers on isolation of the leaking seg-
ment and rescue of injured crew.
Two basic rescue strategies are available to the crew of
a large space platform. In the heroic rescue, all efforts are
expended to recover the injured until the rescuers succumb.
In the greater good strategy, efforts continue until the res-
cuers are jeopardized and the hatches are closed to preserve
a survivable atmosphere. Based on computer simulations,
the best approach for reducing crew loss from depressur-
ization is leaving hatches open and distributing crew in dif-
ferent modules during sleep. Leak isolation procedures for
the ISS are based on a planned hatch closure sequence and
monitoring of the rate of pressure change. The decision to
abandon or remain on board the spacecraft is based on suc-
cess of leak isolation efforts and reserve time (time avail-
able for crew to respond to troubleshooting the leak). For
ISS, evacuation would be initiated when the atmosphere
reaches 9.5 psia or the reserve time is less than 15 min. In
the course of the initial leak isolation of the Mir stations
Spektr module during the 1997 collision and depressuriza-
tion event, astronaut Mike Foale roughly determined initial
depressurization rate by monitoring his own sensation of
Eustachian tube popping. Crewmembers may also use the
sound and feel of rushing air to determine leak location and
hasten leak isolation.
Factors Controlling the Rate and Time
of Decompression
The principal factors that govern the total time of decompres-
sion for a given breach include the cabin volume, size of the
opening, the pressure ratio, and the pressure differential. The
decompression time within a larger cabin volume will be lon-
ger than that of a smaller cabin. For a given cabin volume, the
cross-sectional area of the opening dictates the decompression
rate and time.
In spacecraft operations, the change in pressure per unit time
or rate of pressure change (dP/dt) obtained from downlinked
information available in the Mission Control Center (MCC)
is used to estimate how long it takes for the cabin to reach a
certain pressure. A simple estimate of this time is given by the
equation below. This method gives only a close approxima-
tion because pressure change is not a linear function from one
atmosphere to vacuum, and flow may be influenced by fluid
dynamics particular to the shape of the hole.
253
Time to reach P2 (minutes) = (P1 P2)/(dP / dt( (P1 + P2) / 2 P1) )
P1 (psia) = Initial Cabin Pressure
P2 (psia) = Target Cabin Pressure
dP/dt (psi/min) = Rate of Pressure Change (at the initial
cabin pressure)
The pressure of stabilization (POS) is the pressure that can be
maintained with a given leak; POS is reached when air mass
flow into the habitable volume is equal to air mass flow out.
The POS is dependant upon the amount of gas able to flow
into the cabin with the pressure regulators and is ultimately
limited by the amount of gas available:
POS(psia) = (dP / dtin P1)/(dP / dtout)
Where P1 (psia) = Initial Cabin Pressure, dP/dtout (psi/min) =
Rate of Pressure Change at Initial Cabin Pressure, and dP/dtin
is determined by the combined mass flow of O2 and N2 into
the cabin.
Physiological Effects of Rapid
Decompression
Hypoxia
Hypoxia is the dominant physiological hazard associated
with loss of pressure from a habitable volume. The primary
concerns with hypoxia are performance decrements with
partial depressurization, and eventual catastrophic failure
of oxygen exchange with complete depressurization to
vacuum. Rapid reduction of ambient pressure produces a
corresponding drop in the partial pressure of oxygen and
reduces the alveolar oxygen tension. An accentuated effect
of hypoxia after decompression is due to (1) a reversal in
the direction of oxygen flow in the lung; (2) diminished
ventilation (prolonged exhalation); (3) decreased cardiac
output (impaired venous return). Hypoxia is discussed in
detail in Chap. 22.
Hypothermia
The cabin temperature drop associated with decompression
may result in hypothermia-related injuries, with the extent
and severity dependent on final temperature and associated
injuries following decompression. For example, with rapid
decompression from sea level to 50,000 ft (15,240 m), the
temperature transiently drops from 68F (20C) to 76F
(60C). Hypothermia exacerbates the effects of hypoxia.
Evolved and Trapped Gas Disorders
A major threat from atmospheric pressure reduction is the devel-
opment of evolved gas disorders (decompression sickness and
ebullism) and trapped gas disorders (pulmonary over-inflation
syndromes and barotrauma). Decompression sickness is an ill-
ness that follows reduction in environmental pressures sufficient
254
to cause formation of bubbles from gases dissolved in body tis-
sues. Evolved and trapped gas disorders can occur together when
associated with severe pressure reduction. A man accidentally
decompressed to an equivalent altitude of 74,000 ft (22,555 m)
for 35 min in an industrial vacuum chamber sustained a ruptured
lung, massive decompression sickness, and ebullism. Five hours
following the accident he was still unconscious; he was treated
with a modified U.S. Navy Treatment Table 6A (see Figure 11.2)
in a hyperbaric recompression chamber. He eventually made a
full recovery. Serum levels of the enzyme creatine phosphokinase
(CPK) peaked at 8,000 units 2 days after the accident, suggest-
ing substantial soft tissue barotrauma [4]. In another instance of
exposure to physiologic vacuum (pressure less than 47 mmHg),
a NASA technician evaluating an EVA suit sustained a rapid
decompression to hard vacuum in an environmental space simu-
lation chamber. Prior to losing consciousness, he first noted bub-
bling on his tongue and eyes as the fluid on these mucus surfaces
sublimated. He was recompressed to sea level within seconds
and suffered no untoward sequelae.
Pulmonary Over-inflation Syndromes
The pulmonary over-inflation syndromes are disorders caused
by gas expanding within the lung, resulting in alveolar rupture.
These syndromes include arterial gas embolism, pneumotho-
rax, mediastinal emphysema, subcutaneous emphysema, and
pneumopericardium. The lungs are one of the most vulner-
able organs during rapid decompression. Whenever a rapid
decompression exceeds the inherent capability of the lungs
to evacuate gas, a transient positive pressure will temporarily
build up in the lungs relative to the ambient atmosphere. If the
escape of air from the lungs is blocked or seriously impeded
during a sudden drop in cabin pressure, intrapulmonary pres-
sure can rise rapidly enough to rupture lung tissues and cap-
illaries. Intrapulmonary pressure differential of 1.51.9 psi or
80100 mmHg (109136 cm H2O) over 0.10.2 s has resulted in exerted upon it, as seen in the following equation:
alveolar rupture in animal studies [5]. Human cadaver studies
have shown that a gradient of only 7081 mmHg (95110 cm
H2O) is needed to rupture the lung [6]. Alveolar rupture may
result if the rapid depressurization occurs during momentary
breath holding, as during swallowing or yawning, or if there is
localized pulmonary obstruction, as from asthma or secretions,
and may recur in susceptible individuals [7]. Pulmonary bul-
lae are particularly susceptible to alveolar rupture because of
reduced alveolar wall surface tension. Large pulmonary bullae
and asthma are screened out in primary astronaut selection.
Expanding gas trapped in the lung may enter tissue spaces,
causing mediastinal emphysema, subcutaneous emphysema,
pneumothorax, and pneumopericardium. Gas escaping into
and accumulating in the pleural or pericardial spaces can result
in emergent conditions. Tension pneumothorax may be life
threatening and require urgent thoracostomy as well as admin-
istration of 100% O2. Diagnosis of tension pneumothorax in
the space environment would be based primarily on exam and
clinical symptoms as X-ray capability is currently not available
J.B. Clark
on orbit. Preliminary experiments with a portable ultrasound
device used during parabolic flight have shown that it is pos-
sible to detect pneumothorax by loss of movement between the
visceral and parietal pleura [8]. A diagnostic ultrasound flown
on ISS as part of the Human Research Facility could be used to
evaluate pneumothorax. Crew Medical Officers, crewmembers
specially trained to respond to inflight medical events using
onboard systems and hardware, are trained to perform needle
thoracostomy based on clinical indications.
Pneumopericardium is rare and is usually detected only
with radiographs. The presence of subcutaneous emphysema,
typically noted by palpable crepitus over the site, should lead
to a search for underlying over-inflation conditions. Arterial
gas embolism (AGE) is caused by trapped air forced through
ruptured blood vessels in the lungs and passing directly into
the arterial circulation. Onset of AGE is usually sudden and
dramatic following depressurization. The heart and brain with
their high perfusion requirements are the organs most suscep-
tible to life-threatening arterial gas embolism. Cerebral arte-
rial gas embolism presents with significant neurological signs
and symptoms, including unconsciousness, dizziness, paraly-
sis or weakness, sensory loss, blurry vision, or convulsions.
Trapped Gas Barotrauma
Exposure to decreasing ambient pressure causes the gas pres-
ent in body cavities to expand. Impediments to expansion of
trapped gas in air spaces in the middle ears, sinuses, teeth, and
gastrointestinal tract result in earache, sinus pain, toothache, or
abdominal pain. Essential conditions for barotrauma include a
gas-containing enclosed space, particularly if walled with rigid
bony structure, and ambient pressure reduction at a rate beyond
the capacity of the enclosed space to equalize with the changing
atmosphere. Boyles Law states that with a constant tempera-
ture the volume of a gas is inversely proportional to the pressure
P1 V1 = P2 V2
According to Boyles Law, gases trapped in body cavities
tend to expand as pressure decreases and contract as pressure
increases. The potential for barotrauma is more likely early
in pressure reduction from sea level or one atmosphere abso-
lute (ATA), where the greatest fractional pressure excursions
occur. Pain is more likely to occur during a rapid cabin pres-
sure loss than during a slow decompression. Factors encoun-
tered in the space environment, such as oxygen-enriched gas
mixtures and microgravity-associated fluid shifts, may also
influence inner ear barotrauma. The major barotrauma syn-
dromes are discussed below.
Gastrointestinal Tract Barotrauma
The gastrointestinal (GI) tract normally contains gas at a
pressure equivalent to the surrounding atmospheric pressure.
The stomach and large intestine contain considerably more
12. Decompression-Related Disorders: Pressurization Systems, Barotrauma, and Altitude Sickness
gas than the small intestine. Most GI gas comes from swal-
lowed air and, to a lesser degree, from digestive processes
(fermentation, decomposition). Digestion of vegetables and
fruit commonly produces gas. Chewing food thoroughly can
reduce air swallowed during meals. Relief from trapped GI
gas is obtained by belching or passing flatus. GI tract gas is
primarily nitrogen, with lesser percentages of oxygen, carbon
dioxide, hydrogen, methane, and hydrogen sulfide. Discom-
fort from gas expansion within the digestive tract is frequently
experienced with rapid decrease in atmospheric pressure and
may produce severe pain if distension is significant.
Abdominal distress from expansion of trapped gases within
the GI tract is a potential danger during very rapid or explo-
sive decompression. Rapid decompression might be accom-
panied by sudden emesis, as the gastric bubble seeks pressure
relief. An altered level of consciousness (e.g. from accompa-
nying hypoxia) could predispose to aspiration and chemical
pneumonitis. Displacement of the diaphragm by expanding
stomach gas may impede respiratory movements. Distention
of abdominal organs may stimulate the vagus nerve, resulting
in cardiovascular depression, reduction in blood pressure, and
even shock.
Barodontalgia
The onset of toothache associated with pressure change, bar-
odontalgia, usually occurs during initial ambient pressure
reduction from 14.7 psi to 128 psi. Pain is invariably relieved
upon repressurization, which distinguishes it from pain in the
upper jaw due to maxillary barosinusitis, which worsens with
repressurization. Barodontalgia is usually associated with pre-
existing dental pathology, such as imperfect fillings, pulpitis,
and carious teeth; completely normal teeth are not affected.
Expansion of trapped air under restorations in the absence of
underlying pathology is responsible for only a very small pro-
portion of barodontalgia cases.
Sinus Barotrauma
The paranasal sinuses are air filled, relatively rigid, bony
cavities lined with mucous membranes that connect with
the nose by small openings (ostia). If the sinus openings are
obstructed by swelling of the mucous membrane lining (con-
gestion, infection, or allergic condition), polyps, or redundant
pharyngeal tissue, pressure equalization becomes difficult or
impossible. The opening to a sinus cavity is small compared
to the Eustachian tube and unless the pressure is equalized
during pressure excursions, extreme pain may result. In about
90% of cases, pain develops during repressurization, hence
for space operations is more likely following an EVA as a
crewmember repressurizes from the low operating pressure
of the suit to a 14.3 psi sea level equivalent cabin atmosphere.
During depressurization the expanding air usually forces its
way out past the obstruction. During repressurization, how-
ever, the relative negative pressure within the sinus cavities
255
may effectively lock the natural ostia, resulting in buildup of
pressure and barotrauma.
Sinus blocks among aviators most often occur in the fron-
tal sinus (70%), followed by the maxillary sinus. Maxillary
sinusitis may produce pain referred to the upper teeth and
may be mistaken for toothache. Sinus problems are usually
preventable by frequently performing an equalization maneu-
ver during repressurization and avoiding pressure changes if
congested. If a sinus block occurs during repressurization, the
repressurization should be stopped and a forceful Valsalva
maneuver (closing the mouth, pinching the nose shut, and
blowing gently) should be attempted. If this does not clear the
sinus the individual should return to a lower pressure and per-
form normal Valsalva maneuvers during repressurization; the
subsequent repressurization rate should be slowed. Individu-
als with a relatively large volume of air in the mastoid sinuses
are usually less tolerant to pressure changes.
Treatment for acute sinus barotrauma, whether on the
ground or in space, is based on decongestants and antibiotics
[9]. Repeated barotrauma should be evaluated with computed
tomography (CT) scan of the sinuses when available. Functional
Endoscopic Sinus Surgery (FESS) may be useful in evaluation
of repeated sinus barotrauma in aviators and astronauts.
Ear Barotrauma (Barotitis)
Eustachian Tube Function
The eustachian tube (ET) is ~37 mm long and connects the
middle ear with the nasopharynx. The lateral or tympanic end
of the ET is bony and usually open, whereas the medial or
pharyngeal end is cartilaginous, slit-like, and closed when
relaxed, acting like a one-way flutter valve. Opening of the ET
occurs with contraction of the palate lifters (the levator pala-
tini) and palate tensor muscles (tensor palatini) during acts
of chewing, swallowing, or yawning and by direct air pres-
sure. The cartilaginous and bony portions meet at an obtuse
angle in the narrowest portion of the tube. The most common
cause of acute ET dysfunction is edema or tissue hypertrophy
from infection, inflammation, or allergy. Chronic dysfunction
is usually associated with anatomic abnormalities, such as
scarring and chronic disease. An acute, unexplained unilateral
dysfunction in an older person could be due to a tumor in the
nasopharynx.
The nasopharynx soft tissues surrounding the membra-
nous ET are influenced by gravity. An upright posture aids
tubal patency while a recumbent position can compromise
a marginally patent ET, and a head down attitude can result
in positional obstruction. In space flight ET function may be
compromised by head congestion from cephalad fluid shifts
during the early phase of the mission. Once fluid shifts associ-
ated with early adaptation to microgravity have resolved, ET
function should not be adversely affected.
Symptoms of ET dysfunction are generally fullness in the
ear, mild intermittent discomfort or pain, and a mild decrease
256
in hearing. On otoscopic examination, the tympanic mem-
brane (TM) shows some retraction with either a normal
appearance or slight hyperemia of the vascular strip. The short
process of the malleus is prominent or foreshortened, and the
malleus may angle more posteriorly than usual. In chronic
cases, there is a dimple or retraction of the pars flaccida of
the TM, indicating negative pressure. Silent or undiagnosed
sinusitis can be associated with ET dysfunction, and barotitis
media is directly related to ET dysfunction. As the outside
pressure decreases, greater relative middle ear pressure forces
open the flutter valve at the pharyngeal end of the ET every
0.3 psi to 3.5 psi (15180 mmHg) relative differential. During
repressurization, the collapsed pharyngeal end prevents air
from entering the ET. Increasingly negative middle ear pres-
sure builds and holds soft tissues together. Active opening of
the ET must be accomplished before the differential pressure
reaches 1.51.75 psi (8090 mmHg), or muscular action can-
not overcome the suction effect on the closed ET, and the tube
is locked. Relative negative pressure retracts the TM and pulls
on the delicate mucosal lining, leading to effusion and hem-
orrhage. Pain may be severe, with nausea and occasionally
vertigo. On rare occasions rupture of the TM has resulted in
syncope or shock.
Evaluation of Eustachian Tube Function
The act of swallowing often causes a clicking or crackling
sound, which is made when the moist tissues of the ET
pop open. This sound can be heard by the person or ascul-
tated with a stethoscope placed on the ear and listening for
a crackling sound when the person swallows. Astronauts
have used this ear popping as a subjective measure of pres-
sure changes, such as during the depressurization follow-
ing collision between the Progress resupply vessel and the
Mir space station.
The risk of barotrauma increases with a history of nasal
or middle ear disease, otologic surgery, upper respiratory
infection (URI), perforation, cholesteatoma, chronic use of
decongestant nasal sprays, and previous barotrauma. Mid-
dle ear pathology, which varies with the rate and magnitude
of pressure change, is associated with negative pressure
and includes mucosal hemorrhage and congestion, edema,
serous and hemorrhagic effusion, and leukocyte infiltra-
tion within the middle ear mucosa. The inwardly displaced
TM also undergoes vascular congestion followed by vessel
rupture and interstitial hemorrhage or formation of bullae.
Pressure differentials as low as 0.6 psi (30 mmHg) have
been shown to cause minor barotrauma. TM rupture most
commonly occurs in the anterior portion, over the middle
ear orifice of the ET. Significant force may also cause an
annulus rupture.
Otoscopic appearance can range from TM retraction with
backward displacement of the malleus, a prominent short pro-
cess, and anterior and posterior folds, to hyperemia or hem-
orrhage of the tympanic membrane with varying amounts of
J.B. Clark
serous and sanguineous fluid visible behind the membrane.
The Teed barotrauma classification scheme stages the clinical
observations and quantifies sequential damage [10].
Grade 0 no visible damage
Grade 1 congestion redness around umbo (2 psi/100 mmHg
differential)
Grade 2 diffuse congestion redness of TM (23 psi/100
155 mmHg differential)
Grade 3 hemorrhage within the TM
Grade 4 extensive middle ear hemorrhage with blood and
bubbles (air/fluid level) behind TM
Grade 5 entire middle ear filled with dark blood
Optimally, evaluation techniques would allow identi-
fication of susceptible individuals prior to exposure to
potentially damaging pressure excursions. Static acoustic
impedance tympanometry prior to altitude exposure did not
identify individuals who developed otic barotrauma during
flight but was useful in confirming barotrauma following
flight, although no more useful than taking a history and
performing an ear examination [11]. Assessment of TM
impedance just before and after diving showed a transient
but significant increase in middle ear compliance for dives
to different depths, suggesting a reversible impairment of
the recoiling capacity of the TM elastic fibrils [12]. Pre-
launch examinations will detect acute or chronic disorders.
For long duration space flight (over 30 days), the onboard
crew medical officer is trained to perform ear examinations
prior to EVA.
Ear Barotrauma Syndromes
Pressure-Related Ear Block
An ear block may occur when middle ear pressure is unable
to equalize with ambient air pressure. This normally occurs
because the lower orifice of the ET, which operates as a one-
way flutter valve, fails to function adequately. Swelling of
the ostia from an upper respiratory infection or the cephalad
fluid shift that occurs in microgravity may also contribute to
ET dysfunction. The difference in pressure will cause the TM
to bulge outward as ambient pressure decreases and bulge
inward as ambient pressure increases. An ear block is much
more likely to occur as ambient pressure increases because
the ETs valve-like action allows gas to pass more readily
out of the inner ear than into it. When the ambient pressure
is reduced, middle ear pressure increases, and the eardrum
bulges outward until an excess pressure of 0.20.3 psi (12
15 mmHg) is reached and there is a sensation of ear fullness.
A small amount of air is forced out of the middle ear into the
ET, and the TM resumes its normal position. As the pressure
is released, there is often a click or pop audible to the individ-
ual. Variability in ET lumen size and muscular activity, along
with pharyngeal inflammation or mass effects, may result in
widely varying ET opening times.
12. Decompression-Related Disorders: Pressurization Systems, Barotrauma, and Altitude Sickness
Symptoms of an ear block include ear fullness, pain, muffled
hearing, dizziness, or tinnitus. Middle ear pressure equalizes
naturally with swallowing, yawning, or tensing the oropharyn-
geal muscles that open the ET orifice. If relief is not obtained by
this method, a Valsalva maneuver forces air through the closed
ET into the middle ear and equalizes the pressure. If a pressure
differential of 1.51.75 psi (8090 mmHg) develops across the
middle ear, voluntary maneuvers may be unsuccessful in equal-
izing middle ear pressure. Relief can be obtained by return to a
lower pressure followed by a slower repressurization.
Post Oxygen Exposure Delayed Ear Block
Crewmembers who have breathed O2 enriched air or 100% O2
during a prebreathe prior to staged decompression, during an
EVA, or following extended oxygen mask use as protection
against atmosphere contamination may develop an earache
several hours after O2 use, even though they can clear their
ears adequately. The high O2 concentration largely replaces
air in the middle ear. Cells lining the middle ear gradually
absorb oxygen due to its diffusion properties, which partially
reduces middle ear pressure if there is not a widely patent ET.
While awake an individual relieves the pressure differential
by periodic swallowing, which opens the ET, and equilibrates
middle ear pressure with ambient pressure. During sleep the
middle ear may not be ventilated sufficiently to keep the pres-
sure equalized. Ear pain may awaken an individual from sleep
or may be noticed upon awakening. The symptoms sometimes
include a sensation of ear fullness, pain, and bubbling sounds
from accumulation of fluid in the middle ear. The condition is
usually self-limiting and relieved by an autoinflation maneu-
ver. Prevention of post-oxygen exposure ear block includes
performing an equalization maneuver like the Valsalva fre-
quently during the first 2 h after O2 use to lower the O2 con-
centration by flushing the middle ear with ambient air. EVA
crewmembers are specifically briefed on this concern.
End of Day Barotrauma
Repeated asymptomatic mild barotrauma may result in ET
swelling that eventually progresses to symptomatic baro-
trauma as ET function worsens. Although unlikely in space
flight, this may affect astronauts during ground activities such
as water immersion EVA training.
External Auditory Canal (EAC) Barotrauma
Obstruction of the external auditory canal by foreign body,
cerumen, a tight-fitting cap, or an earplug may result in baro-
trauma to the EAC during a pressure change. The isolated
space in the EAC develops relative negative pressure with an
increase in ambient pressure, which can result in canal and or
TM edema and hemorrhage. Outward displacement of the TM
with decrease in ambient pressure can also result in TM trauma.
Treatment for EAC barotrauma is the same as for otitis externa,
with antibiotic drops and systemic treatment if warranted.
257
Alternobaric Facial Paralysis
Transient facial paralysis is a rare complication associated
with acute middle ear barotrauma, such as would occur with
rapid or explosive cabin depressurization. The likely mecha-
nism is injury to the dehiscent tympanic portion of the facial
nerve from direct pressure or bubbles that transit through the
chorda fenestrum following overpressurization of the middle
ear space. Alternobaric facial paralysis usually resolves spon-
taneously. Return to flight duties would be contingent on
resolution of muscle function, particularly the protective eye
blink and ability to purse the lips required to perform a Val-
salva maneuver.
Caloric Vertigo
A dramatic and common cause of vertigo underwater is a
transient effect due to unequal caloric stimulation of the two
labyrinths from water entering the external canal asymmetri-
cally [13]. Such a syndrome would not be expected during
spaceflight operations but may complicate water immersion
EVA training, scuba, and water survival activities.
Alternobaric Vertigo (ABV)
A number of vestibular conditions resulting in vertigo may be
related to diving and space operations, including optokinetic
illusions, asymmetric vestibular stimulation, inner ear baro-
trauma, decompression sickness, breathing gas toxicity, high
pressure neurological syndrome, sea or space motion sickness,
and noise-induced vestibular stimulation [14]. Lundgren first
coined the name alternobaric vertigo after he found that 26%
of Swedish sport divers surveyed had experienced pressure
related vertigo, most frequently during or immediately after
ascent from diving [15]. He also reported a similar phenom-
enon in aviators [16]. Alternobaric vertigo is the sensation
of initial unequal pressure in the ear followed by dizziness
and vertigo during exposure to changing pressure. A pressure
difference of 0.9 psi (45 mmHg) between the two ears will
asymmetrically increase labyrinthine discharge and induce
nystagmus and vertigo. Many individuals who reported
alternobaric vertigo with diving could reproduce their symp-
toms by performing a Valsalva maneuver. Symptoms usually
last a few seconds to 15 min. Symptoms may be managed
by stopping the pressure change and utilizing equilibrating
mechanisms until resolved. Loud tinnitus, vertigo, nystag-
mus, and bone conduction loss suggest labyrinthine window
rupture. Alternobaric vertigo is usually transient and, other
than momentary disorientation, would be unlikely to interfere
with spaceflight activities.
Inner Ear Barotrauma (IEB)
The inner ear, composed of semicircular canals, vestibule, and
cochlea, is embedded within the dense, compact petrous tem-
poral bone, or osseous labyrinth. Within the bony labyrinth is
a membranous labyrinth that contains endolymph fluid similar
258
in composition to intracellular fluid (high potassium). The
perilymphatic fluid, similar in content to cerebrospinal fluid
(high sodium), is outside of the membranous labyrinth. Figure
12.4 shows the normal anatomy of the ear. IEB should be sus-
pected in cases of barotrauma associated with sensory neural
hearing loss, tinnitus, or vertigo. IEB may persist and lead to
perilymph fistula (PLF).
IEB usually occurs during rapid pressure changes and
associated equalization problems. IEB may be due to
mechanical disruption of Reissners membrane, which
separates the endolymphatic from perilymphatic space.
Mechanisms for round and oval window rupture include
rise in endolymphatic pressure (from increased intra-
cranial pressure via the cochlear aqueduct) or increase in
perilymphatic pressure. In the explosive mechanism, intralab-
yrinthine fluid pressure is greater than middle ear pressure.
A Valsalva maneuver may increase the intralabyrinthine fluid
pressure, via the cochlear aqueduct or the internal auditory
canal, but fail to equilibrate the middle ear pressure and therefore
increase the differential between the middle ear, perilymph,
FIGURE 12.4. Simplified anatomy of the human ear, emphasizing in particular the structures vulnerable to pressure changes
J.B. Clark
and endolymph. The implosive mechanism results from a
rapid increase in middle ear pressure, with inward displace-
ment of the stapes footplate, resulting in rupture of the round
or oval window and perilymph fistula. The implosive injury
mechanism is less common than the explosive injury.
When perilymphatic fluid leaks into endolymphatic spaces,
auditory and/or vestibular symptoms may develop. Symptoms
of a PLF including sudden onset of postural vertigo with or
without hearing loss persisting after barotrauma, positional
nystagmus, gaze evoked nystagmus, and reduced speech dis-
crimination and speech reception threshold [17]. Therapy for
PLF includes bed rest and avoidance of straining or activi-
ties that could increase intracranial pressure. The anatomic
location of PLF has been documented clinically from rupture
of both the oval and round windows, and membranous tears
within the cochlea have been described post-mortem [18,19].
A fourth source of perilymphatic leakage is the microfissure,
the existence of which has been surgically confirmed [20].
The timing of exploratory tympanotomy for PLF is con-
troversial. Some specialists recommend immediate exploration,
12. Decompression-Related Disorders: Pressurization Systems, Barotrauma, and Altitude Sickness
although most would observe over 2448 h for signs of wors-
ening [21]. If no improvement occurred in four to five days,
most recommend surgical exploration [22]. Exploratory tym-
panotomy for suspected PLF with surgical closure as indi-
cated resulted in improved hearing in 49% (23% improved
to serviceable range) [23]. Ninety-five percent of the patients
had elimination or decrease in their vestibular symptoms to
the extent that it no longer interfered with their daily activi-
ties. The high rate of postoperative PLF recurrence has been
reduced with a new surgical technique for PLF closure using
laser graft-site preparation, an autologous fibrin glue but-
tress, and a program of postoperative activity restriction,
with recurrences dropping from 27% to 8%. Complete reso-
lution or significant symptomatic improvement occurred in
89% of patients with vertigo and/or dizziness and in 84% with
disequilibrium.
IEB related hearing loss may result from impaired micro-
circulation of the auditory artery, resulting in inner ear neu-
roepithelium damage. Irreversible hearing loss from IEB
depends on the extent of damage to the organ of Corti [18].
Vertigo associated with IEB or PLF may be more severe and
prolonged than alternobaric vertigo and could be associated
with nausea and vomiting; hence it is more of a concern for
critical spaceflight operations, particularly EVA.
Inner Ear Decompression Sickness
Inner ear decompression sickness (IE-DCS) and IEB can result
in similar symptoms and lead to permanent severe vestibulo-
cochlear deficiency and can occur together [24,25]. IE-DCS
is related to the formation and growth of inert gas bubbles
within microvessels and membranous labyrinth fluids follow-
ing rapid pressure reduction leading to ischemia of the venous
circulation, hemorrhage, and protein exudation. IE-DCS is
usually associated with deep dives but can occur at shallow
depths [26]. Although more common in diving operations, it
is sometimes seen in the aerospace environment. Associated
symptoms of IEB include equalization problems with forceful
Valsalva, and pre-existing nasal or sinus complaints. IE-DCS
is usually not associated with pressure equalization problems
and is not associated with non-otologic neurologic findings.
Treatment for IE-DCS and IEB is different, one treatment
being harmful for the other condition. Recompression therapy
is indicated as soon as the diagnosis of IE-DCS is made and is
contraindicated in IEB [25].
Hearing Loss (Barotrauma Versus Decompression
Sickness)
Middle ear barotrauma (MEBT) and inner ear barotrauma
(IEBT) may be caused by pressure excursions associated
with aviation, EVA, and diving, and in fact are major causes
of diving-induced hearing loss. MEBT should be treated by
prevention and symptoms should be treated by limiting pres-
sure changes and judicious use of decongestants. Otologic
manifestations of decompression sickness (DCS) occur rarely
259
but should be considered as a cause of pressure-related hear-
ing loss. When hearing impairment with or without vestibular
symptoms is an isolated manifestation of type II DCS, it may
be difficult to distinguish from middle and inner ear baro-
trauma resulting in labyrinthine window fistula. Immediate
recompression treatment with hyperbaric oxygen may result
in complete recovery [27]. A perilymph fistula may cause
IEBT. Although reports of IEBT are relatively few, this entity
should be kept in mind and differentiated from other causes of
diving-induced hearing loss [28].
Maneuvers to Equilibrate Middle Ear Pressure
A number of equalization or autoinflation maneuvers have
been developed to aid ET function. Individuals exposed to
variable pressure environments can develop ET awareness
by listening for the crackle and pop of the ET opening. Indi-
viduals can practice equalization or autoinflation maneuvers,
although Shupak showed that successful autoinflation at sea
level does not necessarily reflect middle ear pressure equal-
ization ability during descent in a dive [29].
Valsalva Maneuver
A common procedure for self-inflation of the middle ear space
is the Valsalva maneuver. During the Valsalva maneuver, the
nose and mouth are closed and the vocal cords are open. By
exhaling against closed anatomical outlets, air is forced into
the nasopharynx, with the increased pressure forcing open the
ET and increasing the pressure in the middle ear space. This
can be observed as a bulging of the tympanic membrane on
otoscopic examination, especially in the posterior superior
quadrant. Conditions that make the Valsalva maneuver less
effective include flexion of the head forward, rotation of the
head to one side, pressure on the jugular vein, and placement in
the prone or head down position. Obstacles encountered during
the Valsalva maneuver include straining so hard that venous
congestion in the head prevents opening of the ET, and clos-
ing the vocal cords, which prevents pressure from reaching the
pharynx. One method to prevent vocal cord closure is to close
the nose with the fingers and attempt to blow the fingers off the
nose. The buildup of pressure should be rapid and sustained for
1 s to prevent venous congestion that reduces the efficiency of
ET function. The adequacy of pressurization can be assessed by
observing the fleshy portion above the nares balloon outward
above the pinched fingers. The cheek muscles should be kept
tight and retracted, not puffed out. With this technique, gradi-
ents of 2.674.45 psi (140230 mmHg) can be achieved. A rare
complication of this method is round or oval window rupture.
Frenzel Maneuver
The Frenzel maneuver, taught to Luftwaffe dive-bomber pilots
during World War II, involves closing the glottis, mouth, and
nose while simultaneously contracting the floor of the mouth
and the superior constrictor muscles. This maneuver actually
260
takes less pressure to open the ET but is more difficult to learn.
To perform one must thrust the lower jaw anteriorly, close the
lips, slightly open the jaw, move base of the tongue against the
soft palate, which compresses air in the nasopharyngeal space.
The nostrils are pinched closed and a K or guh sound is Ototoxic antibiotic drops (aminoglycoside antibiotics) should
made. This maneuver raises the back of the tongue and ele-
vates the larynx, effectively making a piston out of the back of
the tongue and compressing air in the back of the throat. The
bobbing the Adams apple technique may be practiced by
watching the nose inflate and the larynx move up and down.
This technique is quick, can be done anytime during the respi-
ratory cycle, does not inhibit venous return to the heart, and
can be repeated many times in rapid succession.
Toynbee Maneuver
If there is no TM movement with Valsalva, a small, quick retrac-
tion movement of the TM may be accomplished by the Toynbee
maneuver. The Toynbee maneuver involves swallowing with
the nose pinched closed. Joseph Toynbee first identified the
crackling sound one hears with opening of the ET during swal-
lowing. An initially positive nasopharyngeal pressure rapidly
becomes a negative pressure, which helps unlock the ET. The
muscles in the back of the throat pull open the ET and allow air
to equalize if a gradient is present. The swallowing necessary
to effect this maneuver can be difficult while breathing dry air.
This technique is not recommended for rapid pressure changes,
as there is no margin for error if the ET does not equalize on
first effort. If a middle ear squeeze is already occurring, it will
be more difficult for the ET to be pulled open.
Beance Tubaire Voluntaire (BTV) Maneuver
The French Navy developed a technique for middle ear
equalization called voluntary tubal opening. This technique
involves teaching an individual to contract the soft palate and
upper throat muscles similar to a yawn. This technique only
works during gradual and predictable pressure changes.
Edmonds Maneuver
This technique is accomplished by combining pressurization
(Valsalva or Frenzel maneuver) with jaw thrust or head tilt,
which more effectively opens the ET.
Treatment of Middle Ear Barotrauma
Treatment is directed toward equalization of pressure, relief of
pain, and prevention or treatment of infection. Pressurization
should be stopped and, if possible, the individual returned to
a pressure where an equalization maneuver can be attempted,
followed by a more gradual pressure change. If barotitis symp-
toms are present without otoscopic signs, pressure environments
should be avoided until all symptoms are resolved, usually
within a week. Individuals with symptoms and objective signs
but no TM rupture may require a longer recuperation. Antibiot-
ics are unnecessary unless purulence is noted in the nasopharynx
J.B. Clark
or the patient notices a worsening of the pain or purulent otitis
is evident by exam. Most cases of frank TM perforation heal
spontaneously. Oral decongestants may be helpful. Antibiotics
are used if clear signs of upper respiratory infection are present.
not be used, as there is a possibility of round or oval window
rupture. Antibiotics should be used for 710 days.
Politzerization or tubal insufflation may be necessary in
cases of thick effusion and ET dysfunction or inability to per-
form an equalization maneuver. Politzerization is the mechan-
ical inflation of the middle ear performed for treatment of
acute ear and sinus blocks, chronic ET dysfunction, or middle
ear disease. An autoinflation device (Otovent) improved neg-
ative middle ear pressure after flight. Seventy-three percent
of adults and 69% of children with an unsuccessful Valsalva
maneuver showed improved or normalized middle ear pres-
sure by inflating the device [30].
The politzerization procedure requires a source of pressure
from an air pump, pressurized air supply, or rubber bag with
a one-way valve. A rubber Politzer bag is useful where a pres-
surized air supply is not available. An air pump should have a
variable control of the pressure and pressure gauge. If no gauge
is present, the starting pressure should just be sufficient to blow
off a lightly applied finger. When a pressure gauge is available,
initial attempts should be made with 10 psi or less (500 mmHg).
A metal or plastic tip is used to seal and deliver the pressure
into the nose. If the patient has a very thin TM, lower pressure
must be tried first. An explanation to the patient is important to
ensure cooperation and prevent sudden movements that could
injure the nose. The politzerization tip should be inserted into
a nostril far enough to afford a good seal without striking the
vestibule or septal walls. The opposite naris is occluded, and the
patient is instructed to repeat K-K-K-K-K loudly and sharply as
a 1-s burst of air is delivered. A characteristic soft palate flutter
sound is heard if the procedure is performed correctly. If no
results are obtained with this technique, the patient is instructed
to swallow: as the thyroid notch rises up, air pressure is again
applied in the nose. For people who have trouble with a dry
swallow, a sip of water may be given. With the water technique,
prolonged or high pressure might cause damage to the tympanic
membrane, and there is a remote possibility of round window
and inner ear damage.
The patients TM should be assessed before and after infla-
tion to determine the success of the procedure. Although not
usually recommended, if symptoms have not resolved after
2 or 3 weeks of intensive therapy, persistent serous fluid may be
removed by needle aspiration, and thick mucous or organized
blood can be removed by myringotomy.
Return to Duty
Mild middle ear barotrauma symptoms should subside within
12 weeks. When equalization function has returned, no
abnormal bubbling sounds are heard, and hearing is normal,
a return to a variable pressure environment can be safely
12. Decompression-Related Disorders: Pressurization Systems, Barotrauma, and Altitude Sickness
accomplished. Decongestants may help relieve mild to mod-
erate barotrauma symptoms. The occasional use of inhaled
decongestants, like oxymetazalone (Afrin) spray, may be
used for prevention or treatment of mild congestion, but a
spray should not be used more than three consecutive days,
to prevent rebound nasal congestion. In one observational
study, twenty patients who suffered IEB while scuba diving
but continued to dive against medical advice were assessed on
an interim basis for 112 years. All patients were instructed
on methods of maximizing ET function, and no further dete-
rioration of auditory or vestibular function was noted. Based
on these preliminary results, recommending that no further
diving after IEB may be unnecessarily restrictive [31]. Upper
respiratory infections and allergic rhinitis increase the risk of
barotrauma in the changing pressure environment. Crewmem-
bers with persistent inner ear symptoms, difficulty with ear
clearing, or persistent nasal or sinus complaints should not
return to variable pressure environments [32].
Altitude Sickness
Altitude sickness occurs in non-acclimatized individuals above
3050 m (10,000 feet) and represents a spectrum of patho-
logic states initiated by an exaggerated vascular response to
hypoxia. Major discernible syndromes include acute mountain
sickness (AMS), high-altitude cerebral edema (HACE), high-
altitude retinal hemorrhage, and noncardiogenic high-altitude
pulmonary edema (HAPE). With the exception of retinopathy,
gradual ascent to allow acclimatization can lessen or prevent
symptoms of high-altitude illness [33]. A number of thorough
reviews of the pathophysiology of acute mountain sickness,
high altitude pulmonary edema, high altitude cerebral edema,
and high altitude retinal hemorrhage are available in the lit-
erature [3439]. The potential for AMS in space operations
exists during staged decompression prior to EVA or following
inadvertent pressure reduction due to partial loss of spacecraft
atmosphere. There has been concern about altitude sickness
during shuttle depressurization to 10.2 psi for planned EVA
operations due to a seeming increase in the frequency of
reported headaches among crewmembers during this lower
pressure period. This was addressed on a recent Shuttle mis-
sion (STS 103), when a portable pulse oximeter was used to
evaluate the crew. Arterial oxygen saturations remained in
the mid 90% range during the lower pressure stage; hence it
is unlikely these headaches stem from altitude sickness. The
increased incidence of headaches seen during the 10.2 psi
phase raises speculation on other potential causes, such as
a change in the atmosphere control system or increased off-
gassing of volatile materials due to the lower pressure.
Acute Mountain Sickness
Acute mountain sickness (AMS) affects otherwise healthy indi-
viduals who ascend rapidly to high altitude where the partial
261
pressure of oxygen (pO2) in the air is reduced. The pathophys-
iology of acute mountain sickness (AMS) may stem from both
hypoxia and hypobaria of high altitude. AMS is reproduced in
an altitude chamber, demonstrating that rarefied atmosphere
is the etiology. Normal effects of altitude exposure include
exertional dyspnea, spontaneous diuresis, nocturnal periodic
breathing (Cheyne-Stokes respirations), frequent awakening
at night, and weird or vivid dreams. The symptoms of AMS
include headache, poor appetite, nausea and vomiting, light-
headedness or dizziness, fatigue, weakness, and poor sleep,
resulting from disturbances in fluid balance brought about by
tissue hypoxia. Hypoxia is often accompanied by an increase
in ventilation (hypoxic ventilatory response), which lowers
CO2 and results in cerebral vasoconstriction and reduced cere-
bral blood flow. The increased ventilation results in greater
oxygen saturation and delivery. Cognitive deficits may be due
to hypoxic effects on sympathetic neurotransmitter function,
and depletion of acetylcholine may contribute to fatigue [40].
The exact incidence of AMS is unknown, although approxi-
mately 25% of lowland visitors to moderate-elevation ski areas
suffer at least mild AMS. There is no race or sex predilection,
but age has a small effect, with younger adults slightly more
susceptible than older adults. Carbon monoxide (CO) poison-
ing may mimic the signs and symptoms of altitude illness and
must be considered if circumstances allow for this possibility
[41]. In a small percentage of patients, AMS can lead to high-
altitude pulmonary edema (HAPE) or high-altitude cerebral
edema (HACE). AMS can be prevented by a sufficiently grad-
ual pressure reduction, which is the best method. However, if
time is a limiting factor, there are several drug therapies that
provide relatively good protection.
Scoring Acute Mountain Sickness
Various systems have been devised to quantify AMS. Scor-
ing systems include both questionnaires (Hackett AMS
questionnaire, Lake Louise AMS self-report questionnaire,
Environmental Symptoms Questionnaire ESQ II and ESQ
IV) and clinical investigation (Lake Louise AMS clinical and
functional AMS assessment). The Environmental Symptoms
Questionnaire (ESQ) contains nine symptom groups, with two
factors representing AMS. The first factor contains symptoms
indicative of cerebral hypoxia and is labeled AMS-C. The
second reflects respiratory distress and is called AMS-R [42].
The AMS scores range between 0 and 9 for the Hackett AMS
score 0 and 38 for the Hackett ESQ II AMS score, and 0 and
13.7 for the Hackett ESQ IV AMS score. The AMS scores
range between 0 and 10 for the Lake Louise AMS self-report,
and 0 and 2 for both the Lake Louise AMS clinical assess-
ment score and the Lake Louise functional score. At moderate
altitude (2,940 m), oxygen saturation correlated inversely with
Hacketts AMS score but there was no significant correlation
with the Lake Louise AMS score, and the Lake Louise AMS
score overestimated AMS incidence at moderate altitudes.
Hacketts AMS score, along with a structured interview and
262 J.B. Clark

physical examination, remains the gold standard for evaluat- TABLE 12.1. Space AMS worksheet.
ing AMS incidence [43]. Mission elapsed time (MET)/Cabin pressure
Savourney et al evaluated the correlation of several acute Symptoms:
mountain sickness (AMS) scoring systems. AMS was scored 1. Headache:
0 No headache
following a 9-h hypoxia exposure in a hypobaric chamber 1 Mild headache
(altitude 4,5005,500 m) that led to the development of AMS. 2 Moderate headache
In this study, AMS questionnaire scoring systems were with- 3 Severe, incapacitating headache
out significant differences between them and were highly 2. GI:
correlated to the clinical AMS assessment score [44]. The sen- 0 No GI symptoms
1 Poor appetite or nausea
sitivity and specificity of the Lake Louise score over 4 points 2 Moderate nausea/vomiting
was 78% and 93%, respectively [45]. The Lake Louise AMS 3 Severe nausea/vomiting, incapacitating
scoring system, used to assess AMS, correlated with maximal 3. Fatigue/weakness:
self-report score observed at altitude as well as the functional 0 Not tired or weak
report and clinical assessment scores in both laboratory and 1 Mild fatigue/weakness
2 Moderate fatigue/weakness
field conditions [46]. 3 Severe fatigue/weakness, incapacitating
An AMS worksheet has been developed for space flight, 4. Dizziness/lightheadedness:
which is essentially a modification of the Lake Louise AMD 0 Not dizzy
self-report questionnaire and clinical and functional assessment 1 Mild dizziness
(Table 12.1). This was conceived to support Space Shuttle flights 2 Moderate dizziness
3 Severe, incapacitating dizziness
involving staged decompression in anticipation of extravehicu- 5. Difficulty sleeping:
lar activity (EVA). Because there is little actual experience with 0 Slept well as usual
altitude sickness during space flight, and because some of the 1 Did not sleep as well as usual
basic AMS-associated symptoms such as headache and fatigue 2 Woke many times, poor nights sleep
are common during space flight independent of cabin pressure 3 Could not sleep at all
Total symptom score:
changes, scoring of these symptoms is not directly transferable. Clinical assessment:
However, determining a numerical score is useful for initial 6. Change in mental status:
assessment and monitoring treatment and resolution. This is 0 No change
discussed further in the final section of this chapter. 1 Lethargy, lassitude
2 Disoriented/confused
3 Stupor/consciousness
Acclimatization 7. Gaze/Eye movements:
0 Normal
Strategies to prevent AMS include allowing 2 days of accli- 1 Mild nystagmus; quickly remits/one direction
matization before engaging in strenuous exercise at high alti- 2 Moderate nystagmus; quickly remits/ > one direction
3 Severe nystagmus; sustained/any direction
tudes, avoiding alcohol, and increasing fluid intake. Physical 8. Facial edema:
conditioning exercise for patients older than 35 years is also 1 Mild edema
recommended before departure. A high-carbohydrate, low-fat, 2 Moderate edema
low-salt diet was thought to aid in preventing onset of AMS, 3 Severe edema
although in one study a high carbohydrate (68% CHO) diet for Total clinical assessment score:
Meds used in past 6 h:
4 days did not reduce symptoms of AMS in subjects exposed
to 8 h of 10% normobaric oxygen [47]. A study assessing car-
diovascular and respiratory physiological responses and AMS
Physical Conditioning
symptoms following induction to high altitude at 3,500 m
(11,483 ft) then to 4,200 m (13,780 ft) compared symptom The effect of previous physical conditioning on acquiring
onset and resolution with the time of altitude acclimatiza- acute mountain sickness at 3,000 m (9,840 ft) after 48 h was
tion. The acutely inducted group was transported by aircraft determined in a study by Honigman et al. Sea-level physical
to 3,500 m within 1 h, whereas the gradually inducted group activity (SLPA) was measured with a validated questionnaire
was transported by road over a period of 4 days. After 15 days assessing patterns of work, sporting, and leisure activities.
at 3,500 m, the subjects were transported to 4,200 m by road. Acute mountain sickness defined as three or more of the fol-
Physiological responses at 3,500 m were stable by day three lowing symptoms (headache, dyspnea, anorexia, fatigue,
in the gradually inducted group, whereas it took 5 days for the insomnia, dizziness, or vomiting) developed in 28%. No statis-
acutely inducted group. Acclimatization schedules of 3 days tically significant difference in mean SLPA scores was found
for the gradually inducted group and 5 days for the acutely between those with and without acute mountain sickness, or
inducted group are essential to avoid high-altitude illness at in individual SLPA indices (work, sport, or leisure). Habitual
3,500 m. Both the gradual and rapid induction groups took sea level physical activity does not appear to play a role in
3 days at 4,200 m to achieve acclimatization [48]. the development of altitude illness at moderate altitude in a
12. Decompression-Related Disorders: Pressurization Systems, Barotrauma, and Altitude Sickness
general tourist group [49]. In two French high altitude expe-
ditions (4,800 m/15,748 ft and 6,542 m/21,463 ft), there was a
positive correlation between periodic breathing and individ-
ual hypoxic ventilatory drive; the periodic breathing latency
decreased and sleep improved with acclimatization [50]. In a
study of retention of acclimatization, lowlanders acclimatized
at 4,300 m for 16 days returned to sea level and after 8 days
were re-exposed to 4,300 m in a hypobaric chamber for 30 h.
Retention of acclimatization after 8 days at low altitude was
sufficient to attenuate the incidence and severity of AMS upon
re-induction to high altitude [51].
Susceptibility
Variability in sensitivity to AMS among individuals is a well-
known phenomenon. A hypoxia challenge test (abnormal
cardiac or respiratory response to hypoxia, especially during
exercise) may identify the most clinically susceptible subjects,
who should be advised to increase acclimatization time and con-
sider taking prophylactic medication [52]. The measurement of
cardiac and respiratory responses to hypoxia (inspired O2 frac-
tion = 0.115) at rest and during exercise at a level of 50% maxi-
mum oxygen consumption (VO2 max) allows the detection of
subjects more likely to suffer from high altitude diseases. Moni-
toring of arterial oxygen saturation (SaO2%) with non-invasive
oximetry provides a simple, specific indicator of inadequate
acclimatization to high altitudes and may differentiate AMS-
resistant individuals from those with impending AMS.
Likely mechanisms involved in AMS susceptibility include
hypoventilation relative to normally acclimatizing individuals
and abnormalities of gas exchange [53]. A low hypoxic venti-
latory drive and an increased pulmonary vascular response to
hypoxia may be predisposing factors to AMS and high altitude
pulmonary edema. A low ventilatory response to hypoxia is
associated with an increased risk for high altitude pulmonary
edema, while susceptibility to acute mountain sickness may be
associated with a high or low ventilatory response to hypoxia
[54]. Individuals susceptible to high altitude pulmonary edema
also show increased hypoxia induced vasoconstriction of pul-
monary arterioles [55]. In addition, AMS susceptible individu-
als frequently lack the spontaneous diuresis normally seen at
altitude. In subjects who traveled to 4,500 m (14,763 ft), hypoxic
ventilatory response, alveolar carbon dioxide tension (PACO2),
and VO2max showed no correlation with AMS scores [56].
Susceptibility to AMS appears to be independent of endur-
ance training, but determined by the sensitivity of carotid che-
moreceptors to hypoxemia and the induced hyperventilation
and tachycardia. Exercising at high altitude is impeded during
the first days of exposure to altitude hypoxia by the symptoms
of AMS. Richalet et al investigated cardiac rate response at
an equivalent altitude of 4,800 m (15,750 ft) in subjects both
at rest and during 5 min of exercise at 50% VO2 max. Cardiac
response to hypoxia at rest is lower in climbers with severe
AMS than in those subjects without severe AMS, and similar
differences were observed during exercise [57].
263
Hypoxia and Simulated Microgravity
Loeppky et al. conducted a study of altitude illness in subjects
lying at 5 degrees head down bed rest (HDBR) to simulate the
fluid shifts and responses of microgravity. Subjects who lived
at 1,646 m (5,400 ft) were studied with and without HDBR dur-
ing 8 days at an actual altitude of 3,255 m (10,678 ft). Plasma
volume (PV) decreased with altitude-related hypoxia in both
groups but further decreased with HDBR. There were no dif-
ferences in electrolytes between HDBR and controls. Diuresis
occurred in both groups but was greater with HDBR than con-
trols. A rise in catecholamines was seen in controls and HDBR,
but only HDBR showed a significant rise in atrial natriuretic
peptide (ANP), which could account for the enhanced diuresis
and decreased PV seen with HDBR [58]. AMS symptoms of
headache, lightheadedness, insomnia, and anorexia were slightly
more prevalent with HDBR, while arterial oxygenation was not
seriously effected by HDBR [59]. The VO2 max increased by
9% without HDBR, but fell 3% after HDBR, which was signifi-
cant, but could be accounted for by inactivity. At altitude the
heart rate increase was enhanced and mean blood pressure was
lower in response to an orthostatic stress (60 degree head-up tilt
for 20 min) following HDBR, than head-up tilt without HDBR.
Head-down bed rest did not significantly impact the ability to
acclimatize to hypoxia in terms of pulmonary mechanics, gas
exchange, circulatory or mental function, nor was pulmonary
interstitial edema or congestion noted during HDBR.
Oxygen Prebreathe and Hydration Effects
AMS may be related to reduced diuresis but not to increased
water intake. In a study of water balance and acute mountain
sickness (AMS), subjects developing AMS over a 4-day expo-
sure at 4,350 m (14,272 ft) demonstrated reduced energy and
water intake, increase in total body water (TBW) and a reduc-
tion in total water loss. Subjects with AMS showed the biggest
shifts (at least 1 L) in extracellular water relative to TBW and
did not show increased urine output expected as compensation
for the reduced evaporative water loss at altitude [60]. In a study
of positive water balance during acute altitude exposure, no sig-
nificant difference in cardiovascular and ventilatory parameters
were seen between normal and overhydrated subjects exposed
to 4,570 m (14,993 ft) for 2 h. Prior O2 breathing reduced the
hyperventilatory and alkalotic responses to altitude, mitigated
the tachycardia response, and led to a drop in blood pressure
despite a similar arterial desaturation in the non-prebreathe
group. Reduced urine flow and increased urine osmolality
observed in two subjects at 4,570 m were not seen in the same
subjects at 4,570 m after O2 prebreathe [61].
Normobaric Hypoxia Versus. Hypobaric Hypoxia
Hypoxia can occur without pressure change, as would occur
if oxygen concentration fell below 20%, and normobaric
hypoxia (1 atm) may be different than hypobaric hypoxia.
264
Subjects exposed to normobaric hypoxia (14% O2) had the
same degree of arterial desaturation but a significantly greater
hyperventilatory response than with hypobaric hypoxia [61].
AMS symptom scores were higher with hypobaric hypoxia at
a simulated 4,564 m altitude for 9 h compared with either nor-
mobaric hypoxia or normoxic hypobaria at equivalent simu-
lated altitudes [62].
Respiratory Effects
Respiratory effects occur at altitude but do not appear to cor-
relate with AMS. In studies of pulmonary function at altitude,
forced vital capacity fell significantly during the first 2 days
of ascent and returned to normal after 3 or 4 days of stay at
4,600 m (15,092 ft). Forced expiratory volume in 1 s (FEV1) did
not change in any period. However, maximal expiratory flow
and maximal mid-expiratory flow rate significantly increased
and remained elevated during the 4-day stay. No correlation
was found between acute mountain sickness symptoms and
changes in ventilatory function [63].
Diurnal Effects
In subjects exposed to 79 h of hypoxia at 4,350 m (14,272 ft)
AMS scores showed remarkable diurnal variations, parallel-
ing plasma cortisol and red green color vision, with maximum
variations seen in the early morning. Cortisol diurnal rhythm
was maintained in hypoxia, although mean morning cortisol
concentrations were higher than in normoxia [64].
Cerebral Blood Flow
Decreased arterial partial oxygen pressure (PaO2) below a
certain level presents a strong stimulus for increasing cere-
bral blood flow. Cerebral vasodilatation and an increase
in cerebral blood flow are associated with acute mountain
sickness (AMS). Using transcranial Doppler (TCD), mean
middle cerebral artery velocity (MCA-V) showed a signifi-
cant increase while vasomotor reactivity (VMR) decreased
at 2,440 m (8,000 ft) [65]. Regional cerebral blood flow dur-
ing short-term exposure to hypoxia at simulated altitudes of
3,000 and 4,500 m for 20 min showed only the hypothala-
mus had increased blood flow, and this at 4,500 m but not at
3,000 m [66]. Middle cerebral artery velocity was assessed
by transcranial Doppler sonography (TCD) in subjects at
490 m, after rapid ascent to 4,559 m, and daily during a 72 h
stay at 4,559 m. Relative change of MCA-V at high altitude
was expressed as percentage of low altitude values. After
ascent to 4,559 m, overall MCA-V increased in subjects with
and without AMS, but the increase was higher in subjects
with AMS and reached statistical significance on day one
and two compared to healthy subjects. The rise of MCA-V
correlated inversely with arterial PO2 on days 2, 3, and 4.
MCA-V did not correlate with blood pressure, arterial PCO2
or hemoglobin [67].
J.B. Clark
Intracranial Pressure
Serial measurements of intracranial pressure have been made
indirectly by assessing changes in tympanic membrane dis-
placement on rapid ascent to 5,200 m. Acute hypoxia at
3,440 m was associated with a rise in intracranial pressure, but
no further difference was found at 4,120 or 5,200 m in sub-
jects with or without symptoms of AMS. Raised intracranial
pressure, though temporarily associated with acute hypoxia, is
not a feature of AMS with mild or moderate symptoms [68].
Hypoxia may alter cerebrospinal fluid (CSF) pressure com-
pliance, resulting in a greater increase in CSF pressure for a
given change in volume [40]. This may result in intracranial
hypertension with supine posture.
Biochemical Markers
Mechanical or inflammatory injury to pulmonary endothe-
lial cells may cause impaired pulmonary gas exchange in
AMS and high altitude pulmonary edema (HAPE). A marker
of endothelial cell activation, E-selectin, which is produced
only by endothelial cells, is increased after ascent to high
altitude (4,200 m) in hypoxemic climbers with AMS and
non-cardiogenic HAPE [69]. Serum concentrations of inter-
leukin-6 (IL-6), increased during altitude hypoxia while other
pro-inflammatory cytokines, including IL-1 beta, IL-1 receptor
antagonist (IL-1ra), IL-6, tumor necrosis factor (TNF) alpha,
and C-reactive protein (CRP) levels remained unchanged at
sea level and during 4 days of altitude hypoxia (4,350 m). The
serum IL-6 increases were related to arterial blood oxygen
saturation but not to heart rate or AMS scores. The major role
of IL-6 during altitude hypoxia may not be to mediate inflam-
mation but rather to stimulate erythropoiesis at altitude [70].
Exposure to altitude hypoxia elicits changes in glucose
homeostasis in the first few days at altitude. Insulin action
decreases markedly in the first 2 days but improves with pro-
longed exposure. Glucose, cortisol, and noradrenaline concen-
trations increased at altitude, while adrenaline, glucagon, and
growth hormone remained unchanged [71]. Aldosterone levels
were elevated on the first day, and atrial natriuretic peptide levels
were higher on both altitude days in subjects at 4,300 m. Alti-
tude and the exercise on ascent resulted in a marked decrease
in 24-h urine volume and sodium excretion. Aldosterone lev-
els tended to be lowest in subjects with low symptom scores
and higher sodium excretion. Atrial natriuretic peptide levels
at low altitude showed a significant inverse correlation with
acute mountain sickness symptom scores on ascent. No cor-
relation was found between changes in hemoglobin concentra-
tion, packed red blood cell volume, 24-h urine volume, or body
weight and acute mountain sickness symptom score [72].
Hypoxia has a suppressive effect on the renin-aldosterone
system; however, beta-adrenergic mechanisms do not appear
to be responsible for inhibition of renin secretion at high alti-
tude. The renin-aldosterone system may be depressed in sub-
jects exercising at high altitude, thereby preventing excessive
12. Decompression-Related Disorders: Pressurization Systems, Barotrauma, and Altitude Sickness
angiotensin I and aldosterone levels, which could favor the
onset of acute mountain sickness. Subjects performed a
standardized maximal bicycle ergometer exercise with and
without pindolol, a nonselective beta-blocker (15 mg/day) at
sea level, as well as during a 5-day period at high altitude
(4,350 m, barometric pressure 450 mmHg). During sea-
level exercise, pindolol caused a reduction in plasma renin
activity (PRA), an increase in plasma alpha-atrial natriuretic
factor (alpha-ANF) level, and no change in plasma aldo-
sterone. Compared with sea-level values, PRA and plasma
aldosterone were significantly lower during exercise at high
altitude. Alpha-ANF was not affected by hypoxia. With
beta-blockade at high altitude, exercise-induced elevation
in PRA was completely abolished, but no additional decline
in plasma aldosterone occurred [73].
Although acclimatization to environmental hypoxia is
necessary to achieve optimal physical performance at alti-
tude, scientific evidence to support the beneficial effects after
return to sea level is equivocal. Unfavorable physiological
responses to physical exercise at moderate altitude exposure
include decreased plasma volume, depression of hemopoie-
sis, increased hemolysis, increased sympathetically mediated
glycogen depletion, increased respiratory muscle work, and
hypoxia mediated immunosuppression [74]. Hypoxia also
generates inducible nitrogen oxide synthase, leading to gen-
eration of potentially damaging free radicals [75].
Associated Infectious Disease
In a study of AMS and infection in hikers walking to Mount
Everest base camp at 5,300 m (17,388 ft), 57% of subjects
developed AMS, and 87% experienced at least one symp-
tom of infectious disease. Coryza (75%), cough (42%), sore
throat (39%), and diarrhea (36%) were especially prevalent.
The incidence of AMS was greater among those with more
symptoms of infection, and the number of symptoms of infec-
tion experienced was positively correlated with AMS score
[76]. There was a 50% increase in the frequency of upper
respiratory and gastrointestinal tract infections during altitude
sojourns in high performance athletes assigned to a 4-week
altitude training camp at 1,5002,000 m [77]. Inflammation-
producing illnesses such as viral respiratory tract infections
contribute to development of high-attitude pulmonary edema
in children but not adults. Release of inflammatory mediators
associated with these illnesses may be tolerated at sea level
but may predispose children to increased capillary permeabil-
ity when superimposed on hypoxia and, possibly, cold and
exercise [78].
High Altitude Pulmonary Edema
High altitude pulmonary edema (HAPE), a severe form of
altitude illness that can occur in young healthy individuals, is
a noncardiogenic pulmonary edema that usually occurs within
25 days of acute exposure to altitudes above 2,5003,000 m.
265
Hypoxia constricts pulmonary vessels, resulting in an increase
in pulmonary vascular resistance. Hypoxic pulmonary hyper-
tension is generally moderate but may become severe during
HAPE and may be associated with right heart failure. Subjects
susceptible to high-altitude pulmonary edema present with a
slight increase in pulmonary vascular resistance at rest and
at exercise and may demonstrate enhanced pulmonary vascu-
lar reactivity to hypoxia [79]. Periodic breathing (PB) at high
altitude is slightly more frequent and arterial oxygen desatura-
tion more severe during sleep in subjects developing HAPE
during the first night spent at 4,559 m altitude. The signifi-
cantly lower arterial oxygen saturation in the HAPE group is
secondary to diminished gas exchange rather than ventilation
[80]. Pulmonary capillary wedge pressure is normal at rest,
and there is an excessive rise in pulmonary artery pressure
(PAP) that precedes edema formation.
Recent observations of high PAP in HAPE-susceptible
subjects who did not develop pulmonary edema after rapid
ascent to high altitude suggest that the inflammatory response
is a primary cause of HAPE rather than a consequence of
edema formation [34,81]. HAPE is often related to AMS. In a
study of pulmonary function and HAPE after 4 h of simulated
altitude exposure (4,400 m), three of four HAPE-susceptible
subjects developed acute mountain sickness (AMS) and two of
the three with AMS developed mild pulmonary edema [82].
Rapid ascent without prior acclimatization may result in
HAPE even in subjects with excellent tolerance to high alti-
tude. Although the hyperventilation response to hypoxia is ben-
eficial, HAPE can occur in susceptible individuals despite the
presence of a normal or high ventilatory response to hypoxia
[82]. Those with HAPE showed a small decrease in forced
vital capacity (FVC) and greater decrease in forced expira-
tory volume over 1 s (FEV1) and forced expiratory fraction
(FEF2575) after arrival at high altitude, with rales or wheezing
noted on physical examination. High ventilatory responses
to acute hypoxia occurred in two HAPE subjects. The six
non-HAPE subjects had minimal spirometry changes and did
not develop signs of lung edema. HAPE is associated with
high concentrations of proteins and cells in bronchoalveolar
lavage fluid, with both large (immunoglobulin M) and small
(albumin) molecular-weight proteins present [83]. An inflam-
matory response and/or a decreased fluid clearance from the
lung is likely, as bronchoalveolar lavage in advanced HAPE
patients shows an inflammatory response with increased cap-
illary permeability.
An increase in capillary permeability may be a consequence
rather than the cause of high-altitude pulmonary edema [84].
HAPE-susceptible individuals react to acute altitude expo-
sure with increased secretion of norepinephrine, epinephrine,
renin, angiotensin, aldosterone, and atrial natriuretic peptide.
This results in sodium and water retention, reduction of urine
output, increase in body weight, and development of periph-
eral edema. The hypoxic pulmonary vascular response is
enhanced in HAPE-susceptible subjects, favoring severe pul-
monary hypertension on exposure to high altitude. Susceptible
266
individuals can avoid HAPE by ascending slowly, less than
300350 meters per day above 2,500 m. Supplemental oxy-
gen and immediate descent are the primary treatment modali-
ties, but if descent is delayed and supplemental oxygen is not
available, treatment with the calcium channel blocker nife-
dipine is recommended until descent is possible. The prophy-
lactic administration of nifedipine prevents the exaggerated
pulmonary hypertension of HAPE-susceptible subjects and
thus prevents HAPE in most cases. Treatment of HAPE with
nifedipine results in a reduction of pulmonary artery pressure,
clinical improvement, increased oxygenation, decrease of the
alveolar arterial oxygen gradient and progressive clearing of
pulmonary edema on chest x-ray. The primary treatment of
HAPE is descent, evacuation, and administration of oxygen.
High Altitude Cerebral Edema
High altitude cerebral edema (HACE) is probably due to hypoxia-
induced changes in blood-brain barrier permeability, resulting
in vasogenic brain edema. HACE manifests a diverse array of
generalized and localized neurological symptoms and signs, such
as headache and impaired consciousness (confusion, lassitude,
mental status changes) [85]. HACE occurs above 4,500 m during
acclimatization, and at extreme altitudes above 7,500 m it is often
fatal [86]. AMS is a subacute form of the frank brain edema seen
in HACE, and differentiating between these two syndromes can
be difficult. AMS may be partially related to cerebral edema sec-
ondary to hypoxic cerebral vasodilatation and elevated cerebral
capillary hydrostatic pressure, resulting in reduced brain compli-
ance and compression of intracranial structures. These primary
intracranial events may elevate peripheral sympathetic activity
neurogenically in the lung and in the kidney [87]. The edema in
HACE is primarily intracellular cytotoxic edema but may also
have a component of vasogenic edema from leaking across the
blood brain barrier [40].
HACE is estimated to occur in about 1% of those persons at
risk. HACE should be suspected in a patient with symptoms
of AMS who develops gait ataxia (cannot walk heel-toe in a
straight line) or mental status changes. A combination of both
ataxia and mental status changes strongly suggests HACE.
Houston and Dickinson recognized a severe form of alti-
tude illness as cerebral edema where neurological signs and
symptoms dominated the clinical picture and recommended
rapid descent, intravenous dexamethasone or betamethasone,
hydration, pharmacological diuresis (furosemide), and hyper-
osmolar agents [88].
Treatment of Altitude Sickness
Carbonic Anhydrase Inhibitors
Acetazolamide is currently the drug of choice for prevention of
AMS, and numerous studies have demonstrated its effective-
ness when started 1224 h before ascent. Acetazolamide can
J.B. Clark
also be used to treat acute mountain sickness, and improve-
ment has correlated with increased arterial oxygen concentra-
tion. Acetazolamide (250 mg twice daily or 500 mg once daily
of a slow release preparation), taken before and during ascent
is probably the treatment of choice for AMS; it improves gas
exchange and exercise performance and reduces AMS symp-
toms. Acetazolamide (125 mg two or three times daily or once
at bedtime) has also been shown to reduce susceptibility to
AMS and the incidence of HAPE and HACE. Twelve climb-
ers attempting an ascent of Mt. McKinley (summit, 6,150 m)
who presented to the medical research station at 4,200 m alti-
tude with acute mountain sickness were randomly assigned to
receive acetazolamide, 250 mg orally, or placebo and again at
8 h. After 24 h, five of six climbers treated with acetazolamide
were healthy, whereas all climbers who received placebo still
had acute mountain sickness. The alveolar to arterial oxygen
pressure difference (PAO2PaO2 difference) decreased slightly
over 24 h in the acetazolamide group but increased in the
placebo group. Acetazolamide improved PaO2 over 24 h when
compared with placebo [89].
Acetazolamide is indicated for established AMS, although
faster acting carbonic anhydrase inhibitors such as methazol-
amide may be preferable. There is not extensive evidence
of the effectiveness of acetazolamide in combination with
other drugs such as steroids and calcium channel block-
ing drugs used for treating acute mountain sickness. Drug
combinations could have additive beneficial effects [90].
Acetazolamide (250 mg oral) was administered to subjects
at sea level and then on the day after arrival at high altitude
(4,360 m), and acetazolamide concentrations were measured
in whole blood, plasma, and plasma water. The elimina-
tion rate constant (lambda z) and clearance uncorrected for
bioavailability were significantly increased, while appar-
ent volume of distribution, mean residence time, and extent
of protein binding, were significantly decreased at altitude
[91]. In a double-blind study, the combination of sustained-
release acetazolamide (500 mg once daily) and low-dose
4 mg dexamethasone twice daily was more effective than
sustained-release acetazolamide alone in ameliorating the
symptoms of AMS after rapid ascent to high altitude (2 days
at 3,698 m followed by two more days at 5334 m). Oxygen
saturation decreased in both groups, but the decrease was
greater in the acetazolamide-placebo group [92].
Glucocorticosteroids
Dexamethasone (4 mg, four times a day) may be used for
short-term treatment or prevention of AMS but should not
be used for more than 23 days [93]. Dexamethasone may
prophylactically reduce symptoms of AMS, in part due to
its euphoric effect. Dexamethasone offers an alternative to
acetazolamide for those with sulfa intolerance [94]. Although
effective in treating cerebral symptoms of AMS, dexametha-
sone is not routinely recommended as a prophylactic agent
[95]. Dexamethasone effectively reduces AMS symptoms
12. Decompression-Related Disorders: Pressurization Systems, Barotrauma, and Altitude Sickness
but does not improve objective physiologic abnormalities
related to exposure to high altitudes and should only be used
when descent is impossible or to facilitate evacuation. Six
male subjects were exposed to a simulated altitude of 3,700 m
(barometric pressure 481 mmHg) in a hypobaric chamber for
48 h on two occasions to assess the efficacy of dexametha-
sone in the treatment of established acute mountain sickness.
Dexamethasone (4 mg every 6 h) or placebo was given in a
randomized, double blind, crossover fashion after diagnosis
of acute mountain sickness. Dexamethasone reduced AMS
symptoms by 63%, compared to 23% reduction by placebo.
In spite of this response, one subject developed mild cerebral
edema on brain CT after both placebo and dexamethasone.
Dexamethasone had no effect on fluid shift, oxygenation,
sleep apnea, urinary catecholamine levels, the appearance of
chest radiographs or perfusion scans, serum electrolyte levels,
hematological profiles, or the results of psychometric tests.
Dexamethasone treatment was complicated by mild hypergly-
cemia in all subjects [96].
Although dexamethasone has shown demonstrated effective-
ness against AMS, illness may recur with abrupt discontinu-
ation of the drug. In a randomized, double blind study, 2 mg
of dexamethasone given orally every 6 h, starting 1 h before a
1-hour helicopter flight from sea level to 4,400 m (400 mmHg),
did not prevent AMS. Subjects with moderate to severe AMS
treated with 4 mg of dexamethasone every 6 h orally or intra-
muscularly for 24 h all showed marked improvement at 12 h,
but if the drug was stopped symptoms increased 24 h after dis-
continuation [97]. In a double-blind, randomized trial compar-
ing acetazolamide 250 mg, dexamethasone 4 mg, and placebo
every 8 h as prophylaxis for AMS during rapid, active ascent
(elevation 4,392 m), the group taking dexamethasone reported
less headache, tiredness, dizziness, nausea, clumsiness, and a
greater sense of feeling refreshed, and reported fewer symp-
toms unrelated to AMS (runny nose and feeling cold). The
acetazolamide group differed significantly from other groups
at low elevations (1,3001,600 m) in that they experienced
more nausea and tiredness and were less refreshed. Prophylaxis
with dexamethasone can reduce AMS symptoms during active
ascent, and acetazolamide side effects may limit its effective-
ness as prophylaxis against AMS [98].
Calcium Channel Blockers Operational Approach to Acute Mountain
The calcium channel blocker nifedipine is effective for pre-
Sickness in Space
vention and treatment of HAPE, but nifedipine is not recom-
mended for prevention of AMS. In a double-blind study of
subjects receiving nifedipine or placebo during rapid ascent
to 4,559 m and a 3-day stay at altitude, lowering pulmo-
nary artery pressure (PAP) had no beneficial effect on gas
exchange and symptoms of AMS in subjects not susceptible
to HAPE. Pulmonary artery pressures (PAP) estimated by
Doppler echocardiography were significantly lower with nife-
dipine, but arterial PO2, oxygen saturation, alveolar-arterial
oxygen gradient, and AMS symptoms were not significantly
267
different between groups at high altitude [99]. Symptomatic
HAPE subjects at 4,559 m treated with nifedipine were able
to continue exercise at altitude without supplementary oxygen
and exhibited clinical improvement [100]. Prophylactic appli-
cation of slow release nifedipine, 20 mg every 8 h, prevented
HAPE in nine out of ten subjects following rapid ascent and
stay at 4,559 m. Seven of 11 subjects who received placebo
developed pulmonary edema at 4,559 m. Nifedipine lowered
pulmonary artery pressure and resulted in clinical improve-
ment in subjects suffering from radiographically documented
HAPE [101].
Hyperbaric Recompression
A number of portable recompression chambers, such as the
Gamow bag, have been developed for use in high altitude
operations, and AMS has been successfully treated with por-
table pressure chambers. Early pressurization to 150 mmHg
for 3 h of unacclimatized subjects who climbed from 1,030 to
4,360 m within 12 h did delay the onset of AMS slightly but did
not prevent or attenuate its severity. AMS score decreased and
SaO2 increased in the treatment group 15 min after leaving the
pressure chamber, whereas the control group had unchanged
AMS score and SaO2. The next morning, AMS score, HR,
and SaO2 were similar for both treatment and control groups
[102]. Climbers with AMS at 4,559 m above sea level were
randomly assigned to portable hyperbaric chamber treatment
for 1 h at 145 mmHg or dexamethasone (8 mg orally then
4 mg every 6 h). AMS symptoms (Lake Louise score, clini-
cal score, and AMS-C score) were assessed 1 h and 11 h after
beginning the different treatments. One hour of compression
caused a significantly greater relief of symptoms of AMS than
dexamethasone. In contrast, after about 11 h subjects treated
with dexamethasone had significantly less severe AMS than
those treated with compression. One hour of compression
at 145 mmHg, corresponding to a descent of 2,250 m, led to
short-term improvement but no long-term benefit. Treatment
with dexamethasone (oral dose of 8 mg followed by 4 mg
every 6 h) resulted in a longer-term clinical improvement.
Optimal efficacy should combine the two methods if descent
or evacuation is not possible [103].
Although AMS has not been documented in space, a pro-
tocol has been developed to implement during contingency
cabin depressurizations and to manage the AMS like symp-
toms that have been associated with planned depressuriza-
tion to 10.2 psia, seen during staged decompression prior to
EVAs performed from the Space Shuttle and ISS airlock.
Pressure reduction from sea level to 10.2 psi is accompanied
by increased oxygen concentration, usually 2425%, and is
hence a normoxic hypobaric exposure. Examining the Lon-
gitudinal Study of Astronaut Health (LSAH) database for the
268
first 89 Space Shuttle flights, 67% of crew experiencing this
lower pressure reported headache. Headache and fatigue are
often experienced during reduced cabin pressure operation on
board the shuttle. Headaches at the lower pressure may be due
to less effective air cleaning, offgassing from powered avion-
ics, residual space motion sickness, or stress associated with
workload preparing for an EVA.
The procedure for AMS in space, outlined in Table 12.2,
was developed particularly for EVA intensive shuttle missions,
such as ISS assembly flights and Hubble Space Telescope
servicing missions. This protocol uses a modified symptom
scoring system (Table 12.1), replacing ataxia, which cannot
be measured in space, with an analog measure of vestibular
cerebellar function that can be tested in microgravity. Oxy-
gen saturation is measured with a peripheral O2 saturation
monitor.
The only medication for the management of AMS in space is
the carbonic anhydrase inhibitor acetazolamide. The potential for
side effects has raised concerns about its use in space. Acetazol-
amide increases sodium and bicarbonate excretion, decreasing
extracellular bicarbonate resulting in hyperchloremia and meta-
bolic acidosis. Carbonic anhydrase inhibitors are sulfonamide
derivatives and may cause crystalluria, sulfonamide-like nephro-
toxicity, hematuria, dysuria, and oliguria. A significant concern
is an increase in calcium excretion, which may increase risk for
nephrolithiasis (renal calculi). Hyperuricemia can develop with
acetazolamide and precipitate gout. Adverse central nervous
system side effects of acetazolamide include drowsiness, seizures,
irritability, vertigo, confusion, and paresthesias. Paresthesias occur
frequently and are manifested as numbness, tingling, or burning in
the distal extremities and mucous membranes. Adverse GI effects
with acetazolamide include nausea, vomiting, diarrhea, exces-
sive thirst, and anorexia. Very uncommon but severe side effects
of acetazolamide include aplastic anemia and Stevens-Johnson
TABLE 12.2. Space AMS protocol.
I. Crew complains of AMS-like symptoms following cabin depressuriza-
tion below 14.7 psia.
II. AMS Worksheet (Table 12.1) is used to assess AMS Score (symptom
and clinical assessment).
III. If symptoms score is 5 or has worsened by 2 or more points when
compared to baseline at 14.7 psia and clinical assessment score is 3 or
has worsened by 1 point, measure SaO2 using pulse oximeter.
A. SaO2 > 94%
Not likely altitude sickness.
B. SaO2 < 94% and changed by 4 points.
Consider trial of O2 via personal oxygen supply mask.
1). Symptoms do not improve on O2 after 1520 min.
a. Not likely altitude sickness.
2). Symptoms improve on O2.
a. Continue O2 for total of 1 h.
b. Remove O2 after 1 h and observe.
3). Symptoms do not return.
a. Continue to observe.
4). Symptoms return.
a. Consider acetazolamide 125 mg to 250 mg every 812 h.
b. Continue acetazolamide for 12 days and reassess.
J.B. Clark
syndrome. Generally, these adverse effects occur infrequently
enough to warrant the use of acetazolamide terrestrially for AMS
with a favorable risk-to-benefit ratio. For space crews, typically
with no physician onsite, the diagnosis would have to be made
remotely and occurs in a setting with multiple other potential
causes of symptomology. The worksheet in Table 12.1 would be
carefully applied in such circumstances.
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13
Renal and Genitourinary Concerns
Jeffrey A. Jones, Robert A. Pietrzyk, and Peggy A. Whitson
Genitourinary (GU) disorders are pervasive in the adult popula-
tion and broadly include the diagnoses of 1520% of patients
who are discharged from hospitals in the United States. The
percentage is higher for ambulatory visits. Along with suscep-
tibility to the common disorders of the general population, the
GU system of astronauts is additionally vulnerable to space-
flight-related stresses, both in flight as well as immediately
preflight and postflight. These stresses may include rigorous
exercise, microgravity, dietary changes, limited availability
of drinking water, thermal stress, effects of other spaceflight-
related disorders such as space motion sickness, and influence
of medications used to treat other spaceflight-related disorders.
Some of these conditions may increase the risk of occurrence
of genitourinary disorders or complicate their presentation.
Exposure to microgravity causes a number of metabolic and
physiological changes. Fluid volume, electrolyte levels, and
bone and muscle undergo changes as the human body adapts
to weightlessness. Changes in urinary chemical composition
occurring as a part of this adaptation process may lead to the
potentially serious consequences of renal stone formation.
With the length of human exposure to microgravity extend-
ing as we maintain a permanent presence on the International
Space Station (ISS), the probability of GU-related illnesses
such as renal stones or infections will undoubtedly increase.
Exploration-class lunar missions for long-duration settlement
and missions to Mars will pose even greater challenges for GU
diagnosis and management as immediate return to Earth will
not be possible. This chapter reviews spaceflight influences on
GU function and disorders that might arise involving this sys-
tem and describes treatment methods and countermeasures.
Spaceflight Factors Influencing
the Genitourinary System
Body Fluid Balance
The dominant factor governing the physiological changes
associated with human space flight is microgravity, also
known as weightlessness. As might be expected, those
adaptive changes most affecting the GU system involve
fluid and electrolyte balance as these systems are reset
toward new homeostatic set points. These changes are
described in more detail in Chap. 27.
The first few days of space flight have much in common
with bed rest on Earth. The loss of the constant 9.8-m/s2 (32 ft/
s2) force of gravity found on Earth results in a redistribution
of body fluids toward the head and central circulation. The
bodys volume sensors perceive the resulting shift of fluids, a
consequence of redistribution, as an overload. Facial puffiness
and nasal stuffiness are common outward manifestations of
this fluid shift.
During the early accommodation to microgravity, crews
experience varying degrees of space motion sickness (SMS),
which lowers their fluid intakeeither due to nausea and
vomiting or diminished thirst [1]. The combination of fluid
redistribution and decreased fluid intake contributes to: (1) a
diminished plasma volume (on average, about 12% less than
normal) [2] and (2) reduced urine output 72 h after arriving in
weightlessness. Reduced urine output often persists through-
out the mission, placing crews at risk of urinary calculus for-
mation due to increased urinary solute concentrations and
osmolality [3].
Renal function was assessed during the 9-day Spacelab
Life Sciences-1 mission (STS-40, June 1991) and the pre-
ceding three longer-duration Skylab missions (May 1973
February 1974). Measurement of creatinine clearance as an
indicator of glomerular filtration rate (GFR) showed a proba-
ble but slight overall increase from 6% to 18% early in flight.
Long-duration flight GFR measurements showed only a few
percent gain over preflight levels. Renal plasma flow is felt
to be increased on landing day, likely due to constriction in
efferent arterioles in the renal cortex resulting from high levels
of angiotensin I [2].
Bone Mineral Loss
Bed rest has been shown to be a reasonable analog to space
flight with regard to bone physiology and calcium kinetics.
273
274
Bed-rest subjects, as well as quadriplegics, show losses in
bone mineral density over time as their gravity-resistant mus-
cular actions are put to rest. Multiple bed-rest studies have
demonstrated consistent demineralization of key regions of
bone. Those key regions also show changes in space flight,
though often to a slightly greater rate and magnitude than
have been recorded in bed-rest studies [47]. The bone loss
observed during and following space flight occurs despite
vigorous in-flight exercise programs required by all crew-
members.
Bed-rest studies have played a key role in developing
countermeasures for musculoskeletal degradation during
long-duration space flight, including performance of physi-
cal exercise and evaluation of pharmacologic agents such as
bisphosphonates. Biomedical results of long-duration mis-
sions, notably those conducted on Skylab and Mir, provide
limited but valuable information to apply toward the develop-
ment of countermeasure regimes for the ISS.
Calcium balance studies conducted on Skylab showed that
200300 mg/day of calcium were lost by astronauts due to both
urinary and fecal excretion [2,8]. Plasma parathyroid hormone
levels were measured as normal during flight, and there have
not been consistent results in the in-flight calcitonin measure-
ments. The main etiology of observed net increases in urinary
calcium losses during space flight appears to be leaching of
bone calcium from the skeletal system due to diminished bone
loading in microgravity.
The Skylab calcium balance studies showed individual
variation, but there was a generally consistent rate of daily
calcium loss in the 28-day (Skylab 2) and 59-day (Skylab 3)
flights, and no suggestion of decline in the rate of loss in the
longer 84-day (Skylab 4) flight. Phosphorous loss varied from
222 to 400 mg/day in Skylab 2 and 4, mainly from the urinary
route. The loss rate in Skylab 3 was much lower for unex-
plained reasons [7,9].
Although physiological findings from the joint Shuttle-Mir
flights showed significant individual variability in the amount
of bone mineral density loss in key regions such as the greater
trochanter, femoral neck, lumbar spine, and calcaneus, over-
all there was a consistent 1.31.5% monthly loss in bone
mineral density. Metabolic investigations showed negative
calcium balance in flight due to decreased intestinal absorp-
tion and increased urinary calcium loss. Postflight, there was
rapid return to zero balance. Additionally, there were inflight
increases in other markers for bone resorption such as colla-
gen cross links occurring in parallel with the increased losses
of calcium [10].
Voiding Challenges
Various operational factors may predispose some individu-
als to GU conditions during space flight. One of these is the
mission schedule, especially during docked operations, which
is often filled with crew activities. Frequently because of
an intense operational timeline, basic needs such as eating,
J.A. Jones et al.
drinking, and voiding are delayed or skipped. Periods of inad-
equate fluid intake and subsequent relative dehydration, espe-
cially when the workload is high, predispose crewmembers
to increased urinary solute concentration, thereby increasing
the risk of forming renal stones. Delays in voiding because
of schedule constraints can also predispose crewmembers to
infection, bladder calculi, and urinary retention due to urinary
stasis in the lower tracts.
Two factors may significantly influence voiding in the
immediate prelaunch timeframe. These are the long period
during which a crew may need to wear a launch and entry
suit, and the semi-recumbent position assumed by Space
Shuttle crewmembers on the launch pad. Under these cir-
cumstances crewmembers must be able to void sponta-
neously without being concerned about the migration of
urine to other locations in the suit, especially in the cepha-
lad direction. Therefore, adult absorbent garments (pull-
up diapers) are worn beneath the liquid cooling garment.
These pull-up diapers have a 12 L capacity. In spite of
these absorbent garments, crewmembers often report dif-
ficulty voiding due to the prelaunch position and the con-
fines of the suit.
While participating in extravehicular activities (EVAs),
a crewmember is maintained within the life support system
of the extravehicular mobility unit. EVAs can be nominally
scheduled for 6.5 h. This means a crewmember may be inside
an EVA suit for as many as 8 h when taking into account
pre-EVA preparation, suit checks, and nitrogen elimination
prebreathe protocols. An EVA astronaut therefore wears a
maximum absorbent garment or an adult diaper when per-
forming an EVA. This same garment is worn during water
immersion EVA training prior to launch.
Urinary retention has been reported early in flight, and is
most likely due to changes in autonomic function and other
microgravity effects. In addition, finding privacy on a vehicle
such as the Space Shuttle is difficult. Since up to seven crew-
members share the one small bathroom area that houses the
waste collection system (WCS), the crew may experience a
delay in access to the WCS. This may contribute to a risk for
urinary retention and infection. Crew coordination for even
these basic human needs is essential for overall health. Fur-
ther attempts to maintain hygiene include: (1) assignment of a
separate funnel adapter for each crewmember in which to col-
lect liquid waste in the WCS (Figure 13.1), (2) biocidal wipes
in the WCS area to clean the surfaces of equipment between
uses, and (3) a hygiene shower hose that connects to the Shut-
tle galley to use with wet and dry wipes to cleanse and dry the
perineum during flight.
The thermal load on the crew during nominal operations on
the Shuttle or ISS is minimal. However, physical demands or
loss of environmental control can lead to undue heat stress.
During the NASA-Mir Program the temperature on the
Russian space station Mir often rose to over 85F (29.5C)
and humidity occasionally exceeded 75%. This produced peri-
ods when the crewmembers clothing was moist, especially in
13. Renal and Genitourinary Concerns
FIGURE 13.1. Urinary conduit and personalized funnel adapter, part
of the Space Shuttles waste containment system (WCS). The hose
attaches to a vacuum system that draws urine into a waste fluids tank,
which is periodically dumped overboard
the perineum, increasing the likelihood of developing fungal
infections such as Candida (Monilia) and urinary tract infec-
tions (UTIs). Several rashes were observed during this period,
and fungal species were felt to be contributory.
Waste Management Systems
During the early years of the U.S. and Russian space programs,
astronauts and cosmonauts did not have a waste collection and
storage system. Instead, individuals voided and defecated into
collection bags. The urine collection bags, known popularly as
Apollo bags, used a condom-like appliance to interface with
the crewmens genitalia. (There were no women astronauts in
the early years of the U.S. space program, the first flew on the
Space Shuttle in 1983.) Today, the so-called Apollo-bags
are still flown aboard space vehicles in the U.S. space pro-
gram as a backup capability in case of WCS failure.
The Space Shuttle has a single WCS that is used to col-
lect urinary and fecal waste. It is located in the aft middeck
area and has a privacy curtain. The Shuttle WCS has a cor-
rugated tube that transports urine from the crewmember to the
phase separator. Each crewmember has his or her own funnel
adapter to interface between the urethral meatus and the tub-
ing. When the WCS is activated, negative pressure is gener-
ated on the storage tank side of the WCS, thereby effectively
aspirating the urine into the phase separator. Due to volume
and weight constraints, only one funnel is flown per crew-
member, each of whom is responsible for cleaning and drying
the funnel between uses. A stowage rack in the WCS area
houses the funnels.
Liquid waste undergoes phase separation (air and fluid) in
the negative pressure stream of collection before it is stored
in a wastewater tank. Wastewater can be dumped overboard
275
as needed. Solid waste is dehydrated to some degree but is
left in the WCS to be retrieved after flight. Activated charcoal
beds minimize dispersion of solid waste odor throughout the
Shuttle cabin. Aboard the ISS, a similar system is used for
waste management in the Russian Segment. It also makes use
of a urine collection hose, but there is a single funnel interface
that is cleaned after each use.
The Russian Elektron device, which was originally developed
for Mir and is now used on the ISS, generates oxygen from
urine using electrolysis to split water into its components
hydrogen and oxygen. Oxygen is used for breathing, and the
hydrogen is vented overboard. In the current ISS configura-
tion, atmospheric condensate water is being reclaimed and
processed to become drinking and hygiene water. Eventually,
it is planned to incorporate a more capable and robust water
reclamation and recycling system that will process both urine
and condensate to potable water.
Urine Collecting Devices
The ability to efficiently collect quantified urine samples is
fundamental to many investigational studies and operational
monitoring and evaluation methods. However, the weight-
less environment adds complexity to this activity, primarily
due to difficulty in fluid handling and air-fluid separation.
Many different sampling devices have been developed over
the years, with varying degrees of success. The first use of a
newly designed polyethylene bag was on board Mir. For this
first flight, the bags were launched to Mir from Russia as part
of a series of inflight metabolic experiments. An improvement
over the previous white vinyl bags in several ways, the new
bag had a flat-lying one-way valve that allowed for a greater
volume of urine flow than did the valves of the commercially
available vinyl bags. This design helped reduce the backpres-
sure felt by crewmembers when voiding and was also able
to accommodate the lithium chloride concentration method
of volume measurement, which was first done using this bag
(previous vinyl bags tended to absorb the lithium chloride).
After several years of use, a polyethylene bag was devel-
oped with an even wider valve to allow more urine to pass.
This new bag also has a sample port that replaces the old
one taken from the Shuttle drink bag port. The new port and
valve are three times greater in diameter than the old port
and valve, thereby allowing for much faster emptying of the
bag. The new device first flew on Shuttle mission STS-97 in
November 2000, with a good degree of success.
In the past, only a commercially available, external, condom-
type latex catheter was used to make the interface between the
male astronaut and the bag. The catheter has earned mixed
reviews from crewmembers, ranging from total dislike to
worked just fine. Enough complaints were voiced to warrant
finding an alternative. One option employs a condom with an
inflatable collar to place around the glans. Another alterna-
tive, the BioDerm wafer, was first flown on STS-96 (May 27
to June 6, 1999) as a hardware evaluation experiment rather
276
than for sample collection. It has been rated as the best pos-
sible means of collecting urine by all of the male crewmem-
bers that tried it. The medical-grade adhesive on the back of
the wafer allows the BioDerm wafer to attach directly to the
penis, providing an easier-to-install, nearly leak-proof, hands-
free method of collection. It is also designed to be worn for as
many as 3 days and has been shown to work well for the 24-h
period of wear necessary for most science experiments. The
condom catheter remains an available option, with the latex
being replaced by silicone to avoid risk of allergic reactions.
In the past twenty years, women have comprised a gradually
increasing fraction of space crews. Initially, female crewmem-
bers collected urine by using a metal ring inside the condom
catheter to press against the perineum. Although this method
allowed for urine capture, there was often leakage or spillage
around the ring, requiring multiple dry wipes to contain the
liquid. Multiple alternative female interfaces were studied in
microgravity during parabolic flight aboard the KC-135 air-
craft and during actual Shuttle flights. Devices that fit over the
labia majora or inside the labia minora inserted into the vagi-
nal introitus, or inflated onto the perineum were all evaluated.
The ease of one-handed application was a key consideration
in design. Results varied by size and shape of the perineum,
as well as personal preference. Most female crewmembers
selected the silicone periurethral device with introitus locator
insert as providing the best urine seal with ease of use. How-
ever, several sizes of the condom-ring system are made avail-
able for those female crewmembers that prefer alternatives.
A device that fulfills stringent science requirements for uri-
nary volume measurement and sampling of specific analytes
has been developed to fly in the Human Research Facility rack
during the final stages of ISS assembly. This will facilitate life
science research without largely impacting crew time. This
urinary monitoring system should also eliminate the cumber-
some task of whole urine volume collection for ground sam-
pling, which is required to complete research objectives.
Clinical Genitourinary Issues in Space
Flight
History
Multiple genitourinary conditions have manifested in space flight
crews dating back to the beginning of the first suborbital flights
in both the U.S. and Russian programs. Initial problems were due
to containment of urine while on the launch pad and subsequently
while in microgravity in an enclosed pressure suit.
Genitourinary tract infections began to appear in the
Russian Salyut and U.S. Apollo eras. In one instance a case
of cystourethritis with Pseudomonas aeruginosa occurred due
to prolonged use of a condom catheter urine collection sys-
tem in microgravity. More recently, a case of prostatitis pro-
gressing to urosepsis resulted in the premature deorbit of a
crew from the Mir space station. Several episodes of urinary
J.A. Jones et al.
retention have occurred that were multifactorial in origin,
some requiring urethral catheterization for relief. Cases of
retention in non-infected female crewmembers with no terres-
trial history of retention appear to have a microgravity-unique
mechanism, perhaps with a psychosomatic component. An
additional factor contributing to urinary retention may be the
use of prophylactic and therapeutic medications to treat SMS
that have anticholinergic side effects. Performance of urinary
catheterization by crewmembers in microgravity has thus far
not been problematic.
Nephrolithiasis
Urinary calculi are both ancient and prevalent. The medi-
cal impact of urinary stones dates to antiquity, with the old-
est known case in a 7,000-year-old Egyptian mummy. [11]
Approximately 5% of the U.S. population will develop clini-
cally significant urinary calculi in their lifetime, with a much
greater percentage having sub-clinical calculi by autopsy inci-
dence. More than 1 million patients will seek medical atten-
tion for urinary stones annually in the United States alone,
with the incidence being greater in males than in females by
a margin of 3:1 and highest in Caucasians than other ethnic
groups. [12] The peak incidence is in the third through fifth
decades, which embraces the vast majority of the active career
astronaut corps.
The time required to form stones varies from individual to
individual, and the minimal time to form stones during space
flight is not known. Patients immobilized due to orthopedic
injury have an increased rate of stone formation, with time
to stone symptoms in this cohort varying from a minimum of
7476 days to a maximum of 6221200 days, and averaging
276362 days, depending on the study group [13,14]. Recur-
rence following a first episode is common. In the absence of
any underlying medical condition, Earth-based clinical stud-
ies have shown an approximate 75% recurrence rate for stone-
formers within 5 years following formation of the first renal
stone. Dietary modifications, increased fluid intake, or phar-
macological treatments can significantly lower these rates in
patients [15,16]. Accordingly, it is NASAs aim to understand
the physiologic changes that occur when humans are exposed
to microgravity and to minimize the potential for renal stone
development in spaceflight crews.
Various types of urinary calculi are found in the general
population. These can be classified by composition into five
basic groups: (1) calcium, (2) uric acid, (3) struvite, 4) cys-
tine, and 5) miscellaneous stones. Calcium stones account for
almost 80% of all urinary calculi, and can be further classi-
fied into calcium oxalate (6575%) and calcium phosphate
(< 5%) composition, with the majority being mixed calcium
stones; only 30% of stones contain a single component.
Approximately 5060% of these patients show elevated cal-
cium excretion in the urine (hypercalciuria). The next most
common type of stone is struvite, otherwise known as mag-
nesium ammonium phosphate (triple phosphate), comprising
13. Renal and Genitourinary Concerns
about 15% of all urinary stones and occurring exclusively
in patients with recurrent or persistent urinary infections
with urease-producing organisms, producing a urinary pH
of greater than 7.2. Uric acid stones make up 68% of the
total and are more common in patients suffering from gout.
Following the first gout attack, 1% of gout patients per year
will develop uric acid stones, with the prevalence being 20%
of the gouty population. Cystine stones are rare, comprising
only 1% of the total. These stones occur only in patients with
cystinuria, which is a genetic disorder of amino acid metabo-
lism. Miscellaneous stones include the remaining rare urinary
calculi such as xanthine, silicate and triamterene stones of
diverse etiologic mechanisms.
Factors in Stone Formation
With normal anatomy, crystals form when the urine is super-
saturated with minerals; i.e., when the concentration of stone-
forming salt exceeds the solubility of the salt in solution and
the solubility product exceeds the threshold for precipitation.
It should be noted that although urine of non-stone-formers is
also commonly supersaturated with respect to calcium oxa-
late, precipitation does not occur because of other factors such
as urine flow and the presence of inhibitors such as citrate
and pyrophosphate. Factors that promote precipitation include
increased concentration of stone constituents (from reduced
urine flow or increased excretion of constituents), and the
presence of a physical substrate on which crystallization may
initiate, such as damage from prior infections or the presence
of a foreign body.
Commonly, conditions involving the increased excretion of
calcium into the urine, or hypercalciuria, underlie stone forma-
tion. Genetic predisposition to stone formation often involves
familiar hypercalciura syndromes. Absorptive hypercalciuria,
where excessive calcium is absorbed from the gastrointes-
tinal tract, may result from excess dietary calcium. Resorp-
tive hypercalciuria involves excess demineralization of bone
mass, releasing free calcium onto the vascular system with
subsequent renal loss. This is a particular concern in weight-
lessness. In nephrogenic or renal hypercalciuria, the kidneys
filter out calcium from the blood but do not allow reabsorp-
tion of the calcium back into the blood from the renal tubules.
Medications and supplements may induce hypercalciuria by
increasing intestinal absorption (vitamin D), adding directly to
the calcium load (antacids, calcium supplements), or enhanc-
ing renal calcium excretion (acetazolamide) [17,18].
Other factors will also bring about this condition. These
include recurrent urinary tract infection, indwelling foreign
bodies in the urinary tract (including catheters), a sedentary
lifestyle or bed rest, and long-term dehydrationthe latter
often due to inadequate intake of fluids and the resulting con-
centration of urine. Clinical renal stone disease is associated
with living in hot, arid climates, which induces sweating and
loss of fluids, and frequent physical activity increasing heat
loads and dehydration.
277
Certain dietary factors predispose an individual to stone
formation. Among these are diets rich in contributors (e.g.,
calcium, purine, dairy excess, oxalate, and sodium), and low
fluid intake. An excess of calcium oxalate or other minerals in
the diet may be due to local geographic factors such as water
or soil conditions. Ironically, a diet that is too low in calcium
may also promote calcium oxalate stone formation. Normally,
a large fraction of intestinal oxalate is bound to calcium and
undergoes fecal loss. With inadequate dietary calcium, hyper-
oxaluria may result from the absorption of unbound oxalate
from the intestine. Urinary acidity also influences stone for-
mation and type; low pH promotes the formation of calcium
phosphate, cystine, and uric acid stones, which precipitate out
of solution below 5.6 pH, whereas a high pH promotes the
formation of struvite and calcium apatite stones.
Anatomical factors found in stone formation include med-
ullary sponge kidney, polycystic kidney disease, and bladder
outlet obstruction, all of which produce increased particle
retention. Most anatomical abnormalities would be screened
out during astronaut medical selection. Underlying illness
may also contribute to stone formation. Among these are sar-
coidosis, hyperparathyroidism, cancer, gout, distal renal tubu-
lar acidosis, and myeloproliferative diseases. Primary and
secondary errors of metabolism may also increase the con-
centration of stone contributors but again are expected to be
screened out during astronaut medical selection.
In the following paragraphs, we will discuss further the
factors that lead to the formation of stones. We will address
issues relevant to human space flight, including stone etiol-
ogy, anatomical factors, disease states and related operational
aspects of crew training and actual space flight.
Inhibitory Factors
Many urinary substances have been shown to display
properties that inhibit the phases of crystal nucleation,
aggregation, and growth. These include ions such as citrate,
magnesium, and phosphate, which bond to form soluble
complexes with urinary calcium and decrease the amount of
ionic calcium available to bond with oxalate. Other inhibi-
tors include Tamm-Horsfall protein, nephrocalcin, uropon-
tin, chondroitin-4-sulfate, heparin, and glycoaminoglycans.
These primarily adhere to the surface of crystals, preventing
or slowing their growth and allowing small crystals to be
removed from the body with each urine void.
Inhibitor compounds can be further classified as natural or
exogenous. Natural inhibitor compounds are inorganic (e.g.,
pyrophosphate and magnesium) or organic (e.g., citrate, Tamm-
Horsfall protein, uropontin, nephrocalcin, uronic acid-rich
protein, glycosaminoglycans, and prothrombin F1 peptide).
Exogenous inhibitor compounds include potassium citrate or
potassium-magnesium citrate, magnesium salt (usually oxide),
allopurinol, thiazide diuretics, and neutral phosphates. These
lead to therapeutic modalities that may prevent stone occur-
rence or recurrence. Inhibitory conditions to stone formation
278 J.A. Jones et al.

thus include a diet low in contributors and high in inhibitors as

well as high fluid intake [19,20].

Flight Operations
Astronaut training and spaceflight preparation involve several
activities associated with long periods in environments that
make it difficult to void or access fluids. High performance
aircraft flying is known to be associated with an increased risk
of stone formation. For U.S. astronauts, aircraft include the
T-38 and Shuttle Training Aircraft, a modified Gulfstream jet,
typically flown by astronauts as part of their training cycle.
Most U.S. training occurs in the relatively warm climates of
Texas and Florida, and along with flight duties vigorous phys-
ical training is required. FIGURE 13.2. Dietary fluid intake and urinary output in six astronauts
Specific spaceflight operations that may contribute to renal during short duration space shuttle flights. BDC (baseline data col-
stone risk include the use of full pressure suits, which may lection) represents the preflight period 10 days prior to launch. E-flt
involve long periods of urinary storage without voiding and is in-flight day 34, L-flt is in-flight day 1213, R0-2 is landing day
possible intentional or unintentional fluid restriction. These though 2 days post landing and R7-10 is 710 days post landing.
include launch and entry suits such as the U.S. Advanced Data represent the means and SEM. * p < 0.05
Crew Escape Suit and the Russian Sokol, as well as extrave-
hicular suits such as the U.S. Extravehicular Mobility Unit
(EMU) and the Russian Orlan. U.S. suits are worn with an
absorbent garment to accommodate voiding, but voiding is
often consciously avoided by crewmembers for comfort and
hygiene reasons. A drink bag is incorporated into the EMU,
providing about 32 oz of water for an EVA sortie. It is not
unusual to lose 12 kg of body mass during a 6-h EVA due
to perspiration and insensible fluid loss. All of this naturally
contributes to stone formation.
Fluid intake can be demonstrated to decrease during
flight for the reasons mentioned above, resulting in reduced
urine output. Figures 13.2 and 13.3 show fluid intake and
output in both short and long duration flight crewmembers
[21,22].
FIGURE 13.3. Dietary fluid intake and urinary output in 11 astronauts
Classic Symptoms and Signs of Stone Formation and cosmonauts during long duration Shuttle-Mir missions. BDC
(baseline data collection) represents the preflight period. E-flt is
There are classic symptoms of stone formation that help in in-flight day < 60, L-flt is in-flight day > 100. R+ day is the numbers
diagnosing this condition. One of the most common symp- of days post landing. Data represent the means and SEM. * p < 0.05
toms is agonizing pain in the lower back, occurring just below
the ribs and spreading around to the front of the abdomen. processes. Stones in the calices and renal pelvis may be only
The severity and character of pain associated with the pres- minimally symptomatic or asymptomatic.
ence of calculus varies by location. A calculus in the calyx, Sites of stone obstruction of the collecting system include
infundibulum, or pelvis of the kidney can produce discomfort the most common, the ureterovesical junction (UVJ); the
that ranges from minimal to moderate. Calculi that pass into second most common, the ureteropelvic junction (UPJ); and
the ureter cause severe to incapacitating pain; this is usually the third most common, the mid-ureter where it crosses the
due to complete or partial obstruction and acute distension iliac vessels at the pelvic inlet. Obstruction at the UPJ tends
of the collecting system. Pain may extend into the groin area to cause pain in the back radiating to the flank. Obstruction in
when a stone passes into the ureter, often in a constant fashion; the mid-ureter causes pain in the flank radiating into the lower
however it also may come in waves as the stone is induced to quadrants of the abdomen, which can be confused with appen-
move through the ureter. In this case, the patient will feel col- dicitis or sigmoid diverticular disease, or in the inguinal region
icky, due to episodic obstruction and subsequent distension into the testicle or labia. Obstruction at the UVJ, in addition to
of the ureter and mucosal irritation inducing hyperperistalsis. groin pain, produces lower urinary tract symptoms typical of
The pain may be nonspecific and mimic other intra-abdominal cystitis, namely, urgency, frequency, and possibly dysuria.
13. Renal and Genitourinary Concerns
On physical examination, the costovertebral angle, lower
abdomen or lower back may be painful to palpation and per-
cussion on the side ipsilateral of the stone. Bilateral pain
suggests another process, such as infection. Peritoneal signs
should not be present, except with the occasional forniceal
rupture and associated urinoma, but then the signs are typi-
cally still focal. Pain is commonly referred to the ipsilateral
groin and gonad, but these regions are non-tender to direct
examination. The rectal examination should be non-tender as
well. Vital signs often reflect adrenergic hyperactivity such as
tachycardia and systolic hypertension, possibly shallow, rapid
respirations, and diaphoresis. Skin may be pale and clammy.
The presence of fever suggests associated infection. Hypo-
tension can occur from a pain-induced vasovagal response or
from dehydration associated with protracted nausea and vom-
iting. Sometimes gross hematuria occurs, but more commonly
it is only microscopic.
Aeromedical Significance
The formation of a renal stone during space flight affects not
only the health and well-being of the afflicted individual, but
may also jeopardize the success of the mission. The severity of
the pain may be significant enough that the crewmember may
not be able to successfully perform duties, such as piloting an
aircraft or spacecraft or operating onboard systems. The rela-
tive remoteness of the spaceflight environment renders com-
plications particularly worrisome. Specifically, the issues for
space flight also include (1) the potential for forniceal rupture
that may temporarily relieve the severe colic but causes a ret-
roperitoneal urinoma subject to infection and diffuse ileus; (2)
infection behind the level of obstruction that, due to increased
pressure, increases the risk for urosepsis; and (3) a crewmem-
bers inability to maintain oral hydration due to the ileus. Any
of these issues could lead to early mission termination.
History of Urinary Evaluation and Calculi
in Space Flight
Aside from the environmental risks noted above, space flight is
associated with known biochemical alterations associated with
microgravity adaptation and earth readaptation that are known
to promote stone formation [21,22]. Table 13.1 shows urinary
data accumulated from 332 astronauts during short duration
Space Shuttle flights. Twenty-four hour urine collections were
taken and analyzed as single samples 10 days prior to launch
and on landing day. Data are the percent fraction of astronauts
exhibiting increased risk for stone formation in the urinary
factors shown. Hypercalciuria is defined as urinary calcium
> 250 mg/day, hypocitraturia < 320 mg/day, hypomagnesia
< 60 mg/day, and supersaturation values for calcium oxalate
and uric acid are defined as >2.0. As is seen, the immediate
post landing period, with its altered chemistries and relative
dehydration, represents a vulnerable time with respect to renal
stone formation.
279
TABLE 13.1. Urinary chemistries influencing renal stone risk, before
and after space shuttle flight.
Analyte Preflight Postflight
Hypercalcuria 20.8 38.9
Hypocitaturia 6.9 14.6
Hypomagnesuria 6.0 15.8
Supersaturation
CaOx 25.6 46.2
Uric Acid 32.6 48.6
Abbreviation: CaOx, calcium oxalate, n = 332.
Data represent the percent fraction of crewmembers that exceed established
risk thresholds for these analytes.
In the history of the U.S. space program, 14 renal calculus
events in 12 astronauts have been recorded out of a total of
332 flown astronauts. Four of these occurred before flight (not
associated with space flight), and ten occurred within 2 years
postflight; two crewmembers have experienced multiple renal
stone episodes. Six of these events occurred prior to 1990, and
eight since 1990.
In the history of the Russian space program, three cosmo-
nauts have been identified with postflight urinary calculi. None
of these were symptomatic preflight or inflight, and the stones
were not detected before space flight. Subsequent evaluation
of these cosmonauts revealed no anatomic or metabolic abnor-
malities to account for the formation of the calculi. One cosmo-
naut developed a presumed renal stone during a long duration
mission that caused severe pain and significantly impacted the
inflight timeline. This apparently passed spontaneously over a
period of days, and the mission was completed.
Metabolic investigations during the three Skylab missions
in the 1970s showed a significant decrease in both fluid intake
and daily urine volume during the first 6 days of the mission,
followed by a return to preflight values in the nine crewmem-
bers who were studied. Additional inflight changes in the
urinary biochemistry included an increase in osmolality and
excretion of calcium, sodium, potassium, chloride, phospho-
rus, and magnesium. Significant decreases in uric acid levels
were observed. These changes may be critical in the develop-
ment of renal stones due to the increase in concentration of the
stone-forming salts in a decreased daily urine volume. Post-
flight results during the first 6 days showed some contrasting
results to inflight data, including a significant decrease in the
urinary excretion of sodium, potassium, chloride, phosphorus,
magnesium, and uric acid. Urinary calcium levels continued
to exceed preflight values. No changes in urinary creatinine
values were detected [3]. The postflight changes may reflect a
physiological adaptation to gravity and may be influenced by
the ingestion of a saline solution taken before landing to mini-
mize orthostatic intolerance. With the exception of urinary
sodium, all of these urinary components returned to preflight
levels 1418 days following landing. [7,9]
As noted in Table 13.1, data collected after space flight,
within the first few hours of landing, indicate changes in the
urine chemistry favoring increased risk of calcium oxalate
280 J.A. Jones et al.

and uric acid stone formation. Preflight and postflight data for a single crewmember of a long duration flight. Further
specifically targeting renal stone risk have further shown that study is ongoing to bolster these data, but the trend toward
crewmembers increase the concentration of salts in urine, increased renal stone risk is evident.
decrease some urinary inhibitors of renal stone develop- Through both space-related research and Earth-based clini-
ment, and increase the risk of calcium oxalate and calcium cal research, NASA has amassed a large database for study-
phosphate (brushite) stone formation. Table 13.2 compares ing risks and countermeasures for renal stone formation. The
values for renal stone risk parameters measured in 24-h urine most obvious and easily implemented reduction in risk could
collections obtained preflight (10 days prior to launch) and be obtained primarily by increasing the fluid intake to increase
postflight (beginning at landing). It is possible that different the daily urine output to 2 L/day. In this way, the excess salts in
mechanisms may increase the risk for renal stone develop- the urine may remain in solution, crystals will not form, and a
ment during different stages of space flight, namely exposure renal stone will not develop. However, without addressing the
to the microgravity environment and readaptation to gravity underlying calcium excretion due to bone loss, this treats the
following space flight. symptoms and not the cause of the increased urinary salts. Addi-
Various factors may account for this increased risk, although tionally, because of the space motion sickness experienced by
actual quantitative inflight data are limited. These factors many astronauts early in flight, increasing fluid intake may not
include the decrease in daily urine output as a result of lower be possible due to decreased appetite and nausea. A retained
fluid intake arising from decreased appetite and increased urinary crystal formed during these early days may grow to a
workload schedules during the flight, as well as from space renal stone during the remaining stay in microgravity.
motion sickness during the first few flight days. Microgravity
exposure associated with space flight causes the bones to lose
calcium and the excess calcium to excrete as urinary waste
Countermeasures and Risk Assessment
(resorptive hypercalciuria). Given that 70% of kidney stones Dietary modification and promising pharmacologic treatments
are calcium containing, the increased load of calcium into the may be used to reduce the potential risk for renal stone forma-
urine increases the risk of calcium stone formation. It has been tion. Diets low in oxalate content and reduced animal proteins
shown that the urine of astronauts is saturated with calcium may be advised. Some of the inhibitor substances are being
salts. Similarly, citrate, an inhibitor of renal stone formation, considered for higher risk spaceflight crewmembers.
has been shown to decrease during early space flight and Potassium citrate is used clinically to minimize the devel-
immediately postflight at landing, thereby increasing the risk opment of crystals and the growth of renal stones. Possible
of renal stone formation [21,22]. Table 13.3 compares pre- side effects, although uncommon, include minor gastrointes-
flight, inflight, and postflight values of key urinary analytes tinal complaintse.g., abdominal discomfort, vomiting, diar-
rhea or nausea, upper gastrointestinal lesionsestimated at
TABLE 13.2. Renal stone risk assessment before and after space- 1 per 100,000 patient-years; and hyperkalemia, which may
flight. occur in subjects with renal disease (a potentiality that has
Analyte Preflight Postflight p value
been screened out in astronaut population) or with potassium-
sparing diuretic ingestion or acute dehydration. These risks
Total volume (L/day) 2.08 (0.06) 1.98 (0.06) 0.076
pH 6.02 (0.02) 5.71 (0.03) <0.001
may be minimized by providing slow-release wax matrix tab-
Calcium (mg/day) 188.4 (5.34) 236.5 (6.48) <0.001 lets, ingesting the dose with meals, ingesting the tablet whole
Phosphate (mg/day) 1043.8 (24.56) 868.4 (18.53) <0.001 without chewing, crushing or sucking the tablet, limiting addi-
Oxalate (mg/day) 36.7 (0.92) 35.8 (0.87) 0.365 tional salt intake, and encouraging high fluid intake. Currently
Sodium (mEq/day) 163.1 (3.56) 119.6 (3.63) <0.001 a study is being conducted at NASA Johnson Space Center
Potassium (mEq/day) 67.1 (1.28) 52.7 (1.10) <0.001
Magnesium (mg/day) 114.3 (2.36) 100.8 (2.18) <0.001
to look at the efficacy of potassium citrate as a prophylac-
Citrate (mg/day) 707.9 (16.46) 623.2 (17.66) <0.001 tic countermeasure for space flight. This agent has been used
Sulfate (mmol/day) 22.4 (0.41) 24.9 (0.48) <0.001 prophylactically during space flight in known stone formers
Uric Acid (mg/day) 655.0 (12.20) 570.7 (13.56) <0.001 who received a medical waiver for short duration missions.
Creatinine (mg/day) 1724.0 (23.2) 1769.3 (28.81) 0.106 Potassium-magnesium citrate is also under clinical study and
Relative urinary supersaturation may soon be approved as perhaps an even more robust inhibi-
Calcium oxalate 1.56 (0.06) 2.26 (0.08) <0.001 tor of stone formation [2327].
Brushite 1.30 (0.07) 0.98 (0.06) <0.001 Inhibiting bone resorption associated with microgravity
Sodium urate 2.62 (0.13) 1.48 (0.08) <0.001
Struvite 2.27 (0.49) 0.60 (0.08) <0.001
should also diminish the risk of renal stone formation. In the-
Uric acid saturation 1.88 (0.09) 2.54 (0.10) <0.001 ory, this could be accomplished by physical loading (exercise
countermeasures) or pharmaceutical agents. Bisphosphonates
These data show significant changes in parameters known to influence renal
are a class of drugs that has demonstrated efficacy in treat-
stone formation for postflight values compared with preflight values for Shuttle
missions less than 18 days in duration. ing elderly patients with osteoporosis by inhibiting the loss
Data represent the means (+/ SEM) before flight and on landing day. Statistical of bone. These agents could potentially prevent the bone loss
analysis by paired t-test, n = 330, except oxalate and calcium oxalate, n = 329. observed in astronauts and thereby avert the stone promoting
13. Renal and Genitourinary Concerns 281

TABLE 13.3. Urinary parameters (analytes, volume, pH, and supersaturation) influencing renal stone risk in a single crewmem-
ber throughout a long duration flight.
Parameter PRE FD < 20 FD < 30 FD < 100 FD > 100 R+0 R+7 R+1014
TV L/day 1.79 1.043 0.973 1.109 1.038 0.54 0.73 1.85
Ca mg/day 211 255 245 436 338 224 113 161
Ox mg/day 35.7 13.1 17.7 38.6 39.9 20.5 27.2 35.5
UA mg/day 676 376 632 659 571 355 523 518
Cit mg/day 691 610 962 1119 765 618 895 1043
pH 5.93 6.14 5.97 5.49 5.34 5.22 6.18 6.28
Na mEq/day 221 141 183 269 158 136 211 119
SO4 mmol/day 25.0 25.6 22.4 34.3 25.4 23.5 14.6 10.3
P mg/day 802 881 1110 1409 1163 544 797 694
Mg mg/day 139 175 132 199 169 109 87 142
K mEq/day 79 80 73 96 80 64 57 101
Cr mg/day 1701 1841 1910 2160 1946 1408 1507 1717
Relative supersaturation
CaOx 1.60 1.24 1.61 4.02 4.53 4.46 1.69 1.19
CaP 1.09 4.14 3.44 2.59 1.57 1.25 2.20 0.97
UAS 2.66 1.11 2.77 5.48 6.11 8.31 2.02 0.67

Abbreviations: PRE, preflight; FD, flight day; R, return day; TV, total volume; Ca, calcium; Ox, oxalate; UA, uric acid; Cit, citrate; Na, sodium;
SO4, sulfate; P, phosphorus; Mg, magnesium; K, potassium; Cr, creatinine; CaOx, calcium oxalate; CaP, calcium phosphate; UAS, uric acid
saturation.

resorptive hypercalciuria. Studies are planned for the ISS to
answer the question of efficacy of bisphosphonates in reduc-
ing renal stone risk.
Renal Stone Risk Assessment
U.S. crewmembers are assessed with the renal stone risk pro-
file (Mission Pharmacal, University of Texas Southwest Lab-
oratories). Although the urinary risk profile does not directly
predict the formation of renal stones, it illustrates to the flight
surgeon and crewmember the current urine chemistry envi-
ronment [2831]. Figures 13.4 and 13.5 show preflight and
postflight renal stone risk profile graphics for an individual.
The graphic provides a convenient and easily interpretable
risk profile understood by flight surgeons and crewmembers.
In our retrospective review of cases and from our review of
the postflight renal stone risk index assessment (RSRI), we
found a 93% correlation between known stone formers and
a high RSRI. All but one case were found to have significant
abnormalities; the one case had minor abnormalities. There
were some false positives in prospective cases, confounded by
urine collection biases, but there were no false negatives.
The risk profile considered in conjunction with the lifestyle
and dietary habits of the individual can be a valuable moni-
toring and education tool. Individuals who are at an increased
risk or have previously formed renal stones can be followed,
patient compliance can be assessed, and the effectiveness of
medical treatment can be determined with this profile. The
renal stone risk profile has proven value in the clinical setting
as a tool for classifying patients as to the etiology of the for-
mation of their renal stones [17,27,30,32]. Table 13.4 shows
the listed physician/patient information derived from the renal
stone risk profile, with guidelines for acting on significant
findings.
The relatively low cost of the renal stone risk profile makes
this a cost-effective methodology, which may mitigate the
potential for a mission impact if a crewmember is afflicted
with a renal stone inflight. Clinical experience has shown
that a program of monitoring the urinary environment and
estimating the risk for renal stone development can lead
to nearly total control of stone disease. The need for stone
removal can be dramatically reduced by an effective prophy-
lactic program. As applied to the U.S. space program, this
health care monitoring program may provide several distinct
advantages. Crewmembers experiencing an increased risk
prior to space flight, who are then exposed to the micrograv-
ity environment and resultant bone loss, hypercalciuria, and
increased urinary sodium, and decreased urinary output may
have further increased their risk of renal stone formation. The
RSRI evaluation would identify the risk prior to flight, gener-
ate appropriate medical intervention, and reduce the potential
risk before, during, and after space flight.
In implementing the schedule of RSRI measurement by 24-h
urine collection, it was determined that all astronauts should
have an annual examinationwith another examination con-
ducted preflight for Space Shuttle crewsonly as indicated
by a history of previous calculi or previously high risk
index. The examination should be given postflight during
the comprehensive medical examination performed 3 days
following return in all crews. Pak et al [18]. concluded that
for terrestrial stone formers, the reproducibility of urinary
stone risk factor analyses is satisfactory in repeat urine sam-
ples and a single stone risk analysis is sufficient for a sim-
plified medical evaluation of urolithiasis. The accuracy of
282 J.A. Jones et al.

FIGURE 13.4. Graphic representation of the renal stone risk profile derived from a 24-h urine collection in the preflight period before a
Shuttle launch, typically obtained 10 days prior to launch. Reproduced with permission from the University of Texas Southwestern
Medical Center at Dallas.

measuring urinary stone promoter and inhibitor substances
is improved by including matrix components, uroproteins,
uromucoid, and glycosaminoglycans in the analysis [20].
Other laboratory analysis for urinary stones include blood urea
nitrogen, serum electrolytes, creatinine, calcium, uric acid,
and phosphorous.
Treatment of Renal Stones
Available treatment options for urinary calculi vary depend-
ing on the size, location, and composition of the calculus. The
vast majority of stones will be calcium oxalate or mixed with
a calcium oxalate component and are therefore easily vis-
ible on x-ray or fluoroscopy. Pure calcium phosphate stones
(brushite) are less common but very radiodense. Pure uric acid
stones represent only 1015% of the total and are completely
radiolucent. They require ultrasound or computed tomogra-
phy (CT) to detect on imaging.
Stones that are less than 5 mm (0.2 in.) in diameter, smooth on
the surface, and drop into the ureter will often pass spontaneously
with hydration and analgesics and, therefore, will not require
therapeutic intervention beyond pain management. Stones larger
than 5 mm or possessing surface irregularities will usually not
pass on their own and will require intervention for removal.
Typically extracorporeal shock wave lithotripsy (ESWL) is
the treatment of choice for radio-dense stones in the calices,
renal pelvis, or upper ureter, although occasionally upper ure-
teral stones require retrograde manipulation to fragment well
13. Renal and Genitourinary Concerns 283

FIGURE 13.5. Renal stone risk profile for the same individual derived from a 24-h urine collection beginning in the immediate post-landing
period. Multiple parameters show elevated risk as compared with preflight values. Reproduced with permission from the University of Texas
Southwestern Medical Center at Dallas.

extracorporeally. Most ESWL devices require radiographic
localization and so are not appropriate for uric acid stones,
although ultrasound may be used to localize the stones. All
stones that are large enough for ultrasound to detect (> 3 mm)
can be treated with ESWL. Cystine and other stones resulting
from metabolic disorders should have been screened out at the
time of astronaut selection and, therefore, should not be an
issue in a spaceflight crew.
Calculi in the mid-ureter are often inaccessible to shock-
wave energy for treatment and require other modalities. Lower
ureteral stones can be treated with some ESWL machines that
treat in the prone position. ESWL can be performed without
invasive procedures and, depending on the required energy
and size and shape of the focusing reflector, using intrave-
nous sedation with or without local anesthesia. If the stone
bulk is 1.5 cm or larger, most urologists will place a stent
cystoscopically in the ureter prior to the ESWL to prevent a
Steinstrasse (German for street of stones) obstruction of
the ureter with a column of stone fragments.
Large stones in the calyx or renal pelvis (partial or
complete staghorn calculi) or stones associated with UPJ
obstruction are often treated with percutaneous nephroli-
thotripsy with or without endopyelotomy. Stones that pass
into the mid and lower (distal) ureter are often treated by
ureteroscopy, which requires dilation of the UVJ followed
by passage of a ureteroscope to the level of the stone. Here,
under direct visualization, the stone can be placed in a bas-
ket and extracted or fragmented with any of several types of
lithotritesultrasonic, electrohydraulic, and laser, Holmium
being the current laser of choice [16].
284
Management of Renal Stones in Astronauts
After a stone has been diagnosed, a crewmember will be taken
off flight status for both space flight and aviation. Should a
stone arise in the final weeks prior to launch, the Aeromedi-
cal Board has the choice of recommending launch delay or
the use of an alternate crewmember for flight. After treat-
ment, a 3-month follow-up survey is conducted with x-ray
examination of kidneys, ureter, and bladder and nephroto-
mograms or spiral CT to ensure clearance of all fragments.
In addition, a comprehensive program is implemented to
reduce the risk of recurrence. The crewmember is required
to increase oral fluid intake (i.e., water, mineral water with
bicarbonate, lemonade and other citrus fruit juices, and clear
sodas); limit sodium intake, and make further dietary modifi-
cations based on the individual risk index. These can include
a decrease in animal protein intake to reduce uric acid in the
urine, and a decrease in oxalates-containing foods such as
beets, spinach, chocolate, strawberries, coffee, Swiss chard,
cola, tea, nuts, wheat bran, and rhubarb. Further, the crew-
member usually receives a test dose of potassium citrate
for determine tolerance to the medication. Other possible
medications that might be considered include allopurinol for
uric acid and gout, potassium citrate with magnesium, and
thiazide diuretics for renal calcium leak. The crewmember
is also advised to avoid caffeine-containing products such as
coffee, tea, and colas.
If a crewmember has been rendered stone-free, a metabolic
stone work-up is performed, including a repeat 24-h urine
collection for renal stone risk profile to rule out a treatable eti-
ology for the stone disease. Due to the extensive screening at
the time of selection, the vast majority of these stones will be
found to be environmental. In these cases, the RSRI will help
identify specific risk factors that may be addressed to prevent
further stone episodes. In some instances, specific agents may
require augmentation in the crewmembers urine to prevent
recurrence; e.g. supplementation of citrate or magnesium if
these stone inhibitors are found to be low.
If the crewmember is found to be persistently stone-free
and has no latent metabolic condition, the Aeromedical
Board reviews the case and considers a waiver for avia-
tion operations and short-duration space flight, typically 2
weeks or less. Preflight tomograms obtained about twelve
weeks prior to flight will ensure that the individual remains
stone free and allow time for treatment options if small
stones are found. For those astronauts with a history of
environmental stones who are flying short duration flights,
certain in-flight procedures are followed to prevent the
formation of further stones. In addition, the flight surgeon
ensures the crew medical officer (CMO) assigned to the
flight, typically a non-physician, is proficient in performing
onboard urinalysis and administering treatment in the event
of inflight recurrence. Even in the case of a single environ-
mental stone in the distal tract with no other predisposing
factors, the individual is not eligible for long-duration space
flight (greater than 30 days duration). Incidentally, all long
J.A. Jones et al.
duration crewmembers undergo screening ultrasound of the
abdomen and pelvis about 6 weeks prior to flight.
Inflight Prevention and Management
In flight, crewmembers follow procedures that prevent the
growth of stones. Specifically, taking oral fluids in amounts
sufficient to maintain adequate hydration is encouraged. If
an astronaut is suffering from severe space motion sickness
during early flight, intravenous fluids may be considered to
guard against dehydration. Also, sodium consumption should
be limited in flight. As noted earlier, potassium citrate or
potassium-magnesium citrate may be useful countermeasures
to stone formation in certain high-risk individuals. Imag-
ing technology is unavailable to diagnose this condition in
the crews of Shuttle flights, but ultrasound is available to the
crews on the ISS. If stones occur in flight, spaceflight crews
can take specific steps to respond and mitigate further risk.
On orbit, the CMO with guidance from ground medical spe-
cialists would monitor an affected crewmembers vital signs,
hydration status, and clinical appearance. Also available to the
CMO are the means to follow urine output, assess urine spe-
cific gravity and certain chemistries, and test for the presence
of leukocytes and hemoglobin in the urine using colorimetric
reagent dipsticks. Dehydration is addressed with oral fluids as a
mainstay; intravenous fluids are available in limited quantities.
It is also the CMOs responsibility to administer medica-
tions as needed. Pain management will be paramount; avail-
able parenteral medications include meperidine, morphine,
and ketorolac (Toradol). Oral medications include oxycodone,
acetaminophen with and without codeine, and nonsteroidal
anti-inflammatory agents. Other available medications that
may be useful for stone management include antiemetics such
as promethazine. Further, the CMO evaluates pain resolution,
strains urine to capture a passed stone, and assesses the crew-
members duty status.
Ultrasound is available, on the ISS, allowing a CMO to
perform an exam with real-time guidance from ground special-
ists. Such guided ultrasound has been performed and shown to
provide adequate diagnostic imagery. Ultrasound may be used
to show visible calculi in UPJ, UVJ, or renal pelvis. It may
also show unilateral distension of the collecting system (either
hydronephrosis or hydroureter) ipsilateral to the side of pain,
if adequate time has passed to allow distention. Ultrasound
may also show loss of ureteral jet in the bladder ipsilateral to
the side of pain.
It is expected that, in the course of pain management and
hydration, most stones arising inflight would pass sponta-
neously. However, it is possible that complications such as
obstruction with hydronephrosis, sepsis, or intractable nausea
and emesis may prompt a medical evacuation. The basic steps
of hydration and pain management would be required during
entry and landing and may be dependent on the return vehicle.
Following recovery from the U.S. Shuttle or Russian Soyuz,
the crewmember would be transported to a medical facility for
definitive treatment.
13. Renal and Genitourinary Concerns
Clinical Genitourinary Issues
Examinations
Many factors are taken into account when selecting candidates
for human space flight. Obvious factors covering the genito-
urinary system include the astronauts health history, which
includes family history (renal disease, tumors, and calculi),
personal medical history (infections, nephropathies, and can-
cer), and personal surgical history (any urological, abdomi-
nal, or inguinal procedures). Astronaut applicants are also
screened for certain symptoms or physical signs, such as pain
or discomfort in the back, lower abdomen, genitals, or rectum
or while voiding or defecating.
Voiding symptoms address issues of urine volume, either
decreased (oliguria) or increased (polyuria); irritative symp-
toms, including frequency, urgency, dysuria, and nocturia;
obstructive symptoms, which include diminished force and
caliber of urine stream, spraying of stream, hesitancy, drib-
bling, straining, and a sense of residual urine following void-
ing; and incontinence.
Not surprisingly, astronaut candidates are subjected to an
exhaustive physical examination that, in renal and genitouri-
nary terms, includes an abdominal and inguinal examination
and a genital examination. Laboratory tests are conducted on
serum chemistries, including electrolytes, blood urea nitrogen,
creatinine, uric acid, calcium, and phosphorous. Urinalysis is
performed to test for pH, specific gravity, protein, glucose, leuko-
cyte esterase, nitrites, hemoglobin, urobilinogen, and bilirubin.
A cystine screen is also performed, supplemented by a cyanide
nitroprusside test if the cystine level is greater than 75 mg/L or
greater than 250 mg/24 h. Microscopic analysis for urinary crys-
tals, red blood cells (RBCs), white blood cells (WBCs), casts,
and transitional epithelial cells is performed routinely.
Renal imaging is performed on prospective astronauts
using ultrasonography. Some international space programs,
for example Russia, also perform routine intravenous pyelo-
gram (IVP) on initial selection. The potential crewmember
must have two kidneys in normal anatomic location with
normal parenchyma and collecting systems. Masses detected
on ultrasound may require further imaging. Smooth, simple
cysts require no further evaluation. Computed tomography
is indicated for evaluation of solid masses or irregular cysts.
Malformations, presence of urinary calculi, or hydronephro-
sis are causes for rejection.
Further tests may be performed when evidence of abnor-
malities arises on standard evaluations that may or may not
be disqualifying. Unexplained asymptomatic hematuria or
pyuria is an occasional cause of such further evaluation.
Functional anatomy of the renal system may be discerned
by IVP or intravenous urogram. Voiding cystourethrogra-
phy may be performed to rule out vesicoureteral reflux and
urethral strictures.
Combined nephrotomographic X-ray and IVP is the imag-
ing approach of choice that is used by NASA physicians
285
when clinical or first line diagnostic evidence suggests
urinary calculi. However, from 10% to 12% of stones will
be radiolucent and may be missed or show up as a filling
defect on an IVP. More advanced imaging modalities may
be employed to evaluate abnormalities in potential astro-
naut candidates. CT scanning provides higher anatomical
detail for evaluation of renal masses as seen on IVP or found
to be solid on ultrasound. Some CT scanners can provide
high-quality axial, sagittal, and coronal views. Spiral CT
images with fine cuts can be used to evaluate the kidneys
for calculi, with the advantage of visualizing both radiolu-
cent and radiopaque calculi in the absence of contrast media.
Spiral CT also provides staging information for evaluation
of genitourinary malignancies and can be used to evaluate
multiple abdominal organs in the evaluation of abdominal
pain of uncertain origin. Such CT scans may involve an ion-
izing radiation dose of 0.5 rem. Magnetic resonance imag-
ing (MRI) may also be used to provide high anatomic detail
in axial, sagittal, and coronal views without the use of ioniz-
ing radiation. Many MRI machines also allow 3-dimensional
reconstruction of suspect areas. The application of T1 and
T2 weighting allows differentiation of tissues within solid
organs without the need for contrast, although gadolinium
can be given to enhance the appearance of tumors. The
powerful magnetic field that is produced by MRI can affect
individuals who have implanted metallic devices; however,
any retained metal bodies are cause for rejection into the
astronaut program.
Cystoscopy may be performed by a consulting urologist in
the evaluation of hematuria, asymptomatic infection in male
candidates, or intraurinary tract anatomic lesions noted on
imaging studies. This procedure involves passing a lighted
scope retrograde through the urethral meatus into the bladder.
Cystoscopy can be performed on an outpatient basis under
anesthesia when rigid instruments are used, or with local
anesthesia when a flexible scope is used.
Urodynamics studies to assess voiding function may be
indicated; these include uroflowmetry, cystometrogram,
and pressure-flow studies. Uroflowmetry measures the
flow rate of urine as the subject voids into a calibrated flow
meter toilet. A cystometrogram measures the pressure in
the bladder as it fills. It requires a small indwelling catheter
in the bladder during filling. The filling media can be water,
contrast enhanced water, or carbon dioxide. Pressure-flow
studies are a combination of uroflowmetry and a cystomet-
rogram that differentiate outflow obstruction from detrusor
(bladder muscle) dysfunction. When used by a consulting
urologist, pressure-flow studies evaluate for either obstruc-
tive or irritative voiding symptoms or urinary incontinence.
These studies allow an objective assessment of the subjects
voiding characteristics by quantifying urine flow and measur-
ing voiding processes. In its most sophisticated form, testing
combines all three of these methods under video recording
and fluoroscopy for post-study review and anatomic and
physiologic correlation.
286
Annual Examination
An astronauts annual examination involves a detailed inter-
vening clinical history, a physical examination, and blood and
urine laboratory tests. The clinical history specifically queries
the subject concerning pain, voiding symptoms, infertility,
and impotence. Physical examination entails surveillance and
screening for tumors (prostate, renal, bladder, gonadal, cervi-
cal, and adrenal), sexually transmitted diseases and urinary
tract infections, and for hernia in the inguinal canal. Annual
examination also includes blood and urine chemistries and
analysis similar to those on initial selection. Imaging studies
and other more targeted laboratory studies may be performed
if clinically indicated, such as in the workup of incidentally
found hematuria or pyuria.
Serum prostate specific antigen (PSA) is measured in
men annually and has become more prominent in recent
years as a screening modality. PSA is a protease secreted by
the prostate as a constituent of seminal plasma that liquefies
the viscous semen. PSA is stored in the lumen of prostate glan-
dular ducts, and a small amount is released into the systemic
circulation where it can be measured in serum. The PSA can
be elevated from several conditions, such as BPH, prostati-
tis, prostatic infarction, vigorous manipulation (especially
biopsy), and, most importantly, cancer. PSA levels slowly
rise with age reflecting the age-related increase in prostatic
size; as such, age-specific reference ranges must be used to
determine if increased values warrant further diagnostic study
[33]. Increased PSA density (the amount of PSA per volume
of prostate tissue as measured on transrectal ultrasound), PSA
velocity (rate of rise of PSA over 12 months, in which there is
concern if the increase is greater than 0.75 ng/ml in a year), and
ratio of free to bound PSA all increase the positive predictive
value of prostatic tumor [34].
Glomerular Disease
Incidental hematuria is a not uncommon finding during routine
health screening in the aeromedical population. In the evalu-
ation of incidental hematuria, normal radiological and direct
imaging studies may rule out pathology of the lower urinary
tract. This would suggest a glomerular process. Nephropathies
such as IgA nephropathy (Buergers disease) or idiopathic
renal hematuria are the most common cause of recurrent
glomerular hematuria, accounting for 1040% of the glo-
merulonephritides. Fewer than 15% of individuals with IgA
nephropathy develop progressive renal insufficiency over a 15-
year period, and 3040% of individuals with IgA nephropathy
develop renal insufficiency in their lifetimes. Indicators of a
poor prognosis include increasing age, hypertension, preexist-
ing renal insufficiency, male gender, and elevated urine protein
(in the nephritic range). A definitive diagnosis is a finding of
IgA deposits in glomerular mesangium on biopsy.
For spaceflight crewmembers with normal renal function
and apparent glomerular hematuria for which no definitive
J.A. Jones et al.
diagnosis is established, we recommend no attempt be made
in definitive diagnosis for several reasons. In the typical inci-
dental finding, there is no evidence of a more severe glomer-
ulopathy. Usually this condition has been present for many
years, with no evidence of progression or findings suggestive
of renal insufficiency. No specific therapy is indicated, unless
renal function begins to worsen. The crewmember will most
likely not experience any health effects from this in his or her
lifetime, much less within his or her career; and finally, per-
forming a renal biopsy carries a not-insignificant risk.
Instead, we recommend a program of monitoring be per-
formed during which unrestricted training is allowed. IgA
nephropathy is a slowly progressive condition, so that semi-
annual monitoring suffices to identify any development of
renal insufficiency before a crewmembers health is affected.
Monitoring should involve a 24-h urine collection at each
annual physical with action thresholds as noted in Table 13.4.
In addition, a urinalysis should be performed every 6 months
between annual exams. Although this test is less sensitive
than the 24-h urine test, it would nevertheless detect any
rapid worsening of renal function manifested by proteinuria,
hematuria, or casts. A 24-h urine demonstrating no worsen-
ing of renal function is desirable no more than 1 year before
the planned end of a space flight. If flight is delayed, it is
recommended that another collection be obtained prior to the
passage of another year. Also, a 24-h urine collection should
be performed 1 month after returning from long duration
flight. In this evaluation, we specifically look at blood urea
nitrogen (BUN), creatinine, creatinine clearance, and total
protein. With reference to a crewmembers baseline, a uri-
nalysis obtained 10 days prior to launch would not be consid-
ered abnormal unless it shows more than ten red blood cells
per high power field or significant proteinuria.
TABLE 13.4. Renal stone risk report, showing suggested actions based
on parameters above the risk threshold.
Renal stone risk assessment
Physicianpatient information
Evaluation should include patient history, predisposing medical conditions,
medications, and lifestyle
Urinary chemistry
Hypercalciuriaa [>4 mg/kg/day or >250 mg/day in F and >300 mg/day in M]
Preflight
v Measure blood ionized calcium
v If elevated, metabolic evaluation, incl. PTH
v Increase fluid intakeb
v Reduce sodium intake
v Urinalysis-microscopic for crystals
v Consider metabolic work-up, to include calcium load test(Pak)
v Absorptive (type I or II 5060%) vs. renal leak 510%
v Treat according to Dxd
(e.g. orthophospahte, thiazides, cellulose phosphate, diet)
Postflight
v Increase fluid intakeb
v Reduce sodium intake
v Follow up urinalysis microscopic for crystals
(continued)
13. Renal and Genitourinary Concerns 287

TABLE 13.4. (continued) the condition and mitigate the need for further treatment. Fail-
Hyperoxalauria [>45 mg/day] ing this, renal dialysis, or in select cases, renal transplant offer
v Dietary counseling, reduce oxalate intakec further therapeutic options.
v Greater than 100 mg/day, consider metabolic evaluation Progressive nephropathy and all other nephropathies, with
Hyperuricosuria [>600 mg/day in F and >750 mg/day in M]
v Dietary counseling, lower purine (meat) intake
the exception of nil disease (minimal change), typically involve
v Increase urine volume significant renal dysfunction. These are likely to require
v Blood uric acid level (possible allopurinol, KCit1) aggressive treatment and will most likely be disqualifying for
Hypocitraturia [<320 mg/day] future space flight (Table 13.5).
v Increase dietary alkali intake (fruits/vegetables)
v Increase urine volumeb
v Consider potassium citrate tabletsd
Hypomagnesiuria [<40 mg/day] In-Flight Management of Genitourinary
v Increase dietary alkali intake (fruits/vegetables)
v Supplement with Magnesium oxided
Problems
Low urine volume
v Increase fluid intakeb In flight, the CMOwho is also an astronaut, a member of
Urinary supersaturation the crew, and may or may not be a physician but will, in any
High calcium oxalate/brushite (>2.0)
case, have basic medical trainingshould have knowledge of
v Increase fluid intakeb the other crewmembers relevant medical history. Further, the
v Dietary counseling avoid calcium excess, reduce sodium intaked CMO should be trained to provide onsite treatment of infec-
v Consider magnesium oxide supplementationd tions, urinary obstructions and retention, urinary calculi, and
v If CaOx is high, consider Kcit, KmgCit other such problems that arise within the crew. An onboard
High urinary uric acid supersaturation (>2.0)
v Increase fluid intakeb
medical checklist provides step-by-step guidance in treatment,
v Review protein ingestion, consider reduction if excessive [>12 oz. and consultation with ground medical specialists is available
beef/pork/poultry per day] at all times. Aside from renal stones and urinary retention,
v Check urinary Ph most genitourinary problems arising during a mission are
(>7.0 predisposes for brushite,<5.5 predisposes for uric acid) expected to be infections. Some of the more common of these
Consider urinary alkalinization
v (potassium citrate)
are discussed below.
v If serum uric acid is elevated, if have gouty symptoms or if having uric
acid calculi
v possible treatment with allopurinol
Urethritis/Cystitis Infections
Assess urinary chemistry and re-evaluate in 6 weeks Irritative voiding symptoms are the hallmark of cystitis,
High sodium urate (>2.0)
v Dietary counseling, decrease sodium intake
although the sufferer may have a honeymoon period of asymp-
v Increase fluid intakeb tomatic bacteriuria for a period prior to onset of symptoms.
High struvite (>75.0) Dysuria is the most common complaint, but typically a patient
v Check urinary pH (>7.00) will also suffer from urinary frequency, urgency, occasionally
v Evaluate for urinary tract infection and treat with appropriate Antibiotic or incontinence, and pain or discomfort in the suprapubic region,
v possible acetohydroxamic acid
v Increase fluid intakeb
lower abdomen, or flank. Moreover, a patient will occasion-
ally have gross hematuria, fever, or back pain. The suprapubic
This information is used for preventive measures and crewmember counseling. region or the area along the course of the urethra will be tender
All passed or extracted stones should be collected and analyzed. to palpation. Cloudy and foul-smelling urine are classic signs
a
Dietary calcium restriction is not advised due its influence on bone and oxa-
late absorption. 8001000 mg/day is appropriate for all patients, from food
of this urinary tract infection, although early infections may
sources, not supplements. exhibit neither. Cystitis is usually not associated with fever or
b
Minimum 2.5 L/day recommended urine volume. leukocytosis. The presence of either of these is indicative of
c
A comprehensive list of food with oxalate contents is available upon request. systemic toxins, most likely due to an ascending infection that
d
Treatment recommendations: will likely progress to pyelonephritis or lobar nephronia.
KCit 20 mEq bid to adjust urinary pH to 6.5. (KMg Cit is also recently being
used clinically for prophylaxis).
Urinalysis is the most helpful and available immediate
MgOx 300450 mg/day. clinical indicator of cystitis, showing positive for leukocyte
Allopurinol 300 mg/day. esterase and, possibly, nitrites on the urine reagent dipstick. It
Orthophosphate 1.5 g elemental P/day divided doses. is not unusual for the hemoglobin test to be weakly positive,
Hydrochlorohtiazide 25 or 50 mg bid. but this is not required for diagnosis. Leukocyte esterase is
positive when the local immune response has been provoked
Should renal function begin to deteriorate, there are few and polymorphonuclear neutrophils (PMNs) are shed into the
general treatment options for progressive IgA nephropathy. urine. Positive nitrites indicate the presence of a bacterium
The first treatment, immunosuppressive therapy with steroids that can convert nitrates to nitrites, usually a gram-negative
or azothioprine (Immuran), can often arrest the progression of enteric species. Microscopic examination of the urine will
288 J.A. Jones et al.

TABLE 13.5. 24-h urine analysis regime for monitoring of IgA nephropathy.
Parameter Normal range Off-nominal range Abnormal range
Protein < 1 g/24 h 1.52.5 g/24 h > 2.5 g/24 h
CrCl (normalized to 1.3 M2BSA) 95120 cc/min < 80 cc/min < 70 cc/min
Action Continue monitoring Repeat in 1 week to 1 month. If repeat is not in Immediate referral to nephrology
normal range, refer to nephrology
Blood pressure
Blood pressure reading 1025 mmHg in SBP > 25 mmHg SBP
515 mmHg in DBP > 15 mmHg DBP
Action Continue monitoring Repeat x3 days consult Nephrology if persists Immediate Nephrology Consult
Urinalysis
# RBCs/HPF 03 310 > 10
Protein on dipstick None 12+ 3 + or >
Action at L-10 None None. Considered consistent with known patho- Repeat in 24 h. If repeat is not in
physiology in this individual normal range, consider standard
hematuria workup or 24 h collection
at discretion of flight surgeon
Action at 6 month check Continue monitoring Continue monitoring. Considered consistent with Perform 24 h urine. If not in normal
known pathophysiology in this individual range, refer to nephrology.
Abbreviations: CrCl, chromium chloride; M2BSA, body surface area in square meters; SBP, systolic blood pressure; DBP, diastolic blood pressure; RBC, red
blood cells; HPF, high power field.
Source: Developed by J. Jones, T. Marshburn, NASA Johnson Space Center, Houston, TX.

often show increased urine sediment, including amorphous
debris, PMNs, and bacteria. If the sample is fresh, the bacte-
ria may demonstrate motility under microscopic analysis. The
onboard CMO will have urinalysis dipsticks and in the future
microscopic resources available to perform these tests.
Organisms are likely to be simple community acquired
species, including E. coli (7990%), Klebsiella (5%), Entero-
bacter (2%), Staphylococcus saprophyticus or epidermidus
(up to 10%), and Streptococcus faecalis (Enterococcus).
Other nonbacterial organisms may also be present, includ-
ing Chlamydia, unreaplasma, mycoplasma, Candida, and
Adenovirus 11 and 21; both are associated with hemorrhagic
cystitis. Upper tract infections will also include Proteus and
Pseudomonas. Proteus mirablis and Klebsiella can contain
ureases that split urea into ammonia, inducing an alkaline
urinary pH. They may thus create a favorable milieu for
the precipitation of magnesium ammonium phosphate (stru-
vite) stones. The means to identify bacterial species inflight
are not yet available on ISS; however, it is planned to add this
capability in later stages of operations.
Treatment of simple cystitis includes oral hydration with
23 L of water daily, oral antibiotics, and symptomatic relief
with an agent such as pyridium. While pyridium provides local
urinary analgesia, it also discolors the urine, turning it orange;
the crewmember should be briefed about this effect prior to its
use. For more severe symptoms, an antispasmodic agent (anti-
cholinergic) may be considered, with careful attention to side
effects. Antibiotics of choice for treating cystitis include oral
nitrofurantoin and combinations of sulfa and trimethoprim.
Second-generation penicillins and cephalosporins are also
effective but are more likely to adversely affect indigenous
normal flora. Later-generation beta-lactams, aminoglycosides,
and quinolones should be reserved for more complicated or
refractory UTIs.
Prophylaxis for a crewmember with a known history of
UTIs may be advisable for the duration of a flight. This is
best performed with a urinary antiseptic such as mandelamine
mandelate, which is converted to formic acid in the urine, or
a urinary-specific antimicrobial agent such as nitrofurantoin,
which is less likely to produce side effects (e.g., diarrhea, vag-
initis, or cutaneous drug reaction). Nitrofurantoin has a broad
spectrum of action against community-acquired organisms
and a low inherent resistance due to multiple sites of action.
Neither of these medications is flown as a matter of course
in the Space Shuttle or ISS medical kits, but either could be
added to the manifest as needed. The sulfamethoxasole/trim-
ethoprim combination, which is flown in the onboard kits, has
a slightly higher but acceptable side effect profile.
Pyelonephritis
Upper tract infections would represent a serious medical event
during a space flight. Management would be highly depen-
dent on the vehicle and mission setting. If the classic signs
13. Renal and Genitourinary Concerns
and symptoms are exhibited, including flank pain, fever, and
shaking chills, immediate consultation with ground urology
specialists is warranted.
Treatment of preflight or postflight pyelonephritis would
vary somewhat in light of the magnitude of systemic systems
exhibited by the patient. If systematic symptoms are minimal
and a close follow-up is possible, it may be appropriate to treat
with oral hydration and high-dose oral bactericidal broad-
spectrum antibiotics such as quinolones. If systemic systems
are moderate to severe, for instance to include toxemia (e.g.,
the patients temperature is higher than 38.5C, the WBC is
greater than 12.5 thousand or shows a significant left shift, or
the patient is shaking with chills/rigors, etc.), the patient should
be hospitalized, urology consulted, and the patient placed on
IV fluids and antibiotics. A renal ultrasound should also be
considered to rule out the possibility of urinary obstruction,
calculus, or lobar nephronia.
On the Shuttle, urine dipsticks may be used to confirm pyuria,
but no laboratory diagnostic means beyond this are available.
Antibiotic treatment options and intravenous fluids are lim-
ited, most likely necessitating an early mission termination to
allow definitive treatment. Treatment of in-flight pyelonephritis
on the ISS could be managed more aggressively than on the
Shuttle, with the goal of preventing progression to urosepsis
and mandatory evacuation. With appropriate ground consul-
tation, a renal ultrasound could be conducted to rule out the
possibility of urinary obstruction, calculus, or lobar nephronia.
Treatment can include intravenous fluids and antibiotics, with
choices including ceftriaxone, imipenem, and amikacin. Cip-
rofloxacin and quinolones are available as oral agents. A Foley
catheter can be placed for a period of acute treatment, and close
monitoring of fluid intake and outputs observed. Blood urea
nitrogen, creatinine, and serum electrolytes can be assessed
with onboard laboratory capabilities. At present the means to
perform a white blood cell count is not available on the ISS, but
an on-board analyzer is planned for later stages.
Close monitoring of a crewmember would be required,
with consideration for medical return if the condition does
not resolve with available treatment or if obvious obstruction
is noted on ultrasonography. Progression to urosepsis would
require stabilization to the extent possible and earth return for
definitive care and relief of any obstructive process.
Prostatitis
As previously noted, prostatitis has occurred during a long
duration mission, prompting an early crew return. Sufferers
usually complain of a dull, heavy ache in the perineum or
anterior rectum that often is worsened by defecation. The
pain may be referred to the glans penis. A low-grade fever is
typically present. The prostate will be tender and boggy on
digital rectal exam. Some sufferers may have accompanying
cystitis. Laboratory tests to support the diagnosis of prostati-
tis include urinalysis by urinary dipstick for leukocyte ester
and nitrites. No imaging capability will be available on the
289
Space Shuttle. However, on the ISS, an ultrasound exam may
be performed with ground guidance to show post-void resid-
ual urine in the bladder and direct imaging of the prostate.
If systemic symptoms are mild in flight, this condition
can be managed with antibiotics, such as trimethoprim/sul-
famethoxasole or ciprofloxacin given orally for 10 days. If
the systemic symptoms are severe, intravenous fluids should
be administered plus intramuscular ceftriaxone every 24 h or
intravenous amikacin every 8 h. If the patient has accompany-
ing retention problems, a Foley catheter should be inserted
for 4872 h. Additional symptomatic relief can be given with
antipyretics, analgesics, and rest.
Bartholins Gland Infection
Painful swelling in the labia majora, usually in the lower half
signals Bartholins gland infection. The area is usually ery-
thematous and may be warm, with possible palpable fluctu-
ance of the gland. Neither laboratory tests nor imaging are
indicated.
If the gland is non-fluctuant and less than 3 cm, it can be
treated with an oral antibiotic such as cefadroxil administered
over a period of 710 days. If the gland is fluctuant and is
greater than 3 cm (1.18 in.), it will require incisional drain-
age. For this, local anesthesia will be required. Drainage into
the vaginal mucosa is preferred, leaving a temporary drain
sutured in place for five or more days. ISS resources would
support such treatment, with appropriate ground medical
guidance.
Epididymitis
Epididymitis typically involves a gradual onset of swelling
and discomfort in the scrotum that is usually unilateral but
can be bilateral. Prenes maneuver, in which pain is relived
by elevating the testes manually, may have little meaning in
microgravity. Epididymitis can produce a fever, sometimes
exceeding 38.5C (101.3F). Exquisite tenderness, which
can be focal in either the testicular head or tail early, may
extend into the spermatic cord, inguinal canal, or lower abdo-
men. The epididymis will be boggy and the spermatic cord
thickened, occasionally with reactive hydrocoele that may be
trans-illuminated.
The common laboratory test is a dipstick that, when posi-
tive for leukocyte esterase, will show pyuria on microscopic
urinalysis. Also, epididymitis can produce an elevated white
blood cell count. On the ISS, ultrasound imaging may con-
firm the epididymis findings, as well as demonstrate increased
Doppler detectable blood flow to the affected testis.
Epididymitis must be carefully managed. If infectious and
diagnosed early, it can be treated with a course of oral antibi-
otics, such as tetracyclines, cephalosporins, or amoxicillin with
or without clavulinic acid. A late diagnosis, especially one with
toxic systemic symptoms, may require the use of parenteral anti-
biotics. Chemical epididymitis may be induced by urine refluxed
290
into the ejaculatory ducts, often due to elevated voiding pressure,
such as may occur during voiding while performing the Valsalva
maneuver. Rest and analgesics are indicated; pain can usually be
managed with non-steroidal anti-inflammatory agents.
Urinary Obstruction/Retention
Etiologies of obstruction include lower tract infections, BPH,
urethral strictures, diverticula, caruncles, calculi, trauma, and
cystourethroceles. Contributors to retention include obstruc-
tion, anticholinergic or sympathetic drugs, high emotional
stress (increased adrenergic activity), advanced age or poor
health. Medications with anticholinergic or sympathomimetic
effects are frequently used when treating space motion sickness
and may aggravate any emotional or psychological tendency
for retention. The clinical presentation of urinary obstruction/
retention is a long period without voiding or overflow inconti-
nence with dribbling or a weak stream. Physical examination
of a crewmember suffering from obstruction or retention will
reveal a distended suprapubic area or lower abdomen, which
may be quite tender. There is no imaging ability available on
the Space Shuttle to confirm the diagnosis. On the ISS, ultra-
sound may be performed and show an enlarged bladder with
a volume greater than 400 cc, and it may show some bilateral
ureteral distension and possibly bilateral hydronephrosis.
Inflight management will require reassurance along with
physical treatment. Although physical factors contribute heav-
ily to cases of retention in space flight, there may also be an
anxiety/psychological component that can be alleviated with
reassurance and relaxation of the crewmember. Moreover, the
crewmember should be assured that the CMO onboard the
Shuttle or ISS can treat this difficulty if required. Treatment
could entail the use of a urinary straight catheter, a Foley cath-
eter, or percutaneous aspiration.
Intermittent sterile catheterization is the preferred manage-
ment form if it is practical to drain the bladder, minimizing the
risk of infection. Each day a foreign body is left in the urinary
system, the risk of urinary tract infection increases. At least
three 1416 French straight catheters should be flown in the
medical kit along with two Foley catheters when retention is
considered to be at an increased risk. With previous episodes
of retention, planning and provision should include three cath-
eters per day times the number of days of the mission.
A Foley catheter may be indicated if the cause of retention is
prostatitis or if there are more than 500 cc of urine retained in
the bladder or significant hematuria after drainage. In the case
of more than 500 cc urine or hematuria, the bladder has been
acutely over-distended, thereby damaging elastic fibers in the
bladder wall. The indwelling catheter will allow the bladder
wall to heal without repeated stress until the underlying cause
of the retention is treated. When used, a Foley catheter should
be anchored and left in position. If the crewmember has a his-
tory of BPH, he is at additional risk and specialty straight and
Foley catheters should accompany that crewmember (Coude
tipped catheters).
J.A. Jones et al.
Percutaneous aspiration should only be attempted as a last
resort to relieve urinary obstruction if the catheter cannot be
passed from below. The means to perform this are provided
on the Shuttle and ISS, although this has not been performed
in space flight thus far. Careful preparation and sterilization of
the suprapubic area would be required, most likely involving
real-time guidance from ground specialists.
Obstruction complicated by infection is a dangerous condi-
tion that can be fatal due to the elevated tissue pressure and
transmigration of bacteria from the obstructed system into the
venous system or lymphatics, leading to urosepsis. Manage-
ment of urosepsis entails hydration and the administration of
antibiotics, with fluids and analgesics as clinically indicated.
Testicular Torsion
Testicular torsion occurs more commonly in men younger than
30 years old, with the peak occurring from the onset of puberty to
18 years of age. This means it is highly unlikely to occur in space
flight given the current make-up of spaceflight crews. However,
it remains possible. Signs and symptoms include acute onset of
severe, unilateral testicular pain, often associated with epigastric
pain and nausea. In these cases, the testes are commonly elevated
with a shortened spermatic cord or have a horizontal orientation.
Prenes maneuver, again a one-G dependent maneuver, either
makes the pain worse or leaves the pain unchanged.
In laboratory tests, the urinalysis and white blood cell count
are normal. With ultrasound imaging, decreased Doppler
blood flow to the affected testis is seen. Following a spermatic
cord block with local anesthetic, it is possible to de-torse the
affected testis with gentle elevation and rotation. Failing this,
immediate evacuation to Earth for open surgical de-torsion is
required to salvage the testes and relieve pain.
Conclusions
Genitourinary issues remain important considerations for human
space missions. Some genitourinary clinical issues are closely
tied to the effects of prolonged microgravity on the human body,
such as increased bone resorption and renal stone risk. Rigorous
development of physical and pharmacological countermeasures
to mitigate the loss of bone mineral calcium and to prevent pre-
cipitation of stone mineral in the urine will be key to lessen the
risk of urinary calculus in long-duration spaceflight missions.
Imaging and minimally invasive management capabilities will
also be important developments for future exploratory space
missions in case of genitourinary contingency. Specific future
technologies should provide improved onsite imaging with
3-dimensional ultrasound as well as a low-power CT or MRI
device. Further, the means for onsite intervention for stones
with a technique involving endoscopic stent placement with
lithotripsy (i.e., miniaturized Holmium laser, endoscopic or
extracorporeal lithotripsy) should be vigorously explored.
In the event a crewmember is affected by nephrolithiasis
when outbound for Mars, onboard treatment is the only option.
13. Renal and Genitourinary Concerns
The possibility of managing a non-passing stone must be con-
sidered carefully. One method of management in this scenario
would be an endoscopic surgical technique, entailing place-
ment of a ureteral stent from a retrograde approach through
the bladder, using ultrasound guidance. This procedure has
been successfully performed in microgravity in a porcine
model in parabolic flight on the KC-135 aircraft [35].
Acknowledgments. The authors would like to acknowledge
the following individuals for their contributions: Glenn
Preminger, MD, Duke University; Donald Griffith, MD,
Baylor College of Medicine; Y. Charles Pak Howard Heller,
MD, University of Texas Southwestern; James Lingeman,
MD, Indiana University Medical Center; Igor Gontcharov,
Institute for Biomedical Problems; Jennifer Villareal, NASA
JSC Engineering; Hubert Brasseaux, NASA Engineering;
Laura Nichols, Lockheed Martin
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Pediatric Urology. 2nd edn. St. Louis, MO: Mosby Yearbook;
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Hanno P, Wein A. (eds.), A Clinical Manual of Urology. Norwalk,
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Hesse A, Tiselius H-G, Jahnen A. (eds.), Urinary Stones: Diagnosis,
Treatment and the Prevention of Recurrence. Basil: Karger; 1994.
Lingeman J, et al. Urinary Calculi ESWL, Endourology, and Medical
Therapy. Philadelphia, PA: Lea and Febiger, Inc.; 1989.
Walsh P, Gittes R, Perlmutter A, Stamey T. (eds.), Campbells
Urology. 5th edn. Philadelphia, PA: W.B. Saunders Co.; 1986.
14
Musculoskeletal Response to Space Flight
Linda C. Shackelford
Locomotion on Earth is accomplished with techniques as var-
ied as the creatures that move and the environments in which
they move. Genetic design and the environment are integral
in determining the locomotion methods and capabilities of
animals and humans. The buoyant environment of the sea is
home to the whale with its massive musculoskeletal system
for propulsion as well as the jellyfish that moves about with
the ocean currents with no rigid skeletal structure. Genotype
provides the basic structure by which creatures locomote.
Interaction with the environment further refines the locomo-
tive structures, thereby influencing the phenotype. Environ-
ment and activity within that environment in turn modifies
form. The musculoskeletal system of vertebrates, comprising
a basically mechanical system integrating rigid articulating
structure (bones) and contractile movement engines (mus-
cles), both influences and is influenced by mechanical forces.
Exertion of force by the musculoskeletal system, either
for locomotion or determined effort and exercise, feeds back
directly to alter shape and performance capability. The influ-
ence of specific exercises on muscle mass and body contours
is easily recognized in humans. Weight lifters and distance
runners have a distinct difference in body morphometry. The
effects of exercise and activity on the skeletal system are less
obvious to casual observers, except in the case of those who
lack muscle activity in a limb at a young age. The paralyzed
limbs of young polio victims, for example, fail to achieve
the same length as normally functioning limbs. Less readily
apparent are the narrow bones and the decreased bone mineral
density in the affected limbs of persons stricken with polio as
children. On the opposite end of the spectrum of skeletal load-
ing and bone mass are competitive weight lifters. The world
record holder in squat lifting has a spinal bone mineral density
that is 13 standard deviations above normal [1].
The determinant of skeletal morphology and density, muscle
mass and function, and soft tissue strength and organization is
not a matter of locomotion versus no locomotion, ambulation
versus suspension, or the presence or absence of gravity per
se. The direct determinant of musculoskeletal strength, density,
and morphology is the degree of musculoskeletal loading.
Thus, a new environment with different loading forces and fac-
tors is expected to change these parameters.
Understanding this principle of relative loading is key to
understanding the human musculoskeletal response to micro-
gravity. Changes in mechanical loading during microgravity
result in a cascade of biochemical, hormonal, and structural
changes in bone, muscle, and connective tissues, each affect-
ing and being affected by the other in a complex feedback
loop as the system seeks an equilibrium in the new environ-
ment. The degree of change varies among individuals, among
the different regions in the same individual, with the degree of
change in activity compared with usual, and with the duration
of the activity change, in this case spaceflight. For the space-
flight crewmember, just as the musculoskeletal system adapts
to microgravity, upon return it must readapt to earth and the
necessity of musculoskeletal activity to maintain upright pos-
ture and locomotion against the force of gravity. Changes in
locomotor control that occur in the microgravity environment
increase the risk of falls upon return to gravity, and micrograv-
ity-induced decreases in bone, muscle, and soft connective tis-
sue strength can increase the risk of injury during readaptation
to the terrestrial environment.
With regard to the human, the dominant spaceflight factor
influencing physiological changes is microgravity, or weight-
lessness. Given that functional loading is known to increase
bone and muscle mass, loss of bone and muscle integrity are
an expected consequence of space flight where such loading is
diminished. Losses of muscle strength and volume have been
measured after 5- to 16-day shuttle missions. Urinary excre-
tion of calcium indicated increased bone resorption during
short duration Gemini, Apollo, and Space Shuttle missions.
Longer duration Skylab and Mir missions were required
to detect changes in bone density. These observed changes
raised early concern that muscle atrophy and bone loss could
increase risks of long-term space flight to unacceptable levels
unless adequate countermeasures were developed to prevent
the losses.
This chapter will focus on the effects of microgravity on
the structural integrity of bone, muscle, and connective tissue,
293
294
with an emphasis on the biomechanical changes, both as cause
and effect. Countermeasures to these adverse effects will be
discussed. Functional musculoskeletal disorders that occur as
a result of adaptation to microgravity and subsequent return
to Earth are also described. Further discussion of biochemical
markers of bone and muscle turnover can be found in Chaps.
27 and 13.
Bone Structure, Function, and Physiology
Bone is highly specialized tissue that comprises the verte-
brate skeletal system and provides the structural framework
that maintains the bodys shape. The skeletal system serves
both protective and mechanical functions. From a static stand-
point, bone forms a rigid shield to protect particularly vulner-
able tissues such as the brain, chest, and pelvic organs. From
a dynamic standpoint, bone provides a system of attachment
points and moment arms to transmit forces of muscular con-
traction into expansion of lungs, movement of body parts,
locomotion, and manipulation of external objects. It is a vital
tissue that grows, undergoes self-repair, and adapts its shape
and structural integrity in response to outside forces. Bone
supplies the protective haven for the formation of blood cells.
It also serves as the bodys main pool of minerals such as
calcium (Ca) and phosphate (P), and supports a vast surface
area for exchange of these minerals with circulating blood.
A detailed treatise on the anatomy and physiology of bone is
beyond the scope of this chapter. This section will review the
basic aspects of bone structure and function to enable better
understanding of observed spaceflight-associated changes.
Anatomy and Structure
The human skeleton reflects the predominantly upright pos-
ture assumed for locomotion and load bearing, and may be
grossly classified into axial (head, neck and trunk) and appen-
dicular (limbs) divisions. Axial elements, such as the pelvis
and spinal column, along with the lower extremities of the
appendicular skeleton, logically bear the greatest gravita-
tionally oriented loads, and so become the major focus for
microgravity unloading. Bone must provide interfaces with
muscle, tendons, and articular cartilage, and its structure and
shape accommodates these based on anatomical region and
function. The scapula comprises a broad, free-floating plate
to anchor the large muscle masses controlling shoulder move-
ment, while the long bones of the extremities are thick-walled
hollow tubes suited to bearing axial loads and serving as lever
arms. The shafts of the long bones are centrally narrowed
compared with the ends, which flare to allow optimum load
distribution in the articular cartilage surfaces of joints. A sheet
of tough fibrous connective tissue, known as the periosteum,
along with a thin layer of undifferentiated cells, cover the
outer surface of most bone. An internal cellular layer known
as the endosteum lines the central cavities of bone.
L.C. Shackelford
Basic structural attributes of all bones include a smooth,
dense exterior cortex and an interior network of cross-linking
plates and trabeculae, which harbor blood and bone marrow.
The relative thickness of the cortex as well as the mass of tra-
beculae vary considerably and are used as a basis for further
classification. Bone can be divided into two basic types based
on structural units; these are represented in all bone but in
varying proportions. Compact, or cortical bone, comprising
about 80% by mass of the human skeletal system, is strong
and dense. The structural unit of compact bone is known as the
osteon, or haversian system. These are cylindrical structures
about 250 microns in diameter and a few mm long, containing
a central canal for nerves and vessels and an extensive and
intricate system of lacunae and canaliculi. These permeate the
structure of concentric cylindrical layers known as lamellae
about the central canal, providing a canalicular network with
a surface area for nutrient and mineral exchange of from 1,000
to 5,000 m2 in adults. Bones that must assume a great deal of
bending and shear forces, such as the long bones of the lower
extremities, are primarily cortical. Figure 14.1 shows the basic
anatomical and structural aspects of mature bone.
Cancellous, or trabecular bone, comprises the remaining
20% by mass of the human skeleton and consists of a lattice
of bony struts and plates arranged in an orderly pattern around
lines of force and strain. This provides significant rigidity
with a minimum amount of structural material, and provides
a space for bone marrow, the site of hematopoietic activity.
Bones that bear primarily axial compressive or tensile loads,
such as the vertebrae, have a greater proportion of cancellous
bone and utilize the trabecular structure to bear the loads.
Mature bone tissue consists of a network of cells, primar-
ily osteocytes, interspersed within an intercellular mineral
matrix composed primarily of impure crystals of hydroxy-
apatite [Ca10(PO4)6(OH)2]. The hardness and compressive
strength of bone are attributed largely to the structure of this
crystal, but this material would be inherently brittle if not for
the lattice of collagen fibers laid down by bone-forming cells,
the osteoblasts. These fibers, along with an organic protein
matrix known as osteoid, are expressed by osteocytes during
bone formation and later mineralized. The resulting compos-
ite material combines the elasticity and tensile strength of the
collagen fibers with the hardness and rigidity of the mineral to
give bone its characteristic properties.
Physiology and Regulation
Remodeling is the basic process by which mature bone tissue
is repaired, renewed, and turned over in response to loads. It is
an ongoing process involving both resorption (or breakdown)
and formation, though not throughout all bone tissue simul-
taneously. In the adult skeleton, 80% of cancellous and corti-
cal bone surfaces and 95% of intracortical surfaces are in a
resting state at any give time, with no active remodeling. The
process of resorption is undertaken by specialized giant cells
known as osteoclasts, formed by the fusion of multiple blood
14. Musculoskeletal Response to Space Flight
FIGURE 14.1. Basic anatomy of mature bone. The long bone at left
reflects the classic tubular shape of the lower extremities, which bear
longitudinal, bending (shear), and torsional loads. It is about 90%
cortical by mass, with the remainder cancellous at the ends. The lum-
bar vertebra at right bears primarily compressive loads and is about
60% cortical and 40% cancellous
monocytes. These sparsely populate the periosteal surface
of cortical bone or the trabeculae of cancellous bone, form-
ing resorptive units known as Howships lacunae. Focal bone
resorption is followed by the influx of osteoblasts and the
formation of new osteons. Following secretion of the osteoid,
osteoblasts become surrounded by the progressively mineral-
ized matrix and differentiate into resident osteocytes.
The regulation of remodeling is multifactorial, comprising
inputs from mechanical loads and blood-borne hormonal ele-
ments as well as local tissue factors. From a simplistic standpoint,
greater loading, both in magnitude and duration of force, causes
a net positive effect on bone density, while relative unloading
causes the opposite effect. The mechanism of this process is
not entirely clear but almost certainly involves localized electri-
cal fields induced by piezoelectric effects resulting from shear
forces within the bone crystal. Loads may be induced directly
from outside forces, as in weight bearing, or by the pull of skel-
etal muscle. As such, bone density may be directly related to
muscle mass. Normal age-related loss of bone mineral occurs
partially in step with gradual loss of muscle mass.
Hormonal mediators of bone and mineral metabolism are
known to affect both rapid (Ca mobilization) and more long-
term effects (remodeling). Parathyroid hormone (PTH), typically
released in response to a hypocalcemic state, stimulates bone
resorption and intestinal absorption of calcium. Blood calcium is
increased to the system to restore normal levels, and any excess
calcium is lost in the urine. Chronic elevation of PTH, as in pri-
mary hyperparathyroidism, is associated with undue loss of bone
mineral. Hydroxy-cholecalciferol, also known as vitamin D, acts
to stimulate intestinal absorption of calcium and phosphate.
The active form of vitamin D (1,25-dihydroxyvitamin D) is
295
formed in the kidney following stimulation by PTH. Calcitonin
decreases blood calcium levels apparently by decreasing osteo-
clastic activity. Other hormonal mediators include testosterone,
which stimulates formation of bone matrix, and glucocorticoids,
which inhibit collagen synthesis and bone formation.
Human bone mass plateaus in young adult life and begins to
decline typically early in the fourth decade. A predictable loss of
bone mineral is thus an index of aging, and any outside pertur-
bations of remodeling must be viewed against this backdrop.
A clinical aspect of bone loss is the risk of fractures associated
with loss of structural strength; osteoporosis is a potential concern
in advanced age among all populations. Efforts in the past few
decades to measure this loss and provide metrics for counter-
measures and treatment have produced several indices, the
most common of which is from the World Health Organiza-
tion (WHO). WHO recommends a definition of osteoporo-
sis based on T-scores, representing standard deviations (SD)
from the mean bone density of young adult Caucasian women.
T-score changes are correlated with clinical data to reflect risk
of fracture. Osteoporosis is present when areal BMD (aBMD)
or aBMC (content) is over 2.5 SD below the mean (2.5
T-score). The presence of fractures denotes severe osteoporosis.
An aBMD or a BMC with T-scores between 1.0 and 2.5
SD is classified as osteopenia, a decrease in density in the
absence of fractures. Individuals with osteopenia may not have
increased fracture risk under normal activities, but may be at
risk of developing osteoporosis in the future [2].
Bed Rest Studies
In seeking to understand the effects of space flight upon the
musculoskeletal system, bed rest has long been used as an
analog for human space flight. In the 1940s physicians were
concerned that prolonged bed rest used as a treatment for cer-
tain illnesses and injuries was possibly related to complica-
tions of the illnesses. Because it was difficult to separate the
physiological effect of bed rest from the illness, studies were
undertaken to characterize the effects of bed rest alone. In 1944
and 1945, four conscientious objectors volunteered for either
a 2- or a 3-week bed rest study. In that study, a doubling of
urinary calcium excretion and decrements in muscle strength
and limb girth were documented [3]. Further investigations
followed, and bed rest studies were used as an analogue to
space flight in the 1960s, starting with the Gemini missions
[4] and continuing to the present time. Even during bed rest,
however, the body is not fully unloaded as in microgravity.
There is an opposition force associated with movement in bed,
and in pathological states the force required to lift a leg is
sufficient to complete a partial stress fracture in the femoral
neck. Because immobilization discourages muscle activity,
bed rest studies with immobilization have been more effective
in inducing bone loss than simple confinement to bed [3,5].
Patterns of bone and muscle loss at bed rest have been simi-
lar to that seen in space flight, though differing in degree of
296
loss. Bone loss in 13 men and 6 women who were at hori-
zontal bed rest for 17 weeks [6] was compared to that in 15
men and 2 women astronauts after 117- to 195-day (average
156 days) missions on Mir and International Space Station
(ISS). Bed rest volunteers incurred about half the rate of bone
loss in the hip, spine, and pelvis as astronauts. Conversely,
bone loss from the calcaneus in space was about half the rate
of bone loss seen in bed rest. The astronauts were required
to exercise 6 days a week, while bed rest volunteers were
required to remain sedentary, lying flat in bed. One study
comparing crewmembers aboard the Mir station using Rus-
sian countermeasures to bed rested subjects demonstrated
similar or slightly greater rates of bone loss inflight [7]. All
bed rest subjects who did not use countermeasures (13 men, 5
women) demonstrated significant losses in at least one region
of the spine and lower extremities. Although there are demon-
strable differences in regional bone loss rates between bed rest
subjects and astronauts, horizontal bed rest studies have been
beneficial in testing efficacy of countermeasures [810].
Bone Loss in Space Flight
Skeletal changes due to microgravity were first noted during
the Gemini missions. Increases in urinary calcium excretion
indicated that bone resorption was increased during space
flight. At that time, means of measuring bone density were
limited to single photon absorptiometry. Because absorption is
related to the thickness of the material the radiation traverses
as well as the absorption coefficient of the material, accurate
measures of bone density change could only be determined
in regions with little overlying soft tissue changes, such as
the distal forearm and calcaneus. As such, measurements were
restricted to the calcaneus, forearm, and wrist and hand for
Gemini and Apollo missions. During the time of the Gemini
and Apollo flights, variability in this technique was published
as about 2%, comparable to the 11.5% error of measure-
ment in current methods. In practice, preflight variability gave
ranges of 2.6% to +1.5% from the mean of three preflight
measures in the os calcis of one of the Skylab crewmembers
[11]. Large bone loss in the calcaneus during the Gemini pro-
gram raised concern that this would be a limiting factor in the
duration of mission deemed safe [12].
Measurements of bone mineral density during the Apollo
missions indicated that bone loss was much less severe than
originally thought. Skylab studies indicated that calcium loss
steadily increased for the initial month in flight and remained
elevated for the duration of the mission, the longest of which
was 84 days [13]. Bone mineral density of the calcaneus was
decreased post flight in one of three astronauts after a 59-day
mission (7.4%) and in two of three Skylab astronauts after
84 days in space (4.5% and 7.9%) [14]. The calcaneus had
not fully recovered in the crew from the 84-day mission at
90 days post-flight. There had been no longitudinal studies of
bone loss and recovery, and bone recovery was considered a
long and indeterminate process [15].
L.C. Shackelford
Later spaceflight studies used an improved method of
assessing bone mineral density using dual energy X-ray
absorptiometry (DEXA). DEXA scans are able to delineate
soft tissue density from bone density by using two different
x-ray energies that are differentially absorbed in soft and hard
tissue. Use of DEXA scans has allowed accurate assessment of
bone density with minimal radiation exposure in regions with
overlying soft tissue such as the spine and hip. A typical radia-
tion dose associated with a whole body DEXA scan gives an
effective dose equivalent (EDE) of about 0.8 mrem to men and
1 mrem to women using an array scanner. The entire series of
whole body, lumbar spine, both hips, heel and wrist scans per-
formed on astronauts results in about 1.4 mrem EDE for men
and 3.6 mrem EDE for women. In comparison, one chest x-ray
is 510 mrem EDE and a CT scan about 100500 mrem EDE.
DEXA scans, Quantitative Computed Tomography (QCT),
and peripheral QCT (pQCT) all have similar precision between
1% and 2% CV [16]. QCT and pQCT give 3D imaging as
opposed to planar DEXA images. This allows structural analy-
sis of bone. Structure is a significant determinant of strength and
quality, and reversibility of architectural changes due to bone
loss and the nature of bone loss with aging require 3D imaging
to be fully addressed. QCT has the advantage of visualizing
the bone architecture of lumbar spine and hip regions but car-
ries a significant penalty of higher radiation doses. Lumbar
QCT can give up to six times the radiation exposure of DEXA
of the lumbar spine [17], but QCT radiation dose is signifi-
cantly less than CT imaging. Because of its peripheral nature,
pQCT radiation doses are in the range of about 0.1 mrem per
slice of the tibial region (up to mid femur, depending on thigh
volume, can be imaged with pQCT). In order to assess risks
of weakened bone at tendon insertions and a potential avul-
sion fracture risk, 3D imaging through DEXA or MRI will
be necessary. MRI is currently being investigated as a means
to perform bone architectural analysis but still has significant
artifacts and hence is not now used in standard practice for
osteoporosis diagnosis and management. Russian studies per-
formed during long duration Salyut and Mir missions showed
that bone density measured by QCT decreased in the posterior
spine. From 1990 until the end of the Mir program, cosmo-
nauts flying four to six-month missions on Mir have received
preflight and postflight DEXA scans to measure changes in
bone density. It was found that the average loss in the trabecu-
lar regions of the lumbar spine, femoral neck and trochanter,
and pelvis was 1.07%, 1.16%, 1.58%, and 1.35% respectively
of the initial value for each month spent in space [1820].
Variations among regions for different individuals and among
regions within the same individual were quite large. No appre-
ciable changes occurred in the upper extremities and skull.
During a typical mission of about six months duration, the
body lost about 1.4% overall bone mineral density, whereas
the trabecular regions of the pelvis, lumbar spine, and femoral
neck typically lost about12%, 6%, and 8% of the initial values
respectively [21,22]. However, some individuals lost as much
as 20% of the initial value in the femoral neck region. No indi-
vidual maintained bone at initial values in all regions.
14. Musculoskeletal Response to Space Flight
Figure 14.2 illustrates the variability of bone loss within
regions in 18 cosmonauts who completed 4- to 14-month mis-
sions on Mir. Eight bed rest control subjects exhibited similar
losses. For any region, there is also considerable variability of
loss within individuals. Cosmonaut recovery was estimated
in repeat fliers by comparing preflight second mission val-
ues to preflight values for the first mission. Most cosmonauts
recovered some of the bone lost, but few fully recovered bone
mineral density in all regions. This raised the concern that the
crew of long duration missions could present with early onset
osteoporosis when bone losses due to space flight and aging
were combined. Whether senescent and postmenopausal bone
losses are independent of previous history of bone loss has not
been determined, and assumption of additive effect as a worse
case scenario gave concern that premature osteoporosis could
be an occupational hazard of long duration space flight [23].
With seven U.S. astronauts having completed missions
aboard the Mir station of 46 months duration, it was deter-
mined that incomplete recovery in all regions by 3 years post-
flight is the exception. Full bone mineral density recovery
occurred anywhere from 6 months to 3 years postflight for the
majority of astronauts. The few who lacked full recovery in
one or two regions had partial recovery in those regions, with
plateau after recovery less than 5% below preflight values.
To assess aging of bone due to long duration space flight in
those who failed to recover, the age of onset of osteoporosis
predicted from normal aging curves using bone density mea-
surements is utilized. Predicted age of onset assessed prior to
long duration space flight was compared to a reassessment
after up to five years postflight recovery period for the seven
astronauts who served as Mir crew. Only one astronaut did
not fully recover to within the range expected from pre-flight
values. There was residual loss at three years in two regions.
These femoral neck and femoral trochanter regions were
predicted to become osteoporotic 6 years earlier, at age 97
as opposed to age103 predicted from preflight values, and 8
FIGURE 14.2. Changes in regional bone mineral density in 18 cosmo-
nauts and five astronauts who completed missions of 414 months
duration on Mir. Some data points are missing on crewmembers.
Comparison is made with control subjects at bed rest for 17 weeks
297
years earlier at age 125 compared to a preflight prediction of
osteoporosis at age 133. (These predictions assume the rate
of bone loss between age 75 and 85 as estimated by cross-
sectional studies remains constant with aging.) Bone density
measurements in these regions were within normal bone den-
sity ranges preflight and post-recovery. The NASA Mir bone
recovery study suggests that long-term risks of premature
osteoporosis are much lower than originally feared.
From the early ISS experience, results of the first 11 NASA
astronauts, nine men and two women, have shown signifi-
cantly less bone loss in the lumbar spine than in the previous
Mir cosmonauts and significantly less loss in the femoral tro-
chanter sub-region of the hip compared to NASA Mir astro-
nauts and to Mir Cosmonauts and astronauts combined. These
differences are present both from the standpoint of loss per
mission and loss per day on orbit and may be attributable to
enhanced resistance exercise initiated early in flight by NASA
astronauts and continued throughout flight. The hip and lum-
bar spine have shown an insignificant trend toward less BMD
loss in ISS astronauts than in ISS cosmonauts. Figure 14.3
depicts comparative bone loss between the first eight ISS mis-
sions and preceding Mir missions.
When astronaut and cosmonaut data on ISS are combined,
bone loss is similar to bone loss reported on Mir. It is noted
that standard deviation of bone loss has been observed to be
large in the cosmonauts who have flown on Mir. A report on
13 men and one woman who flew as Russian and U.S. crew
on ISS Expeditions 2 through 6 notes no significant difference
between ISS crew bone loss and Mir crew bone loss measured
as a percent of the original bone density. Lumbar spine area
BMD by DEXA is reported as 0.9% loss in the lumbar spine
and 1.41.5% in the hip regions. Losses are similar by QCT,
0.9% in lumbar spine integral BMD and 1.21.6% for the
hip integral BMD. Percent loss was largest in the trabecular
regions of the hip (2.22.7%), though the largest actual loss
came from cortical bone at the endosteal surface in the hip.
Cortical losses were 0.40.5% of the original cortical bone
density in the hip [24]. The results combine both U.S. and
Russian crewmember data, and may be in part explained by
the fact that resistance exercise was more utilized by NASA
crewmembers. The Institute for Biomedical Problems in Rus-
sia has historically relied heavily upon treadmill exercise as a
musculoskeletal countermeasure and continues to emphasize
treadmill on ISS [25].
Change in T-score per mission for the lumbar spine aver-
aged 0.33, for the femoral trochanter averaged 0.43, and for
the femoral neck averaged 0.45. Mission duration averaged
171 days, ranging 128 to 195 for the first 11 astronauts on
ISS on expeditions 1 through 8. When the ISS U.S. astronaut
losses were normalized to time, BMD change expressed as
T-score change in the femoral trochanter averaged 0.08, SD
0.04 per month, the femoral neck averaged 0.08, SD 0.04 per
month, and the lumbar spine averaged 0.06, SD 0.04.
Regional bone losses are not predictable for individuals.
The population studied over the last decade has consisted of
almost all men of European and Eurasian descent. As of this
298
writing, one Russian and three American women have flown
long duration missions ranging from 167 to 188 days dura-
tion. Their bone losses have been similar to that of the men.
The longest duration Mir mission, 438 days, produced bone
loss similar to the 46 month missions with exception of the
femoral neck region, which had greater loss than average, but
still showed equal or less loss than in two cosmonauts who
flew 6.5- and 10-month missions. The amount of bone loss in
a 6-month mission was not significantly different than that of
a 4-month duration stay on Mir.
Postflight bone mineral density (BMD) losses are treated
with progressive increases in exercise load. In two instances
of 20% loss BMD of the femoral neck, cosmonauts were cau-
tioned to limit impact loading until sufficient bone had been
recovered [26]. Specific exercises for regional losses have not
been fully developed. Bed rest and ambulatory studies suggest
that resistive exercises in the 511 repetition max load range
are most effective in promoting bone formation [6,2730].
Squat and dead lift exercises are used for increasing spinal
BMD. Heel raises were proven highly effective in maintaining
or increasing heel BMD during bed rest and are used as part of
the post-flight exercise regimen. Appropriate bone-preserving
hip exercises are less well established. It appears that maximal
loading of the femoral trochanter is achieved through a shal-
low single-leg press with the foot centered under the body.
This motion was effective in fatiguing the gluteus medius
during a17-week bed rest study and minimized trochanteric
losses. Though the number of bed rest subjects performing
this exercise is too small to draw conclusions, both free body
diagrams and trends of the bed rest study indicate the single
shallow leg press with foot centered is most effective for
the trochanter [31]. Squats have been shown in ambulatory
studies to promote femoral neck bone formation and restore
mineral density. Wide squats increase the lever arm effect
on the femoral neck, providing more effective exercise for a
given load. Sports activities involving jumping are associated
FIGURE 14.3. Changes in bone mineral den-
sity after spaceflight for the Mir and Inter-
national Space Stations presented as absolute
change per month of flight. ISS data are
from U.S. crewmembers of the first eight
missions
L.C. Shackelford
with increased hip density and may be beneficial in postflight
recovery [32].
Metabolic Aspects of Bone in Space Flight
Though not a musculoskeletal disorder, renal stones may
be related to metabolic changes associated with bone loss.
Urinary calcium excretion has been elevated in all bed rest
subjects, with a plateau loss rate at 34 weeks of bed rest.
Similarly, urinary calcium excretion increases during space
flight, leading to concerns that risk of renal stone formation
may be increased. Postflight renal stones have been reported
in space shuttle crew (see Chap. 13). Immediately postflight,
calcium excretion is elevated. The relative hypovolemia seen
in returning crewmembers in the immediate postflight period
contributes to orthostatic intolerance and results in aldoste-
rone secretion and scant urine production for several hours
following landing, a condition also favoring stone formation.
It is likely that the concentrated urine with hypercalcuria may
result in renal stone nidus precipitation in the initial postflight
hours. Symptomatic renal stones typically present days to
weeks later.
Calcium balance studies were initially the more reliable
method of determining bone loss until the more accurate bone
densitometers were developed but remain central to under-
standing this process. The net calcium balance is estimated
from the difference between calcium excretion in the urine
and feces and the calcium intake in the diet. Increased fecal
excretion of calcium results from decreased calcium absorp-
tion in the intestines. Calcium balance and calcium metabolic
modeling are useful for countermeasure development through
elucidating the mechanisms of bone loss. Metabolic stud-
ies may indicate increased rates of bone loss before they are
detected by bone densitometry. Calcium excretion in the urine
is associated with increased bone resorption, which also results
14. Musculoskeletal Response to Space Flight
in increased collagen excretion. Deoxypyridinoline and pyridi-
noline cross links found in bone, muscle, and connective tissue
as well as the bone specific collagen cross-link, n-telopeptides,
are increased in space flight and bed rest [3335].
Muscle Loss
With strength trained and sprint athletes, muscle cross-
sectional area declines rapidly with inactivity. Force produc-
tion declines along with electromyographic (EMG) activity,
and eccentric force and sport specific power are impaired by
inactivity [36]. Similarly, muscle mass, volume, and strength
are diminished during space flight. Extensors are affected most
rapidly, but both extensors and flexors may lose up to 30% of
isokinetic torque during longer duration missions [37]. The
type II fast fibers have greater loses in humans during space
flight than their type I slow counterparts [38,39]. Increased
urinary excretion of deoxypyridinoline and pyridinoline, met-
abolic markers for the muscle collagen loss, is associated with
space flight muscle atrophy.
Muscle strength losses in the antigravity, or postural mus-
cles, have been measured postflight in short duration shuttle
crewmembers as well as long duration astronauts and cosmo-
nauts returning from Mir and the ISS. Shuttle crew experi-
enced decreased concentric peak knee extensor torque (12%)
but no significant change in peak knee flexor torque during
isokinetic testing at 60 degrees per second. Peak knee exten-
sor torque decreased by 31% and peak flexor torque by 27%
after Mir missions of 117189 days [40]. Muscle volumes
measured with MRI showed decreases from 4% in the psoas
to 17% in the gastrocnemius and the soleus, with intermediate
losses in the anterior leg, quadriceps, hamstrings, and intrin-
sic back muscles, reaching a new steady state at 4 months of
space flight (as estimated by linear regression of 16- to 28-
week missions) and returning to normal 30 60 days postflight.
Neck muscles had no volume loss [41].
Muscle soreness in the hamstrings, quadriceps, calves, and
lumbar region is quite common in the postflight period, as
these postural muscle groups are fully challenged following
prolonged inactivity. Postflight lumbar pain from normal
activity at home that was significant enough to postpone post-
flight isokinetic strength testing has been reported.
Other Musculoskeletal Disorders
Other connective tissue changes noted have been increased
spine length of 47 cm during space flight [42,43] and a 1 mm
increase in single lumbar disc height on MRI with bed rest
[44]. Increased disc height and postural changes, such as loss
of lumbar lordosis, contribute to spinal lengthening. Dur-
ing the first few days of space flight, astronauts frequently
report lumbar pain. Etiology of the back pain is unclear. One
suggested cause is paraspinal muscle imbalance during the
299
adaptation phase in microgravity with resulting mechanical
low back pain (a condition frequently involving some degree
of posterior facet overload or irritation). Another cause may
relate to stretching of the posterior ligaments associated
with spinal lengthening. The nucleus pulposis imbibes fluid
when unloaded and increases in volume. This translates into
increased disc height, which may produce pain due to con-
nective tissue stretch. Similarly, bed rest subjects also experi-
ence low back pain during the first week of bed rest and have
increased disc volume.
There does not appear to be a higher than normal incidence
of postflight bone or muscle injury. One cosmonaut fell down
a hill and sustained a fracture during the postflight rehabilita-
tion period, but Russian physicians did not feel bone loss was
a contributing factor to the fracture considering the magnitude
of the forces during the fall. However, soft connective tissue
injuries have been reported in the feet and back. Astronauts
have reported plantar fasciitis symptoms postflight, which
resolve within a few days to weeks. This is similar to find-
ings following bed rest studies in individuals who have had no
exercise or standing for 17 weeks [6]. Incidence of herniated
nucleus pulposus (HNP) in astronauts is increased in the astro-
naut population as a whole but has not been temporally linked
to space flight [45]. One astronaut experienced acute onset of
back pain when moving about the cabin prior to strapping into
an entry seat after onset of gravity during shuttle descent for
landing. This later proved to be a herniated nucleus pulposus.
Sciatica has occurred inflight and postflight in more than one
cosmonaut. One possible etiology of the higher than normal
incidence of HNP in astronauts post flight is that the enlarged
nucleus pulposis exerts unaccustomed strain on the annulus
with subsequent reloading on return to earth. This increases
the risk of rupture of the annulus during high lumbar disc
loading activities such as bending and rotating.
Treatment of Pain Syndromes
Postflight management of muscle pain consists of gradual
increase in exercise intensity, post-exercise icing, and use of
nonsteroidal anti-inflammatory agents. Tight hamstrings and
calves are present in bed rest subjects and astronauts follow-
ing space flight and may contribute to the sensation of muscle
soreness. Stretching exercises for the back and lower extremi-
ties hasten recovery of flexibility.
Low back pain in flight is commonly treated with postural
adjustment. Periodically tucking into a tight fetal position for
a period of a few seconds has been found to alleviate pain.
Pain may also be relieved by tying the foot of the sleeping
bag to prevent full extension during sleep or by strapping into
one of the shuttle seats to sleep. Spaceflight veterans taught
this technique to new astronauts long before it was recog-
nized by flight surgeons as beneficial. Sciatica symptoms are
treated with modification of activities to reduce spinal loading,
physical therapy, and anti-inflammatory medications. Clinical
300
motor strength and spinal reflex testing must be documented
regularly in persons exhibiting signs and symptoms of sciatica
at the onset of sciatica and continued until sciatica resolves,
whether inflight or postflight. Diagnostic tests such as elec-
tromyography and nerve conduction velocity (EMG-NCV)
studies may be useful in monitoring neurological changes.
EMG changes typically lag neurologic insult by a couple of
weeks, so it is important not to rely on EMG changes to diag-
nose a progressive motor deficit. Presence of a progressive
motor deficit postflight is an indication for referral to a neu-
rosurgeon. Any bowel or bladder symptoms are also cause for
immediate referral.
Plantar fasciitis is frequently observed in crewmembers and
bed rest subjects and was present in several astronauts follow-
ing long duration Mir missions. In a 17-week bed rest study, all
subjects who did not exercise as well as about half of the resis-
tive exercise group developed plantar fasciitis upon resuming
ambulation. The exercising subjects recovered within a few
days of reambulation and the non-exercisers within a week or
two, although one non-exerciser required several weeks for
recovery and one had a relapse about a month later. Two sub-
jects in this study with persistent plantar fasciitis had aggra-
vated the condition with walking several hours a day, one as
a door-to-door salesman, the other on an international tour.
Treatment in astronauts and research subjects reporting symp-
toms of plantar fasciitis consists of stretching the arches prior
to walking and performing flexor digitorum brevis exercises
by gathering a towel laid upon the floor into folds with the
toes. Use of running shoes with good arch supports has proven
highly beneficial in decreasing plantar fasciitis pain post-bed
rest. Plantar fasciitis has not been reported in treadmill use on
orbit and would not be anticipated given the lower than body
weight loads exerted by the device during typical exercise.
Muscle strength testing did not produce appreciable muscle
soreness after 6 or more weeks exercise training while at bed
rest. Overall musculoskeletal function following bed rest with
exercise was near normal. One individual who was a sprinter
prior to bed rest with exercise was able to sprint near his nor-
mal speed the first week out of bed rest. He tried out for a semi-
professional football team upon leaving the study two weeks
after the end of bed rest and functioned at a level comparable
to other players except in coordination testing. He reported he
had difficulty negotiating the rope obstacle course at the same
speed as the other players. Overuse injuries such as patello-
femoral pain and low back pain, which were common to the
alendronate and bed rest control groups, were not present fol-
lowing bed rest in the exercise group. Plantar fasciitis, which
was present in all of the non-exercising bed rest volunteers,
affected about half of the exercise group but resolved quickly
and did not recur in those who exercised.
Physical Countermeasures
The most obvious measure to prevent changes due to unload-
ing in microgravity is to artificially load the bone. Artificial
L.C. Shackelford
gravity has been proposed since long before the first human
space flight, including by such revered pioneers as Russian
visionary Konstantine Tsiolkovsky near the turn of the twenti-
eth century. A force mimicking gravity alone is not sufficient,
as bed rest occurs within a gravity field and results in bone
loss. Active exercise that loads the bone in an overall mag-
nitude and direction similar to that which modeled the bone
is required to maintain mineral integrity. In a 1996 NASA
study evaluating advanced life support systems for lunar and
Mars missions conducted at the Johnson Space Center, four
ambulatory subjects were confined to an enclosed chamber
for 90 days and were found to have lost bone density in the
femoral neck despite use of a bicycle ergometer and hydrau-
lic exercise equipment. A subsequent chamber test in which
a treadmill was used in addition to the cycle ergometer and
hydraulic resistive device produced no bone density changes.
Maintenance of musculoskeletal conditioning is dependent
upon proper loading of the skeleton, which in this compari-
son, treadmill exercise apparently restored.
Human space flight has seen an evolution of exercise
devices and methods as experience in longer duration exposures
to microgravity has accrued. The Skylab IV mission utilized
a Teflon slip plate as a treadmill. The Mir station had a
motorized treadmill that was used in the passive and active
mode. Skylab and Mir both utilized resistance exercise in
the form of a friction rope and 80 lbs bungee cords respec-
tively; in spite of these, crewmembers from both stations
showed increased urinary and fecal calcium and bone loss.
The use of a rope pull apparatus for 80 min a day and that
of longitudinal compression at 80% body weight during bed
rest was found to be ineffective in mitigating bone loss [9].
Similarly, bone loss has occurred during flight despite use
of bungee cord exercises and a full body-loading suit (penguin
suit) utilizing bungee cords from the shoulders to the waist
and waist to the thighs on Mir [21]. These findings contrast
with the normal urinary calcium and preservation of bone
mass during 17 weeks of bed rest with one to one and a half
hours of exercise a day at high resistance [6]. Neither con-
stant compression nor light to moderate resistance exercise
appear to be effective in bed rest or space flight. A high
net vector of load from ground reaction force (compressive
forces) and muscle forces along the trabecular lines for the
individual regions preserve the trabecular architecture and
density and prevent bone loss.
Rate of change in bone strain has also been proven a signifi-
cant factor in maintaining or increasing bone density [46,47].
Hence, preservation of muscle strength is essential to pres-
ervation of bone, but is not sufficient alone. In space as well
as on the ground, bone adaptation is governed by the three
rules stated by C. H Turner: (1) It is driven by dynamic, rather
than static loading. (2) Only a short duration of mechanical
loading is necessary to initiate an adaptive response, and (3)
Bone cells accommodate to a customary mechanical loading
environment, making them less responsive to routine loading
signals [48].
14. Musculoskeletal Response to Space Flight 301

A 17-week bed rest study of resistance exercise as a coun- the ISS expedition crews since the first expedition (shown in
termeasure resulted in no bone loss in two of nine subjects and Figures 14.4 and 14.5). Resistive exercises on orbit include
positive calcium balance in all subjects. The resistance exer- squats, heel raises, and dead lifts as well as upper extremity
cise subjects preserved bone density through hypermetabolic exercises. The number of repetitions that can be performed
state in which bone formation exceeded bone loss [31]. The 17 per day is lower than desired due to hardware limitations.
weeks of bed rest allows adequate time to detect bone changes Therefore, increasing the number of repetitions to compensate
in most regions. A series of bed rest studies conducted over for inadequate load has not been tested on orbit. In addition,
a periods of 13 years in which subjects remained horizontal frequent device failures have further limited effective consistent
for durations of 536 weeks indicated that urinary excretion exercise. Despite such limitations of the equipment, resistive
stabilized by the 17th week of bed rest [9]. Five weeks bed exercise appears to present a promising countermeasure that
rest was not sufficient to produce a significant bone loss in will be developed further with more robust successor devices
the lumbar spine [5]. Subsequent studies conducted at JSC capable of greater loading.
in the late 1980s using DEXA scans to detect bone changes Early initiation of exercise during 17 weeks bed rest allowed
were performed for 17 weeks [7]. This duration corresponds the muscle to maintain and increase strength to load the bone
to the shortest Mir (115 days) and ISS (128 days) expeditions. sufficient to maintain bone mineral density in an hour to an
It should be noted that bed rest corresponds to space flight in hour and a half of resistive exercise a day. Similarly, the
bone loss pattern but not degree of bone loss. Extrapolation
of bed rest or spaceflight data beyond the period of time data
has been measured has in the past been proven to be error
prone. In the case of early Gemini and Apollo flights, mis-
sions beyond nine months were felt to risk serious impairment
from bone loss [49].
Spaceflight exercise countermeasures have been limited
according to the equipment available on Skylab, on Mir, on
the space shuttle, and on ISS. Constraints of launch weight,
volume, and loads imparted to the spacecraft all narrow the
options for exercise hardware. Exercise countermeasures for
shuttle missions (all less than 18 days duration) and Mir mis-
sions have included treadmill, rower and cycle ergometers.
Treadmill exercise is felt to improve postflight gait through
simulation of ground-based walking and gravity-like eccen-
tric loads on the lower extremities [50]. Cycle ergometer as
well as treadmill exercise have been used to preserve aerobic
capacity. Elastic bungee cords were used to preserve muscle
strength on Mir, as was a rope pulled through a resistive pul-
ley (the exergenie) on Skylab. Neither device was beneficial
in preventing calcium loss from the bones, with results overall
similar to bed rest without countermeasures.
The Russian system of countermeasures has consisted
of cycle ergometry, treadmill running, and resistance exer-
cise with bungee cords. Increased physical training occurs
toward the end of the mission. In the first few months of a
long duration mission, cosmonauts frequently missed or had
shortened exercise sessions on the Mir station in order to
meet the demanding schedule of station tending and scientific
activities. Space flight with the Russian countermeasures has
produced bone losses similar to or slightly greater than the
bone loss measured in subjects undergoing 17 weeks of con-
trolled bed rest [7].
The standard suite of capabilitiestreadmill, cycle
FIGURE 14.4. Astronaut Leroy Chiao preparing for a squat exercise
ergometer, and bungeesis available on ISS; however, due on the interim resistive exercise device aboard the International
to compelling ground data with bed rest subjects, heavy Space Station. This requires a harness to distribute the force from
resistive exercise capability has been added. A resistive two loading canisters over the shoulders and through the axial spine
device capable of producing 300 lbs of force and further as the crewmember moves from a deep knee bend to a standing
augmented with bungee cords has been available for use by position (Photo courtesy of NASA)
302
FIGURE 14.5. The classic dead lift exercise utilizes a rigid bar
between the two loading canisters of the interim resistive exercise
device (Photo courtesy of NASA)
improvements in ISS astronauts compared to Mir cosmonauts
may be in part due to a more rigorously adhered to and earlier
implemented exercise schedule as well as the increased inten-
sity of resistive exercise in the former. The astronauts on ISS
begin their intense training as soon as schedule permits and
space motion sickness symptoms subside, usually during the
first week of flight.
These modest improvements have occurred during long
duration ISS flights despite one half of the resistive exercise
time having been missed due to scheduling constraints and
equipment failures. In addition, restriction of load capabili-
ties due to hardware failure to meet original design criteria
have further limited effectiveness of resistance exercise [31].
Success of any resistance exercise program is dependent upon
generating sufficient loads with proper biomechanics to load
the affected regions. Elimination of body weight during exer-
cises emulating lifting in microgravity increases the externally
applied loads required to adequately train the musculoskeletal
system. In the bed rest study, only one woman did not exceed
300 lbs in the horizontal leg press, and two men exceeded
L.C. Shackelford
500 lbs during the 5 repetition maximal exercises at the end
of the study.
Numerous ambulatory studies of resistive exercise to
improve bone mineral density have illustrated that bone for-
mation requires loads of the 511 repetition maximal range for
training. Lower loads of 15 repetitions or more to reach failure
have not been successful in increasing bone density in young
individuals. Also, regions with increased bone density dur-
ing exercise programs vary between studies. This may be due
to slight variations in the exercise regimens that can produce
drastic differences in loading scenarios for individual regions.
This was illustrated in the resistive exercise bed rest study in
which individuals who added a slight hip flexion/extension
movement to the single calf raise experienced little or no bone
loss in the femoral trochanter, while those who held the hip
straight had bone loss equivalent to bed rest controls.
The exercise countermeasures used aboard Mir and Sky-
lab did not prevent musculoskeletal wasting. Resumption
of full activity was gradual, with rehabilitation carefully
monitored by flight surgeons and exercise trainers. As noted
above, injuries other than the higher than expected incidence
of HNP in shuttle astronauts have not occurred. Full recov-
ery of bone lost during long duration missions has occurred
within 3 years in most of the astronauts who flew on Mir.
From this standpoint of no injuries and full recovery during
postflight rehabilitation in most astronauts, it can be argued
that countermeasures are sufficient for long duration mis-
sions with the promise of return to a protective environment
on earth. Possible compromise of ability to perform an emer-
gency shuttle egress in the event of a landing mishap has
caused some concern over muscle strength losses. However,
not all astronauts can complete an emergency egress test pre-
flight in the launch and entry suit. Muscle strength and bone
density losses after shuttle and Mir missions have not had
any mission impact or major health impact to date.
However, exploration missions to Mars, which might
involve transit times of six months or greater in micrograv-
ity, present a new challenge. If not prevented, musculoskeletal
wasting on missions to Mars may limit mobility and ability to
accomplish surface exploratory objectives. Geologic explora-
tion is frequently most productive in areas with high relief
due to the ability to observe and measure multiple sedimen-
tary and volcanic strata without the necessity of drilling. One
limitation of robotic exploration that human exploration may
overcome is negotiation of difficult terrain. Failure to prop-
erly maintain musculoskeletal conditioning and cardiovascu-
lar endurance during four to six month flights to Mars may
limit the advantages of manned exploration of Mars.
A recent resurgence in interest in the use of artificial grav-
ity as a countermeasure to the effects of space flight upon
multiple physiologic functions includes predictions that expo-
sure to mechanical forces integrated over time will preserve
bone [51]. However, spacecraft design may have significant
impact upon the efficacy of artificial gravity for the musculo-
skeletal system. If the spacecraft is designed with ergonomic
14. Musculoskeletal Response to Space Flight
efficiency to minimize work involved in maintaining and
operating the spacecraft and in performing activities of daily
living, the effect of artificial gravity will be nullified and bone
and muscle strength may deteriorate unless exercise counter-
measures are enforced. Development of exercise equipment
capable of delivering loads of 500600 lbs without imparting
significant mechanical stress and vibration to the spacecraft
frame is necessary to test musculoskeletal countermeasures
that will enable astronauts to function as planetary explorers
after 46 months confined to a spacecraft.
Pharmaceutical Countermeasures
Because bisphosphonates inhibit osteoclastic resorption of
bone, they have excellent potential to counter the resorption
that occurs during weightlessness. This class of drug attaches
to the hydroxyapatite crystal at the site calcium pyrophosphate
is normally adsorbed and interferes with osteoclast activ-
ity. One of the first bisphosphonates marketed in the United
States, etidronate, was tested during long duration bed rest
and found effective at higher dosage [9]. The toxic dosage at
which osteomalacic bone forms is very close to the therapeutic
dosage, therefore the drug was not deemed suitable for space
flight. Subsequently, clodronate was tested with good results
other than large bone losses in the calcaneus in one bed rest
volunteer [10,52]. Clodronate was withdrawn from the U.S.
market by the manufacturer because of an adverse reaction
during the clinical trial phase but continues to be marketed in
Europe. The newest generation of bisphosphonates, including
alendronate and risedronate, are aminobisphosphonates. The
medications are the most effective oral antiresorptive agents
currently marketed, with widespread clinical use in the pre-
vention of osteoporosis related fractures.
Results of studies in which bisphosphonates were given
during bed rest were similar for the 1981 report of clodronate
[53] and a more recent 17 week bed rest alendronate study
completed in 2000 [52]. Overall calcium balance was posi-
tive, and regional losses were negligible except for the calca-
neus. Research subjects taking alendronate preserved bone in
a hypometabolic state in which bone resorption was decreased
to a greater extent than bone formation.
Although bisphosphonates decreased or prevented bone
loss during bed rest, normal musculoskeletal functioning was
not preserved. Slow unstable gait and limitation of walking
distances were common to the five men and three women who
used no countermeasure to bone loss at bed rest and to the
nine men who used alendronate as a countermeasure. They
also experienced muscle soreness in the calves, thighs, and
lumbar regions upon reambulation. Maximum single-exertion
(one repetition) strength testing resulted in muscle soreness
for a day or two in the groups that did no strength training. In
contrast, the nine exercise subjects walked with a normal gait
except for some tendency to lose balance on turning around
or cornering quickly. It is interesting to note that this same
cornering imbalance has been noticed in astronauts post flight
303
and attributed to a change in sensorimotor integration of
vestibular signals due to microgravity exposure [54].
Skeletal Considerations for Exploration
Missions
With the recently renewed interest in manned exploration of
the Moon and Mars, the influence of living and working in
partial gravity on bone metabolism has become a concern of
biomedical scientists performing risk assessments to define
research and countermeasure needs for manned planetary
exploration. At a recent conference of the National Space
Biomedical Research Institute, physiologists and physicians
with expertise in bone physiology and biomechanics identi-
fied the risk of developing osteoporosis due to losses in par-
tial gravity added to losses during a weightless flight to and
from Mars as the greatest concern related to the musculosk-
eletal system. Specifically, if losses are unabated during a
6-month weightless flight to Mars, one and a half years on
the Martian surface, and 6 months return in weightlessness,
there exists a possibility of bone loss to a density at which
losses cannot be fully recovered due to bone architectural
changes. These time periods reflect one of the dominant
mission scenarios based on available propulsion methods
and favorable planetary alignment.
At present, there are insufficient data on missions over 8
months in duration to make valid assumptions about rate of
change of bone loss for these longer periods. However, an
estimate of worst case scenario would be bone loss during 400
days of weightlessness at the same rate experienced by astro-
nauts on ISS, accounting for the out and back transit times.
Bone loss on Mars, with partial gravity of 0.38 g coupled with
physical loads of exercise and geologic exploration, would not
be expected to be greater than bed rest on Earth with exercise,
so a worst case scenario for Mars would be the bone change
experienced in 117 days of bed rest, for which there are data,
extrapolated to 547 days (1.5 years). Using this worst case
scenario and adding in 1.7 times the standard deviation to give
a 95% confidence interval in each situation, an estimate of
the maximum T-score change expected in the lumbar spine
would be 2.7, in the femoral neck 2.4 for men or 3.0 for
women, and in the femoral trochanter 2.8 for men and 3.5
for women. (The database for men has a larger SD than that
for women in the hip, hence different T-score changes from
the same BMD loss estimate. Lumbar spine data bases for
men and women have he same SD.)
In terms of fracture risk, the threshold for fragility fractures
is accepted as the BMD that is 2.5 SD below young normal
for Caucasian females. It should be noted these values are
highly speculative in that (1) they assume losses do not abate
with time, contrary to ground-based evidence from spinal cord
injury, (2) they assume continued losses due to disuse on Mars,
which is unlikely with the provision of countermeasures and
the loads associated with exploration, and (3) they incorporate
304
the maximum bone loss within a 95% confidence interval
based upon large SD values of bed rest subjects with exer-
cise, as well as spaceflight crewmembers with current coun-
termeasures that are inadequate and supply half of the load
specified in the requirements for an inflight resistive exercise
device. This worst case scenario does illustrate that the risk of
irrecoverable or catastrophic bone loss is not an insurmount-
able obstacle for a mission to Mars. This risk would be further
diminished by decreasing transit time in microgravity, such as
might be afforded by advanced propulsion systems, and the
expected ease of providing exercise countermeasures with full
loads on the surface relative to the same in microgravity.
Conclusions
In summary, spaceflight crewmembers utilizing exercise
countermeasures available on Mir and Skylab experienced
musculoskeletal decrements similar to those incurred during
terrestrial bed rest studies with no countermeasures. Despite
these changes, full recovery occurred in most astronauts and
postflight injury rates have been minimal. One exception to
the lack of injury is the small increased incidence of HNP in
astronauts, which does not appear dependent upon the mis-
sion length. Currently, spaceflight of 46 months duration
has not resulted in significant hazards to astronauts due to
musculoskeletal deconditioning. However, the decrement of
musculoskeletal strength and endurance following missions
of 46 months in microgravity could prove severely limiting
and possibly hazardous during geologic exploration of Mars.
Preliminary results of ISS flights indicate some improve-
ment in efficacy of bone countermeasures, as well as less
limitation in immediate postflight physical activity as
reported by flight surgeons, although loss of strength and
muscle mass persist. Improvements in hardware and ISS
exercise scheduling are required to fully assess and develop
exercise countermeasures. Artificial gravity continues to
remain an option to prevent musculoskeletal disuse and to
preserve motor coordination, though no test platform for
such an assessment exists at this time.
Greater focus must be placed upon developing the physical
training methods and equipment to ensure that astronauts arrive
safely on the Martian surface with a musculoskeletal system
trained and conditioned to meet the demands of geologic explora-
tion of the hostile surface environment. It is the duty of the scien-
tists, physicians, and engineers working with the space program to
develop means to minimize risk of traumatic and overuse injuries
that could inhibit or curtail useful scientific work while maximiz-
ing the benefits of manned exploration. Humans have performed
geologic exploration of the lunar surface and have lived in space
for durations equivalent to a trip to Mars. Safely accomplishing
Martian exploration is an achievable goal. In accomplishing this
goal, we have learned and will continue to learn about adaptation
to the mechanical forces that act upon and are produced by that
marvelous creation, the human musculoskeletal system.
L.C. Shackelford
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40. Lee, S.M.C., M.E. Guilliams, S.F. Siconolfi, M.C. Greenisen,
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48. Turner CH. Three rules for bone adaptation to mechanical stim-
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51. Lackner JR, DiZio P. Artificial Gravity as a Countermeasure in
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S. Smith. Alendronate as a potential countermeasure to micro-
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Suggested Readings
Morey-Holton, WA, Meulen VD. The skeleton and its adaptation to
gravity. In: Fregly MJ, Blatteis CM (eds.), Handbook of Physiol-
ogy, Chapter 31. Section 4: Environmental Physiology, Volume I.
L.C. Shackelford
Published by the American Physiological Society. New York, NY:
Oxford University Press; 1996: 691719.
Webster SS Jee. Integrated bone tissue and physiology: Anatomy and
physiology. In: Stephen C. Cowin (ed.), Bone Mechanics Hand-
book. 2nd edn. Boca Raton, FL: CRC Press; 2001: 1-11-68.
15
Immunologic Concerns
Clarence F. Sams and Duane L. Pierson
Immune System Function and Significance
for Space Flight
The human immune system is composed of a complex set of
specialized cells, chemicals, and organ systems that interact to
protect the host from pathogenic challenge and aberrant tissue
growth. The immune system consists of two major elements:
innate immunity and acquired immunity. The innate or non-
specific immunity includes the phagocytes and natural killer
cells as well as chemical factors (lysozyme, complement,
etc.) that act to control extra-cellular pathogens. Resistance
of this system to pathogenic entities is not adaptive and is not
increased by repeated exposure. The acquired immune system
itself consists of two functional components: humoral immu-
nity and cell-mediated immunity. These elements adapt and
become more responsive with repeated exposure to pathogens.
Simplistically, the humoral immune system encompasses pro-
tein factors (antibodies) that bind and neutralize their antigen
targets and the specific cells (B cells) that produce the anti-
bodies. The cell-mediated immune system includes the T cells
which regulate many aspects of overall immune response and
directly provide self vs. non-self discrimination. This system
is critical to the control of intracellular pathogens (such as
viruses) and the containment and elimination of malignant
cells. These elements interact to protect the host from a broad
range of medical threats.
Defects in immune function can result in three distinct failure
modes: (1) immunodeficiency, where the immune system fails to
contain infections, (2) autoimmunity, an inappropriate response
to self antigens that damages the host, and (3) hypersensitivity,
an over-reaction of the immune system to innocuous foreign
antigens. Any of these failures can have a significant medical
impact on crewmembers during space flight. Precise regulation
of immune function is critical because an overly active immune
system can be just as damaging as an unresponsive one. Finally,
the interplay of immune changes and environmental exposures
in space flight (e.g., radiation, chemical exposures) can also
induce long-term health risks for the crewmember.
Immunologically mediated disorders can directly affect
spaceflight crew operations, and the operational impact will
depend upon the specific mission activities involved. Among
the disorders that have potential mission impact are (1) infec-
tions, (2) allergic reactions, (3) autoimmune problems, (4)
reactivation of latent viruses, and (5) increased risk for cancers.
An added factor is that an illness that has minimal medical
consequence in a terrestrial situation can have a major oper-
ational impact during space flight. Simple upper respiratory
infections can cause delay of mission and incur significant
programmatic costs. Illness can reduce crew comfort and well-
being, adversely affect crew performance, cause the inability
to complete critical mission tasks, result in early termination of
the mission, or at an extreme, result in loss of life. Due to the
potentially serious consequences of immunologic disorders,
care must be taken to minimize these risks to the crew during
all phases of mission operations.
Spacecraft-Related Risk Factors
for Immunologic Diseases
The crewmember risk for development of immunologically
related diseases represents a balance between the challenges
presented by the environment and the response of the immune
system to those challenges. The spacecraft environment pres-
ents a number of unique characteristics that must be considered
for the evaluation of crewmember medical risks, diagnosis, and
treatment. These factors can increase frequency of insult, degree
of exposure, route of exposure, and options for treatment.
Spacecraft crew compartments are, without exception,
closed ecosystems of limited volume. For example, Shuttle
pressurized volume (crew quarters) is 2700 cu ft. However,
the useable living space of the orbiter is considerably smaller.
The middeck is 9 by 11 by 7 ft and flight deck area is about
7 to 8 by 11 by 6 ft with a curved ceiling that drops to about
3 to 4 ft on the outer edges. Additional space is lost to seats
and stowage (lockers and equipment) located in this volume.
307
308
Within this space, up to seven crewmembers must live, eat and
work for 5 to 16 days at a time. The limited physical separation
of galley and toilet facilities is a good example of the physical
constraints imposed. Such cramped conditions may increase
the risks of pathogen transmission by direct contact. Further,
the limited volume exacerbates the potential for transmission
by aerosols.
The atmospheric restrictions of the spacecraft also exac-
erbate the consequences of chemical releases or combustion
events. Such events may irritate mucosal membranes or expose
the crewmember to potentially sensitizing chemicals or aller-
gens. Because of this, a toxicologic assessment is performed
on all items that are included in the pressurized volume. This
limits the amounts and types of chemicals that can be car-
ried. It also determines the level of containment that must be
provided for the particular chemical agent during crew opera-
tions. As NASA moves to longer duration missions aboard the
International Space Station (ISS), the issue of allergic sensi-
tization of the crewmembers to compounds in the spacecraft
atmosphere is beginning to be considered. Known sensitiz-
ing agents such as formaldehyde and nickel are present in the
spacecraft atmosphere and water, respectively. Exposure to
these agents for an extended time may result in the develop-
ment of allergies to these compounds.
Another obvious characteristic of the spacecraft envi-
ronment is the lack of gravity. This has a number of physi-
ological and operational impacts on the crewmembers, but
a major issue relevant to immune-related disorders is the
lack of sedimentation of larger particulates. Since gravity is
absent, there is a greater exposure to particulates (especially
large particulates >100 m in size) than one would have in
terrestrial settings where such particulates settle out of the
air. These particulates can cause increased ocular and nasal
irritation. This irritation may raise the potential for infec-
tions via the mucosal routes of exposure. The lack of sedi-
mentation of aerosols, skin, and clothing particles may also
result in new potential routes for transmission of disease. For
example, if a crewmember developed a simple herpetic lesion
during flight due to the reactivation of latent herpes, virus
could be shed via spittle or direct sloughing of the lesion
into the atmosphere. The virus, which is typically transmit-
ted by direct contact, could potentially be transmitted to
ocular or nasal sites via atmospheric routes. The potential
consequences of an ocular herpes infection are quite serious
and illustrate the additional complications of operating in the
microgravity environment. Particulates are cleaned from the
atmosphere by circulating the cabin air through a filter.
Air and water must be recycled in the closed environment of
long duration spacecraft such as the ISS or in exploration class
vehicles. This results in significant constraints on the design
of habitability systems and may have further impacts on crew
health related to the approaches used or failures in atmospheric
or potable water conditioning systems. Problems with life sup-
port equipment can result in significant environmental impacts
to the crew. During the joint USRussian NASA Mir missions,
malfunctions in the life support systems resulted in cabin tem-
C.F. Sams and D.L. Pierson
peratures above 40C and high humidity in the spacecraft. In
addition to the increased stress on the crew from the heat load,
growth of microorganisms such as fungi and molds were also
increased. Release of spores or contact with fluids contain-
ing microorganisms during these events provides the increased
potential for development of infections.
The limitations of air and water systems also restrict the
options for personal hygiene. Facilities for personal bathing
and laundering of clothing are currently unavailable due to the
impacts of microgravity on fluids handling, ability to recycle
water, and power required. The result of these limitations is
the use of sponge baths for personal hygiene and utilization
of clothing for multiple days before discarding. This strategy
increases the likelihood that minor skin irritation and rashes
may occur. Rashes, abrasions, and other skin irritations are
common during space flight, and dermatological ointments
are among the more commonly used medications on orbit.
While these are rarely a significant health threat, they may
reduce crew comfort and productivity. The limited hygiene
may contribute to the risk of infecting abrasions or other
breaks in the skin and can exacerbate activities of special
mission operations such as suited space walks.
Special mission operations such as extravehicular activity
(EVA) also have unique medical issues with respect to poten-
tial infectious insult. Crewmembers universally experience
abrasions, blisters and other skin problems from contact with
the suit during EVA. The characteristics of the pressurized suit
result in numerous hot spots where hard points in the suits
interact with crewmember movements. These abrasions can
impact the ability to perform repeated EVAs. In addition, the
requirement of the crews to constantly access stowed gear and
perform routine maintenance activities increases the incidence
of minor scrapes, cuts, and contusions on the hands during
flight. Crewmembers anecdotally report that these minor cuta-
neous injuries are slow to heal during space flight, and this
can increase the likelihood of developing an infection. While
some antibiotics are available, the inability to culture and
identify microorganisms during flight can limit diagnosis and
treatment options. In some cases this can result in the applica-
tion of an inappropriate treatment regimen due to a lack of the
basic microbial information from the infected tissue.
Due to the size and complexity of long duration spacecraft,
there is a very real potential of establishing stable ecosystems
within the habitable space. Variations in humidity and airflow
at different locations in the vehicle can induce locally high
humidity or condensation that is stable over time. This sup-
ports the establishment of microbial ecosystems that contain a
variety of simple to complex microorganisms. The Mir Space
Station had this specific problem when stable condensates from
the atmosphere formed on cold water lines behind equipment.
Although these condensates were routinely mopped up and
cleared, they developed stable microbial colonies populated
by a variety of uni- and multi-cellular organisms including
algae, bacteria, ciliates, and protozoa (Table 15.1). The crew
can be repeatedly exposed to these organisms during main-
tenance activities, and protective gear must be provided for
15. Immunologic Concerns
TABLE 15.1. Microorganisms isolated from Mir surface condensate.
Fungi Bacteria
Candida guilliermondii Alcaligenes faecalis
Candida lipolytica Bacillus circulans
Cladosporium species Bacillus coagulans
Fusarium species Bacillus licheniformis
Hansenula anomala Bacillus pumilus
Penicillium species Bacillus species
Rhodotorula glutinis CDC Group IVC2
Rhodotorula rubra Citrobacter brackii
Citrobacter freundii
Comamonas acidovorans
Corynebacterium species
Flavobacterium meningosepticum
Presumptive Legionella species
Pseudomonas fluorescens
Serratia liquefaciens
Serratia marcesens
Unidentified gram-negative rods (3)
Yersinia frederiksenii
Yersinia intermedia
use when necessary to limit exposure. A further concern with
stable microbial ecosystems in spacecraft is the potential for
genetic mutation of microbes due to the continuous radiation
exposure while in space. While this has not been documented
in samples collected to date, the potential for alterations in
virulence or other characteristics must be considered.
The radiation inherent in the space flight environment
results in significant exposure to the crewmembers over the
course of a long duration mission. The biological response
to continuous exposure to the energy spectrum experienced
during flight in high inclination earth orbit or during missions
outside the protective environment of the Van Allen belts is
not currently known. However, the hematopoetic tissue is
among the more radiation sensitive organ systems and one
would expect changes in immune function and surveillance to
occur in parallel with an increased incidence of genetic muta-
tion at the cellular level in the crews. The combination may
result in an increased risk of carcinogenesis over the course of
an astronauts career. Acute exposure to solar events outside
the Van Allen belts has the potential for catastrophic doses
that could result in hematopoietic and immune system failure
and an increase in morbidity and mortality.
Overall, the physical and operational factors discussed
above that are associated with space flight have a significant
impact on the environmental challenges that the crewmembers
immune system must respond to. The spacecraft environment
may also induce changes in the immune system itself, some
of which may be unique to microgravity flight and others that
are a result of general stresses to the human during adaptation
to a novel environment.
Chronic Stress and Isolation
Analog Population Studies
Physical and psychological stresses are known to cause immune
alterations, and these factors may be significant contributors to
309
the effects seen during space flight. Due to the limited numbers
of individuals who have flown in space, analog studies have
been useful to assess the potential impacts of stress-induced
immune dysregulation. Data from studies of students during
exam periods and military cadets during training indicate sig-
nificant immune effects from psychological stress. Additional
data from submarine crews, Antarctic expedition crews, and
isolation chamber studies have made it clear that numerous
factors associated with space flight, independent of the micro-
gravity exposure, can and do cause immune alterations which
can place the subjects at risk.
Cytokines and Immune Function
The human immune response has been extensively studied in
a variety of pathophysiologic conditions including acute and
chronic stress. The components of immunity, cell-mediated
(CMI) and humoral (HI), are designed to handle interactions
between various forms of internal and external antigenic chal-
lenges. CMI, coordinated primarily by thymic-dependent (T)
and natural killer (NK) cells, is primarily responsible for host
defense against intracellular pathogens and neoplastic trans-
formation. HI, coordinated by B cells that synthesize antigen-
specific immunoglobulins, is primarily responsible for host
defense against most extracellular pathogens. Thus, a person
with an infection with improperly functioning CMI would
have increased susceptibility to intracellular pathogens such
as viruses, fungi, and mycobacteria, while an abnormal B cell
function would increase susceptibility to extracellular patho-
gens such as bacteria and parasites. Both T cell and B cell
functions are dependent upon a subset of T cells referred to as
helper T cells (TH) that function by producing soluble glyco-
peptides called cytokines. These cytokines are largely respon-
sible for the function of specific arms of the immune response
(cellular vs. humoral). Type 1 help supports cellular responses
and includes interleukin (IL)-2, IL-12 and interferon (IFN)-g
while type 2 help supports humoral responses and includes
IL-4, IL-5 and IL-10 (Figure 15.1) [1].
When an antigen is encountered and processed, the specific
cytokines produced by TH cells influence the relative cellular
vs. humoral response to that antigen. If a cellular response is
needed for host defense to a pathogen (i.e. viral), a cytokine
imbalance that favors a humoral response is clinically the same
as a deficiency of total immune response. TH cells have recently
been divided into subpopulations based upon differential cyto-
kine production profiles. TH1 cells (T helper cells producing
type 1 cytokines) support primarily CMI; TH2 cells promote
HI. Clinically, this is important not only in infectious diseases
but also in hypersensitivity diseases. Clinical hypersensitivity
occurs when immune responses to a given antigen, although
mechanically intact, create disease in the host. An easily rec-
ognized example is allergic rhinitis caused by allergen-specific
IgE bound to mast cells. It has been established that an isotype
switch from IgM to IgE in allergen-specific B cells is directed
by type 2-specific cytokine control (i.e. IL-4) and antago-
nized by type 1 cytokines (i.e., IFN) [2]. Thus, this disease can
be viewed as an immune dysfunction caused by abnormal
310
FIGURE 15.1. Simplified representation of Type I and Type 2 cyto-
kine balance and the regulation of different arms of the immune sys-
tem. While the in vivo situation is considerably more complex than
this simple representation, Type 1 cytokines generally support cell-
mediated immunity and type 2 cytokines favor B cell differentiation
and humoral immune function. IL, interleukin; IFN, interferon; TNF,
tumor necrosis factor
activity of one or both TH subpopulations in susceptible per-
sons. The balance of cytokines produced is thus critical to the
maintenance of appropriate immune system function, and dys-
regulation can result in adverse clinical outcomes.
Though space flight provides an environment with unique
stressors where astronauts live and work, it also includes
stressors that are experienced in terrestrial settings. These
stressors impact the central nervous system (CNS) resulting
in neuroendocrine changes that alter the cytokine balance and
induce differential expression of immune functions. Specific
examples of such stressors include confinement, isolation,
fear, anxiety, psychosocial stressors, sleep deprivation, and
physical discomfort. Any one or combination of stressors
may induce immune dysregulation due to the influence of
the neuroendocrine changes on the immune system. This bi-
directional communication between the CNS and immune
systems has been well studied, and much is known about
how physical and psychological stress affects the human
immune response.
The neuroendocrine regulation of the immune system
occurs through both the glucocorticoid hormones of the
hypothalamic-pituitary-adrenal (HPA) axis as well as the
neurotransmitters of the sympathetic nervous system [3]. The
glucocorticoids are potent anti-inflammatory agents and affect
the production of specific cytokines and other proinflamma-
tory agents (e.g., prostaglandins). Glucocorticoids inhibit the
production of IFN-g, IL-1, IL-2, IL-6, IL-8, IL-12 and TNF-
A and GM-CSF, all proinflammatory cytokines associated
with TH1 function. They also up-regulate the TH2 cytokines
C.F. Sams and D.L. Pierson
FIGURE 15.2. An illustration of pathways associating space flight
stress to the potential clinical outcomes with mission and crew health
impacts. CRF = corticotropin releasing factor; ACTH = adrenocorti-
cotropic releasing hormone
IL-4 and IL10, effectively inducing a shift in TH1/TH2 cyto-
kine balance. This shifts the immune system away from the
differentiation of macrophages, natural killer (NK) cells, and
cytotoxic T cells of the cell mediated immune system and
toward differentiation of the eosinophils, mast cells, and B
cells that support antibody-mediated response. Glucocorti-
coids also up-regulate the expression of B2-adrenergic recep-
tors on lymphocytes. These receptors are the primary immune
target for the sympathetic neurotransmitter noradrenaline.
Noradrenaline is thought to suppress the function of lympho-
cytes via interaction with the B2 receptor, but these responses
vary with immune cell type and tissue location.
From the above discussion, it is apparent that the CNS modu-
lates immune function via the action of glucocorticoid and sym-
pathetic hormones while the immune system modulates itself
and CNS function via the action of cytokines. This complex, bi-
directional interplay provides a mechanism for tightly coupling
immune response to neurologic function. This feedback system
maintains the critical balance of immune function required to
ensure optimal health. Disturbing this balance causing either
over-stimulation or suppression of the immune system will
have significant clinical consequences (Figure 15.2).
Closed Chamber Immune Studies
An examination of in vivo cell-mediated immune function
was recently performed in subjects during an extended test of
a closed, atmospheric recycling system at the Johnson Space
Center [4]. The subjects were sealed in a test chamber for
90 days during which atmospheric oxygen was generated
from expired carbon dioxide (CO2) using recycling systems
employing a mixed biological (plants) and chemical recycling
system. The chamber subjects were required to maintain and
repair hardware that was located within the test chamber.
This chamber test was a test bed for systems that will eventu-
ally be utilized on ISS or exploration missions. Delayed-type
hypersensitivity tests (DTH skin tests) were performed on the
15. Immunologic Concerns
subjects shortly before entering the chamber. In addition, tests
were performed 45 days into the chamber study and two days
before chamber exit (day 88). Another test was performed 30
days after chamber exit. Several individuals who were work-
ing on the chamber system, but not confined to the chamber,
were used as a control group.
The DTH tests are scored by both the number of antigens
that elicit a cutaneous response (minimum 2 mm induration)
and by the area of the response. The chamber group exhibited
a decrease in the number of antigens they responded to dur-
ing the chamber confinement. This was not observed in the
control subjects. When a composite score (CMI score) that
factored in both the number and size of response was deter-
mined, the chamber subjects exhibited a unique decrease in
DTH response after 90 days in the chamber (Figure 15.3).
The sample size (n = 4 chamber and 4 control subjects) was
not sufficient to reach statistical significance within the nor-
mal subject variability. However, from either the individual
responses or the CMI score, it is evident that the chamber
exposure down-regulated the cell-mediated immune function
in all of the chamber participants. None of the control subjects
exhibited this response.
A potential consequence of the dysregulation of the immune
system is the reactivation of latent viruses. The effects of both
acute and chronic stress on the reactivation of EBV have been
extensively studied [5]. EBV shedding patterns were fol-
lowed in Antarctic expeditioners before, during, and after 8
to 9 months of isolation. Increased EBV shedding was accom-
panied by decreased cell-mediated immunity as measured by
delayed-type hypersensitivity (DTH) skin testing [6]. Similar
results have been obtained in a variety of stress models. Glaser
et al demonstrated the proliferative response to Epstein Barr
FIGURE 15.3. Mean cell mediated immunity (CMI) Scores in 4 cham-
ber and 4 control subjects by relative chamber day. C-30 is 30 days
before chamber entry. C+45 and C+90 are 45 and 90 days in the
chamber, respectively. E+30 represents 30 days after chamber exit.
The mean CMI score for control subjects was relatively unchanged
throughout the study period [4].
311
virus polypeptide antigens was decreased during examination
periods in healthy medical students [7]. Further studies during
the examination and basic training period of military academy
cadets demonstrated examination stress induced the reactiva-
tion of latent EBV without changes in latent herpes simplex
virus (HSV)-1 or HSV-6 [8].
Immune Alterations and Medical Events
During Space Flight
Evidence suggests space flight causes a dysregulation of the
immune system. U.S. and Russian space scientists have inves-
tigated human immune responsiveness following space flight
since the late 1960s [9]. Russian scientists have reported
reduced in vitro proliferative responses after 140-day mis-
sions that were associated with lymphopenia in crewmem-
bers [10,11]. Reduced NK cytotoxicity and decreased in
vitro interferon production after space flight have also been
documented [10,11]. Further evidence of in vitro immune
dysregulation was reported by French and Russian investiga-
tors from 5 cosmonauts who resided between 26 and 166 days
on board the Russian space station Mir [12]. They reported
reduced numbers of cells expressing IL-2 receptors 48 h after
stimulation in culture, without changes in the number of T
suppressor/cytotoxic (CD8+) or T helper/inducer (CD4+)
cells. The supernatants from these cultures contained normal
levels of IL-1 and increased amounts of IL-2. Taylor and Jan-
ney reported reduced delayed-type hypersensitivity responses
to a panel of intra-dermally applied recall antigens on flight
days 3, 5, or 10 from ten astronauts when compared to their
preflight control values [13]. This demonstrates that altera-
tions in cell-mediated immunity do occur in vivo and supports
the hypothesis that the immune system is functionally altered
during space flight.
The immune changes associated with space flight have
been postulated to increase the potential for infectious dis-
ease in crewmembers. Analysis of medical records during
the early Apollo missions indicated that about 50% to 60%
of the crewmembers experienced some symptoms of infec-
tious illness during the preflight or in-flight time period.
To minimize the mission impact of these incidents, the
Health Stabilization Program (HSP) was implemented prior
to Apollo 14 (discussed further below). The program limits
exposure of the crew to potentially infectious individuals and
significantly reduced the incidence of reported illnesses dur-
ing subsequent Apollo missions. The HSP program remains
an element of the current Shuttle and ISS medical support
program and continues to minimize the incidence of illness
in the crews. However, even with the HSP in place, a sig-
nificant number of Shuttle missions have included reports
consistent with infectious disease during the immediate pre-
flight and in-flight time periods. This suggests a reduction in
immune function is associated with the stress of preparing
for and executing space missions.
312 C.F. Sams and D.L. Pierson

Postflight Crewmember Immunologic Assessment

In a preliminary study, we have recently evaluated the cyto-
kine production of various lymphocyte subpopulations in
conjunction with serum and urine stress hormones before and
immediately following space flight. Whole blood samples
from 27 astronauts were collected at three time points (10
days preflight, landing day and 3 days postflight) surround-
ing four recent Space Shuttle missions. The duration of these
missions ranged from 10 to 18 days. The assays performed
included serum/urine stress hormones, comprehensive sub-
set phenotyping, assessment of cellular activation markers,
and intracellular cytokine production following mitogenic
stimulation. Absolute levels of peripheral granulocytes were
significantly elevated following space flight, but the levels
of circulating lymphocytes and monocytes were unchanged.
After three days of exposure to unit gravity, the percentages
in most of the subjects had returned to near baseline. No sig-
nificant alterations regarding levels of circulating monocytes
were seen following space flight. Lymphocyte subset analysis
demonstrated trends towards a decreased percentage of T cells
and an increased percentage of B cells. Nearly all of the astro-
nauts demonstrated an increased CD4:CD8 ratio, which was
dramatic in some individuals [14].
Although no significant trends were seen in the expression
of the cellular activation markers CD69 and CD25 following
exposure to microgravity, significant alterations were seen in FIGURE 15.4. Mean percentages of T cells (CD3+) and T cell
cytokine production in response to mitogenic activation for subsets (CD4+ and CD8+) that respond to stimulation by producing
specific subsets. T cell (CD3+) production of IL-2 was sig- cytokines (A) IL-2 and (B) IFN gamma. Samples were collected
nificantly decreased on landing day, as was IL-2 production 10 days before launch (preflight), on landing day, and 3 days after
by both CD4+ and CD8+ T cell subsets for most subjects landing (postflight). [13] *Significant differences (p < 0.05) and
(Figure 15.4A). Production of IFN was not altered after error is represented as standard error of the mean. IL; interleukin;
flight in either T cells in general or in the CD8+ T cell subset. IFN, interferon.
However, a decrease in IFN production in the CD4+ T cell
subset was observed on landing day (Figure 15.4B). Serum to the reduced orthostatic tolerance and other physiological
and urine stress-hormone analysis indicated significant phys- changes. During the Mir 18/STS71 mission, during which
iologic stresses in astronauts following space flight. Taken three long-duration flyers were returned from a four-month
together, these results demonstrated alterations in the periph- mission on Mir, we examined the subpopulations of circu-
eral immune system of astronauts immediately after space lating white cells during flight (within 24 h prior to land-
flight of 10 to 18 days duration. However, due to the physical ing) and compared them with data obtained before flight
stresses of landing, postflight measurements are affected by and immediately after landing. The inflight samples were
confounding variables that make evaluations of space flight obtained by venipuncture and stained during flight using
vs. reambulation effects difficult. Assays that will tolerate the the Whole Blood Staining Device [15]. All ground samples
delay of in-flight sampling, such as the ones posed here, will were also stained using the same device. The data are lim-
provide a true investigation of the effects of space flight on ited to three subjects, in whom an apparent redistribution
the human immune system. of white blood cell populations was uniquely observed on
landing day (Figure 15.5). The circulating cells were not
significantly altered during flight compared to the preflight
Inflight Versus Postflight Changes in Circulating samples. The circulating cells also returned to preflight dis-
tributions within 9 days after flight. These changes were
Immune Cell Populations observed in crewmembers that had been in orbit for 115
It remains unclear whether the data collected from crew- days. These data indicate that re-exposure to unit gravity has
members immediately after space flight reflects the changes a significant impact on the crewmember immune cells and
occurring during flight or an acute response to return to the that this must be considered during interpretation of pre- and
unit gravity environment. It is apparent that reentry and postflight immune studies relative to immune changes dur-
reambulation are significant stressors on the flight crew due ing flight. It is also apparent that the influence of this acute
15. Immunologic Concerns
FIGURE 15.5. Relative percentage of natural killer (NK) cells in cir-
culating peripheral lymphocyte populations. Cells were identified as
CD16/56 positive CD3 negative cells by flow cytometry. Data are
expressed as the percentage of labeled cells over total lymphocytes.
Samples were collected 150 and 35 days before launch (L-150 and
L-35), 24 h before landing (FD-11), on landing day (R+0), and nine
days after recovery (R+9)
response to unit gravity should be evaluated for its potential
impact on crew health during the postflight period.
Viral Reactivation During Space Flight
Another potential risk from immune dysregulation dur-
ing space flight is the reactivation of latent viruses. Most
individuals carry a variety of latent viruses that cannot be
screened out by quarantine. These viruses can be reactivated
and expressed during episodes of decreased immune func-
tion. For this reason, external advisory groups have identi-
fied latent viruses as an infectious disease risk in astronauts
before, during, and after space flight. Eight herpes viruses
have been identified that infect humans. This family of dou-
ble stranded DNA viruses includes herpes simplex type-1
(HSV-1), herpes simplex type-2 (HSV-2), cytomegalovirus
(CMV), Epstein-Barr virus (EBV), varicella-zoster virus
(VZV), human herpesvirus-6 (HHV-6), human herpesvirus-
7 (HHV-7), and human herpesvirus-8 (HHV-8). Following a
primary infection, these viruses are capable of establishing a
lifelong relationship with their human host. Typically, they
exist within the host in a latent state, undetected and with
no symptoms. However, in response to various stressors and
the subsequent diminishment of immune function (especially
the cell-mediated immune system), these viruses may reacti-
vate and be shed in saliva, urine, and other body fluids. Some
of these viruses (e.g., VZV) may remain latent for decades
before reactivating.
An analysis of reactivation and shedding of latent Epstein
Barr virus (EBV) during space flight was performed during
313
recent Space Shuttle missions (n = 11) [16]. Saliva specimens
were collected and the extracted DNA analyzed by a poly-
merase chain reaction (PCR) assay for specific herpes viruses.
The frequency of EBV in daily saliva samples was 29% prior
to flight (for a period of 1 month beginning at 6 months before
launch), 16% during spaceflight, and 16% for the first two
weeks following space flight. This compares with a 2% to 5%
frequency of EBV shedding found in a control population.
After the flight, IgG levels of EBV viral capsid antigen were
significantly increased over preflight levels.
To determine if EBV behaved similarly to other herpesvi-
ruses or was unique, Mehta and colleagues examined CMV
shedding patterns in astronauts [17]. Seventy-one astro-
nauts serving as crewmembers on space shuttle flights par-
ticipated in the study. Fifty-five (75%) were seropositive to
CMV. Approximately 25% of the urine specimens from the
seropositive astronauts contained CMV DNA, whereas just
1 of 61 (1.6%) control subjects shed CMV in their urine.
For the 55 seropositive astronauts, CMV IgG levels did not
increase from the baseline collection point (22 months
before launch) through the landing phase. However, the 15
CMV shedders exhibited significant increases in CMV anti-
body titers. Examination of VZV demonstrated increased
reactivation and shedding in astronaut saliva specimens,
whereas control subjects showed no evidence of reactiva-
tion of VZV. Shedding of VZV in astronauts occurred dur-
ing and after flight but not during the preflight phase. No
symptoms were associated with the VZV shedding. This is
significant because subclinical shedding of VZV has not
been previously reported. A rise in VZV IgG titers was also
seen consistent with the VZV shedding data. HSV 1 and 2
exhibited no significant increase in reactivation and shedding
in astronaut saliva.
The observed increases in stress hormones, viral reactiva-
tion, and viral antibody titers indicate that stress associated
with spaceflight phases (prior, during, and after) impacts the
immune system through the hypothalamic-pituitary-adrenal
(HPA) axis and allows latent viruses to reactivate, multiply,
and be released in body fluids. Further, the number of cop-
ies of virus shed during the inflight episodes was greater
than that observed during shedding episodes preflight or
postflight (Figure 15.6). This suggests an altered ability
of the immune system to control or contain the reactiva-
tion and shedding of the virus. The increase in viral shed-
ding represents a potential crew health risk. Therefore, the
changes in virus specific immune response must be exam-
ined in order to determine the mechanisms mediating the
increase in viral release.
Infectious Disease
Development of infectious disease represents interplay
between exposure of the host and its ability to deal with the
infectious challenge. A number of strategies are utilized with
314
FIGURE 15.6. Epstein-Barr virus shedding associated with Space Shuttle
flight, as measured during preflight, inflight, and postflight collection
of samples for later analysis via polymerase chain reaction
astronauts to minimize the likelihood of exposure to pathogens
and to maximize host defense. Crewmembers are selected as
basically healthy individuals and have adequate host defense
mechanisms under typical terrestrial exposures. Normal host
defense mechanisms include the skin and mucosa found in
the respiratory tract, GI tract, and GU tract. Unless damaged
by trauma, puncture, or incisions, the skin is a most effec-
tive barrier to microorganisms. The mucosal membranes are
coated with secretions containing lysozyme and immunoglo-
bins, which also provide an effective barrier to microorgan-
isms. In addition, healthy persons live symbiotically with
their own microbial flora. This normal flora is composed of
bacteria and fungi and also provides some protection against
introduction of other pathogenic species. The crewmembers
host defense is furthered bolstered by appropriate vaccination
against likely infectious pathogens. Management of immu-
nization history, general crew health, and exposure mecha-
nisms provides the best approach to minimize crew health
risks during flight.
The control of exposure mechanisms addresses a number
of factors including the Health Stabilization Program, which
limits exposure of the crew to potentially infectious individ-
uals the week prior to launch, and numerous checks of the
spacecraft to minimize environmental exposure of infectious
agents to the crew. Bi-directional transfer of microorganisms
between crewmembers and the spacecraft has been repeatedly
documented, and establishment of stable microbial ecosys-
tems on space stations such as Mir has been previously dis-
cussed. In order to manage this issue, regular sampling and
cleaning of spacecraft environments is performed to monitor
and manage microbial flora.
In the Space Shuttle, air and surface sampling are done
twice before each Shuttle flight: once about four weeks before
launch and again at two days before launch. Samples are taken
again at landing. Sometimes samples have been collected in
C.F. Sams and D.L. Pierson
flight. In general, microbial counts show moderate increases
during a Shuttle flight and these flora typically reflect organ-
isms originating from the humans on board. Water for crew
consumption is produced by the fuel cells that react cryo-
genic hydrogen and oxygen to produce electricity and power
the Shuttle. However, the water storage tanks are launched
charged with water and tested four times before each flight.
Water produced in-flight must pass through a microbial check
valve, which contains an antimicrobial iodinated resin, before
it can be considered potable. Recently, a second resin was
added to extract the iodine from the purified water, in order to
prevent iodine accumulation by the crewmembers.
Similar strategies are utilized for ISS with regular sampling
of air, surface, and water systems. The environmental monitor-
ing, ongoing maintenance of crew health, and availability of
inflight medications provides a system to manage the infectious
risks that potentially occur during the mission. While all expo-
sure cannot be eliminated, it is possible to utilize this strategy to
minimize adverse effects on the crew and inflight operations.
Hypersensitivity and Allergic Reactions
The strategy for controlling allergic, autoimmune, or hypersen-
sitivity reactions during flight is very similar to the approach
for infectious diseases. The first line of defense is prevention.
Individuals with a history of clinically significant allergies,
asthma, or autoimmune problems are eliminated during the
astronaut selection process. The most common medications
that are used by the crews are tested prior to flight to deter-
mine whether the crewmember will exhibit any idiosyncratic
reactions, allergic responses or other intolerance. Food items
and any compounds that the crewmembers must take inter-
nally for onboard experiments (via ingestion or injection) are
tested before flight to ensure they are do not cause an adverse
reaction. While these steps can minimize the likelihood that
an allergic response will occur during flight, they cannot
eliminate the possibility of an inflight event. Medications are
provided for the inflight treatment of allergic disorders. How-
ever, it must be acknowledged that management of a signifi-
cant allergic event (e.g., anaphylaxis) would be exceedingly
difficult during space flight.
During a recent experiment, an immunization with a pneu-
mococcal vaccine was performed inflight. Approximately
30% of the flight subjects experienced significant injection site
soreness with inflammation and redness compared to less that
5% of the control subjects reporting soreness alone (1 out of
21 subjects). No control subjects developed redness or notice-
able inflammation at the injection site. The timeline of the
response was consistent with an Arthus or immune complex
reaction. While this has been reported as a possible response
to this vaccine, it is striking that such dramatic responses were
seen here almost exclusively in the flight subjects. It is pos-
sible that changes to tissue perfusion or immune regulation
may contribute to this response.
15. Immunologic Concerns
It is currently unclear whether the changes that occur in
the immune system during flight alter crewmembers suscep-
tibility to hypersensitivity reactions or allergic response. In
terrestrial settings, it is observed that shifts in immune regu-
lation can result in the alteration of clinical outcomes from
other stimuli. The potential consequences of a hypersensitivity
or allergic problem during flight can be quite serious. It is
imperative that medical officers are aware of the potential for
altered sensitivity to ingested or injected agents during flight
in order to adequately prepare for any eventuality.
Conclusions
While no illnesses or infections have been linked to altered
immune response due to spaceflight, it is apparent that changes
in immunity can potentially impact the crew during space
flight. Neither the extent of space flight induced immunologi-
cal changes nor their consequences to the crew can be fully
determined at the present time. Factors such as the physical and
psychological stressors associated with space flight appear to
be the major contributors to the observed immune alterations,
although direct effects of microgravity on cells of the immune
system or their regulation cannot be ruled out. The complex
interplay of these immune changes with the unique environmental
challenges present in the spacecraft must be fully understood to
minimize the impacts on flight operations.
Experience suggests that the risks associated with immune
system changes can be effectively managed during short
duration flight, since there is little evidence of immune-related
disorders causing significant crew distress on flight of less than
30 days. However, as mission durations increase and the inter-
play of adverse environmental factors, radiation, viral changes,
and immune dysregulation extends over greater and greater
intervals, it becomes more difficult to confidently predict
the projected outcome. Much more study of immune factors
during space flight and the fine balance between immune regu-
lation and clinical response in healthy normal individuals will
be required to make realistic projections of crewmember risks
during and after extended space flight. The ground-based study
of analogue populations and correlation of immune dysregula-
tion and clinical events will shed more light on this scenario.
This information will provide the basis for mission planners
and flight surgeons to design systems that minimize the poten-
tial for adverse events and increase productivity, comfort, and
safety of the crew during flight and upon return to Earth.
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16
Cardiovascular Disorders
Douglas R. Hamilton
Long- and short-term exposure to microgravity significantly
alters the cardiovascular system [19]. In this chapter, we
describe the cardiovascular changes and the strategies used
to manage problems in operational space medicine that arise
as a consequence of those changes. Most descriptions of
the effects of microgravity on the cardiovascular system have
focused mainly on the physiological mechanisms that contrib-
ute to cardiovascular changes. Flight surgeons need to under-
stand these important physiological effects on the human
cardiovascular system so that they can place them within the
operational context of a space mission. Crewmembers may
also have subclinical cardiac abnormalities that could be exacerbated
by the adaptive responses of the cardiovascular system to
microgravity.
To help readers of this text understand the cardiovascular
issues facing space medicine flight surgeons, this chapter
uses an operational approach and considers issues that arise
during each phase of a space mission, beginning with crew
selection and proceeding through launch, on-orbit activities,
atmospheric reentry, and postflight recovery. Both the U.S.
and the Russian space programs have implemented extensive
research programs to understand the alterations in cardiovas-
cular physiology that are induced by exposure to micrograv-
ity, changes that may eventually manifest themselves in the
form of impaired cardiovascular performance such as post-
flight orthostatic intolerance, decreased exercise capacity, or
on-orbit cardiac arrhythmias [810]. The current literature
has devoted little attention to the various clinical complications
and operational problems that can arise from the deleterious
effects of microgravity on the cardiovascular system [11]. The
focus here is on two of the primary goals of operational space
medicine: (1) to prevent the occurrence of cardiovascular
illness or impaired performance in space flight and (2) to reha-
bilitate or treat impaired cardiovascular function in a manner
that minimizes the effect on the mission while maximizing
crew health and performance.
To date, operational space medicine experience has benefited
from the clinical observation of crews on numerous missions
and from the results of life science research in the area of
cardiovascular physiology [7,12]. This chapter addresses the
challenges associated with determining how much overt cardio-
vascular pathology is acceptable in terms of the overall risk to
a mission.
Risk of Cardiac Disease in Aviation
Populations
The primary goal of the flight surgeon is to maintain the car-
diac health and performance of space travelers through preven-
tion of cardiac disease. This goal is achieved by considering
the prevalence of cardiac abnormalities in the astronaut cohort
in the context of the positive and negative predictive value of
tests used to screen and monitor their cardiac function. In this
context, primary prevention refers to the means by which car-
diovascular disease is prevented among those patients without
prior manifestations of such disease. Secondary prevention
refers to the means by which cardiovascular disease is mitigated
among those patients with clinically manifested disease. In
the case of the astronaut, cardiac disease requiring secondary
prevention is usually grounds for removal from active duty.
During space travel, several environmental and operational
factors can affect the cardiovascular system. The signs and
symptoms secondary to the presence of these factors must
be distinguished from overt cardiac disease. The means with
which to mitigate the effects of these risk factors are com-
monly referred to as countermeasures. Countermeasures have
sometimes been referred to as secondary prevention even
though overt disease is not necessarily present.
In the earlier phases of human space flight, flight surgeons
relied on provocative tests that had poor positive predictive
value (PPV) for determining the risk of cardiac events in the
astronaut cohort; risk factor assessment was the mainstay
of prognostication for the purposes of developing preven-
tive strategies. Unfortunately, substantial variations among the
astronaut cohort (e.g., age, sex, race, occupation, national-
ity, culture, occupational exposures) prevent flight surgeons
from deriving accurate data on the incidence and prevalence
317
318
of cardiac abnormalities in that cohort, despite its relatively
small size. Accordingly, risk data for the astronaut population
must be extrapolated from the prevalence of cardiac disease in
similar cohorts, such as military and civilian aviators.
The clinical presentation of sudden cardiac death, myocardial
infarction, unstable angina, and most ischemic arrhythmias
will cause abrupt incapacitation or significant impairment of
crewmember performance [1315]. Coronary atherosclero-
sis or coronary artery disease (CAD) is the largest cause of
morbidity and mortality in industrialized nations [13]. In the
United States, CAD is responsible for more than 1,000,000
deaths per year, nearly half of which are sudden, unexpected,
and the first manifestation of CAD [1618]. Atherosclerosis
usually begins to occur during the second and third decades
of life [19], and a nonlinear correlation exists between the
amount of coronary artery calcium and luminal narrowing
found at the same anatomic site [20]. Coronary atherosclerosis
is an insidious process that results in the intimal deposition
of lipid- and calcium-laden plaques and is absent in normal
arteries [21,22]. The primary mechanism leading to acute
coronary syndromes (sudden death, myocardial infarction,
unstable angina) is plaque rupture. The initiating event in an
acute coronary syndrome (ACS) however is endothelial cell
damage, followed by a pro-inflammatory response char-
acterized by endothelial dysfunction, cell injury, leukocyte
recruitment, increased monocyte adhesion, impaired nitric-
oxide relaxation, and plaque formation that eventually leads
to rupture [23]. The endothelial activation by pro-inflamma-
tory cytokines creates a tissue-factor-mediated prothrombotic
setting, which further promotes the formation of clot upon
plaque rupture [2426].
Calcification within lipid-laden plaques may eventually lead
to rupture, after which clots can form because of the release of
highly thrombogenic material. In many cases, clots are lysed
and reincorporated into the originating site of plaque. Plaque
calcification may not occur until after lipid atherosclerosis
is already significant. Surprisingly, many myocardial infarc-
tions seem to occur from vessels with less than 50% stenosis
[21], suggesting that plaque structure rather than narrowing of
the lumen is a major factor in determining the probability of
a clinical coronary event. In most cases, plaque rupture and
healing is an ongoing process that promotes further narrowing
of the arterial lumen. Plaque that is unstable and vulnerable to
rupture has been characterized as having a large lipid core and
thin fibrous cap; stable plaque, in contrast, has a small lipid
core and is capped by a thick fibrous layer [21]. The relation of arte-
rial calcification to the probability of plaque rupture second-
ary to venerable plaque is still unclear [27,28]. Significant
evidence exists to relate the extent of coronary calcification to
plaque burden, yet evidence of a strong correlation between
either factor and venerable plaque is lacking [21,29].
The pathophysiological key to predicting acute coronary
events is the identification of factors that result in an unsta-
ble or vulnerable plaque [30,31]. Recent data from Ridker
et al. demonstrate the utility of measuring high sensitivity
D.R. Hamilton
C-reactive protein (CRP) in the stratification of risk for
primary prevention of cardiac events independent from Fram-
ingham risk scores [3237]. Risk factors such as hypertension,
lipid profiles, smoking, sex, age, and C-reactive Protein (CRP)
levels may help to predict disease or to guide screening; how-
ever, the existence of coronary artery calcium in an astronaut
should be considered to be abnormal. Atherosclerotic calcium
is a harbinger of an insidious pathologic process that may take
decades to manifest itself clinically. The Combined Albany-
Framingham Study revealed that of all cases of sudden cardiac
death secondary to CAD, 50% were not preceded by warn-
ing symptoms [38]. The detection and prediction of athero-
sclerosis has changed considerably over the past few decades
because of the increasing accuracy of noninvasive imaging of
coronary calcium and simple blood tests [39].
Although the mortality rate from CAD has declined since
1970, the hospitalization rate from CAD increased by 25%
from 1970 to 1986, indicating that improved early diagnosis
and intervention can modify the outcome of this disease [40].
CAD in aviators is usually considered clinically significant
(SCAD) if a single lesion narrows the diameter of the coronary
artery by 50% or more. Minimal CAD (MCAD) is associated
with lesions producing less than 50% stenosis. A long-term
study by Proudfit and colleagues [41] showed that the rate of
cardiac events among patients with MCAD ranged from 1.5%
to 3.0% per year over a 10-year period and that positive find-
ings on a treadmill stress test or a thallium scan did not predict
future cardiac events or survival in that cohort.
The ability to identify astronauts who will develop SCAD
at some time during their career is very limited. A long-term
study of patients with normal coronary anatomy (as deter-
mined by angiography) documented rates of cardiac events
(e.g., sudden cardiac death, myocardial infarction, angina, and
ischemic arrhythmias) as high as 0.65% per year over a
10-year follow-up period [41]. In that study, patients under-
went the more invasive cardiac tests after experiencing
positive findings on an exercise test [42] or experiencing
symptoms [43] significant enough to convince a clinician to
rule out abnormal coronary anatomy. Whether these patients
had the same cardiac risk factor profile as the present U.S.
astronaut cohort is unclear, but it can be assumed that neither
cohort had significant comorbid conditions.
Oswald and others [15] determined that cardiac event rates
of 0.5% per year have been found in numerous U.S. population
studies of healthy men aged 3554 years, yet the annual rate
for military aviators of the same age range is less than 0.15%.
This significant difference in cardiac event rates among mili-
tary aviators probably results from the comprehensive selec-
tion physical examination and annual medical evaluations that
military aviators undergo throughout their careers [44], which
may identify and subsequently control significant risk factors
such as diabetes mellitus, gross obesity, hypertension, and
tobacco use [45]. This reduction in cardiac rates for military
aviators may also be due to their advanced level of education,
which is associated with lower cardiac event rates. Frequent
16. Cardiovascular Disorders
physical examinations ensure that military aviators are coun-
seled on these risk factors more often than the general public.
Also, military aviators are keenly aware that their health status
is tied to their occupations.
Determining the risk of an astronaut becoming incapacitated
during a space mission because of a cardiac event is difficult
because of the difficulty in extrapolating the unique aspects of
space travel to aviation analog environments. The quantifica-
tion of acceptable cardiac risk for space missions has not been
clearly defined. Perhaps a starting point to bound the risk can
be found in the in aviation community, where there is a broad
consensus that the risk of professional pilots becoming inca-
pacitated should not exceed the rate of mortality from cardiac
causes for a 60-year-old man in Western Europe, that is, ~1%
per year [14,4649]. This guideline, the 1% rule, provides
a metric by which aviation medicine decisions regarding car-
diovascular certification are often based. The rationale for the
1% rule is simple. A cardiovascular risk of 1% per year (102)
for a pilot is equal to a risk of ~106 per hour, as each year
consists of 8,760 h (i.e., <104 h). Because an average flight
lasts roughly 100 min and because not more 10% of that time
is regarded as critical, the risk of incapacitation of pilots aged
6065 years at critical times (i.e., during takeoff and landing)
is about 107 per hour of flight. These incidence rates decrease
by a factor of ~10 for 45-year-old pilots and by a factor of 100
for 30-year-old pilots [14]. Although the desired individual
cardiovascular risk of less than 109 per hour (for a 30-year-
old pilot) is beyond the capability of humans of any age, it
is still consistent with airworthiness standards for extremely
improbable unanticipated catastrophic failures of any engine,
system, or structure and for aircrew error or aircrew incapaci-
tation [50].
A risk of 109 per hour can be obtained by adding a sec-
ond aircrew member to the flight deck. Simulation studies
have shown that monitoring pilots can lead to the detection
and recovery of 99% of threatened crashes caused by sudden
and subtle pilot incapacitation. For a 60-year-old pilot, such
monitoring reduces the cardiovascular risk of a threatened
fatal accident due to sudden incapacitation to 109 per hour
for a 2-person crew. However, this failure risk model does not
include all-cause mortality, which for some populations (60-
to 65-year-old male pilots from England or Wales) is twice
(2.2% per year) the cardiovascular mortality rate of 1% per
year [46].
The concepts of critical phases of flight in commercial and
military aviation refer to those portions of a flight where pilot
incapacitation would result in possible mission loss. In the
Space Shuttle paradigm, mission loss can be interpreted as
any significant cardiac event in any crewmember that requires
a deorbit to a definitive treatment facility. Again, using a 1%
rule for cardiac events, the chances of mission loss during
a 16-day flight with a 6-person crew becomes 0.3% per flight
[(1/(365 days/year) (1-[10.01 annual risk of cardiac event/
year]6(crewmembers/mission)) 16 days 100 = 0.257%]. The worst-
case risk of an incapacitating cardiovascular event for crews
319
on the International Space Station (ISS) over a 1-year period
is still 1% per person per year if all other space-related factors
are ignored. This expected rate of critical medical events will
need to be decreased for mission beyond low earth orbit.
Cardiovascular selection standards for astronauts are based
solely on the risk of cardiac events; hence such standards may
be inappropriate if they are applied blindly to reduce over-
all mission risk. Pilot-related accident rates depend on flying
experience and as such decline steadily with increasing expe-
rience up to age 60 years [51]. A small increase in accident
rates has been observed among pilots older than 60 years, but
65-year-old pilots with normal experience still have lower
accident rates than do 45-year-old pilots [51]. Therefore it
is important to not presumptively remove experienced older
pilots from spaceflight crews on the basis of these cardiovas-
cular risk models unless overt and untreatable abnormalities
have clearly been identified.
The current model for ISS astronaut selection is based
on the military and civilian aviation 1% rule [52]. However,
medical support for long-duration space flights requires that
missions be terminated in the event of any significant cardiac
event. (Submarine crews, on the other hand, are selected and
trained on the assumption that the mission will proceed regard-
less of the severity of any cardiac event in any crewmember.)
Because current medical technology cannot effectively pre-
dict the occurrence of future cardiac events during long mis-
sions, current selection standards for astronauts, which rely
on tests that are effective for evoking the 1% rule, may not be
appropriate for long-duration ISS missions.
Most cardiovascular abnormalities are grounds for disquali-
fication from flight because they represent a significant risk
to the safety of the affected crewmember and that of the crew
and may well affect the success of the mission. Flight surgeons
can serve as crew advocates helping crewmembers maintain
their operational flight status. Nevertheless, flight surgeons
are responsible for identifying cardiovascular abnormalities
and for enforcing programmatic space medicine examination
standards [44,53].
Prevalence of Cardiac Events in Aviation
Populations
CAD is the leading cause of permanent disqualification from
flying status among aviators worldwide, and it is the leading
cause of nonaccidental premature deaths in all military and
civilian aircrews [5457]. Autopsy studies of Korean War
casualties by Enos and others [58] found gross atherosclerosis
in 73% of hearts examined, at least 15.3% of which had at
least 50% stenosis. McNamara and colleagues [59] performed
autopsies on 105 soldiers who were killed in action in Vietnam
(mean age, 22 years) and found gross evidence of CAD in at
least 45% and SCAD in 5% of hearts examined. It should be
noted that although these cohorts had clinically silent CAD,
there was a very high incidence of cigarette smoking and they
320
obviously did not receive the same level of selection screening
as an aviator or the current astronaut corps.
Pettyjohn and McKeen [60] reviewed 6,500 autopsies from
records at the Armed Forces Institute of Pathology of deaths
occurring in aircraft accidents or mishaps and found that 816
cases (13%) had been diagnosed with pre-existing heart dis-
ease at the time of the accident. Of these 816 cases (592 mili-
tary and 135 civilian), 89.1% had CAD. This autopsy series
compared the severity of CAD, year of death, and crew posi-
tion within the military 5-year age groups. CAD was found
in 86.6% of the 20- to 34-year-old military group. Moderate
and severe CAD was present in 17.1%. Booze and Staggs
[13] reviewed the autopsy reports of 710 commercial pilots
who died in aviation accidents and found that 61% had some
findings of coronary atherosclerosis, of which 2.5% were con-
sidered severe. Another study by Underwood-Ground [61] of
288 military, commercial, and private pilots killed in avia-
tion mishaps and 132 healthy men aged 1862 years who died
accidentally revealed no significant difference in the preva-
lence of coronary artery disease between the aviators and the
control group. The mean age in these four groups was less than
40 years, which is less than the mean age of the current U.S.
astronaut population (44 years). Another study of apparently
healthy U.S. Air Force aviators reported a rate of myocardial
infarction, angina, and sudden cardiac death of 0.02% per year
from 1988 to 1992; the mean age of the aviators who had a
cardiac event was 44 years [15]. Notably, 61% of the events
in that study were myocardial infarctions and 21% were sudden
cardiac deaths. Angina, the most prominent presentation in
ischemic heart disease, represented only 18% of the cardiac
events. These findings suggest that denial or underreporting
was of significant concern in this population [15].
Taneja et al reviewed 534 autopsies, performed from 1996
to1999 of deaths from fatal fixed-wing general aviation air-
craft accidents (82% were older than 40 years) and found the
prevalence of cardiovascular abnormalities in general and cor-
onary artery stenosis in particular to be 43.82% and 37.64%
respectively [62]. They also found that 41 of the 534 (7.6%)
had severe atherosclerosis of the left coronary artery. Nissen
et al. [63] examined a series of transplant donors assessed by
using Intravascular Coronary Ultrasound [64], and showed that
coronary atheromas were found in 17% of those younger than
20 years, 37% of those aged 2029 years, and 60% of those
aged 3039 years, whereas angiography results were negative
in 97% of these donors. Necropsy data indicate a similar age-
related prevalence and suggest that atherosclerosis risk fac-
tors are mostly likely contributing to pathological changes at
a very early age. Intravascular Coronary Ultrasound showed
that CAD is characteristically diffuse and involves the entire
arterial tree, with insidious progression to include the forma-
tion of multiple, potentially rupture-prone plaques that are
not associated with vessel stenosis. [63] These findings indi-
cate the need for aggressive and early systemic intervention
that targets modifiable risk factors to reduce CAD in the astro-
naut population.
D.R. Hamilton
Commercial pilots are routinely examined for disqualifying
illness and injury by the civil aviation authorities of their
respective countries. The requirements for these standards are
published by the International Civil Aviation Organization
and the European Joint Aviation Authorities. A recent study
by rva and Wagstaff [65] examined the permanent ground-
ing of 275 Norwegian pilots over 20 years in a cohort repre-
senting 48,229 person years. Of the 275 groundings, 97 (35%)
were for cardiovascular reasons with the majority occurring in
the age range of 4060 years, which is very close to the age
range of our current astronaut corps. Of the 97 cardiac causes
for grounding, 36 (36%) were for MI, 33 (34%) for CAD,
18 (19%) for arrhythmias, 3 (3%) for cardiomyopathy, and
7 (7%) for peripheral vascular disease. Data from Canadian
[66], Russian [67], United States Air Force [68,69] and com-
mercial pilots [70,71] also found that cardiovascular findings
were the most common cause of permanent grounding.
As noted earlier, the first manifestations of CAD can be
arrhythmias with presyncope, syncope, or even sudden car-
diac death, with potentially catastrophic aviation outcomes.
Richardson and Celio [72] reviewed the cases of 430 patients
(428 men; mean age, 40.3 years) who had been diagnosed
with supraventricular tachycardia (SVT) and were evaluated
10 years later. Of these patients, 42 (10%) were found to have
hemodynamically significant SVT, and 21 (5%) were found to
have asymptomatic recurrent sustained SVT [72,73]. Although
SVT characteristics, frequency, and occurrence in pairs were
not predictive of future sustained SVT, the presence of reen-
trant tachyarrhythmias or recurrent sustained SVT were pre-
dictive of subsequent recurrent sustained SVT.
Folarin and colleagues [74] studied 24-h Holter recordings
from 303 patients (a subset of a group of 1,575 individuals
with normal findings on cardiac catheterization) and found
that only 36 individuals (12%) had no ectopy. Notable find-
ings were the presence of isolated atrial (73%) and ventricular
(41%) ectopy, atrial (14.5%) and ventricular (4%) pairs, non-
sustained SVT (4%), and nonsustained VT (17 beats) (0.7%).
Results from that study indicated that ectopy was very com-
mon, even among asymptomatic individuals with no evidence
of cardiac disease (CAD, valvular, or conduction disorders).
Another study in which patients with VT were followed by
Holter monitoring showed that among 98 subjects with non-
sustained VT, 92% had fewer than five runs of VT in a 24-h
period, 63% had a 3-beat triplet, and 71% had only a single
episode [72]. In a 10-year follow-up study of 193 aviators with
asymptomatic nonsustained VT (more than two consecutive
premature ventricular contractions [PVCs] at a rate of more
than 100 beats per minute for less than 30 s), Gardener and
others [75] found that 9 (5%) had hemodynamic symptoms
syncope in 1, presyncope in 5, and sudden death in 3. Of those
193 aviators, 103 had no evidence of cardiac disease (CAD,
valve pathology, or cardiomyopathy) but were subsequently
diagnosed with idiopathic nonsustained VT. These investigators
concluded that cofactors such as caffeine ingestion, choles-
terol levels, and VT characteristics were not predictive of VT
16. Cardiovascular Disorders
and that the existence of nonsustained VT was not predictive
of future sustained VT.
Occurrence of Cardiac Disease
in Spaceflight Crews
Over the past 40 years, the standard diagnostic tools for
detecting CAD have evolved from noninvasive, provocative
tests to include more definitivebut invasivediagnostic
imaging. Concurrent advances in noninvasive imaging and
use of serum markers for estimating cardiovascular risk have
made less-invasive techniques such as these more accurate for
detecting cardiac abnormalities as well as better predictors of
cardiac risk. Data on the incidence of CAD in early space-
flight crews are unreliable because of the poor sensitivity and
specificity of the noninvasive diagnostic methods used at the
time. An evidence-based cardiovascular risk model based on
more recent incidence data is being developed to compare
the relative cardiovascular risk for U.S. astronauts to that for
analog populations such as commercial and military aviators,
submarine crews, and others [76].
In the early phases of the U.S. space program, the presence
of arrhythmias was taken as presumptive evidence of cardiac
abnormality, and the first grounding of an astronaut for cardiac
reasons was done because of an arrhythmia [1,5]. The incidence
of arrhythmias during actual space flight can be assessed only
for those intervals when a crew is being physiologically moni-
tored. Use of electrocardiographic (ECG) monitoring is now
restricted to periods of stressful or high-risk activities; however,
monitoring on previous missions documented several types
of arrhythmias in apparently healthy astronauts. The appear-
ance of premature atrial contractions, PVCs, and ST-segment
or T-wave changes was generally associated with strenuous
activity during extravehicular activities (EVAs), exercise, and
application of lower-body negative pressure (LBNP).
Apollo 15 was the first U.S. space flight during which
cardiac arrhythmias other than the occasional PVC were
observed. At 178 h into the mission, shortly after the lunar
module had returned from the moon and docked with the
command module, the Apollo 15 lunar module pilot experi-
enced five unifocal PVCs within a 30-s interval, a significant
increase over the one or two PVCs per hour experienced dur-
ing the translunar-coast phase of the mission. Approximately
1 h later, that same crewmember experienced a 22-beat run of
nodal bigeminy. During the postflight debriefing, the crew-
member recalled experiencing profound fatigue at the time
of this bigeminal rhythm [6,77,78]. Postflight analysis of the
medical data obtained during this mission indicated that the
Apollo15 crewmembers may have been hypokalemic, and
retrospective analysis found their lunar EVA workloads to be
excessive. Twenty-one months after the Apollo 15 mission,
the lunar module pilot experienced a myocardial infarction
[6,77,79]. No evidence of CAD had been detected before flight
by the noninvasive (exercise ECG) testing used during that era,
321
and no invasive coronary diagnostic imaging information was
available to determine the extent of CAD before flight.
Testing associated with the Skylab Program also revealed sig-
nificant arrhythmias in several crewmembers, including a 3-beat
VT complex (triplet) occurring with exercise, an atrial-ventricular
block during LBNP recovery, a junctional rhythm at rest after
LBNP, and an episode of multifocal PVCs after an EVA [1].
During the first four flights of the Space Shuttle in the
orbital flight test program, crews underwent continuous ECG
monitoring during launch and landing. Nine of the 14 crew-
members had frequent PVCs, and two crewmembers had fre-
quent PVCs during landing. One of these 14 crewmembers
was noted to have occasional PVCs, never exceeding 23
ectopic beats per minute, during pretest altitude (chamber)
and water immersion exposures. Despite having a normal
serum electrolyte profile, this crewmember also experienced
uniform PVCs after the onset of gravitational loading during
reentry, with rates as high as 16 ectopic beats per minute [80].
Nevertheless, the benign nature of these arrhythmias, along
with the logistics of providing monitoring for larger crews,
did not warrant monitoring on subsequent Shuttle missions.
Approximately one third of Shuttle crewmembers have
exhibited PVCs during EVAs. One crewmember experienced
sustained ventricular bigeminy for 10 min, and another had
frequent premature atrial contractions. Analysis of ECG
tracings from seven crewmembers and test subjects during
simulated and actual EVAs from 1992 to 1995 showed no dif-
ference in the frequency of ectopy between astronauts and test
subjects [81]. Although the number of subjects was too small
to draw any significant conclusions, these results may imply
that arrhythmias experienced during EVA were not due to
microgravity per se and that the increased ectopy seen in earlier
Shuttle flights could have been attributable to other factors.
A retrospective Holter analysis of 160 EVAs over the last
20 years (104 from shuttle, 4 from ISS, and 52 from joint ISS -
STS missions) was performed by Hamilton et al. [82]. During
the period from 1984 to 2002, NASA performed 160 EVAs
averaging 300 42 min duration (mean Standard Devia-
tion), a cumulative length of 42 days, 16 h, and 54 min and
78% of this time was monitored by flight surgeons in mission
control. The average ectopic beat per EVA was 0.31%, how-
ever some EVAs had ectopy greater than 10%. Remarkably,
this study found 77 out of 160 (48%) EVAs showed a sinus
arrhythmia compared to only 9 (5%) seen on preflight Holter
reports. The causal relationship between space travel and this
finding has not been elucidated, however down regulation of
the sympathetic system with parasympathetic dominance has
been hypothesized as one of many contributing factors [82].
The average heart rate for these EVAs was 82.9 beats per
minute and the average age at EVA was 45.04 17.63 years.
A Shuttle based EVA was not extended to 8 h because of increas-
ing bigeminy and trigeminy seen on during the first 6 h. Typi-
cally if the crew has finished all their planned tasks during an
EVA, the crew surgeon can authorize an extension of the EVA
based on the biophysical data they receive during the first 6 h.
322
The Russian space program has also accumulated a great
deal of ECG data [2,12,83], in part because the Russian pro-
gram of health maintenance requires considerable routine
monitoring. In addition to ECG monitoring during EVAs, all
cosmonauts undergo ECG and respiratory-rate monitoring
during launches and dockings of the Soyuz. On many lon-
ger Russian missions, ECG monitoring was conducted every
23 weeks at rest and during exercise, LBNP, EVA, and after
flight [84,85]. In the Russian space program, the most com-
mon arrhythmias are extrasystoles, with supraventricular
more common than ventricular [2,9,86].
The Russian space program has reported observing changes
in R-, S-, and T-wave amplitude beginning in the second and
third months of flight [87]. This increase may simply reflect
microgravity-induced anatomic changes of the heart relative
to other thoracic structures. The decrease in T-wave amplitude
could also be due to changes in potassium metabolism, which
could also be related to ventricular ectopy [87]. A crewmember
during the Mir-2 mission in 1987 developed a persistent tachyar-
rhythmia during EVA that resulted in the mission duration being
shortened from 11 months to 6 months; the crew returned safely
in a Soyuz capsule [88]. A cosmonaut was reported to have suf-
fered a massive myocardial infarction at the age of 49 years, just
2 years after his third short-duration flight [85]. Moreover, the
Russian medical community reported to NASA having observed
~31 abnormal electrocardiograms, 75 arrhythmias, and 23 con-
duction disorders during the past 10 years of Mir operations.
During the joint U.S.Russian NASAMir Program, ambu-
latory ECG recordings (Holter recordings) were obtained
from several crews. Significant abnormalities were found in one
Mir cosmonaut who had no previous history of cardiovascular
disease [89]. Preflight Holter recordings revealed ventricular
couplets, multiform premature ventricular complexes, and a
5-beat episode of SVT with no episodes of ventricular tachyar-
rhythmias. A Holter recording made during the second month
of orbit (Figure 16.1) revealed an asymptomatic, nonsustained,
14-beat run of VT [89]. We now know that a late diastolic PVC
precipitated this event and that the peak rate of the arrhyth-
mia was 215 beats per minute. Because those results were not
available until after the flight, the cosmonaut who experienced
this abnormality successfully completed the mission and was
returned to Earth by the Space Shuttle as nominally sched-
uled. Unfortunately, this cosmonaut was diagnosed with CAD
several months after this mission.
Several studies in which healthy adult subjects have under-
gone Holter monitoring indicate that the prevalence of ectopy
ranges from 40% to 93% and increases with age, suggesting
that the regular use of Holter recordings on orbit might reveal
more frequent arrhythmias [90]. U.S. astronauts are selected
after an aggressive cardiac workup [53] that attempts to rule
out any significant abnormalities, although angiography is not
routinely performed. Nevertheless, the cardiovascular selec-
tion criteria for astronauts may not be entirely effective if the
arrhythmias found by Holter recordings [74,75,77,9092] are
considered to be abnormal for this population.
D.R. Hamilton
Figure 16.1. Nonsustained ventricular tachycardia (VT) from a
2-channel Holter recording during long-duration spaceflight. The 14
beats of tachycardia were initiated by a late diastolic premature beat.
Nonspecific ST elevations are evident after the event. (From Fritsch-
Yelle, et al. [89] Used with permission.)
These cardiovascular close calls imply that our current
screening tests used before missions are insufficient for ruling
out the possibility of cardiac events on orbit. Most cardiovas-
cular-risk stratifications in the military and civilian aviation
communities focus on reducing the impact of cardiac events
during the critical portions of flight. Other environments, such
as missile submarine operations, may place mission success
above the health of the individual crewmember suffering from
a cardiac event. The cost and risk to the mission of a cardiac
event outside these boundaries is tolerable to the military and
civilian medical programs. This may not be the case for a
permanent human presence in space, because the current pro-
gram requirements dictate that an ISS crewmember suffering
a cardiac event must be evacuated to Earth. If a Space Shuttle
is not present at the station, the resulting deorbit aboard Soyuz
could represent a $500 million cost to the space program. The
question thus arises of whether space medicine flight surgeons
should be applying cardiovascular selection and retention
standards that are much more conservative than the current
military standards if they are to mitigate this apparent gap
between incidence of cardiac events on orbit and our ability to
predict or prevent them.
Cardiovascular RiskMitigation Strategies
for Spaceflight Crews
Comprehensive cardiovascular medical care for spaceflight
crews requires a balanced approach between prevention and
treatment. The most effective means of delivering cardiovascu-
lar care in space to date has been through medical screening
16. Cardiovascular Disorders
for cardiac abnormalities before selection and through using
primary and secondary prevention and countermeasures
[53,93] before, during, and after flight. This approach is
expected to minimize the need for treatment and any medi-
cal interference with mission objectives. Yet despite the best
attempts of flight surgeons to apply aggressive screening and
countermeasures, episodes of cardiovascular abnormalities
have occurred during or after space flight.
Acquiring cardiovascular data, whether intended for opera-
tional or research use, in a manner that controls for the crews
sleep, diet, mission-related activities, medications, exercise,
and preflight and postflight activities without interfering with
the primary mission objectives has proven difficult on most
short-duration space flights. This problem was addressed
during selected short-duration missions in which gathering
operational and physiological data was the primary mission
objective [1,7,9395]. Results from these studies have proven
useful in identifying causal relationships amidst the multitude
of historical medical observations and descriptive studies dat-
ing back to Project Mercury and the Vostok Space Project.
Cardiovascular events occurring during or after a mission
can be considered in two categoriesevents that are a conse-
quence of the expected cardiovascular physiological changes
induced by space flight and events that are a consequence of
preexisting subclinical cardiovascular abnormalities that may
be exacerbated by space flight. Most studies of the cardio-
vascular system and space flight are of one of three types [7],
namely (1) descriptive studies that report the cardiovascular
response of a crewmember during or after a mission (usually
either case reports of individual cardiovascular anomalies that
may have been caused by space travel and may have opera-
tional implications in the future, or cohort studies [prospec-
tive or retrospective] of the risk or incidence of an observed
cardiovascular anomaly caused by space travel in a significant
number of space travelers); (2) mechanistic studies, which are
usually structured to control many variables so that a causal
relationship between space travel and the observed cardio-
vascular phenomenon can be explained by using a model of
microgravity-based pathophysiology; and (3) prevention and
countermeasure-validation studies, which are usually con-
ducted after the mechanism responsible for the cardiovascular
pathophysiology is understood well enough to form a cardio-
vascular risk-mitigation hypothesis.
Using a methodical approach to mitigating cardiovascular
medical events has proven useful in assessing causal relation-
ships between space flight and observed changes to the cardio-
vascular system. The limited quality and quantity of medical
data that can be collected during most spaceflight missions has
made it difficult to establish an evidence-based approach [96]
to on-orbit cardiovascular medical care. Consequently, flight
surgeons have had to rely on limited experience and anecdotal
data to implement on-orbit risk mitigation strategies and to
make real-time clinical decisions [97,98].
Flight surgeons must be careful to balance the effect of chang-
ing an apparently successful cardiovascular risk-mitigation
323
procedure or investigating a new procedure in light of the
medical risk to the crew [99] and the potential effect on the
overall mission. In attempts to protect deconditioned and
possibly compromised crews during early space missions,
scientists in the U.S. and Russian space programs imple-
mented a set of countermeasures before the basic mechanisms
underlying the human physiological response to microgravity
were well understood. One example was the combined use
of pharmacologic agents, fluid-loading, exercise (treadmill or
cycle ergometry), and LBNP to prevent orthostasis upon land-
ing. The success of these combined countermeasures is still
unclear, and their simultaneous use may well interfere with
the independent validation of individual countermeasures.
Most of the clinical experience in applying effective car-
diovascular countermeasures in the U.S. space program is
currently limited to crews that complete landings considered
nominal (i.e., those that satisfy the parameters established
before flight by Agency planners) after brief exposures to
microgravity and to the few long-duration exposures experi-
enced during the Skylab, Shuttle-Mir, and ISS programs. It is
hoped that when the ISS is complete, additional prospective
controlled studies can be performed to help optimize counter-
measure strategies [100] for microgravity and reduced-gravity
exposures for missions to Mars (one-third g ravity), Earths
moon (one-sixth gravity), or beyond.
Prevention of Cardiovascular Disease
in Spaceflight Crews
The primary means of minimizing the effect of medical events
on the mission, in the space program and the military, is to
use conservative selection and retention medical standards
together with aggressive primary and secondary prevention
programs. The medical resources aboard spacecraft are opti-
mized to reduce the mass, power, and volume required. This
factor, coupled with the limited expertise of the crew medical
officers (CMOs), most of whom are not physicians, mandates
that prevention, rather than treatment, be the focus of cardio-
vascular risk mitigation on orbit.
Although the rates of mortality and morbidity from CAD
have declined in the United States and other industrialized
nations, CAD nevertheless remains the leading cause of death
and disability in most industrialized nations. As discussed
previously, heart disease can manifest initially as a suddenly
incapacitating event (angina, myocardial infarction, arrhyth-
mias, thromboembolic events, or syncope) or as sudden car-
diac death with no prodromal symptoms. Approximately 25%
of patients with premature CAD do not exhibit any of the clas-
sically recognized risk factors [101103]. More than 200 new
risk factors and markers (e.g., C-reactive protein, homocyste-
ine [104], fibrinogen, and some infectious agents) have been
identified and tested for their correlation with CAD [105107].
Serum cholesterol and its fractional components also remain
useful as surrogate risk factors. In a study of asymptomatic
324
aviators with abnormal findings on noninvasive tests for CAD,
analysis of 250 cardiac catheterizations showed that 4% of
those without CAD and 88% with angiographically demon-
strated CAD had a total cholesterol/high-density lipoprotein
(HDL) ratio higher than 6.0 [40,108].
Of interest was the cholesterol measured in all female
active astronauts in 2002 (average age = 44.0) being less than
165 (mg/dl) with the mean being 150. The cholesterol in all
male active astronauts in the same year was greater than 164
(mg/dl) with 43% falling between 166 and 199 (mean choles-
terol = 182, average age 39.8) and 57% having a cholesterol
greater than 199 (mean cholesterol = 220, average age = 48.0).
The average age of U.S. astronauts in 2002 was 44.0 6.7
and 44.5 5.6 for females and males respectively (Mean
Standard Deviation). Since the first manned flight, the average age
at selection was 35 3.5 and 36 3.5 and at discharge or
death was 41.2 3.8 and 44.3 6.2 for females and males
respectively. The average age of the retired astronauts
is presently 48.7 5.3 and 60.5 9.3 for females and males
respectively. Clearly the US female astronaut cohort has a
lower cardiac risk based on Framingham risk scores.
The 10-year risk of having a cardiac event in the 2002
active and 2002 retired astronaut corps as a function of age
has been calculated using the prediction method of Wilson
et al. [109,110] Of interest is the distribution of 10-year event
risk Framingham risk scores (FRS) in the astronaut popula-
tion as of the year 2002 where 40.1% of males and all females
have a FRS of less than 3% with mean age of 39.6 and 44.0
respectively. The remaining corps has 51% of males in the
FRS range of 5% to 9% (mean age 46.6) with 8% of males
having a FRS greater than 10% (mean age 55.8). The risk of
having a cardiac event of 5% or greater over the next 10 years
in 59% of the males in the active corps may need to be reex-
amined if missions on the ISS get extended to one year or we
engage in 3 year Exploration Class missions.
Examining these risk data, it is evident that the current
astronaut selection process seems to be effective in creating
a cohort that has less cardiac risk than an age- and gender-
matched cohort in the general population. Nonetheless, cardiac
events have occurred in this astronaut cohort in close temporal
proximity to missions. There is a general consensus that only
about 50% of CAD events can be explained by the traditional
Framingham risk factors. Approximately 8590% of indi-
viduals dying of CAD and ~70% of individuals free of CAD
related death over a 2139 year follow-up have at least one
traditional risk factor [111]. Traditional risk factors explain
differential CHD rates across countries better than they do
across individuals within a country. Framingham risk scores
may not be a useful means of estimating CAD risk of indi-
vidual astronauts but may be useful in examining the overall
cardiac risk of the astronaut corps. Furthermore, using U.S.
astronaut cohort and individual cardiac risk information to
derive an international crew selection criterion for missions is
difficult since these populations may not behave in a manner
similar to Framingham data based on U.S. cohorts. Clearly,
D.R. Hamilton
using risk factor analysis alone will not prevent disease from
occurring during short- and long-duration space missions.
After astronaut selection, modification of cardiac risk factors
such as smoking, cholesterol levels (total lipoprotein, low-density
lipoprotein [LDL], and HDL) [108,112], hypertension, obesity,
sedentary lifestyle [113], and, for women, postmenopausal sta-
tus [114] is addressed by a Cardiac Wellness program admin-
istered by the Flight Medicine Clinic at the Johnson Space
Center [115]. Other risk factors such as hypercholesterolemia
and hypertension are potentially disqualifying conditions that
must be evaluated by the Aerospace Medicine Board.
Many studies have been conducted to examine the cost-
effectiveness of lipid-reducing therapy and when such therapy
should be initiated in various populations [116121]. The
Lipid Research Clinics Coronary Primary Preventive Trial
reported that a 1% reduction in total cholesterol level reduced
the risk of CAD by 2% [121]. These results should be consid-
ered in light of those of another study by Byington et al. [122],
who found that angiographic changes observed during statin
therapy did not predict reductions in cardiovascular events.
Angiographic changes may not reflect a reduced intimal lipid
burden in these individuals, which could serve to stabilize vul-
nerable plaque in an existing disease process [21,23,39,123].
A fully trained astronaut or cosmonaut is a significant asset
and may warrant a preventive approach that is more aggres-
sive than published risk-mitigation guidelines [124126].
A study of 27,939 women by Ridker et al. [127] showed that
the magnitude of risk reduction associated with random allo-
cation to statin therapy is just as large for subjects with high
CRP as it is for subjects with high lipids. Moreover, this study
concluded that those with elevated CRP levels but low LDL
levels (a group that includes almost 30 million Americans)
may actually benefit from Statins just as much as did those
with overt hyperlipidemia. More recent data push this concept
even further; we now have evidence that CRP predicts vascu-
lar risk across a full spectrum of LDL levels and adds prog-
nostic information at all levels of the Framingham Risk Score.
Of significance is the challenge raised when an astronaut
has a 5% 10-year Framingham risk score with a coronary
artery calcium score of 200. Would a statin be appropriate for
maintaining certification for long-duration space travel? CRP
thresholds of less than 1 mg/L, 13 mg/L, and greater than
3 mg/L corresponding to low (<10%), medium (1020%), and
high (> 20%) risk for CAD respectively, have now been endorsed
by both the American Heart Association and the Centers for
Disease Control and Prevention [128,129]. These discrete CRP
values approximate tertiles for an aggregate, asymptomatic
population of over 40,000 persons. The high-risk subgroup has
an associated CAD event relative risk of approximately twofold
when compared to the low-risk tertile [128].
The CRP levels between 2 and 3 mg/L and above 3 mg/L,
are 11% and 11% respectively, in the active astronaut popula-
tion as of 2002. The CRP levels between 2 and 3 mg/L and
above 3 mg/L, are 8.7% and 7.7%, respectively in the retired
astronaut population. Given that 50% of all acute MIs occur in
16. Cardiovascular Disorders
patients without hyperlipedmia, the improved predictive abil-
ity of adding CRP scores to overall cardiac risk assessment of
the astronaut corps may help reduce mission risk and decrease
the need for tertiary prevention strategies to become part of
the mission design [129]. If the CRP threshold is breached, it
would indicate a need for prompt preventive therapy such as
HMG Co-A reductase inhibitor [130132]. Finally, it should
be remembered that CRP is an acute phase reactant produced
by the liver during periods of stress. As such, it may be inac-
curate during critical illness, infection, or liver dysfunction.
In summary, military selection standards and countermea-
sures were used during the infancy of the U.S. and Russian
space programs, and the modifications that were made were
based primarily on hypothetical predictions as to the cardio-
vascular response to the unique environment of microgravity
predictions that later proved remarkably accurate [5]. Deter-
mining the threshold for acceptable risk of an incapacitating
cardiac event in a healthy population of astronauts is difficult
because no comparative cohort, nor any battery of tests, has
adequate positive or negative predictive power to rule out a
cardiac event from happening during a 5-month ISS mission
or 3-year Mars exploration mission.
Although there is a paucity of similar research in space
medicine, a retrospective study performed by Hamilton
et al. [133] compared derived 12-lead ECGs [134144] col-
lected as part of periodic fitness examinations (PFE) on the
ISS to prelaunch exercise stress tests. A PFE is performed on
a cycle ergometer which has a preprogrammed load profile
prescribed by ground based exercise countermeasure experts.
Data gathered from these 26 on-orbit PFEs lasting 20 min, and
not exceeding 80% of the maximum aerobic capacity, showed
no ECG anomalies including no ST or T-wave changes in
any US astronauts. Another retrospective study by Hamil-
ton et al. [145] of 295 astronauts illustrates the inadequacy
of exercise treadmill tests (ETT) and Thallium treadmills
(TT) as the predictor of ACS in a low-risk cohort. This was
a longitudinal study that followed the incidence of cardiac
events following 2,069 ETTs, and follow-up TT and cardiac
catheterizations in the active and retired astronaut corps from
1977 through 2000. In the active astronaut ETTs (n = 1,330),
10 had positive tests (ECG findings only), 29 had borderline
tests, 1 had an indeterminate test, and 1,289 had negative tests.
No cardiac events were reported in the active group over
the 23-year length of the study. In the retired astronaut ETTs
(n = 739), there were 40 positive tests, 40 borderline tests, 7
indeterminate tests, and 652 negative tests. One cardiac death
was seen within a year of ETT in the positive group (n = 40)
and 4 cardiac events (3 sudden deaths and 1 MI) in the nega-
tive ETT cohort. When both active and retired astronaut
groups are combined (n = 295, 2,240 person-years), they rep-
resent a follow-up time ranging from 1 to 23 years. Of 1,941
negative ETTs there were two cardiac events within 2 years
and another two within 4 years of the test. Of the 51 positive
ETTs there was one death within 1 year of the ETT. In this
study, the gross incidence of cardiac events in the combined
325
active and retired population is 0.22%/per person/year and all
cardiac events occurred within 4 years of the last ETT with
80% of these ETTs being normal. Clearly the ability of ETT
to predict cardiac events in the active or retired U.S. astronaut
cohort is very poor.
Cardiovascular Selection Standards
An astronaut selected by NASA for pilot or mission specialist
training is initially screened for significant overt cardiovascu-
lar disease through a physical examination similar to the U.S.
Air Force or Federal Aviation Administration class 3 physical
examination [146]. This medical screening is then followed
by NASA astronaut cardiovascular selection medical screen-
ing (Table 16.1), which has much in common with U.S. Air
Force class 1 and class 2 physical examinations [44,53,92].
After selection, all spaceflight crewmembers undergo annual
medical evaluations to evaluate and certify their cardiovascu-
lar fitness for flight. The scope of this examination is outlined
in the NASA Astronaut Medical Evaluation Requirements
Document [53].
Cardiovascular Screening Tests
Modern evidence-based medical practice attempts to rule
out overt cardiovascular disease by using screening tests that
focus on a patient population with known cardiovascular
risk factors. When cardiovascular diagnostic tests of known
specificity and sensitivity are applied to a cohort of patients
whose history or symptoms suggest possible cardiovascular
disease, the positive and negative predictive value of these
tests increases. However, when these tests are used to screen
very healthy cohorts such as military pilots or spaceflight
crews, their diagnostic and prognostic value diminishes [19].
Nevertheless, periodic evaluation facilitates the detection of
serial changes that may reflect the development of a signifi-
cant abnormality [19,147].
The cardiovascular portion of the astronaut selection physi-
cal examination is conducted as part of an overall comprehen-
sive selection medical examination. These tests include 24-h
Holter monitoring, resting echocardiography, standard 12-lead
electrocardiography, and an treadmill exercise stress test con-
ducted according to a Bruce protocol [148], which entails
steady increases in treadmill grade and speed every 3 min until
the test is terminated by the subject or test conductor.
Electrocardiography
Taken alone, electrocardiography is very nonspecific for the
detection of CAD [90,149] in healthy individuals, but it is still
used routinely as a screening tool for military aviators and
astronauts [44,53]. In a study by Joy and Trump of 16,000
electrocardiograms from 14,000 aviators and air traffic
326 D.R. Hamilton

Table 16.1. Cardiovascular causes for rejection in section and retention examinations for U.S. astronauts.
Examination type
Rejection criteria Selection Annual
Clinically significant hypertrophy or dilation of the heart or an ejection fraction of <50% at rest
Recumbent untreated blood pressure: Systolic > 140 mmHg or Diastolic > 90 mmHg
Recumbent treated blood pressure: Systolic > 140 mmHg or Diastolic > 90 mmHg
Recurrent symptomatic orthostatic hypotension
Pericarditis, myocarditis, or endocarditis or a history of these conditions requires further evaluation
History of findings of major congenital abnormalities of the heart or the great vessels:
Uncomplicated dextrocardia and other asymptomatic abnormalities may be acceptable.
History of atrial or ventricular septal defect or patent ductus arteriosis that has been successfully repaired with a negative
1-year postoperative cardiac evaluation on a case-by-case basis
Any clinical evidence of coronary artery disease, myocardial infarction, or angina pectoris at any time
Electrocardiographic findings as follows:
Persistent tachycardia with supine resting pulse rate of more than 100
Clinical evidence of cardiac arrhythmia, conduction defect, abnormalities on resting or
Holter electrocardiography such as:
Atrial flutter or fibrillation and ventricular tachycardia or ventricular fibrillation
History of single episode of atrial flutter or fibrillation with no evidence of underlying cardiac disease is evaluated
on a case-by-case basis and may be disqualifying. Atrial tachycardia requires further evaluation and may be disqualifying.
One episode of 3-beat ventricular tachycardia (triplet) with no evidence of underlying cardiac disease is evaluated on a
case-by-case basis and may be disqualifying
Conduction defects such as first-degree A-V block, right bundle branch block, and second-degree block (Mobitz), unless
occurring as isolated findings when evaluation reveals no cardiac disease
Left bundle branch block or second- or third-degree block
Paroxysmal supraventricular tachycardia
ECG evidence of old or recurrent myocardial infarction, ischemia at rest or after stress, or myocardial disease
Maximal exercise test that induces significant arrhythmias
Conduction defect or ECG abnormality requires further cardiac evaluation
History of recurrent thrombophlebitis or of thrombophlebitis with persistent thrombus, Evidence of circulatory obstruction,
or deep venous incompetence
Varicose veins if more than mild in degree, or if associated with edema, skin ulceration, or scars from previous ulceration
Peripheral vascular disease
Cardiac tumors:
Cardiac tumors of any type
Cardiac tumors, unless benign and successfully resected without residual cardiac disease after 6 months, are reviewed on a
case-by-case basis
All valvular disorders of the heart, including mitral valve prolapse, require further evaluation and may be disqualifying
Failure to meet NASA exercise stress-test standards
Source: From NASA, Space and Life Sciences Directorate [53].

controllers, 19 of 103 subjects with minor ST-segment and
T-wave changes were found to have abnormal findings on
exercise stress tests, and only five had SCAD [150]. A U.S.
Air Force study found that among 147,571 resting electro-
cardiograms, 480 required additional evaluation by 24-h
Holter monitoring because of ectopy [73,90]. Of these Holter
recordings, 51% were found to be abnormal; 11% of those
individuals with abnormalities on Holter recordings were
returned to duty after an exercise treadmill test or stress
echocardiography showed normal findings. Investigation of
the other 40% of abnormal Holter recordings by the U.S. Air
Force Aeromedical Consultation Service resulted in only 4%
of individuals being permanently disqualified.
The U.S. Air Force requires only that a resting electrocar-
diogram be obtained every 5 years for aircrew members who
are older than 35 years [90]. The annual NASA astronaut
examination does not require 24-h Holter monitoring, and
the exercise stress test is repeated only at ages 30, 35, and
40 years and then every other year until age 50. After age 50,
the ETT is required annually. For those annual examinations
when the Bruce protocol is not required, a submaximal cycle
or treadmill test is conducted. This test is designed to screen
out significant coronary heart disease and arrhythmias without
imposing additional morbidity from the test itself. As a case-
finding tool, the resting 12-lead electrocardiogram may reveal
certain specific abnormalities such as Wolff-Parkinson-White
syndrome, other conduction abnormalities, or hypertrophic
cardiomyopathy [73, 90,91,151].
Exercise Testing
Graded exercise testing with a treadmill or cycle ergometer
and ECG analysis is a common means of screening for CAD.
In aviators, treadmill exercise testing to rule out SCAD has
16. Cardiovascular Disorders 327

a PPV of less than 25% [152,153]. An 8-year study of 548 cific lesions detected on EBCT could be seen by fluoroscopy,
military aviators found that graded exercise stress testing had suggesting that EBCT is more sensitive but less specific than
a sensitivity of 16% and a PPV of 26% for clinically evident fluoroscopy for detecting calcific lesions. The CAF findings
CAD [92,154]. A treadmill stress test study of 888 men and are clear that asymptomatic CAD is prevalent in these military
women over a 5-year period found that ST-segment depression cohorts despite the fact that these studies were not conducted
in men older than 40 years had a PPV of 17% for CAD [155]. as medical screening tests.
The PPV for ruling out SCAD by angiography or clinical find- Barnett et al. reviewed a database of 1,504 coronary angio-
ings in asymptomatic aviators or spaceflight crewmembers grams obtained between 1979 and 1999 from asymptomatic
who have abnormal findings on a treadmill or cycle ergometer military aviators [163]. Subjects were grouped into three
exercise stress test is probably in the range of 2025% [92]. categories: SCAD (n = 323), MCAD (n = 252), and normal
Nevertheless, a committee of experts from the American Col- (n = 929). The SCAD group was further divided into two sub-
lege of Cardiology and the American Heart Association has groups, those showing 5070% stenosis and those showing more
given the class 2 recommendation (i.e., for which there is con- than 70% stenosis [163]. Annual rates of cardiac events (cardiac
flicting evidence or lack of consensus within the committee) death, nonfatal myocardial infarction, and coronary revascular-
for screening men older than 40 years and women older than ization) were determined during the 2 years, 5 years, 10 years,
50 years with electrocardiography and exercise stress testing and 15 years after the angiography. Notable were the annual
who are engaged in occupations in which impairment may cardiac event rates of 9.1% for those with SCAD and more
endanger public safety [154]. Patients with an intermediate than 70% stenosis and 6.0% for all individuals with SCAD
or high probability of having CAD according to findings on during the first 2 years after the angiography (Table 16.3).
an exercise stress test may benefit from further screening and During follow-up, only 24% of the SCAD group reported
stratification with diagnostic imaging methods that measure experiencing anginal symptomsa finding that imposes a sig-
coronary artery calcium burden, such as electron-beam computed nificant challenge to flight surgeons, who must detect disease
tomography (EBCT) [155158]. and attempt to prevent cardiovascular-related mission-impact
events [163]. The rate of cardiac events among those with
asymptomatic SCAD ranged from 3.5% to 6.0% per year over
Nuclide and Coronary Artery Calcium Imaging the 15-year follow-up period, a rate comparable to that among
Stress radionuclide imaging is not considered a primary symptomatic SCAD cohorts. Subjects with MCAD had annual
screening test, mostly because of its cost and inherent risk of event rates of 0.6% at 2 years, 0.4% at 5 years, and 1.1% at
significant morbidity. In a study of 845 asymptomatic young
male aviators who underwent coronary angiography after positive
findings on noninvasive tests, the PPV of an abnormal thal- Table 16.2. Predictive value of treadmill testing, thallium scan, and
lium exercise scintigram for SCAD was only 25% [159]. coronary artery fluoroscopy versus coronary angiography for detect-
Information on more sensitive radionuclide imaging tech- ing clinically significant coronary artery disease.
niques applied to healthy aviator cohorts [160], such as single Positive Negative
photon emission CT, is very limited at this time. predictive predictive
Test type Sensitivity, % Specificity, % value, % value, %
Fitzsimmons and colleagues studied 759 military aviators
with SCAD that had been diagnosed by coronary angiogra- Treadmill 54.5 48.8 15.9 85.8
Thallium scan 55.1 62.0 20.5 88.6
phy and calculated the sensitivity, specificity, PPV, and nega- Coronary artery 67.6 70.9 29.2 92.5
tive predictive values for treadmill testing, thallium scanning, fluoroscopy
and coronary artery fluoroscopy (CAF) (Table 16.2) [161].
The 29.2% PPV for CAF in this cohort indicates that CAF is Source: Adapted from Fitzsimmons et al. [161].
the best noninvasive diagnostic method currently used by the
military to rule out SCAD.
Loecker and colleagues [162] used CAF to screen 1,466
aviators, 613 of whom had undergone coronary angiography Table 16.3. Annual cardiac event rates (%/year/person) among avia-
for abnormal findings on CAF, exercise treadmill testing, or tors with minimal or significant coronary artery disease.
exercise thallium scintigraphy. In that study, CAF was found Clinically Clinically
to have a PPV of 68% for any measurable CAD. A study of 220 Minimal CAD significant CAD significant CAD
male aviators (mean age, 42.3 years) conducted from 1990 to Time since with <50% with 50%70% with >70%
1995 by Smalley et al. [54] compared coronary angiography diagnosis stenosis stenosis stenosis
with graded exercise testing, thallium scintigraphy, and CAF 2 years 0.6 1.2 9.1
and showed that CAF had a PPV of 81% for all CAD and 34% 5 years 0.4 2.5 4.7
10 years 1.1 2.6 4.0
for SCAD. Although fluoroscopy can detect moderate to large
15 years 1.9 4.6 4.6
calcifications, its ability to detect small calcific lesions is lim-
ited. In a study reported by Wexler et al. [28], only 52% of cal- Source: From Barnett et al. [163].
328
10 years [164]. The poor predictive value of these tests is of
significant concern, considering that myocardial infarction in
an asymptomatic nonmilitary cohort can be relatively com-
mon even when coronary vessels have only minimal evidence
of disease [27].
The more difficult issue for flight surgeons is when asymp-
tomatic MCAD is found in a trained and experienced crew-
member. In another study, the progression of MCAD was
followed serially in 44 of 252 military aviators with an angio-
graphic diagnosis of asymptomatic MCAD [165]. Progres-
sion of MCAD to SCAD occurred in 11 (25%) of those 44
aviators; of those 11 aviators, 7 had had negative findings on
noninvasive tests at the time of repeat catheterization, ~3 years
later [166]. Notable in the group that progressed from MCAD
to SCAD were the findings of higher total and LDL choles-
terol levels and lower HDL cholesterol levels, suggesting that
lipid-modifying medications should be considered for crew-
members with this type of abnormal lipid profile.
Electron-Beam Computed Tomography
Schmermund et al. [167] used EBCT and angiography to
evaluate 118 patients (mean age, 57 years) who had experi-
enced unstable angina or an acute myocardial infarction. Of
those 118 patients, 110 had angiographically proven SCAD
and 106 had evidence of calcium deposits on EBCT. Of the
12 patients who had negative findings on EBCT, 9 had expe-
rienced a myocardial infarction; their mean age was 12 years
younger than the group that had positive findings on EBCT
and a myocardial infarction. Interestingly, the nine patients
who experienced a myocardial infarction and had negative
EBCT scores all had significantly increased LDL profiles and
all were smokers.
Coronary artery calcium can be detected directly and inde-
pendently of the magnitude of stenosis causing ischemia [168].
Serial determinations of coronary calcium load may be a better
predictor of CAD progression and long-term cardiovascular
prognosis [39,54,169172], and thus CAF and EBCT may
turn out to be useful screening methods for selecting aviator
and spaceflight crewmembers. However, both CAF and EBCT
involve radiation exposure, which is a concern in screening a
healthy astronaut or cosmonaut population. The possible role
of EBCT as a screening tool in asymptomatic subjects has not
been rigorously evaluated [20,39,173], and thus its greatest
usefulness may be as a sensitive test for confirming the pres-
ence of CAD in aviators [172,174177].
Coronary artery screening by EBCT is quite cost-effective
compared with other diagnostic modalities, especially when
the pretest probability or likelihood of disease is low to mod-
erate [28,175]. It remains to be determined whether the mere
presence of coronary artery calcium is a reasonable standard
for selecting out on the basis of cardiovascular disease or
whether some minimal level of calcium burden can be identi-
fied as being associated with an acceptable cardiovascular risk
for the astronaut or the mission [29,176182].
D.R. Hamilton
Results from the 5-year Prospective Army Coronary
Calcium Study, which was started in October 1998, should
provide information regarding the utility of EBCT in predict-
ing the occurrence of CAD and cardiac events in a young,
asymptomatic population [172,180,183]. This study should
also clarify the incidence [180] and progression of CAD and
correlate calcium load with cardiac event risk. Interestingly,
the presence of calcium detected by EBCT may be a reliable
predictor of soft events such as coronary revascularization
but a weak predictor of hard events such as death or myo-
cardial infarction [184], in part because EBCT is much more
sensitive for detecting presymptomatic CAD and facilitating
intervention and because hard, fibrocalcific plaques may be
more resistant to rupture than soft, minimally calcified, lipid-
rich plaques [172].
The immediate role of EBCT or carotid sonography for
spaceflight crewmembers might be as a means of ruling out
the presence of SCAD [185] or occult CAD in asymptomatic
middle-aged men and women [39,178,186189]. This capability
might help flight surgeons select out astronaut or cosmonaut
candidates with MCAD [189] and may provide temporary
flight certification (with annual examinations) for specialized
U.S. astronaut cohorts (e.g., payload specialists or non-Agency
astronauts) with asymptomatic MCAD for short-duration
flights within a 2- to 3-year period [190,191]. Most certainly,
stress echocardiography, carotid sonography, CAF, and EBCT
technologies should be monitored closely as future ways of
screening candidates, following older astronauts or cosmonauts
with suspected or proven asymptomatic MCAD, and selecting
crews for lunar or planetary exploration-class missions.
Other Tests
The sensitivity and specificity of stress echocardiography are
superior to those of graded exercise stress testing and compa-
rable to those of radionuclide imaging [192]. Although other
noninvasive diagnostic imaging modalities expose crewmem-
bers to radiation (a particular occupational concern in this
cohort), stress echocardiography does not. Sonography of the
carotid arteries to rule out gross atherosclerosis by measuring
the intimal-medial thickness might also be used as a screening
test for CAD. Several studies have been conducted to correlate
the severity of carotid and coronary atherosclerosis [107,193],
and at least one other study used carotid intimal thickening to
predict the risk of cardiac events [194]. The ability to detect
coronary calcifications with magnetic resonance imaging is
limited because of the low signal intensity on both T1- and
T2-weighted spin echo images, primarily because of the low
density of mobile protons in calcified lesions [28].
Mission-Related Investigations
Although most cardiovascular abnormalities revealed during
the examinations for selection, annual evaluation, or mission
16. Cardiovascular Disorders
readiness are disqualifying, some minor cardiovascular condi-
tions can be waived by NASAs Aerospace Medicine Board.
This board must consider the risk of waiving a mild cardiovas-
cular condition (e.g., an old borderline first-degree atrioven-
tricular conduction block) versus the loss of a skilled astronaut
whose training has incurred significant program expense.
Even though our ability to apply prospective, evidence-based
findings to career-affecting decisions such as these is quite
limited, flight surgeons are nevertheless responsible for ensur-
ing that a crew is medically ready for flight. From a cardiovas-
cular perspective, the final test of a crews medical readiness
for a long-duration space flight is determined 30 days before
launch with resting and ambulatory electrocardiography,
treadmill exercise testing, pulmonary function tests, and oper-
ational tilt tests.
The operational tilt test involves 6 min in a supine posi-
tion followed by 10 min at an upright position, representing
an 80-degree tilt. In both positions, subjects are monitored
with 2-dimensional echocardiography, Doppler sonography
(to determine cardiac output and total peripheral resistance),
3-lead electrocardiography (including measurement of heart
rate), manual blood pressure measurements every 1 min, and
continuous noninvasive measurements of blood pressure. The
tilt test is used for all first-time Space Shuttle flyers, those
flying their first long-duration (>30 days) mission, and those
who have shown functional orthostatic impairment on previ-
ous missions [53]. The cardiovascular examination conducted
immediately after landing also involves a physical examina-
tion by the flight surgeon, an operational tilt test, and resting
electrocardiography within hours of landing. Pulmonary func-
tion testing takes place within 3 days of landing, and another
operational tilt test is conducted 10 days after landing. Additional
tests are used for astronauts and cosmonauts returning from
3-month or longer tours aboard the ISS, who require more
extensive long-term follow-up.
Cardiovascular Issues During Launch
Before launch, crewmembers are acutely aware that they are
sitting atop rockets that will accelerate them into space to an
orbital speed of 17,500 miles per hour. Given their elevated
adrenergic state and the position-induced central volume
loading secondary to their near-supine posture in the vehicle,
it is hardly surprising that crewmembers would experience
increased heart rates during that time. Indeed, routine monitor-
ing of U.S. and Russian spaceflight crews reveals that heart
rates are typically highest during launch, entry into orbit,
EVA, and reentry. Russian data from the Vostok and Vosk-
hod launches indicated that cosmonauts heart rates during
the launches were higher than during similar acceleration profiles
in a centrifuge; specifically, heart rates were 39% higher than
the centrifuge baseline as early as 10 min before launch and
remained 52% higher than centrifuge-baseline rates through
the first orbit [69].
329
Thermal Loads
From the flight surgeons perspective, a Space Shuttle launch
starts when crewmembers don their advanced crew-escape
suits (ACESs) 46 h before launch. The ACES rejects heat by
means of a liquid-cooling garment composed of Capilene fab-
ric lined with plastic tubing that circulates coolant water from
an external portable individual cooling unit [195]. This cooling
method eliminates the need for forced airflow through the
suit, a design that was used in the Mercury, Gemini, Apollo,
and early Space Shuttle programs.
High cabin temperatures have at times overwhelmed the
limited heat extraction capability of the individual cooling
units. These units radiate their heat into the cabin, and their
efficiency is less than 20%; thus, for a 70-kg man radiating
76 kcal/h (300 BTU/h) into the ACES, the individual cooling
unit imposes more than 380 kcal/h (1,500 BTU/h) per crew-
member on the cabin atmospheres cooling system. The total
thermal load from the crews cooling units, in combination
with the payload heat sources and the vehicles prolonged
exposure to sunlight on the launch pad, may exceed the capac-
ity of the cabin cooling systems before launch. Elevated cabin
temperatures in turn degrade the performance of the individual
cooling units, thereby diminishing their cooling capacity and
raising the internal temperature of the ACESs. Crewmembers
thus experience increased peripheral vasodilation and insen-
sible fluid loss, possibly impairing their orthostatic tolerance
in the event of an emergency egress from the vehicle. Flight
surgeons must be aware of these factors and be prepared to
advise launch management personnel regarding the ability of
crewmembers to function in off-nominal cabin temperature
conditions.
Launch Position
Space Shuttle crews are placed in the vehicle ~2.5 h before the
anticipated launch time. Depending on the temporal launch
window for a successful launch and the duration of flexible
pauses built into the countdown for troubleshooting of poten-
tial problems, crewmembers may be in the vehicle for as long
as 4 h before the flight control team authorizes a launch or
defers to another launch window. The launch seat configura-
tion places the crew in a modified supine position, with an
~90-degree hip and knee flexion, to direct the launch accelera-
tion forces in the +Gx (anteroposterior) direction.
In the Russian Soyuz space capsule, its crewmembers are
also in a +Gx orientation relative to acceleration for about
90 min before launch; however, the cosmonauts legs are
folded more closely towards their chests than are the legs of
Shuttle crewmembers. The Russian launch escape system does
not rely on transatlantic abort landing sites; its use of a rocket-
propelled capsule escape system facilitates crew emergency
egress during system failures on the pad or during ascent. The
combination of the vertically configured rockets and capsule
and the lack of emergency return-to-launch site constraints
330
makes Soyuz less sensitive to adverse weather conditions.
This means that the Russian vehicle is much less prone to
launch delays than is the U.S. Space Shuttle, and Soyuz crews
typically spend less than 4 h in the launch position.
With regard to cardiovascular system effects, maintaining
the launch position for prolonged periods leads to significant
venous blood volume being placed above the heart, thereby
increasing the preload to the heart (i.e., central venous pres-
sure [CVP] and ventricular end-diastolic volumes) and cardiac
output [196]. The body interprets these physiological changes
as an acute increase in intravascular volume and compensates
by reducing intravascular volume though diuresis, reduced
thirst, and insensible water loss. During the first 48 h on orbit,
the intravascular volume lost through these compensatory
mechanisms may be partially replaced by the vascular influx
of extravasated fluid from the lower extremities. Spending 4 h
in the legs-up launch posture can result in significant cephalad
shifts of both intravascular and interstitial leg volume. Although
the increase in cardiac preload upon exposure to micrograv-
ity may be partially mitigated by the posturally induced diure-
sis that occurs on the launch pad, volume changes induced by
sustained time in this launch posture may impair the ability of
the crewmembers to respond to an on-pad emergency because
of potentially significant intravascular hypovolemia and the
resultant orthostasis upon standing [197,198].
The series of complicated tasks that must be performed by
the flight crew in the cabin to properly configure the Shuttle
during countdown, the sealed nature of the ACES, the vehicle
orientation, and the arrangement of the seats do not allow
use of the Shuttle waste control system while the Shuttle is
on the launch pad. Shuttle crewmembers therefore wear an
undergarment containing a fluid-absorbent material that permits
crewmembers to urinate inside the ACES if necessary. Crew-
members sometime prefer to restrict their fluid intake from
12 h to 24 h before launch and to fly dry; this self-induced
preflight hypovolemia may exacerbate an existing orthostatic
intolerance in susceptible crewmembers, and flight surgeons
must be vigilant in confirming adequate volume status of all
crewmembers before launch.
The issue of orthostatic intolerance around launch times
is not as crucial during Russian launch operations because,
as noted earlier, launch delays are not common. The Soyuz
does not expose crewmembers to significant Gz accelera-
tions during launch-abort maneuvers, and crewmembers
are not expected to exit the vehicle without assistance after
landing. Russian flight surgeons occasionally administer
a diuretic (e.g., furosemide) several hours before launch
to decrease prelaunch volume and to help mitigate the
expected cephalad fluid shifting process after arrival in
microgravity.
Emergency Egress during Launch
The limited fault prediction and mitigation capability of early
propulsion systems, the reduced mobility of early launch
D.R. Hamilton
suits, and the extremely confined configuration of the cap-
sule environment required that launch vehicles be designed
to include crew escape systems capable of lifting the whole
crew capsule to safety (e.g., the Mercury, Apollo, Salyut,
and Soyuz launch vehicles) or propelling the individual crew
members away from the failing vehicle with ejection seats
(e.g., Gemini, Vostok, and Voshkod launch vehicles). The
increased size of the Space Shuttle crew cabin and crew
complement, however, made previous launch escape design
philosophies prohibitively complex and expensive. As a
result, Shuttle emergency egress plans call for the crew to
escape through either the side hatch or the flight deck win-
dows depending on whether the vehicle is in the launching
or landing phase of the mission.
A potentially confounding factor with regard to crew egress
is the 41-kg ACES, which allows Shuttle crewmembers to
breathe 100% O2 at 3.5 lbs per square inch (psi) in the event of
cabin depressurization during a launch or landing. The Shuttle
crew safety system requires that the crew be able to exit
the vehicle quickly, whether it is on the launch pad or in stable
flight [191]. After the crew has spent up to 4 h before launch
in the supine position wearing an ACES, it is pertinent to ask
whether members of that crew would be able to perform an
emergency egress while the launch pad or from the Shuttle
while in flight.
When an emergency occurs on the pad at T minus 30 min,
the crew must be able to exit the vehicle without help from
ground personnel, as no one is allowed near the launch pad
then. The crew, who will be wearing ACESs, must conduct an
orderly, single-file exit through the Shuttle hatch and onto the
launch tower via a walkway. After exiting the vehicle, the crew
is to move rapidly to the opposite side of the launch tower and
use the crew escape system, which consists of a large gondola
that rapidly moves the crew away from the launch pad along
a steep cable to a bunker or an armored personnel carrier. The
crew must be able to perform an emergency egress for an
abort as late as 3 s before liftoff and be able to ambulate 380 m
upwind from the Shuttle [199].
The Space Shuttle can also prematurely separate from its
central fuel tank and solid fuel boosters during a launch phase
abort. During the initial portions of the launch phase, clearly
some intervals exist in which crew escape is not an option;
however, depending on when the mission departs from a nom-
inal flight plan, the Shuttle may be able to glide back to the
original launch site or to various trans-Atlantic contingency
landing sites. In launch scenarios in which the vehicle does
not have sufficient energy to reach these contingency sites,
the crew must be able to exit the Shuttle during stable flight,
through the side hatch, and parachute to safety [191]. Subjects
wearing the ACES can complete simulations of Shuttle egress,
but significant increases in mean in-suit CO2 concentration
(4.5%) and heart rates (150 beats per minute) have been noted
at the end of a 5-min period of walking at 5.6 km/h (3.5 miles/h)
during such simulations [199,200]. Results from these stud-
ies indicate that the present ACES configuration is compatible
16. Cardiovascular Disorders
with egress from the Shuttle if the crew is not experiencing
any significant orthostatic intolerance.
As noted, the current Russian Soyuz booster system uses a
solid-rocketpowered launch escape system that lifts the crew
compartment away from a disabled or an exploding launch
vehicle. In this case, the cosmonaut crew does not need to exit
the vehicle rapidly while the Soyuz is on the launch pad. This
abort system was activated on the Soyuz T-10 mission during
a fire that broke out while the Soyuz was still on the launch
pad, requiring ignition of the emergency abort booster. Russian
crewmembers Vladimir Titov and Gennadi Strekalov were
exposed to 1517 Gx but landed safely about 4 km downrange.
In the event that future astronauts or cosmonauts experience
an event like that on Soyuz T-10, flight surgeons must ensure
that the crew has the cardiovascular capability to carry out an
emergency egress. Aeromedical flight rules for the U.S. Space
Shuttle [201] have been written to ensure that the crew cabin
temperature and time spent in the launch position are restricted
such that the crewmembers cardiovascular status will not
impair their ability to perform an emergency egress during
any aspect of nominal or off-nominal phases of launch.
Cardiovascular Issues During Orbital Flight
The transition from Earth to a microgravity environment causes
several short- and long-term changes in the crews cardiovas-
cular system and may affect crewmember performance during
orbital flight. Any space mission is operationally oriented, and
brief spaceflights in particular have busy timelines and full
schedules. Sometimes aggressive schedules may require that
the crew devote the time nominally scheduled for cardiovas-
cular countermeasures and personal activities to completing
other mission-critical tasks. In the Russian experience, some
crewmembers on long-duration missions have not complied
with their prescribed cardiovascular countermeasures during
the midportion of their missions, electing instead to use the
time scheduled for countermeasures for other purposes and
attempting to catch up with their physical conditioning later
in the mission.
On Earth, the normal activities of daily living require numer-
ous rapid transitions between upright, sitting, and supine pos-
tures. Such transitions require that the heart and blood vessels
be able to adjust quickly to a wide range of preload and after-
load conditions. These frequent changes in posture demand
exquisitely responsive cardiovascular control centers that can
influence effector mechanisms to the heart and blood vessels
on almost a beat-to-beat basis. This central cardiovascular con-
trol is provided by the medulla, and afferent input comes from
neural receptors throughout the cardiovascular system. System
output is provided by the efferent sympathetic and parasym-
pathetic autonomic nervous systems [202]. In space flight,
however, weightlessness removes the variance in gravitational
stimuli to the system. As a consequence, feed-forward and feed-
back gains and set points are altered until a new hemodynamic
331
homeostasis is established [203]. Flight surgeons must be able
to determine when such alterations in cardiovascular control
become maladaptive on orbit and upon return to Earth, when
they may manifest as orthostatic intolerance.
Fluid Shifts
On Earth, a large pressure gradient exists from our head to
our feet when we are standing. The mean arterial pressure in
a healthy human being is about 70 mmHg at the level of head,
100 mmHg at the level of the heart, and 200 mmHg at the level
of the feet. The ankle veins sustain a pressure of~100 mmHg in
a standing individual; this pressure decreases upon walking or
sitting, but it never falls below 30 mmHg [204]. During normal
activities of daily living, plasma volume is regulated to within
25 ml above or below the individuals total volume (0.8%)
[205]. An immediate effect of the transition to microgravity is
loss of the hydrostatic gradient in the venous vascular system,
resulting in a cephalad shift [205] of roughly 12 L [206],
an amount larger than the shifts involved in moving from an
upright stance to a supine position or to a head-down-tilt pos-
ture on Earth [207]. This shift is thought to occur because the
mechanisms that normally act to counter the pooling of blood
in the lower extremities in humans continue to act even in the
absence of gravity.
The concept of a headward fluid shift was reinforced by a
study that examined the effects of removing, by phlebotomy,
15% of the total blood volume of seated subjects who were
immersed in water to the level of the suprasternal notch [208].
Water immersion causes an immediate cephalad intravascular
fluid shift caused by loss of the venous and arterial hydrostatic
gradients, with commensurate loss of venous pooling of blood
in the lower extremities. Subjects who had not been subjected
to phlebotomy experienced a 22% increase in cardiac output;
those whose blood volume had been reduced by phlebotomy
showed no such increase. Urine flow increased by 368% and
sodium excretion by 200% in the normal blood-volume group
as compared with increases of only 73% and 120%, respectively,
in the phlebotomized group [208].
When a person is exposed to microgravity or is immersed
in water, the venous volume is shifted toward the head,
towards the primary volume sensors of the heart, which
the body perceives as a volume overload even though the
total body water and intravascular volumes are normal by
terrestrial standards. Although these microgravity-induced
changes in extracellular and plasma volumes may be appro-
priate adaptive responses during microgravity exposure, the
resulting fluid redistribution and loss of blood volume can
be considered profoundly hypovolemic by terrestrial stan-
dards. This spaceflight-induced loss of blood volume is
thought to be the most significant contributor to postflight
orthostatic intolerance [209].
Upon insertion into orbit, a crewmember is considered to
be hypervolemic by microgravity standards. Displacement of
intravascular fluid from the systemic capacitance vessels to
332
the upper body stimulates neurohumoral activity and changes
in vascular tone that result in a rapid reduction in intravascu-
lar volume through diuresis, reduced thirst, insensible losses,
and sometimes space motion sickness [95,210212]. Space
motion sickness may be exacerbated by these fluid shifts
[213]. Associated reductions in thirst and appetite, and possi-
bly nausea and vomiting, may serve incidentally to correct the
microgravity-induced volume overload. [210,212,213]
The signs and symptoms resulting from fluid shifts in
weightlessness were among the first physiological effects
noted in humans during space flight [5,214,215]. Fluid shifts
are readily visible as facial puffiness and enlargement of the
external neck veins, with noticeable decreases in leg size
[216]. Crewmembers have described such fluid shifts as feeling
like fullness in the head or nasal stuffiness similar to chronic
sinus congestion.
As noted above, the intravascular volume lost through
insensible losses and possibly through diuresis may be
replaced by further intravasation of interstitial fluid from the
lower extremities. The total loss of fluid from the vascular and
tissue spaces of the lower extremities, 12 L, corresponds to
a volume change of about 10% [217]. Apollo astronauts lost a
mean of 4.6% of their body weight during 6- to 12-day missions
[218], and Skylab astronauts lost from 1% to 4% of body
mass during their first week in space [219]. Russian cosmo-
nauts have lost from 4% to 8% of body weight after missions
lasting 419 days [220].
Under normal terrestrial conditions, a 4% decrease in
weight resulting from fluid loss constitutes significant clinical
dehydration. If 50% of the weight loss experienced by crews
of early Russian and U.S. space missions was from fluid loss,
these crews were in fact clinically dehydrated according to ter-
restrial standards. More recent Russian findings obtained by
using a radioisotope method during a 438-day flight revealed
reductions in extracellular, vascular, and interstitial volumes
by 910% on the fourth and fifth days of flight and reductions
of 18% on the 434th day [12]. Intracellular fluid level was
found to be unchanged during these experiments.
Results from Spacelab Life Sciences (SLS) missions SLS-
1 and SLS-2 have shown, surprisingly, that total body water
level, measured with an isotope-dilution technique [221], was
unchanged despite decreases in extracellular fluid and plasma
volumes [222]. During these missions, the total body water
of crewmembers was found to be 57.2% of their body mass
before flight and 57.1% of their body mass during flight. Such
drastic shifts in lower-extremity extracellular and intravascu-
lar fluid as occur in microgravity were unexpected. Moreover,
the proportion of extracellular fluid in these crewmembers
was 41.1% of total body water before flight and 35% dur-
ing flight [222]. These results imply that the 2 L of fluid lost
in the vascular and interstitial compartments of the lower
extremities [223] were lost to the body (with a resultant loss
in total body mass) or were partially relocated in the intracel-
lular space (with a resultant change in the distribution of water
among the vascular, extracellular, and intracellular spaces).
D.R. Hamilton
Volume reductions such as this would be caused mostly by the
loss or transport of protein out of the vascular space and the
movement of fluid into interstitial compartments that, because
they are normally above the heart (i.e., the face and neck),
do not normally experience any significant venous pressure.
In humans, the capillary structures above the heart may be
more permeable to plasma proteins, thus causing proteins to
shift from the vascular space in the presence of extended peri-
ods of heightened venous pressures [224]. The results of the
SLS-1 and SLS-2 experiments imply that loss of total circulat-
ing protein may account for the reduction in plasma volume
through changes in oncotic pressures alone.
After a reduction in blood volume (mostly through loss of
plasma volume and red cell mass) [225231], a crewmem-
ber will reach a new state of intravascular hydration that is
euvolemic for microgravity but is profoundly hypovolemic
for Earth-gravity conditions. It is currently unknown how the
human will respond to acute exposures to 1/6 (Moon) and 1/3
(Mars) gravity after reaching microgravity euvolemia. The
amount of diuresis during the first 23 days of space flight has
been a topic of some debate, but findings from the SLS-1 and
SLS-2 missions indicate that urinary output actually decreased
during the first 2 days of space flight [222]. This decrease in
urinary output was not caused by a decrease in glomerular fil-
tration rate (which increased during the early in-flight period)
and was consistent with the lack of significant reduction seen
in serum antidiuretic hormone level. The physical and emo-
tional stress of launch could possibly have prevented the cen-
tral nervous system from inhibiting the release of antidiuretic
hormone, despite the perceived volume overload from the vol-
ume sensors of the heart. An increase in the left ventricular
(LV) cardiac chamber volume upon transition to microgravity
has been well documented by echocardiography and is con-
sistent with the observed fluid shifts [196,216]. The normal-
ization of LV cardiac volume to near-preflight values occurs
after the crewmembers plasma volume is reduced to the new,
microgravity-euvolemic state.
Volume Status and Central Venous Pressure
An essential component of the bedside physical examination
is determining the volume status of the cardiovascular system.
This assessment is made by examining the extremities for
edema or poor skin turgor; by measuring the jugular venous
pressure (as an approximation of CVP), the aortic blood pres-
sure and peripheral pulse contour and volume; and by pulmo-
nary and cardiac auscultation. Exposure of an individual to
microgravity greatly alters these physical findings. The typi-
cal bedside cardiovascular examination of patients in micro-
gravity should be modified accordingly. This modification
begins with a basic understanding of the altered physiology of
healthy individuals.
At the bedside, CVP is determined by observing the move-
ment of the venous pulse in the external jugular vein. This
simple bedside observation is useless in microgravity because
16. Cardiovascular Disorders
the external jugular vein is continuously distended. Methods
of measuring CVP in crewmembers in microgravity have
used two types of pressure transducer technologies. The first
involved use of an open-ended, polyurethane 4-French catheter
connected to a differential pressure transducer, with the ref-
erence port positioned at the hydrostatic level of the mida-
trium [232]. Proper placement of the intravascular catheter
tip was confirmed by anteroposterior and lateral fluoroscopy
[196] just before launch. The second system used a fiberoptic
central venous catheter with a pressure transducer placed at
the catheter tip [233]. The distance between the transducer
and the level of the midatrium was measured radiographically
immediately after orbital insertion so that all pressures could
be referenced to the same hydrostatic level.
Interestingly, both of these techniques revealed that CVP
decreased upon insertion into microgravity [196,233,234].
Assumption of the required supine legs-up posture before
launch leads to an increase in CVP from 56 cm H2O to
1012 cm H2O. During launch, CVP increases to 1517 cm
H2O, probably because of the 3.0 Gx hydrostatic loading of
the venous system from the displaced vascular volume of the
legs and the heightened adrenergic state caused by the crew-
members situational awareness of the unique circumstances
surrounding rocket propulsion. At main-engine cutoff after
insertion into orbit, crewmembers experience an abrupt transi-
tion from 3 Gx to microgravity, and the CVP decreases from 15
to 17 cm H2O to ~2.50 cm H2O [196,233].(The distention of
the external jugular veins noted at main-engine cutoff and con-
tinuing throughout both short- and long-duration space flight,
however, implies that CVP is always greater than 0 cm H2O.)
During some microgravity measurements of CVP, the LV
end-diastolic dimension was also measured by echocardiog-
raphy and was found to increase from a mean of 4.60 cm to
4.97 cm within 48 h of exposure to microgravity. This result,
combined with the simultaneous measurement of end-systolic
dimensions, demonstrated that the LV stroke volume increased
from 56 ml preflight to 77 ml during space flight [196]. Left
atrial diameter was found to increase by ~13% during para-
bolic flight, which suggests that increased preload to the left
ventricle is very rapid at the onset of microgravity [235].
This finding may seem surprising because increases in cardiac
output and cardiac end-diastolic volumes on Earth are usually
precipitated by an increase in CVP.
Clinicians working on Earth have generally been able to
imply a causal relationship between changes in cardiac pre-
load and changes in CVP. During ground-based simulations
of microgravity such as head-down bed rest, CVP increases
by 34 cm H2O above that observed when a subject is supine
[236,237]. Water immersion studies have shown that upon
immersion, CVP increases immediately to a level 5 cm H2O
above the pressures measured during head-down bed rest
[238]. These CVP measurements differ remarkably from
those experienced during parabolic flight [239] and space
flight [196,233,240]. These results and the analysis of other
cardiovascular variables [241] imply that ground-based car-
333
diovascular microgravity analog models do not completely
simulate the microgravity environment in space.
The reduction in CVP of ~15 cm H2O in combination with
increased cardiac output in space has been suggested to result
from decreased intrathoracic pressure causing a decrease in
external cardiac constraint greater than the decrease in CVP,
which effectively increases cardiac chamber transmural pres-
sure [233,242,243]. The role of pericardium in external cardiac
constraint [244247] has not been considered in the published
discussions of these results. Nevertheless, the microgravity-
induced changes in the position of the diaphragm [248] and its
anatomic relation to the pericardium warrants investigation.
This anatomic distinction is important because a fall in CVP
with a simultaneous increase in LV end-diastolic dimension
implies that either pulmonary venous pressure has increased
or LV pericardial constraint has decreased. Terrestrial clinical
studies have shown an increase in LV end-diastolic volumes
with a commensurate fall in pulmonary wedge pressure when
nitroglycerin is administered [245,249251].
It has been proposed that the Gauer-Henry reflex (inhibi-
tion of antidiuretic hormone caused by atrial distension) [252]
is diminished in microgravity because of a reduction in CVP,
which implies a commensurate reduction in atrial distention
[248]. The reduction in CVP upon transition to microgravity
should bring about a reduction in right atrial transmural pres-
sure; yet paradoxically, LV end-diastolic volume increases
immediately upon insertion into microgravity.
Typically, right atrial and ventricular end-diastolic trans-
mural pressures parallel each other [244]; in combination
with a reduced CVP, the observations are consistent with a
decrease in overall ventricular pericardial constraint, resulting
in an increased LV end-diastolic volume [247] and increased
left atrial dimension [235,250]. This reasoning implies that
the increase in LV end-diastolic dimensions measured dur-
ing orbital flight may result from reduced LV pericardial
constraint, which in turn could result from decreased CVP or
from a microgravity-induced diaphragmatic rearrangement.
Unfortunately, no echocardiographic evidence is available
on whether right ventricular end-diastolic volumes change
within 24 h of achieving orbit; such a finding might help to
explain the paradox of increased cardiac output with reduced
CVP. The transmural pressure of the human right ventricle
that yields normal end-diastolic volumes is ~2 cm H2O when
the CVP is ~10 cm H2O [244]. This relation implies that the
decrease in CVP upon insertion into microgravity is very
close to the decrease in right ventricular pericardial con-
straint, with right ventricular end-diastolic volumes decreas-
ing only slightly. If reduced overall pericardial constraint
permits the left ventricle to increase its end-diastolic volume
at the same or even at lower end-diastolic pressure, then
the right ventricular afterload would decrease, thus permitting
the right ventricle to maintain its stroke volume at slightly
lower end-diastolic volumes. Echocardiographic studies of
the right ventricle upon insertion into microgravity would be
needed to test this hypothesis [253].
334
As a result of the decrease in blood volume associated with
weightlessness, a crewmember who experiences hypovolemic
shock in space may not be able to recruit pooled venous blood
in the same manner as a patient in a terrestrial emergency, who
would be placed in a Trendelenberg (headdown supine) posi-
tion or supine with legs raised [198,254]. On the other hand,
the increased capacitance of the venous system secondary to
the microgravity-induced reduction in intravascular and inter-
stitial volume after several days of space flight might allow a
crewmember to tolerate a greater extent of left-to-right heart
failure (e.g., as a complication of an acute myocardial infarction)
than would be the case under terrestrial circumstances.
It is important to understand that the apparent micrograv-
ity-induced change in venous capacitance may result from the
venous system operating at smaller volumes. Nevertheless,
it remains to be seen whether a crewmember with left-heart
failure would be able to recruit any additional venous pooling
reserve before manifesting symptoms of pulmonary edema.
Heart Rate and Blood Pressure
Heart rates during space flight have been reported to be higher,
lower, or unchanged from preflight values and can vary even
in the same crewmember during the same flight [255]. Differ-
ences in the definition of baseline (i.e., before the experiment
or during routine activities) and the combinations of counter-
measure protocols and provocative cardiovascular research
experiments undertaken during flight undoubtedly contribute
to this variance. Variances in heart rate associated with dif-
ferent phases of sleep have also been shown to change during
long-duration space flight [256]. In most crewmembers, the
physiological and psychological stresses of launch lead to def-
inite increases in heart rate [93]. Both the values of and vari-
ance in heart rate and diastolic pressure during orbital flight
were reduced when measured during Space Shuttle missions
that did not involve other provocative cardiovascular tests
[255]. Diurnal variations in heart rate and diastolic pressure
also were reduced during short-term space flight [255]. The
fact that diastolic blood pressure and heart rate decrease [255]
and cardiac output increases [257] implies that in micrograv-
ity the body is probably working with a reduced level of sym-
pathetic activity and peripheral vascular resistance.
These new set points in the cardiovascular control centers
may contribute to an impaired response to orthostatic challenge
upon return to Earth. The activities of daily living on Earth
involve frequent shifts between supine, sitting, and standing
postures. The bipedal human body is unique in that it exposes
the cardiovascular system to a variety of preload and after-
load conditions during changes in posture. Consequently, the
cardiovascular regulatory centers are continually stimulated to
adjust peripheral resistance, venous vascular capacitance, chro-
notropic and inotropic states, and vascular volume to counter
the risk of syncope. Reduced variance in blood pressure during
orbital flight may cause the central cardiovascular regulatory
center itself to become deconditioned or detuned.
D.R. Hamilton
Cardiac Rhythms
The presence of arrhythmias in military aviators, unlike nor-
mal clinical populations, is not always associated with cardiac
abnormalities. When monitored in ambulatory settings [74]
or during mission simulations, ectopy is a common finding in
apparently healthy aviators exposed to extreme accelerations
and other induced stresses. Under these circumstances, flight
surgeons are challenged to determine whether arrhythmias or
ectopic beats are of occupational or pathologic origin. In the
early U.S. and Russian space programs, ECG monitoring took
place throughout the missions, and the results were visible in
real time at the flight surgeons console. As mission durations
increased and it became apparent that microgravity itself posed
little risk of inducing arrhythmia or overtly abnormal heart
rates, the requirement for ECG monitoring was limited to only
the more stressful or mission-critical phases of space flight.
Real-time ECG monitoring was performed continuously
during the Mercury, Gemini, and Apollo spaceflight programs
and during the launch and landing of the first four Space Shut-
tle missions. NASA has successfully completed more than
100 Shuttle missions without routinely monitoring the cardio-
vascular status of the crew during launch, nominal on-orbit
operations, and landing. Real-time monitoring is required,
however, during EVAs, LBNP procedures, any exercise that
takes a crewmember above 85% of his or her predicted maxi-
mum oxygen consumption (VO2max), and other potentially haz-
ardous investigational activities. Russian program flight rules
also require that an adequate ECG signal must be received
before Soyuz rendezvous/docking activities or any EVA
involving an Orlan space suit can proceed. Although lack of
adequate ECG information to the flight surgeon console does
not preclude EVAs in the Space Shuttle program, it is required
for EVAs that involve crewmembers who have been in space
for more than 21 days (e.g., an ISS crew).
Periodic Cardiovascular Evaluations
The cardiovascular fitness of crewmembers aboard the ISS
is evaluated periodically by means of a cycle ergometer or a
treadmill exercise evaluation with ECG and blood pressure
monitoring. Before such evaluations, the crew is given an
exercise prescription that is designed to prevent them from
exceeding 85% of their predicted VO2max (maximal O2 uptake)
during the exercise. The crews ECG tracings are recorded
with four electrodes connected to a conversion network to
provide the standard 10-electrode, 12-lead electrocardiogram.
For simplification purposes, 4-lead EASI electrodes (leads E,
A, and I of the Frank lead system plus an additional S lead
positioned over the superior end of the sternum) [258260]
(Figure 16.2) are placed and the acquired data are stored
and downlinked for retrospective analysis. A study by Drew
et al. [261] in which 540 patients were tested with this 4-
lead system showed that the agreement with standard 12-lead
electrocardiography was 100% for arrhythmias, 100% for
16. Cardiovascular Disorders
Figure 16.2. EASI lead system used on the ISS for cardiac monitoring
during periodic fitness exams. This system derives 10 signals for a
12-lead electrocardiogram from the Frank E, A and I electrodes and
an addition sternal S lead. A converter device is used to reduce
the patient electrodes to 5 from 10. This makes the setup and use of
the electrocardiographic system easier and more reliable in micro-
gravity. (Adapted from Drew BJ, et al. [261].)
acute infarction, 95% for angioplasty-induced ischemia, and
89% for transient ischemia. Although the 4-lead EASI electrode
system has been used in terrestrial settings [261268], cor-
relation of the EASI 4- to 10-electrode electrical conversion
for full 12-lead ECG monitoring under the conditions of
microgravity-induced fluid and anatomic shifts has not been
validated either at rest or during exercise.
Cardiovascular Issues During Reentry
Adequate preparation of crewmembers whose cardiovascular
systems are deconditioned for reentry, landing, and vehicle
egress after exposure to microgravity is a serious concern for
flight surgeons. Cardiovascular deconditioning comprises a
spectrum of microgravity-adaptive changes that may become
maladaptive upon return to earth; these include reduced blood
volume, increased ectopy, reduced baroreceptor gain response,
and cardiac atrophy, which alone or collectively can manifest
as orthostatic intolerance and impaired exercise capacity.
Flight surgeons supporting a long- or short-duration space
mission strive to ensure that the crew is in the best possible
condition to tolerate the cardiovascular stress of the transi-
tion between microgravity and Earth gravity. The transi-
tion includes reentry acceleration force profiles that involve
exposures to 1.72.2 Gz for ~20 min on the Space Shuttle or
1.33.8 Gx for ~10 min on the Soyuz (Figure 16.3). For Soyuz
spacecraft leaving the ISS, deorbit opportunities in which
the capsule would arrive in Kazakhstan occur approximately
every 21 h; forces experienced during nominal reentry profiles
peak at ~4 Gx. For contingencies requiring immediate evacu-
ation to the ground, emergency landing opportunities which
335
Figure 16.3. Nominal Shuttle and Soyuz reentry acceleration
profiles. Curves reflect acceleration in the vehicle +x axis; Soyuz
crewmembers are recumbent while Shuttle crewmembers are seated
upright. Orthostatic reentry acceleration (head to foot, +Gz) for
Shuttle crewmembers increases steadily over a 20-min period to
~1.65 +Gz and declines to 1 G prior to the 1.36 +Gz to 1.5 +Gz expe-
rienced in the final turning maneuver one minute prior to touchdown.
Trans-thoracic acceleration for crewmembers in the Soyuz increases
steadily through early reentry, peaking at 4.43 +Gx at 200 s from the
onset of acceleration forces
might utilize steeper trajectories are available within 45 min
of Soyuz separation from ISS. However, this strategy might
expose crewmembers to up to 8 +Gx during reentry to an
emergency landing site that might not have adequate medical
support capabilities in place. Moreover, high +Gx loads on a
crewmember in the Soyuz during an emergency deorbit would
certainly stress an already compromised cardiopulmonary
system. Postflight findings from the 34-h flight of Mercury
9 revealed an increase in the astronauts heart rate from 132
beats per minute while supine in the capsule to 188 beats per
minute, with presyncopal symptoms, after 1 min of standing
upon return. The 2-man crew of Soyuz 9 were unable to exit
the vehicle at landing after their 18-day mission, presumably
because of cardiovascular deconditioning.
The ability of crewmembers to ambulate after an emer-
gency landing became a concern of the U.S. and Russian
space programs after early astronauts and cosmonauts
were noted to have problems with egress and postflight ortho-
static intolerance. This concern was heightened when it was
realized that changes made to the launch escape garments
after the Space Shuttle Challenger accident increased the
weight and thermal loads on Shuttle crews, which resulted
in substantial increase in the incidence of orthostatic hypo-
tension symptoms after flight (unpublished observation, RT
Jennings, MD, 2000). As noted earlier in this chapter, the
increase in thermal loading caused by the suit modifica-
tions may affect future crews by causing afterload reduc-
tion though vasodilatation, increased insensible fluid loss,
and impaired vagal withdrawal to orthostatic challenge
[269,270].
Introduction of the liquid-cooled ACES and more rigorous
use of the gravity-suit pressure settings have reduced the ther-
mal impact imposed by the heavy escape suit. Egress from
336
the Shuttle after landing remains difficult, however, because
the ACES and parachute together weigh 41 kg [199]. (The crew
is not required to wear the parachute portion of the ACES
during egress on the ground, which reduces the weight to
27 kg.) Egress may be further aggravated by the necessity
for a rapid deorbit burn under emergency conditions, which
may preclude completing fluid-loading countermeasures
before reentry. In an emergency, the Shuttle may have to
land at an emergency site in a country that does not have
trained rescue personnel available to assist the crew in
leaving the vehicle. Under these circumstances, the crew
may have to exit the vehicle unaided by deploying a 20-kg
inflatable slide from the side hatch or by climbing through
the top window of the flight deck and rappelling down the
side of the vehicle [195]. Finally, the crew may need to
bail out of the vehicle during stable flight and descend
to Earth by parachute. Crewmembers that have been on
orbital flights for several months may not have the cardio-
vascular reserve for such activities while wearing a 41-kg
pressurized suit.
Maintaining cardiovascular fitness throughout space mis-
sions has been proposed as a means of mitigating the pos-
sibility of impaired performance during expedited emergency
landing and other emergency scenarios. Current flight rules
stipulate that anyone who has been in orbital flight for more
than 30 days is required to be returned to Earth in the supine
position (i.e., exposed to only +Gx acceleration) to reduce the
chances of orthostatic intolerance during reentry and landing.
This requirement raises concern over whether a crewmember
could reasonably effect a self-egress from a recumbent seat
system during an emergency after a long mission. In the event
of an off-nominal landing, long-duration flight crews return-
ing on the Shuttle may need to rely heavily on assistance
from their shorter-duration and less deconditioned crewmates
for egress. In a study by Lee et al. [199], healthy subjects who
were not deconditioned performed simulated egress from the
Shuttle while wearing the ACES; these subjects deemed the
effort needed to walk 380 m, with the gravity-suit inflated to
1.5 psi (77.5 mmHg), difficult but not impossible. The ortho-
static response of a deconditioned crewmember after a long-
duration space flight may be further impaired by an increase
in core body temperature [269] resulting from impaired ther-
moregulationa condition that has been documented after
both long- [271] and short-duration [272] space flights. It
seems reasonable to plan for a short-duration Shuttle crew-
member to be available in the middeck area to assist any
long-duration crewmembers in egressing the vehicle during
emergency situations.
Orthostatic Intolerance
Orthostatic intolerance during reentry, landing, and egress is
one of the flight surgeons greatest concerns. Serious impair-
ments in crew performance can happen to perfectly healthy
and physically fit crewmembers. The ability to screen or test
D.R. Hamilton
individuals for susceptibility to orthostatic intolerance has
not been reliably established. Operational problems posed
by orthostatic intolerance depend on the space vehicle flown
and its mission profile. In the past, use of space vehicles that
returned on ballistic flight paths while the crews were in a
legs-up supine position during Gx acceleration did not pose
significant concerns with regard to cardiovascular perfor-
mance during reentry. Vehicle control during maximum Gx
on such missions was mostly automatic, and the need for a
crewmember to fly the vehicle occurred only four times, on
Mercury 9, Voskhod 2, Soyuz 1, and Apollo 11.
The Space Shuttle is a unique spacecraft in that its crew
experiences reentry forces in the +Gz body vector as opposed
to +Gx body vector common to all other spacecraft. This +Gz-
induced loading, in combination with microgravity-induced
cardiovascular deconditioning, can have deleterious effects,
especially because the vehicle is controlled by the crew during
critical landing phases. Use of inflatable anti-gravity garments
and ingestion of isotonic fluids (fluid-loading) before reentry
have been used to mitigate the risk of syncope during flight and
upon assuming an upright posture after landing (Figure 16.4).
To date, orthostatic intolerance has not manifested itself
as a significant operational hazard to astronauts and cosmo-
nauts during reentry and landing, largely because the landings
have been nominal and ground support personnel have been
immediately available at the primary landing sites. However,
the ability of all astronauts in an ACES, or cosmonauts in a
Sokol suit, to perform an autonomous emergency egress from
the Shuttle or the Soyuz spacecraft continues to be a significant
concern regardless of mission duration (Figure16.4). [199,273]
Postflight orthostatic hypotension, with syncopal or pre-
syncopal symptoms, has been noted in many returning Space
Figure 16.4. Heart rate response to entry and landing for crewmem-
bers returning on the Shuttle. Comparison of short- and long-duration
flights. The 34 short-duration spaceflight crewmembers (represented
by the open circles) returned to Earth sitting upright, which loaded
them in the +Gz axis while the three long-duration crewmembers
(represented by the open squares) returned to Earth recumbent, which
loaded them in the +Gx direction. Note the significant increase in the
heart rates of recumbent crewmembers prior to standing
16. Cardiovascular Disorders
Shuttle crews; this phenomenon, which reflects cerebral hypo-
perfusion similar to hypovolemic shock, is thought to result
from a subjects inability to recruit enough venous blood
volume to mount an appropriate baroreflex-mediated sym-
pathoexcitation and vagal withdrawal, which normally leads
to cardiac acceleration and arteriolar and venous constric-
tion [274]. Syncope and presyncope are caused by numerous
factors [275278], but the final manifestation is hypoperfusion
[279,280] of the brain, which causes impairment of con-
sciousness with a commensurate loss of postural tone. Eight
to ten seconds loss of cerebral blood flow (< 30 ml/minute
per 100 g of brain tissue) or arterial pressure (systolic pressure
< 70 mmHg or mean atrial pressure < 40 mmHg) results in a
loss of consciousness, with electroencephalographic inactiv-
ity ensuing 1214 s later [278].
The ability of the cerebral circulation to autoregulate its
vascular resistance to maintain parenchymal blood flow over
a wide range of perfusion pressures has been well docu-
mented. Bed-rest studies by Zhang et al. [281] have shown
that cerebral autoregulation may also be impaired after bed
rest, and this impairment may further exacerbate orthostatic
intolerance after exposure to microgravity. Although syncope
certainly has deleterious effects, other side effects of cerebral
hypoperfusion such as seizure and postsyncopal confusion
could also profoundly affect a mission.
Orthostatic intolerance is classified according to the
changes observed in the subjects heart rate and arterial pres-
sure. In type 1 orthostatic intolerance, diastolic and systolic
blood pressure decrease without an appropriate increase
in heart rate. This presentation of symptoms may indicate
an excessive blunting of the cardiac mechanoreceptors and
baroreceptors to a hypotensive challenge. Type 2 orthostatic
intolerance, on the other hand, presents as an increase in heart
rate with normal or increased diastolic pressure. Sweating,
palpitations, marked weakness, and an overall uncomfortable
feeling indicative of a marked increase in sympathetic respon-
siveness may accompany these symptoms. Such an increase in
sympathetic activity of the cardiovascular system is thought to
be caused by excessive stimulation of the baroreceptor reflex
induced by profound hypovolemia secondary to dependent
venous pooling, which is further exacerbated by micrograv-
ity-induced reductions in blood volume. The appearance of
these symptoms in crews returning to a 1-G upright posture
after microgravity exposure implies that cardiac mechanore-
ceptor and baroreceptor function is present but that the sym-
pathetic response may be blunted by the previous exposure to
microgravity. These symptoms can be followed by a profound
bradycardia and hypotension secondary to vagal stimulation
of the heart (Bezold-Jarisch reflex), commonly referred to as
vasovagal syncope.
Orthostatic hypotension, with presyncope, has been observed
in Space Shuttle crews after flights lasting as few as 4 days
[282,283] and has been reported to occur in 1520% of Shuttle
crewmembers who flew between 1988 and 1990, before use of
liquid-cooled garments became routine [284]. Investigations
337
conducted by Fritsch-Yelle and colleagues found that 8 of 29
crewmembers observed after flight were unable to complete
a 10-min stand test because of orthostatic intolerance; most
of these crewmembers were female [285]. Subsequent obser-
vations of 91 crewmembers who flew on the Space Shuttle
(17 women and 74 men) showed that 6 women (35%) and 5
men (7%) became presyncopal on landing day [285]. Waters
and colleagues [286] studied the cardiovascular responses to
standing in 35 Shuttle astronauts after 5- to 16-day missions.
In that study, 100% of the women and 20% of the men experi-
enced presyncopal symptoms in response to a stand test after
landing. The authors attributed these findings to a combina-
tion of inherently low systemic vascular resistance, a strong
dependence on volume status, and a hypoadrenergic response
to orthostatic challenge. These investigators also found that
the presence of high vascular resistance and hyperadrenergic
activity was protective against presyncopal symptoms during
a stand test.
In another study, Buckey et al. [209] found that after 1014
days of space flight, two thirds of crewmembers experienced
orthostatic intolerance manifested by an inability to remain
standing for 10 min when evaluated within 4 h of landing. One
crewmember, who was observed after the landing of the SLS-
1 mission, demonstrated that orthostatic intolerance upon
assuming an upright posture can occur without precipitous
change in heart rate [275]. (The absence of gravity during
short-term space flight [<16 days] led to a reduction in plasma
volume [17%] and extracellular fluid [415% of total body
water] within the first 24 h of flight [275], despite the fact that
total body water was not significantly decreased.) [222,287]
Cardiac pressure pulses are monitored by cardiopulmo-
nary, aortic, and carotid baroreceptors; they elicit beat-to-beat
changes in sympathetic and vagal cardiac efferent nervous
activity. Cooke and colleagues [288] examined the spectral
characteristics of electrocardiograms from three cosmo-
nauts before, during, and after a 9-month mission and found
reduced vagal-cardiac neural outflow and a blunted vagal
baroreflex gain that did not return to normal until 2 weeks
after the mission. Another common method of determining
the gain of the carotid baroreceptor response is to impose external
positive or negative pressure on the neck and subtract that pres-
sure from the measured or calculated carotid artery pressure at the
same hydrostatic level to derive a carotid transmural pressure.
(The carotid transmural pressure is the distending pressure
experienced by the carotid bodies that provide afferent signals
to the baroreflex control centers.) Positive external neck pres-
sure will decrease the carotid baroreceptor transmural pres-
sure; this change elicits a homeostatic reflex mechanism that
increases heart rate through efferent vagal withdrawal. A stim-
ulus-response relationship can be derived when measurements
collected with a neck chamber capable of delivering positive
and negative external pressure are correlated with changes in
heart rate (Figure 16.5) [255,283,289293].
Studies conducted after head-down bed rest [236,237,294
297] or after space flight [255,283] have shown that a minimal
338
orthostatic challenge produces a blunted heart rate response
to a given change in carotid body transmural pressure in
many subjects. The diminished carotid baroreceptor response
in spaceflight crewmembers manifests as reduced slope and
reduced range of the R-R interval response to simulated
changes in arterial pressure (Figure 16.5) [298,299].
Interestingly, carotid baroreceptors do not seem to significantly
modify arterial vascular resistance when studied indepen-
dently [298,299] or concomitantly [292] with volume-induced
stimulation of the cardiopulmonary baroreceptors. These
studies also revealed that arterial resistance in the forearms
could be altered by acute changes in CVP despite stabilized
aortic blood pressure, pulse pressure, and arterial dp/dt (rate
of change in pressure with time). Thus, the control of blood
pressure upon standing after exposure to microgravity may
not depend on vascular volume status alone [292,298,300].
Studies of patients with congestive heart failure (CHF) in
hypervolemic or euvolemic states have shown that impair-
ments in the carotid baroreflex function [290,301,302] are
responsible for many syncopal and presyncopal events in
such patients. Blunted carotid baroreceptor response may be
a significant contributor to the orthostatic intolerance seen
after return from space [209]. Convertino [302] suggested that
more effective orthostatic countermeasures for long-duration
space flight may need to include ways of increasing baroreflex
gain. If a crewmembers baroreflex gain diminishes during
orbital flight because of reduced central cardiovascular stimu-
lation, interventions such as LBNP [216,241,303] or exercise
[304,305] might impose baroreceptor challenges, with or
Figure 16.5. Effect of microgravity on the carotid baroreceptor
response relationship. Diagrammatic representation of the effect
of microgravity adaptation causing a rightward shift in the carotid
baroreceptor response curve (the so-called microgravity effect).
Microgravity deconditions baroreceptor response, resulting in larger
changes in carotid transmural pressure needed to effect the same
changes in heart rate (the so-called delta R-R interval response)
compared to 1-gravity controls. Exercise and/or LBNP (the so-called
exercise or LBNP effect) may provide a means of shifting the carotid
response curve back to the 1-gravity control curve
D.R. Hamilton
without changes in cardiac-vagal reflex gain (Figure 16.5),
similar to the daily orthostatic challenges experienced during
life on Earth [84].
Other investigations have addressed the role of catechol-
amines in postflight orthostatic tolerance. In one study [306],
LBNP was delivered by means of the Russian Chibis space
suit to a 52-year-old cosmonaut at 4 days after a 438-day mission,
and epinephrine and norepinephrine levels were measured.
Significant increases in catecholamine levels upon exposure
to LBNP at that time returned to normal levels by 90 days
after return. These case-study results seem to indicate a down-
regulation or impaired sensitivity to catecholamine hormone
receptors after space flight.
Results from the Extended Duration Orbiter Medical Proj-
ect indicate that after missions lasting longer than 10 days, the
neurohormonal response to postflight orthostatic challenge is
blunted and manifests as a decreased ability to maintain arterial
pressure and heart rate upon standing [7]. Postflight measure-
ments of plasma norepinephrine and epinephrine, collected
while the subjects were supine, were 34% and 65% higher
than preflight control values; these values further increased to
65% and 91% above control values when the subjects stood
[307]. Notably, the supine and standing epinephrine levels had
returned to normal at 3 days after landing, but the norepineph-
rine levels remained elevated [285]. This study also showed
that supine heart rate and systolic blood pressure were 18%
and 9% higher than preflight control measurements, and
standing heart rate and diastolic pressure were 38% and 19%
higher than preflight control measurements. Of the 29 crew-
members studied, 8 were unable to complete a 10-min stand
test on landing day because they became presyncopal and were
forced to sit down to prevent syncopal collapse. Investigators
observed that these 8 subjects displayed arterial pressure and
heart rate responses that resembled those of partial adrenergic
failure; also, the standing norepinephrine levels of the pre-
syncopal group were significantly lower than those of crew-
members who were able to complete the stand test. Plasma
volumes were no different in the groups, however, and thus the
mechanism responsible for the presyncope was thought to be
reduced peripheral vascular resistance secondary to impaired
sympathetic release of norepinephrine. Reduced peripheral
resistance also may have been due to receptor downregulation
resulting in an impaired smooth muscle response to adrenergic
stimulus, or possibly to changes in autonomic effector nerve
function [300]. Before flight, supine and standing peripheral
vascular resistance values were lower in the presyncopal group
than in the nonpresyncopal group [285,286]. These findings
might provide flight surgeons a way of identifying individuals
who may benefit from more aggressive cardiovascular coun-
termeasures before reentry.
Midodrine, a peripheral alpha-1 agonist, may be useful for
producing sufficient arterial and venous constriction to help
crewmembers prone to orthostatic intolerance become less
susceptible to presyncope when they stand after returning from
space flight [308,309]. Drugs such as phenylephrine, ephed-
16. Cardiovascular Disorders
rine, pseudoephedrine, ergotamine, midodrine, and indomethacin
have been tested in terrestrial settings for patients prone to
orthostasis caused by autonomic disorders, and some of these
drugs might have a role in mitigating orthostasis after space
flight.
On Earth, most of the blood stored in the lower limbs is
in the deep venous structures, which have sparse sympathetic
innervation and little smooth muscle [310]. Thus venous
capacitance is significantly influenced by the passive compli-
ance of the vessels combined with the external constraint of
the surrounding muscle and interstitial structures and fluid. As
such, changes in adrenergic tone may not invoke significant
changes in the capacitance of the deep vascular venous space.
The capacitance of the venous system in the lower extremities
can be modified by external skeletal muscle mass and tone.
Leg muscle atrophy and reduced tone secondary to disuse in
microgravity may also contribute to increased venous capaci-
tance and therefore to increased postflight orthostatic intoler-
ance [311].
Impaired Exercise Capacity
During the Gemini and early Soyuz programs, many crew-
members experienced a decline in exercise capacity after
return, as determined by changes in their heart-rate responses
and reductions in O2 consumption during a quantified work-
load. Measurements obtained before and after the Apollo 7
through Apollo 11 missions with a heart-ratecontrolled cycle
ergometer set to rates of 120, 140, and 160 beats per minute
[312] revealed significant declines in exercise performance (spe-
cifically, workload tolerance, O2 consumption, systolic blood
pressure, and diastolic blood pressure) at the 160 beats-per-
minute setting immediately after flight [206].
Skylab crewmembers similarly showed a decrease in exer-
cise performance, with most of the cardiovascular responses
returning to normal by ~3 weeks after return. In contrast to
these findings, exercise studies conducted during flight proved
that crewmembers could perform submaximal exercise (70%
of preflight VO2max) with no significant changes relative to
preflight values. In fact, some Skylab crewmembers showed
a decrease in heart-rate response, implying that the astronaut
could increase his exercise capacity on orbit. The Skylab find-
ings are difficult to compare directly with other findings from
long-duration microgravity exposures, however, because the
atmospheric pressure in Skylab was 5.0 psi (258 mmHg) with
an O2 concentration of 70%. The resulting partial pressure of
oxygen prevented hypoxia, but the reduced atmospheric pres-
sure may have reduced the ability of the crew to adequately
thermoregulate during exercise.
The Russian experience with exercise is somewhat dif-
ferent, showing significant decreases in exercise capacity
depending on the mission duration. Cosmonaut crewmembers
of the 140-day Salyut-6 and 237-day Salyut-7 missions dem-
onstrated heart rates 17% higher and stroke volumes 30%
lower than preflight values, despite daily 150-min exercise
339
sessions toward the end of the missions [313315]. Grigoriev
and colleagues [12] reported similar results from 18 cosmo-
nauts examined during Mir missions lasting as long as 366
days.
Microgravity-induced intravascular hypovolemia has
been implicated as a contributing cause of abnormal exercise
capacity upon return to Earth gravity. A study of six astro-
nauts during Space Shuttle missions SLS-1 and SLS-2 found
no difference between VO2max measured during flight and that
measured 2 weeks before flight; however, a 22% reduction in
VO2max was found immediately after flight [9]. This reduction,
which occurred after 9 days of space flight, was similar in mag-
nitude to the decrease in VO2max noted after the 84-day Sky-
lab mission. Ground-based studies using microgravity analog
models have shown a direct relationship between reduction
in VO2max and the percent reduction of plasma volume. Nota-
bly, one such experiment with 10 fit subjects demonstrated an
average of 16% reduction in VO2max and plasma volume com-
pared with only 6% reduction in VO2max and plasma volume
with unfit subjects [223].
Levine and colleagues [146] noted significant reductions in
plasma volume (17%), baseline pulmonary capillary wedge
pressure (PCWP) (18%), stroke volume (12%), LV end-dia-
stolic volume (16%), LV pressurevolume intercept (33%),
and orthostatic tolerance (24%) in subjects after 2 weeks of
head-down bed rest. The authors of that study concluded that
a bed-rest-induced decline in ventricular compliance is a con-
tributor to the impaired cardiac response to orthostatic stress
after space flight. The 5% reduction in heart mass noted in
combination with the reductions in PCWP, plasma volume,
and stroke volume [146] is also consistent with the concept
of a smaller heart operating within a less compliant portion of
the pericardial pressure-volume relationship [247]. In another
study, Perhonen and colleagues [316] challenged volunteers
with simulated orthostatic G loads from LBNP or diuretics
in a 14-day, head-down-tilt bed-rest study and documented a
similar leftward shift in the LV end-diastolic function curve.
The LV pressurevolume relationship of the heart is signifi-
cantly influenced by the pericardial pressurevolume relationship.
Assuming that LV transmural pressure is a function of PCWP
alone, without considering the influence of the pericardium on
the LV pressurevolume relationship, may lead to erroneous con-
clusions regarding shifts in LV transmural pressurevolume func-
tion curves [247] and commensurate Starling responses. Tyberg
and colleagues [247] have shown that subtracting the mean right
atrial pressure from PCWP is a better predictor of changes in LV
transmural pressure and that LV transmural pressure is a better
estimate of preload than PCWP alone. The studies by Levine et al.
[146] and Perhonen et al. [316] used PCWP alone as a measure-
ment of LV transmural pressure changes. Although these studies
showed that the PCWPLV end-diastolic volume relation shifted
to the left, the true LV transmural end diastolic pressureLV end-
diastolic volume relation may not have shifted as significantly.
The use of supine LBNP or acute diuresis to simulate ortho-
static +Gz loading after flight may induce the same blood
340
volume shifts seen in microgravity, but it remains to be seen
whether the external constraint of the heart is altered in a
similar manner. The mechanics of ventricular preload during
an acute orthostatic challenge after bed rest or microgravity
require further examination [253].
Lee and others [317] studied 30 crewmembers who per-
formed various levels of exercise before and during flight
missions lasting 916 days. They found that the group that
performed moderate- to high-level exercise during flight had
less orthostatic intolerance to a 10-min stand test after flight.
Moreover, performing higher-level exercise during flight
seemed to have had a protective effect on the increase in heart
rate and the fall in pulse pressure that are experienced by all
crewmembers upon return (Figure 16.6). Further research is
needed to determine whether this effect was due to a change
in the carotid-cardiac baroreflex set point [275,318], altered
splanchnic vasoconstriction [319], increased plasma vol-
ume [315,320], or decreased venous capacitance caused
by increases in lower-extremity muscle tone and interstitial
volume [321,322]. Regardless, these results suggest that in-
flight exercise [317,323] may be an important component of a
comprehensive orthostatic countermeasures program for both
long- and short-duration missions [324].
One of the most significant operational workloads is the
exertion associated with EVAs, when crewmembers may work
Figure 16.6. Space flight-induced change in physical work capacity
with various exercise regimens during flight. The percent degrada-
tion in exercise capacity from preflight controls was measured
on astronauts postflight and compared to the exercise they received
on orbit. NONE = no on-orbit exercise; RUN C = exercising on
treadmill regularly; RUN I = exercising on treadmill intermittently;
BIKE I = exercising on a cycle ergometer intermittently; and ROW I
= exercising on a rowing machine intermittently
D.R. Hamilton
for 6 h or longer in a mechanically restrictive space suit, with
mean metabolic expenditures of about 200 kcal/h (800 BTU/h)
and 5- to 10-min peaks of more than 380 kcal/h (1,500 BTU/h).
The current configuration of the U.S. extravehicular mobility
unit (EMU) space suit, which is used to perform EVAs, allows
a crewmember to drink 947 ml of fluid; the Russian Orlan
space suit, which is also used to perform EVAs, has no supply
of drinking water. Russian measurements of body mass before
and after EVAs indicate that cosmonauts lose 0.72.2 kg of
fluid during a typical EVA. EVA-induced dehydration, with its
commensurate reduction in plasma volume, can exacerbate an
existing decline in exercise capacity caused by long-duration
exposure to microgravity. Thus flight surgeons should ensure
that crews are well hydrated before undertaking an EVA.
Reentry Countermeasures
Countermeasures such as fluid and salt loading have proven
effective in reducing the incidence and severity of syncopal
and presyncopal symptoms upon return from short-duration
space missions [7,93]. A combination of pharmacologic [325]
and mechanical [7,241] countermeasures may be more effec-
tive than mechanical countermeasures (e.g., LBNP, treadmill
or cycle ergometry exercise, or use of a gravity suit) alone
in preventing postflight orthostasis. Since the bioavailabil-
ity, elimination half-life, volume of distribution, and clear-
ance of drugs used for countermeasures are largely unknown
[326,327], the use of several countermeasures simultaneously
may interfere with the independent assessment of each indi-
vidual countermeasure.
Results from the Extended Duration Orbiter Medical Project
suggest that most crewmembers are in a negative energy balance
during short-duration space flight and that most weight loss is a
result of reduced muscle mass [7]. The findings on electrolyte
balance are quite variable, and no evidence exists to suggest that
a well-hydrated and well-nourished crewmember would experi-
ence dangerous extremes in serum electrolyte levels.
Unfortunately, in many circumstances crewmembers find
themselves unable to drink or eat adequately. During the
first several days of space flight, crewmembers may experi-
ence space motion sickness, which can manifest as malaise,
fatigue, suppressed appetite, nausea, and vomiting. The crew
activity schedule sometimes keeps crews from ingesting
adequate amounts of fluid, which may exacerbate an already
hypovolemic state relative to the terrestrial standard. Further,
low urine volume and increased levels of calcium excreted in
the urine from microgravity-induced musculoskeletal unload-
ing are key risk factors in the development of nephrolithiasis
[328330]. Crewmembers are therefore encouraged to drink
adequate amounts of fluids and to maintain a regular exercise
schedule [328,331].
During handovers when the transport vehicle (Shuttle or
Soyuz) is docked to the ISS, crewmembers returning from
long-duration missions will be able to fully access all ISS
exercise countermeasures facilities for daily use. Methods and
16. Cardiovascular Disorders
opportunities for prescribed exercises will also be provided
on the Space Shuttle for crews returning from long-duration
space flights.
At a minimum, equipment aboard the ISS for exercise
countermeasures consists of a treadmill, a cycle ergometer,
and a resistive exercise device. Other types of countermea-
sures available on board can include LBNP, whole-body
elastic-loading suits (e.g., the Russian Penguin suit), thigh
cuffs (e.g., the Russian Brazlet device), pharmacologic
preparations, and electromyostimulator systems. At the end
of an ISS mission, when the crew is returning home via the
Space Shuttle, orthostatic countermeasure and exercise equip-
ment include: fluid/salt-loading, anti-gravity garments (e.g., the
pneumatic gravity suit, the Russian Kentaver elastic antigrav-
ity garment), active cooling (i.e., a liquid-cooling garment),
recumbent seating (provided for crewmembers returning from
flights longer than 30 days), and pharmacologic preparations.
In-Flight Exercise
Regular exercise is part of the flight schedule on Space
Shuttle and ISS missions to preserve physiologic function
during entry and following landing. Space Shuttle Opera-
tional Flight Rules [201] require that the commander, pilot,
and mission specialist (or flight engineer) who are support-
ing the landing exercise once every other day after being in
flight for more than 3 days. Daily physical exercise (1.5 h
of varying amounts of resistive and aerobic exercise) is also
scheduled for ISS crewmembers. Exercise prescriptions are
tailored to meet the needs of each crewmember, but all fol-
low a basic schedule. Intense exercise (e.g., at levels > 85%
of the preflight maximum VO2max) requires ECG telemetry
and continuous air-to-ground voice communications during
portions of the test and continuing throughout the recovery
period. By definition, the recovery period lasts at least 5 min
but it can be extended at the flight surgeons discretion. For
space flights on which no trained physician is on board or
real-time ECG monitoring capability is lost [332], exercise
is to be limited to 85% of VO2max. When a trained physician
crewmember is on board the ISS, he or she can continuously
monitor a crewmembers electrocardiogram during exercise
above the 85% workload limit. Monitoring is required when
vigorous exercise is part of a research protocol, but not for
routine daily exercise.
Intense monitored exercise, during programmed exercise
sessions as part of a research protocol, or in the course of stren-
uous operational activities such as EVAs, is to be terminated if
any the following cardiac rhythm disturbances occur: sustained
abnormal SVT (defined as paroxysmal atrial tachycardia, atrial
fibrillation, atrial flutter, or other SVT of unidentified etiology
lasting longer than 10 s); VT; exercise-induced bundle branch
block; R-on-T PVCs; unexplained inappropriate tachycardia;
multifocal PVCs; onset of second- or third-degree heart block;
increasing ventricular ectopy (in which more than 30% of the
total beats are unifocal PVCs); maximum heart rate greater
341
than explainable by exercise stimulus; chest pain, dizziness,
or other symptoms of intolerance. Intense exercise is also to be
terminated if the subject asks to stop.
Fluid Loading
Early bed-rest studies revealed the usefulness of oral rehydra-
tion with saline solutions in the form of bouillon to protect test
subjects from orthostatic stress by LBNP [303,333] or +Gz
acceleration [334] by transiently expanding plasma volume.
Oral rehydration with salt and water is considered a reentry
countermeasure in both the U.S. and Russian space programs.
Studies by Prisk and colleagues [242] showed that fluid load-
ing prevented the sharp reduction in cardiac output and stroke
volume observed during a stand test conducted after 17 days
of head-down bed rest. Results from the SLS-1 Space Shut-
tle mission, on which no fluid load reentry countermeasures
were performed, found that stroke volume and cardiac output
decreased by 27% and 14%, respectively [242]. Results from
the SLS-2 and Neurolab missions showed that fluid load-
ing was effective in preventing the fall in cardiac output and
stroke volume seen in crewmembers from the SLS-1 and D-2
missions [209]. Buckey and colleagues [209] noted that fluid
loading alone may not be completely effective in preventing
orthostatic intolerance and that an appropriate increase in car-
diac afterload may also need to occur to protect against pre-
syncope and syncope after flight.
Because ionized compounds provide ~95% of plasma
osmolality in humans, it seems logical to use oral fluids com-
posed mostly of water and electrolytes to increase plasma
volume [335]. The independent and combined effects of
LBNP and oral fluid-loading with saline have been stud-
ied to determine the optimal means of expanding plasma
volume. Oral rehydration alone was found to produce the
largest increase in plasma volume [333]. Studies by Bungo
and others [80,336] revealed that Shuttle crewmembers who
ingested saline experienced a 29% reduction in the expected
heart-rate response and a reversal in the fall of mean blood
pressure when exposed to orthostatic stress after return from
space flight. Greenleaf and colleagues [335] also found that
in dehydrated subjects at rest, the cation content (e.g., sodium
ions) of a fluid-loading solution is more effective than other
ingredients (carbohydrate) that increase osmotic content for
increasing plasma volume. Interestingly, in that study the
final plasma volume after 70 min of exercise at 70% of peak
VO2max was not affected by the osmotic or electrolyte content
of the ingested fluid [335].
These results have led to the use of fluid-loading with nor-
mal (0.9%) saline as an operational countermeasure before
reentry and landing. Experiments conducted by Frey and oth-
ers [337] showed that 1.07% oral saline may be more effective
than 0.9% saline in maintaining plasma volume after reentry
(Figure 16.7), although use of the higher concentration has
been associated with diarrhea [338]. The operational require-
ment in the Space Shuttle Program is a fluid load of 15 ml
342 D.R. Hamilton

normal saline (0.9% NaCl) per kilogram of preflight body landing. If a 1-orbit wave-off occurs (as is common because
weight, to be ingested 12 h before landing. of weather problems at the landing site) and the fluid-loading
Basing the prescribed volume of isotonic solution on a protocol for deorbit has been completed, the protocol is
crewmembers preflight body mass helps to ensure that the repeated with half of the originally prescribed amount. If the
fluid load is adequate for larger crewmembers and is not exces- delay extends beyond 1 orbit (i.e., more than 3 h), the entire
sive for smaller crewmembers (Table 16.4). ASTROADE fluid loading protocol must be repeated because renal clear-
and other flavored isotonic solutions provide plasma volume ance or loss of fluid to the interstitial spaces will have negated
expansion similar to that of water and salt tablets and may be the effect of this countermeasure.
more palatable for some crewmembers. Flight surgeons must
approve use of any alternative solutions before flight. Isotonic
fluid-loading is required for all crewmembers before deorbit Gravity Suit Protocol
and is to be initiated no earlier than 1.5 h before the deorbit burn The Space Shuttle reentry profile imposes a steadily increas-
[201]. At that time, each crewmember must consume 8 oz of ing +Gz acceleration on the crew over a 20-min period, peak-
water and two salt tablets, or 8 oz of other approved solutions, ing at 1.65 Gz before rapidly declining to 1 G after the Shuttle
every 15 min until the total prescribed dose is achieved. has shed most of its kinetic energy. The crew also experiences
To prevent gastric irritation and an inappropriate increase a sharp increase in acceleration from 1.36 +Gz to 1.5 +Gz
in plasma osmolality, which may exacerbate dehydration, it is during the final turning maneuver, where the Shuttle, under
important that sufficient amounts of water be consumed with manual control by the pilot, banks to align itself with the run-
the salt tablets. Crewmembers are instructed before launch as way for the final approach and touchdown. Any presyncopal
to the proper amount of salt and fluid to ingest, and reminders or syncopal events experienced by the pilot or commander at
are given during the private medical conference on the day of that time could be catastrophic.
Space Shuttle commanders, pilots, and mission specialists
have experience with flying high-performance aircraft and
preventing +Gz-induced loss of consciousness. Present-day
fighter pilots use a pressurized air bladder gravity suit [339] to
help prevent these deleterious effects during high +Gz maneu-
vers, and all Shuttle crews use a similar 5-bladder gravity suit
(the CSU-13B/P suit [195]) for reentry. Inflation of air blad-
ders in the lower extremities of the suit prevents venous blood
from pooling in the lower extremities and displaces blood
toward the heart [339,340]. The onset of +Gz forces during
Shuttle reentry is initially gradual (0.0012 Gz per second for
15 min) and typically reaches a plateau at 1.5 Gz for 5 min.
In addition to using gravity suits, fighter pilots also use an
antigravity straining maneuver, which is a repetitive modified
Valsalva maneuver combined with isometric limb contractions
Figure 16.7. Effect of oral fluid loading with various fluid types to help maintain aortic root pressures and cerebral perfusion
on changes in plasma volume as a function of time relative to land- during high +Gz maneuvers. Prolonged use of the antigrav-
ing. Water, normal saline (0.9%), or hypertonic saline (1.075%) was ity straining maneuver to prevent presyncopal symptoms or
ingested in a quantity of ~910 ml (32 oz) 2 h prior to landing with +Gz-induced loss of consciousness are not feasible for the lon-
plasma volume changes calculated by hemodilution. ger-duration Shuttle reentry acceleration profiles. The Shuttle
gravity suits take longer to inflate than those used in fighter air-
Table 16.4. Fluid loading requirements for astronauts returning to craft (60 s to reach 1.5 psi [77.5 mmHg] vs. 1.5 s, respectively).
earth via the space shuttle. A centrifuge study performed by Krutz and others [341]
Fluid load
determined that inflating the Shuttle gravity suit to 1.5 psi
(77.5 mmHg) 10 min before +Gz onset was effective in pro-
Amount
of approved
tecting dehydrated subjects exposed to a radial acceleration
Preflight No. of 8-oz alternative profile similar to a Shuttle +Gz reentry profile. These subjects
body weight (237-ml) drink No. of salt solution, were given a diuretic to simulate after-landing intravascular
lb (kg) containers tablets OR oz (ml) hypovolemia. This study also found that inflating the suit
<120 (<54) 3 + 6 24 (710) early maintained the eye-level blood pressure at a higher level
120155 (5470) 4 + 8 32 (946) and reduced the peak heart rates. Information gained during
155190 (7086) 5 + 10 40 (1,183)
this study led to the Shuttle flight rule requiring all crewmem-
>190 (>86) 6 + 12 48 (1,420)
bers to inflate their gravity suits before the reentry interface
Source: Adapted from NASA National Space Transportation System [201]. that marks the onset of acceleration forces on the vehicle.
16. Cardiovascular Disorders
The anti-orthostatic protection provided by a gravity suit may
diminish over time periods beyond 30 s, as manifested by the
inability to maintain LV end-diastolic volume, when the grav-
ity forces exceed 3.0 +Gz [342].
The air bladders in the Shuttle suit inflate in 0.5-psi
(26-mmHg) increments to a maximum of 2.5 psi (130 mmHg)
[195]. Space Shuttle Operational Flight Rules [201] require
that the suits be inflated to 0.5 psi (26 mmHg) after entry inter-
face and to at least 1.0 psi (50 mmHg) at 1 G during return from
flights of more than 11 days. The gravity suits must remain
inflated until the Shuttle wheels come to a stop. The suit must
be inflated before the onset of symptoms; this is especially
important to help prevent orthostatic problems after longer-
duration flights. Crewmembers can increase the pressure of
the gravity suit during any portion of the reentry profile should
they have symptoms that require it. Gradual deflation of the
bladders after landing also minimizes symptoms by reducing
blood pooling. If a crewmember elects to deflate the bladder
before egress, deflation will be accomplished progressively
over 10 min.
As noted earlier in this chapter, crewmembers returning from
long-duration flights in the shuttle do so in a recumbent seat
system in which their feet are elevated into a middeck locker
a position not unlike the launch position. In this position, the
abdominal bladder in the gravity suit may impose undue dis-
comfort, especially when combined with a complete fluid load
countermeasure. Under some circumstances, this pressure
increases the risk of vomiting the fluid load before landing.
Because this posture protects the crewmember from reentry
+Gz stress, flight surgeons typically recommend that such crew-
members initially inflate the suit to 0.5 psig onlyjust enough
inflation to remove the creases from the suit. The pressure can
be increased as needed, but the crewmembers are forewarned
about the abdominal discomfort that this can cause.
Lower-Body Negative Pressure
LBNP refers to the application of pressure over the lower
body that is below the ambient cabin pressure. Enclosing the
subject below the level of the iliac crest in an airtight chamber
achieves the desired configuration for lower-body decompres-
sion [84]. This decompression causes the intravascular volume
to shift towards the lower extremities in a manner similar to
the orthostatic load caused by assuming an upright posture in
1 G. LBNP has been used as both a countermeasure and as
a method of screening for orthostatic intolerance before and
during flight [304,343].
In the Russian space program, LBNP is delivered during
space flights with a device called the Chibis, a set of corru-
gated pneumatic trousers that can develop a negative pressure
of 1.0 psi (50 mmHg) [2,12,84,344,345]. The Chibis loads
the body in a different manner than the LBNP devices used
on Skylab and the Space Shuttle [84]. The Russian system
includes a built-in foot support that requires a cosmonaut to
stand in the device, which loads the pelvis with the feet sup-
343
ported and loaded by airtight boots. The body support in the
U.S. LBNP system, in contrast, is provided by a saddle or seat
that lets the feet dangle, thereby mechanically unloading the
lower extremities. If the intent of LBNP is to maximize the
orthostatic challenge to the cardiovascular system, this system
is probably more effective than the Russian system. However,
if the intent is to mechanically load the musculoskeletal and
cardiovascular system in a manner similar to postflight standing,
the Russian Chibis is probably the more effective of the two
[346]. Loading the lower extremities during LBNP leads to
increased muscle tone and thus decreased venous compliance
and capacitance, thus providing a protective effect against the
caudal fluid shift induced by LBNP.
The Russian experience with the Chibis device is extensive
and has been used in all but one of the Salyut and Mir space
station missions. As the crew usually returns to Earth on a
Soyuz spacecraft and the time between the last use of the
LBNP and landing is typically less than 24 h, Russian investi-
gators have found in-flight LBNP to be an effective counter-
measure against orthostatic intolerance. On the other hand, if
the Space Shuttle is being used to return crewmembers from
the ISS, the time between the last use of LBNP and landing can
be several days depending on the mission plan after the Shut-
tle undocks from the ISS. Findings obtained from Extended
Duration Orbiter Medical Project investigations with Shuttle
crews suggest that LBNP may not be effective unless it is con-
ducted within 4 h of landing [7].
The hope is that when ISS construction is complete, more
prospective controlled studies will be performed to better
understand operational protocols such as the soak coun-
termeasure, which combines LBNP and fluid-loading. This
countermeasure is mandatory for cosmonauts; however, it is
optional for all remaining ISS crewmembers because it has
yet to be standardized.
Given the risk of LBNP to induce presyncope and syncope
under nominal circumstances, ECG telemetry and continuous
air-to-ground voice communications are required during por-
tions of the LBNP ramp test when the decompression is less
than about 0.5 psi (2630 mmHg). A second crewmember is
required to remain nearby during all LBNP operations while
the first crewmember is in the LBNP device [201,347]. This
second crewmember serves as the test operator, assisting his or
her crewmate during depressurization and exit from the device
as needed, e.g., during rapid egress or if the crewmate becomes
incapacitated. If the ramping must be stopped because of
reaching one or more termination criteria (Table 16.5), the
LBNP device will be recompressed to ambient pressure. Both
the Chibis and the U.S. LBNP device have a dead-man
switch, held by the subject, which allows rapid repressuriza-
tion to cabin atmosphere in the event of syncope. It is interest-
ing to note the investigations of Convertino et al. [348350]
which found an increase in stroke volume on subjects undergo-
ing LBNP (60 mmHg) using an impedance threshold device
(ITD). The ITD acutely increases central blood volume by
making the mean thoracic pressure negative with respect to the
344 D.R. Hamilton

Table 16.5. Termination criteria for lower-body negative pressure ramp operations.
Termination criteria
g s Drop in heart rate > 15 beats per minute in 1 min
g s Drop in blood pressure (either a systolic drop > 25 mmHg or a diastolic drop > 15 mmHg in 1 min)
g s Systolic blood pressure 70 mmHg
g Any of the following significant cardiac arrhythmias:
Heart rate < 40 bpm for person whose resting heart rate is > 50 bpm
Three or more beats in a row of supraventricular or ventricular tachycardia
Evidence of heart block other than first degree
Premature ventricular complexes (PVCs) that meet any of the following criteria:
6 PVCs in 1 min
PVCs that are closely coupled (qr/qt < 0.85)
PVCs that fall on the T wave of the preceding beat (R on T phenomena)
PVCs that occur in pairs or in runs
Multiform PVCs
s Severe nausea, clammy skin, profuse sweating, lightheadedness, tingling, dizziness
s Subject request at any time
g s Loss of ECG monitoring at the surgeons console or voice downlink during portions of ramp protocols below 30 mmHg
of decompression (40 mmHg and 50 mmHg)
g s Resting heart rate greater than the maximum heart rate observed during preflight presyncopal LBNP testing

Abbreviations: g, ground initiated; s, subject initiated.

Source: Adapted from National Space Transportation System [347].

local atmospheric pressure. This device uses a passive valve to
control the inspiratory flow as a function of thoracic negative
pressure. The ITD is being proposed as an acute treatment of
hemorrhagic shock on Earth and a possible post-flight ortho-
static countermeasure for long- and short-duration crews.
Treatment of Cardiovascular Illness
in Low Earth Orbit
As ISS assembly nears completion, medical planners are antici-
pating the next steps in exploring space beyond low Earth orbit.
Cardiovascular events have consistently been ranked as pos-
ing one of the greatest risks for short and long-duration space
travel based on the probable incidence versus impact on mis-
sion and crew health. [351,352,353] NASAs Medical Policy
Board, which considers cardiovascular abnormalities a medi-
cal problem likely to be encountered during exploration-class
missions, has established a design requirement for stabilization
and effective timely treatment in addition to the requirement
for stabilization and evacuation of seriously ill or injured crew-
members [93,305]. This medical event management strategy
is similar to the emergency medical support plans for injured
workers on an offshore oil platform or other remote location
that involves occupational environmental hazards.
Acute myocardial infarction is considered the prototypic
cardiovascular problem for which required medical capabili-
ties are defined. On Earth, ~7% of patients admitted to a hospi-
tal with an acute myocardial infarction experience cardiogenic
shock [354]; 50% of these patients are in shock at the time of
admission, and the remainder develop symptoms within 48 h
[355]. Cardiogenic shock after an acute myocardial infarction
is usually precipitated by a reduction in LV function secondary
to infarction of the left ventricle (79%) or right ventricle (3%),
papillary muscle dysfunction (7%), or ventricular septal rup-
ture (4%) [355,356]. Randomized controlled trials of patients
with acute myocardial infarction on Earth have shown that oral
aspirin [357,358], thrombolytic therapy [359361], angioten-
sin-converting enzyme inhibitors [362364], early percutane-
ous transluminal coronary artery angioplasty [365,366], and
beta-blocker therapy [367] can decrease mortality if applied
emergently in a hospital setting. Studies have also shown that
low-molecular-weight heparin and platelet glycoprotein IIB/
IIIA inhibitors have been effective for managing acute coro-
nary syndromes [368373]. Therapies such as these may be the
only way of dealing effectively with ischemic syndromes and
myocardial injury during orbital space flight because defini-
tive therapy is currently impossible aboard those vehicles.
A review of the equipment and procedures required to deliver
this type of emergent health care on Earth is beyond the scope
of this chapter; however, suffice it to say that this capability is
not required in the current medical system on board the ISS.
Outcome studies have shown that the risk of mortality from
an acute myocardial infarction can be reduced if the patient
is given therapies such as those noted above within 424 h
[357367]. If mitigation of cardiovascular mortality and mor-
bidity risk is a requirement for crewmembers currently slated
for ISS missions, then the prompt transport of these patients to
a tertiary medical care facility on Earth within 24 h is the only
means of accomplishing this.
The medical resources aboard the ISS were designed to
treat minor illness and to transport crewmembers that require
advanced medical care. The current Integrated Medical System
(IMedS) has two components, the U.S. segment Crew Health
Care System and the Russian medical system. The IMedS was
designed to include ways of resuscitating crewmembers through
16. Cardiovascular Disorders
the use of procedures and hardware similar to those used in the
American Heart Associations Advanced Cardiac Life Support
training. Most of the Advanced Cardiac Life Support capabil-
ity comes from the Crew Health Care System portion of the
IMedS, which contains a pacing defibrillator, a 100% O2-only
transport ventilator, and an advanced life support pack that
contains the cardiac drugs and equipment needed for resus-
citation. With these resources, an unconscious crewmember
could be intubated and external cardiac pacing administered
as necessary; however, performing these procedures on a con-
scious patient in severe respiratory distress would be quite
challenging for a CMO who is not a physician [374380].
The unique environment of microgravity combined with
the habitational design of the ISS require that affected crew-
members be electrically isolated from the vehicle with a crew
medical restraint system before any defibrillating shock is
delivered. This restraint system, described further in Chap.
4 (Space Flight Medical Systems), has been validated on the
Space Shuttle and in parabolic flight aboard the KC-135;
results of these tests indicate that non-physician crewmembers
and test personnel can deploy and deliver the first defibril-
lation shock within 2 min of calling a code. Whether car-
diac drugs in common use on Earth [381] would be effective
during a resuscitation in space flight needs to be examined
in light of the changes experienced by the cardiovascular and
other physiological systems during space flight [325,326].
The decision to include aggressive life-saving measures in the
IMedS design was based on findings from terrestrial paramedic
and hospital-based advanced cardiac life support. On Earth,
advanced cardiac life support capability is designed around
the ability to transport a patient to a definitive care facility in
time to deliver advanced emergency medical care [382].
Although the Crew Health Care System portion of the IMedS
was designed to stabilize an acutely ill crewmember for trans-
port to a definitive care facility within 24 h, the availability of
a crew return vehicle that could support a patient in that condi-
tion is still to be determined. The design of a new crew return
vehicle (still in the planning stages when this chapter was
written) includes the ability to provide advanced life-support
capability similar to that found in most terrestrial air transport
ambulances. The current ISS lifeboat is the Russian Soyuz
spacecraft, which was not designed to provide supplemental
medical care during any phase of deorbit. The inability of the
crew on board the Soyuz to provide pacemaker capability, to
deliver supplemental O2, or to provide any ventilation support
imposes serious limitations on the transport of a critically ill
patient. Also of concern are the nominal peak reentry accel-
erations of up to 3.8 Gx, which would stress the cardiovascular
and pulmonary reserves of a disabled crewmember. CMOs,
under the guidance of the ground-based flight surgeon, would
therefore need to wean a patient from 100% O2 in the ISS
before that patient is transferred to the Soyuz for deorbit.
In most cardiovascular emergencies, many aspects of a
patients physical examination (e.g., circulatory volume status,
vital signs, level of consciousness) are important. The abil-
345
ity of the Mission Control-based flight surgeon to monitor an
affected crewmember during the resuscitation and stabilization
phases of a medical emergency is limited by the intermittent
nature of communications to the ISS, which on average are
available only 50% of the time [332]. This communication
may be limited to a single air-to-ground voice loop and to the
rhythm strip output of the defibrillator. Blood pressure, O2 sat-
uration, and other important critical-care information will be
unavailable to the flight surgeon unless crewmembers verbally
relay this information to the flight surgeon on a voice loop.
As discussed previously, evaluation of a patients circu-
latory volume status in space is complicated by the physi-
ological alterations induced by microgravity and the lack of
clinical experience and training of the CMOs. The absence
of classical bedside findings (e.g., jugular venous pulsations,
lower-extremity fluid shifts, and probable loss of dependent
venous lung zones) makes determining volume status a chal-
lenge even for a critical care specialist at the microgravity
bedside, let alone for a non-physician CMO with only 12 h of
training in advanced cardiac life support. Thus flight surgeons
must integrate their traditional medical training and experi-
ence in terrestrial medicine with the physiology and expected
pathophysiology of space flight. For example, when the prin-
ciples of terrestrial cardiac pathology are used in treating an
acute myocardial infarction during flight, increased shortness
of breath and the presence of diffuse pulmonary crackles can
indicate extremely elevated pulmonary venous pressures and
diastolic failure secondary to significant systolic failure or
papillary muscle dysfunction. The concept of euvolemia is
different in microgravity from that on Earth, and the physical
findings indicative of abnormal volume status are currently
unknown. The increase in venous capacitance secondary to
microgravity exposure may allow the patient to buffer sig-
nificant volumes of fluid before right-sided heart failure mani-
fests itself. From a space-medicine clinical perspective, this
may mean that the amount of central venous volume required
to increase left atrial pressure to levels that induce pulmonary
edema is greater in microgravity than on Earth, thereby
possibly providing a protective effect on the lungs.
This potential physiological advantage may be negated,
however, by the fact that in microgravity, all regions of the
lung may be susceptible to pulmonary edema at the same time
because of the loss of dependent pulmonary venous zones.
The ability to classify the severity of heart failure according
to terrestrial categories such as Killip class, which is based
on the degree of alveolar flooding (crackles) detected during
pulmonary auscultation, may not be possible in micrograv-
ity. When patients on Earth have basilar crackles secondary
to high-pressure pulmonary edema from CHF, the mid-lung
pressure is ~20 cm H2O, which means that the pressure at the
bases is about 30 cm H2O. Under microgravity conditions,
pulmonary venous pressure will probably need to increase to
30 cm H2O to cause global alveolar flooding. However, when
this occurs in microgravity, the auscultation of crackles
anywhere in the thorax may be a harbinger of fulminant
346
pulmonary edema that does not increase gradually with time,
as would be the case on Earth, but rather may appear suddenly
without warning.
Detection of the early signs and symptoms of pulmonary
edema may be essential to effective treatment in microgravity,
given its potential to be acutely life-threatening [383385].
The physical signs indicative of pulmonary venous pressures
of 30 cm H2O in a patient in microgravity are unknown. The
microgravity-induced cephalad fluid shifts and changes in
lower-extremity intravascular volume may render use of a
venodilator (e.g., nitroglycerin) ineffective in the immediate
treatment of pulmonary edema [249,251]. Phlebotomy, LBNP,
or thigh cuffs [215,386] to induce lower-extremity venous
pooling and to reduce LV end-diastolic pressure may be more
effective for treating CHF on orbit. The physical sign of CHF
after several days of exposure to microgravity might be the
appearance of non-edematous, volume-overloaded lower
extremities that look normal by terrestrial standards but that
are clearly larger than the normal chicken legs appearance
in microgravity. In general a patient requiring cardiac critical
care in microgravity should be considered to be similar to one
on Earth in a critical care unit bed placed in 6 degree head
down tilt [387].
Flight surgeons may need to assess acute changes in circu-
latory volume status by means of calf circumference measure-
ments. A device that uses anthropometric landmarks at several
points on the leg to measure calf circumference is manifested
on the ISS. Calf circumference is usually measured every
2 weeks as a way of tracking calf muscle loss, but these mea-
surements could also provide a baseline from which to follow
acute changes in leg volume in the event of CHF. Changes in
circulatory volume status might also be detected by measuring
acute changes in body mass, which may reveal an unappreci-
ated change in venous volume.
A crewmember who must be returned to Earth after in-
flight treatment of respiratory distress secondary to an acute
myocardial infarction may experience significant exacerba-
tion of CHF during the reentry Gx acceleration experienced in
the legs-up recumbent position in the Soyuz spacecraft. The
CHF in such a crewmember may dramatically improve upon
being given 100% O2 by mask and being placed in an upright
seated position in a padded chair outside the spacecraft after
landing. This simple maneuver alone may take advantage of
the reduced intravascular volume incurred by long-duration
microgravity exposure; that reduced volume should acutely
drop the preload to the heart when the crewmember first
stands despite the myocardial-infarction-induced CHF in
microgravity. In this case, the cardiac deconditioning incurred
by microgravity along with the terrestrial 1-Gz loading of the
venous system may provide the same benefit as administering
nitroglycerin and a mild beta blocker to a patient after a myo-
cardial infarction on Earth.
Flight surgeons must make real-time clinical decisions on
the basis of limited telemetry data and unskilled observations
D.R. Hamilton
reported by the CMO. This information must then be used to
guide the CMO in preparing the patient for transfer into the
Soyuz escape vehicle and eventual deorbit. Flight surgeons
must also be able to communicate the diagnosis and prognosis
of the affected crewmember to the flight director and the mis-
sion management team.
The ability to return a crewmember from the ISS to one of
several possible primary landing sites in Kazakhstan or Rus-
sia with the Soyuz escape vehicle is limited to approximately
three consecutive orbits every 24 h. Depending on the crew-
members illness, it is questionable if enough onboard medi-
cal resources exist to stabilize a patient for this length of time.
The timing of the next primary landing site opportunity could
also require that a patient be transferred to the Soyuz rapidly,
within 1 h from the onset of the initial emergency; otherwise,
the next landing opportunity would be delayed by an addi-
tional 24 h.
For a Soyuz landing, Mission Control in Moscow maintains
control of vehicle operations. All communications are con-
ducted with the very high frequencies that are not used by U.S.
space-to-ground systems. Therefore, all medical communica-
tions will be handled by the Russian Medical Support Group.
All medically relevant voice communications will need to be
relayed by the Russian Medical Support Group to the lead
flight surgeon in the U.S. Mission Control Center. Once the
Soyuz has undocked from the ISS, it must loiter for two
orbits (~3 h) before it re-enters and lands at a nominal landing
and recovery site in Kazakhstan. While the Soyuz spacecraft
is in orbit, the Russian ground medical officer will be able to
communicate with the crew less than 20% of the time.
If returning to the ground is time-critical, the Soyuz is
capable of deorbiting within 45 min onto several emergency
landing sites distributed throughout the world, including the
continental U.S., but expedited deorbits such as these would
expose the crews to gravity loads in excess of +8 Gx, which
could strain an already seriously compromised cardiopulmo-
nary system. Flight surgeons will need to decide whether an
affected crewmember would be better served by exposure to
8 Gx in an expedited deorbit so as to reach a tertiary care facil-
ity within 812 h from the beginning of the cardiac event or by
waiting as long as 24 h for a 3.8-Gx exposure and potentially
deorbiting to a desolate part of Kazakhstan and incurring the
increased risk of mortality during this time [388]. The parameters
driving this decision are still more complex because the decision
may need to be made in real time by the flight director, flight
surgeon, and mission commander without the benefit of external
expert consultation.
Treatment of Cardiovascular Illness
on Exploration-Class Missions
Crews on exploration-class missions will obviously be lim-
ited in their ability to transport an acutely ill crewmember
16. Cardiovascular Disorders
to a definitive care facility on Earth. Another problem with
the emergent treatment of acute cardiac disorders is the
unpredictability of the outcome. On Earth, patients with poten-
tially fatal yet treatable respiratory distress or a arrhythmia
have been resuscitated successfully; thus aggressive resusci-
tation measures should always be considered for a disabled
crewmember given the general excellent health of crewmem-
bers as a group.
Yet another problem in providing advanced cardiac and
trauma critical care on very remote missions is the possibility
that a patient-crewmember may require long-term and com-
prehensive care after surviving the initial medical emergency.
The design of the medical facilities that will be needed to miti-
gate cardiovascular illness (and other medical contingencies
as well) on an exploration-class mission thus must be based
on the overall level of medical risk that the space program
designers are willing to accept [76,389]. Obviously, preven-
tion of illness should be the primary goal in selecting a crew
for an exploration mission and maintaining the health of that
crew. Nevertheless, treatment of chronic cardiovascular ill-
ness on an extended-duration mission may compromise the
primary objectives of that mission.
Designers of a medical care facility for an exploration-
class mission must consider the resources needed to manage
a chronically ill patient for the duration of a mission. Treat-
ments for cardiovascular conditions that require acute therapy
(thrombolytics [359361,390], ventilator support, or others
[391]) or chronic therapy (anticoagulation [357,358,392] or
antihypertensives) [362364,367,393,394] must be balanced
against the mass, volume, and logistics that providing these
treatments would require. The cardiovascular deconditioning
and fluid loss associated with microgravity (and perhaps
with one-third gravity or one-sixth gravity) may impair a
crewmembers response to a hypovolemic challenge such
as hemorrhagic shock [254]. It is possible that the inability
of the body to mount an appropriate response to shock may
decrease survival under such extreme conditions even further.
New concepts for the treatment of cardiogenic, hypovolemic,
or septic shock need to be considered for these types of missions
[198,254].
On the first planned long-duration mission to Mars, a crew-
member experiencing an acute myocardial infarction who
survived the initial event would probably be attended by a
CMO and the remaining crewmembers, which could well
prevent these individuals from performing payload activities
or otherwise compromising the original mission objectives.
Depending on the timeline, treatment in such circumstances
may require a mission abort and an expedited return to Earth
(not an option). If the risk is high that a certain cardiovascular
event would require extensive treatment and crew resources,
mission planners must decide to mitigate that risk or accept
the possible consequences [389]. This decision process will
establish the medical philosophy (e.g., necessary training for
the flight surgeon and crew, selection standards) and mission
347
resources (e.g., mass, volume, power) required to mitigate the
potential effects of a cardiovascular problem on exploration-
class missions.
The cardiovascular selection criteria for a crew that will be
assigned to an exploration-class mission must rule out existing
abnormalities and minimize the risk of future abnormalities
to the extent possible with current technology. This process
represents a significant challenge for flight surgeons in terms
of preventing and treating cardiovascular abnormalities. Most
large-vessel coronary vascular diseases are not symptomatic
until stenosis of the vessel reaches about 70% or 80%.
How would a flight surgeon develop the criteria to deter-
mine what degree of coronary stenosis would disqualify a
crewmember for a 3-year Mars mission that is launching
10 years from nowa determination that will be made at the
time of final selection of the crew? An important factor to
consider would be the risks associated with invasive screen-
ing and diagnostic procedures such as angiography. Should
a flight surgeon suggest that a candidate for a particular crew
be evaluated for atherosclerosis of other organs on the basis of
coronary angiography findings? Would that flight surgeon use
invasive tests such as these for selecting crewmembers for a
lunar mission, where evacuation to Earth may take only 2 days
but would incur significant cost and risk to others?
Unless cardiovascular diagnostic and prognostic technol-
ogy advances significantly during the next 10 years, flight
surgeons will find it very difficult to rule out the possible
appearance of cardiac disease in a crewmember slated for a
mission in which expedited return to Earth is impossible and
the mission is to last 3 years. Newer noninvasive technologies
such electron-beam and fine-slice spiral CT may hold prom-
ise in that their PPVs are better than those of current invasive
diagnostic methods for determining calcium burden and rul-
ing out future significant cardiovascular abnormalities.
In selecting a crew for an exploration-class mission, the
question posed by the flight surgeon should focus on what
constitutes a significant cardiovascular abnormality for the
mission. Although new tests may be more sensitive in detect-
ing coronary calcium load and possible stenosis, the process
by which subclinical CAD progresses to an overt cardiac event
remains unknown. If we decide to travel to Mars before 2015,
our ability to prevent significant cardiovascular events during
a 3-year mission may be no better than it is today unless more
prospective data can be collected on subclinical cardiovascu-
lar abnormalities and their natural history.
Cardiovascular selection and screening for a Mars mission
will probably require a long-term approach. A cadre of Mars
mission candidates may need to be selected several years in
advance of the mission. Any minor cardiovascular abnormali-
ties revealed during the selection process, if not immediately
disqualifying, should be followed up over time. Because no
data currently exist to guide flight surgeons in diagnostic
dilemmas such as these, the natural history of the disease may
need to be inferred on the basis of an invasive prospective
348
diagnostic approach, which may precipitate medical compli-
cations that could disqualify a crewmember. Future advances
in noninvasive diagnostic methods to prevent this from hap-
pening are fervently sought.
Conclusions
Flight surgeons face real challenges in the prevention, detection,
and treatment of cardiovascular disease in space crewmem-
bers. The delivery of cardiovascular care in low Earth orbit
and future exploration-class missions requires an aggressive
preventive medicine approach [395]. As the international
space programs move into a new era of interplanetary travel,
diagnostic and treatment capabilities in space will be essential
to mitigate the risks of extreme cardiovascular decondition-
ing, overt illness, or novel microgravity-induced cardiovascu-
lar abnormalities. Such medical problems are most likely to
arise on long-duration space flights, which will invariably be
characterized by less-predictable mission parameters, com-
munications delays, and the impossibility of an emergency
return to definitive care facilities on Earth.
Subclinical, asymptomatic cardiovascular abnormalities
that might be discovered in a spaceflight crew or aviator
cohort do not seem to carry the same prognosis or natural
history as in standard clinical populations. This disconnect
imposes a significant responsibility on flight surgeons, who
must strive to maintain the flight-readiness status of a limited
number of extensively trained crews who may be candidates
for low Earth orbit missions ranging from 10 to 100 days
and for exploration class missions lasting 1,000 days. Given
the limited positive and negative predictive value of present
cardiovascular diagnostic technology, flight surgeons must
apply very conservative standards for selection and contin-
ued flight-readiness status. Long-term studies that use future
noninvasive cardiac screening methods for detecting subclini-
cal abnormalities may provide solutions to the dilemma of
having to be overly conservative with a very healthy cohort.
The limited ability of current diagnostic technology to pre-
dict or prevent the occurrence of cardiovascular disease in
this very specialized cohort before and during space flight
requires that risk mitigation, in the form of treatment, be
considered in the overall context of designing short- and
long-duration missions. Requirements that define the means
to treat only a select few cardiac events may not be enough
to mitigate cardiovascular illness and to minimize the effects
of such illness on the mission. Because the diagnosis, prog-
nosis, and appropriate treatment of cardiovascular illness
in space is not entirely predictable, the medical knowledge
and systems used to treat patients in space may need to be
applied in a creative fashion.
Millions of years of evolution have led to the development
of robust and highly adaptive cardiovascular systems for
organisms living on Earth. The ISS provides a unique plat-
form from which to observe the long-term effects of altered
D.R. Hamilton
gravity on biological systems. One hopes that humankind will
use this precious resource to unlock the gravitational enigma
of the cardiovascular system before reaching out in earnest to
explore beyond earth orbit [396].
Acknowledgment. I thank the following people who helped
edit this manuscript: Drs. Alec Navinkov, Bojana Djordjevic,
John Tyberg, John B. Charles, Kira Bacal, Jean-Marc Comtois,
Gary Gray, P. Vernon McDonald, Victor Hurst, Smith L. John-
ston, Andrew Kirkpatick, Hal Dorr, Thomas Marshburn, Jay
Buckey; Mike Barratt; Mr. George Beck; Mr. Ben Voigt; and
Ms. Genie Bopp.
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17
Neurologic Concerns
Jonathan B. Clark and Kira Bacal
Among other functions, the neurological and neurovestibular
systems serve to support positional awareness and motor
control. Because gravitational cues and visual references
play a role in this support, it is not surprising that the space-
flight environment profoundly influences static and dynamic
positional sense and subsequent motor function. Human
adaptation to this unique environment is being investigated
to understand how performance may be optimized in every
flight phase. Proper neurovestibular function ensures space-
flight crew safety in the complex and unfamiliar visual and
motion milieu of microgravity and because of reliance on
mechanical display information, enhances ability to operate
a vehicle safely.
The neurovestibular system creates a consistent, conscious
map of head and body orientation as well as an internal orien-
tation reference that will correct for absent or erroneous visual
and somatosensory systems. It primarily stabilizes the eyes
(the visual system) by means of (1) the vestibular ocular reflex,
which is related to maintaining a stable world during move-
ment; and (2) the vestibular spinal reflex, which preserves
body alignment and establishes an appropriate relationship
between the head and body. The character of the vestibular
and visual systems interaction depends on a specific task or
relevant operational requirement. For example, whereas a
crewmember depends on the visual vestibular ocular reflex
to track a stationary target while turning, that same individual
suppresses the vestibular ocular reflex when tracking a head-
fixed target, such as a head-mounted display, while turning.
A persons pursuit system (slow eye movement) is used to track
and identify moving objects, and the saccade system (fast eye
movement) is necessary to acquire objects in the peripheral
visual field and scan instruments. Visually induced optoki-
netic nystagmus occurs when a person views a moving back-
ground. This adds to the optical data that generates a sense of
speed over terrain.
During initial adaptation to microgravity, spaceflight crew-
members experience conflict between the linear acceleration
detectors (otolith organs) and other sensory systems affected
by position. Motion disrupts oculomotor control, which com-
promises the retinas ability to hold an image still or to shift
gaze to another object in a controlled fashion. This could
potentially adversely affect crucial activities on orbit, such as
rendezvous and docking, robotic arm operation, and extrave-
hicular activities. Crucial activities during the landing phase
of the Space Shuttle, which lands like a conventional aircraft,
include switch throws, vehicle controller inputs, and acquisi-
tion of visual information from cockpit instruments and terres-
trial landing aids. Oculomotor dysfunction could compromise
these activities after prolonged space flight or while the crew
is in a visually deficient environment when such problems
are more likely to occur. The corrective eye movements (sac-
cades) necessary to compensate for oculomotor disruption to
reacquire the target can significantly delay reaction time. Prior
spaceflight experience would be expected to reduce this effect
based on the sensorimotor learning and the observation of
reduced incidence and severity of motion sickness that occurs
in veteran space flyers.
Specific types of eye movement impairment related to
spaceflight include alterations in eye-head coordination, tar-
get tracking, and optokinetic reflex function [13]. Sensory
illusions include misperception of location and directional
cues due to loss of spatial orientation and motion-generated
spatial and temporal visual illusions [4]. Sensorimotor altera-
tions include a postflight decrement in postural control and
locomotion as well as disruption in the head-trunk coordi-
nation related to the modification of vestibulospinal reflex
function and proprioceptive function [5]. Transition problems
experienced by crews during readaptation to earth gravity (g)
may manifest as a near-instantaneous return to the microgravity
adaptive state, or g state flashback. This phenomenon could
lead to sudden motor control dysfunction and increased visual
dependency after gravity state transitions [6]. Specific opera-
tional problems associated with the neurological effects of
spaceflight are discussed in the next section.
361
362
Operational Concerns due
to Neurologic Adaptation
Manual Control of Spacecraft Reentry
and Landing
Alterations in eye-head coordination and the sensory illusions
of crews in microgravity might lead to difficulty reading flight
instruments and checklists, interpreting ground-based landing
aids, estimating altitude, and making gaze transitions inside
and outside the spacecraft cockpit. Analysis of Space Shuttle
pilot landing performance following missions of 5 to 18
days duration has suggested an inverse correlation between
mission duration and the accuracy of landing speed, position,
or touchdown vertical velocity [7]. In a sensorimotor control
study conducted on four mission specialists before and after a
14-day Shuttle flight, subjects were tasked with maintaining a
normal upright position while they were seated in a modified
Link aircraft trainer [8]. The trainer was configured with a
motor that would tilt the cockpit as much as 12 degrees later-
ally left or right in the roll plane (1 degree-of-freedom) at up
to 10 degrees per second at frequencies of 0.014 to 0.668 Hz.
Manual corrective control inputs, which were made with a
control wheel, were tested in the dark and with visual sur-
round feedback. The crewmembers tested preflight showed
no test session learning effect and were able to null motion
at low frequencies (<0.25 Hz) in both dark and visual feed-
back conditions. Two crewmembers tested in the dark within
hours after landing were unable to control tilt orientation as
well as they had preflight (20% to 50% worse performance on
normalized root mean square error). In this example, the first
crewmember had returned to normal by one day after landing
(R+1), and the second crewmember had returned to normal by
two days after landing (R+2). When accurate visual cues were
present, the crewmembers tested in the immediate postflight
period were able to null low-frequency tilt and showed no dec-
rements as compared to their preflight performance, demon-
strating the heavy reliance on visual cues postflight.
There is also concern about possible sensorimotor control
problems associated with the interaction between neuroves-
tibular effects and high workload with crew fatigue. This
concern is subjectively corroborated by postflight debriefs
of returning crewmembers. The profound fatigue associated
with motion sickness has been termed Sopite syndrome.
Extravehicular Activity (EVA)
Sensory illusions during EVA may cause outside suited
crewmembers to become disoriented and provide incorrect
inputs to the robotic arm (the remote manipulator system,
or RMS) operators during joint EVARMS operations. Such
complex operationsrequiring high-level coordination
between direct crew visual observations, camera views, and
control system feedbackare common with International
Space Station (ISS) assembly and maintenance tasks. EVA
J.B. Clark and K. Bacal
missions on planetary surfaces, i.e. within a gravitational
field following a period of prolonged weightlessness during
transit, would also be a potential problem, as the majority
of crewmembers experience clumsiness in their movements
in the postflight period following Earth return [9]. It may be
prudent to delay surface EVAs for a few to several days follow-
ing long periods in weightlessness until adequate adaptation
has taken place.
Rendezvous and Docking, Robotic Operations
Crewmembers who are performing rendezvous and docking
between spacecraft and RMS operations rely on visual infor-
mation to execute appropriate motor control inputs. Neuroves-
tibular dysfunction may result in inappropriate commands and
controller inputs, although these activities are performed
frequently with success. Historically, neurovestibular dys-
function may have been partially implicated in the Russian
space station Mir-Progress resupply vessel collision and in
a satellite being bumped during a capture attempt by the
Shuttles robotic arm.
Post-Bailout Motion Sickness
Simulation exercises involving astronauts have been con-
ducted to evaluate the emergency scenario of bailing out
from the Space Shuttle during entry and landing, then await-
ing recovery in life rafts on an open ocean for several hours.
In these drills, some crewmembers become seasick even in
mild sea swells. It is anticipated that when performing an
over-water bailout after spaceflight, crewmembers who had
been very recently adapted to a microgravity environment
will experience motion sickness that could lead to decreased
performance and efficiency in a survival situation. This might
adversely affect survival (dehydration, electrolyte depletion,
inability to perform self-rescue maneuvers), particularly
if recovery is prolonged beyond several hours. The Apollo
spacecraft landed in water on a parachute system. Nine of 25
Apollo crewmembers experienced seasickness post-egress or
prior to egress during recovery. To reduce the incidence of
motion sickness following landing, pharmacological inter-
ventions may prove useful, as they did for some Skylab crew-
members. Two of the 9 Skylab astronauts, on the first crewed
flight, were seasick in their capsule after landing, and the last
6 Skylab crewmembers took anti-motion-sickness medica-
tion before landing [10].
After the 28-day Skylab 2 mission (May 25June 22, 1973),
the command module landed and remained upright in a heavy
sea. None of these crewmembers took anti-motion-sickness
drugs before entry. Although the commander experienced no
seasickness, the pilot and scientist pilot experienced mild and
severe symptoms, respectively. Prior to the splashdown of the
58-day Skylab 3 command module (July 28September 25,
1973), the crew had taken anti-motion-sickness drugs (sco-
polamine/dextroamphetamine sulfate), and although the sea
17. Neurologic Concerns
state was twice as heavy as the one to which the Skylab 2
crew had been exposed, the symptoms did not occur. All of
the Skylab 4 (November 16, 1973February 8, 1974) crew-
members took the same anti-motion-sickness drugs and were
symptom-free during recovery at sea [10]. This suggests that
anti-motion sickness medications should be available to crews
after an overwater bailout as part of the survival kit.
Unaided Vehicle Egress
Decrements in postural and locomotor control, along with
motion sickness, may lead to impaired egress ability, includ-
ing difficulty in leaving the seat (getting out of restraints),
moving to the hatch, and moving away from the Shuttle or
Soyuz in an emergency or performing post-landing duties.
Findings based on crew assessment by attending flight sur-
geons at Space Shuttle landings estimate that approximately
5% of crewmembers returning from short duration flights of
18 days or less would be unable to perform a nominal egress
at the side hatch, in large part due to neurovestibular impair-
ment. In an off-runway contingency where side hatch egress
was unavailable, approximately 15% of crewmembers would
be unable to perform the more difficult egress through the
overhead emergency escape hatch. Along with neuroves-
tibular factors, orthostatic intolerance and muscular strength
issues may also contribute.
Neurological Dysfunction Associated
with Spaceflight Adaptation
Motion Disturbances
The primary clinical manifestations associated with neuro-
logical changes during spaceflight are space motion sickness
(SMS) and postflight neurovestibular symptoms. SMS, which
is the form of motion sickness associated with microgravity,
is a subset of space adaptation syndrome. Since SMS is only
weakly correlated with the motion sickness associated with
ship or air travel, or with symptoms upon exposure to rotation
or parabolic flight, prediction of its occurrence in first-time
flyers is difficult (Chapter 10). Experiencing SMS during
spaceflight is not protective against or predictive for terrestrial
motion sickness after flight, nor is it associated with pres-
ence (or absence) of postflight neurovestibular symptoms [9].
Spaceflight experience is somewhat protective against SMS
on subsequent flights, as the incidence is less among repeat
flyers than first time flyers. Nausea is a frequent component
of in-flight SMS, as well as postflight symptomatology. Post-
flight nausea is seen more frequently in female crewmembers,
but gender has not been found to be associated with any of the
other neurovestibular symptoms seen after space flight, nor
have age, mission duration, previous spaceflight experience, or
in-flight SMS been associated with any postflight neuroves-
tibular symptoms [9].
363
SMS is a frequent occurrence during the early days of
spaceflight, typically effecting only minor timeline changes.
However, more significant consequences have been seen. SMS
caused an EVA to be rescheduled during Apollo 9 (March 3 to 13,
1969), the first in-flight timeline change due to a medical
cause. No SMS occurred on the lunar surface or in the return
to microgravity after lunar exploration during the Apollo mis-
sions. The Apollo 15 (July 26 to August 7, 1971) lunar mod-
ule pilot experienced delayed postflight symptoms following
Earth return that persisted for seven days following recovery.
He perceived a 30 head-down, tilted sensation when supine
and persisted when he turned onto his side. The tilted sensa-
tion was not present when he was fully awake, regardless of
postural position. Positional and caloric vestibular nystagmus
tests, audiometry, and otolaryngology evaluation were normal
5 days postflight [11]. Symptoms most likely attributable to
SMS occurred during one Shuttle EVA with nausea and vom-
iting occurring in the suit during airlock repressurization.
Postflight neurovestibular symptoms have been described
in a variety of ways in the literature. In one review, relative
frequencies of several postflight symptoms were assessed
via crewmember survey. These included: clumsiness in move-
ments (69%, n = 410); difficulty walking straight line (66%,
n = 403); persisting sensation aftereffects (60%, n = 324);
vertigo while walking (32%, n = 393); vertigo while standing
(29%, n = 397); nausea (14.7%, n = 346); difficulty concen-
trating (10%, n = 284); vomiting (8%, n = 347); dry heaves
(3%, n = 291); blurred vision (<2%, n = 396) [9]. The major-
ity of respondents in this study reported only mild symptoms,
though 12% and 14% (respectively) used the term moder-
ate to describe their clumsiness and difficulty walking a
straight line.
Acute Performance Effects with Exaggerated
Spacecraft Maneuvering
Disorientation and vertigo can occur with spacecraft maneu-
vering and may produce acute performance effects in crew-
members. Vestibular stimulation can result in nystagmus,
which adversely affects a crewmembers visual acuity during
the acceleration and deceleration phases of rotation. Tracking
and visual acuity are more significantly impaired while rotat-
ing in the roll plane than in the pitch or yaw plane. Nystagmus
is usually greater and visual acuity worse with acceleration
than with deceleration [12].
On March 16, 1966, after pilot Neil Armstrong and copilot
David Scott had rendezvoused and docked their Gemini VIII
spacecraft with the Agena target vehicle, they experienced
a disorienting event when an uncommanded thruster firing
resulted in a high spin rate and a tumbling vehicle. The Gemini
orbit attitude and maneuvering system engine had erroneously
fired several times, resulting in a counterclockwise roll and
left yaw motion. The 25-pound-thrust engine was capable
of generating acceleration of 2.5 to 3.0 degrees/second [2].
Fourteen minutes after the initial rocket engine firing, the
364
astronauts undocked the two vehicles in an attempt to stop
the roll. This only resulted in an increased roll rate to more
than 330 degrees/second for over a minute. During the next
six minutes, Armstrong and Scott performed various actions,
including disabling the maneuver electronics, disengag-
ing circuit breakers, and firing the reentry control jets. They
obtained partial control 20 min after the initial roll maneuver
occurred, and recovered full control 3 min after that. Because
the reentry control system had been fired, an immediate abort
of the mission was required. The spacecraft splashed down
safely but at a landing site far from the recovery forces. As
a result, Armstrong and Scott had to remain on board their
spacecraft for an additional three hours. In this case, disori-
entation and oculomotor disturbance, as well as SMS, could
have seriously impaired performance, since the astronauts had
to reach over their heads to disengage the maneuvering engine
circuit breakers, a move traditionally provocative of spatial
disorientation [13].
When this incident occurred, the Gemini VIII crew was
undertaking a first-time activity of rendezvous and docking,
never before performed in the human spaceflight program.
Both astronauts were rookie space flyers who had experienced
microgravity for only seven hours following launch. Anxiety
could have been a factor in the disorienting event, since the
men had not experienced simulation of roll in microgravity.
The command pilots heart rate was reported to be 156 beats
per minute for a sustained period that could be due to response
to rotational g forces or anxiety [13]. In spite of this, the crew
was able to regain control of their spacecraft.
Similar to the aviation environment, deleterious effects of
unanticipated and exaggerated spacecraft acceleration can
include disorientation, dizziness, impaired vision, nausea, and
anxiety. After this incident, new recommendations for space-
craft design were implemented and supplemental considerations
for astronaut selection criteria and medical screening, as well
as for astronaut conditioning, were proposed. Recommenda-
tions included designing instrument displays and controls so
that left-right head rotations and up-down arm motions were
minimized.
A similar unanticipated thruster firing resulting in an
unusual attitude event occurred on Apollo 10 (May 18 to
26, 1969) during initial checkout rendezvous and docking of
the command module and the lunar excursion module. This
resulted from a mission control center direction for an incor-
rect switch setting, but the crew quickly recognized the prob-
lem and recovered from this incident.
Perceptual Effects and Illusions
of Space Flight
In the absence of normal gravitational, proprioceptive, and
postural cues, astronauts working in microgravity rely more
on their vision to maintain spatial orientation and to establish
the direction of down than do their earthbound counterparts
J.B. Clark and K. Bacal
[14]. Space flyers in the confines of the relatively small
Soyuz, Mercury, Gemini, and Apollo capsules rarely encoun-
tered orientation problems, but astronauts in the larger vol-
umes of the Skylab space station or the Space Shuttle have
often reported disorientationparticularly when they are
unrestrained or in visually unfamiliar orientations, such as
when working upside down in the spacecraft or when view-
ing another crewmember who is upside down relative to the
viewer. Visual reorientation illusions, in the absence of head
movements, can trigger SMS during the first several days in
weightlessness and may result in delayed recurrence of space
sickness. For example, EVA crewmembers may feel uncom-
fortable working in the Space Shuttle payload bay when the
payload bay faces the Earth. EVA crewmembers working far
out on a structure have occasionally reported a sensation that
they might fall off or fall to Earth, which has been termed
EVA acrophobia.
Disorientation could contribute to navigation difficulties for
crews working inside a large, multi-axis space station. On both
the Russian Mir space station and the ISS, some modules con-
nect at 90-degree angles through central nodes, with hatches
potentially located in the six cardinal directions. Visiting
astronauts touring Mir occasionally reported experiencing dif-
ficulty with orientation, particularly when traversing the central
node. Even after spending several months in space, some Mir
crewmembers reported difficulty visualizing 3-dimensional
spatial relationships among the modules. Orientation on the
ISS after the station has been fully assembled may prove a
significant challenge since the ISS will have as many as four
multi-axis nodes and numerous modules. To optimize space
use on modules, equipment is mounted on walls, ceilings, and
floors where it may create multiple apparent visual verticals,
depending on which workstation the astronaut is using. Loca-
tions that do not have obvious floors and ceilings, such as the
tunnel connecting the Space Shuttle middeck with the Spacehab
module in the payload bay, are even more likely to generate
disorientation. To provide a local visual frame of reference on
the ISS, the deck (floor) and overhead (ceiling) are painted
different colors in a scheme that has been standardized for all
of the modules.
Disorientation and navigation difficulties are an operational
concern to crewmembers, especially when traversing modules
to respond to caution and warning events. This may pose a
particular difficulty in an emergency evacuation to the crew
return vehicle in the event of a depressurization or fire, where
visual cues may be reduced or obscured. Preflight training in a
water immersion facility for EVA crewmembers and a virtual-
reality lab for robotics operators may enhance visual orienta-
tion memory in conditions of unfamiliar visual cues. To aid
escape to the return vehicle, particularly when a rapid egress
is needed in darkness, lighted directional aids and emergency
exit placards have been added.
Ground-based studies of orientation have been conducted
in the 2.4-m (8-ft) York Tumbling Room of York Univer-
sity, where the subjects gravitoinertial vector and interior
17. Neurologic Concerns
surroundings can be independently controlled [15]. The
visual scene is sufficiently compelling that many supine sub-
jects (with respect to the gravity vector) feel upright when
the visual vertical is aligned with their body axis [16]. Ani-
mal studies have shown that the brain constructs an internal
spatial representation of the environment for orientation and
navigation, using information related to the bodys location in
the environment as well as the heads direction in the visual
environment. Visual reorientation illusions increase as a func-
tion of age, possibly related to increased dependence on visual
polarity [17].
About 80% of space flyers experience perceptual illusions
during or after flight, and illusion intensity is increased with
flight duration [18]. These may be of several different types.
Illusory self-motion, the perception that occurs when viewing
a moving visual scene, is known as vection. Vection may be
perceived as linear or rotational motion [19]. Illusory motions
of the surrounding or stationary objects include visual stream-
ing (blurring), visual scene oscillation (oscillopsia), object
position distortion, visual axis distortion (tilting or inversion),
and platform stability illusion. Elevator illusion is described
as a sensation of the floor dropping when doing a squat to
stand, and levitation illusion is the sensation of things float-
ing in space. During initial adaptation to microgravity, the
perception of vertical vection appears as inverted vection
[20]. This may contribute to the inversion illusion, in which
crewmembers experience a sense of being upside down early
in space flight.
For Space Shuttle astronauts, the perception of self motion
or surround motion is greatest during entry, followed by wheel
stop on the runway in the landing phase, and then by actual
on-orbit experience. Illusions are more often associated with
pitch or roll head movements than they are with yaw head
movements. Roll head movements may be perceived as a lat-
eral translation. Larger amplitude or faster head movements
are more likely to produce illusions of self or surround motion.
Perceptual illusions that affect gain disturbance include altered
position, amplitude, or rate after movement. These are seen
with an incidence of 40% of crewmembers inflight (n = 18)
and 100% of postflight crewmembers (n = 24). The intensity
and duration of perceived motion during entry and landing is
related to mission duration (flight duration 10 or less days),
prior spaceflight experience, and increased habitable volume
(more maneuverability) [21]. Temporal distortion, where the
self or surround motion lags behind actual motion, occurs with
an incidence of 40% inflight and 90% postflight. Path dis-
turbance, which is the phenomenon in which angular motion
elicits a perception of linear motion, occurs with an incidence
of 30% during flight and 70% after flight.
Astronauts on the Skylab missions reported that, with eyes
closed or lights out, they lost the sense of where everything
was in relation to themselves. The central nervous system
(CNS) may require an up and a down in space to cre-
ate an external spatial map, a perceived image of the outside
world. Proprioceptive mechanisms in joints, tendons, and
365
muscles that normally provide positional sense on Earth may
not provide accurate limb information in microgravity. This
could contribute to a loss of the internal spatial map (a normal
body image). Another possibility is that dysfunction of both
external and internal spatial maps results in loss of spatial
orientation.
Detection thresholds for linear acceleration in all three
body axes were assessed on the Spacelab-1 mission (STS-9,
November 28 to December 8, 1983). Preflight motion per-
ception thresholds were higher (less sensitive) in the Z axis
(0.077 m/s2 (0.253 ft/s2) ) than in the X and Y axes (0.029 m/s2
(0.095 ft/s2) ). Inflight, three crewmembers exhibited greater
thresholds (less sensitivity) than they exhibited preflight, with
4.3 times greater threshold in X and Y axes, and 1.5 times
greater threshold in the Z axis [22]. An astronauts awareness
of limb and body position may be altered by motion percep-
tion changes in microgravity. Astronauts have had difficulty
in positioning their legs precisely during inflight drop tests,
in which a subject is quickly pulled downward by an elastic
cord. In-flight self-motion perception tests revealed that early
inflight drops were perceived like those preflight. Drops late
in-flight were described as sudden, fast, hard, and transla-
tional. Immediately postflight drops were perceived like those
late in-flight. Astronauts reporting they did not feel they were
falling but rather that the floor came up to meet them [23]. In a
perception study astronauts secured by their feet to the Space
Shuttle floor with eyes closed had difficulty knowing leg posi-
tion with respect to their trunk by flight day 7 [23,24].
In an inflight study of pointing accuracy, subjects pointed
to five remembered positions (center, up, down, left, and
right) on a target screen with a handheld light, starting with
the hand close to their chest [25]. The external spatial map
was assessed by having the astronauts keep their eyes closed
between each light pointer target session, whereas the percep-
tion of the internal spatial map was assessed by having the
subjects open their eyes and memorize target positions. Eyes
were kept closed during the light pointer target session only.
Subjects in weightlessness exhibited a pronounced downward
pointing bias for all five targets, but when the subjects were
able to see the external world between each point, performance
improved. Subjects also made greater errors after flight than
before space flight, recovering to preflight performance level
by the seventh postflight day.
The primary factor influencing pointing errors in space
flight is the loss of a subjects external spatial map. Mainte-
nance of a stable external spatial map depends on the presence
of normal gravitational forces. The postflight recovery pattern
suggests that both the otolith organs and the CNS may influ-
ence this phenomenon [25]. The operational implication of
pointing errors would be critical during switch throws in a
visually obscured environment, such as if there were smoke
in the cabin. Crewmembers might be particularly vulnerable
when using reach/grasp extension devices such as the Space
Shuttle or Soyuz swizzle stick to make switch throws on
panels out of reach due to suit and restraint systems.
366
Rendezvous and docking operations constitute a high-risk
phase of space flight during which the crew is vulnerable to
perceptual illusions and sensorimotor control errors. Adverse
effects of perceptual illusions during rendezvous and docking
operations were likely contributing factors to an in-flight
collision. This incident, which involved loss of crewmember
situational awareness, occurred during the NASA-Mir Program
Progress resupply ships docking. It clearly emphasizes how
multiple factors can influence human performance.
On June 25, 1997, an unmanned Russian Progress supply
vehicle collided with the Russian Mir space station during a
test of the Mir manual docking system. Typically, rendezvous
and docking of the Progress used an automated system, with
a manual system available as backup. When using the manual
system, the Mir crew had to visually acquire the incoming
vehicle and control the terminal rendezvous phase based on
the Progress orientation, range, and closure rate using an
external reference frame. During the actual docking phase, a
crewmember had to virtually fly the Progress using visual
input from a video camera with an internal reference frame
located on Progress. In this instance, the Mir commander, who
was guiding the Progress capsule to a manual docking using
the tele-operated system in the Mir core module, reported to
Mission Control that the Progress had come in very fast and
could not be stopped. The Progress struck a solar array on the
Spektr module and caused a depressurization of the module
(and with it the station). The Spektr module was quickly iso-
lated and sealed off, and its pressure eventually dropped to
vacuum.
During prior rendezvous events, crewmembers had
reported experiencing difficulty with visually acquiring the
incoming spacecraft, in part related to Mir solar arrays visually
obscuring the arriving Progress ship and loss of visual refer-
ence with the background of Earth [26]. It is unlikely that
a crewmember could accurately describe the position, velocity,
and closure rate of a moving object in 3-dimensional space
without having a reference point. Russian and U.S. neuroves-
tibular experts also believe that the difficulties crewmembers
had in establishing an accurate spatial coordinate reference
frame of the different modules made it difficult for the crew-
members to know instinctively which window they should be
looking out after moving between modules. During the first
docking attempt, one crewmember described the crew as
moving from one window to another in an attempt to find the
incoming Progress. Following is that crewmembers account of
his experience [27]:
The commander would pick his spot according to where he could
best see the incoming Progresssomething that none of us could
predict with any confidence. As lookouts, [we] began to survey
the heavens, looking for the approaching spacecraft. Although I
saw some fantastic views of the Himalayas on [Earth], I had not
yet spotted the Progress. [The other crewmember] also reported no
sighting. Though I was moving from one Mir window to another,
I could still not see the approaching spacecraft. We all began to wor-
ry. More time passed. For some reason I was no longer hearing
either [of my crewmembers] over my headset. I floated back to
J.B. Clark and K. Bacal
the base block to see what was happening. [One crewmember]
was flying frantically back and forth between his control station and
the nearest porthole-sized window on the floor. I flew to a window
that faced the same general direction as the window [that the other
crewmembers] were using and did so just in time to see the Progress
go screaming by us.
The following additional comments were made by another
Mir crewmember about the incident:
It was difficult to make out the [Progress]. It looked very similar to
the clouds. Through the porthole, I could see the ship gliding below
us. It was full of menace, like a shark.
Later, after an unsuccessful attempt to manually dock the
incoming Progress, a crewmember recalled [27]:
The only way I could determine whether [the commander] had done
the right thing was by yelling to [the other crewmember]. He queried
as to how the Progress was responding to his latest move. For [me],
accurate description was an impossible task.
Disorientation was also a factor in the attempt to arrest the
spin on the Mir space station following the Progress collision.
Crewmembers fired the thrusters on the Soyuz docked on Mir
and had difficulty determining the effect on spin rate. This
was complicated by the multiaxial motion of the spacecraft.
Strategies for Spatial Orientation
Firm body contact with a motionless surface can provide
tactile cues and reduce illusions and SMS in the weightless
environment. Adaptive strategies to microgravity and its
associated altered orientation cues involve subjectively and
cognitively deciding what is up and what is down [14]. For
crewmembers who use the visual spatial strategy, the Earth is
down or the vehicle floor is down. Forty-six percent of astro-
nauts and 58% of cosmonauts seem to use this strategy. For
crewmembers who are using the internal Z-axis strategy, their
feet indicate down. This strategy is used by 46% of astro-
nauts and 34% of cosmonauts. A mixed visual spatial-internal
Z-axis strategy, which is a combination of both, is used by 8%
of astronauts and 8% of cosmonauts. Astronauts who use the
visual spatial strategy have noted that encountering another
crewmember who is upside down with respect to the reference
plan can result in sudden neurovestibular symptoms (disori-
entation or motion sickness) in flight [28]. It is not known
whether the orientation strategy is the same over successive
spaceflight experiences. One recommendation is to inform
crewmembers that the use of the visual spatial strategy can
result in adverse symptoms when presented with conflicting
visual orientation cues.
Neuromotor Dysfunction and Assessment
Neurosensory control of motor activities is disrupted after
space flight. For most Space Shuttle crewmembers on short-
duration missions lasting fewer than 16 days, recovery of
17. Neurologic Concerns
normal (preflight) function requires four to eight days after
return to Earth. The time course of recovery of normal func-
tion after long-duration (>30 days) missions has not been well
characterized, but recovery does require a longer period (days
to weeks). To ensure that crewmembers are sufficiently recov-
ered to return to normal daily activities and duties, standard
clinical neurological assessment techniques must be supple-
mented with more sensitive measures of sensorimotor control.
A short battery of sensorimotor control tasks on long-dura-
tion crewmembers after flight has been proposed by NASA
medical personnel to establish the characteristics of postflight
recovery of neurological functionparticularly of balance
control, locomotor coordination, and eye-head coordination.
Interaction of various nervous system componentswhich
are responsible for visual image stability, balance, and gait
controlis necessary for optimal performance of an astronaut
or cosmonaut conducting planetary exploration and for ambu-
latory humans on Earth.
Terrestrial patients with various clinical deficits will exhibit
performance impairment that can lead to falls and an inabil-
ity to see and avoid hazards. The same is true of returning
astronauts and cosmonauts, who are otherwise healthy but
whose microgravity adaptation has left them with clinically
significant neurologic impairments during the readaptation
period. Functional assessment tests should be applied that are
(1) easily administered, scored, and interpreted; (2) adaptable
to on-orbit use; (3) integrated with other tests to enhance or
supplement diagnostic and predictive power; and (4) corre-
lated with known clinical substrates. Other possible applica-
tions of these tests include assessment of fitness for duty (the
ability to maintain acceptable performance) after a pharma-
ceutical countermeasure, assessment of injury risk during an
exercise training session, and tracking of error potential during
robotic operation after a virtual-reality training session. Func-
tional assessment tests could evaluate the potentially adverse
effects of countermeasures as well as optimal countermeasure
use, including timing and duration.
Currently within NASA, astronauts are evaluated according
to medical requirements with mandatory established clinical
assessment methods. Supplemental medical objectives may
be required to evaluate the application of emerging technolo-
gies in clinical space medicine. The Functional Neurological
Assessment Project is part of this integrated approach to a
countermeasure validation and evaluation program. Determi-
nation of measures of performance will directly affect coun-
termeasure development for future low Earth orbit operations
and planetary exploration missions, as well as for possible
technology transfer to terrestrial clinical populations.
The Functional Neurological Assessment Project will
obtain baseline data from a healthy normative population and
from a clinical patient population; evaluate effects of gravi-
tational variables (tilt, centrifugation, platform perturbation)
and effects of operational constraints (EVA suit, terrestrial
exploration vehicle); and will facilitate on-orbit assessment.
Its three core subsections are gaze performance (oculomotor),
367
ambulation (locomotion), and postural stability and balance.
Specific oculomotor deficiencies may render pilots more
susceptible to disorientation and motion sickness [29].
An operational vestibular test battery used by the U.S. Navy
employs screening tests of vestibular function to rapidly assess
vestibular performance and quantitative tests that compre-
hensively evaluate vestibulospinal and oculomotor function.
These tests have been used on NASA crewmembers when
clinically indicated. The screening tests include the Dynamic
Visual Acuity Test (visual acuity during active head move-
ment) and the Modified Sensory Organization Test (balance
on an unstable platform while making head movements with
eyes closed). Current applications of the operational vestibular
test battery include assisting in the diagnosis and the dispo-
sition of flight personnel with vestibular disorders and in
determining the timing of return-to-flight status after resolu-
tion of vestibular dysfunction.
This experience is being applied by NASA to long-duration
spaceflight crews in the form of a functional neurological
assessment. Potential applications of the operational vestibu-
lar test battery include aid in the decision to return to terrestrial
activities (e.g., exercise, driving, aircraft flight) after space
flight, determining adequate adaptation after countermeasure
and rehabilitation programs, and identifying medication that
will not adversely affect spatial orientation performance.
Preflight screening of astronauts and cosmonauts who are
more susceptible to performance deficiencies (selecting out)
and identification of aircrew with optimal or enhanced
vestibular function (selecting in) have been discussed but
remain controversial in the space medical community. Clear
associations between demographic characteristics (such as
age, gender, one-G piloting experience) and performance
metrics (such as inflight SMS or postflight neurovestibular
symptoms) remain elusive [9], and in their absence it is diffi-
cult to develop, let alone validate, appropriate select in criteria.
Better assessment methods and predictive indices may make
such screening worthwhile in the future.
Oculomotor Effects of Microgravity
Gaze, which is coordinated eye-head movement in the direc-
tion of the ocular axis, is the sum of eye position with respect
to the head, and head position with respect to space. A rapid
movement of eyes from one fixation point to another is known
as a saccade. When directed toward a target off the primary
visual axis, gaze usually consists of a combined fast saccadic
eye movement and vestibular ocular response that shifts the
ocular axis onto the target. The oculomotor system that con-
trols gaze undergoes constant recalibration and adjustment to
ensure optimal stability of images on the retinal fovea. The
fovea of the eye, which provides a high level of discriminative
visual acuity, subtends a visual angle of 0.25 to 4.0 degrees.
Gaze deviation of more than one degree off the foveal center
results in a two- to threefold reduction of visual acuity. For
optimal visual acuity, a target must be maintained within about
368
0.5 degree of the foveal center. The time for a target to fall on
the fovea depends on CNS control of head and eye movement,
distance, and direction the head and eye must move to foveate
(move the macular retina onto the optical axis of the target),
as well as on the size of the target. Retinal image stability may
be disrupted by nystagmus or fast eye movement deviations
known as saccadic intrusions. When assessing eye move-
ments, the gain of the eye movement refers to the velocity of
the slow eye movement (slow phase velocity) compared to
the stimulus velocity. This stimulus may be the target motion,
subject motion, or visual field motion.
Space flight is known to influence the oculomotor system.
During changing gravitoinertial forces, compensatory eye
movements may be inappropriate, leading to degradation of
oculomotor function. The yaw vestibular ocular reflex (VOR)
demonstrates minimal effects during or after flight. A Space
Shuttle investigation showed a slight decrease in gain in flight,
which returned to preflight level by flight day 7 [30]. Pitch
VOR gain has been shown to increase during parabolic micro-
gravity flight, decrease for the first 4 days of spaceflight,
return to normal during flight on the Space Shuttle, increase
14 h after landing compared to in-flight values, and return to
normal baseline values after flight. Optokinetic nystagmus
(OKN) refers to the eye movements induced by a moving
visual field (optical flow or background motion). The slow
phase eye movement is normally in same direction of back-
ground motion. Compared to preflight, the optokinetic nys-
tagmus gain resulting from horizontal (left or right) moving
background decreases early in flight and returns to normal
later in flight, while optokinetic nystagmus with vertical (up
or down) moving background shows a downward drift or
deviation during spaceflight and an upward drift after flight [1].
The downward ocular drift in microgravity may represent a
loss of the tonic influence of gravity on the linear acceleration
detectors (utricular sacculus of the inner ear), which provides
neural stimulus to lift the limbs and eyes upward to compen-
sate for the downward pull of gravity [1].
Saccades showed accuracy undershoots and velocity
decreases during flight on the early Space Shuttle missions.
Slow and inaccurate saccades and delayed saccade latency
correlated with SMS susceptibility [31]. Visual-enhanced
VOR gain increased postflight over preflight values in cosmo-
nauts in all planes after long-duration spaceflight [32]. Pursuit
amplitude decreased (undershot) in flight. VOR suppression
was reduced on R+0, and difficulty with VOR suppression
also correlated with susceptibility to SMS [33]. Postflight
gaze showed significantly decreased gain in the horizontal and
vertical planes with a greater reliance on fast eye movements
(saccades). Smooth pursuit was also degraded postflight.
Oculomotor dysfunction occurs during and after a gravitoin-
ertial transition, such as from 1-G to microgravity or during
reentry transition from microgravity to hypergravity and back
to terrestrial gravity. The horizontal and vertical VOR, elicited
by active yaw and roll head movement at 0.2 Hz, was stud-
ied in six cosmonauts during and after spaceflight. Changes
J.B. Clark and K. Bacal
in horizontal VOR evoked by yaw head movements during
the adaptation to microgravity suggest central reprogram-
ming. Horizontal and vertical eye movements were recorded
during roll head movements that were not obvious preflight.
One long-duration cosmonaut demonstrated unidirectional
downbeat nystagmus, independent of head movement direc-
tion, lasting the entire mission. This may have been a result
of reduced otolith influence on semicircular canal function.
The space pattern of visual-vestibular interactions during
postflight readaptation depended on the time spent in micro-
gravity. The visually enhanced VOR (compensatory eye
movement evoked by head movements with visual feedback)
seems to dominate when a conflict arises between space and
terrestrial patterns of sensory interactions [34].
Studies of neurovestibular effects in long-term microgravity
demonstrate periodically abnormal spontaneous and induced
oculomotor reactions interspersed with normal adaptive peri-
ods [35]. Changes in eye movements in microgravity occur
primarily for pitch or roll head movements, which normally
stimulate the otolith organs, although the relationship between
eye movements and self-motion perception remains to be
determined [3]. One perceptual model of spatial orientation
incorporates our sense of where we are in the environment
by linking vestibular, visual, and somatosensory informa-
tion with experience of inertial and gravitational forces. On
Earth, these relationships are established even in the absence
of active behavior, while in microgravity these linkages must
be actively established for stability in the environment, such
as by grasping a handrail to traverse [36]. On Spacelab-1,
caloric stimulation revealed that caloric nystagmus of the
same direction as on Earth could be evoked in the weightless
environment. This suggests a non-convective component to
the normal thermal stimulation of the hair cells [37]. Visual
input may be effective in reducing sensory conflict in micro-
gravity [38].
In normal gravity, peak eye movements were slower
than the visual display velocity when vertical head motion
and optokinetic stimulation were in the same direction, and
equal to the optokinetic display velocity when head motion
and optokinetic stimulation were in opposite directions. In
parabolic-flight microgravity, peak eye movement was about
equal to the visual display when head rotation and optokinetic
stimulation were in the same direction, and faster than display
velocity when head rotation and optokinetic stimulation were
in opposite directions. The interaction of vestibular and opto-
kinetic nystagmus was nonlinear in microgravity, especially
with downward optokinetic stimulation [2]. Neurosensory
motor functions supporting three-dimensional orientation
in space are disrupted or modified by sustained exposure to
microgravity. This results in the degradation of the visual and
visual-vestibular systems controlling smooth pursuit, visual
scan, and the vestibular-assisted optokinetic system.
Neural plasticity is the mechanism used to recalibrate
sensory-motor systems and allow learning and adaptation.
Plasticity in the spatial orientation system is distributed in the
17. Neurologic Concerns
cerebellar cortex (floccular and parafloccular lobules) and to
the brainstem nuclei (vestibular nuclei, olivary nuclei, nucleus
prepositus hypoglossi, and interstitial nucleus of Cajal). The
cerebellar cortex controls the timing of movement and guides
learning in the brainstem nuclei and the gain of oculomotor
systems via neurons within the neural integrator. End-gaze
nystagmus is the hallmark of dysfunction of the neural
integrator, which is the neural system that mathematically
integrates velocity-coded signals (to move the eye off axis)
into position signals (to hold the eye off axis). Measurements
of gaze-holding nystagmus, holding gaze in an eccentric posi-
tion, or rebound nystagmus, present in primary eye position
after sustained eccentric gaze, are simple clinical tests of the
neural integrator that provide a way to monitor neural plas-
ticity and the effects of adaptation or readaptation to altered
gravitoinertial environments.
Extended Duration Orbiter Medical Project and Shuttle-Mir
gaze-holding experiments indicate that the neural-integrator
centers in the cerebellar cortex and brainstem nuclei, which
maintain target acquisition, may occasionally be maladaptive
and disrupt oculomotor stability (Figure 17.1). Monitoring the
recovery time associated with the neural-integrator gain pro-
vides a means of quantitatively estimating when crewmembers
have returned to a physiologically normal state postflight and
are capable of engaging in the activities of daily living and
standard crew duties. In the gaze-holding protocol, the subject
views transiently displayed targets at 30 degrees in vertical
and horizontal planes, and attempts to maintain gaze on the
remembered location after the target disappears. The amount
Figure 17.1. Ocular stability with vertical head movement 10 days
preflight (L-10) and on landing day (R + 0) following Shuttle flight.
Pronounced ocular instability is demonstrated postflight
369
of gaze drift is compared with preflight performance and is
evaluated for specific abnormalities, such as eccentric gaze-
evoked nystagmus, rebound nystagmus, left-right or up-down
asymmetry, and cross-plane eye movements. Oman et al. [28].
speculate that the CNS may respond to weightlessness by
reducing the vestibular component driving CNS integration in
favor of visual inputs.
Postural and Gait Effects of Microgravity
Sensory-motor disturbances associated with microgravity are
observed with postural responses to movement during space
flight. A generalized loss of extensor muscle tone and increase
in flexor muscle tone observed in flight resulted in a forward
lean during running on the onboard treadmill as the flight
progressed [39]. Postural stance in microgravity assumes the
fetal-type posture immediately upon insertion into orbit, with
an even greater degree of flexion noted with vision occluded
and with previous spaceflight experience. Astronauts expe-
riencing sudden drops with an elastic pull cord felt as if
the floor was moving up, not as if they were moving down
[23]. Using muscle vibration to stimulate the tonic vibratory
response, preflight stimulation of the foot dorsiflexor muscles
results in forward sway, while inflight the forward response is
diminished [40].
Vestibulospinal reflexes in microgravity can be assessed
with the tendon (T) reflex or Hoffman (H) reflex, which is the
electrophysiological equivalent of the muscle stretch or deep
tendon reflex. The T reflex was found to be potentiated post-
flight (increased amplitude) for Skylab crewmembers. On the
Mir-Kvant 241-day expedition, the T reflex showed a fourfold
increase in amplitude on R+6 days [41]. On the Spacelab-1
mission, H reflex potentiation was suppressed on flight day
6 and was increased early after flight, returning to normal by
R+6 days [23]. Increased H reflex potentiation before and
after flight correlated with SMS.
The decrease in amplitude of the T or H reflex in-flight
and the increase postflight indicate decreased vestibulospinal
input in microgravity as well as increased vestibulospinal
input after return from microgravity and correlates with deep
tendon reflex changes inflight and postflight. Returning astro-
nauts are found to be diffusely hyperreflexic on return day
compared with preflight. This finding nearly normalizes by
R+3 for Space Shuttle crews. Postflight ataxia and postural
disequilibrium lasts from one to six days postflight for
short-duration missions, and from a few to several weeks after
long-duration missions. Factors related to postflight ataxia
include initial severity of SMS and mission duration. Using
the Fregly Rail Test for gait stability, the Apollo 16 crewmem-
bers at R+4 days were all unstable with eyes closed. One Sky-
lab astronaut at R+2 days was unstable even on a solid floor
[42]. After the 48-day Skylab 2 mission, crewmember bal-
ance on the narrow rail with eyes open was affected until R + 7
days [43]. Gait effects postflight were related to spaceflight
duration in the Soyuz series. Postflight gait effects persisted
370 J.B. Clark and K. Bacal

15 to 30 min for 2-day flights, 2 days for 6 to 8 day flights,

14 days for 16-day flights, and 25 days for 18-day flights
[44]. Inflight exercise appears to be somewhat protective of
postflight ataxia. After the 10-day Spacelab-1 mission, four
astronauts, standing with eyes closed (Sharpened Romberg),
were able to remain erect only 14% of their preflight stance
time on landing day (R + 0) and only 21% of their preflight
stance time on the first postflight day (R + 1) [45]. Stabilometry
(static force plate), used by the Russian space program, con-
sists of 1 to 2 min of balance assessment with eyes open or
closed, in normal stance (Romberg) or with head tilt [46]. In
the Soyuz series, stabilometry showed a postflight increase in
sway amplitude, primarily in the pitch plane, and a decrease
in sway frequency. Instability was related to length of flight,
with stabilometry using calibrated perturbations measured at
R+6 showing that recovery times were prolonged up to R + 11.
Postflight postural testing revealed labile or under-dampened
Figure 17.2. Recovery of balance function following short duration
response to translations, indicating decreased ability of senso-
(<18 days) space flight. The Normalized Equilibrium Score is based
rimotor responses to external perturbations [41]. Sensorimotor on maximum peak-to-peak anterior to posterior sway compared to
responses to external perturbations recover within hours after the theoretical limit of postural sway of a normal subject (sensory
landing. Following spaceflight, astronauts often report a sense organ condition 6see text). A normalized preflight baseline is rep-
of turning when they are attempting to walk in a straight line. resented by 1.0. The 5th percentile is considered a threshold of clini-
They also experience disequilibrium when rounding corners. cal impairment
Vestibular inputs to the antigravity muscles result in a change
in the distribution of tonic muscle activity, with an increase in
ankle dorsiflexor and a decrease in ankle plantar flexor activity.
Two levels of neural response, strategy and synergy,
maintain our control of gait and balance. Strategy is the orga-
nizational principle applied to maintain balance in response
to the magnitude of perturbation without regard to load. For
small displacements, the ankle movement predominates. With
larger displacements, the hip movement is used to maintain
stability. Synergy is the neural program of response to the task
and muscle loads. These two levels of neural response fac-
tor into the recovery of neurovestibular function after space-
flight. The majority of recovery occurs within hours, and full
recovery occurs within days after short-duration spaceflight
(Figure 17.2).
Gait and balance effects are related to spaceflight duration
and previous spaceflight experience (Figure 17.3). Postflight
findings on spaceflight crews include affecting a wide-based Figure 17.3. Postural equilibrium scores preflight and postflight in
gait, leaning toward the supporting leg; taking shorter, smaller rookie astronauts and experienced astronauts with 1 or 2 previous
steps while walking; and having a forward step accelerate at missions. The Composite Equilibrium Score is a summation of six
standard equilibrium tests in different sensory organ conditions (see
impact (stomping gait). Other gait effects noted among return-
text)
ing crews include the sensation of turning while walking a
straight path; the lateral pulsion (pushing outward) sensation,
as if being pushed by a giant hand while turning a corner; difficulties. On several occasions after Space Shuttle flights,
exaggerated pitch-roll sensation while walking; and the loss astronauts reported transient significant disequilibrium that
of orientation while in a visually deprived environment [47]. lasted for minutes and vertigo lasting seconds to minutes
Altered vestibulospinal reflexes may make astronauts and that occurred one to three weeks after landing and resolved
cosmonauts more prone to musculoskeletal injuries immedi- without sequelae. These flashbacks were triggered by motion
ately postflight due to altered muscle loading. stimuli such as vehicle, platform, or head motion, presumably
Exposure to sensory visual vestibular conflict (e.g., walk- due to otolith stimulation.
ing on plush carpet in the dark, or on an escalator or a moving Following an eight-day Space Shuttle flight (International
walkway) may result in postflight dizziness and ambulation Microgravity Lab-1), four astronauts underwent yaw exposure
17. Neurologic Concerns
on a rotating chair at R + 1. None reported any subjective
change in postural equilibrium [48]. One astronaut had sig-
nificant postural instability at R+0 but, as measured by com-
puterized dynamic posturography, recovered normal balance
function by R + 5. This astronaut then underwent exposure to
eccentric pitch rotation followed immediately by posturogra-
phy testing, which showed a decayed balance function simi-
lar to the R + 1 equilibrium score. The R + 1 equilibrium score
was also significantly impaired compared to the astronauts
normal preflight levels [48]. The rotation stimulus was brief
and mild. It consisted of sinusoidal oscillation (0.05 to 0.8 Hz
at 60 degrees per second, producing peak centripetal accelera-
tion of 0.05 Gz and 0.27 Gx) and trapezoidal angular velocity
(60-second ramps at 120 degrees per second, producing peak
centripetal acceleration of 0.22 Gz and 0.1 Gx). This disrup-
tion of postural control after pitch rotation otolith stimulation
could represent a reversion to a microgravity sensorimotor
control paradigm.
Four days after flight, another crewmember was riding on
an escalator and developed acute disequilibrium due to the
exaggerated perception of translation with the visual and
motion environment. Yet another Space Shuttle crewmember,
who was driving an automobile three weeks postflight on a
curved highway overpass, experienced an excessive lateral
translation perception that required pulling off the highway.
In another instance, a Space Shuttle crew, three weeks post-
flight, was on a moving platform in a parade. Each time the
platform motion started or stopped, the crewmembers noted
persistent translation for several seconds.
A mission specialist flying in a T-38 aircraft (rear cockpit)
three weeks postflight noted an exaggerated roll perception
after the pilot had initiated a roll break maneuver approach-
ing to land. This maneuver typically results in a brief 2 to
4+Gz exposure and roll acceleration. One long-duration crew-
member, two months postflight, reported transient vertigo and
unsteadiness while standing in ocean waves on a beach. These
flashbacks have been reported to be similar to the symptoms
experienced in the immediate postflight period (R+0), and
all occurred after readaptation to terrestrial gravity would be
expected. These findings have implications for a safe return
to daily activities and underscore the need for objective mea-
sures of fitness for duty.
These findings also have operational significance for lunar
and Mars missions. Since persisting sensation aftereffects are
known to occur in the majority of crewmembers after expo-
sure to microgravity [9], activities involving human control
of complex systems, such as operation of rovers and robotic
devices, should be delayed until after the crewmembers have
had a chance to adequately adapt to their new environment.
Balance Assessment
A standard and objective means of balance assessment is
required to perform a functional neurological evaluation of
returning spaceflight crews. The Neurocom Equitest dynamic
371
platform posturography, a medical device that quantifies the
functional status of balance, is used extensively in the ter-
restrial setting to clinically assess vestibular disorders. This
device evaluates the interaction and integrity of the ves-
tibular, somatosensory, and visual systems by assessing the
response of these systems to specific sensory perturbations
that degrade balance. Balance, the ability to maintain the
body center of gravity over the base of support, is assessed
by force transducers in the platform and is scored by a com-
puter. The system includes a computer-controlled movable
force plate platform and a full visual field surround. The
Equilibrium Score is based on maximum peak-to-peak ante-
rior to posterior sway compared to the theoretical limit of
postural sway of comparable subject. The balance function
score is expressed as a percentage between 0 and 100, where
a score of 0 indicates a fall and 100 denotes perfect stability.
A component of platform posturography, the sensory organi-
zation test (SOT), uses absent or conflicting somatosensory,
vestibular, and visual stimuli during six different test condi-
tions to evaluate the subjects ability to organize dynamic
visual, vestibular, and proprioceptive sensory input into useful
information for maintaining balance. In SOT condition 1,
the subjects eyes are open and the platform and visual sur-
round are stable. During SOT condition 2, the subjects eyes
are closed (no visual sensory input), fixed stable support is
present (normal somatosensory input), and the integrity of
the vestibular and somatosensory systems is evaluated con-
currently. In SOT condition 3, the subjects eyes are open,
the platform is stable, and the visual surround moves with
body motion (sway referenced), giving the subject inaccu-
rate visual information. During SOT conditions 4, 5, and 6,
the platform moves with the subject (sway-referenced). In
SOT condition 4, the subjects eyes are open, the platform
moves (sway referenced), and the visual field is stable. In
SOT condition 5, with the subjects eyes closed and unstable
platform support, the swayed reference provides inaccu-
rate proprioceptive information and visual sensory input is
absent; hence, the vestibular system is evaluated indepen-
dent of proprioceptive and visual input. During SOT con-
dition 6, the subjects eyes are open and the platform and
visual surround are both sway-referenced. SOT conditions
5 and 6 require an operationally functioning vestibular system
to maintain balance.
Normal subjects maintain their balance by ignoring inac-
curate orientation information and are able to maintain their
balance and not fall under all 6 SOT conditions, although
their balance scores are generally lower and their body sway
is greater under absent or conflicting sensory input. The pat-
tern of abnormal balance scores may indicate a dysfunctional
sensory system. Abnormalities on SOT conditions 3 and 6
indicate a preference for accurate visual information (visual
predominance). When a subject is given erroneous visual cues,
the subject who is visually dominant (visual preference) can-
not suppress inaccurate information, which means balance is
disrupted. Abnormalities on SOT conditions 5 and 6 indicate
372
vestibular dysfunction, while abnormalities on SOT condition
2 indicate proprioceptive system involvement. The aphysi-
ologic response is seen when equilibrium scores are not con-
sistent with the expected decline in normal performance with
more difficult tests. When a subjects equilibrium scores are
lower (worse) on easier tests with a stable platform and eyes
open, than with harder tests with a sway-referenced platform
and eyes closed, this indicates less than maximal performance
on the part of the subject. The subjects reduced performance
may occur because of poor instruction or insufficient practice
(training effect), fatigue, or voluntary reduced effort.
The Neurocom Equitest computerized dynamic posturog-
raphy system is an FDA approved medical device that is used
by NASA to track the recovery of vestibulo-spinal integra-
tion and spatial orientation in crewmembers returning from
spaceflight missions. For several days postflight, a crewmem-
ber may perform normally on test conditions with accurate
visual, vestibular, and/or somatosensory inputs but may have
significant degradation or even hazardous performance dur-
ing sensory conflict situations such as walking on a moving
sidewalk or an escalator. This clinical test battery can simu-
late sensory conflict situations that expose that crewmember
to potential disorientation or fall potential [6]. Three random-
ized trials of 20 s each are performed on each of the six SOTs.
Performance assessment is based on peak body sway during
each condition. Interpretation is based on currently available
normative population data, with the lower limit of normal
defined as below the fifth percentile of the population. The
population used is an asymptomatic normal population or
active astronaut population. Failure on this test battery would
be a score below the fifth percentile compared to the average
general population. This approach is used in clinical practice
in deciding when patients can return to driving after recovery
from vestibular disorders [49].
Fitness to return to driving after events involving vestibular
dysfunction is in part based on symptom recurrence and prog-
nosis [50]. The ISS Program has implemented the postflight
tests mentioned above to determine objective milestones for
return to function for its crewmembers. Individual variability
in readaptation timelines is seen in returning crewmembers,
necessitating objective measures. One returning long-duration
ISS crewmember, while riding as a passenger in a car 18 h
after landing, reported experiencing a significant pitch down
sensation when the cars brakes were applied. By contrast,
another returning ISS crewmember flew as a copilot in a light
aircraft 20 days after spaceflight and reported no problems.
Long-duration spaceflight crews are typically returned to
flight status in high-performance aircraft after the 30-day
postflight (R+30) examination. One long-duration crewmem-
ber expressed concern about returning to high-performance
aircraft duties, so a posturography medical evaluation was
performed on this crewmember while doing pitch and roll
head movements at about the R+30 period. Test results were
normal as compared to the population controls, and the crew-
member returned to active flight status without difficulty.
J.B. Clark and K. Bacal
A road test has been recommended for evaluating chronic
stable vestibular disorders [51] with regard to driving an auto-
mobile, and ocular stability has been suggested as a criterion
to determine driving ability [52]. Astronauts returning from
the ISS have gone back to driving five to seven days postflight
without apparent problems, usually starting with driving in
low-threat areas (empty parking lot), followed by more chal-
lenging city driving. Posturography is used to assess crew-
members at R+5 as a measure of visual vestibular integration.
It is recommended that balance function should be better than
the lower fifth percentile general population before return to
driving [49].
Assessment of Locomotor Oculomotor Interaction
During normal ambulation, gaze is stabilized from the top
down with pitch head movements and vertical eye movements
acting in a synergistic fashion. After space flight, astronauts
and cosmonauts typically hold their heads fixed with relation
to their trunks in order to resolve complex movements in their
vestibular systems although this response might also be due in
part to relative weakness in posterior neck antigravity muscu-
lature [47,53]. This head fixation strategy results in an altera-
tion between pitch head movements and trunk translation.
A locomotor coordination test battery has demonstrated
alterations in head-trunk coordination during terrestrial loco-
motion after spaceflight. Change in head-trunk coordination
disrupts gaze stabilization during ambulation and may lead to
disorganization in locomotor control. Postflight alterations in
lower-limb kinematics and in muscle activation patterns are
observed, particularly at the gait heel-strike. These alterations
are present for several days after short-duration spaceflight
(< 30 days). The ability to maintain gaze stability during loco-
motion requires normal function and integration of a number
of sensory and motor subsystems, including the vestibulo-
ocular reflex, vestibulo- and cervico-colic reflexes, limb loco-
motor pattern generators, and heel-strike energy modulation
systems. Disruption of any of these subsystems leads to
altered dynamic visual acuity and impaired modulation of
shock wave transmission to the head during locomotion and
also serves as a global indicator of sensorimotor disintegration
after space flight [53].
The performance outcome of locomotor disruption is the
impairment of gaze stability while a subject is walking and
the resultant increase in potential for musculoskeletal injury.
Dynamic visual acuity during locomotion, which is a reli-
able and sensitive indicator of clinical vestibular function,
is assessed during treadmill locomotion as the subject walks
at 6.5 km/h(4 miles/h) and reads aloud numbers of varying
sizes on a computer screen that is 2 m (6.56 ft) ahead at eye
level. Performance is assessed based on the number of correct
responses. To assess heel-strike, subjects walk at a freely cho-
sen pace on a 6- to 8-m (19.69- to 26.25-ft) ground track with
a built-in force plate that measures the relative amplitude of
the shock wave, transmitted from the heel to the head.
17. Neurologic Concerns
Figure 17.4. Recovery of visual function while ambulating follow-
ing space flight. Solid square is mean, box is standard error of mean
(S.E.M.) and line is standard deviation (S.D.). The number of sub-
jects assessed is given below each data set
Eye-head coordination aids us in maintaining visual acuity
while walking and moving and simplifies information transfer
between the head and trunk for efficient control of movement.
Dysfunction of eye-head coordination results in blurred vision
during visual pursuit of a moving target and delay in visual
target acquisition. Dynamic visual acuity, which is decreased
to 70% of preflight dynamic visual acuity on landing day, does
not return to normal for several days after a short-duration flight
(Figure 17.4). Static visual acuity is not seen to change appre-
ciably after spaceflight. (Transient reduced color vision and
visual acuity have been reported during long-duration space
flight immediately after the performance of squats on the
resistive exercise device, presumably from Valsalva-related
reduced retinal blood flow.)
Clinical Implications of Neurological
Disorders in Space Flight
General physical environmental alterations and hazards of
the spaceflight environment include microgravity, pressure
changes, toxic atmospheric conditions, vibration, noise, tem-
perature, electromagnetic radiation, altered visual and vestibular
cues, and orbital debris impact. Spaceflight has been associ-
ated with various problems affecting the central and peripheral
nervous system inflight and postflight [54]. The microgravity
373
environment of space may directly affect synapses. On Space
Shuttle missions Space Life Sciences-1 and -2, the number
of synapses on macular hair cells increased both in flight and
postflight [55]. Results of these flight experiments indicate
that neurological adaptation to microgravity may not be lim-
ited to CNS phenomena. Peripheral plasticity of sensors may
occur as compensation for loss of gravity bias. This has led to
speculation about possible long-term secondary consequences
to the CNS, such as premature neuronal death or apoptosis.
Vestibular Dysfunction
The altered gravitoinertial force that is associated with the
microgravity of spaceflight and its effect on vestibular function
has important implications for the diagnosis and treatment of
vestibular disorders in humans on Earth as well [56]. Terres-
trial neurovestibular dysfunction is manifested in similar ways
to those seen on orbit: by perceptual symptoms of vertigo
(spinning sensation); postural symptoms of disequilibrium or
ataxia (unsteadiness or imbalance); oculomotor symptoms of
oscillopsia (moving visual images); and vegetative symptoms
of lethargy, stomach awareness, nausea, and vomiting. Thus
neurovestibular symptoms are similar, whether due to altered
physiological stimulation or pathological dysfunction. Physi-
ological neurovestibular syndromes include spatial disorienta-
tion, vehicle-associated motion sickness (aircraft, car, boat),
and visual motion sickness (simulator sickness).
The causes of pathologic vestibular dysfunction include
peripheral, central, and systemic etiologies. Peripheral ves-
tibular dysfunction may occur with benign paroxysmal
positional vertigo, vestibular neuronitis, perilymph fistula,
Menieres disease (endolymphatic hydrops), alcoholic posi-
tional vertigo, and toxic vestibulopathies. Central causes of
vestibular dysfunction include migraine disorders and lesions
of the brainstem or the cerebellum. Migraine-associated ves-
tibular dysfunction may be similar to space adaptation syn-
drome, particularly the postflight neurovestibular symptoms
[57]. Vertigo is seen in 25% to 70% of migraine patients,
and a history of motion sickness is seen in 25% to 60% of
migraine patients. Any stimulation of the vestibular system
(caloric irrigation) or visual system (moving stripes) can trig-
ger migraine attack. Pharmacological treatment of vestibular
migrainesuch as calcium channel blockers, gamma-amino
butyric acid agonists (gabapentin and sodium valproate), and
carbonic anhydrase inhibitors (acetazolamide)might be
effective therapy (in addition to conventional measures such
as benzodiazepines and vestibular suppressants) for postflight
neurovestibular symptoms, particularly in the nearly one-third
of crewmembers who report some vertigo [9,24,58].
In a study of the perception of self-orientation during micro-
gravity vestibular investigations on a Space Shuttle Spacelab
flight, four astronauts underwent passive whole-body rota-
tion during a seven-day orbital mission. During pitch (Y-axis
rotation with the otoliths at a 0.5-m (1.64-ft) radius), subjects
experienced a constant force of 0.22 Gz at the otoliths and
374 J.B. Clark and K. Bacal

+ 0.36 Gz at the feet during the 60-s constant rotational veloc-
ity profiles. In these subjects, a 0.22-Gz otolith stimulus did
not provide a vertical reference in the presence of a gradient
of +Gz stimulation to the trunk and legs [59].
The peripheral and central vestibular system may influence
autonomic function in normal subjects for whom vestibular-
induced autonomic responses may be provoked during or after
vestibular laboratory testing, vehicular motion, time spent in
simulators, and exposure to microgravity, as well as in clini-
cal patients [60]. In normal subjects, vestibulo-autonomic
effects may impact the diagnostic testing, clinical diagnosis,
and treatment of vestibular disorders. Vestibular control of
cardiovascular function is evidenced by direct and indirect
connections between the vestibular system and brainstem
neurons that control heart rate, blood pressure and breathing
[61,62]. In some patients with vestibular dysfunction, these
vestibular-autonomic effects may lead to anxiety disorders,
panic attacks, and agoraphobia, and may also play a role in
vestibular-induced orthostatic intolerance [63].
Orthostatic intolerance postflight has been attributed to
changes in lower-extremity hemodynamics, baroreceptor
reflex alterations, diminished exercise tolerance and fitness,
hypovolemia, and altered beta-adrenergic receptor sensitivity
[64]. The otolith organs play an important role in regulating
blood pressure during postural changes on Earth. Plasticity
of the otolith organs during spaceflight may therefore also
contribute to postflight orthostatic hypotension by imposing
vestibular influences on cardiovascular control.
Cephalad Fluid Shift
The microgravity-associated cephalic fluid shift might be asso-
ciated with acute neurologic deterioration. This fact has raised
concerns about an undetected brain tumor or an Arnold-Chiari
malformation and brain herniation under similar circum-
stances and has caused consideration by the space medicine
community of neurologic imaging of the brain as a screen-
ing criterion for space flight. Trans-cranial Doppler used to
study the middle cerebral artery showed an increase in middle
cerebral artery velocity on flight day 1 in those with SMS
compared to those who did not experience SMS. From flight
day 2 through flight day 5, blood flow acceleration decreased,
which is an index of vessel distensibility and an indication
of changing cerebral resistance. The failure to increase cere-
bral vascular resistance may be related to SMS symptoms.
Changes in intracranial fluid dynamics could affect a vascu-
lar tumor or an arteriovenous malformation. Fluid shifts may
also contribute to neurovestibular effects via a patent cochlear
aqueduct, which transmits intracranial pressure to the inner
ear. Thus far, CNS imaging has not been implemented as a
medical selection tool, primarily due to the limited clinical
yield and chances of false positive findings (see Chapter 3).
Oculomotor Effects
Since 1996, crew surgeons have performed a standardized
clinical neurologic evaluation on Space Shuttle astronauts
both preflight and postflight using a neurologic function rating
scale. A summary of these results is found in Table 17.1.
Oculomotor, gait, and postural effects are well known after
space flight, although the performance correlates are not yet
established. The potential exists for as yet undetected long-
term effects on neurological function due to incomplete read-
aptation or maladaptation after spaceflight. In a review of
postflight eye movement responses, spontaneous eye move-
ments were observed in 7 of 19 cosmonauts after short-duration
missions, and in 24 of 27 cosmonauts after long-duration
missions compared to preflight oculomotor responses. Gaze
fixation was impossible as eyes continued to oscillate, and
typical jerk nystagmus developed into square wave jerks [65].
Gaze rebound nystagmus developed in 37% of cosmonauts
postflight. Oculomotor findings returned to normal in most
cosmonauts within 8 to 10 days after short-duration missions
and by 14 days after long-duration missions, although 11 cos-
monauts had not returned to normal by 75 days and 3 cosmo-
nauts had not returned to normal after 3 to 4 years.

Table 17.1. Functional neurological assessment rating scale (112 astronauts 19962000)a.
None Mild Moderate Severe
R+0 R+3 R+0 R+3 R+0 R+3 R+0 R+3
Headache 94% 97% 3% 3% 2% 0% 1% 0%
Dizziness/Faintness 83% 98% 14% 2% 3% 0% 0% 0%
Vertigo/Spinning 88% 99% 9% 1% 2% 0% 1% 0%
Gaze/Ocular movements (nystagmus) 45% 93% 51% 7% 4% 0% 0% 0%
Finger to nose (close eyes touch nose, open eyes touch finger) 81% 99% 19% 1% 0% 0% 1% 0%
Drift (close eyes, extend arms, palms up) 90% 99% 9% 1% 0% 0% 1% 0%
Rising from chair (without use of arms) 86% 99% 11% 1% 1% 0% 2% 0%
Standing/Romberg (feet together, arms extended, close eyes) 30 s 78% 97% 21% 3% 0% 0% 1% 0%
Leg lift/Hop (close eyes, lift leg, hop 3 times, alternate) 60% 99% 26% 1% 9% 0% 3% 0%
Tandem/Heel-to-toe walk (5 m) 43% 98% 37% 1% 18% 0% 2% 0%
Dynamic equilibrium (close eyes walk 9 m turn 180 and return) 53% 93% 41% 7% 3% 0% 4% 0%
R, return day.
a
Assessment performed on returning Shuttle crewmembers on landing day (R + 0) and three days following landing (R + 3).
17. Neurologic Concerns
Figure 17.5. Video Oculography (VOG) tracing of horizontal (H) on
upper line, and vertical (V) eye movements on lower line demonstrat-
ing horizontal square wave jerks (SWJ) in a crewmember following
long duration spaceflight. Although minimally present preflight, SWJ
were magnified in postflight studies and persisted in this individual.
This tracing was made five months postflight. Scale: 10 degree/block
in y axis, 1 s/block in X axis
One long-duration astronaut exhibited frequent square wave
jerks, which is an eye movement attributed to altered CNS func-
tion (Figure 17.5). A square wave jerk is a saccadic intrusion
(fast eye movement deviation) that takes the eye off its original
axis for about 200 milliseconds, is infrequent, and generally
occurs with a frequency of less than 20 per minute in the dark
[66]. Although in this case these square wave jerks were pres-
ent before flight, they increased dramatically in number after
flight, and remained more frequent more than four months
after spaceflight. The crewmember remained asymptomatic
and denied oscillopsia. The postural instability after space-
flight resembles mal de debarquement (debarkation sickness
or land legs), which was first appreciated centuries ago, after
crews had returned to land following long ocean voyages. Mal
de debarquement is often a disabling condition [67].
Headache
Headache is a common complaint in space flight. Data from the
NASA Longitudinal Study of Astronaut Health, examining 89
Space Shuttle flights with 508 crewmembers over 4,443 flight
days, revealed headache in 304 of 439 (69%) males and 38 of
69 (55%) females. Headache often occurs early after orbital
insertion and has been attributed to cephalic fluid shifts. In this
context, it is also thought to be a component of SMS. Other
potential causes of headache in space flight include locally
375
elevated carbon dioxide (CO2) levels, exposure to toxic fumes,
and decompression sickness. Symptoms of headaches, nausea,
and central vasodilatation occurred in some crewmembers on
Mir and during docked Space Shuttle operations with the Mir
or the ISS. This combination of symptoms (i.e., headaches,
nausea, and central vasodilatation) is not typically known to
occur on other Space Shuttle flights. Potential causes include
localized CO2 increase, hypoxia, reemergence of SMS, excess
heat and/or humidity, carbon monoxide (CO) or other con-
taminants, or a combination of factors.
As an example, a crewmember experienced a headache
while working in a fixed location in the SpaceHab module
early during transfer operations to the Mir; symptoms pro-
gressed as work continued. This crewmember experienced
nausea and vomiting as the headache worsened, and symp-
toms were relieved only when the crewmember took breaks
in the Space Shuttle flight deck. Air samples obtained at that
time showed no contaminants or accumulation of human
metabolic products, though the sampling technique may have
been flawed. These symptoms were different from the crew-
members SMS symptoms, which were predominantly nausea
and vomiting without a strong headache component. Crew-
members on other missions with docked operations had also
noted occasional air hunger, breathlessness, and headaches
during the docked phases of Shuttle-Mir flights. Symptoms
were worse when all of the crewmembers were present in the
aft base block of Mir, and resolved after short breaks in the
Space Shuttle. No atmospheric abnormality unique to the Mir
or the ISS has absolutely been implicated in this symptom
complex, although a portable CO2 detector has been devel-
oped to rapidly assess local concentrations of CO2 to better
characterize these events.
Although hypercarbia symptoms exhibit some variability
in character and intensity between individuals, the symptoms
are usually consistent for each individual. ISS and EVA crews
undergo controlled preflight CO2 exposures to familiarize
them with their specific symptom complex. For a sea-level
cabin, symptoms are usually not present at 1% or less CO2
(7.5 mmHg), although fatigue and headaches are possible
above 2% CO2 (15 mmHg). Terrestrially, at 1 atmospheric
pressure, CO2 percentage is normally 0.03% (0.2 mmHg),
whereas normal human activity may result in CO2 levels of
0.13% (1 mmHg) in a typical room. Space Shuttle CO2 levels
on average are about 0.26% (2 mmHg) during normal in-flight
operations, though these may be higher in areas of inadequate
air mixing (see Chapter 22). Headache is not a common ini-
tial presenting symptom of heat stress; sweating, nausea, and
vomiting are more commonly associated with heat stress.
Space Shuttle crewmembers who have experienced headache
and other potentially CO2-related symptoms have noted that
the ISS modules have not been uncomfortably warm.
Other entities possible during space flight may also involve
headache as a symptom. Acute hypoxia may include head-
ache and be associated with fatigue, visual changes, and skin
flushing. Symptoms of headache, nausea, and vomiting are
376
seen in acute altitude sickness, and can occur within 24 h of
exposure to a lower pressure but not usually within several
hours. Symptoms of SMS rarely develop late in space flight
unless crewmembers are exposed to a visual reorientation illu-
sion or a significant gravito-inertial force, (e.g., a rotating chair
experiment). It is conceivable that the gain of visual-enhanced
VOR could change because of the proximity of the visual sur-
round in enclosed spaces after a crewmember has adapted to
more open habitable volumes, and this transition could induce
SMS symptoms. The reemergence of SMS, although a pos-
sible cause of these symptoms, would require further study
and may be diagnosed in part by exclusion.
Back Pain and Nerve Entrapment
Back pain is commonly associated with space flight. It often
manifests as a generalized axial skeletal ache that is signifi-
cantly mitigated by flexing into the fetal position. Axial skele-
tal elongation is suspected, because crewmembers often grow
in seated height from preflight by a few to several centimeters,
although statistical correlation with back pain and postflight
height increase has not yet been performed. Rarely crew-
members report sensory loss associated with spaceflight back
pain. One crewmember developed upper-extremity numbness
(proximal bilateral arms and chest in a cape-like distribution)
in flight that persisted for weeks after a short-duration mission.
This crewmember also flew on a long-duration mission and
developed a large area of lower-extremity saddle anesthesia
in flight. Symptoms persisted for several months postflight.
An extensive work-up with neuroradiologic studies to evalu-
ate for cranio-cervical junction abnormality, spinal cord syr-
inx, and tethered spinal cord revealed no pathology. Another
long-duration crewmember developed bilateral distal finger
and toe paresthesia and numbness that began several months
into the mission. These symptoms correlated with postflight
findings of reduced vibration and proprioceptive function in
the affected extremities. Symptoms resolved several months
postflight. A Space Shuttle crewmember reported a pins-
and-needles sensation in the legs late in a short-duration
spaceflight. During the mission, this crewmember had been
exposed to unexpected 15-cm (5.9-in.) vertical falls (Gz)
using an elastic bungee harness that generated simulated gravity
forces (0.33-, 0.67-, and 1-g) [68].
Neurologic Countermeasures
A Vestibular Countermeasures Task Group of clinical and
academic experts has been organized by NASA at the John-
son Space Center to assess the development and implemen-
tation of countermeasures to lessen or alleviate the adverse
effects associated with neurological adaptation to spaceflight
and return to Earth. Neurological countermeasures to opti-
mize health and safety are required, but it is recognized that
countermeasures to maintain or improve performance of one
J.B. Clark and K. Bacal
physiological system may cause or exacerbate problems in
other physiological systems; as such, these countermeasures
must be carefully developed. The countermeasure development
process normally includes (1) basic science and laboratory
research; (2) clinical efficacy research; (3) cost-effectiveness
and risk versus benefit evaluation; (4) operational effective-
ness evaluation; (5) assessment of interference with other
countermeasures or spaceflight operations; and (6) eventual
acceptance as an operational countermeasure after operational
validation. Evaluation of countermeasures should establish the
functional link between physiologic perturbations and opera-
tional performance deficits.
The Vestibular Countermeasures Task Group has addressed
and categorized several neurosensory disruptions that are caused
by space flight: (1) SMS, (2) the entry/landing syndrome, and
(3) severe disturbances after long-duration spaceflight. NASA
countermeasures can be divided into those designated as cur-
rently accepted procedures and those in development, where
research is incomplete or the efficacy is not yet established.
Accepted countermeasures against SMS include (1) crew
training, briefing, and timeline adjustment; (2) medication
administration, with understanding of side effects and interac-
tions; (3) development of individual outcome predictors; and
(4) development of coping procedures.
Countermeasures that address entry/landing syndrome include
(1) crew briefings for education and awareness; (2) preflight
training and in-flight landing task simulators, such as the portable
in-flight landing operations trainer simulator; (3) operational
landing requirements and procedures to create a best available
vestibular environment; and (4) exercise protocols to prevent
antigravity muscle loss.
Countermeasures or which there is only anecdotal evidence
include (1) crew briefing on risks versus benefits of head move-
ments during entry and immediately post-landing, (2) egress
training for ill or impaired crewmembers, (3) careful medication
use and (4) dual-adaptation protocols using preflight adaptation
training.
For major neurosensory disturbances after long-duration
missions, such as persistent sensation aftereffects, clumsiness,
difficulty walking a straight line (ataxia), and vertigo, the only
accepted countermeasure is assisted egress. Further analy-
sis is under way to determine (1) contributions of pre-entry
fluid loading to postflight vomiting; (2) relationships between
in-flight exercise, preflight rotation tolerance, and post-landing
postural control; (3) the neurological effects of recumbent
positioning during entry; and (4) data from crew debriefs.
Another area to be developed is analysis of the interactions
between the different neurosensory disturbances, or normal
readaptation time course and symptomatology.
Ground-based programs, such as virtual-reality-based
approaches that use projected or portable head-mounted virtual
environment systems, could be developed to train crewmem-
bers to orient and navigate through spacecraft without regard
to their body orientation. A light, miniature, head-movement
monitoring system was proposed as a future countermeasure
17. Neurologic Concerns
to be used for crew training to adapt head movement strategies
that minimize SMS, visual reorientation illusions, and reentry
and postflight disorientation. Prediction of CNS sensorimotor
patterns of response would allow appropriately trained astro-
nauts and cosmonauts to maintain the dual-adaptive states
that are appropriate for both the terrestrial and microgravity
environment, thereby minimizing problems during landing
and egress.
Dual adaptation training could be performed in a terrestrial
environment on a large-radius centrifuge, with visual dis-
plays that allow crewmembers to make active pitch and roll
head movements in a microgravity field while minimizing or
avoiding Coriolis and cross-coupling effects. A small-radius
centrifuge on orbit, such as the Skylab M131 chair and the
Space Shuttle Neurolab chair, might aid adaptation back to
terrestrial environments. Crewmembers could use a modified
space-based treadmill with proprioceptive and visual cues
provided by tactile and virtual-reality devices to maintain pos-
ture and kinematic strategies appropriate for 1-G.
Anecdotally, one ISS crewmember ran on the treadmill-
vibration isolation system for 1 to 2 h a day while viewing
a digital video movie on a computer screen 1.5 to 2 m away.
This provided a challenge to the ocular stabilizing function
of the crewmembers vestibular system that was similar to
the dynamic visual acuity test performed on a treadmill. This
crewmember, who usually suffers postflight neurovestibular
symptoms, reported fewer symptoms after this flight and was able
to egress the Space Shuttle unassisted after the long-duration
ISS mission. Running on a treadmill while maintaining a
visual fixation target may thus be an effective countermeasure
for neurovestibular adaptation and deserves further evaluation,
particularly in light of findings that in-flight exercise appears
to have a protective effect against post-flight neurovestibular
symptoms such as clumsiness and difficulty walking a straight
line, while post-flight exercise is associated with a decrease in
difficulty concentrating [9].
Spatial orientation is normally maintained by input from
the visual, auditory, vestibular, and somatosensory systems
that provide redundant and concordant information. The
tactile situational awareness system has demonstrated that
spatial orientation can be continuously maintained by provid-
ing proprioceptive orientation cues to a reference point, such
as where down is to a pilot in an aircraft or where a hatch is
to a diver underwater [69]. The system uses a harness worn
over the body fitted with an array of tactors, small mechani-
cal actuators, providing skin pressure or vibration cues that
continuously update the crew with a haptic presentation of
position and velocity information. Position and motion infor-
mation could be provided to an EVA astronaut or cosmonaut
over large structures such as the ISS, thereby reducing disori-
entation and illusions [70]. During a launch abort scenario,
the Space Shuttle commander could have 3-dimensional
situational awareness of the closest abort landing site or could
be able to make a piloted reentry and landing without directly
visualizing instrumentation. In the event of an emergency
377
egress with reduced visibility (caused by smoke or water) or
unusual attitude, Space Shuttle crewmembers could be aware
of their orientation if provided such tactile directional cues to
the escape path.
A rotating artificial gravity device may be a viable coun-
termeasure to prevent the physiological deconditioning
associated with microgravity [71]. The ISS is devoted in part
to investigating problems of human long-duration spaceflight
and will eventually afford the opportunity to evaluate counter-
measures that could be used for an exploration-class mission to
Mars. The neurovestibular implications of rotational artificial
gravity must be assessed, however, before this countermeasure
can be accepted. A major consideration of artificial gravity is
the trade-off between the radius and the rotation rate required
to achieve a desired gravity levela trade-off that influences
rim velocity and gravity gradient (radius). If intermittent gravity
is provided, e.g. on a short arm centrifuge, then there may be
sensory problems related to shifting between gravitational and
microgravity environments. In addition, a short radius implies
a substantial gravity gradient along the rotational arm, with
the outward body experiencing a greater centripetal force than
further inward.
Another fundamental task is determining what constitutes
an adequate gravity level and whether to apply a given grav-
ity level continuously or intermittently (i.e., exposure time).
An adequate artificial gravity stimulus, combined with active
head movements and locomotion, could potentially avoid
reentry disorientation and post-landing postural instability if
astronauts and cosmonauts could adopt a dual-adaptive state.
Vestibular disturbances that are associated with cross-coupled
Coriolis acceleration when making out-of-plane head move-
ments are directly proportional to the rotation rate and can
create sensory conflict leading to SMS. Rotation rates of
1 to 2 rpm are easily tolerated, and incremental adaptation can
provide tolerance up to 6 rpm. In the microgravity environ-
ment, 10 rpm may be possible. At 10 rpm, a 10-m (32.8-ft)
radius produces 1-G and a 5-m (16.4-ft) radius produces about
0.5-G.
Intermittent exposure to artificial gravity may prevent
deconditioning of otolith-ocular and vestibulo-sympathetic
reflexes in microgravity. During the 1998 Space Shuttle
Neurolab mission (STS-90, April 17 to May 3, 1998), four
astronauts were exposed to centripetal accelerations with con-
stant velocity centrifugation of 0.5-G and 1-G at the head
during rotation on a short-arm (0.5 m radius) human centri-
fuge. Rotations were performed in two configurations; seated
with the body vertical axis parallel to the axis of rotation
and with the direction of motion through the chest (face or
back first), or lying supine along the rotating arm with the
axis of rotation approximately at the navel. Exposures were
conducted both preflight and postflight as well as during the
16-day orbital spaceflight. Subjects were oriented either left
or right ear-out (Gy centrifugation) or supine along the cen-
trifuge arm with head off-axis (Gz centrifugation). Preflight
centrifugation, which produced 0.5-G and 1-G along the Gy
378
(interaural) axis, induced roll-tilt perceptions of 20 and 34
degrees for actual gravito-inertial acceleration vector tilts of
27 and 45 degrees. Preflight 0.5-G and 1-G Gz centrifugation
generated perceptions of backward pitch of 5 and 15 degrees,
respectively. Perception of tilt was underestimated early in
flight during Gy centrifugation, but was close to the gravito-
inertial acceleration after 16 days in orbit. In-flight roll-tilt
perception during Gy centrifugation increased from 45 to 83
degrees at 1-G and from 42 to 48 degrees at 0.5-G. The differ-
ence of in-flight versus preflight tilt perception suggests that
non-vestibular inputs, such as an internal body vertical and
somatic sensation, may be used in perceiving tilt.
Clment et al. have suggested that ambiguity of the otolith
graviceptor response to linear acceleration in microgravity
might result in tilt being perceived as translation. Since linear
acceleration during in-flight centrifugation was always per-
ceived as tilt, not translation, the findings do not support their
Otolith Tilt Translation Reinterpretation hypothesis [72]. The
gain of the ocular counter roll, which is a torsional (rotational)
eye movement and one type of otolith-ocular orienting reflex,
was maintained in flight and postflight, in contrast to previous
postflight ocular counter roll studies that showed decreases
in ocular counter roll gain. Intermittent exposure to artificial
gravity (centripetal acceleration) was postulated as a coun-
termeasure to deconditioning of the otolith-ocular orienting
reflex during the spaceflight mission.
In keeping with this proposed protective effect, all four
rookie crewmembers on the Neurolab mission who partici-
pated in the experiment had normal postflight orthostatic
tolerance, an unlikely occurrence given that orthostatic
intolerance occurs in about 64% of returning rookie astro-
nauts. This emphasizes the link between the neurovestibular
system and the cardiovascular systems influence on post-
flight orthostasis.
Further studies to evaluate postflight otolith deconditioning
and orthostatic intolerance are needed before intermittent cen-
trifugation artificial gravity should be considered as a counter-
measure in long-duration missions. Bed-rest deconditioning
studies using a short-radius centrifuge could determine the
radius, gravity level, and rotation rate most likely to pro-
vide an acceptable environment for intermittent stimulation
in order to prevent bone, muscle, and cardiovascular decon-
ditioning. Other studies using a slow rotating room will be
necessary to assess human factors issues and the problems of
adaptation schedules. After we have conducted ground-based
studies, a small-diameter human centrifuge might be accom-
modated on the ISS to study intermittent gravity stimulation.
If this yields promising results, definitive studies for long-
duration protection could be carried out with a large (1-km
(0.62-mile) ) tethered Variable Gravity Research Facility in
co-orbit with the ISS.
A short-arm centrifuge could be an effective counter-
measure to maintain dual adaptation by allowing adequate
terrestrial sensory-motor functioning in space flight, while
simultaneously allowing for adaptation to the microgravity
J.B. Clark and K. Bacal
environment. Entry/landing syndrome has been suspected
when a Space Shuttle commanders operational performance
measures (touchdown velocity and vertical velocity at touch-
down) have not correlated with preflight performance on the
Space Shuttle landing simulator (the Shuttle training aircraft).
This centrifuge might be effective in preventing the potentially
devastating operational consequences of entry/landing syn-
drome resulting from spatial illusions and subsequent neu-
rovestibular effects during manual landing. The shuttle has an
autopilot feature that could be used to mitigate this risk.
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18
Gynecologic and Reproductive Concerns
Richard T. Jennings and Ellen S. Baker
The seven U.S. Mercury astronauts, all of whom were male, were
selected by NASA in 1959 to make the first human space flights.
Nevertheless, the era of human space flight started not in the United
States but in the Soviet Union with the single-orbit flight of a male
cosmonaut, Yuri Gagarin, on Vostok 1 in April 1961. The Sovi-
ets also inaugurated female participation in space flight. The first
woman to fly in space was Valentina Tereshkova, who spent 3 days
on Vostok 6 in 1963. Nineteen years later another Soviet woman,
Svetlana Savitskaya, ventured into space on the flight of Soyuz-T7
in August 1982. In June 1983, the first female U.S. astronaut, Sally
Ride, joined this elite group of female spacefarers.
The process by which the first astronauts were chosen for
the U.S. space program was initiated in the late 1950s. The
U.S. Government determined that the first groups from which
astronauts were to be selected would be limited to military test
pilots. Although several women were able to complete the med-
ical selection examinations (the same ones given to the men),
none of them qualified for the simple reason that all military test
pilots at that time were men. This policy thus effectively delayed
space flights by U.S. women for 2 decades [1]. The first U.S.
astronaut class to include women was formed in 1978; of that
class of 35, 6 were women. To date, more than 45 female career
astronauts (pilots or mission specialists) have been selected for
the U.S. space program. One female Canadian astronaut and
three female payload specialists have flown on the shuttle.
Dr. Sally Ride, the first female U.S. mission specialist to
fly, launched in 1983 on Space Shuttle flight STS-7. Since
Dr. Rides flight, more than 40 female mission specialists or
pilots have orbited the Earth as astronauts in the U.S. space
program. (When this book was written, 4 additional female
payload specialists and 1 female cosmonaut had flown aboard
the Space Shuttle.) The first woman to serve as a Space Shut-
tle pilot was Eileen Collins, who piloted the STS-63 mission
in 1995. Collins also served as the first female commander of
a Space Shuttle mission, STS-93 in 1999. Dr. Shannon Lucid,
who is a member of the astronaut class of 1978, from 1996
until May 2002 previously held the record for the longest
space flight by any U.S. astronaut. Dr. Lucid flew 75 million
miles during her mission on board the Russian space station
Mir, a flight that lasted 188 days (from 22 March 1996 to 26
September 1996). She and 5 other female astronauts share the
record for the greatest number of space flights completed by
U.S. women. (Each has completed 5 flights.) More recently,
Sunita Williams completed a 194 day mission aboard the ISS,
and Peggy Whitson became the first woman ISS Commander.
At the conclusion of her second ISS increment, Dr. Whitson
will have accumulated more than 350 days in space.
Despite the delay in admitting women to the U.S. space program,
being female actually offers some advantages. The weightlessness
that is part of life in microgravity negates some of the male advan-
tages of size and strength. The closed environmental systems that
are found on all spacecraftwith limited amounts of O2, water, and
food, and with the need to process solid, liquid, and exhaled waste
productsfavor smaller individuals. Since the general implica-
tions for women participating in high-performance aircraft and in
spacecraft have been reviewed elsewhere [25], they will not be
addressed here in great detail. Suffice it to say that, although men
and women differ in their ability to withstand extremes of hypoxia,
decompression, temperature, acceleration, isolation, stress, and
impact, these differences are generally small and often depend
more on acclimation and individual variation than on sex.
Regardless of the relative assets and liabilities of using men or
women in future space crews, these crews will include people of
both sexes. It is therefore prudent that the reproductive and gyne-
cologic issues associated with selecting, training, and assigning
female crewmembers to space missions be examined. This chap-
ter addresses gynecologic medical standards and female astronaut
selection, reproductive and operational gynecologic considerations
during training and space flight, pregnancy after space flight, and
gynecologic considerations for long-duration space flights.
Gynecologic Medical Standards
and Female Astronaut Selection
The prevention of gynecologic or other medical problems in
space begins with the selection process and continues with
aggressive preventive-medicine programs during the astronauts
381
382
Earth-based career. The medical selection criteria for female
Space Shuttle astronauts are generally identical to those for
male Space Shuttle astronauts, except for reproductive-system
standards and radiation-exposure limits.
Radiation-exposure limits are based on guidelines issued by
the National Council on Radiation Protection and Measurements.
These limits allow a maximum lifetime increase in cancer risk
of ~3% for all space crewmembers [6]. As the missions become
longer and space crews travel greater distances from Earth, the
radiation standards will have to be reviewed periodically and
are likely to become even more conservative to maintain the
maximum excess risk at 3%. Current career exposure limits for
women at all ages are lower than those for men (see Chapter 23).
Radiation standards, along with other medical selection standards
for astronauts, are reviewed periodically; the difference in radia-
tion limits for women and men essentially reflects the increased
incidence of breast and thyroid cancer among exposed women
relative to the incidence among exposed men. In addition, due to
reduced risk of early death from cardiovascular disease, women
live approximately 15 years longer than men, thus allowing more
time for post-flight carcinogenesis.
Gynecologic selection standards have evolved, and generally
have been relaxed as spaceflight experience has progressed.
For example, standards for the 1978 astronaut class disquali-
fied women who had a history of endometriosis. This was done
because microgravity was expected to increase the likelihood of
retrograde menstruation, and exposure of the peritoneal cavity
to menstrual products would further increase the risk of endo-
metriosis [710]. Another concern, raised by studies of rhesus
monkeys, was that exposure to space radiation could increase
the risk of endometriosis [1115]. A more recent concern
regards the possible effect of space-induced immunosuppres-
sion on the incidence of endometriosis [1618]. Current stan-
dards allow a history of endometriosis but disqualify candidates
with endometriosis that results in severe dysmenorrhea, those
with endometriomas, or those with extensive pelvic adhesive
disease. Candidates with a history of surgically treated endo-
metriosis are evaluated by the Johnson Space Center Aerospace
Medicine Board on a case-by-case basis.
Premenstrual syndrome must interfere with the performance
of duties to disqualify a female candidate from the U.S. space
program. Any gynecologic malignancy is disqualifying for selec-
tion and for space flight, except for successfully treated cervical
carcinoma in situ. Many existing Space Shuttle or International
Space Station (ISS) medical standards will probably become
more stringent for exploration-class missions to the Moon or
Mars given the reduction in treatment options afforded crews
by mission length, remoteness from Earth, spacecraft treatment
limitations, the inability to provide real-time medical consul-
tation, and the inability to return to Earth in a timely fashion.
Conversely, the medical standard for spaceflight participants or
tourists on short flights to low Earth orbit will probably be less
stringent than the standards for career astronauts.
Astronauts who are already in training and who develop a
disqualifying condition are often granted a waiver if the medi-
R.T. Jennings and E.S. Baker
cal threat is or can be eliminated or mitigated. For example, a
woman with a history of corpora hemorrhagica who requires
operative intervention might be given oral contraceptives and
allowed to participate on a long-duration mission in low Earth
orbit. Leiomyomata uteri that are symptomatic or cause men-
orrhagia may be successfully treated by surgery. It is possible
that a female astronaut with a successfully treated gyneco-
logic malignancy that has a high cure rate, such as well-dif-
ferentiated endometrial cancer, could be granted a waiver
for short-duration space flights; a waiver for a long-duration
space flight, such as a mission to Mars, is unlikely, however.
Decisions regarding waivers are usually made on a case-by-
case basis by NASA and the ISS Multilateral Space Medicine
Board after a thorough review of the condition, input from
outside specialty consultants, successful therapeutic interven-
tion, and a complete recovery. Waivers are not typically issued
during astronaut candidate selection; in fact some candidates
are deemed disqualified but surgically correctable (e.g., symp-
tomatic leiomyomata, benign ovarian neoplasia, cholelithiasis,
or inguinal hernias). Pending successful treatment, some
disqualified candidates may become eligible for selection in
that same cycle.
As part of the extensive week-long astronaut selection
medical evaluation and interview process, each female
astronaut-candidate finalist undergoes pelvic and abdomi-
nal sonography, proctosigmoidoscopy, gynecologic exami-
nation, and Pap smear. Candidates aged 35 years or more
undergo mammography. To date, the mean age for female
astronaut-candidate finalists is 32 years. The gynecologic
conditions found during the selection examinations are prob-
ably similar to those found in equally educated women of the
same age in other professions. A review of gynecologic find-
ings during the selection examinations in 1994, 1996, 1997,
and 1999 showed that 20 of 90 women had a history of cur-
rent or treated cervical dysplasia. The 88 female finalist can-
didates examined in 1991, 1994, 1995, and 1996 had a total
of 5 ovarian masses that required further evaluation, and 9
had leiomyomata uteri. Endometriosis is a common finding
during selection, and 3 of 21 astronaut-candidate finalists in
1999 had a history of surgical treatment of endometriosis.
No female finalists have been disqualified because of a gyne-
cologic condition found at the time of the selection exami-
nation. However, several applicants have been disqualified
by the record review that takes place during the selection
prescreening process. Several female astronaut-candidate
finalists were required to undergo surgical procedures or
biopsies to rule out disqualifying pathology or neoplasia
in ovarian masses, breast masses, or breast microcalcifica-
tions. So effective is this preselection examination that, to
date, no active female U.S. astronaut has been permanently
grounded because of a gynecologic condition that developed
after selection.
A situation that causes difficulty in many selection cycles
is a current pregnancy in female astronaut-candidate final-
ists. Pregnancy itself is not a disqualifying condition, but
18. Gynecologic and Reproductive Concerns
the selection examination cannot be completed during the
pregnancy. Existing pregnancy has caused a few candidates
to delay their selection examination or to postpone the entire
selection process until a subsequent cycle.
Reproductive Considerations During
Training
Astronauts currently spend most of their time receiving generic
training and performing leadership and support roles for the
U.S. space program. Mission-specific training for either short-
duration Space Shuttle or long-duration ISS flights usually
begins from 1 to 2 years before an assigned mission. Astro-
nauts are required to fly regularly in T-38 aircraft, maintain
SCUBA qualification, undergo physiologic training in an alti-
tude chamber, and practice planned extravehicular activities
(EVAs) in underwater facilities such as those at the Sonny
Carter Neutral Buoyancy Laboratory in Houston, Texas or the
Hydrolab in Star City, Russia.
In addition to the experience they accrue in the Neutral
Buoyancy Laboratory, crewmembers assigned to perform
EVAs are given additional experience in the U.S. extravehicu-
lar mobility units (EMU) or the Russian Orlan suits (space
suits) inside a vacuum chamber. During their training, astro-
nauts perform an in-suit 100% O2 prebreathe procedure at
70.3 kPa (10.2 psi) or 101.3 kPa (14.7 psi) before undergoing
decompression in a vacuum chamber to an in-suit pressure
of 29.6 kPa (4.3 psi). Pregnant astronauts are precluded from
participating in this activity, among others, throughout the
pregnancy.
Since the T-38 training aircraft is equipped with an ejec-
tion seat, pregnant crewmembers are not allowed to fly in it
after the first trimester. The cabin altitude in the pressurized
T-38 may reach 5,490 m (18,000 ft), but all crewmembers
breathe supplemental O2. Accidental decompression at alti-
tude occurs occasionally; and since NASA T-38 operations
are common up to 13,110 m (43,000 ft) altitude, this risk
has to be considered. No astronaut has developed altitude
decompression sickness from T-38 operations, but some
episodes have occurred during training upon exposure to
vacuum. This fact alone warrants the exclusion of pregnant
astronauts from the vacuum chamber. Similarly, special
precautions are taken to avoid decompression-related ill-
ness if underwater EVA or SCUBA training occurs before
aircraft operations.
Women who are known to be pregnant are not allowed to
practice EVA in the Neutral Buoyancy Laboratory. The rationale
for this preclusion involves the duration of the dives during
EVA training, which last up to 8 h; the depth of the Neutral
Buoyancy Laboratory, 12.2 m (40 ft); and the limited
|information available about prolonged diving during preg-
nancy. In addition, oxygen-enriched air is used in the Neu-
tral Buoyancy Laboratory, and very little data are available
regarding the combination of use of this air, diving, and
383
pregnancy. NASAs restraint in this regard agrees with that
of many authorities who suggest that for pregnant women,
the risk of accidents, decompression sickness, or inadvertent
exposure to teratogens and the requirement for high-partial-
pressure breathing gases usually outweigh any short-term
training benefit [19].
NASA high-altitude physiologic training involves simulat-
ing ascents to 10,670 m (35,000 ft) cabin altitude and several
minutes of exposure to hypoxia at 7,620 m (25,000 ft). Preg-
nant astronauts are prohibited from participating in these
activities. In addition, EVA crewmembers are given hypercar-
bia experience with a rebreathing system starting with 100%
O2 that results in brief exposures of up to 8% CO2 at sea level.
Pregnant astronauts are precluded from this activity as well.
Water survival courses, Space Shuttle emergency egress and
escape slide training, and periodic parachute training are also
not permitted during pregnancy.
No pregnancy testing is currently performed before at-
risk training activities, although this policy is periodically
reviewed. Female astronauts are expected to self-report preg-
nancy. Pregnant astronauts are not usually allowed to train
in parabolic flight because of the potential for trauma while
flying unrestrained in the large cargo area. The effects on the
fetus of repetitive flights with 40 to 60 parabolas involving
free-fall simulations of microgravity and 2-gravity pullouts
per flightall of which are typically performed during KC-
135E or DC-9 trainingare not known.
In summary, the multiple constraints on training for female
astronauts who are pregnant often result in planned delay of
pregnancies until after the first or second space flight. These
career considerations often lead to childbirth at relatively
advanced maternal ages.
Operational Gynecologic Considerations
Pregnancy and Contraception
A few unique operational considerations are required for
female crewmembers on current Space Shuttle and ISS
flights. Pregnancy is disqualifying for space flight because of
concerns regarding exposure to radiation and toxins, decom-
pression sickness, the potential adverse effect of microgravity
on early embryogenesis, and the risk of on-orbit pregnancy
accidents such as spontaneous abortion, ectopic gestation, or
preterm labor. Each female crewmember is tested for preg-
nancy during preflight medical examinations beginning 10 days
before launch, and women who are found to be pregnant are
removed from the flight. Although astronauts have used essen-
tially every form of contraception, the disqualifying nature of
pregnancy for space flight has led to an increase in the pre-
flight use of contraceptive methods that have reported low
method-related failure rates. Crewmembers are encouraged
to continue their current contraceptive methods or methods
during training and in flight. Most contraceptive methods
(e.g., intrauterine devices, levonorgestrel implants, and oral
384
contraceptives) have also been continued during Space Shuttle
missions. No method-related incidents or complications have
been experienced.
For medical reasons, depot leuprolide acetate with estro-
gen/progesterone addback has also been used in space
flight. Oral contraceptives on short-duration missions offer
the opportunity to reduce the volume of menstrual efflux
and to shift the menstrual cycle so as to avoid menses on
orbit. On long-duration missions continuous menstrual
suppression is often used. A pill-free week each month is
not necessary while using low-dose oral contraceptives for
suppression; indeed, continual therapy may offset some
other problems associated with space flight such as hygiene
and osteoporosis.
Menstruation and Hygiene
Despite considerable initial concern about female crewmembers
experiencing menstruation in space flight, menstruation
has not presented a problem. Before the first U.S. female
crewmembers flew in space, consultants met with the
NASA Medical Operations group in Houston to discuss
menstruation in microgravity. This group recommended
that female crewmembers consider depot medroxyproges-
terone acetate, oral contraceptives, or danazol to manage
menstruation during space flight. Oral contraceptives with
30 to 35 g of ethinyl estradiol were deemed most prac-
tical. Debrief data from the Space Shuttle Program have
confirmed that menstrual efflux and required hygiene mea-
sures are similar to those experienced on Earth. There have
been no reported symptoms that would suggest retrograde
menstruation. Female astronauts on the Space Shuttle have
access to multiple sanitary products for menstruation,
including pads, minipads, and tampons in plain and deodor-
ant versions. For launch, EVAs, and landing, crewmembers
of both sexes have a maximum-absorbency garment avail-
able that can retain up to 2 L (4.23 pints) of urine, blood, or
feces. These garments replace the absorbent material used
in an adult diaper with the super-absorbent material found
in urine containment devices.
A unique area of difference for female crewmembers in
space flight involves urination. Each crewmember has his
or her own urine cup that can be integrated into the Space
Shuttle waste collection system. The cups for women
are shaped differently than those for men to accommodate
anatomic differences. Nevertheless, several women have
reported difficulty in drying after urination. This may be
due to urine entering the vaginal orifice by surface tension
or remaining in the distal urethra. Regardless of the cause,
the small amount of wetness that occurs after urination is a
minor annoyance noted by only a few women. Finally, crew-
members of both sexes have occasionally experienced diffi-
culty initiating urine flow while on orbit, and the only cases
of urinary retention requiring the use of a catheter have been
in women.
R.T. Jennings and E.S. Baker
Pregnancy After Space Flight
The vast majority of female finalists for astronaut candidate
selection have not borne children. During the 5 astronaut selec-
tion cycles between 1989 and 1997, 99 female finalist can-
didates were examined. Only 18 of the 99 had given birth, and
the total number of living children among this 18 was 24. As
alluded to earlier in this chapter, the delay in childbearing is
often the result of educational and career objectives that involve
decisions about both marriage and children. Because of the
constraints on training that pregnancy causes, many female
astronauts prefer to delay their first pregnancy until after they
complete 1 or 2 space flights. This decision, not surprisingly,
has led to deliveries at relatively advanced maternal ages. The
average maternal age at the time of delivery for the 15 children
born to 13 U.S. female astronauts after flight is 41 years. The
mean maternal age of the 12 postflight pregnancies that ended
in spontaneous abortion is also 41 years.
Because of the relatively advanced maternal age of female
astronauts, there has been considerable need for infertility
services and assisted reproductive technology (ART). The
incidence of benign gynecologic disease also increases with
age. The success rates for ART in female astronauts have been
low but in keeping with those of other ART patients of simi-
lar age. The number of astronauts attempting ART is still too
small to allow any further conclusions to be drawn except to
state that the poor per-cycle fecundability is probably related
to age rather than space flight.
Considerations for Long-Duration
Space Flights
Endometriosis
The role that gravity plays in menstrual efflux is unknown, but
considerable concern has been expressed about the potential
risk of retrograde menstruation and the risk of endometriosis
associated with radiation exposure. Many studies over the last
half century have linked endometriosis to the peritoneal depo-
sition of menstrual products [710]. However, debrief reports
from the Space Shuttle Program have shown no evidence that
women who menstruate in space flight have any increase in
shoulder pain, abdominal symptoms, or reduction in their
normal menstrual flow pattern that might suggest retrograde
endometriosis.
Long-term follow-up of rhesus monkeys that were exposed
to high-dose single-energy protons, mixed-energy protons,
x rays, and electrons has shown increased rates of endome-
triosis over the subsequent 2 decades as compared with
controls. Most of the monkeys that developed endometriosis
had massive disease, and increased mortality in individual
monkeys was experienced before advanced diagnostic tech-
niques were available [1115]. Recent studies have associ-
ated endometriosis with abnormal immune function, and this
18. Gynecologic and Reproductive Concerns
could partly explain the increased risk of endometriosis after
radiation exposure. Immune function seems to be depressed
during space flight. The combination of radiation exposure,
decreased immune function, and tendency to nulliparity in
many female astronauts could theoretically place these astro-
nauts at increased risk of developing endometriosis [1618].
Human endometriosis is a benign condition that is medi-
cally manageable, and thus endometriosis would not be
expected to develop rapidly or to cause sudden incapacita-
tion. Exceptions to this would be the sudden rupture of a large
endometrioma or bowel-related complications. With appro-
priate intervention, however, it is unlikely that endometriosis
that develops on a long-duration mission would interfere with
duties. Should endometriosis develop in a female crewmember
during a long-duration mission, many nonsurgical treatment
options are currently available to treat the condition. These
treatment options include prescribing oral contraceptives,
progesterone analogs, danacrine, and depot gonadatropin-
releasing hormone (GnRH) agonists, perhaps combined with
low-dose estrogen/progesterone addback.
Menstrual Cycling
Because the longest Space Shuttle flights have been only
18 days, no studies of the effects of microgravity on menstrual
cycling in female astronauts have been possible because the
menstrual cycle is typically 28 days. Only 4 women had par-
ticipated in long-duration space flights when this chapter was
written (1 U.S. astronaut [Shannon Lucid] and 1 Russian
cosmonaut [Elena Kondakova] flew on the Russian space sta-
tion Mir, and two U.S. astronauts [Susan Helms and Peggy
Whitson] flew on board the ISS). These missions were about
6 months in duration. The ISS, however, offers the opportu-
nity to collect data from a cohort large enough to overcome
privacy concerns. For a variety of reasons (discussed in the
section on Prevention, Diagnosis, and Treatment), however,
many female astronauts prefer to continue taking hormonal
contraceptives while on orbit; therefore, accumulating infor-
mation on spontaneous menstrual cycles in space is expected
to require several years.
Reproductive Function and Osteoporosis Risk
Loss of bone calcium associated with space flight is a major
concern. Experience accrued from the Skylab, Shuttle-Mir,
and ISS programs has shown that bone density is lost at a rate
of about 1% per month, despite the use of existing physical
countermeasures. Whether the loss will continue at this rate
during longer exposure to microgravity is uncertain. Post-
menopausal women have a greater risk of developing clinically
significant osteoporosis than do men. Although osteoporosis
is more common in women of certain ages on Earth, no space-
flight findings yet suggest that women of astronaut age are
at greater risk of microgravity-related bone calcium loss than
are men.
385
Bone density in premenopausal women normally increases
until the fourth decade of their life. Once a woman enters
menopause, accelerated loss occurs unless estrogen is replaced
exogenously [2024] or bisphosphonates are employed.
NASA recommends that hormone replacement therapy (spe-
cifically estrogen therapy) be used during long-duration space
flights in postmenopausal female astronauts. Studies are ongoing
regarding bisphosphonates for space flight.
In addition to receiving adequate estrogen therapy and
resistive exercise, consumption of calcium and vitamin D
are also important in maintaining bone density. A lingering
concern has been expressed that the strenuous exercise pre-
scription necessary to prevent bone loss, muscle atrophy, and
cardiovascular deconditioning in microgravity would result
in anovulation, hypoestrogenemia, and accelerated bone loss
in younger female astronauts [2537]. Many factors are asso-
ciated with this increased risk, including baseline hormonal
functioning, nutritional status, body mass, stress, preflight
fitness level, and duration, type, and intensity of the required
exercise.
The risks of anovulation, reduction in estrogen levels, loss
of calcium, and increased incidence of fractures are well doc-
umented in women who have trained extensively for activities
such as distance running or ballet. These risks are increased
for individuals with nutritional deficiencies. Impact exercise,
such as running, and resistive exercise may reduce calcium
loss in hypoestrogenemic women as compared with other
exercise programs, but hypoestrogenemic runners are still at
increased risk of fractures. Female astronauts in this category
who may be at increased risk can be identified before flight
so that appropriate countermeasures are initiated early in
training.
The neurovestibular problems seen in astronauts after land-
ing are manifested in part by gait abnormalities and motor
coordination difficulties. These problems increase the risk of
falls and fractures because of the astronauts reduced bone
density. To address this issue, NASA has established a vig-
orous, well-supervised rehabilitation program for astronauts
returning from long-duration space flight. This program is
designed to accelerate the recovery of functional capabilities
and to return crewmembers to baseline while minimizing the
risk of injury. For female astronauts, the use of oral contra-
ceptives, impact exercise, resistive exercise, and hormone
replacement therapy is expected to mitigate most of this risk
[3841]. Studies of selective estrogen receptor modulators,
calcitonin, and bisphosphonates such as alendronate are war-
ranted to determine whether bone mass can be maintained as
well with these or other compounds [42,43]. Selective estrogen
receptor modulators may also offer the opportunity to reduce
the risk of female crewmembers developing breast cancer
while on long-duration missions, although only tamoxiphen is
currently indicated for breast cancer prophylaxis.
Similarly, other pharmaceutical agents offer a medical
backup should any crewmember be unable to perform appro-
priate exercise countermeasures because of injury, hardware
386
failure, or spacecraft environmental constraints. Even on
short-duration Space Shuttle flights and on longer-duration
Mir missions, constraints on performing exercise counter-
measures are not infrequent. The possibility of encountering
similar problems on an ISS or exploration-class missions is
even greater because of the longer duration of such missions.
Prevention, Diagnosis, and Treatment
Preventive Concepts
Long-duration flights aboard the ISS or to the Moon or Mars
present special problems because these missions will be much
longer than those experienced previously, and ready return to
Earth may not be possible. A mission to Mars will last ~3
years. In addition to the time required away from Earth, the
gravitational force experienced by crewmembers during tran-
sit and on the planet surface will vary. Transit will most likely
take place at microgravity, whereas the force on the planet
surface will be 38% of the gravitational force on Earth [44].
Gravitational force on the Moon is one-sixth that on Earth,
and the ISS will be at microgravity. The radiation exposure
rate will be highest during transit to Mars, since the surface
of Mars offers some radiation protection from galactic cosmic
radiation and solar particle events because of its radiation-
blocking mass and CO2 atmosphere.
From a gynecologic perspective, several concepts will
be important for women on any of these long-duration mis-
sions. Concepts that also apply to male crewmembers include
prevention of illness, conversion of surgical conditions to
medically treatable conditions, and provision of surgical
capability. Preventing pregnancy will be imperative during
both the preflight and in-flight periods. The potential difficul-
ties associated with pregnancy in space flight have been well
documented [4547], but for all practical purposes, the radia-
tion dosage expected for a Mars mission will exceed 0.5 Sv
(50 rem) per year, and the yearly radiation dose expected on
the ISS is 0.25 to 0.4 Sv (25 to 40 rem). The National Council
on Radiation Protection and Measurements recommends that
the total radiation dose to which pregnant women are exposed
should not exceed 0.005 Sv (0.5 rem) [48]. The International
Council on Radiation Protection pregnancy limit is 0.002 Sv
(0.2 rem). Exposures over 0.1 Sv (10 rem) may be associated
with microcephaly and mental retardation [4954]. In addi-
tion, the risk of toxic chemical exposure, reduced atmospheric
pressure, altered breathing gas concentrations, and possible
microgravity effect on early embryogenesis associated with
normal and contingency operations preclude planned
pregnancies. These factors thus make pregnancies during
space flight very ill-advised at this stage of the program.
Several animal reproduction studies have been conducted
in microgravity; a few have been done on the Space Shuttle
[5559]. Although some of the problems noted in these stud-
ies may relate to factors such as launch vibration or experi-
R.T. Jennings and E.S. Baker
mental conditions rather than microgravity, several of these
problems have raised concern about species-specific problems
with early embryogenesis. At some time in the future and after
extensive animal studies have been conducted, it may be pos-
sible to consider space-based human pregnanciesprovided,
of course, that adequate radiation shielding is established on
the lunar or Martian surface, both for the pregnant woman and
later for the growing child. Until the risks of pregnancy are
more fully understood and we are able to deliver appropriate,
fully implemented care, the prevention of unintended preg-
nancies in space flight will remain a more important focus.
Any prevention program for long-duration space flights
begins with selection standards and administering care on
Earth. Each astronaut is examined annually with emphasis
placed on prevention of illness. This examination includes
a physical, extensive blood analysis, periodic exercise toler-
ance tests, mammography or breast MRI, colonoscopy, and
bone density analysis. Great attention is given to appraisal of
health risks, lifestyle counseling, and early medical interven-
tion as indicated. For crews assigned to exploration-class mis-
sions, the flight-specific examinations will be much more
thorough and spaced appropriately for the mission profile.
Women will most likely be screened by using abdominal and
pelvic sonography so that any abnormalities can be addressed
early in the pre-launch timeline. Additional screening for
renal stones and coronary artery disease is also likely to
be done with crewmembers destined for long-duration
space flight.
Many Earth-based prevention concepts are appropriate for
gynecologic care for women in space flight. As is true on
Earth, the noncontraceptive benefits of oral contraceptives
can be helpful; such benefits include reduction in menses and
menses-related hygiene requirements, dysmenorrhea, mit-
telschmerz, and benign breast problems. The reduction in
menstrual efflux may help minimize the loss of red blood cell
mass and blood volume associated with space flight (typically
about 10%). Women may take low-dose oral contraceptives
in a continuous fashion and reduce the frequency of menses
to 3 or 4 times per year. This practice provides significant
benefit for several reasons, since women who are taking oral
contraceptives are less likely to form ovarian cysts that could
undergo torsion and are also less likely to experience other
surgical conditions such as corpora hemorrhagica, upper geni-
tal tract abscess, or endometriosis. Oral contraceptives provide
an effective way to manage dysfunctional bleeding and reduce
the chance of either endometrial hyperplasia or menorrhagia.
Finally, birth control pills also reduce the risk of ovarian can-
cer by 50%.
Women who have completed their families can consider
undergoing endometrial ablation before prolonged space
flight. This evolving technology offers several office-based
methods of safely ablating the endometrium with intra-
uterine therapy. Endometrial ablation provides several
advantages over hysterectomy, including reduced risk of
postoperative adhesions and subsequent bowel obstruction
18. Gynecologic and Reproductive Concerns
during flight. Finally, even though formation of a few
adhesions is likely, elective laparoscopic appendectomies
for both male and female astronauts may be indicated
before prolonged lunar or Mars missions.
The level of radiation exposure occasioned by a space flight
to Mars poses a dilemma for astronauts who might later choose
to produce children. Space flight involves exposure to galactic
cosmic radiation, solar particle radiation, trapped radiation,
and secondary radiation produced when high-energy particles
are stopped by shielding material. Thus during spaceflight,
crews are exposed to a combination of protons (charged H2
nuclei), alpha particles (charged He nuclei), neutrons, high
linear energy transfer particles, gamma rays, and x rays, the
effects of which on humans have not been modeled completely
on Earth. The risk of acute gamete genetic damage is probably
not overwhelming for women, and it is less likely than the risk
for men because of the constant and relatively rapid division
rate of spermatogonia. Additional information on the effects
of radiation exposure is given in Chapter 23.
Many questions remain about the long-term reproductive
impact for individuals of either sex. Women who would like
to become pregnant after a prolonged trip to the Moon or Mars
will probably be offered the opportunity for preflight stimu-
lation of ovarian cycles and cryopreservation of embryos,
oocytes, or ovarian tissue. Since the success of ART, the rate
of spontaneous abortion, and the rate of genetic defects in
embryos depend considerably on the age of the female gam-
ete at the time the embryos are collected, fecundability should
be enhanced by cryopreservation of embryos in women who
elect to delay pregnancy while their natural fertility potential
is declining. Hopefully, cryopreservation of ova or ovarian
tissue will advance to the point that women can preserve their
gametes for future fertilization and transfer. However, when
this chapter was written, the success rate for thawing multi-
cell embryos is much better than that for thawing single-cell
oocytes. Of course some of this discussion is moot, because
many female crewmembers will either have completed their
families or will not want to experience future pregnancies.
Avoiding Surgery on Long-Duration Space Flights
Another important issue for long-duration space flight is the
need to convert surgical conditions into medically treatable
conditions, or at least mitigating surgical conditions so that
they can be treated later after a return to Earth. For women, an
excellent example of this is the successful treatment of early
ectopic pregnancies with methotrexate.
Previously, ectopic pregnancy was considered a surgical
emergency; but with early diagnosis and medical therapy
with methotrexate, many ectopic pregnancies can be man-
aged medically on an outpatient basis. Another such therapy
that is now available includes the use of GnRH agonists with
estrogen/progesterone addback for leiomyomata uteri, endo-
metriosis, adenomyosis, or dysfunctional uterine bleeding. In
gynecologic practice, GnRH agonists have in the short term
387
helped to reduce menorrhagia and uterine size, to convert
cases requiring abdominal surgery into those in which vaginal
procedures can be performed instead, and to increase hema-
tocrit levels before surgery. For certain cases of menorrhagia
that are resistant to hormonal management, placing a Foley
catheter with a 30-ml balloon in the endometrial cavity could
obviate dilation and curettage.
In space flight, these and other options will be available
to treat individuals or to delay definitive surgical procedures
until a crewmember is returned to Earth. We believe that the
development of alternative treatment methods for diagnos-
ing and managing gynecological and other potential surgical
problems should continue. We also hope that additional inno-
vative treatment modalities that incorporate planned on-board
medical equipment and supplies can be developed.
Diagnostic, Surgical, and Distant-Care Capabilities
To date, no human beings have undergone surgery in space, but
human surgical procedures have been accomplished during zero
gravity parabolas in aircraft. Even with the use of preventive mea-
sures and minimizing the need for surgery, enabling technology
will need to be developed for microgravity and reduced-gravity
surgical intervention. Projections from analog environments with
equally fit individuals who were isolated for 2 to 3 years suggest
that surgery will not be required often in a crew of 4 to 8 healthy
young astronauts. Nevertheless, trauma is a real risk in space
flight, and minimally invasive surgery such as laparoscopy will
be an important adjunct to abdominal sonography and laboratory
analysis to manage severe blunt trauma in space [6063]. Sonog-
raphy and digital x ray are expected to be the principal modes
of diagnostic imaging on a Mars mission or a lunar base, and
it is imperative that we understand the effect that microgravity
has on both normal and abnormal physical findings. In addition,
the selection and training of crewmembers, including training in
medical treatment, will be an integral part of the treatment options
available for exploration-class missions.
Microgravity surgical techniques are already under devel-
opment, and several procedures have been conducted during
parabolic flights on aircraft. Laparoscopy, laparotomy, thora-
coscopy, advanced cardiac life support, advanced trauma life
support, sonographic diagnostic imaging and percutaneous
bladder puncture, and telemedicine procedures have all been
accomplished in animal models during the repeated 20- to 25-s
parabolas provided in the NASA Reduced Gravity Program
[6472]. Additional surgical experience was obtained on the
Neurolab mission, flown on STS-90 in April and May 1998,
which included performing the first on-orbit surgical procedure
that the animals survived postoperatively.
Use of zero gravity aircraft fosters the logical, stepwise
development of surgical techniques for microgravity. The
steps involved have included studying restraint systems,
sterile technique, and fluid and blood control and performing
laparotomy, laparoscopy, and thoracoscopy in animal models.
During the development period, surgical isolation systems,
388
surgical overhead canopies, restraint systems for both patients
and surgeons, and techniques for scrubbing, gowning, glov-
ing, and draping were tested. Results of these studies have
been reassuring. Capillary and venous bleeding can be
controlled by using local measures, and arterial bleeding may
be associated with projectile dispersion of blood droplets. The
canopies have been helpful with containing arterial bleed-
ing, and we have found that direct pressure with an absorbent
sponge can change a projectile arterial bleeder into a dome of
blood. Since most bleeding areas form domes or coat body
surfaces because of surface tension, blood or fluid is not
usually released into the cabin atmosphere; however, these
blood domes must be removed periodically to allow appropri-
ate operative exposure. The zero gravity flights have demon-
strated that traditional suction devices are not successful, and
that dispersed blood droplets will occasionally form fragments,
providing potential atmospheric contamination. Loose-weave
sponges have been found to work better for blotting than tight-
weave sponges, and sponges should be applied gently to avoid
fracturing or propelling droplets.
Laparotomy has been accomplished on experimental ani-
mals without difficulty on the KC-135E. Although experi-
menters had no problem returning the abdominal contents
to the abdomen, care was required in entering the peritoneal
cavity since the intestines do not fall away from the incision
when the tented peritoneum is entered. Laparoscopy has been
performed repeatedly on porcine models on the KC-135E and
DC-9; this procedure has produced favorable results in micro-
gravity as compared with the same procedure at 1 gravity. Sur-
gical balloon devices for creating operative abdominal space
were used successfully during the KC-135E series, but the
initial success with traditional laparoscopy made the balloon
devices less desirable. However, in the KC-135E studies, a
pneumoperitoneum was established at 1 gravity before flight.
The initial pneumoperitoneum could be difficult to establish
in microgravity, and an open technique of laparoscopy could
be required. Direct trocar insertion is unlikely to be an accept-
able surgical technique in microgravity because of the lack
of gravitational separation of the viscera from the abdominal
wall at the trocar insertion site.
With the current experience base, it seems that laparoscopy
for treatment of in-flight surgical intra-abdominal conditions
and gynecologic problems in women offers many advan-
tages, e.g., reduced requirement for anesthesia, containment
of blood, debris, and fluids, and the use of minimally inva-
sive surgical techniques. Laparoscopy also minimizes the
size of the exposed incision and should lead to faster surgical
recovery, a reduced chance of infected wounds, reduced need
for analgesics, and reduced short-term disability. Incisional
length and duration of exposure may be important factors in
microgravity, where airborne particulate size and number are
greatly increased over those encountered at 1 gravity. Video
downlink available with laparoscopy provides the advantage
of either real-time or store and forward second opinions from
Earth-based consultants. Eventually, laparoscopy in low Earth
orbit on the ISS or on a lunar base may be possible through the
R.T. Jennings and E.S. Baker
use of surgical telerobotics. However, the potential 1-way time
delay of more than 20 min for a transmission to reach Mars
will present a problem for real-time consultation and render
telerobotic procedures unusable. Crew medical officers for
exploration-class missions may not be physicians, and thus
they must be trained to provide medical care independently of
the ground and to use consultation services.
Although considerable work lies ahead to develop laparos-
copy as an enabling medical treatment technology for human
space flight, early animal data suggest that laparoscopy will
be a practical and effective way to approach surgical-gyne-
cologic and other abdominal abnormalities. Moreover, con-
tinued development of smaller equipment with improved
multifunctional capabilities and the potential for Earth-based
experts to direct less-capable care providers makes endoscopy
an ideal option for surgical care of gynecologic problems in
space flight.
Conclusions
The possibility of long-duration missions aboard the ISS and
exploration-class missions to the Moon and Mars makes this
potentially an even more challenging and exciting phase for
space medicine than the past 46 years. Although space flight
was initially seen to be a male preserve, women soon became
involved integrally and have performed well.
The medical data collected to date regarding women in
space flight have been very reassuring. No medical or gyneco-
logic problems have developed that cannot be addressed with
current or planned intervention capabilities. Nevertheless, it is
safe to assume that innovative and independent medical care
capability will be required for exploration-class missions.
Moreover, diagnostic, therapeutic, telemedicine, and robotic
capabilities as well as crew training in the use of these capa-
bilities will need to be enhanced for long-duration missions.
Thus, there is a need to further develop and refine preven-
tive measures and microgravity physiological countermea-
sures and to enable medical and surgical technologies. Mission
success will require assurance that female crewmembers who
develop medical, surgical, or gynecologic conditions can be
successfully treated. With appropriate attention to planning,
it is unlikely that medical problems will impede the participa-
tion of women in the exploration of space.
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19
Behavioral Health and Performance Support
Christopher F. Flynn
This chapter reviews the stressors and countermeasures that affect
crew behavioral health and performance during space flight. This
review is based on the experiences of crewed space flight in both
the Russian and U.S. programs, including Space Shuttle flights
lasting from 1 to 3 weeks, Mir space station flights lasting longer
than 1 year, and findings from analog environments that are simi-
lar in terms of isolation and other features to the in-flight envi-
ronments on the Space Shuttle and on the Mir and International
Space Stations (ISS).
Significant physical and psychosocial stressors challenge
crews during mission training, space flight, and mission recov-
ery. In fact, at least one crew has been dissolved before a long-
duration flight because of incompatibility [1]. Severe stress
experienced by crews during Mir and NASA-Mir flights prob-
ably contributed to mission-limiting cardiac dysrhythmias and
the appearance of emotional symptoms among crewmembers
[2,3]. Fatigue and overwork conditions have also affected long-
duration crews. Journalists have identified these conditions as
important factors contributing to the depressurization accident
on the Mir space station in 1997 [4]. Psychological stressors
known to have affected long-duration crews include the death
of a family member; significant interpersonal frictions, both
between crewmembers and between space crews and ground
crews; overwork and underwork; and life-threatening near-
evacuation events on board a spacecraft, which to date have
included fire, depressurization, and loss of power. Although
Russian space mission aborts were officially related to diag-
noses of intractable headaches, chronic prostatitis, and cardiac
dysrhythmias, behavioral conditions were equally important
in the early termination of these missions [5,6].
Both flight surgeons and crewmembers must be aware of
these stressors and the countermeasures that need to be taken
to maintain the behavioral health and mission performance of
a crew. This chapter offers space medicine clinicians a focused
approach to the known risks to behavioral health and perfor-
mance by focusing primarily on the long-duration mission. An
overview of likely problems with behavioral health (both psy-
chiatric and psychological) and performance of long-duration
crews is also provided, as is an outline of potentially helpful
countermeasures. Operational medicine experts who have
reviewed pertinent space analog and spaceflight data agree
that behavioral problems are one of the most significant influ-
ences on mission success [5,7]. After such a disorder has been
identified, it must be aggressively treated to prevent the dete-
rioration of crew health and mission performance.
Maintaining Crew Performance
and Behavioral Health
Role of the Flight Surgeon
The relationship between flight surgeons and their crews is crit-
ical for addressing spaceflight factors that will affect crew per-
formance. The great reluctance of professional aviators to being
considered in less-than-optimal condition is a widely accepted
psychological finding [811]. Professional aviators, astronauts,
and cosmonauts generally are extremely self-sufficient, hard-
working, and success driven [1214]. Although these traits are
of tremendous benefit to a crew that must complete its mission
objectives under adverse conditions, the downside is the aver-
sion of individual crewmembers to reporting any perceived
illness. Indeed, crewmembers are likely to consider an
admission of task saturation, over-fatigue, excessive stress, or
concentration-impairing clinical depression as a personal fail-
ure. Rather than reporting these conditions to get help in deal-
ing with them, it is far likelier that a crewmember will try to
remain stoic about them, thereby retreating from appropriate
help. The dilemma for flight surgeons is that they will not be
able to help without first receiving the crewmembers report.
This is especially unfortunate because aggressive intervention
is likely to produce a good outcome [1519].
Thus flight surgeons must be prepared to listen to a crew-
members report of distress in a manner markedly different
from the way in which physicians would normally listen to
a patients report. Humans display psychological distress by
speaking about it, when they are more self-aware, or by dem-
onstrating distress through a change in behavior, when they
391
392
are less self-aware. Sometimes they use both methods [20].
For this reason, flight surgeons should pay close attention to
both obvious and subtle characteristics of an interaction with a
crewmember, because flight crewmembers can be so success-
ful at compartmentalizing (i.e., denying the existence of)
emotionally distracting thoughts and feelings that sometimes
they may not be fully aware of their own significant level of
stress.
The wise flight surgeon would not ignore even an indirect
hint of difficulties from a crewmember. However, this does
not mean that the flight surgeon should aggressively ques-
tion a crewmember, for aggressive questioning can generate
a strong defensive reaction against prying. [17,21] Instead,
flight surgeons should encourage further discussion. They
should leave the door open to more visits and attempt to get a
better understanding of the crewmembers concerns, pay more
attention to how that crewmember is doing at work and at rest,
consult with a behavioral specialist when available and, when
data are supportive of a conclusion, share this information
with the crewmember and propose a solution. Astronauts, cos-
monauts, and aviators all have a tremendous advantage over
the general population in terms of correcting their behavioral
health problems owing to their overall intelligence, adapt-
ability, and problem-solving skills. Once a problem has been
clearly identified by such individuals, it is highly likely that
the problem will be corrected. One good example is the well-
documented treatment and occupational recovery of aviators
treated for alcoholism [15,18,19].
The worst-case scenario is a crewmember who is reacting
to emotional distress who does not seek help and is demon-
strating a negative change in personality and behavior. Such
a crewmember may well act out in excessive, perhaps risk-
seeking behaviors, as if needing to prove something, and has
temporarily lost the ability to exercise good judgment. When
questioned about it, the crewmember will deny any significant
stressor, although collateral history will confirm the appear-
ance of new behaviors that are the equivalent of a flashing neon
sign giving warning. Aptly termed a failing aviator, such
an individual is not going to go quietly. [22] Unfortunately,
despite the need for help, this crewmember will typically push
away those who wish to help until a powerful person in the
crewmembers life forces a change. This powerful person may
be a supervisor, a spouse, a pastorsomeone who will put a
limit on destructive behaviors and demand intervention.
In light of the physical and emotional demands of space
flight, crew health will suffer unless flight surgeons can work
successfully with all members of the crew to which he or she
has been assigned. If a flight surgeon has been able to earn the
trust of a crew and their close family members before flight,
he or she can develop a partnership with that crew that encour-
ages problem identification and problem solving. By using a
supportive relationship, flight surgeons can learn about each
crewmembers usual response to stress as well as their typical
coping skills. When stress begins to build later, the observant
flight surgeon can identify changes in behavior early, without
C.F. Flynn
talking about stress, and can help redirect crewmembers to
resume their typical coping measures. To maintain the well-
being of a crew, flight surgeons must be aware of the physical
and behavioral stressors of space flight and be able to build a
supportive, trusting relationship with each crewmember.
Role of the Family
Regardless of a crewmembers self-sufficiency, family stabil-
ity is understood to be a very important stress-coping factor
in health and a significant factor in flight safety [2326]. The
pressures of space flight can strain even the best of family
relationships, especially when preflight training deployments
may take a crewmember away from home for as much as half
the year. Deployments such as these are typically followed by
total separation during a 4- to 6-month flight. Upon return to
Earth, the crewmembers expectant family, which has survived
its own stresses and strains during the mission, welcomes
home a physically limited and emotionally exhausted person,
which creates an additional burden on the family. Flight sur-
geons must consider the stability of a family relationship when
assessing an astronauts or cosmonauts preparation for a 4- to
6-month mission. Key issues to consider include an imminent
divorce, an overwhelmed and angry spouse, a severely ill
child, and the familys and crewmembers response to con-
tinued separation. In these situations, talking to a behavioral
health consultant to identify mission risk would be advanta-
geous to the flight surgeon.
Role of the Mission
The isolated and confined environment of space flight, com-
bined with the intensity of small-team operations, creates an
environment that has its own unique and powerful stressors.
The timeline of a short-duration mission keeps a crew sched-
uled to the minute, with a demanding and sometimes impossi-
ble workload. Even when interpersonal friction exists between
crewmembers, time passes quickly because of the brief time
spent on orbit and the high workload. Although the pressure
to complete all tasks before return can greatly affect time for
sleep and exercise, the shorter training time before flight and
the brief physiologic recovery time after landing are relative
advantages for short-duration crews.
Long-duration crewmembers, on the other hand, typically
experience 1848 months of preflight training. Although this
training takes place on Earth and typical coping techniques
can be used, these crewmembers are often separated from
their families and from other culturally familiar means of
relaxation. Stress begins to build. Unless this stress is reduced,
long-duration crewmembers will carry it on their rigorous and
demanding missions. Once in orbit, crewmembers are iso-
lated from their typical coping mechanisms, confined with
their crewmates, and facing the inevitable physical deterio-
ration from microgravity. On landing day, when relief might
be expected, they face a legion of doctors and scientists who
19. Behavioral Health and Performance Support
poke, prod, inject, collect, and analyze them before they can
really be considered as having returned from space flight.
Approach to Maintaining Performance
Flight surgeons must understand the behavioral problems that
limit crew performance. At NASAs Johnson Space Center,
attention is focused on four key elements that support crew
behavioral health and performance support. This approach is
built from a simple model in which performance is defined
as a two-step processto think and to act. According to
this model, crews first assimilate information cognitively
and decide on a course of action based on previous training,
current situational awareness, and anticipated threats to the
mission (think). The crews must subsequently have the moti-
vation, sense of purpose, and physical strength and coordina-
tion to carry out the course of action (act).
When performance is considered from the behavioral per-
spective, several basic elements contribute to the ability to
think and to act: sleep and circadian physiology; behavioral
health; psychological adaptation; and the human-system
interface in the on-orbit workplace. Sleep deficit and circa-
dian troughs (periods in which alertness and concentration
are at their nadir) significantly affect clarity of thought and
psychomotor aptitude; these constitute issues of sleep and
circadian health [2733]. A healthy individual has a brain that
is neither injured nor exposed to toxins and is not experiencing
psychiatric illness (behavioral health). When this person is
isolated from family and the usual coping skills, confinement
and small-team operations require the use of countermeasures
to maintain that persons motivation to perform (psychologi-
cal adaptation). These countermeasures are important in an
environment where improper work schedules may not allow
sufficient time for completing assigned work, where inap-
propriate task sequencing may hinder efficient completion of
those tasks, where poor workplace design and environmental
conditions may sap motivation, and where inadequate tools
with which to maintain mission-critical skills throughout
flight may be provided, thereby limiting effectiveness (human-
systems interface issues).
These four elements are closely interrelated. For example,
inadequate sleep and circadian desynchrony (jet lag) can
affect an individuals concentration and mood. Depression
decreases motivation. In the confined spaceflight environ-
ment, small-team operations must adapt accordingly; team-
work can help accomplish tasks more efficiently, decrease
workload, and improve motivation. An overbooked work
schedule will lead to extension of the working hours, which
in turn creates sleep loss. Thus flight surgeons should con-
sider each of these four elementspsychological adaptation,
sleep and circadian rhythms, human-to-system interfaces, and
behavioral healthin enabling crew performance to be
maintained. Each element is described in further detail in the
following section.
393
Expected Behavioral Problems Arising
from Space Missions
Psychological Adaptation Problems
Problems with psychosocial adaptation cause deterioration
in crew cohesion and crewmember motivation. Such dete-
rioration has been identified in both space analog studies
(e.g., polar teams, submarine crews, and aviation operations)
and observations of space flight crews, especially from the
Russian cosmonaut medical care system. Important preflight
stressors that can affect crews include family separation and
cultural misunderstandings [2] as well as the risk of injury
during rigorous physical activities, particularly survival train-
ing or extravehicular-activity training that could prevent a
crewmember from being certified for flight. After flight, the
crews readaptation to family living and the demands of the
workplace requires significant awareness and effort.
International space crews may encounter cultural differ-
ences in leadership style, communication, preflight train-
ing, identification of in-flight mission success criteria, and
postflight differences in schedules, all of which may lead to
friction [34]. Cultural differences in the workplace have the
potential for producing nearly constant friction or irritation in
interpersonal interactions that can break down team commu-
nication and coordination [35]. Despite the best intentions of
crewmembers, unless cultural differences are recognized and
accounted for during mission preparation, such differences have a
high likelihood of negatively affecting mission success [3538].
In one analog study in which measurements of stress were begun
before the mission, scores did not drop significantly between
preflight training and the first highly stressful weeks of the
mission. This finding suggests that preflight stress is signifi-
cant and must be managed to prevent launching an already
exhausted crew [36].
Once a mission is under way, stress to the crew arises from
isolation from the usual coping mechanisms, confinement,
dependence on a very small team of colleagues for emotional
and work support, physical deterioration, and increased reli-
ance upon distant assistance or management teams, which
limits personal autonomy. If not properly addressed, the stress
on crewmembers, individually and as a group, can affect the
beginning, the midpoint, or the [third] quarter of the mis-
sion [3,3943]. Studies of stress experienced by isolated
teams in space analog settings suggest that a range of com-
mon psychological adaptation complaints can flare at these
times, including mild cognitive impairment, disturbances in
time sense, motivational decline, sleep deprivation, psycho-
somatic symptoms, anger, anxiety, depression, social conflict,
and social withdrawal [42,4446]. An important distinction
to be made is that between symptoms and disorders.
Although teams preparing to winter over in Antarctica were
screened psychologically and psychiatrically before their mis-
sions, 12% still experienced significant psychological adap-
tation symptoms, and 3% developed full psychiatric disorders
394
[47]. In the U.S. experience during seven missions aboard the
Russian space station Mir, which lasted from 115 to 188 days,
only one astronaut reported experiencing significant in-flight
depressive symptoms, thus reflecting a similar 14% incidence
of problems [3].
Additional problems that commonly arise in isolated groups
include interpersonal tension, the development of subgroups,
and the tendency to restrict communication with distant sup-
port team personnel. If the group is multinational, subgroups
may form along national lines in response to the commander
or the external management. Isolation and confinement can
worsen subgroup friction [46,4850] and break down the sub-
groups further. Such breakdowns in crew cohesion have been
noted in space flight as well [1,38].
In summary, findings from both space analog settings and
spaceflight missions suggest that neither crewmember selec-
tion nor professionalism can prevent all of the problems that
arise from the psychosocial stressors experienced by space-
flight crews.
Sleep and Circadian Problems
Sleep deficit and circadian desynchrony occur in spaceflight
crews when excessive workloads break the work-rest cycle,
when emergencies interrupt normal sleep scheduling, and
when mission requirements (e.g., extravehicular and dock-
ing activities) are scheduled during normal sleep periods.
Events such as these can occur before, during, and after flight.
Sleep and circadian stressors begin with the preflight training
deployments that result in jet lag. Key problems associated
with this are reduced ability to concentrate and changes in
mood. In the course of landing, crews may return to a land-
ing site that is not operating at on-orbit time; moreover, they
may experience desynchrony again during a transoceanic
flight home. Changes in the physiology of sleep are similar
in spaceflight crews and in polar winter-over teams, as both
environments involve loss of normal day - night cues. In a
study of teams wintering over in Antarctica, subjects experi-
enced a complete absence of stage IV sleep and sizable reduc-
tions in the amounts of stage III and rapid eye movement sleep
[51]. Occasional use of sleep encephalographic recordings to
document changes in sleep physiology in spaceflight crews
has produced inconsistent findings. For example, a dramatic
lessening of delta sleep (stages III and IV) was noted in one
study but not in another, and rapid eye movement latency was
found to have shortened more in one study than in another.
However, other more consistent findings have been minimal
circadian phase disruption and that, at present, the factors
that reduce adequate sleep on orbit are workload, the effect of
microgravity, and the discomforts of the spaceflight environ-
ment [52 54].
Because of work demands, an average nights sleep for a
spaceflight crewmember, regardless of the duration of the mis-
sion, is slightly more than 6 h [55,56]. Flight surgeons therefore
should recognize that moderate performance decrements and
C.F. Flynn
increased sleepiness have been noted in air traffic controllers
(work that involves cognitive skills) after restriction to 5 h or
less of sleep. Performance and levels of alertness are impaired
after as little as 2 h of an individuals normal sleep time is
lostand crewmembers normal sleep times are not measured
before flight in the U.S. space program. Tasks involving cog-
nition and vigilance are among the first to be affected when
the amount of sleep is suboptimal. Most critically, a tired indi-
vidual rarely recognizes that he or she has dozed off from
excessive fatigue [2733].
In brief, long- or short-duration spaceflight crews can be
expected to incur substantial risks to performance because
of expected problems with sleep deficit and circadian
desynchrony.
Human-to-System Interface Problems
This subsection outlines anticipated problems at the interface
between the crewmembers, their environment, and their work
schedules. This interface problem is made more complex by
individual variation in the response to the spaceflight environ-
ment, such as the duration of space motion sickness symp-
toms; the adaptation time needed to demonstrate effective
psychomotor skills in microgravity; the time needed to train,
retrain, and sharpen mission critical skills; personal work-
load limits; task saturation; the physical fit to workstations
and space suits; work relationships with ground management
teams; the time required for physical and emotional postflight
recovery; and variations between the crewmembers and the
space agencys definitions of what constitutes mission suc-
cess. Flight surgeons must remain alert to the ways in which a
crew can be affected by these factors in the operational envi-
ronment.
Since each crewmember has a unique way of learning
material before flight, crewmembers can benefit from indi-
vidualized preparation and retraining materials. This benefit
can translate into the mission itself where each crewmember,
although part of a group, is likely to feel isolated in the alien
atmosphere of space. Isolation negatively influences cognitive
capabilities and task performance. In a study of 16 people who
wintered over in an Antarctic station, expected improvements
in complex task skills and a prospective memory task did not
occur over the course of the mission [57,58]. Astronauts or
cosmonauts thus need to understand how to retain mission-
critical skills for long periods after their preflight training.
Since many months can elapse between preflight training and
completion of a task on orbit, the potential for in-flight error
must be prevented to maintain optimal performance.
Although work monotony creates stresses for the long-
duration crewmember, the extreme time pressure in a shorter
flight also creates stresses as well [42,46]. Nominally, sched-
uling limits the workday to fewer than 8.5 h; but with exercise,
meals, and hygiene activities, the workday easily stretches to
13 h. The history of crewed space flight suggests that despite
the best effort of flight activities managers, ground schedules
19. Behavioral Health and Performance Support
rarely reflect the on-orbit reality. This discrepancy is because
flight schedules, which are based on terrestrial work times, are
optimized before flight to fit as many operational tasks, proj-
ects, and experiments as possible into the crew schedulenot
to satisfy an individual crewmembers work limits, primarily
because schedulers expect that fully trained crewmembers
will be able to meet the operational expectations of the sched-
ule, and not the other way around.
On orbit, the reality is that equipment for planned use may
be difficult to locate, and equipment malfunctions can lengthen
the time needed to complete a task. Space motion sickness
can negatively affect a crewmembers efficiency, and contin-
gencies will disrupt timelines. Crew performance suffers as
workloads build and task saturation occurs, thus impairing
a crews attention to detail and increasing the risk of error
[42,43,50,59,60]. When time spent on a physically demand-
ing task extends past the scheduled time, physical overuse
injuries can result. Moreover, if a space agencys definition
of mission success requires completion of all scheduled tasks,
the crewmembers may face an impossible dilemmato con-
tinue to work with impaired performance or to reduce work
and risk mission success. Differences in expectations of work
completion have historically created tensions between ground
managers and mission crews, adding to stress levels and ham-
pering communications [39,48,61,62]. Poor performance by
the support team in their preflight, in-flight, and postflight
assistance to a mission crew can grind communications and
teamwork to a halt. This is not only a psychological issue, but
a workplace management issue as well.
After flight, a lack of individual fit to the work schedule
can lead to crew frustration and anger because many managers
and some crewmembers consider the end of the flight to be the
end of the mission. However, mission related tasks extend for
months and, for some life science experiments, years after the
end of the mission. This misconception that the crew is free
once the spacecraft has landed tends to push the individual
crewmember toward too early a reintegration into a space
agencys ground-based work responsibilities [34]. Despite
the fact that the crewmember has just returned to Earth, physi-
cally debilitated from microgravity and emotionally distanced
from family members, he or she begins to reorient to high
workload expectations that are more appropriate to individuals
who have never left Earth. Careful management and explicit
support is required for the crew to successfully counteract the
final mission problems of physical debilitation and emotional
distancing from the family. Flight surgeons must therefore be
strong advocates for crews to stay focused during this neces-
sary part of the mission, which in the Russian system lasts for
as long as 34 months after return to Earth.
Behavioral Health Problems
Behavioral health problems that affect performance include psy-
chiatric and cognitive disorders. Before, during, and after flight,
problems with psychological adaptation, the human-system
395
interface, and sleep or circadian stressors can, if sufficiently
severe, lead to disorders that require healthcare intervention.
Even without these stressors, the onset of a new behavioral ill-
ness in an astronaut or a cosmonaut is quite possible because
of the natural occurrence of these disorders. A review of polar
analog and submarine studies reveals that 14% of team mem-
bers developed frank psychiatric illness during 48-month
missions [47,63] despite careful psychiatric and psychological
screening at the time they were selected. This finding under-
scores the importance of selection in reducing the impact of
negative behavioral health events on the mission, even though
the selection process does not completely prevent the occur-
rence of such events.
Postflight readaptation is a significant stressor both for
crewmembers and for their families, because both are dealing
with the burdens of a mission that is continuing with postflight
medical data collection, mission debriefings, and public affairs
demands. Any family problems that were present before flight
will not have evaporated, and new problems will have been
experienced during the mission. Reconnecting between fam-
ily members is stressful. Studies of readaptation in military
families suggest that up to 5% of families developed signifi-
cant problems during the 3 months after return and that these
challenges may not lessen any sooner than that [2,6467].
Behavioral health problems noted in analog populations
have been primarily categorized as characterological (person-
ality disorder) or emotional (mood, thought, psychosomatic, or
anxiety disorders) [2,68]. In a review of 150 subjects participat-
ing in Soviet isolation experiments lasting from 7 to 365 days,
Gushin et al. reported apathy, anxiety, depression, illusions,
[and] hallucinations in subjects, although the report did not
mention whether full disorders were present or whether any
missions were terminated early because of these conditions
[42]. Similarly, in-flight neurophysiological changes effected
by microgravity have not been clearly characterized, although
neurotransmitter effects are suspected from documented alter-
ations in peripheral catecholamines and sleep [46,5256] and
from minor changes in cognition [42,58,6971]. Although
animal studies have demonstrated that stress-related neuronal
changes can develop from the effects of space flight, limita-
tions in on-orbit molecular-level study restrict the pertinence
of this finding in humans [72]. In fact, Russian physicians
believe that the cosmonauts are likely to develop asthenia,
a condition described as nervousness and mental weakness
manifesting as tiredness, quick loss of strength, low sensation
threshold, unstable mood, and sleep disturbance, [46] during
space missions that last 4 or more months [73]. Myasnikov
and Zamaletdinov have also described other expected states,
including euphoria, depression, neuroses, and accentuation of
negative personality changes [46]. Whether these states occur
simply as symptoms or as full behavioral health disorders is
unclear, but anecdotal reports suggest that behavioral health
problems have been severe enough to contribute to the early
return of three long-duration mission crews (Soyuz-21 in
1976, Soyuz-T14, in 1985, and Soyuz-TM2 in 1987) [6].
396 C.F. Flynn

Changes in cognition must also be considered a threat to Table 19.1. Ages at which new psychological disorders typically
on-orbit crew performance. Recognized risks for neurologic appeara.
or cognitive insults include exposure to toxic substances, trau- Ranking: Age range
matic head injuries, hypoxia, decompression, electrical inju- Disorder Men aged 2564 years Women aged 2564 years
ries, and adverse reactions to medication. Anecdotal findings Major Depression 1: 2529 2: 2529
on cognitive effects during long-duration missions suggest that 4: 3034 and 3539 4: 3034
crews have experienced time and space distortions, decreased 5: 3539
task performance over time, mental inertia, difficulty concen- Bipolar (manic 3: 2529 and 5559 2: 2529
trating, memory problems, and slowing of intellectual activi- depression)
4: 3539, 4549 and 3: 3034 and 3539
ties [74]. However, objective measures obtained in the 1990s 6064
have shown only minor, albeit consistent cognitive changes 4: 4549 and 5559
such as increased response time to testing, reduced accuracy Obsessive 1: 3539 3: 2529
of response, impaired performance on dual-task tracking, and Compulsive 2: 3034 4: 3034
changes in visual-spatial recognition capability [69,75,76]. 3: 2529 5: 5054
In one long-duration flight study, these alterations were more 4: 6064
5: 4044 and 5054
problematic in the first 1020 days of flight and did not persist Panic 1: 3034 1: 2529
afterward [69,70,77]. 2: 4044 2: 3034
Finally, flight surgeons must consider the risk of behavioral 4: 3539 4: 3539
illness based on the incidence of illness in the crewmembers 5: 2529 5: 4044
country of origin. For example, during any 1 year in the United Alcohol 3: 2529 3: 2529
Abuse/dependence 4: 3034 and 3539 4: 3034
States, at least 8% of men and 13% of women will experience
5: 4549 5: 3539
major depression [78], the third most frequent diagnosis in
a
The rankings shown are from life tables of individuals aged 2564 years, the
U.S. adults aged 2564 years [79]. International differences
age range typical of the U.S. astronaut corps.
must also be considered; for example, the annual rate of new Source: Data from Burke et al. [81].
cases of depression diagnosed in Taiwan is more than 3 times
less than that in the United States and more than 6 times less
than that in Alberta, Canada [80]. Nevertheless, major depres-
sion, manic depressive disorder, and obsessive-compulsive chological support group was not modeled after the Russian
disorder are highly likely to develop for the first time in North psychological support group, the specialties represented in
American and Western European individuals aged 2570 years the 2 groups are very similar; both groups focus on improv-
(Table 19.1) [81]. The need to remain vigilant for behavioral ing the changeable aspects of a crewmembers personal factors
illness after selection is underscored by findings that nearly and work environment, namely knowledge, experience, capa-
half of all waivers for psychiatric disorders for U.S. Naval avi- bilities, workload, work schedules, fatigue level, coping skills,
ators were requested for those who were older than 30 years mood, and motivation [82].
[16]; in another study, U.S. Air Force aviators who required Long-duration mission crews require psychosocial sup-
psychiatric hospitalization ranged in age from 30 to 45 years port to maintain motivation and coping capabilities. In this
[15]. Therefore, flight surgeons must recognize the continu- respect, preventive countermeasures problems that need to be
ing risk that a spaceflight crewmember may develop a new addressed include primarily selection, preflight training, and
psychiatric disorder, even when no such history is present. preflight/in-flight/postflight psychosocial support of crew-
members and their families.
Countermeasures I: Monitoring
and Prevention Strategies Monitoring
In the U.S. program, monitoring a crews adaptation to the
After recognizing the multiple stressors that can affect a crew, spaceflight environment is based largely on self-reports
a flight surgeon would be wise to enlist specialists to help in received from the crews. A crewmember can report a change
monitoring the behavioral health and performance of indi- in adaptation in several ways, e.g., through weekly sched-
vidual crewmembers to prevent any serious deterioration. At uled private medical conferences with the flight surgeon,
Johnson Space Center, the behavioral health and performance electronic correspondence, or twice-a-month scheduled
group that assists flight surgeons consists of individuals private psychological conferences with a representative of
skilled in aerospace psychology, occupational and industrial the behavioral health and performance group. The Russian
psychology, occupational and aviation psychiatry, clinical psy- spaceflight program includes an additional stepanalysis of
chology, and clinical psychiatry. This group also collaborates communication between ground and space crewsthat uses
closely with specialists in human factors, professional train- a psycholinguistic method to rate a cosmonauts adaptation
ing and development, and flight medicine. Although this psy- to space flight.
19. Behavioral Health and Performance Support
Prevention
Selecting-In
During selection of astronaut applicants in the U.S. space pro-
gram, the behavioral health and performance group works to
identify individuals who bring well-developed teamwork and
coping skills to the program (select-in), as well as to iden-
tify individuals who are at increased risk for behavioral illness
stemming from the spaceflight environment (select-out)
[12,25,8385]. Generally, although use of psychological tests
and specialist interviews is more similar than different among
International Space Station partners, some partners also rec-
ommend use of rigorous computerized simulation, confine-
ment in a test chamber, and field training exercises [39,8688]
in the evaluation process.
Training
After being selected, U.S. astronaut-candidates psychological
adaptation skills are sharpened through seminars and field
exercises that teach the candidates about the challenges of
isolation, confinement, cultural differences in team members,
psychological self-awareness and self-regulation, small-team
operations, leadership, and followership. [8590] Recom-
mended training includes having the astronaut-candidates
work in small groups of 26 individuals with experts who
have reviewed polar and spaceflight expeditions. Participation
in field exercises in difficult and isolated environments (e.g.,
winter and water survival training, confined-chamber train-
ing) give these men and women the chance to experience their
own reactions to challenging operations and offers them the
opportunity to develop better self-awareness of the more chal-
lenging aspects of these environments and to learn new coping
techniques or confirm the usefulness of seasoned coping tech-
niques. Teamwork skills also can be developed [85,88]. Once
a mission crew has been formed, mission training events may
be observed to identify potential problems with crew compat-
ibility [1,50,88,91]. If compatibility problems occur and cannot
be remedied before flight, the crew should be dissolvedas has
occurred at least once in international space flight [1].
Communication
Communications with family remain a critical coping mecha-
nism for deployed or on-orbit crews. Ensuring a crewmem-
bers ability to communicate with home is a central effort of
psychosocial support. Astronauts and cosmonauts report that
making connection with their families is one of the most enjoy-
able times in flight [2]. Cosmonaut Lyakhov, on his Salyut-7
mission, said, For us the letter [from home] is an extraor-
dinary event. We read [it] over and over many times. In the
same mission, Cosmonaut Aleksandrov stated, I received a
letter from [my wife] via Teletype. More joy [89] Weekly
audio or video conferencing is available to deployed crews
during preflight training, a capability that continues into the
mission. Family communication time must be scheduled into
397
the mission timeline, currently at a minimum of 15 min per
week. Crewmembers also are launched with computer-based
family albums that include electronic photos, video and
audio clips, and special-event messages from family members
to offer additional reminders of home. These help families
communicate, even without two-way connections. E-mail has
also become an important asset to maintain communication
between the crewmember and his or her family, as well as
facilitating in-flight communications between the crew and
the ground support team.
Active Rest
A leisure support plan is developed with each crew before flight
with the goal of assembling as many items as possible to be
sent into orbit with them. Leisure support may include favor-
ite computer software, music on compact discs, electronic and
paperback books, and films on videotapes or digital videodiscs.
A leisure activity library on board the International Space Sta-
tion includes electronic books and popular movies. Resupply
vehicles also provide a means of delivering, about once every
3 months, 4.5 kg (10 lb) of special-request foods, videotapes,
compact discs, and letters from Earth to crewmembers [86].
Family Support
Families must not only endure preflight separations for train-
ing but also manage the normal fears and struggles of having a
loved one in a distant and hostile environment. They must also
be ready to give extra support when that family member returns
to Earth. As much as crewmembers require support to main-
tain optimal performance, family members also benefit from
communication with that crewmember and the Earth-based
extended family and from learning about the stressors they
can expect and the support they will receive to help them meet
expected and unexpected family needs. The behavioral health
and performance group works with crew families to maintain
communication flow, to coordinate and provide education on
cultural aspects of the crew (to help during crew and family get-
togethers), and to provide information on stress points during
long-duration missions. Before flight, the family actively partic-
ipates with the psychosocial support staff in preparing the fam-
ily album that goes into orbit with a crewmember, in planning
communication events, and in supplying special surprises for
resupply packages. These activities keep crew families involved
in the mission and keep them aware of their own importance in
maintaining a crews behavioral health and performance.
Monitoring and Preventing Sleep
and Circadian Health Problems
Monitoring
The use of hypnotics for aiding sleep on orbit by nearly 30%
of crewmembers [56,72,92] demonstrates that crews are
398 C.F. Flynn

concerned about getting sufficient sleep on orbit. The major Prevention

issue confronting them is the degradation of performance
from sleep deficit and from work being performed during cir-
cadian troughs. Experience shows that the hardware required
to monitor sleep deficits and circadian problems can be aggra-
vating to the point where a crewmember may be reluctant to
gather data even when the tools are available. At present, sleep
hours and circadian phases are monitered indirectly from
the ground-based work-rest schedule. Not surprisingly, this
method is inaccurate; the ground team may be unaware that
a crewmember, after signing off for the night, has continued
to work into his or her scheduled sleep time. Until crews have
convenient objective monitors, self-reporting remains the only
tool with which to monitor the sleep and circadian problems
that crews experience.
Advances in actigraphy, in which a wristwatch-sized activ-
ity monitor is worn on an individuals nondominant wrist to
monitor movement and sleep patterns, have advanced sleep-
monitoring techniques and show promise for spaceflight
application. Actigraphy is less cumbersome than having to
assemble and wear monitoring electrodes, and except for
downloading the data it does not add any work to an already
full workload. Sleep studies of non-spaceflight workers wear-
ing actigraphs or participating in sleep encephalography have
revealed that motivated individuals report roughly 1 h of addi-
tional sleep than could be validated by objective measures
[28]. In other words, the individual reports, in all sincerity,
having slept an hour longer than was actually the case, and
that individual also expects to be able to perform better than
expected if too little sleep had been obtained. Thus even if a
crewmember keeps logs of decreased sleep or circadian dis-
ruptions caused by working past a planned schedule, reporting
these data to the flight surgeon may create another problem
for both parties. If a crewmember reports that he or she is not
following the schedule, then that crewmember may be rep-
rimanded; however, without an accurate report, the ground
support team will continue to expect more work to be accom-
plished than is possible within the timeline [93].
One of the best techniques to prevent sleep- and circadian-
related problems in space flight is to follow both on-orbit and
postflight schedules. The work-rest schedule created for a
crew is organized with the goal of maintaining adequate sleep
and a regular circadian cycle, including appropriate sleep-
shifting schedules. The use of 1 h of the presleep period
to relax is an excellent sleep-hygiene technique, as long as
it is not interfered with by excessive workload. Other non-
pharmacologic measures to reduce sleep disturbances include
avoiding exercise for several hours before sleep, not consum-
ing caffeinated beverages after the equivalent of 3 p.m., estab-
lishing a routine lights-out time each night, and maintaining
a comfortable atmospheric temperature. The use of hypnotics
can also be helpful.
The decision of which hypnotic to prescribe is determined
primarily by the period of sleep that is disrupted. Difficulty
falling asleep or staying asleep early in the sleep period can
be successfully treated with a hypnotic that has a short half-
life. Alternatively, when sleep difficulties arise in the middle
or the end of the sleep period, agents with longer half-lives
may be more useful (Table 19.2). Prolonged use of hypnotics
is of concern because of the potential for rebound insom-
nia, particularly when the use of shorter half-life agents is
stopped [98]. Although hypnotics can benefit a crewmember
who is suffering from sleep deficit, it is important to recall
that hypnotics will not help reset the circadian phase. In
other words, even if a crewmember may be getting sufficient
sleep, work performed during the circadian trough will be
at subotimal levels. Melatonin can be used both before and
after flight to promote circadian shifting, but clinical studies
have not shown it to be useful as a hypnotic [99]. Since on-
orbit power constraints preclude the use of light therapy for
treating circadian-shift difficulties in crewmembers, sched-
uling their shifts during their usual sleep times is the primary
countermeasure that can be used to optimize circadian influ-
ence on performance.

Table 19.2. Selected psychotropic medications for use on orbit.

Provided on Russian
Class of medication missions Provided on US missions Half-life (hours) Therapeutic dosage Dosing schedule
Antipsychotic Chlorpromazine 340 252,000 mg Daily or BID
Haloperidol Haloperidol 1530 1100 mg Daily or BID
Sedative, antianxiety Phenazepam 1018 0.51 mg BID or TID
Diazepam Diazepam 2090 240 mg BID or TID
Lorazepam 1020 16 mg TID or QID
Sedative/hypnotic Flurazepam 50160 1530 mg Daily
Antidepressant Amitryptiline 946 100300 mg/day Daily
Sertraline 2666 50200 mg/day Daily
Nortryptiline 1856 50150 mg/day Daily
Hypnotic Zolpidem 23 510 mg Daily
Nootropic Piracetam 57 400800 mg BID or TID
Abbreviation: BID, twice a day; TID, 3 times a day; QID, 4 times a day.
Source: Data from Aleksandrovskiy and Novikov [94], Perry et al. [95], Albers et al. [96], and Jenkins and Hansen [97].
19. Behavioral Health and Performance Support
Monitoring and Preventing Human-System
Interface Problems
Some human-system interface issues (e.g., the interior color of
a space station, or the location of fixed equipment) cannot be
changed, but other problems can be identified and corrected.
During a 135-day simulation study, researchers noted that sub-
jects began to allow small degradations to occur in noncritical
tasks rather than sacrificing performance on primary tasks [59].
If the stress (e.g., overwork, isolation-confinement) had contin-
ued, the next step would have been to not perform noncritical
tasks. This method of managing workload, task-shedding, is an
effective way to reduce error in the primary task. However,
this method can lead to problems on orbit when a crewmember is
scheduled to perform multiple tasks that are all considered essen-
tial to the mission. The only alternatives then are to shed the
task to another crewmember or to increase the individual level
of effort in an attempt to maintain performance on all tasks,
something that may be impossible for an already exhausted
and overworked crewmember to achieve.
These findings underscore the importance of recognizing
that individual differences in reaching task saturation can be
managed to reduce error in complex work environments. The
development of flexible work schedules, the accurate predic-
tion of workload, the effective maintenance and retraining of
crewmembers to maintain efficiency in completing mission-
critical skills, and the limiting of excessive noise, tempera-
ture, and off-nominal stowage are countermeasures that will
decrease the energy drain on spaceflight crews.
In reviewing more than 25 years of military aviation mishaps,
researchers concluded that human error occurs not solely because
of inadequate rest and circadian desynchrony, but because of a
larger combination of problems. These problems, all of which
are obstacles to optimal performance, include alterations in
visual cues, attempting performance during circadian nadir,
increases in cumulative fatigue levels, excessive focus on a
single aspect of the work environment, and the inability to
appropriately prioritize a sequence of required tasks [loss of
situational awareness] [100,101]. Through development of
monitoring tools and ways of training crewmembers to rec-
ognize and correctly react to these problems, crewmember
performance can be maintained. Unfortunately, with regard to
research into human-system interface problems, our knowl-
edge and technology has not advanced apace with that in other
areas of spaceflight research [51].
Monitoring
The Workplace Environment
Stowage is a critical issue with regard to monitoring the work-
place environment, especially when stowed items interfere with
rapid access to required equipment. A work timeline quickly
becomes invalid if locating equipment is time-consuming.
Problems with stowage may also create insufficient room to
399
accomplish assigned tasks. Alexsandrov, during his 150-day
Salyut-7 mission, remarked about this stowage problem: [It]
is getting increasingly difficult to move around the work-
ing compartmentcases of food and various equipment are
everywhere. And we still havent taken out the containers with
the additional solar batteries from the Kosmos [biosatellite]
or more than 10 other large units. [89] Currently, stowage
monitoring is managed before flight by estimating the avail-
able volume on orbit.
Monitoring of other environmental characteristics (e.g.,
noise and temperature) and the requisite responses are dis-
cussed elsewhere in this book (see chapters 24 and 22). Of
importance to crew performance, however, is the effect of
factors such as these on cognition and decision-making. Few
definitive studies exist today to guide flight surgeons in pre-
venting problems in these areas, other than studies that focus
on physiologic injury and decreased stamina in individuals
subjected to high levels of noise and temperature [12104]
aspects of the workplace that can be monitored and adjusted.
Work Effectiveness
Various methods are used to monitor work capability with
the goal of preventing loss of crew effectiveness through
work overload, task saturation, overuse injury, task sequence
monotony with decreased attention, and atrophy or degrada-
tion of mission-critical skills [60,105]. One strategy involves
monitoring the accuracy and timeliness of the completion of
a work task (e.g., real-time monitoring of input reaction time
or lapses of attention to the task). A considerable difficulty
associated with such real-time assessments is the additional
engineering required to monitor a crewmembers current
performance, to compare it to that crewmembers nominal
response on that task, and to override the current input if it is
inaccurate. Another strategy is to predict work performance
by periodically assessing changes in cognitive function scores
[59,71] or reaction time [104] on a representative task. Prob-
lems associated with the representative-tasks method include
the limits associated with predicting performance degradation
using these tools and the addition of another timelined task
into a crewmembers already full workday [106].
Observing physiological changes (e.g., changes in speech
parameters [107], blood pressure, skin resistance, heart rate,
[104,108,109] eye activity, electroencephalogram findings
[110], respiratory rate, and evoked potentials) [111] is another
way of monitoring work effectiveness. This approach requires
individualized calibration, has limits in its predictive value,
adds hardware for a crew to wear and maintain, and requires
baseline measurements on tasks that must be proven to be
representative of anticipated mission tasks. Moreover, the
microgravity environment also calls into question the validity
of using preflight physiological baseline data as an effective
on-orbit baseline [112115].
Workload and work performance are primarily moni-
tored through self-reporting, but this approach also has
its limits. Individuals tend not to be able to accurately
400
judge impairments in personal performance when they are
overworked. In one review of workload assessment, aviators
consistently rated their workload at 6070% of capacity, even
when they were task-saturated and their performance had sig-
nificantly degraded [110]. The strengths and limits of these
methods have led to disagreement as to how best to monitor
workload and work performance in space flight [116].
Prevention
Suggestions from Isolation Studies
Current steps being taken to prevent the deterioration of work
capability caused by human-system interface problems during
space flight are based on findings from isolation studies. Rec-
ommended strategies include (1) clearly identifying mission suc-
cess criteria before beginning operations; (2) identifying tasks
that can be dropped during a mission because of contingency
workload; (3) distributing the workload effectively among the
crewmembers; (4) maintaining a flexible work schedule that
can respond to changes in the mission; (5) enforcing regu-
larly scheduled days off; (6) giving the crew a high degree
of control over the schedule; (7) recognizing that postflight
operations are a significant additional burden and are part of
the mission; and (8) developing a close working relationship
between the crew and ground support team so that individual
crewmember requests will be answered quickly and accurately
[42,58,88,117,118].
A point to reinforce is the need to schedule non-working
days for recuperation. Enforced days off have been an impor-
tant factor in sustaining performance in high-workload set-
tings [50,119], because hard workers will work past their
limits unless recuperation time is scheduled and enforced.
Suggestions from Space Flight
Experience has taught that training crewmembers to recognize
their own optimal level of stress for maintaining work perfor-
mance has been considered advantageous by the Russian med-
ical system. As some professional athletes do, crewmembers
may be able to use sports psychology techniques to keep their
task performance within an acceptable range. Self-regulation
strategies for long-duration cosmonauts are taught by Russian
specialists in addition to techniques that enhance awareness
of the self and the body. Since this training is closely linked
to Eastern-style yoga, with which U.S. astronauts are less
familiar, Western-style sports psychology techniques may be
a more workable concept for U.S. astronauts [50,120].
Ground-based work schedules are another vital part of
improving work effectiveness by attempting to manage over-
work and task monotony. Studies are needed, however, to
validate just how accurately these schedules can predict work
time on orbit and to minimize deficits in performance caused
by monotony.
Finally, retraining in mission skills needed on orbit might be
improved if negative trends in performance can be identified
early. Tools that could rapidly clarify such negative trends
C.F. Flynn
require further development and validation, but they are defi-
nitely needed.
Monitoring and Preventing Behavioral
Illness
Monitoring
In the U.S. space program, monitoring of behavioral health
in the preflight, in-flight, and postflight phases of space flight
depends largely on self-reporting. On Earth, physiologic mea-
sures have been investigated as potential indicators of current
behavioral illness and as predictors of the onset of new illness
[121123]. However, these measures, which are not easily
adapted to use on orbit, are not being used to screen crews
[124]. Instead, flight surgeons are using self-report question-
naires from the crews, direct discussion with individual crew-
members, or evaluations of crew communication with the
ground as monitoring tools [78,125].
The Russian space program has developed other methods
of evaluating stress response, including analysis of voice har-
monics, self-reports of mood change, observations of changes
in facial expressions, changes in circulatory endocrine levels
[86], and analysis of voice communications [46].
Currently on the ISS, crewmembers monitor their cognitive
health with a computerized cognitive self-assessment tool.
This tool, which relies on baseline scores obtained before
flight, is used in monthly on-orbit testing to maintain a recent
baseline in case of neurologic injury (from a physical mis-
hap, toxic exposure, decompression event, hypoxia, and other
causes). This cognitive assessment tool can also present a suc-
cinct summary of critical data immediately to the crewmem-
ber and crew commander for decision-making.
Prevention
Selecting Out
The natural history of behavioral illness suggests that bio-
logical (genetic and organic) as well as environmental (psy-
chological and social) factors give rise to illness [126]. The
prevention of behavioral illness in space flight, our first pre-
vention strategy, is based primarily on two constructs, the
first that psychiatric selection strategies attempt to reduce the
likelihood of future illness by identifying past or current risk
factors, and the second that behavioral health interventions
are performed in an attempt to interrupt the progression from
manageable to abnormal stress levels in crews [127].
The use of psychiatric selection for space flight is consistent
with its use for choosing crews for winter-over tours in Antarctica.
This method, after it was implemented in the late 1950s [128],
was shown to reduce the number of untoward psychiatric events
in polar teams, and it continues to be considered useful today by
managers of isolated-confined team operations [51,129].
19. Behavioral Health and Performance Support
Internationally, psychiatric evaluation at the time of astro-
naut or cosmonaut selection has been successful in identifying
and disqualifying, as appropriate, applicants who have a diag-
nosable psychiatric (axis I) condition (typically between 4%
and 9% of the total applicant group) [13133]. Over the past
30 years, this psychiatric select-out process has relied heav-
ily on the clinical judgment of psychiatrists with extensive
experience evaluating aviators or other operations-based per-
sonnel. Their psychiatric evaluation focuses on those personal
qualities that would be expected to significantly interfere with
performance or would indicate a low threshold for developing
emotional distress and behavioral illness [25,134,135].
Heightened Self-Awareness
A second set of prevention strategies builds on a crewmem-
bers personal coping resources, reduces the environmental
stressors that are present, and establishes a preflight relation-
ship with behavioral health specialists for later interventions
on orbit as needed.
Behavioral health specialists can help by teaching crewmem-
bers how to identify symptoms of excessive stress, improve their
personal self-awareness, and make optimal use of coping tech-
niques. The perceived stress burden of crewmembers is occasion-
ally monitored by specialists, but this method could be enhanced
by objective measures of a crewmembers mood and stress lev-
els [86,94]. To remain mission-effective, a crew must maintain
a balance between the burden of mission stressors and available
energy for personal coping. When this balance falls too much
toward stress, the risk for behavioral illness increases.
A study supporting this concept demonstrated that most individ-
uals who developed major depression exhibited a greater number
of symptoms of depression during the year before diagnosis than
did a group that did not develop depression. Moreover, individu-
als with an acute onset of depressive symptoms had a 4.4 times
greater chanceand those with chronic depressive symptoms
had a 5.5 times greater chanceof developing a major depression
than did those who were not ill [136]. Therefore, new behavioral
illness in spaceflight crews could be reduced by identifying symp-
toms of illness early and suppressing those symptoms by reducing
accumulated stress or by increasing coping energy through rest,
relaxation, exercise, talking with others, receiving counseling or
pharmacologic treatment [137], maintaining good social connec-
tions to other crewmembers, and communicating with family and
ground team members [138,139]. Helping crews develop effec-
tive strategies to combat the negative effects of overstress is a key
function of the behavioral health and performance group.
Countermeasures II: Diagnosis
and Treatment of Behavioral Illness
Whether before, during, or after flight, the diagnosis of prob-
lems with behavioral health and performance can be aided
by using the four-factor concept (Figure 19.1). The first step
401
Four Primary Factor of Human Performance
Low Fatigue Healthy Brain and Mood
(Sufficient Sleep) (No Behavioral Illness)
Alert Focused Concentration
(Circadian Rhythm normalized) (No Cognitive Impairment)
[Sleep/Circadian Assessment] [Behavioral/Cognitive Healdth]
To Think + To Act = To Perform
Adapted to Workplace Good Physical Interface to Workplace
(Adapted to Environment) (Habirability, Workstation design)
Motivated Sensible Approach to Workload
(Support During Flight) (Work schedules, Work sequence, Personal limits)
[Psychological Adaptation] [Human-to-System Interface]
Figure 19.1. Four primary factors of human performance.
in this concept is to assess how the factors of sleep/circadian
rhythm, psychological adaptation, humansystem interface,
and behavioral health are being managed by a crewmember.
When symptoms are present, the flight surgeon may need to
make changes in one or more of these areas. Although adjust-
ments may be needed in the other areas as well, our primary
focus in this subsection is the diagnosis and response to behav-
ioral illness in a crewmember.
We anticipate that certain disorders are likelier than others
to develop on orbit, including asthenia, mood disorders (mania
and depression), psychotic disorders (thought disorders, organic
disorders, and delirium), anxiety disorders, and adjustment dis-
ordersincluding psychosomatic disorders and grief reactions
[46,137]. The following sections cover diagnostic issues for
these conditions and the countermeasures that are available on
orbit. Table 19.2 provides an overview of psychotropic medica-
tions that have been considered the minimum to have available
on extended-duration flights in low Earth orbit.
Challenges for Diagnosis
Although findings from laboratory and physical examinations
are important, the critical tool in psychiatric diagnosis is the
focused interview, conducted by a skilled behavioral health
specialist who is sitting with a patient. The standard method of
organizing information is the mental status examination, the
principal components of which are shown in Table 19.3.
Reliable diagnosis of behavioral illness in a space-based crew
is difficult for several reasons, chief among them being the inabil-
ity of a behavioral health specialist to be physically present with
the patient. Telemedicine techniques have been used as a diag-
nostic tool in terrestrial psychiatry, but under these circumstances
another physician is present with the patient. Used as a single tool,
telepsychiatry is inadequate for assessing and managing psychi-
atric emergencies such as psychosis or suicidal intent [140,141].
When a crew and a behavioral health specialist have established
a good relationship before flight, however, telepsychiatry could
402 C.F. Flynn

Table 19.3. Components of a mental status examination.

Component Normal response Look for abnormality if
Alertness Alert Lethargy, variability of alertness over 24 h suggests
delirium
Orientation Consistently and correctly identifies self, location, Variability of response over 24 h suggests delirium
and date
Speech Normal in rate, word choice, and content Pressured, rapid speech suggests mania
Nonsensical speech suggests psychosis
Mood Even, stable Labile, excessive sadness, happiness, or anxiety
Affect Cooperative Fright or irritability could suggest psychosis,
depression, anxiety
Thought processes Goal-directed Disrupted with psychosis, delirium, severe anxiety
Concentration Can perform serial subtractions with fewer than Disrupted with psychosis, delirium, severe anxiety
2 errors
Attention Can repeat 6 numbers forward and backwards Disrupted with psychosis, delirium, severe anxiety
Follows verbal commands (including repetition) Cooperative and accurate Disrupted in neurologic injury, psychosis
Memory Able to recall 3 objects at 0, 1, and 5 min as well Disrupted in delirium, severe anxiety
as past events
Reliability and insight Logical reasoning intact Odd behavior or speech suggests psychosis
Drawing Can draw a clock with requested time correctly Disrupted construction ability suggests neurologic
without hints injury
Source: Modified from Kaplan and Sadock[124].

be a helpful diagnostic adjunct for both the flight surgeon and
the on-board crew medical officer (CMO). Before or after flight,
diagnoses can be made by ground-based behavioral health spe-
cialists; once a crew is on orbit, however, the CMO is the most
vital asset for differential diagnosis and management. Although
CMOs are currently trained to recognize psychiatric disorders,
greater training and experience will be beneficial before explora-
tion-class missions are begun.
A second problem associated with reliable diagnosis of behav-
ioral illness in space flight is that the on-orbit environment can
create symptoms that mimic behavioral illness. Short-duration
space flights typically induce symptoms of tension, sleep distur-
bance, and psychosensory discomfort in crews. The heavy work-
loads and high pressure of these flights can make crewmembers
scramble like a squirrel in a wheel. [46] It is normal for crews
during long-duration missions to experience symptoms such as
asthenia, euphoria, depression, worsening of interpersonal rela-
tionships, sleep disturbance, accentuation of negative personality
traits, anxiety, anger, boredom, mental slowing, and transcenden-
tal experiences [46,74,142,143]. Symptoms that worsen signifi-
cantly, however, can reflect frank disorders, specific examples of
which are described in the remainder of this section.
Specific Disorders: Their Form
and Treatment
Asthenia
Asthenia or neurasthenia, which is produced by monotony and
cumulative fatigue, refers to the development of weakness, lack
of energy, irritability, problems with attention and memory,
unstable mood, and sleep disturbances. On space station mis-
sions, asthenia is thought to develop no sooner than the fourth
month on orbit, and it requires intervention to prevent a chronic
course [2,46,144]. Although neurasthenia is not a diagnosis
currently used in the United States, it is well known and used
in Eastern European psychiatry. Indeed, its use seems to sig-
nificantly overlap U.S. research diagnostic criteria for major
depressive disorder [144].
Treatment
Russian medical specialists treat neurasthenia with nootropic
medications such as piracetam and additional support mea-
sures [145,146]. These support measures include reducing
difficult job tasks in the evening hours, reinforcing the work-
rest schedule with crewmembers, and increasing the ground
support teams focus on the personal requests of the affected
cosmonaut [2,46,94].
Euphoria and the Development of Mania
The Russian experience with long-duration missions suggests
that episodes of elevated mood generally do not persist for
more than 3 days after completion of a critical task of personal
significance [46,94]. When a crewmembers mood remains
irritable and expansive, when that crewmember becomes
resistant to recommendations from the ground team, or when
he or she continues to overestimate how well things are going
on the spacecraft, this crewmembers condition is much closer
to what would be considered hypomania. A worsening of this
hypomanic state to include at least 3 symptoms such as gran-
diosity, racing thoughts, distractibility, loss of judgment in
decision-making, pressured speech, hyperactivity, or lack of a
19. Behavioral Health and Performance Support 403

need for sleep for 4 or more days would indicate development Table 19.4. Comparison of symptoms common to long-duration.
of a manic state [147]. Spaceflight and depressiona.
Mania has a lifetime prevalence of 1% in the U.S. popula- Occurring in most
tion [80], and it occurs frequently as a new-onset disorder in Usually present in patients with major
crewmembers on long- depression in 8 cross-
the age ranges typical of spaceflight crews (Table 19.1). The
Symptom duration missions national study sites
differential diagnosis on orbit includes endocrine dysfunction,
Depressed mood Variably 8 of 8 sites
toxin exposure, central nervous system abnormalities, and
Loss of normal interests Yes 0 of 8 sitesb
abnormal mood occurring as a response to medications, espe- and pleasures
cially steroids or antidepressants in people with undiagnosed Loss of energy, fatigue Yes 8 of 8 sites
bipolar disease [148]. Sleep disturbance Yes 8 of 8 sites
Suicidal thoughts, No 7 of 8 sites
Treatment hopelessness
Poor concentration Variably 6 of 8 sites
According to Russian medical specialists, hypomanic crew- Significant feelings of No 5 of 8 sites
members will benefit from brief but consistent information worthlessness or guilt
Poor appetite, weight loss Yes 3 of 8 sites
regarding job performance when combined with recommen-
Significant agitation or No 0 of 8 sitesc
dations to strictly observe rest schedules [46,94]. The more withdrawal
severe mania requires medications to effectively control a
Symptoms needed for a diagnosis of major depression are 2 weeks of
symptoms. The use of benzodiazepines to reduce psycho-
depressed mood or loss of normal interests and pleasures plus any 4 of the
motor agitation and irritability can be very helpful initially other symptoms listed here.
[149,150]. Loss of reality-based thinking requires the addition b
This symptom criterion, as phrased here, was not used in the cross-national
of antipsychotic medication. study.
c
More than one medication is usually required to treat mania, Withdrawal was not used as a symptom criterion in the cross-national
especially in the acute phases. First, a benzodiazepine helps to study.
Source: Data from Myasnikov and Zamaletdinov[46], Weissman et al. [80],
slow the manic patient. Second, an antipsychotic medication and American Psychiatric Association [147].
should be used to treat any hallucinations or extreme thought
disturbances. Optimal management of mania requires long-
term use of a mood-stabilizing agent, such as lithium, anti-
whether the symptoms reflect a combination of lesser prob-
convulsants, or long-acting benzodiazepines. Use of these
lems. The natural history of untreated depression suggests
medications, however, warrants thorough endocrine, cardiac,
that only 50% of adults will recover at 12 months from the
and blood-chemistry analyses before therapy is begun. Ongo-
onset of the illness [152,153]. Tracking the persistence and
ing monitoring of medication levels is also required. Thus,
severity of the symptoms that are present is the best method
given the level of medical assessment currently available on
for CMOs and flight surgeons to establish a diagnosis of
orbit, a crewmember with mania would require immediate
depressive disorder. A crewmember who has experienced
return to Earth for more definitive treatment. A narrowed on-
depressed mood or loss of interests for 2 weeks plus 4 other
orbit differential diagnosis of mania would include exposure
symptoms, as noted in Table 19.4, would meet the terrestrial
to a toxic chemical or an aberrant reaction to medication,
diagnostic criteria for the disorder. Grief is a special type of
neoplasm, infection, or thyrotoxicosis [151].
depressive symptom, but if a crewmember is experiencing
the multiple, severe, and prolonged symptoms that meet the
Depression criteria for a depressive disorder, the diagnosis is warranted.
The short list of differential diagnosis of major depres-
One of the difficulties associated with diagnosing depressive
sion on orbit includes medication side effects, exposure to
disorder in a long-duration crewmember during a mission is
toxins, neoplasm, endocrine dysfunction, and vitamin defi-
the presence of symptoms that are common to both long-
ciency [151].
duration flight and the disorder. The lifetime prevalence of
major depression in U.S. adults is roughly 5%; this disorder is
Treatment
twice as common in women as in men, and occurs frequently
as a new disorder in the age range of spaceflight crews [80] Conservative measures to be used in treating a crewmember
(Table 19.1). Table 19.4 [46,80,152] compares the presence with depressive symptoms include maintaining a strict focus
of symptoms typical of long-duration flight with those symp- on workload and adequate rest. Another important technique
toms that occur across cultures in patients with major depres- is to regularly provide feedback with emphasis on positive
sive disorder. evaluation of the quality and importance of work being per-
Since so many symptoms are common to long space formed. It is best not to repeatedly question the crewmembers
flight and depression, CMOs must decide whether a crew- mood and general state [46,94], although tracking symptom
member is experiencing a full depressive disorder or severity with a simple numeric score would be useful.
404
Use of medication is the next consideration. The problems
associated with using medication to treat a crewmember, par-
ticularly one on a long-duration mission, are crewmember
compliance with taking the medication and the potential risk
to the crewmember from taking the medication. Antidepres-
sant medication is effective in about 67% of patients; however,
CMOs must monitor the affected crewmembers very carefully
because of the the risk for self-injury, which increases as the
depression starts to improve [155] but tends to wax and wane
during the early recovery period [156]. Hence the CMO needs
to assess whether the patient is tolerating and taking the medi-
cation. At least 2 antidepressant medications will be present
on orbit to improve the chance for good compliance.
With regard to the potential risk to the crewmember, the risk
of self-injury must be considered. Once a depressed person
begins taking medication, the risk of self-injury may increase
because of the improvement in sleep and energy as the antide-
pressant medication starts to work. Unfortunately, although a
depressed person may still feel hopeless, he or she is not help-
less and may then have enough energy to carry out self-harm.
Because 4060% of people who have committed suicide had
major depression [157], the CMO must ask frequently about
suicidal ideation.
Talking about suicide does not cause suicide. Rather, not
talking about suicide is a more common problem. Indeed,
50% of individuals who commit suicide see a physician in
the month preceding death, and 40% of those individuals had
clearly communicated their intent to someone close to them
[158160]. All comments must therefore be taken seriously,
and even a welcome change in reported suicidal intent can be
misleading. In one study of hospitalized patients who com-
mitted suicide, 64% reported to staff members that they no
longer had suicidal ideation in the period immediately preced-
ing their death [156]. On Earth, an antidepressant may take
nearly a month to produce the full effect; antidepressant use
on orbit has not been documented. Therefore, monitoring to
ensure that the crewmember is taking all prescribed doses of
medication will be an important function of the CMO, as is
increasing the dosage and managing the side effects until a
therapeutic dosage is reached.
Psychotic Disorders, Including Organic Mental
Disorders and Delirium
The common thread in the diagnosis of psychotic disorders
is the loss of ability to consistently maintain logical thought
processes. Organic mental disorders and delirium may occur
because of a severe mood disorder, a severe thought disor-
der, a toxic exposure, a severe medical injury, severe sleep
deprivation, or a severe psychological maladaptation caused
by stress or isolation and confinement [42,47,74,161].
Experience with isolated and confined teams and on-orbit
crews has demonstrated risk for toxic exposures in space flight
that can cause brain injury [7]; examples of this are the nitro-
gen tetroxide exposure during the Apollo space program and
C.F. Flynn
the ethylene glycol, smoke, and freon exposures during the
NASA-Mir Program. Another risk is that of new-onset psycho-
sis, types of which in the age range of spaceflight crews include
mania, severe depression, or severe obsessivecompulsive dis-
order (Table 19.1). Whatever the etiology, a crewmember with
psychosis cannot be trusted and must be closely supervised or
even physically restrained.
Psychosis should be recognized as an independent risk fac-
tor for self-harm regardless of whether the patient is depressed.
Studies have shown that psychosis was present in 50% of
hospitalized patients who later committed suicide [156].
New-onset psychosis is uncommon in older age groups, and
delirium as a result of medical illness is a poor prognostic sign
that indicates an increased risk of mortality [162]. Although
psychosis could quite possibly occur, its diagnosis has not
been documented in space medicine literature [143].
An important symptom to identify in psychotic individuals
is hallucinations. Especially worrisome are command auditory
hallucinations, because a person with this type of hallucination
is at high risk of following those commands. Command hallu-
cinations are typically verbal instructions to do something that
involves extremely poor judgment or even destructiveness,
e.g., hurting oneself or others, opening the door of the space
station, etc. Additional symptoms indicative of psychosis
include at least 24 h of confusion, emotional lability, disorga-
nized speech, delusions, and disorganized behavior [147]. The
CMO must have a high index of suspicion for hallucinations
or psychosis in a crewmember whose behavior has dramati-
cally changed, because psychotic individuals do not always
express symptoms wildly. In one study of schizophrenic
patients, 40% had poverty of speech, 88% were socially with-
drawn, and not more than 34% demonstrated formal signs of
thought disorder in verbal communications [160]. The CMO
may need to ascertain psychosis by carefully observing an ill
crewmember for nonsensical behaviors. Signs could include
frequent distraction from a conversation, losing track of the
conversation, poverty of speech, jumping from topic to topic
during a conversation, mutism, poor eye contact, or inappro-
priate affect [164].
A special type of psychosis is delirium, the hallmark of
which is the coming and going of confusion over 24 h.
Visual hallucinations are more frequent in delirium than in
other types of psychosis. Throughout the day, an individual
with psychosis will show a wide range of symptoms, some-
times being completely confused in behavior and thinking
and other times able to report fairly accurately in reality-based
conversation. Typically, delirium is caused by a severe illness
or injury, an abnormal reaction or a withdrawal from medica-
tion, a severe infection and fever, an endocrine dysfunction, a
vitamin deficiency, an intracranial abnormality, or an expo-
sure to a toxin [162]. Symptoms include reduced awareness
of the environment, reduced ability to focus and sustain atten-
tion, cognitive deficits of memory, and disorientation to time,
place, or person [147,162,165]. Insomnia is often a problem at
night, whereas the person is unable to stay alert and awake
19. Behavioral Health and Performance Support 405

at periods of normal daytime. People who are delirious are Anxiety Disorders
usually agitated when they are confused.
Organic mental disorders may present as delirium or psy- Symptoms of anxiety range from discomfort to disorder. The
chosis, and exposure to a chemical can present as disrupted CMO must judge whether the level of anxiety experienced by
brain function. Some toxins can cause a rapid change in a crewmember is within the scope of normal. For example, a
behavior or cognition (because of confusion and disorienta- severe level of anxiety in the face of a near-death event would
tion), whereas chronic exposures to chemicals such as mer- be considered normal. However, such an experience may also
cury, copper, or lead can lead to slower changes in cognition. lead the crewmember to develop a posttraumatic stress reac-
Ten percent of patients who have suffered a mild head injury tion that is both chronic and abnormal. The critical question
have ongoing neurocognitive sequelae, including behavioral for diagnosis is whether the observed reaction is comparable
change [166]. to a normal response. Anxiety symptoms are not the same as
an anxiety disorder. To warrant a diagnosis of disorder, the
patient must have experienced a sufficient number of symp-
Treatment toms for a specified period.
The differential diagnosis for anxiety on orbit includes other
Once a crewmember is recognized as having psychosis, physi-
mental disorders, medication effects (including withdrawal
cal restraint is necessary until pharmacologic control is suc-
from a medication), exposure to toxins, endocrine dysfunc-
cessful. Medication must be used to improve the psychotic
tion, or other general medical illness [169,170]. This subsec-
symptoms [46,132,161]. Antipsychotic drugs, which are avail-
tion provides an overview of the anxiety disorders most likely
able on orbit, are very effective at stopping psychosis, but they
to occur in the age range of spaceflight crewspanic disorder
also have side effects that can require the use of additional
and obsessivecompulsive disorder.
medications. Anticholinergic side effects (e.g., blurred vision,
Panic disorder has a lifetime prevalence of 1.4% in U.S.
dry mouth, tachycardia, constipation) are less prominent with
adults, and occurs frequently as a new disorder in the age ranges
highly potent agents such haloperidol, but extrapyramidal
typical of spaceflight crews (Table 19.1). The diagnosis of panic
effects (e.g., parkinsonism, dystonia, akathisia) are more fre-
disorder requires recurrent panic attacks and worry or change
quent, occurring in about 60% of patients receiving antipsy-
in behavior because of the attacks for at least 1 month [147].
chotic medications [167]. The potentially lethal side effect of
Panic attacks are discrete episodes of intense anxiety that have
neuroleptic malignant syndrome may develop in about 0.2%
an abrupt onset and at least four additional symptoms such as
of patients treated with an antipsychotic medication. With its
palpitations, sweating, trembling, shortness of breath, a chok-
hallmark symptoms of hyperthermia (temperature higher than
ing sensation, chest discomfort, nausea, dizziness/lightheaded-
38 C) in 98% of patients, muscular rigidity in 97% of patients,
ness, feelings of unreality, fear of losing control, fear of dying,
and worsening confusion in 97% of patients, this syndrome
a sense of impending doom, paresthesias, chills, or hot flashes.
tends to develop within 1 month of starting to take the offend-
[147] Panic disorder often goes undiagnosed for months or
ing medication and develops rapidly over 2472 h [168].
years because the affected individuals tend to fear that they are
Antipsychotic medication should be given intramuscularly
crazy and do not report symptoms to healthcare providers.
to treat hallucinations, agitation, and thought disorder. A long-
Obsessivecompulsive disorder has a lifetime prevalence of
acting benzodiazepine may also be given intramuscularly for
2.5% [79] and occurs frequently as a new disorder in the age
additional calming effects. Repeating the doses 60 min later
range of astronauts and cosmonauts (Table 19.1). Individu-
may be considered if necessary, although this should be done
als with this condition recognize that the fears and behaviors
cautiously, with consideration of the medications half-life
experienced are unreasonable but they are unable to overcome
(Table 19.2) and accumulation [96].
them. Obsessions are defined as intrusive, distressing recur-
Treating the person with delirium or an organic mental dis-
rent thoughts or impulses that the person recognizes as being
order requires a different approach than treating a person with
self-generated but cannot be controlled despite attempts to
simple psychosis. The first step for the flight surgeon is to
suppress them. Compulsions are repetitive behaviors that a
consider whether a toxin, a medication, or an illness is the
person feels driven to perform to reduce distress over a dreaded
underlying cause. If fever, high blood pressure or pulse rate,
outcome [147]. The classic example of obsessivecompulsive
high white blood cell count, or abnormal bloodwork is pres-
disorder is the person who fears death from infection and thus
ent, the flight surgeon should begin treating the underlying
washes his or her hands so frequently that injury results.
problem as well as giving antipsychotic medication. For the
delirious patient, it is also important to consider the patients
ability to clear a dose of medication. An antipsychotic is still
Treatment
the drug of choice to stop hallucinations in patients, but small Fortunately for the CMO, anxiety disorders respond quickly to
doses of a high-potency agent are best [161]. Use of a benzo- benzodiazepines and sometimes to antidepressant medication.
diazepine in delirium is atypical, because any sedating medi- The primary consequence of using benzodiazepines for anxi-
cation may worsen the confusion, and therefore the agitation, ety is the development of physiologic dependence and altered
of the delirious individual. cognition. Although all anxiety conditions will respond to
406 C.F. Flynn

benzodiazepines, antidepressants are also effective in treating tion sessions with the crewmember, encouraging extensive
panic disorder and obsessivecompulsive disorder [95,171]. use of psychological support measures, recommending
Doses of benzodiazepines are typically based on the half-life strict compliance with workrest schedules, and officially
of the medication, with doses overlapped so as to maintain notifying the crewmember of inaccuracies, errors, and vio-
the clinical effect. When used for treating anxiety disorders, lations in their work [46,94]. Encouraging the crewmem-
antidepressants are administered at the same dosage level as ber to discuss the stressful experience and attempting to
for depression [46,94,96] (Table 19.2). help that crewmember develop alternative strategies to the
adversity are typical responses to these conditions as well.
Talking to a ground-based behavioral health specialist
Adjustment Disorders may also help a crewmember, but the degree of help will
depend on the relationship that was developed between the
Physical symptoms of severe stress reactions may include
crewmember and the behavioral health specialist before
tachycardia, rapid breathing rate, diarrhea, nausea/vomiting,
flight [61].
and sweating. Behavioral symptoms can also be recognized as
part of a response to stress. The behavior of people suddenly
caught in a catastrophe can be broadly characterized as 1 of Treatment of Psychiatric Emergencies
3 typesrelative calm (1020%), stunned (75%), and highly
Because about 40% of all patients who are seen in psychi-
inappropriate (1015%) [172]. When the physical symptoms
atric emergency rooms require hospitalization [97], once a
of severe stress reactions create significant problems for an
psychiatric condition has become problematic in flight, the
individual or are excessive in comparison to the precipitat-
CMO and the flight surgeon must remain vigilant to the
ing stressful event, this defines an adjustment disorder [147].
possibility of a psychiatric emergency. Such an emergency
CMOs must realize that a crewmember may not want to report
can arise from the illness or from the side effects of thera-
suffering from the stressful event that occurred. Adjustment
peutic medications. The primary goal of the CMO in such
disorder is one of the most common psychiatric diagnosis and
a situation is to quickly gain control of the patient to pre-
can occur at any age [173].
vent injury to the patient or to other crewmembers. How-
Some individuals will react to a calamity with depressive
ever, before rushing in, the CMO should develop a plan
symptoms and a decrease in work motivation, whereas oth-
of action to take control of the situation rather than risking
ers may become more withdrawn or irritable. If the severely
injury to the rest of the crew by an unpredictable crewmem-
disruptive event is the loss of a loved one or a close friend,
ber. Control may require physical restraint using duct tape
a grief reaction can be expected, as has happened in Salyut
around the crewmembers arms and torso or legs. Table
and NASA-Mir missions. Other individuals with depressive
19.5 [158,159,164167,174] outlines possible responses to
symptoms may develop new physical symptoms, or they may
anticipated behavioral health emergencies that could occur
experience more physical discomforts than usual [137].
on orbit [95,96,161,162,167,168].
After a Russian Progress supply vessel collided with the Rus-
sian space station Mir on June 25, 1997, routine physical assess-
ments of the crew commander demonstrated a new set of cardiac
rhythm changes. The Russian medical group diagnosed this
Medical Disposition
somatic change to be a result of severe psychological stress in
The disposition of a space-based crewmember with a
the aftermath of the crash [2]. Clearly stress can induce somatic
behavioral health disorder is the primary decision point
changes, not just alter an individuals perception of illness.
in determining whether to return the ill crewmember to
Accentuation of negative personality traits is also a hallmark of
Earth or to attempt treatment on orbit. Flight surgeons
increased stress. The sign of this type of problem is a worsening
should work to optimize the four factors that influence
of personality quirks that would be noted before flight, includ-
behavioral health and human performance. Patients with
ing impulsivity, subjective overestimation of ones capabilities,
inadequately treated psychiatric illness are moderately to
the appearance of hostile interpersonal reactions with ground
severely dysfunctional in a work setting [175]. Since 50%
crew or other crewmembers, predominantly negative responses
of individuals with depressive disorder can be expected
toward work rest schedules, and a labile mood. These negative
to recover in 6 months from the onset of treatment, crew-
reactions to stress will impair normal work capacity and inter-
member response to antidepressant therapy will be a key
personal relationships and so can best be described, in U.S. diag-
factor in a stay or return decision [153]. Less severe
nostic terminology, as adjustment disorders.
anxiety disorders will respond quickly to treatment with
benzodiazepines, whereas response to antidepressant
Treatment
can take 34 weeks. It is certain that while adapting to
The Russian medical group responds to adjustment disor- the medication used, the patient will not be an optimal
ders by instituting a businesslike approach in communica- crewmember.
19. Behavioral Health and Performance Support 407

Table 19.5. Responses to psychiatric emergencies.

Presenting problem Restraint required Medication suggested Watch for
Suicidal Constant observation, at minimum Diazepam 2.5 mg po q 12 h for anxiety More energy = more danger
Begin antidepressant Psychosis = more danger
Violent Chemical/physical Haloperidol 5 mg IM q 12 h Look for medical illness, psychosis,
Diazepam 5 mg IM q 12 h toxic exposure
Dystonia (264% of patients given None Benadryl 50 mg IM Recurrence
antipsychotics) Decrease antipsychotic dose (if pos-
sible) or switch
Akathisia (2175% of patients given None Benadryl 25 mg po TID Recurrence
antipsychotics) Propanolol 10 mg po TID
Diazepam 2.5 mg po BID
Decrease antipsychotic dose (if pos-
sible) or switch
Neuroleptic Physical Normal saline 250 ml/h IV Loss of urine output
Malignant Syndrome Diazepam 5 mg IM q 8 h Continued hyperthermia
(0.2% of patients given Amantadine 100 mg po BID
antipsychotics) Stop neuroleptic
Keep as cool as possible
Delirium Chemical/physical Haloperidol 1 mg IM q 812 h Medical illness, toxin
Psychosis Chemical/physical Diazepam 5 mg IM q 12 h Dystonia, akathisia, parkinsonism,
Haloperidol 5 mg IM q 12 h neuroleptic malignant syndrome
Severe Anxiety As indicated by cooperativeness Valium 25 mg IM q 8 h
Diazepam 2.5 mg po q 12 h
Abbreviation: BID, twice a day; IM, intramuscular; IV, intravenous; po, by mouth; q, each; TID, 3 times a day.
Source: From Kaplan and Sadock[161,162,167], Casey [168], Perry et al. [95], Albers et al. [96], and Jenkins and Hansen[174].

Another consideration is that space medical standards
preclude certifying a crewmember taking psychoactive med-
ication for flight. Therefore, a decision to continue the flight
and certify the recovered crewmember for on-orbit duties is
likely to require several steps. First, the other crewmembers
must be able to assist or absorb the ill crewmembers
mission-critical tasks until full function has returned. Sec-
ond, a good response to medication must have removed the
illness symptoms. Finally, since means of assessing cogni-
tive function is available on orbit, such means should be used
to determine when the treated crewmember has returned to
baseline mental capacity.
Before flight, a condition that is self-limited and rapidly
treated should not require removal of a crewmember from a
mission. However, if that condition keeps a crewmember from
completing the required training, removal from the flight is
likely. A return-to-flight opportunity could be indicated after
624 months of good functioning off medications, depend-
ing on the disorder. Fortunately, the excellent problem-solving
capabilities, superior adaptability, and motivation in astronauts
and cosmonauts are very favorable assets in behavioral health
treatment [176178]. In a study of 7 years of outcome data
from psychiatrically hospitalized military aviators, an encour-
aging 65% achieved return-to-flight status [15]. After flight,
a delay in recertification for flight would be warranted until
good prognosis is assured. By keeping in mind the 4 factors
that can influence behavioral health and human performance,
flight surgeons can work to optimize these areas and create a
positive outcome for a crewmember.
Conclusions
This chapter provides a review of the important risks to maintaining
a spaceflight crews behavioral health and performance, includ-
ing the effects of expected spaceflight conditions; expected
behavioral symptoms and behavioral health disorders; and
prevention, monitoring, diagnosis, and treatment strategies for
medical disposition. The four-factor model described gives
flight surgeons an efficient approach for recognizing expected
problems and for planning countermeasures for these problems.
The 4 factors in this modelpsychological adaptation, sleep
and circadian rhythms, human system interface, and behavioral
health issuesare considered as distinctly independent but at
times overlapping elements required to maintain human perfor-
mance for space missions. To improve and maintain a crews
mission performance, better tools are needed to monitor changes
in these four areas, and countermeasures need to be identified
and validated. From this perspective, the ISS will be an excel-
lent test bed in which to improve these capabilities. Experience
on the station is a necessary next step because exploration-class
missions will require much better tools to clarify diagnoses, use
prophylactic measures, and institute treatment of deficits in the
four factor areas.
408
Despite the significant and cumulative negative stressors
that are known to challenge spaceflight crews, this chapter
would be incomplete if it ended without identifying a likely
positive effect of space flight on a crewmembers behavioral
health. In one study of cosmonauts who participated in space
flights lasting up to 1 year, analysis of data gathered 23 years
after landing revealed a significant improvement in the cosmo-
nauts emotional stability, self-confidence, self-assessment,
and interpersonal problem-solving techniques [46]. Similar
salutary effects have also been noted in Antarctic winter-over
individuals, who in general had fewer first hospitalizations
after deployment than did a control group and who also devel-
oped more independence and self-reliance after the mission
[129]. By joining together early to prepare for known mission
stressors, flight surgeons and spaceflight crewmembers can
not only maintain behavioral health and mission performance
on orbit but can also maximize any potential positive behav-
ioral health effects of the space mission experience.
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20
Fatigue, Sleep, and Chronotherapy
Lakshmi Putcha and Thomas H. Marshburn
Early in the history of human space flight, scientists realized
that several factors in the space environment might adversely
affect human function and performance. Potential disturbances
in circadian rhythms and the consequences of such distur-
bances on performance efficiency and the well-being of space
crewmembers were among the principal concerns expressed
[1]. In addition to environmental changese.g., microgravity
and ultrashort light-dark cyclesseveral operational reasons
were cited for the possible development of sleep disturbances
and fatigue during space flight [2,3], including an abnormally
long working period (the high-workload effect), continuing
deviations in the sleep-wake schedule duration (the migrating
day effect), phase shifting of sleep periods relative to Earth-
based sleep time (the shift-work effect), and cyclic noise dis-
turbances. The safety hazards associated with sleepiness and
fatigue may have serious consequences for astronauts and
cosmonauts as well as their supporting ground crews.
In the current space flight environment, imposed 24-h
schedules often conflict with physiological and psychologi-
cal rhythms of space crews, thereby changing their work-rest
periods from their accustomed ground-based sleep-wake
cycles. Although the consequences of this change remain
largely unknown, this chapter is intended to provide a snap-
shot of trends in the assessment of sleep and fatigue, perfor-
mance implications in space flight, and methods of monitoring
and managing sleep and fatigue in operational settings. Also
addressed are specific space flight issues related to risk assess-
ment and to sleep and fatigue management strategies for cur-
rent and future long-duration space flights.
Sleep
Sleep is a vital physiological function. The 24-h sleep-wake
cycle is a complex, active physiological state characterized
by two distinct types of sleepnon-rapid eye movement
(NREM) sleep and rapid eye movement (REM) sleep [4].
In humans, NREM sleep can be further subdivided into four
distinct stages, based primarily on electroencephalographic
(EEG) characteristics obtained through polysomnography.
Sleep stages also reflect the depth of sleep, with stage 1 being
the lightest and stage 4 being the deepest stage of sleep. The
distribution of an individuals sleep among these four stages
can be affected by many factors, chief among them being age
and developmental stage; other factors that influence the pat-
tern of sleep stages within a nighttime sleep period include
the use of drugs or alcohol, exercise, and specific sleep dis-
orders.
Sleep stages are most often characterized by measuring
EEG patterns, but electrooculographic (eye movements) and
electromyographic (muscle tone) patterns may also help in
identifying sleep stages. Stage 1 sleep, the lightest phase of
NREM sleep, is characterized by an EEG pattern called the
alpha rhythm. Typical alpha waves occur rhythmically at 8
13 cycles per second and indicate a state of relaxed wakeful-
ness with eyes closed [5]. Stage 1 is normally considered the
relaxed and transitional stage preceding sleep onset. Another
characteristic of stage 1 sleep is the presence of slow, rolling
eye movements.
The appearance of distinct sleep spindle and K complex
EEG waveforms characterizes stage 2 NREM sleep. Stage 2
sleep is generally free of eye movements and is distinguished
from stage 1 sleep by a higher arousal threshold, meaning that
a more intense stimulus is required for arousal from stage 2
sleep.
Stage 3 and stage 4 NREM sleep are collectively called
slow-wave sleep. The EEG pattern of stage 3 and stage 4 sleep
is characterized by delta waves, which are of higher amplitude
(> 75 mV) and slower frequency (0.52 cycles per sec) than
those of stage 1 or 2 sleep. Slow-wave sleep is often consid-
ered the deepest sleep, and no eye movements are evident.
More detailed descriptions of sleep and EEG characteristics
can be found in the Encyclopedia of Sleep and Dreaming [6].
Many of the physiological changes that occur during NREM
sleep are caused in part by a shift of the autonomic nervous
system such that the parasympathetic system predominates;
REM sleep, however, is accompanied by an increase in sym-
pathetic activity. Systemic blood pressure has been shown
413
414
to decrease by 515% during NREM sleep [7]. Analyses of
heart rate variability during sleep in healthy male and female
subjects have confirmed differences in autonomic nervous
system activity between waking and sleeping and between
NREM and REM sleep; specifically, REM sleep was char-
acterized by increased sympathetic dominance secondary to
vagal withdrawal [8]. Autonomic functioning during waking
and sleep also varies according to sex, with men tending
to show decreased vagal tone during waking and increased
sympathetic dominance during REM sleep as compared
with women. Other physiological functions affected by sleep
include those of the respiratory, gastrointestinal, renal, endo-
crine, and immune systems along with changes in thermal
regulation and memory formation [7].
The temporal structure of sleep and wakefulness is believed
to have evolved to maximize flexibility and to ensure that
transitions from one state to the other are smooth. Sleepiness
shows a biphasic rhythm over 24-h periods, with a first and
greatest level of sleepiness experienced between 3:00 a.m.
and 5:00 a.m. and a second, less intense level of sleepiness
between 3:00 p.m. and 5:00 p.m. Afternoon sleepiness occurs
independent of food consumption, but its effect can be exacer-
bated by consuming a meal [9].
Most people require about 8 h of sleep to maintain physi-
ological balance, and most adults report sleeping 77.5 h per
24-h day [10]. The recuperative value of sleep depends on its
duration and continuity [11]. Both sleep requirements and
sleep structure change with age. Younger individuals require
more sleep than do their adult counterparts, and changes in
sleep structure, such as experiencing more sleep interruptions,
are common in older adults.
Inadequate sleep is endemic in industrialized societ-
ies. Many of us are chronically sleep-deprived [12,13]. The
monophasic sleep pattern, which implies a single sleep period
per day and is characteristic of most industrial societies, is of
purely social origin. The existence of a biphasic sleepiness
rhythm implies that at least one additional period of sleepi-
ness would be experienced per 24-h period. Growing evidence
suggests that even adult humans can benefit from polyphasic
sleep (i.e., multiple sleep periods over the course of a day)
rather than the more typical monophasic sleep pattern [14]. In
a recent survey conducted by the National Sleep Foundation
[15], 75% of those questioned reported experiencing daytime
sleepiness, and 32% reported that that sleepiness was severe.
Although the 32% with severe daytime sleepiness reported
that their sleepiness interfered with their daytime activities,
82% of all of the subjects surveyed believed that daytime
sleepiness had a negative effect on their productivity.
Some evidence points to the existence of a basic trait that deter-
mines the balance between sleep-promoting and wakefulness-
promoting mechanisms in an individual. Two distinct profile
types of sleep characteristics (somnotypes) have been identified:
the sleepy and the alert. People with the sleepy somnotype can
fall asleep easily, whereas those with the alert somnotype find
it more difficult to fall asleep and stay asleep. Considerable
L. Putcha and T.H. Marshburn
evidence exists to indicate that those who need less sleep to
feel alert should sleep less at night and nap less during the day
[16]. This dimension of individual difference is independent
of morning and evening types [17].
The performance effects of sleep stress, that is, sleep
deprivation or compromise, are complex. Sleep deprivation
impairs alertness, cognitive performance, and mood [16].
Sleep-deprived people typically show declines in overall per-
formance, particularly in mental operations that depend on the
prefrontal cortex [18]; simple psychomotor performance and
physical strength and endurance, however, seem to be unaf-
fected by sleep deprivation [19]. Fragmented or brief sleep is
thought to have little restorative value for individuals deprived
of sleep, and indeed has effects similar to those of sleep depri-
vation [20].
Shift work is often associated with increased rates of car-
diovascular disease and accidents [21]. Discordance between
the circadian rhythms of stress-related biological variables
and work-sleep schedules, particularly those of shift work-
ers, could also reduce work efficiency. In one study, 24-h
electrocardiographic (ECG) recordings from shift workers
indicated that weekly changes in shift work (from first shift
[6:00 a.m.2:00 p.m.] to second shift [2:00 p.m.10:00 p.m.]
to third [10:00 p.m.6:00 a.m.]) were associated with changes
in the 24-h oscillation of cardiac sympathetic and vagal auto-
nomic modulation [21]. The finding in that study that indices
of cardiac sympathetic modulation were reduced during night
work was thought to be related to the presence of sleepiness or
diminished alertness, which in turn could result in errors and
accidents [21]. This finding may also underlie the higher rate
of cardiovascular diseases described in shift workers [22].
Sleep loss has practical implications for aerospace opera-
tions and is of concern to the Transportation Safety Board and
the Aviation Safety Board. Loss of sleepas determined by
EEG, ECG, and subjective ratingshas led to high fatigue
ratings among airline pilots, particularly those on long-haul
or overnight flights [23,24]. Self-reports of fatigue have been
accompanied by changes in EEG and ECG variables, partic-
ularly on flights involving long duty hours and consecutive
night work, which may place excessive demands on mental
and physiological capacity [25].
Although electroencephalography is the considered the
gold standard for sleep monitoring, it is also expensive
and time-consuming. Modified self-winding accelerometers
known as actigraphs, usually worn on the test subjects
nondominant hand like a wristwatch, were introduced in the
1950s to measure human physical activity. Several actigraphs
have been developed since that time and have been used to
monitor sleep [26].
Actigraphy provides a continuous measurement of the motor
component of behavior [26]. In principle, the technique involves
transforming the physical attributes of body movements into
analog signals that can be directly recorded or further trans-
formed into digital counts and scored in electronic memory for
prolonged periods [27]. The motion sensor of an actigraph
20. Fatigue, Sleep, and Chronotherapy 415

generates a signal voltage each time it is moved. This signal

can be filtered or amplified according to various selectable
settings to measure changes in overt behavior reflected in
actigraphy readings. When a person is awake there is move-
ment of the arms and when a person is asleep, this movement
is much less. So, actigraphy can be used as an indirect mea-
sure to determine and record when an individual is asleep and
awake. Actigraphy is now used as a tool in sleep research,
psychiatry, and chronobiology.
One of the main uses of actigraphy has been the assessment of
sleep [28]. Several automatic sleep-wake detection algorithms
have been developed and refined for use with actigraphy that
have been shown to correlate well with traditional EEG sleep
assessments, although the strength of the correlation depends
on which algorithm is used.
Actigraphy has been used as an objective measure of sleep Figure 20.1. Sleep restraints and sleep quarters on the mid-deck of a
during space flight. A recent study showed high correlations Space Shuttle. (Photo courtesy of NASA)
between actigraphy and polysomnographic measurements for
sleep duration and efficiency and for the number of minutes of
wakefulness between bedtime and wake time [29]. However,
the actigraph used in that study did not detect an instance of a
long interval between going to bed and the onset of sleep.

Sleep in Space
Substantial, albeit mostly anecdotal, evidence exists that sleep
is often impaired in microgravity. Some crewmembers state
that arousal from sleep is common and sleep quality is poor, so
they use sedatives in attempts to promote sleep. This practice,
which does not ensure restful sleep, can result in diminished
efficiency during work time. Continuous reductions of sleep
time and increases in sleep latency have been reported in earlier
missions [30], and more pronounced sleep disturbances have
been reported by dual-shift crews [3133].

The Spacecraft and Spaceflight Environment

A unique problem for spaceflight crews who would like to
achieve restful sleep in microgravity is to assume a supine
sleeping posture. To achieve this sleeping posture during a
mission, crews use sleep restraints (Figure 20.1) that anchor
them to the sleep area so as to prevent their floating. On
dual-shift missions, astronauts and cosmonauts sleep in
lightproof, noise attenuating bunk areas. On the Interna-
tional Space Station, crewmembers have sleep stations that
can be used as a rest or break area in addition to serving as a
sleep area (Figure 20.2).
The environmental conditions most likely to disturb sleep
and impair performance during space flight in low earth orbit
are thought to be noise, the short light-dark cycle, tempera-
ture, confinement, and frequent changes in the sleep wake
cycle. Results from a noise-monitoring study on a Space
Shuttle mission indicate that mission operations were not Figure 20.2. Cosmonaut Yuri Usachev relaxes in a personal sleep
significantly impacted by noise, but crewmembers had to use compartment on the Russian segment of the International Space Sta-
earplugs during sleep [34]. Crewmembers also experienced tion. (Photo courtesy of NASA)
416
interference with their ability to concentrate, relax, sleep,
and communicate verbally during that flight, and some of the
crewmembers reported fatigue and headaches from the noise
levels. The flight deck, the sound pressure level of which
was 63 dBA, was considered the most acceptable of all three
habitable areas during this flight (flight deck, middeck, and
SpaceHab module). Crewmembers rated the noise level in the
SpaceHab as unacceptable even under minimum background
noise conditions [34]. These noise conditions, coupled with
other environmental or physical aspects of the sleep quarters
(e.g., heat, CO2 build-up, posture, bed comfort) often contrib-
ute to less-than-optimal sleep conditions in space.
Results of a study of Spacelab mission sleep-activity sched-
ules and a simulation of shifting work-rest periods showed
distinct increases in awake time, decline of the sleep effi-
ciency index, and desynchrony of circadian rhythms [35,36].
Based on these findings, the space medicine community has
recommended that planning in-flight work-rest schedules
must include consideration of circadian rhythmicity in order
to prevent sleep disturbances [37]. On some Space Shuttle
missions, the crew works in two teams, in which the work
and sleep periods of each team are staggered by several
hours in a dual-shift schedule, to increase productivity. In
one analysis of sleep on Space Shuttle missions, Santy and
colleagues reported shorter sleep duration and greater use of
sleep medications during dual-shift missions than on single-
shift missions [38].
In another study, Monk and colleagues measured sleep and
circadian rhythms in four astronauts aboard an orbiting Space
Shuttle [39]. Although the circadian rhythms of core body
temperature, urinary melatonin sulfate, and cortisol did not
significantly change in these four astronauts during the mis-
sion, the duration of both total sleep (mean, 6.1 h/day) and
delta sleep was shorter during flight than before flight. Dijk
and others reported similar decreases in sleep duration (to
about 6.5 h/day) in five astronauts on two subsequent Space
Shuttle missions [40].
Medical debriefing records from 239 astronauts on 44 dif-
ferent Space Shuttle missions of 317 days duration were
recently evaluated with regard to work-rest schedules and
sleep characteristics. On average, these astronauts slept for
a mean of 6.19 h during each 24-h subjective day during
missions. Crews worked on a single-shift schedule on 28 of
these missions and a dual-shift schedule on the other 16 mis-
sions. The mean ( standard deviation) sleep durations were
6.23 0.92 h on single-shift missions and 6.13 0.97 h on
dual-shift missions. Crewmembers on some of these missions
underwent light-assisted sleep-shift entrainment before flight,
which is discussed later in this chapter.
All of these results point to the existence of a sleep debt
that could result in fatigue and performance decrements dur-
ing space flight. It should be borne in mind, however, that the
complexity of in-flight sleep schedules and other confounding
factors such as use of sleep medications, a noisy and subop-
timal sleep environment, work demands, and preflight sleep
L. Putcha and T.H. Marshburn
entrainment protocols that vary from flight to flight have lim-
ited any meaningful assessments of sleep in space.
Fatigue
Fatigue is a universal complaint that accompanies almost
every illness, whether mental or physical, and often signals
the occurrence of some abnormality [41]. Described as a per-
ception arising from a complex interplay of somatic and psy-
chological factors [42], fatigue is a subjective self-evaluation
of sensations and is associated with discomfort, decreased
motor and mental skills, and increased aversion to performing
tasks [43]. Fatigue is considered to be a protective mechanism
that alerts the individual to the need for rest. The assessment
and management of fatigue in human beings involves a wide
range of activities addressing physical, psychological, cogni-
tive, and spiritual dimensions [41].
Fatigue can impair information processing and reaction time
and can also result in errors that can lead to accidents [9,44].
Although identifying fatigue as a contributing factor in an
accident can be difficult, estimates of the percentage of acci-
dents involving fatigue have been made for different modes of
transportation. These estimates vary from very low to as high
as about one third of all accidents. For example, about 21%
of aviation accidents, 3.6% of fatal highway accidents, and
33% of train accidents have been attributed to human factors,
especially the general issue of fatigue [45]. The transporta-
tion industry recognizes fatigue as a major contributing fac-
tor in accidents; the aviation industry and the U.S. Air Force
are undertaking systematic research to develop fatigue models
that can predict performance failures [46].
In the operations world, fatigue is viewed as a simple con-
dition that is related to the amount of time spent working on
a given task [47]. However, recent knowledge suggests that
fatigue results from a complex interplay among several fac-
tors, including the duration and quality of sleep, shift work,
circadian rhythms, drug and alcohol consumption, and time of
day. Indeed, sleep, waking performance, and alertness are all
profoundly influenced by circadian rhythms [4851].
Fatigue is believed to be a response to stress, but measures of
energy expenditure (in caloric output) and impairment of per-
formance often do not correlate with an individuals perceived
level of fatigue. A well-motivated person can compensate for
a feeling of weariness [52]. The complexity of the relationship
between stress and fatigue may reflect individual variations
in temperament, coping styles, the ability to perform a task,
and mental and physical fitness as well as environmental fac-
tors related to comfort, such as noise, light, temperature, and
humidity [52,53].
Information collected from U.S. Air Force flight crews
on acute and cumulative fatigue and other stressors during
Operation Desert Shield emphasized that an individuals
sleep history, recent duty-day cycles, subjective fatigue
level, scheduling patterns, nutrition, and billeting facilities
20. Fatigue, Sleep, and Chronotherapy
all contributed to fatigue and low levels of alertness [54]. Part
of that study also included collecting data on sleep, task load,
fatigue, and stress of extended-range operations from pilots on
long-haul routes involving two consecutive night flights with
a short layover between them. Those pilots lost an average of
9.3 h of sleep, resulting in an increase in fatigue rating that
reached critical levels during the return flight. Motor activity,
brainwave activity, and heart rate measurements all indicated
drowsiness and low states of vigilance and alertness during
both night flights that was greater extent during the second
flight. These results suggest that extended duty schedules may
impose excessive demands on the mental and physiological
capacity of crews [23].
Any study of fatigue must consider the conceptual distinc-
tions among the measures of fatigue that are most appropri-
ate to the goals of that study [55]. For example, physiological
variables such as blood pressure, pulse, or hematologic mea-
surements (e.g., complete blood count, sedimentation rate) are
not good indicators of early fatigue; rather, measurement of
heterophorias, use of questionnaires, or other subjective eval-
uations are more effective markers of early fatigue [56].
Operational flight surgeons are often responsible for deter-
mining the aeromedical readiness of aircrew members, whose
accumulated flight time often exceeds standard limits. Fatigue
surveillance and monitoring have been used to ensure opera-
tional safety in aircrews that must complete extended missions
[56]. Measurements of body temperature, salivary melatonin
and cortisol levels, motion (by actigraphy), and subjective
measures have also been used to monitor fatigue and circadian
cycles in pilots [57].
Fatigue During Space Flight
Most of the information available on fatigue in space is
anecdotal, as no systematic or scientific studies of fatigue
in astronauts or cosmonauts have been conducted on either
short-duration or long-duration space flights. In part, this gap
results from the lack of sensitive measures or methods with
which to estimate fatigue in space. Some investigators have
suggested that the work demands on crews during extended
space flights resemble those of lengthy sport trials in which
athletes are stressed by confinement yet expected to maintain
a high level of performance while staving off fatigue and per-
formance decrements [58]. If so, then perhaps astronauts and
cosmonauts could use coping strategies and recovery tech-
niques analogous to those used by athletes to avoid serious
functional impairments.
Instances of overt, serious functional impairment of space
flight crews caused by adverse psychological responses have
not been documented in the U.S. space program to date. How-
ever, transient disorientation, spatial illusions and visual dis-
turbances, sleep disturbances, and instances of substandard
performance have been reported [59]. Operational experience
accruing on the International Space Station will help in char-
acterizing this important performance factor.
417
Circadian Rhythms
Many endogenous physiological functions undergo cyclical
variations over time. The periodicity spectrum of biological
functions includes ultradian rhythms, which have a period of
less than 20 h; circadian rhythms, with a period of about 24 h;
and infradian rhythms, with cycles lasting longer than 28 h
[60].
Human circadian rhythms generally are synchronized to
the 24-h day resulting from the Earths rotation. The photo-
period, defined as the ratio of daylight to darkness hours, is
considered the primary external synchronizer (zeitgeber) of
biological rhythms. The internal circadian pacemaker, located
in the suprachiasmatic nucleus of the brain [51], synchronizes
the various biological rhythms with each other. Each rhythm
has a distinct waveform that can be characterized in terms
of amplitude (the distance between the mean value and the
peak [maximum] or trough [minimum]); phase (the time ref-
erence point of the rhythm); acrophase (the time of maximal
or minimal value); and mesor (the mean value). A phase shift
refers to an advance or a delay of the reference point of either
the biological rhythm or the timing of the environmental cue,
typically while maintaining the duration of the period. The
consequences of circadian rhythm changes, whether resulting
from shift work, transmeridian flight, or changes in the length
of subjective day, have been called desynchronosis, dysrhyth-
mia, dyschrony, jet lag, or jet syndrome [61].
Markers of Circadian Rhythms
In addition to sleep and alertness, several vital physiologic
functions show circadian rhythmicity, including gastrointes-
tinal, cardiovascular, and immune functions; thermoregula-
tion; and DNA synthesis (Table 20.1). Even birth and death
seems to have circadian patterns that peak at night [45]. Figure
20.3 shows examples of physiological and biochemical mark-
ers that can be used to determine an individuals circadian
rhythms. For example, melatonin and core body temperature
are the hands of the biological clock and can be used as
markers for determining the phase and amplitude of circadian
rhythms in humans [51].
Core body temperature is a common means of estimat-
ing internal clock times and is often measured continuously
over several days to get a reliable determination of the mini-
mum (bathophase) of temperature rhythm. The trough of
the cyclic diurnal variation in core body temperature occurs
between 3:00 a.m. and 5:00 a.m., a time when alertness, per-
formance, and mood are also at their lowest levels. Most phys-
iological systems tend to exhibit lower activity levels between
12:00 a.m. and 6:00 a.m.
As means of collecting and measuring melatonin have
become available, the rhythm of this pineal hormone has
become an important marker of the endogenous human circa-
dian system. The phase response curve of melatonin, although
still not fully characterized, seems to be approximately oppo-
418 L. Putcha and T.H. Marshburn

Table 20.1. Organ systems and functions affected by circadian site in phase to that of body temperature, i.e., the nocturnal
rhythms. decline of body temperature is the opposite of the rise in
System Function melatonin, and peak melatonin values are associated with the
Kidneys Urinary excretion of K+, Na+, Cl, Ca++, Mg++, trough temperature values. This strict relationship is observed
H2O, H+ during light-induced phase shift [63] as well as under normal
Endocrine systems Cortisol, growth hormone, insulin, rennin, aldoste- conditions. Melatonin measurements can be used to follow
rone, prolactin, testosterone, thyrotropin, lutein-
both chronic and acute effects of changes in the light-dark
izing hormone, gonadal steroids, melatonin
Gastrointestinal system Acid secretion, liver function
cycle on the human circadian system.
Pulmonary System Bronchoconstriction Another common marker of circadian rhythmicity is corti-
Cardiovascular system Blood pressure, cardiac output, heart rate, myo- sol level. Although cortisol rhythms show a series of pulses
cardial infarction, ischemia during the 24-h day, circulating cortisol levels have a consis-
Hematologic system Leukocyte counts, hemostasis, clotting factors tent circadian rhythm in which the major peak occurs early in
Immune system Immediate hypersensitivity, leukocyte function,
the morning (soon after rising), a smaller peak occurs in mid-
detoxification of bacterial toxins
Other Thermoregulation afternoon, and the lowest levels occur in the early evening
Metabolism of salicylates, amphetamines, sulfon- hours [64]. Measurements of cortisol levels, however, are
amides, opiates, anesthetics, histamine, heparin, easily confounded, as this stress hormone becomes elevated
and other drugs during stressful conditions [65].
DNA synthesis by bone marrow, intestinal tract
cells
Resistance and susceptibility to chemotherapy and
radiotherapy
Circadian Rhythms in Space
Source: Modified from Kryger et al. [51]. Early investigations of the effects of the space environment on
sleep-wake cycles and performance in primates indicated that
circadian rhythms of the various parameters persisted, but the
microgravity environment significantly influenced tempera-
ture regulation and circadian timing [6668]. Ground-based
space flight simulation studies with humans (e.g., bed rest,
antiorthostatic bed rest, and isolation) have shown evidence
of phase shifts of circadian rhythms [6974]. In most of these
studies, however, hypokinesia may have been the main factor
contributing to the changes.
To better understand the interaction of work-rest activity
schedules and biological rhythms during confinement in a
closed life support system, NASA conducted two separate
studies in which 8 healthy subjects lived in an isolation
chamber at the Johnson Space Center for 60 or 91 days. The
work-time light intensity inside the chamber was lower (50
100 lux) than baseline levels (10001500 lux). Although no
significant differences in sleep variables were noted between
baseline and chamber stay periods, melatonin acrophase was
delayed by about 23 h during the chamber stay period as
compared with baseline values. Both the lighting and circa-
dian rhythm effects in this study were thought to be similar
to those observed during space flight or other ground-based
simulation studies [75].
Circadian rhythms of oral temperature and urinary calcium,
potassium, and 17-hydroxycorticosteroid levels were measured
in 2 astronauts before and after the 9-day Spacelab-1 mission
(STS-9; November 28December 8, 1983) [76]. As this mis-
sion was to be conducted in two shifts, with the study subjects
working nights while two other astronauts worked during
the subjective day, the study subjects underwent sleep-shift
entrainment before launch. Preflight and postflight data were
analyzed with a cosinor method to determine the acrophase (the
Figure 20.3. Daily rhythms of key circadian markers. From Rhoades time at which the study variable was at its peak) during each
and Tanner [62] 24-h period. The acrophase for urinary calcium had shifted
20. Fatigue, Sleep, and Chronotherapy
in both astronaut-subjects, and the acrophase for potassium
excretion had shifted in one astronaut-subject, at the postflight
measurement. The acrophase for steroids had not changed
[76]. In addition to inducing circadian desynchrony, the dual-
shift work-rest schedule may have contributed to anecdotal
reports of crew fatigue on this mission.
A subsequent study involved use of a preflight time-shift
protocol and preflight, in-flight, and postflight measure-
ment of levels of adrenocorticotropin, cortisol, prolactin, and
growth hormone in saliva in four astronauts [77]. The results
indicated that the time-shift protocol prevented any major
chronobiological disturbances from occurring during flight,
and levels of all of the substances measured were maintained
at reasonably low levels in flight. Further, no major changes
were evident in the cortisol rhythm during flight. Dijk and col-
leagues [40] later reported that urinary cortisol levels seemed
higher during Space Shuttle flight relative to preflight levels,
but this increase was not statistically significant. No obvious
changes in urinary cortisol levels were noted during the early
days of this mission, but the cortisol rhythm seemed to be
delayed relative to sleep schedule later in the flight. Normal
cortisol rhythms were restored after landing.
With regard to sleep, preflight patterns of non-REM and
REM sleep were found to continue during the 1965 Gemini
VII mission [78]. In one astronaut, in-flight measurements of
core temperature and subjective alertness revealed a delayed
rhythm during the 8-day space flight and a change in the
structure of non-REM/REM cycles [79]. The latter finding
was thought at the time to be evidence that sleep structure did
not adapt to space flight conditions; however, the problems
experienced by this crewmember (shorter sleep periods with
disruptions) may have resulted from difficulty with thermal
comfort and finding a comfortable sleeping position.
In a more recent study of sleep and circadian rhythms, Gun-
del and colleagues [80] reported that the circadian phase of
body temperature was delayed by about 2 h during a long-dura-
tion flight aboard the Russian space station Mir as compared
with baseline findings. The authors concluded that observed
disturbances in sleep did not seem to result from either the
circadian phase delay or changes in sleep structure.
Finally, results obtained from four astronauts on a 17-day
space flight indicated that circadian rhythms in orbit were
very similar in phase and amplitude to those on the ground
and were appropriately aligned for the required work-rest
schedules for that mission [39]. Similar trends were reflected
in mood, alertness, and performance scores. No changes in
these variables were noted between the early and later days of
the mission. However, overall sleep duration and duration of
slow-wave (delta) sleep were both shorter during flight than
before.
Light and Circadian Rhythms
Light has profound and multiple effects on human circadian
rhythms and thus on sleep and performance. These effects can
419
be elicited by sunlight or artificial light and depend on the tim-
ing and intensity of exposure. Daily exposure to light entrains
rhythms to environmental cycles and also maintains internal
synchrony among various physiological processes [50,81
87]. Bright light is known to be a strong zeitgeber of circadian
rhythms [81,85], but the contributions of other environmental
cues to circadian rhythms are less clear.
During the subjective night (the time a person perceives as
being nighttime), exposure to light of sufficient intensity can
shift the phase of free-running or entrained circadian rhythms.
In addition to these clock effects, light has masking
effects on overt circadian rhythms. For example, light expo-
sure can acutely suppress nocturnal melatonin synthesis and
attenuate nighttime declines in temperature and performance
[56,8892]. As a result, altered exposure to light can, directly
or indirectly, disrupt circadian rhythms, sleep, performance,
and well-being.
Several situations on Earth disrupt circadian rhythms, in
part because of changes in light. Traversing time zones, shift-
ing ones usual work schedule, or living in constant or unac-
customed lighting conditions (e.g., caves or the Arctic) all
have documented effects on physiological rhythms and per-
formance. Space flight could also be expected to have such
effects because of the lack of a natural 24-h light-dark cycle.
Most human space missions in low Earth orbit expose the
crews to sunrises about every 90 min. Such unusual patterns
of light exposure may have adverse medical and operational
consequences, but few data have been collected to document
the illumination conditions during Space Shuttle operations.
Although a free-running circadian rhythm, similar to that
found in human subjects in isolation, was speculated to occur
in space [93], Gundel et al [80]. dismissed this idea after their
investigations on Mir revealed that crewmembers circadian
systems do not show a free-run pattern but rather a phase
delay.
The Light Environment Aboard Spacecraft
The daily alternation between light and darkness synchro-
nizes human circadian rhythms to the 24-h day. A nonlinear
relationship exists between the intensity of the light stimulus
(measured in lux or foot candles) and the biological response
it elicits. One lux of light is that emitted by a single candle
(one international candela) viewed from a 1-meter distance;
a typical dinner candle emits about 12 lux, a small artificial
lamp, about 180 lux, and a 60-watt, white incandescent bulb,
about 855 lux. The range of light intensity in work environ-
ments is quite large, typically ranging from 2002,000 lux
depending on work conditions. Light intensity outdoors on a
sunny day can range from 10,000100,000 lux depending on
weather conditions and geographic location.
During space flight, both the intensity and timing of illumi-
nation differ markedly from the patterns of light exposure on
the ground. Space Shuttle crews are exposed to light from two
sources: interior fixtures, which provide low-intensity artificial
420
illumination, and direct or indirect sunlight, which comes
through the heavily filtered windows of the flight deck and
varies according to the spacecrafts orbital path, altitude, and
orientation (facing the Sun versus Earth).
Although such unusual patterns of light exposure may have
adverse medical and operational consequences, few data have
been collected to document illumination during flight opera-
tions aboard the Space Shuttle. The single systematic study
performed to date involved the use of Actillumes (Ambulatory
Monitoring, Inc., Ardsley, NY), digital monitoring systems
containing a linear accelerometer to record motion and a pho-
tometer to measure light. Two of these devices were mounted
on the flight deck and middeck, and two astronauts wore
wristwatch-style devices on their nondominant arm through-
out the mission.
Illumination on the flight deck consisted of infrequent,
brief spikes of very high luminance on a low-illuminance
background that cycled every 88 min (mean illuminance, 83.8
432 lux; range, 018,479 lux). Although the high-intensity
spikes probably accounted for most of the variability in light
exposure, such spikes were very brief; during the 14,900 min
of recording, luminance levels were 2,000 lux or more less
than 0.4% of the time. On the middeck, luminance levels were
lower but more consistent than those on the flight deck (mean,
11 7 lux); at no time did middeck illuminance exceed 86 lux.
The recorded 88-min periodicity was the same on the middeck
and flight deck. As the Space Shuttle middeck has only one
small window, the source of the periodicity on the middeck
was probably the indirect illumination from the flight deck.
The luminance measured by the actillume devices was higher
than that measured by the fixed devices, but data from both the
mobile and the fixed devices had the same periodicity. Finally,
the mean work-time luminance levels were lower during flight
than on the ground.
Clearly, light exposure during space flight differs from that
on Earth in both timing and intensity. Both mean light inten-
sity and the time of exposure to high luminance levels were
drastically lower in flight than on Earth. Decreased light expo-
sure has been linked to sleep and mood disorders and to loss
of circadian entrainment and coupling [94]. The observation
that in-flight luminance levels were similar to those reported
in a survey of natural light exposure among 40- to 64-year-old
adults [95] led to speculation that circadian and sleep deficits
during space flight might resemble age-related sleep changes
[96]. The relatively common use of sleep medications dur-
ing space flight [97] seems to support this speculation. Thus
changes in the timing and intensity of illumination on the
Space Shuttle flight deck and inadequate illumination in the
middeck could disrupt the circadian rhythms, sleep, perfor-
mance, and well-being of shuttle crews.
On the other hand, illuminance patterns recorded dur-
ing this single flight may or may not be typical of most
Space Shuttle missions. In a recent investigation on two
other Space Shuttle flights [40], subjective daytime illu-
minance aboard the spacecraft was reported to be very low,
L. Putcha and T.H. Marshburn
ranging from only 5.0 lux to about 79.4 lux. However, light
exposure during missions could differ not only because of
the orbital path and orientation of the spacecraft, but also
because of specific mission activities. The lighting con-
ditions on the Space Shuttle flight deck presumably dif-
fer from those in the Spacelab or other payload modules
or aboard the International Space Station; certainly they
would differ substantially from light exposure conditions
during extravehicular activities.
The minimum light intensity necessary for circadian
entrainment or phase shifting is currently under investigation.
A light stimulus as weak as that produced by ordinary arti-
ficial lamps (about 180 lux) can phase-shift the endogenous
circadian rhythms of plasma melatonin and cortisol [98].
Although some information is available regarding the light
intensities necessary to mask or change endogenous cycles
such as these, little is known about the exposure duration
necessary to achieve such effects; thus the high-luminance
spikes recorded on the Space Shuttle flight deck may or
may not affect endogenous circadian rhythmicity.
Strategies for Improving Sleep
and Performance in Space
Light therapy and pharmacologic countermeasures are now
used in the U.S. space program to enhance the sleep and per-
formance of astronauts scheduled for shiftwork aboard the
Space Shuttle [38,96,99,100]. It is also accepted by the crew
health providers at NASA that even astronauts who are not
scheduled for shiftwork during a mission would benefit from
similar interventions to reduce sleep disturbances and stabi-
lize circadian rhythms during space flight.
The limited information collected to date suggests that use
of sleep-shift protocols before launch can prevent chronobio-
logical disturbances [101]. Gundel and colleagues have sug-
gested other improvements such as introducing a nap schedule,
which has been shown to alleviate spontaneous sleepiness of
civil aviation pilots in the cockpit [102].
Another means of improving sleep and performance
in operational environments is the use of pharmacologic
agents. Midazolam (for sedation) in combination with flu-
mazenil (for recovery) is used to promote rest and maintain
performance during U.S. military operations; this combina-
tion has been shown to eliminate performance impairment
[103]. When sleep is not possible, the U.S. Army endorses
the use of caffeine at doses of 300600 mg to enhance alert-
ness; this practice can improve performance for 1012 h
after 48 h of sleep loss [104,105]. In another study, dextro-
amphetamine was shown to improve helicopter pilot perfor-
mance during short periods of sleep loss without producing
adverse side effects [106]. This drug has also been effective
in sustaining pilot performance and in reducing feelings of
fatigue, confusion, and depression without significant side
effects [107].
20. Fatigue, Sleep, and Chronotherapy 421

Entrainment Strategies for Space Shuttle

Crewmembers
An objective of the preflight use of light-assisted schedule
entrainment is to prepare crewmembers for launch activities
as well as in-flight work-sleep schedules. Part of the cur-
rent preflight protocols thus include the gradual adjustment
of sleep schedules so as to support activity schedules during
flight. Sleep schedules may be phase advanced, in which the
new bedtime is moved earlier (similar to moving eastward
across time zones) or phase delayed, in which the new bed-
time is moved later (similar to moving westward across time
zones). Phase delays are typically more effective in entraining
new sleep schedules, but the success of either type of phase
shifting can be enhanced with appropriate light therapy. Cur-
rently, no supplemental light treatments are administered dur-
ing space flight.
In an attempt to extend the time crews can work aboard
the Space Shuttle, NASA adopted use of dual-shift missions,
in which two teams of crewmembers work in two separate
shift groups. To entrain crews for such schedules, a preflight
period of sleep shifting, assisted by bright light treatment to
shift endogenous circadian rhythms, is currently used begin-
ning during the preflight quarantine period until the end of
the mission (Figure 20.4). Approximately 28% of the 44 mis-
sions from STS-40 to STS-99 had dual-shift work schedules;
the remaining flights had single-shift schedules. The phase-
advance times for all missions, both single- and dual-shift,
ranged between 1.2 and 12.0 h, and the phase-delay times
ranged between 0.3 and 14.5 h (Figure 20.5).
Figure 20.5. Frequency distribution of sleep-shift phase advances
and phase delays (both shown in hours) for Space Shuttle flights. The
Y-axis refers to the number of Shuttle flights

The entrainment protocols are designed specifically for

Figure 20.4. Diagram of a representative light-assisted sleep-shift
entrainment protocol for a dual-shift Space Shuttle mission
each mission to maintain in-flight activity schedules for that
mission; no standard protocols for entrainment are available.
The entrainment and phase-shift maintenance protocols prac-
ticed by the U.S. space program obviously differ from the
shift-operations entrainment programs used for shift work-
ers on Earth, in part because no real-time light maintenance
treatment is provided on the Space Shuttle. Another unique
aspect of these experimental shift protocols is that the entrain-
ment protocols often include manipulation of sleep schedules
during flight, again without supplemental light treatment.
Concerns about the safety and effectiveness of using these
complex protocols for promoting sleep and alleviating fatigue
in space flight crews during missions point to the need for
further studies to better quantify operational performance and
fatigue levels during flight so that the most effective sleep
adjustments can be planned and implemented.
Limited information exists on the effectiveness of using
these preflight sleep-shift protocols to promote sleep and
enhance performance during space flight. Preliminary testing
suggested that preflight sleep-shift protocols were effective
422
Figure 20.6. Influence of phase advance and phase delay on sleep
duration in space crewmembers
in preventing chronobiological disturbances [101]. Another
group studied the effectiveness of preflight light-assisted
sleep entrainment for astronauts on dual-shift missions by
testing rates of excretion of melatonin sulfate and cortisol in
urine and saliva as markers of circadian shift. Results from
that study indicated that the sleep-shift protocol was suc-
cessful in producing phase delays in melatonin and cortisol
rhythms [108].
Some anecdotal evidence from crew medical debrief
records is also available regarding the effectiveness of pre-
flight sleep-shift protocols and in-flight adjustment of sleep
schedules on space operations. Crewmembers on nine sin-
gle-shift Space Shuttle missions underwent preflight sleep
entrainment to delay their sleep schedules, and crewmembers
on seven, single-shift flights underwent preflight entrainment
to advance their sleep schedules. Crewmembers in the first
(phase-delay) group slept an average of 6.61 0.78 h per 24-
h period during their missions, whereas crewmembers in the
other (phase-advance) group slept an average of 6.08 0.81 h
per 24-h period during flight (unpaired t test, P < 0.01) (Figure
20.6). Crewmembers who had not undergone entrainment
reported sleeping an average of 6.06 1.01 h per 24-h period.
Thus, although preflight entrainment may be beneficial for
delayed sleep schedules, it does not seem to improve sleep
for crewmembers on advanced sleep schedules. Moreover, the
amount of sleep obtained across all space flights, regardless of
shift schedules or sleep shifts, seems consistently low, ranging
between 6.1 and 6.5 h per 24-h period. Such sleep decrements
have been observed regardless of whether crewmember circa-
dian rhythms remain entrained and undisturbed during flight.
Conclusions
For the immediate future, certain changes could be made to
ensure that crewmembers sleep patterns, shifted or not, are
undisturbed and remain entrained. Crewmembers scheduled
to work the night shift on their missions could benefit from
preflight phase-shifting so that their phase-response curve
L. Putcha and T.H. Marshburn
coincides with the planned in-flight work-rest schedule, which
would enhance the quality of their sleep during flight. Confin-
ing light exposure to these crewmembers to their subjective
night period during flight would minimize the potentially dele-
terious effects of changes in light-exposure patterns and inten-
sity in space. Mission planners and medical personnel should
design sleep schedules that are regular and capable of main-
taining entrainment in addition to meeting the other sched-
uling requirements of missions. Improved in-flight lighting
that affords more continuous bright light in both the middeck
and the flight deck would be helpful in circadian entrainment,
although this improvement would require equipment upgrades.
Padding should be provided for sound dampening in sleeping
quarters. In-flight pharmacologic interventions might benefit
from a change in focus toward increasing alertness rather than
attempts to induce sleep. Finally, interventions after landing
may be useful in aiding postflight readjustment, which has
occasionally been reported as difficult.
In summary, our operationally significant observations doc-
umented to date are as follows. First, sleep onset and quality
during flight in shift-work crews, even with the use of sleep
medications, is less than optimal. Second, circadian rhythm
delays, as indicated by melatonin acrophase measurements,
are longer during flight than the values targeted during pre-
flight light-assisted sleep-shift entrainment, and these shifts
are maintained during flight. Third, circulating melatonin lev-
els of shift-work crews during their subjective work time are
higher during flight than before. Fourth, spacecraft lighting,
especially in the Space Shuttle middeck and in ISS, is less
than optimal in terms of both intensity and exposure pattern
during flight.
In conclusion, based on the limited information available
on the sleep, light-exposure, and circadian rhythms of astro-
nauts and cosmonauts during short-duration single-shift and
dual-shift space flights, we propose the following operational
recommendations, which may help to enhance crew health
and performance during space flights: (1) Consistent in-flight
sleep times should be maintained throughout the mission. (2)
If shifting is needed, circadian rhythms should be delayed
rather than advanced during flight. (3) Sleep shifting protocols
and schedules should be standardized and the amount of shift-
ing should be minimal. (4) In-flight lighting conditions should
be improved. (5) Means of dampening sound (e.g., padding)
should be provided in sleep quarters. (6) In-flight interven-
tions to improve alertness should be provided, and use of sleep
aids should be minimized. (7) Postflight intervention options
for circadian retraining and enhancing rest should be provided
as needed.
Finally, additional research on sleep and fatigue in space
may help in optimizing the above strategies and uncover
nuances of space flight that may be further points of focus
for countermeasures. This might include: (1) collection of
comprehensive, real-time sleep data during space flights; (2)
analysis of data from all flights including short-duration
and long-duration, single shift and dual shift schedules for
20. Fatigue, Sleep, and Chronotherapy
circadian rhythms and sleep variables; (3) testing and valida-
tion of intervention protocols to facilitate sleep and augment
performance; (4) optimization and standardization of preflight
entrainment protocols; and (5) supplementation of preflight
programs with inflight entrainment protocols that can support
crew activity schedules.
Acknowledgments. The authors appreciate the technical sup-
port of Drs. Stephen F. Sarabia and Chantal A. Rivera and the
library research by Kim P. So and Janine C. Bolton.
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21
Health Effects of Atmospheric Contamination
John T. James
Safe air for breathing is the most immediate resource required
by spaceflight crews. Clearly, gross parameters of the breath-
ing atmosphere, such as temperature, pressure, O2 tension,
and water vapor content, must be maintained within physi-
ologically acceptable ranges. Even if these properties are well
controlled, exposure to the trace contaminants and particles in
the atmosphere confers a significant health risk. This chapter
describes strategies for minimizing toxicologic risks to crew
health, outlines how toxic exposures can be recognized in the
crew and the space environment, and describes how crews and
their environment can be restored to healthy conditions after
accidental exposure to a toxic compound.
General Principles of Managing Exposures
to Toxic Compounds in a Spacecraft
An axiom in spaceflight toxicology is that the risk of air con-
tamination is managed first and the consequences of plausible
failures managed second. Risk can be viewed as the probabil-
ity that an unwanted event will occur multiplied by the seri-
ousness of such an event when it occurs. For example, the risk
from a rare, serious event may be comparable to the risk from
a likely, inconsequential event.
Human space flight is an inherently risky activity, and the
risks associated with air contamination must be managed in
this context. Health risks from air contamination cannot be
controlled so as to eliminate all risk to the crew; however, such
risks can be controlled to acceptable levels within the context
of human space flight. Since certain defined failures (e.g., fire
or smoke in the cabin, leaks from spacecraft systems, excess
CO2 in the atmosphere, etc.) can be anticipated, the manage-
ment of their consequences is guided by flight rules regarding
atmospheric monitoring, protection of the crew from expo-
sure, decontamination procedures, and treatment of exposure
victims.
Another axiom of spaceflight toxicology is that the human
occupants of a space vehicle and the environment of the
vehicle that they occupy must be viewed as an integrated
human-vehicle system. Thus the patient should be treated
first, but the patients environment may need to be treated
(decontaminated) as well. For example, if a crewmember dis-
covers a foreign body in his or her eye, the flight surgeon, after
immediately treating the patient, also must determine whether
the environment needs to be treated to remove any additional
particles. Air contamination in spacecraft is unique in that air-
borne particles, which would settle out of the atmosphere at
Earth gravity, remain suspended indefinitely in microgravity.
These particles could pose a lasting threat to the crews eyes
and respiratory systems.
Similarly, after a system leak, aerosols of low-volatility
liquids (e.g., ethylene glycol) can accumulate rapidly on any
cool surface. As the accumulated liquid slowly evaporates, its
vapors can present a long-term health threat to the crew if the
surfaces exposed to that liquid are not cleaned. Moreover, accu-
mulated liquid can provide a substrate for microbial growth,
which can produce toxic metabolites. If carbon monoxide
(CO) enters the spacecraft atmosphere in high concentrations
and is inhaled by the crew, both the crew and the environment
must be treated to achieve a successful outcome.
Carbon Monoxide
Sources
A fire or smoldering combustion is one of the most feared
events in a sealed environment, especially in a space vehicle,
which invariably will have limited escape options. A major
health threat from combustion in a sealed space is the produc-
tion of highly toxic products that can have both immediate
and delayed toxic effects on crewmembers. Although not the
most toxic of combustion products, CO has proven to be one
of the most hazardous because it is produced in large quanti-
ties in most fires. In microgravity, since convection does not
renew O2 in the vicinity of a fire, less oxidation of the fuel
occurs and a larger portion of CO is produced than in a com-
parable Earth-based fire. In addition, the magnitude of the fire
427
428
can be misleading in terms of the amount of CO produced, an
observation that has been well illustrated by the two fires that
occurred on board the Russian space station Mir during the
NASA-Mir Program.
The more highly publicized fire that took place on Mir,
which occurred in the solid-fuel O2 generator, was an immedi-
ate threat both to crew health and to the integrity of the sta-
tion. On Mir, the solid-fuel O2 generator was used by the crew
to provide backup O2 when the O2 tension dropped below
160 mm Hg. The generator produced O2 through controlled
heating of a cartridge containing potassium, lithium, and
magnesium perchlorate that was ignited at 400C (750 F)
[1]. For unknown reasons, one of the cartridges activated by
a crewmember on 23 February 1997 caught fire and burned
out of control for several minutes. (The length of time that
the fire burned is disputed. Compounding this hazardous sit-
uation was the fact that 6 people were on board Mir at the
time, and the fire was blocking the route to one of the Soyuz
escape vehicles.) The occupants of the station quickly donned
respirators, and approximately 3 h after the fire had been
extinguished, air samples were taken in grab sample canis-
ters. Several months elapsed before all of the canisters were
returned to Earth and an analysis of their contents was com-
pleted. That analysis showed CO concentrations of 1620 mg/
m3 (1823 ppm), depending on where the sample was taken
[2]. This CO level posed no immediate threat to crew health
since the 24-h spacecraft maximum allowable concentration
(SMAC) for this compound is 20 ppm [3].
A second less highly publicized fire on Mir, on 26 Febru-
ary 1998, led to the release of much higher concentrations
of CO and caused symptoms in at least 1 crewmember. That
fire was started by the low-temperature catalytic oxidizer.
(The low-temperature catalytic oxidizer consisted of a front-
end, replaceable charcoal filter; a pair of regenerable filters
that could operate in the sorption mode to remove con-
taminants from the air or in the thermal desorption mode to
remove contaminants from the filter beds; and a back-end
catalytic oxidizer to oxidize H2 and CO.) The fire appar-
ently started in the Kvant-1 module, when regenerated filters
were switched into the flow stream before they were allowed
to cool, thereby igniting paper filters in the unit. The crew
observed a little smoke, but the fire was quickly contained
and the incident was considered minor until readings from
a portable monitor indicated CO concentrations of 400 ppm
(i.e., 20 times the recommended safety level) (Figure 21.1)
[4]. The decay profile suggested that the CO level in the sta-
tion was elevated for at least 80 h. A canister sample, taken
28 h after the fire began and analyzed in a ground-based lab-
oratory later, showed a CO concentration of 130 ppm when
the CO sensor was reading 95 ppm, indicating that the true
CO concentrations were higher than the readings given by
the portable monitor. The crew seemed fine for several hours
after the incident, but that evening and the next morning,
at least one crewmember reported having a headache and
nausea.
J.T. James
Figure 21.1. Readings from the CO sensor after the low-
temperature catalytic oxidizer burned on Mir
Other less spectacular and more predictable sources of CO
include human metabolism and a minor contribution from off-
gassing of materials. The catabolism of hemoglobin produces
approximately 32 mg of CO per person per day [5]. For a space
vehicle with 100 m3 (3,531 ft3) of free volume occupied by 3
people, this translates into a concentration accumulation of
1 mg/m3 per day, or roughly 1 ppm/day. A failure in the cata-
lytic oxidizer that removes CO thus can result in potentially
unhealthy concentrations (i.e., concentrations above 20 ppm)
in approximately 20 days. The contribution from CO off-
gassing is very small, as documented in a 209-h test of the
International Space Station (ISS) Node 1 module for contami-
nant accumulation in the absence of human occupants or air
scrubbing. Throughout that test, CO was present at no more
than trace levels [6].
In spacecraft, CO is controlled by catalytic oxidizers that
convert it to CO2, which is removed by replaceable alkali
canisters or by one of several regenerable sorbent beds. The
capacity of these systems is ordinarily scaled with appropri-
ate safety margins to maintain the CO concentration below
5 ppm at a nominal rate of CO generation. Unfortunately,
these systems can be easily overwhelmed when a fire pro-
duces large concentrations of CO in the range of a few hun-
dred ppm, as it did on Mir in 1998. Under these conditions,
the crew must be isolated from the contaminated atmosphere,
often for many hours, until the slow process of CO scrubbing
is completed. Additional CO scrubbing capability is available
on some spacecraft. Although respirators are available on all
spacecraft, they may not offer prolonged protection from a
CO-contaminated atmosphere.
Mechanism of Toxicity
Inhaled CO displaces the O2 bound to hemoglobin and has
an affinity for hemoglobin approximately 250 times that of
O2. The resultant carboxyhemoglobin (COHb) molecule can
severely reduce the delivery of O2 to body tissues, especially
those tissues (i.e., the heart and the lung) with limited anas-
tomotic development and high metabolic activity. So if the
21. Health Effects of Atmospheric Contamination
concentration of CO is only 0.08% (800 ppm), or 1/250th the
normal concentration of O2 (21%), for example, 50% of the
hemoglobin sites available for O2 binding are occupied by CO
at equilibrium. CO not only competitively reduces the forma-
tion of oxyhemoglobin in the lungs, it also inhibits the release
of O2 to the tissues by causing tighter binding between O2 and
the hemoglobin. Since the rate at which CO binds to hemo-
globin can be rather slow for a sedentary person, symptoms of
toxicity can be delayed for several hours. The binding of CO
to cytochrome oxidase and myoglobin may also contribute to
the pathophysiology of CO poisoning.
Warning Properties
One of the most important aspects of CO toxicity is its com-
plete lack of warning properties. CO is a colorless, odorless
gas, the presence of which cannot be detected by human senses
even in high concentrations. The onset of the symptoms of CO
poisoning can be such that the victim is unaware of the accu-
mulation of CO in the breathing atmosphere. This lack of a
warning property has resulted in the severe poisoning of many
persons who place themselves in semi-closed environments
with a source of combustion [7,8].
Airborne Concentrations that Cause Toxic Effects
The symptoms caused by CO exposure depend on a combina-
tion of the airborne concentration of CO, the activity level of
the victim, and the length of the exposure. These factors can
be combined in the Stewart equation to predict COHb con-
centrations in blood as an index of toxic effects resulting from
short exposures:
COHb(%) = 3.317 105 [CO]1.036 RMV t
where [CO] is the atmospheric concentration of CO in ppm,
RMV is the respiratory minute ventilation in L/minute, and t
is the exposure time in minutes [9]. For exposures to high con-
centrations that last longer than 1 h, the Coburn-Foster-Kane
equation is recommended [10], but this sort of exposure is
unlikely on board current spacecraft because of CO monitor-
ing and ready access to respirators. The Coburn-Foster-Kane
equation takes into account the dynamics of CO uptake and
release in the lungs as the blood and airborne concentrations
approach equilibrium. However, neither the Stewart equation
nor the Coburn-Foster-Kane equation provides an accurate
estimate of COHb levels when a victim has been exposed to
widely varying concentrations of CO. The symptoms associ-
ated with different levels of COHb are shown in Table 21.1.
Since the correlation between toxic effects and COHb
varies somewhat, the information given in Table 21.1 should
be taken only as a rough guide.
In a practical situation, COHb can be estimated by using the
Stewart equation and the measurements that are immediately
available to the flight surgeon. For example, if a crewmember
is exposed to CO at a concentration of 1,000 ppm for 10 min
429
Table 21.1. Symptoms of CO poisoning based on levels of COHb
in nonsmokers.
COHb Poisoning Symptoms
510% Subclinical Reduced exercise capacity, slower reaction
time
2030% Mild Headache, nausea, impaired dexterity and
judgment
3040% Moderate Throbbing headache, nausea, vomiting,
impaired dexterity and judgment
4050% Severe As above plus possible syncope
5060% Extreme Convulsions and coma
>60% Death
Abbreviation: COHb, carboxyhemoglobin.
and is moderately active during that time (i.e., with an RMV
of 15 L/min), the COHb can be calculated as follows:
COHb(%) = 3.317 105 1,0001.036 15 10 = 6%
According to Table 21.1, such an exposure would not be
expected to elicit any obvious symptoms in the crewmember.
Clinical Presentation
The characteristic ground-based presentation of a CO-
poisoned patient can include weakness, fatigue, confusion,
impulsiveness, and incontinence. Abnormal motor and sen-
sory findings may also be present [11]. In spaceflight crews,
subtle effects of CO exposure (Table 21.1) may be difficult to
distinguish from the effects associated with headward fluid
shifts and space motion sickness. Among the symptoms of
space motion sickness are impaired concentration, headache,
nausea, and vomiting [12]. Space motion sickness is very
common in crews of most space vehicles. Moderate to severe
symptoms have been experienced by 30% of crewmembers on
board early Space Shuttle flights [12]. Symptoms usually dis-
appear within 2 days of orbital insertion, although they have
lasted as long as 3 days into flight. Symptoms, such as those
cited in Table 21.1, that occur later than 3 days into flight could
suggest CO poisoning rather than space motion sickness.
If CO originates from a fire, simultaneous exposures to
other toxic compounds (e.g., hydrogen cyanide [HCN]) are
likely. Some of these compounds can produce symptoms that
are magnified beyond those associated with COHb formation.
In addition, hypoxia due to the removal of O2 from the breath-
ing atmosphere during combustion can also play a role. The
combined effects of CO and HCN exposure seem to be no
more than additive on a fractional-dose basis. The uptake of
HCN and CO should be assumed to be increased in propor-
tion to any increases in RMV caused by CO2 from the fire and
from use of the CO2 fire extinguishers present on many space
vehicles. Any narcosis induced by CO2 exposure should be
independent of that induced by CO, HCN, or hypoxia [10]. At
relatively low levels of CO, interaction with hypoxia seems to
be unimportant; however, at exposures to high concentrations
430
of CO, the effects of hypoxia are likely to be additive when
combined with those from CO [10].
Differences in Individual Susceptibility
Astronauts are generally in good health and the individual
responses to CO exposure are unlikely to vary much unless
the astronaut smokes. This is because people who smoke are
much less susceptible to the central nervous system (CNS)-
depression effects of CO exposure than are people who do
not smoke [13]. Exposures to CO at 111 ppm for 12 h led
to COHb levels of approximately 7%levels that impair the
vigilance of nonsmokers but not of smokers. Persons with
impaired lung function or with cardiovascular disease are
much more likely to experience symptoms from exposure to
a specific concentration of CO; however, such persons would
not qualify as astronauts.
Sampling and Analysis
Atmospheric CO can be measured in real time on board mod-
ern space vehicles, or archival canister methods can be used
to sample the air for later ground-based analysis. Currently on
the ISS, an electrochemical sensor is used in the compound
specific analyzer for combustion products to warn of CO accu-
mulation or release from a fire. This commercial instrument
(Industrial Scientific Corporation, Pittsburgh, PA) has a data
logger and a downlink capability so that it can be used to man-
age CO pollution in spacecraft. (Additional sensors selected
for the ISS compound specificanalyzer for combustion prod-
ucts include HCN, HCl, and O2.) The instrument was found to
perform well in combustion atmospheres generated by hard-
ware typical of that used in space vehicles [14]. An adapter
called the CO breath sampler, which is available from the
manufacturer but has not, as of this writing, been manifested
for the ISS, permits indirect measurement of COHb by cor-
relation with the CO concentration measured in the victims
breath [15]. A confounding factor for space applications, and
the reason the adapter has not been manifested for the ISS, is
that the user must inhale a breath that is relatively free of CO,
and this could only be done in a CO-polluted space vehicle if
the victims breath was inspired from a respirator and expired
into the sampling device.
Detector tubes for CO are also available on board the
ISS to assist in the measurement of CO if a fire occurs. A
pump is used to aspirate air through a glass tube containing
chemicals that produce a colored stain when they react with
CO. (The length of the stain indicates CO concentration.)
This method is totally independent of the electrochemical
sensor. The availability of 2 methods to measure CO high-
lights the high risk associated with this compound. The
probability of a fire on ISS during the lifetime of the station
is high, and consequences of a fire could be catastrophic
if appropriate preparations have not been made to manage
those consequences.
J.T. James
Archival samplers have been used for many years to obtain
air samples for ground-based analysis. For the Space Shuttle
and ISS crews, an evacuated SUMMA-treated canister that
has a 350-mL volume is used to obtain an air sample. For the
Space Shuttle, air samples are usually collected near the end
of the mission. On board the ISS, canister samples are taken
when the hatch to a new module is opened and the crew enters
that module or when air pollution is suspected. These archival
samples can be useful in understanding the magnitude of air
pollution but only long after the event has been resolved.
Protection and Treatment after Exposure
Only limited resources are available on board a space vehicle
to treat a crewmember who is exhibiting symptoms of CO
exposure. Since CO production will most likely be associ-
ated with a fire, the most important action is to ensure that
a respirator has been donned as quickly as possible after the
fire is detected and that the crew has been moved to the least
polluted portion of the space vehicle. If the fire has been
extinguished, closing the hatch between the module in which
the fire occurred and the remainder of the space vehicle is
desirable. (This action could preclude measurements of the
CO concentration in the isolated module and could thus make
planning to recover the module more difficult.) Unfortunately
even the best precautions are no guarantee against a crew-
member being exposed to high levels of CO. Inhalation treat-
ment using 100% O2 will reduce the half-life of COHb from
56 h to 0.51 h, and the patient exposed to CO should be so
treated until the blood COHb concentration has been reduced
to 1520% [11]. Obviously, the patient must also remain on
the respirator regardless of COHb concentration if the concen-
tration of CO in the cabin has not been reduced to safe levels.
U.S. space vehicles use a portable breathing apparatus to
provide immediate respiratory and eye protection in the event
of CO exposure. Approximately 15 of O2 at a consumption
rate of 15 L/min is available in a pressurized cylinder. With the
arrival of the O2 tank on ISS mission 7A, the portable breath-
ing apparatus was able to be connected to an O2 port. The
portable breathing apparatus can be used in positive pressure
mode or on demand mode. (It does not provide an adequate
seal for crewmembers with beards, however.) The Russian
segments of the ISS contain a rebreather type of gas mask that
can provide protection for 20120 min depending on ventila-
tion rate [1]. The chemical reaction that produces the O2 in
the Russian gas mask is activated by respiration, which means
that there is a delay of 2030 s after the mask is donned before
the O2 becomes available.
Decontamination of the Environment
Various types of catalytic oxidizers are used on spacecraft to
control the nominal load of CO into the atmosphere, but the
capacities of these oxidizers are insufficient to rapidly remove
large amounts of CO from the atmosphere after a fire. In a
21. Health Effects of Atmospheric Contamination
well-mixed atmosphere, the level of pollutant will be reduced
by at least 80% after two complete volumes have passed
through a filter that maintains 100% sorption efficiency. The
ambient temperature catalytic oxidizer that is used in the
Space Shuttle consists of platinum-coated charcoal with a
prefilter to remove other pollutants that could poison the
catalyst in the primary filter. The flow through this filter is
only 1.7 m3/h, however, and the Space Shuttle free volume is
65 m3, so 76 h would be required to make 2 complete volume
passes through the filter. An option in the Space Shuttle is to
replace one of the LiOH canistersLiOH canisters scrub CO2
from the air on board the Space Shuttlewith the hydrazine
adsorber element, a large ambient temperature catalytic oxi-
dizer filter that is capable of scrubbing approximately 1 cabin
volume in 1.5 h.
The Russian service module of the ISS uses a palladium
catalyst canister operated at ambient temperature and a flow
of 20 m3/h [1]. Thus the service module, with its free volume
of 100 m3, will require 10 h for two complete passes of air
through the catalytic oxidizer. The U.S. modules of the ISS
use a high-temperature catalytic oxidizer with a flow rate of
4.6 m3/h to remove CO [16,17]. With free volumes of 98 m3,
the laboratory and habitation modules will each require about
43 h for a two-volume scrub of CO from the air. The ultimate
solution under certain contingencies may be to depressurize
the polluted module, assuming that the module has been iso-
lated from the module in which the crew has sought refuge.
Most space vehicles have provisions for at least a partial
depressurization-repressurization cycle.
Formaldehyde
Sources
Formaldehyde is a highly irritating compound that can enter
a space vehicles atmosphere through leakage of fixatives
from payload experiments, off-gassing of hardware, thermo-
degradation of certain polymeric materials (e.g., Delrin), and
incomplete oxidation of contaminants in the environmental
control system. The hazard rating of formaldehyde solutions
in payload experiments, which is based on its potential for
eye irritation, is critical if the solutions are between 0.25%
and 1.0%; it is catastrophic if the concentration is above 1.0%
[18]. During the Mir-18 mission, while the crew was conduct-
ing fixation operations as part of the Fundamental Biology
Experiment, several drops of paraformaldehyde solution were
released into the environment. A postflight inspection of con-
tainment bags showed that the inner level of containment had
been breached [19]. The crew suffered no known harm from
this exposure, and measures were subsequently taken to mini-
mize the risk of recurrence.
In a potentially hazardous incident, formaldehyde off-
gassing of hardware during a ground-based testpart of the
Lunar-Mars Life Support Test at the Johnson Space Center
431
in Houston, Texasnearly caused an abort of the test [20].
This happened because the hardware had not been screened
for off-gassing properties. Air samples that were taken dur-
ing the first few days of the test showed rising formaldehyde
levels, and eventually one of the crewmembers reported
respiratory irritation. Approximately 15 days into the test,
an effort was made to remove any material that could off-gas
formaldehyde, after which the formaldehyde levels dimin-
ished significantly, the respiratory irritation disappeared,
and the test was completed without further problems with
formaldehyde (Figure 21.2).
In an incident of formaldehyde exposure on board the
Space Shuttle during STS-40, a motor in the Space Shuttles
middeck refrigerator overheated and the motor housing,
which was made of the formaldehyde polymer Delrin, had
thermally degraded to produce quantities of formaldehyde
that were both irritating and nauseating to the crew [21].
The crew was able to minimize exposure by staying out of
the middeck as much as possible. The cause of the incident
remained unknown until the refrigerator was disassembled
on the ground (Figure 21.3).
Finally, investigations of the catalytic oxidizer used in the 90-
day Lunar-Mars Life Support Test, after that test was complete,
revealed that incomplete oxidation of methanol, possibly as a
result of a poisoned catalyst, was resulting in the unit releasing
formaldehyde into the effluent stream [22]. In summary, these
four separate incidents indicate that formaldehyde can originate
from numerous sources on board a space vehicle and that con-
trolling the risk of crew exposure can be a challenge.
Figure 21.2. Profile of formaldehyde accumulation in the ground-
based Lunar Mars Life Support Test. Excess materials off-gassing
caused the accumulation from day 1 to day 15. Reprinted with per-
mission from SAE paper number 981738 1998 Society of Auto-
motive Engineers, Inc. 28th Conference on Environmental Systems;
1316 July 1998; Danvers, MA
432
Figure 21.3. The small motor in the refrigerator that generated form-
aldehyde when the Delrin was overheated
Mechanisms of Toxicity
Formaldehyde is a highly reactive compound with 2 major
toxicologic propertiesit acts an irritant to the eyes and respi-
ratory system; after prolonged exposure, it is carcinogenic in
rodents and perhaps in humans. The compound irritates the
upper respiratory system, where its stimulation of the olfac-
tory and trigeminal nerve endings causes the affected person
to try to hold his or her breath. When the breath can no longer
be held, normal respiration resumes, and if the exposure con-
centration is sufficiently high and prolonged, tissue inflamma-
tion, tissue necrosis, and eventually cancer are possible.
At moderate concentrations, inhaled formaldehyde is pri-
marily captured in the nasal passages, where it binds to glu-
tathione in the cytosol of nasal cells, is oxidized principally
by formaldehyde dehydrogenase, and is then released from
the glutathione by S-formyl glutathione hydrolase as formate
and CO2 [23]. The molecular mechanism by which formal-
dehyde causes nasal irritation is unknown. If the amount of
formaldehyde present exceeds that which the formaldehyde
dehydrogenase can metabolize (> 6 ppm in rats), free formal-
dehyde can reach the nuclei of nasal cells, where it forms DNA-
protein cross-links. These cross-links, and the cell replication
subsequent to inflammation from tissue damage, are thought
to lead eventually to nasal cancer, at least in rats [24]. Also,
if concentrations are sufficiently high or minute ventilation
is high, formaldehyde can reach deeper into the respiratory
system and elicit pulmonary irritation.
Warning Properties
The warning properties of formaldehyde can be considered
adequate for most conditions of exposure. For most people,
the odor threshold is from 0.5 to 1 ppm, and mild irritation is
felt at 23 ppm [25]. Although controversy exists as to which
levels of exposure humans can tolerate without increasing the
J.T. James
Table 21.2. Estimated toxic responses to acute exposures to formal-
dehyde vapor [11,25,27,28].
Formaldehyde concentration Effects to expect
<0.25 ppm 1020% of those exposed may have a
respiratory response
0.250.5 ppm up to 20% of population finds exposures
disagreeable
0.51 ppm Most persons sense the odor of formalde-
hyde
13 ppm Mild irritation in most people
45 ppm Many people find this intolerable for any
length of time
530 ppm Lower airway and pulmonary effects such as
cough, chest pain, dyspnea, wheezing
50100 ppm Pulmonary edema, inflammation, pneumonia
risk of cancer, the concentration predicted to increase the can-
cer risk no more than 1 in 10,000, with 95% confidence for
a 180-day exposure, was estimated to be about 1 ppm [26].
Hence, the odor of formaldehyde, and certainly any respira-
tory or eye irritation from it, can be considered a warning that
the space vehicle atmosphere must undergo increased scrub-
bing or that a new source of formaldehyde must be identified
and contained.
Airborne Concentrations that Cause Toxic Effects
Target organs for formaldehyde are the eyes and respiratory
system. Susceptibility to formaldehyde vapor varies consider-
ably among individuals; however, Table 21.2 can be used as a
general guideline for acute exposures lasting several minutes.
Clinical Presentation
Relatively mild acute exposures to formaldehyde will result
in burning and tearing of the eyes, upper airway irritation,
rhinitis, and throat irritation. Since these symptoms are char-
acteristic of any primary irritant, their presence by no means
specifically suggests exposure to formaldehyde. Formalde-
hyde does tend to have a characteristic odor, however, and the
irritant symptoms, along with crew identification of an alde-
hyde-like odor, are suggestive evidence of excess airborne
formaldehyde. The crew of STS-40as cited in transcripts
of the STS-40 air-to-ground commentsindicated an alde-
hyde odor from the refrigerator when the Delrin polymer was
apparently being pyrolized by overheating of the motor.
The evidence is unclear whether olfactory fatigue will
reduce a crews ability to sense the odor of formaldehyde or
to experience the symptoms listed above. It seems reasonable
to expect a crew to be less aware of an odor from a given air-
borne concentration of formaldehyde if the odor builds slowly
rather than being suddenly present. Conversely, the irritant
properties of formaldehyde do not seem to become more toler-
able with prolonged exposure. In fact, there is some evidence
that respiratory sensitization may be possible. According to
21. Health Effects of Atmospheric Contamination
one expert panel, the role of formaldehyde as an irritant and
potential allergen affecting nasal mucous membranes is
recognized Some individuals may become highly respon-
sive to low doses leading to debilitating rhinitis, conjuncti-
vitis, and asthma. [29]
Differences in Individual Susceptibility
Some concern has been expressed that in Earth-based pop-
ulations, people with asthma could experience asthmatic
symptoms as a result of formaldehyde exposures. In one inves-
tigation, of 230 asthmatic patients studied, eight displayed an
immediate bronchial reaction when inhaling 2 ppm formal-
dehyde for 30 min [30]. At present, persons with asthma are
disqualified by U.S. astronaut selection criteria; however the
U.S. criterion could change in the future.
Even among people who do not have asthma, a portion of
the population is extremely sensitive to formaldehyde vapor.
After reviewing the data on formaldehyde, the Threshold
Limit Value Committee of the American Conference of Gov-
ernmental Industrial Hygienists, Inc., noted an unusually
broad range of reported susceptibility of humans to the irri-
tating properties of airborne formaldehyde. The Committee
concluded that It is plausible that a similar portion (1020%)
who are more responsive may react acutely to formaldehyde
at very low concentrations, <0.25 ppm. If formaldehyde
exposures are suspected on board a space vehicle, the reported
level of symptoms may vary widely because of individual dif-
ferences in susceptibility.
Sampling and Analysis
At present, no real-time analytical method exists that is suit-
able for use in a spacecraft and can quantify formaldehyde
at the long-term SMAC of 0.04 ppm. (A revised value of
0.10 ppm has been approved recently.) Formaldehyde concen-
trations have been measured on the Space Shuttle, the Mir, and
the ISS using sorbent badges to sample the air; later, ground-
based colorimetric analysis by ultraviolet spectrophotometry
is used to quantify the formaldehyde [31]. The badge can be
placed on the uniform of a crewmember or located on a wall;
however, it is essential that an adequate cross-flow of air be
present or undersampling will result. Sample times can range
from 8 to 24 h, and the limit of detection is 0.010.02 ppm,
depending on sample time and dispersion in blank values.
Although their small size and ease of use make the badges
ideal for space flight, a real-time method is needed to assist
the flight surgeon and environmental engineers in the event of
a contingency involving formaldehyde.
Protection and Treatment after Exposure
Given the irritating properties of formaldehyde, no crewmember
would tolerate a toxic inhalation exposure to it unless he or she
was unable to escape to a clean module or to don respiratory and
433
eye protection. Symptoms of exposure disappear quickly once
appropriate protection has been put in place. If the source
of formaldehyde is a spilled liquid, goggles, respirator, and
impermeable gloves should be worn as protection. Skin con-
tact should be avoided, as skin sensitization is possible with
all aqueous formaldehyde solutions. Repeated exposures must
be avoided because they could lead to sensitization to form-
aldehyde. In fact, there is a report that after a 140-day and a
175-day Russian mission on board the Salyut space station,
the Russian crews returned with a sensitivity to formaldehyde
that they did not have before flight [32].
Decontamination of the Environment
Formaldehyde can be removed from the environment by using
charcoal filters and humidity condensers. The absorption effi-
ciency of activated charcoal for formaldehyde is limited, but
space vehicles with large charcoal filters can partially scrub the
air by this means. In space vehicles where the humidity con-
densate is not recovered (e.g., the U.S. Space Shuttle), much
of the formaldehyde can be condensed from the air along with
the water vapor. Formaldehyde has been regularly found in the
Space Shuttle humidity condensate, which indicates that a load
of formaldehyde is entering the air and that condensation is an
effective removal mechanism. In space vehicles in which the
humidity condensate is recovered for purification and reuse by a
crew, airborne formaldehyde can present a risk to water quality.
Ethylene Glycol
Sources
Ethylene glycol (EG) is a colorless, odorless, water-soluble
liquid that has a low vapor pressure and a sweet taste. It is
familiar to most people as the major ingredient in the anti-
freeze used in the cooling systems of automobile engines. It
was used in the Apollo space vehicle, where concern over its
leakage into the cabin was sufficient that the Apollo astro-
nauts were given training in detection of its presence in the
atmosphere [33]. The only source of EG on board modern
spacecraft is in heat-exchange loops, where it can be used in
large quantities to redistribute heat. During the NASA-Mir
Program, large amounts of EG escaped several times from the
Mir cooling loops. The escaped material was difficult to clean
up and at times elicited toxic symptoms including respiratory
irritation and, when large drops were encountered, eye irrita-
tion. Airborne EG was also captured in the water-vapor con-
densation system; at times, this condensed water could not be
purified to potable standards [34]. Thus, recycled water, which
is used for drinking and to reconstitute food, can become a
source of EG exposure for a spaceflight crew.
Because of these toxicologic concerns, EG has been
replaced with triol in the Russian segments of the ISS and
is not used in any of the U.S. segments of the ISS. Triol
434
consists of a 3032% solution of glycerin in water that also
includes up to 8% additives to control corrosion and micro-
bial growth (personal communication from Valeri Ryumin
to Frank Culbertson, 24 May 1999.) Future space habitats
could see a return to the use of EG in applications where heat
exchange is required.
Mechanism of Toxicity
EG is relatively low in toxicity, but it can be lethal to adults
when it is ingested in quantities that exceed 100 mL. Since EG
is most often ingested accidentally, considerable research has
been dedicated to our understanding of EG toxicity by oral
ingestion. However, oral ingestion is not considered a major
route of exposure in spacecraft since the water will be moni-
tored for changes in total organic carbon, which will reflect
the presence of EG. The primary concern during space mis-
sions regards the inhalation by spaceflight crews of EG vapor
or aerosol as well as skin or eye irritation during contact with
large, free-floating drops formed after an EG release.
When inhaled as a vapor or an aerosol, EG can irritate the
upper respiratory tract. Once EG enters the body, the potential
exists for CNS effects and renal toxicity. Respiratory irritation
is apparently caused by the interaction of EG or its metabolites
at receptors in the respiratory tract. CNS effects are caused by
EG or an aldehyde that is formed by oxidative metabolism
[35]. Oxalic acid, which is another of the metabolites of EG, is
thought to increase the probability of calcium oxalate crystals
forming in the kidneys and to contribute to EG-induced renal
toxicity. The direct effects of EG metabolites on the tubular
epithelium may also cause necrosis.
EG can cause eye irritation when direct contact is made
between the liquid and the surface of the eye. In animal models,
the degree of irritation depends on the concentration of EG in
solution and the length of exposure. Repeated topical exposures
of rabbit eyes to EG caused a strong irritation response at a 40%
concentration in balanced salt solution, a reduced response at
4% concentration in balanced salt solution, and no response at
0.4% in balanced salt solution [36]. Single administrations do
not seem to elicit an irritation response [37]. This observation is
consistent with reports that emerged during the NASA-Mir Pro-
gram that crewmembers who repeatedly got airborne EG drops
(40% in water) in their eyes experienced eye irritation.
Warning Properties
The warning properties of EG by inhalation exposure are upper
airway irritation and a sweet taste in the mouth. Inhaled EG has
little acute toxicity. During brief exposures, the upper airway
is irritated at concentrations that are unlikely to cause injury. If
the exposure is prolonged, however, EG concentrations that are
below the irritation or taste threshold can be sufficiently high
to increase the risk of tissue injury. The irritation response to
EG is summarized in Table 21.3. Exposures of up to 100 mg/m3
(about 40 ppm) could be undetected by crewmembers.
J.T. James
Table 21.3. Irritation caused by ethylene glycol vapor and
aerosol.
EG concentration (ppm [mg/m3]) Response
25 [60] No effect
50 [130] Pharyngeal irritation and sweet taste
common
73 [190] Subjects could tolerate exposure for
15 min
80 [200] Pain in tracheobronchial tree
95 [250] Tolerable for no more than 12 min
120 [300] Intolerable to breathe
Source: Modified from Wong [38].
Airborne Concentrations that Cause Toxic Effects
It is estimated that prolonged exposures at or below 5 ppm to
EG will not result in detectable CNS depression [38]. This
estimate was based on the finding that no effects were found
in a psychometric test of 20 men exposed to EG at 12 ppm for
30 days [39]. Likewise, no renal effects (as measured by urine
specific gravity, serum urea nitrogen, serum creatinine, and
creatinine clearance) were found in the same group of men;
hence, exposure to up to 5 ppm EG for a prolonged period
is unlikely to cause kidney injury. The 5 ppm limit is well
below the 12-ppm, 30-day experimental exposures because of
a statistical safety factor that takes into account that only 20
men were exposed. It is reasonable to expect that sensitive
individuals may not have been represented in that numerically
limited test population.
Clinical Presentation
Ingestion of EG causes a series of clinical effects that can be
grouped into 4 stages. At the first stage, which occurs with the
first 12 h after ingestion, a victim of EG poisoning may have
sufficient CNS depression to appear drunk. A second stage,
which occurs 1236 h after EG ingestion, entails cardiopul-
monary effects such as tachypnea, tachycardia, hypotension,
and cyanosis. A third stage involves renal failure character-
ized by proteinuria, blood cells in the urine, and calcium
oxalate crystals in the urine. A fourth stage, which involves
neurologic symptoms, has been suggested to occur in some
victims approximately 2 weeks after the ingestion [40]. Such
severe symptoms as appear in these four stages are extremely
unlikely to occur after inhalation of EG vapor or aerosol. In
the event of a major EG vapor or aerosol release that cannot be
controlled, the flight surgeon should be cognizant of the pos-
sibility of minor CNS and renal effects in crewmembers.
Differences in Individual Susceptibility
Although inter-individual differences have not been specifi-
cally documented in human susceptibility to EG poisoning,
this issue has received little study. Initial metabolism of EG
21. Health Effects of Atmospheric Contamination
involves alcohol dehydrogenase and aldehyde dehydrogenase,
each of which, from studies of ethanol metabolism, is known
to vary widely in its catalytic activity in the human population.
Reduced inherent aldehyde dehydrogenase activity, common
in persons of Asian descent, could predispose such persons
to a higher susceptibility to inhaled EG vapor. This higher
susceptibility could be the result of the accumulation of alde-
hydes, which are thought to cause many of the toxic effects of
EG. It should therefore be expected that certain persons may
be unusually sensitive to the effects of EG exposure.
Sampling and Analysis
The accepted exposure limits to EG for Earth-based workers
are approximately half the vapor saturation concentration of
80 ppm at 20 C (68 F). An extremely stagnant, nearly closed
environment is required to vaporize a liquid to half its satu-
ration concentration; hence, unless aerosols are produced by
mechanical means, there is little need to measure EG in the
atmosphere on Earth on a real-time basis. For this reason,
rapid analytical methods for EG in the air are not particularly
well developed.
One method for sampling and analyzing EG, among other
substances, is the use of Draeger tubes. (This method was
used on board the Mir space station during the Shuttle-Mir
Program.) These devices were flown on Mir because of persis-
tent leaks of EG from the stations coolant loops and concerns
about crew health from prolonged exposure to EG. Draeger
tubes indicate EG concentration by the length of pink stain
produced by a colorimetric reaction when air is drawn into the
tube. Estimates of EG concentrations after a leak on Mir are
shown in Figure 21.4.
Figure 21.4. Persistence of ethylene glycol in the Mir atmosphere
(estimated with Draeger tubes). Concentrations are from the Kvant
module (diamonds), where the leak occurred and from the Core mod-
ule (squares), where the crew spent most of their time. Reprinted
with permission from SAE paper number 981738 1998 Society
of Automotive Engineers, Inc. 28th Conference on Environmental
Systems; 1316 July 1998; Danvers, MA
435
Protection and Treatment after Exposure
If a large amount of EG has been released into spacecraft air,
eye and respiratory protection should be used until the spill
has been cleaned up. A crewmember may be able to toler-
ate EG exposures up to 25 ppm for 24 h, but longer exposures
should be limited to 5 ppm. Since EG does not spread rapidly
in spacecraft atmospheres, movement of sensitive persons to
an area in the spacecraft where lower EG concentrations are
found may be an option. If the patients eyes have been repeat-
edly exposed to liquid EG, use of the eyewash station avail-
able on all U.S. vehicles may be necessary.
Decontamination of the Environment
EG is extremely persistent in a spacecrafts environment. It
readily condenses on cold surfaces or impinges on other sur-
faces, where it forms a reservoir for continuing release of EG
into the air and for microbial growth in the condensed state.
Absorbent towels should be used to remove obvious areas of
EG contamination. When clearing areas of contamination, it
would be wise for a crewmember to wear protective gloves
as a precaution. (Some space vehicles have a handheld, wet-
dry vacuum that could be used to capture large drops of EG
floating in the air.) In normal circumstances, much of the EG
present in air will be removed by the water-vapor condensing
system, where it will present a challenge to the water purifica-
tion system [34].
Freons and Other Halocarbons
Sources
Freons and halocarbons have 3 major uses on modern space
vehicles. Certain Freons are used preflight as hardware clean-
ing agents; others are used in heat-exchange loops; and Halon
1301 (bromotrifluoromethane) is used as a fire extinguishant
in the Space Shuttle. Low concentrations of certain chloro-
fluoro hydrocarbons are found in the course of routine sam-
pling of the Space Shuttle atmosphere as a result of hardware
cleaning, but they do not have the potential to enter the air
in high concentrations. In contrast, perfluoropropane, which
is used in some ISS coolant loops, is normally not detected
but has been found in high concentrations when accidentally
released. Halon 1301 is available in large quantities inside the
Space Shuttle and would be released in the event of a major
fire. Traces of it are routinely found in the Space Shuttle air,
but no accidental or fire-related releases have occurred since
Space Shuttle flights began in 1981.
Mechanisms of Toxicity
This group of halocarbons has very low toxicity and has never
been suspected of inducing toxic effects in Space Shuttle
crewmembers. The primary effect of this class of compounds
436 J.T. James

is cardiac sensitization leading to rhythm disturbances; how- Table 21.4. Halocarbon spacecraft maximum allowable
ever, this effect is generally noted only at concentrations above concentrations.
1%. Freons and halocarbons are thought to act by sensitizing Common
the heart to epinephrine, so exposure in stressful conditions name Chemical name 180-day SMAC Effect to prevent
may be somewhat more risky than in sedentary conditions. Halon 1301 Bromotrifluoromethane 1,800 ppm CNS depression
Some Freons and halocarbons have been found to cause CNS Freon 11 Trichlorofluoromethane 140 ppm Cardiac arrhythmia
depression but only at very high concentrations. Halon 1301, Freon 12 Dichlorodifluoromethane 95 ppm Cardiac arrhythmia
Freon 21 Dichlorofluoromethane 2 ppm Hepatotoxicity
for example, has been shown to cause no more than a 5% CNS
Freon 22 Chlorodifluoromethane 1,000 ppm Cardiac arrhythmia
functional decrement in 2 of 13 performance measures in Freon 113 1,1,2-trifluoro-1,2,2-tri- 50 ppm CNS depression
humans exposed for 24 h to a 1% concentration [41]. Freon 21 chloroethane
(dichlorofluoromethane), which is used in the external cool- Freon 218 Octafluoropropane 11,000 ppm Cardiac arrhythmia
ant loops of the Space Shuttle and could indirectly enter the CNS effects
spacecraft cabin, has been shown to cause hepatotoxicity after Abbreviations: CNS, central nervous system; ppm, parts per million.
prolonged exposures; hence, its limits are much lower than the Source: NASA JSC-20584, Spacecraft maximum allowable concentrations
limits of other members of this class. This hepatotoxicity may for airborne contaminants, June 28, 1999.
be due to metabolism of Freon 21 in the liver to phosgene-like
compounds that are very reactive [42]. Many members of this
class of compounds have been shown to cause ozone deple- many Freons and will also be used periodically to quantify
tion in Earths atmosphere, so their use on this planet is being trace contaminants in the station atmosphere [43].
phased out.
Since Halon 1301 is intended to extinguish fires on the
Space Shuttle, the question invariably arises as to the toxic- Treatment after Exposure and Decontamination
ity of its pyrolysis decomposition products. Upon exposure of the Environment
to flames or to surfaces at temperatures over 480 C (900 It is very unlikely that Freon compounds will escape into the
F), Halon 1301 decomposes to form hydrogen bromide and atmosphere in concentrations that are sufficient to cause ill effects
hydrogen fluoride (among other less important compounds), or symptoms, so crewmembers are unlikely to need treatment.
both of which are much more toxic than Halon 1301 [10]. The Many Freons are extremely difficult to remove from the atmo-
major toxic effect of these products is mucosal and respira- sphere with conventional environmental control and life support
tory irritation at very low concentrations. This effect, together system designs. So the flight surgeon should expect to see a slow
with the acrid odor of these compounds, provides a built-in decline in airborne concentrations over several days or weeks as
warning system that these compounds are present before their the Freon gradually disappears from the environment.
concentrations become truly hazardous. The presence of these
products is generally an issue only for deep-seated fires that
require a long time to be extinguished.
Airborne Carcinogens
Warning Properties and Toxicologic Guidelines Sources
This class of compounds has no warning properties discernable Although several carcinogens are found consistently in space-
at concentrations that can be toxic to the individual. Because craft air, only rarely do the combined effects of airborne
toxic concentrations are high for most members of this group, chemical carcinogens exceed the 180-day exposure guide-
control can be readily achieved by limiting the amount that lines, which were set to keep the increased lifetime risk of
could be released into the atmosphere. Table 21.4 shows the cancer below 1 in 10,000. Some common carcinogens and
SMAC guidelines for several members of this group and the their sources are given in Table 21.5. The steady-state con-
toxic effects that the guidelines were set to avoid. Often refrig- centrations of the pollutants listed are well controlled by the
erator cooling systems are designed to use an amount of Freon environmental control and life support system, but when cer-
that would not present a toxic hazard even if all of the Freon tain materials become overheated or burn, the products can
were to be released into the spacecraft environment. include the carcinogens benzene and furan.

Detection and Quantification of a Freon Leak
Medical support personnel should be aware that, if crewmem-
bers are exposed to a Freon in the atmosphere, the most likely
clue is a detectable decrease in pressure in the source system.
The volatile organics analyzer, the use of which began on the
ISS with flight 7A (launched on 12 July 2001), can quantify
Mechanisms of Toxicity and Warning Properties
Carcinogens are broadly classified as causing cancer by genetic
or epigenetic mechanisms. Except for isoprene and furan, all of
the compounds listed in Table 21.5 have been shown to react
directly with DNA and to cause mutations. These compounds
are genetic carcinogens, and the risk associated with exposure
21. Health Effects of Atmospheric Contamination
Table 21.5. Sources of carcinogens and their limits in spacecraft
air.
Compound Source 180-day SMAC
Acetaldehyde Human metabolism, 2 ppm
materials off-gassing
Benzene Materials off-gassing, 0.07 ppm
polymer pyrolysis
1,2-dichloroethane Hardware off-gassing 0.2 ppm
Furan Hardware off-gassing, 0.025 ppm
heating of organic
material
Isoprene Human metabolism, 1 ppm
plants
Abbreviation: SMAC, Spacecraft maximum allowable concentration.
to known concentrations is calculated by using a linear model
[44]. According to this model, the risk of cancer is kept con-
stant if the exposure time is increased by some factor and the
concentration is reduced by that same factor. For long expo-
sures, the levels estimated with this model to attain an accept-
able risk of cancer can be extremely low.
Furan and isoprene cause cancer in rodents, but there is little
evidence that either compound is carcinogenic in humans.
The weight of evidence for furan suggests that it or a metabo-
lite affects DNA through indirect mechanisms. This deduction
leads to an approach to cancer risk that recognizes a threshold
exposure concentration, below whichregardless of the time
of exposurethere is no increased risk of cancer [42]. For dif-
ferent reasons, isoprene is also thought to be a threshold-type
carcinogen. Genotoxicity data on isoprene are most consistent
with aneugenic activity (such as spindle disruption during cell
division). Isoprene is produced endogenously, and the cancer
data in rodents suggest a threshold effect [45].
Of the carcinogens listed in Table 21.5, only acetaldehyde
has a significant warning property. The SMAC in Table 21.5 for
that compound was actually set to prevent mucosal irritation.
If acetaldehyde did not have this irritant property, the SMAC
for 180 days of continuous exposure would be 4 ppm to protect
against the increased risk of nasal cancer [46]. Nasal tumors
were observed in rodents that were exposed to high concentra-
tions of acetaldehyde for many months. The SMACs for the
other carcinogens in Table 21.5 are so low that no warning
property exists, thus reinforcing the need for periodic monitor-
ing of spacecraft atmospheres for compounds that could be car-
cinogenic to the crew if exposures were prolonged.
Differences in Individual Susceptibility
Many important factors affect the susceptibility of humans to
carcinogens. Genetically determined differences in the metab-
olism of carcinogens to active or inactive species can affect
susceptibility. Differences in the ability to repair DNA lesions
can also affect susceptibility. The very young are considered
most susceptible to chemical carcinogens. Of particular inter-
est to spaceflight risks is the potential for increased suscepti-
437
bility due to changes in host immune function and co-exposure
of crewmembers to non-chemical carcinogens. Immune sur-
veillance for non-host cells provides a protective mechanism
against cancer, but spaceflight crewmembers have been
known to experience changes in immune function (see Chap.
15). The relatively high radiation environment of space has
resulted in the SMACs for benzene being set at lower concen-
trations than otherwise because of the possible interaction of
radiation and benzene in inducing leukemia [47].
Protection of the Crew and Decontamination
of the Environment
Inspection of Table 21.5 indicates that most carcinogens origi-
nate from materials off-gassing; hence, the risk of exposure to
carcinogens in space flight can be controlled by screening
materials for carcinogen-causing compounds. This prac-
tice provides a high degree of protection for the crewmem-
bers as well as the environment. Additional protection is
afforded by the scrubbing capabilities of the air revitaliza-
tion system. Even after the serious solid-fuel O2 generator
fire on board Mir in 1997 (during Mir Expedition EO-23),
the air revitalization system was able to scrub the benzene
concentrations from a peak of approximately 0.2 ppm to
0.02 ppm in 32 h [2]. Donning respirators after a fire will
provide individual protection until the vehicle atmosphere
has been scrubbed to risk levels judged acceptable based
on the SMACs.
Noxious Compounds: Sulfurous
Compounds
Sources
As space missions last longer and are conducted farther
from Earth, the problem of trash and waste management
becomes critical. A typical rate at which trash is generated
on Space Shuttle flights is 2.5 lbs (1.1 kg) per person per
day, of which 27% is liquid [48]. When biological wastes
are stored for long periods, bacterial action can produce
extremely noxious compounds that can certainly affect the
crews well-being if not their health. Bacteria can metabo-
lize certain types of stored chemical wastes, stored human
waste, and discarded food. Materials that initially have little
or no odor can, after long-term storage, generate volatile,
noxious compounds. Eventually, the management of waste
and trash in space may involve incineration to volatile com-
pounds and ash that can be recovered and used in a closed
habitat. One of the challenges of building such a system is
the removal of sulfur dioxide and other potentially toxic
compounds [49].
Sulfur compounds are a major component of the gases that
are generated from human metabolism. In one human study
[5], dimethylsulfide was produced at about 0.1 mg/day by
438
about a third of the participants, but almost all of the subjects
produced large amounts of other sulfides. (These amounts
averaged 6 mg per day.) If sulfur compounds are not scrubbed
from the air, they can present a noxious odor within the cabin,
especially for arriving crews that have not adapted to the
odors.
Warning Properties of Noxious Compounds
By definition, noxious compounds possess good warning
properties at first exposure. Subsequent or continuing expo-
sures, however, can lead to olfactory fatigue and to a loss of
sensitivity to the detection of those compounds. Moreover, a
slow accumulation of noxious compounds may go undetected
by the crew.
Clinical Presentation and Individual Susceptibility
Invariably, abrupt exposure to products from stored waste and
trash will result in crew complaints about unpleasant odors.
Individual thresholds for odor detection vary greatly and
depend on whether the noxious compound enters the cabin
suddenly or has accumulated slowly because of a small leak.
Typically, a crew can determine approximately where the
unpleasant odor is originating from and can minimize the time
spent in the offending area.
Air Sampling and Analysis
The human nose can be extremely sensitive to noxious com-
pounds, so analytical methods may lack the sensitivity of the
human nose to identify specific compounds even when
those compounds can be readily smelled. In Space Shuttle
flights, in approximately half of the times when crews took an
air sample because of a detectable odor in the spacecraft air,
an analytical chemist was able to identify likely candidates for
the cause of the smell. An example of this occurred on STS-
55 when the crew was using a contingency waste container
to store biological wastes. After doing this for several days,
crewmembers reported that the odor coming from the bag,
which had to be periodically compressed for emptying into
space, was overpowering. An air sample was taken from the
area using a grab sample canister, and subsequent ground anal-
ysis by gas chromatography and mass spectrometry showed
the presence of 3 noxious methyl sulfides. After the mission,
a study of the contingency bag showed that the same sulfides
and odors (as confirmed by crewmembers) could be produced
when biological waste was stored in the bag. Although the
bag was adequate to contain liquid waste, the volatile sulfides
produced by bacterial action could readily penetrate its walls.
Given this event and anecdotal reports of noxious air, it seems
likely that odors will be a fact of life in space flight. Although
resource limitations during space flightweight limitations
and storage limitations, among othersmake it impractical
to carry analytical means of detecting and identifying specific
J.T. James
noxious compounds, a broad-spectrum analyzer such as a gas
chromatograph/mass spectrometer (although not necessar-
ily in orbit) would be capable of identifying and quantifying
many noxious compounds.
Protection of the Crew and Decontamination
of the Environment
On the Space Shuttle, crewmembers are protected from
exposure to odors by an acid-treated charcoal filter called
the odor-bacteria filter. This filter, which is part of the waste
management system, contains 2.3 kg of acidic charcoal and a
0.45-m bacteria filter. A spare filter is carried in the event
it is needed to augment the nominal scrubbing capability on
board the spacecraft. Since sulfurous compounds can poison
components of the air revitalization system, operation of these
systems may need to be curtailed during a contingency. This
naturally could delay the decontamination effort.
Ammonia
Sources
The primary source of ammonia inside a spacecraft is human
metabolism. The amount of ammonia produced per person
is expected to be in the range of 300 mg/day depending on
the amount of sweating and the level of exercise performed
[16,50]. Ammonia assists with heat exchange in some exter-
nal coolant loops and could enter the internal compartments
by leaking from the external loops to the internal loops, and
then into the cabin atmosphere. In addition, if a crewmember
became contaminated with ammonia during an extravehicular
activity, some of the contaminant could reach the interior of
the vehicle when the crewmember enters the airlock. The prob-
ability of this happening is considered very low, however.
Mechanism of Toxicity and Warning Properties
Ammonia irritates mucous membranes and causes a burning
sensation in the eyes, nose, and throat. Unfortunately, sensory
fatigue develops with prolonged or repeated exposures [51].
In massive exposures, tissues are injured by the formation of
ammonium hydroxide, which dissolves the tissues in the
same way as an alkali burn would. Tissue is also injured by the
heat released as the ammonia dissolves in the aqueous coat-
ings of the mucous membranes [52].
The warning property of ammonia exposure is its odor and
irritation of mucous membranes. In non-adapted, non-expert
persons, the odor intensity and degree of irritation can provide
a rough estimate of airborne ammonia concentration. These
subjective responses are summarized in Table 21.6 [5254].
The degree of irritation increases with time and would be
substantially less in persons who are adapted to ammonia
exposure [55].
21. Health Effects of Atmospheric Contamination
Table 21.6. Sensation of odor and irritation from initial, brief expo-
sures to ammonia [54].
Ammonia concentration Degree of irritation
5 ppm Odor threshold in sensitive persons
2030 ppm Some sense a slight irritation
50 ppm Odor threshold in non-sensitive
persons, perceptible to moderate
irritation
80 ppm Distinctively perceptible irritation
110 ppm Irritation is a nuisance
140 ppm Nuisance, offensive, and unbearable
irritation
Sources: Data from Wong [52], World Health Organization [53], and Verberk
[54].
Clinical Presentation and Differences
in Individual Susceptibility
Subtle ammonia exposures from excess accumulation of
ammonia in the atmosphere may be difficult to identify. If
concentrations increase slowly, crewmembers will adapt to
these concentrations and will not exhibit clinical symptoms
until levels are well above those indicated in Table 21.6. The
most likely complaint from the crew will therefore be the odor
of ammonia. In the absence of analytical detectors, the most
plausible scenario is one in which an arriving crew opens the
hatch to the atmosphere of the parent vehicle and reports an
odor of ammonia. To avoid this, it was common practice on
the Russian space station Mir to operate the air contaminant
removal system more frequently than usual when a new crew
was expected to arrive soon.
Differences in individual susceptibilities are obvious from
the study performed by Verberk [54]. In this study, people with
no known history of exposure to ammonia were questioned
after a single exposure. In the extremes, an expert subject
reported no irritation at 140 ppm for 0.5 h, and a non-expert
subject reported distinctly perceptible irritation at only 50 ppm
for 0.5 h. In a spacecraft environment, a flight surgeon should
expect differences in individual susceptibilities to be obscured
by the loss of sensitivity as ammonia accumulates in the air.
Air Sampling and Analysis
Ammonia is rarely monitored in spacecraft air because it has
good warning properties and is not very toxic. On board the
ISS, ammonia is periodically estimated with detector tubes
provided by Russian environmental experts. Similarly, ammo-
nia levels were monitored during a 90-day ground-based test
of a sealed chamber containing a 4-person crew. In this test,
ammonia was quantified by using a commercial electrochemi-
cal sensor that was calibrated at 6.4 ppm using a permeation
tube. Ammonia concentrations in the chamber increased from
undetectable (<0.1 ppm) at the start of the test to 1.2 ppm on
day 87 of the test [56]. Although the instrument used in this
439
ground-based test is far too large, heavy, and power-consuming
to be used to monitor spacecraft air, a smaller electrochemical-
sensor instrument is being considered for ISS.
Protection of the Crew and Decontamination
of the Environment
Ammonia is not highly absorbed by ordinary activated char-
coal, but activated charcoal treated with 10% phosphoric acid
effectively removes ammonia. This type of charcoal is used
in the trace contaminant control filters of the ISS, but these
charcoal filters cannot be thermally regenerated. Hence, such
filters would be unable to control a large release of ammonia
into the cabin.
Airborne Particles and Dust
Sources
Substantially more free-floating particles are present in the
Space Shuttle atmosphere than in a typical home or office,
especially particles larger than 100 m [57]. High-efficiency
particle air filters improve this condition on U.S. segments of
the ISS by removing 99.97% of particles larger than 0.3 m
[1]. Nominally, sources of airborne particles include desqua-
mation of skin cells, flaking of paint, release of lint from fab-
rics, and handling of food [58]. Particles from other sources
can enter the atmosphere when containment fails. For exam-
ple, brown dust has escaped from the Space Shuttle waste
management system, LiOH dust has been released from CO2
removal canisters used on the Space Shuttle, and particu-
late material has escaped from animal containment facilities
[50]. Smoke particles are also an important component of the
products of pyrolysis of polymers, and this fact can be used
to detect fires in spacecraft. Extremely toxic dusts or fumes
from condensation of the metal vapors that are produced when
alloys are heated in metal furnace experiments could escape
only if their required three levels of containment were to fail
[18]. The use of glass is carefully controlled on spacecraft to
prevent broken glass particles from entering the atmosphere.
When this chapter was written, NASA was considering a
return to the lunar surface and possibly undertaking a human
flight to Mars as well. Dust in the lunar landing vehicles cre-
ated a nuisance during the Apollo program, especially when
microgravity was reestablished after liftoff from the lunar
surface. The Apollo 12 crew indicated that the dust made
breathing difficult without their helmet visors down, and that
their vision was affected by the density of floating particles
[59]. This dust, which adheres readily to space suits, was
brought into the vehicles interior by crewmembersdespite
their attempts to brush off their suits before entering the lunar
module [60]. Although such dust may not be an acute health
hazard, prolonged inhalation while stationed in a lunar out-
post could affect health. A Russian report concluded that lunar
440
dust is moderately fibrogenic to rat lungs when administered
by intratracheal instillation [61]. Recent studies of simulated
lunar and martian dusts have shown that each has potential for
fibrogenic activity in mouse lungs, but that the martian simu-
lant was more active than the lunar simulant [62].
Mechanisms of Toxicity
Particles can be hazardous to the crew because of their
mechanical properties, their chemical properties, or their
infectious nature. Since all particles float in spacecraft
atmospheres, there is a much greater probability that parti-
cles will enter the eyes and respiratory systems of crewmem-
bers. Large particles will generally elicit a blink response
to protect the eye. Since particles larger than 10 m do not
penetrate the respiratory system beyond the upper airway,
they do little damage. Lint particles in particular have been
responsible for mechanical discomfort to the eyes. LiOH
dust, which has been accidentally released from Space
Shuttle CO2 removal canisters, is highly irritating to the eyes
because of the caustic nature of the chemical in the parti-
cle. Brown dust arising from the waste management system
may cause immediate discomfort, but there may also be an
increased risk of eye infection if the material is not removed
thoroughly and quickly.
Warning Properties and Clinical Presentation
Crewmembers will be immediately aware if airborne particles
are threatening to injure them or affect their health. A par-
ticle that can cause mechanical injury will be immediately
detected if it lodges in the eye. Particles that cause chemical
injury to the eye will be obvious because of the associated
pain, which will occur as soon as the chemicals begin to dis-
solve in the topical fluid of the eye. If an unhealthy level of
smoke is generated from a fire, the event will be obvious to
the crew. Hence, crewmembers will have a warning that they
should don respiratory and eye protection until the particles,
and other toxic combustion products, are removed from the
atmosphere.
Sampling and Analysis
Although particles on board spacecraft have been experimen-
tally characterized, the risk of health effects is sufficiently
well controlled that routine monitoring of particles, except for
smoke detection, is considered unnecessary. In experiments
on board the Space Shuttle, a cascade impactor was used to
separate particles according to size into four fractions [57].
The relative mass of each fraction was determined gravimetri-
cally after the instrument was returned to a ground-based lab-
oratory. A companion instrument, the Space Shuttle particle
monitor, was used to count the number of particles passing
through a light beam in real time; however, that instrument
gave no indication of the size of the particles detected [57].
J.T. James
Smoke detectors can provide an index of airborne particle
concentrations under certain conditions. For example, on
STS-28 when 5 (2 in) of a Teflon-sleeved teleprinter cable
was burned by an electrical short, a smoke detector gave a rise
from 114 to 180 g/m3, but remained well below the alarm
level of 2,000 g/m3. The Space Shuttle smoke detector uses
an aerodynamic flow stream to distinguish particles larger than
2 m, so it responds entirely to respirable particles. Particles
are counted according to their ability to acquire charges and
reduce ion current to the detector [63]. The ISS smoke detec-
tors detect particles of about 0.3 m by measuring the ability
of the particles to scatter light from an infrared laser diode
light source. Smoke density is measured by a combination of
light attenuation (obscuration) and light-scattering methods.
Protection and Treatment after Exposure
Protection from airborne particles can be accomplished by
wearing goggles and dust masks, which are readily avail-
able to all crewmembers. If particles do reach the eyes of a
crewmember, however, the Space Shuttle and the ISS have
eye-wash devices available to flush material from the eye.
The devices look like swim goggles with tubing connecting
each of the eyepiece cups, and tubing to deliver water to one
cup and remove water from the other cup. These eye-wash
devices are located near the galley, where they can be quickly
connected to a water outlet that provides slightly pressurized
water. Provisions are made for adaptation of the device to
flush one eye [64].
Decontamination of the Environment
to Remove Particles
Airborne particles can be removed from spacecraft air by the
environmental control and life support system particle fil-
ters, but the rate of removal and the size of particles removed
vary considerably from one space vehicle to another. The key
design parameters of these filters are the flow rate through
the filter bed and the minimum particle filtration size. On the
Space Shuttle, particles are removed by the cabin air filter,
which has a mesh size of 4070 m and a flow of approxi-
mately 540 m3/h [50]. This means that relatively large particles
can be rapidly scrubbed from the Space Shuttles free volume
of 65 m3; however, particles in the respirable range (i.e., those
smaller than 10 m) will not be removed efficiently. The pres-
ence of nuisance particles in Space Shuttle air has resulted
in the addition of an orbiter cabin air cleaner to reduce the
amount of airborne dust [65]. This air cleaner, which is placed
in an opening between the Space Shuttle flight deck and the
middeck, is designed to create turbulence sufficient to pro-
duce flow through areas that were previously stagnant. The
filter is made of 400 mesh (38.5-m pore size) stainless steel
with an effective area of 0.46 m3 and a flow of 200600 ft3/min
(721 m3/min). The orbiter cabin air cleaner is required to be
carried on all Space Shuttle missions lasting 50 or more
21. Health Effects of Atmospheric Contamination
person-days [65]. In a contingency, the handheld vacuum
could be used to capture large, floating particles.
On the U.S. segment of the ISS, particle removal capability
is more advanced than it is on board the Space Shuttle. The
ISS requirement is to restrict the airborne concentration of
particles to less than 0.05 mg/m3 (105 particles per cubic foot)
for particles larger than 0.5 m. Cabin air bacteria filters meet
this requirement by scrubbing 99.97% of particles 0.3 m and
larger from the atmosphere. The filters, with a nominal flow
of 70 ft3/min (2.5 m3/min), are composed of borosilicate fibers
and are protected by a 20 20 mesh screen that is periodically
vacuumed. Six filters are located in the U.S. Laboratory mod-
ule, and 4 filters are located in Node 1.
Conclusions
As human space missions reach deeper into space, crews must
become more independent of ground controllers. With this in
mind, future analytical instruments for air pollutants must pro-
vide data that are complete and that can be readily interpreted
by onboard personnel who are neither toxicologists nor physi-
cians. As environments reach 100% closure for distant mis-
sions, the challenges of managing air pollutants will increase.
Moreover, the addition of new pollutant sources (e.g., plant
growth chambers, waste incineration, and dust) on celestial
bodies will demand new strategies for providing safe air for
crewmembers to breathe.
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22
Hypoxia, Hypercarbia, and Atmospheric Control
Kira Bacal, George Beck, and Michael R. Barratt
Space is characterized by absenceabsence of air, absence
of pressure, and absence of radiation protectionall basic
elements necessary to support life on Earth. The human crew-
members who are today venturing into space, arguably the
most hostile environment into which humans have yet ventured,
must carry with them not only their food and water but also
artificial atmosphereslife support systems. The design of
these life support systems is extraordinarily complex [13].
This chapter focuses on how spacecraft designers provide and
maintain a breathable, Earthlike atmosphere in human space
vehicles. Also addressed are the dominant physiologic effects
that occur whenever contingency situations arise.
As challenging as it is to attempt to reproduce an Earth-
like atmosphere inside a spacecraft, the tasks before environ-
mental control systems designers are more complex because
they must balance operational requirements and constraints
with human resource needssome of which conflict with one
another. Atmospheric pressure, composition, temperature, and
humidity must all be selected and maintained within healthy
limits for space flyers. Within these limits, a great deal of vari-
ability can remain. For example, if a lower habitable atmo-
spheric pressure is selected for a spacecraft, a spacewalker
incurs less risk of decompression sickness in decompressing to
suit pressure (see Chapter 11). This lower atmospheric pressure
also means that the spacecraft hull does need not to be strength-
ened to withstand a higher internal pressure and that smaller
stores of gas (oxygen and nitrogen) are required. However,
the artificial nature of such a lower habitable atmospheric
pressure environment may compromise the usefulness and
generalizability of certain experiments that are normally
performed in the standard sea-level atmosphere. Moreover,
the higher oxygen concentration required to maintain acceptable
oxygen tension at a lower overall pressure could lead to an
unacceptable fire risk.
So, one of the most fundamental tasks for life support system
designers is to assess the competing needs of different groups.
How can a system provide a safe and comfortable living envi-
ronment for the crew, facilitate safe spacewalks, permit good
science, and yet prevent undue safety concerns? Answering
this question, a basic design challenge, establishes only a
basis for nominal operating conditions; planning for systems
mishaps requires another layer of consideration.
Space operations may entail exposure to both hypoxic and
hyperoxic gas mixtures as well as to hypobaric or hyperbaric
ambient pressures. A mishap involving any of these condi-
tions may be quite hazardous and may require immediate
action by the creweven as the physiologic changes associ-
ated with these conditions impair the crews ability to take
action. Acute depressurization, or loss of pressure, has in fact
already led to tragedy in the case of Soyuz 11 (June 1971),
in which cosmonauts Georgi Dobrovolksy, Vladislav Volkov,
and Viktor Patsayev died when a pressure equalization valve
opened prematurely during early atmospheric reentry.
To avoid similar tragedies, space medicine clinicians must
be intimately familiar with the hazards of the space flight envi-
ronment. They must prevent, anticipate, identify, and treat the
conditions that are associated with disorders of atmospheric
composition (such as hypoxia or hypercarbia). To do so, they
must understand not only the inner workings of the human
body but also the atmospheric standards that must be satisfied
by the spacecraft life support system.
This chapter reviews atmospheric standards with particular
attention to pathophysiology and operational issues associated
with pressure, temperature, humidity, and trace contaminants.
Next follows a discussion of the physiologically relevant
atmospheric gases oxygen and carbon dioxide along with their
associated clinical conditions (e.g., hypoxia and hypercarbia).
The chapter concludes with a review of the environmental
control systems found on board past and present spacecraft.
Atmospheric Pressure and Its Control
The International Civil Aviation Organization standard Earth
atmosphere is characterized as dry air composed of 20.948%
oxygen, 78.084% nitrogen, 0.0314% carbon dioxide (CO2),
0.934% argon, and other trace gases. Dry air comprises an
atmospheric pressure at sea level of 760 mmHg (14.7 pounds
445
446
per square inch [psi]) and an atmospheric density at sea level
of 1.225 kg/m3, held by a constant acceleration due to gravity
of 9.8 m/s2 (32.2 ft/s2), with a temperature at sea level of 15C
(59F) [4]. The major gas constituents of physiologic concern
that require monitoring for space travel are oxygen, nitrogen,
CO2, and water vapor. Other gases, such as carbon monoxide
(CO), are also monitored because of their hazardous nature.
An artificial atmosphere control system must regulate the
spacecraft temperature, pressure, humidity, and composition.
It also must remove CO2, ensure sufficient amounts of oxygen,
regulate pressure, and clear the air of trace contaminants.
Respirable gases for cabin atmosphere replenishment may
be transported to and stored on a space platform in 2 basic
forms: as tanked air consisting of a sea-level mix of nitrogen
and oxygen or as individual gaseous components. The former
approach avoids potential problems with the need to mix gases
and is more convenient for servicing a sea-level atmosphere.
(Introducing a small amount of oxygen into the atmosphere as
needed compensates for oxygen consumption by the crew.)
Conversely, maintaining separate stores of tanked oxygen
and nitrogen affords flexibility in controlling cabin atmospheric
composition, which can vary with the cabin pressure. Such
a system would allow the staged decompression of an entire
crew cabin, as in the Space Shuttle, or an isolated module such
as the International Space Station (ISS) airlock, in support of
extravehicular activity (EVA) prebreathe operations. At an
intermediate pressure, the oxygen concentration is increased
as needed to provide a physiologically adequate partial pressure
of oxygen (ppO2). Variable oxygen consumption and leak
scenarios can also be more effectively managed with such
a system than with a mixed-gas system. The Space Shuttle
uses cryogenically stored oxygen and nitrogen, whereas the
ISS makes use of both tanked air and separate oxygen and
nitrogen reserves.
Ideal Gas Laws
Dynamics of cabin atmosphere control are best understood
within the framework of the ideal gas laws. As such, it is useful to
be familiar with the relevant equations and their physiologic
consequences.
Boyles law (P2/ P1 = V1/ V2, where P = pressure and V = volume)
describes how gas volumes vary with changes in ambient
pressure. As a physiologic correlate, gas expansion associ-
ated with decreasing ambient pressure can lead to abdomi-
nal discomfort as enteric gas volume increases during rapid
ascent to altitude.
Charless law relates the volume and temperature of a gas
held at a constant pressure (V1/V2 = T1/T2, where V1 and V2
are initial and final volumes, and T1 and T2 are initial and
final absolute temperatures). As a corollary, for a gas held
at a constant volume, pressure is proportional to absolute
temperature. This relationship reflects the greater molecular
movement and higher collision rate associated with increased
K. Bacal et al.
temperature and underlies the temperature increase felt by the
occupants of a hyperbaric chamber as pressure increases.
Avogadros law states that equal volumes of all gases contain
equal numbers of molecules, when pressure and temperature
are held constant. A gram molecular weight (mole) of any gas
occupies 22.4 L at atmospheric pressure and 0C (32F) and
contains 6.02 1023 molecules (known as Avogadros num-
ber). This relationship serves to unite Boyles and Charles
laws into the general gas law (PV = nRT, where P, V, and T are
pressure, volume, and absolute temperature of a gas, n is the
number of moles of the gas, and R is a derived gas constant).
Daltons law (Pt = P1 + P2 + + Pn,, where Pt = total
pressure and P1, .Pn are individual constituent gas partial
pressures) describes the relationship of partial pressures in a
mixture of gases and underlies the phenomenon of hypoxia at
altitude. As overall ambient pressure drops, the pressure of the
constituent gases falls as well. For example, at sea level pres-
sure (760 mmHg) or (14.7 psi), ppO2 is 0.21 760 mmHg or
160 mmHg. At 5,486 m (18,000 ft), however, ppO2 is halved at
0.21 380 mmHg or 80 mmHg.
Henrys law relates the amount of gas dissolved in a liquid to
its partial pressure (C1 = kP1, where C1 is the concentration of a
gas in solution, k1 is a solubility factor, and P1 is the partial
pressure of the gas in contact with the liquid). This law explains
why exposure to altitude and decreased ambient pressure causes
gas to come out of solution, facilitating the creation of nitrogen
bubbles as seen in decompression sickness.
Pressure
As described by the gas laws, as altitude increases through the
stratosphere, atmospheric pressure decreases while the relative
proportions of constituent gases remain the same. The change
in barometric pressure is not a linear one, however. Pressure
changes with altitude are most extreme at lower altitudes;
(ascending from sea level to 2,440 m (8,000 ft), ambient
pressure drops by a quarter from 1 atmosphere (1 ATA) at
760 mmHg (14.7 psi) to 0.75 ATA at 570 mmHg (11.0 psi). An
additional 3,050 m (10,000 ft) of ascent is required for baro-
metric pressure to decrease another quarter, occurring at an
altitude of 5,486 m (18,000 ft). As a result, equivalent changes
in altitude may yield different physiologic responses depending
on the starting and ending ATA values.
Just as the pressure exerted by the atmosphere decreases as
one ascends from sea level toaltitude (Table 22.1), the ambient
pressure increases as one goes deeper underwater. The greater
density of seawater, roughly 1,000 times that of air, means that
relatively small excursions in vertical distance result in much
more significant pressure changes.
The human requirement for a pressure environment may
be defined by several distinct stages of physiologic effects.
The saturated vapor pressure of water at body temperature
is 47 mmHg (0.9 psi). At ambient pressures below this, body
tissues undergo spontaneous boiling, a phenomenon known
22. Hypoxia, Hypercarbia, and Atmospheric Control 447

Table 22.1. Pressure changes associated with altitude excursions. the fire hazard, whereas inadvertent increases in nitrogen
Altitude Pressure could lead to hypoxia or localized asphyxiation. The complexity
Meters Feet ATA mmHg mbar psi that use of a second gas adds to the life support system is one
0 0.0 1.0 760 1013 14.7
of the factors that led to the use of single-gas environments
1524.0 5,000 0.8 627 835 12.1 in early U.S. crewed spacecraft.
3049.0 10,000 0.7 517 689 10.0 It is important to understand how the risk of decompression
4573.0 15,000 0.6 426 568 8.2 sickness affects the design of a spacecraft environmental
6098.0 20,000 0.5 352 469 6.8 system. For any mission whether one flown in low Earth orbit
7622.0 25,000 0.4 291 388 5.6
9146.3 30,000 0.3 240 320 4.6
(e.g., those of the ISS or Space Shuttle) or to an extraterrestrial
body, ready and convenient access to the outside of the
Abbreviations: ATA atmospheres absolute, mbar millibars, psi pounds per spacecraft is desirable for assembly, maintenance, or scientific
square inch.
activities. Whether for routine exploration or unexpected repairs,
the time required before the transition from the cabin environ-
as ebullism (see Chapter 11), that leads to rapid cooling and ment to the vacuum of space should be as short as possible to
the creation of gas cavities as well as massive damage to minimize the overall operational overhead associated with EVA.
pulmonary and other tissues [5,6]. As a result, a minimum Because current space suits operate at fairly low pressures (222 to
barometric pressure of at least 47 mmHg (0.9 psi) is required 295 mmHg [4.3 to 5.7 psia]), a lower cabin pressure would mini-
just to keep body fluids in solution. The altitude at which this mize the nitrogen washout time. Minimizing the cabin pressure
pressure is reached is roughly 19,200 m (63,000 ft), which is also decreases the required hull strength and overall weight of
known as Armstrongs line. the vehicle, thereby requiring less propellant and less energy
The atmosphere must also provide a breathable composition expenditure to deliver to an orbital or surface site.
of gas with sufficient pressure for the alveolar exchange of Concerns have also been expressed within the space medicine
oxygen and CO2. Thus the ambient or barometric pressure community that chronic exposure to low barometric pressures,
is integrally linked to the physiologic availability of oxygen. particularly in combination with low ppO2, may have delete-
Along with the 47 mmHg of water vapor, a normal tension of rious effects on the human body. Combining low ambient
40 mmHg CO2 is present in the alveoli. Ambient pressure must pressures with higher concentrations of oxygen to avoid insuf-
exceed these combined pressures before further gas exchange ficient oxygen tensions in the body also increases the risk of
can occur. Therefore, the threshold atmospheric pressure for fire, as was demonstrated in the Apollo 1 tragedy in which
any degree of alveolar gas exchange is 87 mmHg (1.68 psi), three U.S. astronauts (Virgil Grissom, Edward White, and
which is equivalent to an approximate altitude of 15,240 m Roger Chaffee) perished in a fire during a pad exercise on
(50,000 ft). Above this altitude, humans must wear a pressure January 27, 1967, when the Apollo capsules 100% oxygen
suit to prevent hypoxia. At a lower altitude, around 10,668 m atmosphere was pressurized to 827 mmHg (16 psia) for a
(35,000 ft), barometric pressure is 179 mmHg (3.46 psia); if preflight test.
pure oxygen is breathed, normal physiologic functions can be
maintained. Ascending between these two altitudes requires
Units of Pressure
that oxygen be delivered under progressively increasing
positive pressure. Familiarity with the various units used to measure pressures
Although loss of pressure is thought of as an off-nominal in different operations and environments is helpful in under-
(i.e., unusual or unplanned) event, as occurred during a standing barophysiology. The use of particular units has often
Progress cargo ships collision with the Mir space station in been driven by historical precedent, operator preference, or
June 1997, it is important to note that the ambient pressure convenience. Early physiologic experiments, for example,
of any spacecraft will fall over time because of gas leakage used mercury manometers developed to study atmospheric
unless the gas is replenished [7]. As the total pressure drops, pressures; exposing a pressurized gas or liquid to a column of
so too will the partial pressure of each component gas. Thus mercury in a glass tube and measuring the resultant change in
vehicles must carry or create a supply of gas or gases by linear height was easily accomplished. Early altitude experiments
which, through judicious introduction into the environment, expressed pressure changes indirectly by equating phenomena
the vehicle crew can regulate their cabin pressure. For a dual to their altitudes, measured in feet or meters, rather than to
oxygen-nitrogen environment, each gas must be present in the pressures at which the phenomena occurred. Similarly, the
its proper proportion. In practical terms, this means that the first underwater hyperbaric investigations were operationally
system must ensure that sufficient stores of oxygen are present oriented and expressed results in a practical unit relevant to
to maintain an adequate alveolar oxygen tension (PAO2) and their applicationdepth of seawater.
nitrogen supplies are used to regulate proper ambient pressure. It is important to note that physiologic calculations must
It is easy to imagine how the improper use of either oxygen be performed using absolute pressure, which includes the
or nitrogen could lead to problems in the closed environment of barometric pressure exerted in a system by the surrounding
a spacecraft. The release of too much oxygen would increase atmosphere. Gauge pressure, by contrast, is a relative pressure
448 K. Bacal et al.

that does not account for atmospheric pressure. As an example, Table 22.2. Oxygen partial pressures of standard atmospheric air
the units on pressure gauges commonly found on gas cylinders with increasing altitude.
are shown as pounds per square inch gauge (psig), sometimes Altitude PB PIO2 Equivalent
abbreviated to psi. When a gas cylinder is empty, its gauge (feet) (mmHg) (mmHg) % O2 at sea level
reads zero despite the fact that the ambient pressure is not 0 760 159 20.9
zero. The operational units of meters (or feet) of altitude and 5,000 627 131 17.4
of seawater are also relative gauge pressures. 10,000 517 108 14.4
The units typically used to express pressure in hypobaric, 15,000 426 89 11.8
20,000 352 74 9.6
normobaric, and hyperbaric operations are millimeters of
25,000 291 61 7.8
mercury (mmHg), psia, kiloPascals (kPa), bars, meters or feet 30,000 240 50 6.2
of seawater (msw or fsw), and ATA. The mathematical rela-
tionship of these units is as follows: Abbreviations: PB atmosphere pressure, PIO2 partial pressure of inspired oxygen.

1 ATA = 760 mmHg = 14.7 psia = 101.3 kPa = 10.1 msw (33 fsw),
and
1 bar = 0.987 ATA = 100 kPa
For example, the absolute pressure experienced by a patient
in a sea-level hyperbaric chamber pressurized to 18.3 msw
(60 fsw) is [18.3 msw (1 ATA/10 msw)] + 1 ATA (local atmo-
spheric pressure) or 2.8 ATA.
Inspired Partial Pressure
The amount of oxygen inhaled with each breath depends on
both the percentage of oxygen in the inspired air (concentra-
tion) and the ambient pressure. From these two values, the
physiologically significant absolute pressure or partial pressure of
a gas is derived. Therefore, the partial pressure of an inspired
gas (PIGas) is defined as the product of the fractional concen-
tration of the inspired gas (FIGas) and the local barometric
pressure (PB).
PIGas = FIGas PB (1)
The fraction of inspired oxygen is expressed as FIO2, and
the partial pressure of the inspired oxygen is denoted PIO2.
The partial pressure of inspired nitrogen is PIN2 = FIN2 PB.
According to this equation, the inspired ppO2 (P1O2) at sea
level, where PB is 760 mmHg (14.7 psi) and the concentration
of oxygen in the air is 21% (FIO2 = 0.209), is calculated as
(760 mmHg 0.209) or 158.8 mmHg (3.1 psi).
ISS flight rules state that the minimum pressure for any
habitable element is 400 mmHg (7.7 psia), although a level as
low as this would only be reached during a dire emergency
such as a cabin leak. With the equation above and the recogni-
tion that flight rules allow the maximum emergency FIO2 to
be 32.1% because of fire risk, the resulting partial pressure
of inspired oxygen at this lower pressure would thus be
128 mmHg (2.47 psia).
Table 22.2 shows ppO2 values, and hence PIO2 values, for
atmospheric air associated with decreasing ambient pressures
with increasing altitude. Although the percentage of oxygen
in the atmosphere does not vary as the pressure decreases, the
relative amount of oxygen diminishes as compared with its
sea-level value. As such, measurements of oxygen concentration
alone cannot be used to establish the safety of an area. If the
barometric pressure is low enough, even an atmosphere of
100% oxygen cannot support life.
Alveolar Gas Equation
By the time atmospheric gas reaches the alveoli during res-
piration, it has been warmed to body temperature and satu-
rated with water vapor during its travel through the respiratory
system. The ppO2 is further reduced from its inspired level
by dilution as the inspired gas mixes with end-alveolar gas,
which has higher levels of CO2. Therefore, the partial pres-
sure of the oxygen that fills the alveoli during inspiration,
PAO2 (where A represents alveolar), is a result of inspired
gas mixing with water vapor and CO2. The equation govern-
ing this mixing, the alveolar gas equation, is:
PAO2 (mmHg) = PIO2 (PACO2/R)
+{PACO2 FIO2 [(1 R)/R]} (2)
where PAO2 is the alveolar partial pressure of oxygen (alveolar
oxygen tension), PIO2 is the inspired partial pressure of oxy-
gen, PACO2 is the alveolar partial pressure of CO2, R is the
respiratory exchange ratio (CO2 produced/oxygen consumed),
and FIO2 is the fractional concentration of inspired oxygen.
Although this equation is accurate, if we assume there is
negligible CO2 in the inspired air, it has limited use outside of
the laboratory. Operational crews and clinicians rarely have ready
access to measurements of alveolar CO2 tension or R. However,
the bracketed term in the above equation is a correction factor for
R and is usually relatively small. Assuming average conditions
and a body at rest, when R is typically 0.8, FIO2 is 0.21, and PACO2
is 40 mmHg (0.8 psi), alveolar CO2 levels are approximated
by arterial PaCO2, and the term in the square brackets is never
greater than 2 mmHg (0.04 psi) and can be ignored. The following
more practical equation can then be derived:
PAO2 = (PB PH2O) FIO2 (PaCO2 1.25) (3)
where PAO2 is the alveolar partial pressure of oxygen (alveolar
oxygen tension), PB is the barometric pressure, PH2O is the water
vapor pressure (47 mmHg or 0.9 psi at 37C [98.6F]) ), FIO2 is
the fraction of inspired oxygen, PaCO2 is the arterial CO2, and
1.25 is the inverse of R, where R is assumed to be 0.8.
22. Hypoxia, Hypercarbia, and Atmospheric Control
This equation is convenient for determining alveolar oxy-
gen at rest, where PaCO2 is assumed to be 40 mmHg (0.8 psi).
During activities that might lead to hyperventilation, such as
hypobaric operations, the PaCO2 will vary from 40 mmHg
(0.8 psi) and the assumption is no longer valid. Further, dur-
ing periods of physiologic stress, R will move toward 1 as the
metabolic rate increases. Such conditions may occur in space
operations, particularly during tasks that involve high meta-
bolic rates (e.g., EVA).
Constituent Gases: Oxygen
When ambient pressure decreases, such as during ascent to
altitude, the ppO2 in the atmosphere, and subsequently the
PAO2, falls as described by Daltons law. In most people, a
normal PAO2 is generally accepted to be 100 mmHg, as is
typical when the ppO2 is near 160 mmHg (3.1 psi), the ppO2
at sea level. For the average person who is living at or near
sea level and is acclimated to that altitude, subtle physiologic
decrements begin when PAO2 nears 80 mmHg (1.54 psi) and
gradually worsen until consciousness is finally impaired at a
PAO2 of 30 mmHg (0.58 psi) [8].
At a threshold altitude of 3,050 m (10,000 ft), the ambient
pressure is 523 mmHg (10.1 psi), ppO2 is 109 mmHg (2.1 psi),
and PAO2 is 60 mmHg (1.16 psi), a value that is no longer
sufficient to oxygenate body tissues fully without adaptation
responses [9]. At this PAO2, hyperventilation at rest is present
even in healthy individuals and it is generally considered a
threshold for hypoxia. The U.S. Air Force mandates the use of
supplemental oxygen whenever cabin altitude exceeds 3,050 m
(10,000 ft); under certain conditions, such as night flying, that
limit may be even lower. Other organizations have slightly
different threshold levels. The Federal Aviation Administration,
for example, uses 3,810 m (12,500 ft) as its altitude criterion
for use of supplemental oxygen.
In the U.S. Space Shuttle Program, the crew compartment can
undergo staged decompression from sea level to 527 mmHg
(10.2 psi) to augment nitrogen washout in preparation for
EVA. If the oxygen concentration is held constant at 0.21
during these times, the crews PAO2 would be 50.8 mmHg, as
calculated using the alveolar gas equation:
PAO2 = FI O2 (PB PH2O) (PaCO2 1.25)
= 0.21(527 47) (40 1.25) = 50.8 mm Hg
However, NASA considers this PAO2 to be unacceptably low.
As a result, the Space Shuttles atmospheric oxygen concen-
tration is increased to 23.8% during operations at 527 mmHg
(10.2 psi), yielding a PAO2 of 64.4 mmHg (1.25 psi), which is
deemed acceptable.
Aside from manipulating cabin atmosphere oxygen concentra-
tion, another way of maintaining a physiologically acceptable
PAO2 at lower ambient pressure is with supplemental oxygen
masks, such as those that aviators wear. Oxygen is not a benign
substance, however, and its use must be controlled as carefully
449
as that of any other biologically active drug. Although short-term
use of increased FIO2 during an emergency is unlikely to cause
medical problems, increasing the duration of exposure also
increases the risk of oxygen overdose or toxicity.
At sea-level pressures, breathing 100% oxygen has been
shown to cause chest discomfort and atelectasis within a day
[5,10]. However, like physiologically beneficial effects, the
degree of oxygen toxicity depends directly on the ppO2 and
the duration of the exposure. At low ambient pressures, such
as 190 mmHg (3.7 psi), a pure oxygen atmosphere (FIO2 = 1)
will maintain an acceptable PAO2:
PA O2 = 1.0(190 47) (40 1.25) = 93 mm Hg,
which is close to normoxia.
As described above, the physiologic consequences of
hyperoxic environments depend on oxygen partial pressures.
By contrast, high concentrations of oxygen carry an unacceptable
fire risk. These two properties can act in combination, as
was the case in the Apollo 1 fire. As noted earlier, that fire was
due not only to the pure oxygen environment of the capsule,
but also to the fact that the environment was pressurized to
greater than sea level for the ground test. These two aspects
absolute partial pressure and concentrationexist in uneasy
balance for the designers of environmental systems, driving a
perpetual compromise between fire prevention and physiologic
requirements.
Oxygen Transport and the Oxyhemoglobin
Dissociation Curve
In subjects with normal ventilation and gas exchange, the
ppO2 in the lungs controls how much oxygen is delivered to
the tissues. After crossing the alveolar-capillary interface,
the oxygen from inspired air travels throughout the body
via the circulatory system in two forms: dissolved in the
plasma and bound to hemoglobin. The amount dissolved
in the plasma is a function of the ppO2 in the alveoli, PAO2.
The arterial partial pressure of oxygen (PaO2) is, in turn,
proportional to the PAO2 and is tied to the diffusion constant
for oxygen across the alveolar-capillary membrane. Blood
plasma can hold 0.003 ml of dissolved oxygen per 100 ml.
The other means by which oxygen is transported within the
body is via hemoglobin. This method accounts for the vast
majority of oxygen delivered to the tissues. Oxygen bonds
reversibly with hemoglobin to create oxyhemoglobin. Each
hemoglobin molecule can carry four oxygen molecules, which
results in the transport of 1.39 ml of oxygen per gram of hemo-
globin or 20.8 ml of oxygen per 100 ml of blood (assuming 15
grams of hemoglobin per 100 ml of blood).
In addition to affording greater transport capacity, oxy-
hemoglobin has several other physiologic advantages that
manifest in its dissociation curve (Figure 22.1). First, the
plateau at high oxygen tensions ensures that small decrements
in alveolar oxygen have little effect on the uptake of oxygen
450
Figure 22.1. Oxygenhemoglobin dissociation curve. CO2, carbon
dioxide; DPG, diphosphoglycerate
by the blood. Thus minor increases in altitude, for example,
do not cause a proportional decrease in oxygen transport.
Without this trait, humans would be unable to leave coastal
areas and settle in other regions; the adaptive benefit of such
a property is obvious.
Second, the steep portion of the curve demonstrates that a
small drop in the ppO2, as occurs at the tissues, will be accom-
panied by a large amount of oxygen offloading. Where a great
deal of oxygen is present (e.g., in the lungs), the oxyhemoglobin
remains intact. Where little oxygen is present (e.g., in the
tissues), the molecule dissociates and oxygen is made available
to the active tissues. In this fashion, the ppO2 in the blood and
thus the gradient driving diffusion of oxygen into the tissues
are maintained.
Although the curves basic shape does not change, its
position can shift laterally in response to various homeostatic
perturbations. Physiologically, this is equivalent to a change
in the affinity between hemoglobin and oxygen. Blood levels
of CO2 and hydrogen ions influence this affinity to the bodys
advantage. A shift to the right is induced in the terminal vas-
culature, where higher CO2 levels reduce the affinity of the
hemoglobin for oxygen and facilitate its dissociation from the
heme groups at any given oxygen tension to supply the tis-
sues. In the lungs, where blood CO2 levels are diminished as
CO2 diffuses into the alveoli for exhalation, a leftward shift of
the curve facilitates enhanced blood oxygenation. This shift
in the blood oxyhemoglobin dissociation curve in response
to altered blood levels of CO2 and hydrogen ions is known
as the Bohr effect. Conversely, the binding of oxygen with
hemoglobin causes displacement of CO2 and thus influences
CO2 transport, a phenomenon known as the Haldane effect.
Oxygen dissociation from hemoglobin in the terminal vascu-
lature leads to increased CO2 binding; in the lungs, increased
oxygenation induces CO2 release and subsequent ventilation.
A rightward shift can also be caused by other conditions,
such as higher temperature. In general, conditions such as
K. Bacal et al.
Figure 22.2. Relationship of barometric pressure, inspired oxygen ten-
sion (PIO2), and oxygen saturation (SaO2) with increasing altitude while
breathing ambient air. The narrowing of the difference between PIO2 and
SaO2 at increasing altitude results from increased ventilation. (Hackett
PH, Roach RC [11].)
these are associated with increased tissue workload or
metabolic rate, requiring an increased offloading of oxygen
to the tissues to meet metabolic demands and an increased
uptake of CO2. The biochemical modulating substance 2,3-
diphosphoglycerate (2,3-DPG) also shifts the oxygen dissoci-
ation curve to the right. 2,3-DPG is present in red blood cells,
and its concentration increases in hypoxic conditions. Such
an increase, as is found in humans and animals living at high
altitude, shifts the curve, facilitating the release of oxygen to
the hypoxic tissues.
As described above, barometric pressure, percentage of
oxygen, and available hemoglobin all interact to determine the
actual oxygen content available to the tissues. A disruption in
any of these parameters will impair the physiologic transport
of oxygen according to the oxygen content equation. The content
of oxygen in arterial blood (CaO2) is measured in ml of O2 per
100 ml blood and is often expressed as volume percent:
CaO2 (vol%) = (Pa O2 0.003)
+ (hemoglobin 1.39 SaO2) (4)
where CaO2 is the content of oxygen in the arterial blood, aver-
aging 20.4 ml/100 ml blood (vol %), PaO2 is the partial pressure
of oxygen dissolved in plasma (average value 80 to 100 mmHg),
and SaO2 equals the fraction of hemoglobin saturated with
oxygen, which typically ranges from 95% to 100%. Hemoglobin
is expressed in units of grams of hemoglobin per 100 ml blood.
The relationships between altitude, barometric pressure,
PIO2, and SaO2 are shown in Figure 22.2.
22. Hypoxia, Hypercarbia, and Atmospheric Control
Acute Hypoxia
This section addresses the physiologic results of breathing
cabin atmospheres that contain inadequate oxygen, which
could result from a cabin leak (resulting in hypobaric hypoxia)
or an environmental control mishap in which cabin pressure is
maintained but oxygen regulation is inadequately controlled
(resulting in normobaric hypoxia).
Hypoxia is a state of oxygen deficiency in the tissues
and cells that is sufficient to cause impairment of function.
Whether from exposure to altitude or breathing sea-level gases
in which the FIO2 is less than 0.21, acute hypoxia is marked by
immediate physiologic responses triggered by sensitive target
tissues. The magnitude of these changes and their operational
impact depend on the PIO2.
To ensure adequate PAO2 on the ISS under normal condi-
tions, flight rules require that the ppO2 in a habitable environ-
ment remain between 146 mmHg (2.82 psia) and 178 mmHg
(3.44 psia). Assuming an ambient pressure of 734 to 770 mmHg
(14.2 to 14.9 psia) during normal operations, the correspond-
ing upper limits of oxygen concentration on the ISS are 24.1%
for most of the structure and 30% for the joint airlock. The
Space Shuttle has an upper limit of 30% depending on the
ambient pressure. (Both the ISS airlock and the Space Shuttle
can be decompressed to a pressure intermediate between sea
level and the extravehicular mobility unit [EMU] space suit
pressure of 222 mmHg (4.3 psia) to facilitate nitrogen washout
before EVA. This intermediate pressure is usually 526 mmHg
[10.2 psia].)
In off-nominal situations, these limits are relaxed to
accommodate the emergency, because PAO2 must be main-
tained, even under extreme conditions, to allow crewmem-
bers to carry out their necessary tasks. As an example, if
cabin pressure were to drop to 400 mmHg (7.7 psia), the
oxygen concentration should then be increased to 32.1%
to ensure that the ppO2 does not fall below 122 mmHg
(2.35 psi). This value corresponds to a PAO2 of 63 mmHg
(1.22 psia), which NASA considers adequate to permit the
crew to function in an emergency. It is important to note
that as barometric pressure decreases, the acceptable lower
limits of ppO2 and oxygen concentration must rise to main-
tain PAO2 because of the saturation of breathing gases with
water and their dilution with alveolar CO2. Table 22.3 lists the
acceptable pressures and oxygen concentrations for the ISS
under off-nominal conditions.
Table 22.3. Off-nominal International Space Station cabin atmosphere
constraints.
Ambient Pressure Minimum ppO2 O2 Concentration
(mmHg [psi]) (mmHg [psi]) (%)
760 [14.7] 120 [2.32] 15.7
490527 [9.510.2] 122 [2.35] 2324.7 maintain a high index of suspicion for all forms of hypoxia
400 [7.7] 128 [2.47] 32.1
451
Types of Hypoxia
The four generally recognized physiologic classifications of
hypoxiahypoxic, hypemic, stagnant, and histotoxicare
based on the relative position of the insult in the chain of oxygen
delivery to the tissues.
Hypoxic hypoxia occurs when gas exchange at the alveolar-
capillary interface is inadequate, such as from a dimin-
ished ppO2, an obstruction in the airway, a disease process
in the lungs (such as pneumonia), or a ventilation/perfusion
mismatch. In hypoxic hypoxia, the supply of oxygen to the
blood is compromised in some way. This form of hypoxia
is seen at altitudes greater than 3,050 m (10,000 ft), the
lower level of the physiologically deficient zone. For
some individuals, a much lower altitude may be suffi-
cient to produce significant effects because of underlying
conditions such as high carboxyhemoglobin levels from
smoking, anemia, or cardiac insufficiency. Conversely,
acclimatization to a lower ppO2 will increase the threshold
altitude at which physiologic effects are seen. In general,
the space medicine patient population will have few, if
any, of these preexisting conditions.
Hypemic or anemic hypoxia, by contrast, results from a
reduction in the oxygen-carrying capacity of the blood. Anemia,
hemorrhage, CO toxicity, and hemoglobinopathies are examples
of conditions in which oxygen is available in the lungs but the
blood is incapable of transporting it from the lungs to the tissues
in sufficient quantities.
In stagnant or ischemic hypoxia, as the name implies, the
hypoxia results from inadequate circulation. Congestive heart
failure, hypovolemia, venous pooling, occluded blood vessels,
and acceleration forces (such as those in high-performance
aircraft and spacecraft during launch and landing) are all
causes of stagnant hypoxia because they diminish the bodys
ability to transport oxygen-enriched blood from the lungs to
the tissues.
Finally, in histotoxic hypoxia, oxygen is available to the
body, the blood is able to transport it, and the cardiovascular system can
circulate the blood to the tissues, but the tissues are incapable
of using the oxygen efficiently. Such cases result from the
tissues having been poisoned by toxins such as cyanide
or alcohol, leading to impairment of the cytochrome chain and
therefore to the end use of oxygen at the cellular level.
Although hypoxic hypoxia is the form most commonly
seen in aerospace operations, multiple forms can be present
simultaneously and can have additive effects. For example,
in the event of a debris or micrometeorite penetration on a
space platform, the module may be punctured, leading to leak-
age of the cabin atmosphere (hypoxic hypoxia). Simultane-
ously, a crewmember may be injured and suffer blood loss
(anemic hypoxia). If a fire occurs, CO and other combustion
by-products may be created, leading to hypemic and histo-
toxic hypoxia. As a result, aerospace medicine clinicians must
based on environmental circumstances.
452
As noted above, hypoxic hypoxia occurs in the presence of
an insufficient supply of oxygen across the alveolar-arteriolar
interface, leading to a diminished PaO2. As the ambient ppO2
decreases, the oxygen gradient between deoxygenated hemo-
globin and alveolar air is reduced, resulting in reduced diffu-
sion from the alveoli to the bloodstream (Fickes equation).
Hypoxic hypoxia is one of the major physiologic risks asso-
ciated with aviation and space operations, which take place in
environments involving risk of acute depressurization of the
crew compartment or pressure suit. One such example was the
Soyuz 11 tragedy, in which the Russian flight crew died when
a small and inaccessible valve designed to equalize cabin and
ambient pressures during the final stage of the descent was
jolted open immediately after the deorbit burn. The cabin
depressurized during descent at 168 km (104.4 miles), an alti-
tude incompatible with life. At the time, Russian operating
procedures did not call for the routine use of either pressure
suits or supplemental oxygen. Similarly, before the Space
Shuttle Challenger accident, U.S. Shuttle astronauts did not
wear pressure suits during launch or landing.
The use of closed-atmosphere control systems presents
another risk of hypoxia during space operations. Closed
systems generally add oxygen to the atmosphere based on
metabolic demand, environmental feedback, or both while
continuously removing CO2 from the air. If the system
should fail to add oxygen, the FIO2 would fall continuously
with metabolic consumption. Moreover, given the insidious
nature of symptoms of hypoxia, affected individuals may
not notice until they are too impaired to take corrective
action. The situation is even more dangerous if the system
continues to remove CO2 as the FIO2 diminishes, because
no hypercarbic reaction would occur to alert the crew. Factors
such as these drive the requirements for redundant and
reliable monitoring systems in spacecraft.
Physiologic Effects of Acute Hypoxia
Perhaps the most critical effects of acute hypoxia are those that
affect the central nervous system. To maintain consciousness
requires an adequate flow of oxygen to the brain. The brain,
even at rest, has one of the highest oxygen consumption rates
of all tissues. Unlike other tissues, such as muscle, the brain
can only minimally increase from its resting state the number
of open capillary beds or the volume of blood flow through it.
As a result, it is particularly vulnerable to hypoxic effects.
As the brains oxygen supply is impaired, increasing levels of
hypoxia result in greater cognitive and motor impairment and
the inability to perform useful work. The neurologic effects
of hypoxia are believed to be mediated both directly, through
effects on the neurons, and indirectly, through the chemore-
ceptors and reticular formation.
Hypoxia produces characteristic changes in brain electri-
cal activity on electroencephalography as well as two-phase
response of the cerebral circulation. Below an equivalent alti-
tude of 4,570 m (15,000 ft), equal to 429 mmHg of ambient
K. Bacal et al.
pressure, diminished PaCO2 predominates because of second-
ary hyperventilation and cerebral vasoconstriction occurs,
reducing blood flow to the brain. At altitudes above 4,880 m
(16,000 ft), however, diminished PaO2 predominates and the
vasculature dilates, increasing cerebral blood flow and oxygen
delivery to the neural tissues. The magnitude of this response
is limited by the increase in cerebral blood pressure, which can
raise intracranial pressure and contribute (in chronic hypoxic
states) to the development of altitude-related illnesses.
Hypoxia is also associated with a modification of the
blood-brain barrier permeability. As the brains capillary beds
dilate in response to an increased capillary pressure, the bar-
rier opens transiently and vasogenic edema develops [12].
The latent recovery from central hypoxia further suggests that
hypoxia alters the uptake and release of both excitatory and
inhibitory neuroeffectors, causing a net increase in inhibitory
agents [13]. In severe hypoxia, this inhibition may have neu-
roprotective effects because it reduces the metabolic demands
of the brain (and those of the organism as a whole) by reducing
motor activity.
Even before neurologic effects of hypoxia become evident,
compensatory cardiopulmonary changes occur in response to
the drop in alveolar oxygen levels. The decrease in PaO2 triggers
the carotid body to stimulate the medullas central respiratory
center, increasing respiratory rate and minute ventilation.
This rise in ventilation, known as the hypoxic ventilatory
response, is regulated by the carotid body and serves as the
primary means by which the body seeks to maintain PaO2. The
response also has the simultaneous effect of decreasing PaCO2
levels through increased ventilation. As might be expected,
anything that blunts the hypoxic response (e.g., respiratory
depressants or chronic hypoxia) will interfere with the bodys
ability to compensate for acute hypoxic conditions.
In the lungs, a decrease in alveolar ventilation causes
pulmonary vasoconstriction, redistributing lung perfusion
and shunting blood away from the unventilated hypoxic
alveoli. Although this reflex has beneficial effects in the
case of regional hypoxia, it is detrimental in a hypoxic
environment such as at high altitude. In hypobaric hypoxia,
because all of the alveoli are filled with hypoxic gas, the
hypoxia-induced vasoconstriction occurs globally. This
generalized alveolar vasoconstriction leads to increased
pulmonary artery pressure.
Simultaneously, in an effort to increase oxygen delivery to
the tissues, the accompanying increase in heart rate raises
cardiac output, although stroke volume initially drops slightly.
Mean arterial pressure is generally unchanged despite the
increase in sympathetic tone. These changes are magnified
significantly when exercise is superimposed on the hypoxic
event (Table 22.4). Hammond, Wagner, and colleagues studied
the response of healthy men exposed to hypobaric hypoxia at
3,050 and 4,570 m (10,000 and 15,000 ft) during rest and
rigorous cycle ergometry and demonstrated that the physiologic
responses to hypoxia are similar for both hypobaric and
normobaric hypoxia [14,15].
22. Hypoxia, Hypercarbia, and Atmospheric Control 453

Table 22.4. Cardiopulmonary performance during exercise (cycle ergometry) at sea level and at altitude.
Altitude
10,000 ft (PB 523 mmHg)
Sea level Workloads 15,000 ft (PB 429 mmHg)
Physiologic
Parameters Rest 60 W 120 W 180 W Rest 60 W 120 W 180 W Rest 60 W 120 W 180 W
.
Ve, L/min 10.7 28.5 49.1 76.5 10.7 31 52.9 86.5 12.7 35.3 67.2 101.9
HR, beats/min 89 121 146 165 91 131 153 173 102 143 164 172
VO2, ml/min 380 1,170 1,950 2,660 370 1,160 1,800 2,530 370 1130 1750 2270
PaO2, mmHg 95 98 97 94 56 48 47 48 39 33 34 35
PaCO2, mmHg 34 36 37 34 32 34 33 29 30 30 28 26
.
Abbreviations: W watt, PB barometric pressure, Ve oxygen consumption, HR heart rate, VO2 volume of oxygen, PaO2 alveolar oxygen pressure, PaCO2 alveolar
carbon dioxide pressure.
Source: Data from Wagner PD, Gale GE, Moon RE, et al. [14]. Used with permission.

Maintenance of core body temperature (Tb) also plays a
significant role in oxygen consumption. Cold exposure and
decreased core temperature initially increase the hypoxic
response because of the increase in metabolic rate. When the
ambient temperature is below the thermoneutral range (24C
[75F] in air, 28C [82F] in water), mammals shiver and
perform other behaviors in an attempt to produce more heat
and raise their .core temperature. For most animals, oxygen
consumption (VO2, expressed in ml/min) increases by 11%
for every degree Celsius that their core temperature drops. In
addition to the additive effects of hypothermia on hypoxia,
hypoxia alone can contribute to hypothermia because the
resultant hyperventilation further cools the body [16].
Ample evidence shows that moderate hypothermia (Tb of
2528C) and profound hypothermia (Tb of 1520C) have
neuroprotective effects during hypoxia. In highly specific
conditions, such as certain surgeries, hypothermia is used to
minimize the damaging effects of prolonged tissue hypoxia.
This phenomenon is familiar through widely publicized cases
of persons who made neurologic recoveries after prolonged
immersion in icy waters. Unfortunately, the diminished vulnera-
bility of the hypothermic human body to hypoxia is irrelevant
for aerospace operations, as the effects of the hypothermia
itself render the individual operationally useless.
Symptoms of Acute Hypoxia
The clinical manifestations of these various physiologic
responses to hypoxia are quite variable. Signs and symptoms
of hypoxia can range from the subtle to the overt. Subjective
sensations can be very broad and range from a vague sense of
apprehension to frank air hunger, vision changes, numbness, or
paresthesias. Nonspecific symptoms of acute hypoxia include
fatigue, nausea, headache, dizziness, hot or cold flashes, and
mood disturbances such as lethargy, euphoria, belligerence,
and sleepiness. Also seen are decrements in color, night and
peripheral vision, increased respiration rate and depth, loss of
fine motor control, decreased muscular coordination, and
cyanosis. Perhaps most dangerous to crewmembers in the
space flight environment are the mental changes that occur
that may not be perceptible to the affected pilot or space flyer
who is simultaneously called upon to recognize and remedy
the situation. Such changes include poor concentration, men-
tal confusion, poor judgment, lack of insight, deterioration in
mental performance, short- and long-term memory loss, and
eventually unconsciousness.
Because none of these signs and symptoms is pathogno-
monic for hypoxia, crews and clinicians alike must maintain
a high index of suspicion for hypoxic events. Unfortunately,
confusion, poor insight, and other mental changes often
predominate in acute hypoxia, making it even harder for
affected individuals to realize their condition and placing
even greater responsibility on the aerospace clinician to rec-
ognize these signs.
Although the rate of onset varies depending on the acuity of
the hypoxic insult, both rapid and gradual onsets of hypoxia
can be dangerous. In rapidly occurring hypoxia, the crews
may become incapacitated so quickly that they may have
no opportunity to react. In hypoxia that occurs more slowly,
symptoms may develop so gradually that the crew may not
realize what is happening. Many case reports have described
subjects being entirely unaware of their deteriorating mental
state during the hypoxic event. Retrograde amnesia has also
been reported in several investigations [17].
The clinical presentation of acute hypoxia can vary depend-
ing on the hypoxic insult and the concomitant circumstances.
Many factors can compound the severity of the symptoms and
resulting impairment, including increased physical activity,
the ambient temperature, the presence of underlying illness,
and the ingestion of drugs such as morphine and other neuro-
depressants or alcohol.
Effective Performance Time (Time of Useful
Consciousness)
An acute hypoxic exposure is an operational emergency.
Immediate responsive action is often required, either to correct
the situation or to effect an escape. The remedial actions necessary
454
may require the operator to move about, work through a set
of procedures, or develop a nonscripted solution. Inherent in
all of these actions is the need to think clearly and to perform
efficiently. However, as described above, hypoxias effects on
the brain tend to prevent purposeful activities.
In an attempt to understand these effects and plan appropri-
ate responses for loss of pressure events, two specific opera-
tional indices have been developed. Effective performance
time (EPT) or time of useful consciousness (TUC) refers to the
period beginning with initial hypoxic exposure during which
an afflicted crewmember may continue to perform operation-
ally relevant duties. Reserve time (RT) is the period between
the initial exposure to hypoxic conditions and complete loss
of performance capacity. These indices relate operational
considerations to the physiologic effects of an acute hypoxic
insult by representing the length of time that a person can
be expected to perform purposefully under various levels of
hypoxia (Table 22.5). The EPT is the most specific and the
most operationally useful measure for the purposes of train-
ing and for establishing preplanned responses. Although these
indices provide a means by which altitude can be linked to
general operational capabilities, significant shortcomings are
associated with the current EPT tables with regard to space-
flight operations. The EPT differs among individuals for a
given exposure and is also influenced by factors such as the
speed of the depressurization (rapid or explosive depressur-
izations can reduce EPT by 50%), physical activity (which
diminishes EPT), metabolic rate, and underlying physical
condition (poor condition also reduces EPT).
As is often the case in aerospace physiology, EPT tables
were designed with data largely derived from healthy young
military aviators seated at rest in altitude chambers. This fact
is of particular interest to space medicine, because space fly-
ers are often older than such subjects (tolerance to hypoxia
decreases with age) and may be physically deconditioned
after extended stays in a microgravity environment. These
differences could lead to variations in the EPTs among the
aerospace population. In addition, reversing the inciting event
in the space environment usually requires performing active
work, and the effect of such activities on EPT has not been
well documented.
Table 22.5. Effective performance times with increasing altitude.
Altitude Effective performance timea
5,500 m [18,000 ft] 2030 min
6,700 m [22,000 ft] 10 min
7,600 m [25,000 ft] 35 min
8,500 m [28,000 ft] 23 min
9,100 m [30,000 ft] 12 min
10,700 m [35,000 ft] 3060 s
12,200 m [40,000 ft] 1520 s
Above 13,100 m [43,000 ft] 912 s
a
Also known as time of useful consciousness; can be reduced by up to 50%
by rapid decompression.
Source: From Pickard [18]. Used with permission.
K. Bacal et al.
In the aviation environment, a depressurization rarely
involves much physical activity on the part of the pilot: put-
ting on an oxygen mask located within easy reach, initiating
a rapid descent with the aircraft controls, issuing instructions
to other crew or passengers, all of which are done within a
small area. In contrast, a space crewmember confronted
with a leaking space station may have to locate and switch
to a supplemental oxygen supply, vacate and seal the leak-
ing module or modules, establish communications with the
ground, and perform complex troubleshooting procedures
that may entail moving to several different workstations and
locations. Although some tasks may be easier in a weightless
environment (e.g., donning a portable breathing apparatus),
other tasks (e.g., moving masses) may be significantly harder
because of the need for body fixation. Finally, the physiologic
changes associated with adaptation to microgravity may affect
the EPT estimated from the current tables. In summary, space
medicine clinicians must use caution when applying terrestrial
EPT tables to design space flight-related limitations and
operational guidelines. Until more is known, applying a conser-
vative margin is prudent.
Hyperventilation
Hyperventilation can mimic hypoxia in its symptoms and
can occur simultaneously with hypoxia. Whether induced
by hypoxia, stress, or faulty breathing equipment, hyperventi-
lation can also lead to significant psychomotor impairment.
Because the level of CO2 in the blood (PaCO2) exerts a powerful
influence on the bodys respiratory drive, hyperventilation and
its attendant elimination of excessive amounts of CO2 can
have far-reaching effects. The primary influence of hyperventi-
lation is mediated through acidbase disturbances. CO2 exists
in equilibrium with blood bicarbonate, the dissociated form of
carbonic acid. Reduction of CO2 levels via hyperventilation
causes bicarbonate levels to decrease as the equilibrium shifts
to favor the formation of CO2. The acute effect, before longer-
term blood chemical buffering responses occur, is an eleva-
tion in arterial blood pH. Among other responses, the leftward
shift in the oxygen-hemoglobin dissociation curve results in a
decreased ability of hemoglobin to offload oxygen in the ter-
minal vasculature (the Bohr effect). Cardiac output and blood
pressure fall, as does peripheral vascular resistance. Cerebral
vasoconstriction also induces a central stagnant hypoxia that
leads to impaired cognitive performance and potentially loss
of consciousness. Alkalosis also increases the sensitivity of
the peripheral nerves. Muscle spasms of the limbs and face
can occur at PaCO2 tensions of 15 to 20 mmHg. Clinical symp-
toms of hyperventilation resemble those of hypoxia: anxiety,
dizziness, numbness, muscle tightening or tremors, tingling,
faintness, cognitive and visual impairment, and nausea.
Hyperventilation during ascent to altitude causes an approx-
imately linear fall in PaCO2. At the summit of Mt. Everest, at
8,848 m (29,028 ft), the PaCO2 in a group of climbers was a
surprisingly low 7.5 mmHg [19]. Individuals with both a good
22. Hypoxia, Hypercarbia, and Atmospheric Control 455

pulmonary system and hypoxic drive were able to maintain

their PAO2 at about 35 mmHg despite being exposed to altitudes
over 7,010 m (23,000 ft), resulting in an estimated pulmonary
capillary oxygen tension of 28 mmHg. This calculated value
was confirmed by actual measurements taken during a simulated
Everest summit ascent [20].
As is true for recognizing hypoxia, crewmembers must have
a high index of suspicion to recognize hyperventilation or any
change in respiratory pattern and take appropriate action.
When hypoxia or hyperventilation is suspected, remediation
and treatment should begin immediately.

Recognition and Treatment of Acute Hypoxia

Oxygen, in addition to being required for fundamental metab-
olism, can also be regarded as a drug. Accordingly, its applications
should be guided by an understanding of its operational benefits
and its physiologic effects. The greatest difficulty in treating
acute hypoxia is early detection and recognition. Altitude
chamber training, in which space flight crews are trained to
recognize their own symptoms, can be helpful for becoming
aware of and preparing for insidious events.
Once hypoxia has been recognized, the treatment is simple:
resolve the oxygen deficiency. The method for doing so will
depend on the type of hypoxia being experienced. For hypoxic
hypoxia resulting from exposure to altitude, use of supple-
mental oxygen may suffice. Histotoxic hypoxia due to cyanide
poisoning requires significantly more intensive treatment and
support. Certain aspects of aerospace operations and the means
by which hypoxia can develop during flight are unique. For
example, aviators need not worry about pockets of hypoxic gases
in their environment, but this is a very real concern in space travel
due to inadequate gas mixing and uneven cabin ventilation.
Because of the potential for hypoxia in the training or
space environment, astronauts and cosmonauts must undergo
periodic altitude chamber training (annually for the Russian
Space Agency, every 3 years for NASA personnel) to remain
adept at recognizing their individual symptoms (Figure 22.3).
Because of the insidious nature of the process by which hypoxia
develops, recognizing it in other team members is emphasized
as well, because an unaffected space flyer may realize what
is happening before the hypoxic person can. Crewmembers
are reminded to be cautious in unventilated or poorly ventilated
modules and to be vigilant in monitoring each other for the signs
or symptoms of hypoxia (e.g., tachypnea, poor concentration,
repeated errors, or mood changes). On the ISS, a portable
oxygen analyzer is used as a first-line check in poorly venti-
lated and potentially hypoxic atmospheric pockets. The analyzer
is also to be deployed whenever a crewmember exhibits
hypoxia-like symptoms.
When a hypoxic atmosphere is confirmed to be present,
the appropriate response depends on the vehicle involved.
Crewmembers on the Space Shuttle are trained to use quick-
don masks, which provide supplemental oxygen through
hoses that connect to oxygen ports. In the event of a cabin
Figure 22.3. NASA Type II Altitude Chamber Profile used for altitude
training and hypoxia demonstration for astronauts, pilots, and other
flight crew. At 28,000 ft equivalent altitude, subjects remove oxygen
masks and perform mathematics problems and other cognitive tasks
until hypoxic symptoms are recognized and self-recovery (mask
donning) is performed. (PIO2, inspired oxygen pressure.)
leak, pressurized launch and entry suits are to be donned as
the next level of protection. Aboard the ISS, given its larger
volume, both quick-don masks and walkaround bottles are
used. Flight rules require the station crew to vacate and isolate
an ISS module should its ppO2 drop below the equivalent of
breathing air at 2,440 m (8,000 ft). The station itself must be
evacuated if the overall ppO2 level drops to an oxygen equivalent
altitude of 3,050 m (10,000 ft) for longer than 24 h. These
levels were established by NASA to address concerns regard-
ing the development of altitude sickness and high-altitude
pulmonary edema in such situations.
Chronic Hypoxia
Acute hypoxia is an inherent hazard of space operations. The
results of exposure to slight hypoxia on a chronic basis,
however, may not be as severe. When an individual is exposed
to diminished oxygen tensions for periods longer than 2 weeks,
that persons body begins to adapt to the new conditiona
process known as acclimatization. Previous research has dem-
onstrated that humans can adapt to altitudes as high as 4,500 m
(14,770 ft) and yet be able to perform relatively strenuous
physical tasks at such altitudes [21]. The highest human habi-
tations exist at 5,300 m (17,500 ft) above sea level, demon-
strating the strength of this adaptation process.
456
Adaptations generally assume two general forms: those
that enhance metabolic use of oxygen at the end site, such as
changes in the cytochrome system that improve the efficiency
of mitochondrial utilization of oxygen, and those that increase
oxygen-carrying capacity, including increased cardiac output,
hyperventilation, increased pulmonary circulation, changes
in cellular membranes that enhance oxygen diffusion across
them, increases in red cell mass or the oxygen-binding affin-
ity of hemoglobin, and capillary angiogenesis (particularly in tis-
sues that are vulnerable to hypoxia). Some of these responses
are apparent immediately,
. such as increased. heart rate, oxy-
gen consumption (Ve), and cardiac output (Q), whereas other
responses can take weeks to become manifest.
Lambertsen further describes the factors involved in the
complex adaptation to chronic hypoxia as (1) a sustained
increase in respiratory drive and alveolar ventilation; (2) an
adjustment of blood and central nervous system acid-base
relationships; (3) an increase in the rates of hemoglobin and
erythrocyte formation, which increase arterial oxygen-carrying
capacity; and (4) an increase in cardiac output [22]. Details of
these processes are given below.
At the onset of hypoxia, acclimatization begins as a sus-
tained increase in alveolar ventilation resulting from stimu-
lation of the hypoxic chemoreflex. The increase in minute
ventilation lowers PACO2 in the process of raising the PAO2 and
subsequently the PaO2. The effectiveness of the reflex can be
shown with the alveolar gas equation. The sustained increase
in ventilation, with its resultant drop in CO2 and hydrogen
ion levels in the arterial blood and tissues, leads to a respira-
tory alkalosis. In response, the renal excretion of bicarbonate
increases so as to restore normal acid-base balance. As a result
of the new, sustained decrease in bicarbonate buffering capac-
ity, pH values eventually return to normal over the course of
4 to 7 days. The carbonic anhydrase inhibitor acetazolamide,
used as a pharmacologic adjunct to altitude acclimatization,
facilitates this process by increasing bicarbonate loss. The
central chemoreceptors, driven by the arterial tension of CO2,
eventually reset themselves to a lower PaCO2, providing a way
of measuring the extent of acclimatization [23].
Simultaneous with these changes, the arterial oxygen-car-
rying capacity increases as a result of both the increase in
hemoglobin levels and the leftward shift in the oxyhemoglo-
bin dissociation curve brought about by the respiratory alka-
losis. Increases in hemoglobin and red cell mass result from
hypoxias rapid stimulation (within 2 h) of erythropoietin pro-
duction [24]. Hypoxia also stimulates an increase in 2,3-DPG
levels, which decreases hemoglobins affinity for oxygen
(a shift of the oxyhemoglobin curve to the right), thus facilitating
release of oxygen at the tissues and offsetting the leftward
shift caused by the alkalosis.
In addition to cardiovascular adaptation to chronic hypoxia,
alterations can also occur in fluid balance and regulation.
The ongoing loss of bicarbonate is accompanied by a general
diuresis during initial adaptation. Upon exposure to altitude,
peripheral vasoconstriction caused by hypocapnea appears,
K. Bacal et al.
thus increasing central blood volume and leading the barore-
ceptors to suppress the release of antidiuretic hormone. As a
result, plasma volume diminishes and osmolality rises, effects
that contribute to the hemoconcentration characteristic of
chronic hypoxic states.
The time needed for adaptation is believed to be a function
of the exposure altitude or level of hypoxic challenge [25].
Different body systems adapt at various rates, although some
changes (such as increased resting ventilation) can be seen
immediately whereas others (such as increased serum norepi-
nephrine levels) occur within the first few days [25].
Among the changes that take place over a longer time are
those mediated by growth factors and other chemical mes-
sengers [24]. Vascular oxygen sensors activate expression of
vascular endothelial growth factor 1, which counters hypoxia-
induced ischemia by promoting angiogenesis in the heart and
brain, thereby improving perfusion in these organs. In the
liver and the kidneys, hypoxic stress causes expression of
erythropoietin, which increases red blood cell mass [26], and
hemoglobin and hematocrit levels, thus enhancing the bloods
oxygen-carrying capacity. Bebout and others demonstrated an
11.3% increase in hemoglobin levels after a 2-week hypoxic
normobaric exposure with PIO2 of 91 mmHg [27].
Hypoxia also induces enlargement of the heart, particularly
the right ventricle; protein and nucleic acid synthesis increase
in several organs (notably the heart and brain) and decrease
in others (e.g., the reproductive organs) [2]. Other conditions
associated with chronic hypoxia that are more maladaptive
and seen at altitudes of 3,500 m (11,500 ft) and above include
weight loss, poor sleep patterns with altered sleep stages,
weakness, chronic headaches, malabsorption, diminished renal
function, microcirculatory sludging due to polycythemia, and
right heart strain due to pulmonary hypertension [28].
Implications of Hypoxic Acclimatization
for Space Operations
Selecting an operational environment for a space platform,
whether an orbiting vessel, a surface habitat, or a space suit,
requires balancing several operational factors. With these fac-
tors in mind and with the specific intent of preventing decom-
pression sickness, some groups have proposed using a hypoxic
environment in Martian habitats. For example, for the minimal
Martian atmosphere (ambient pressure of 5 mmHg [0.6 kPa]
and gaseous components of CO2 [95.7%], nitrogen [2.7%],
and argon [1.6%]), Conkin suggested a 414-mmHg (8.0-psia)
habitat atmosphere with an operational PAO2 of 77 mmHg [29].
The overall goal was to reduce the risk of decompression sick-
ness associated with surface EVAs by minimizing the pressure
differential between the habitat and the EVA suit.
In addition to the potential use of nominally hypoxic atmo-
spheres, contingency situations such as the loss of consum-
able gases or diluted environments resulting from fire or toxic
gas release could arise that would force the prolonged use of
22. Hypoxia, Hypercarbia, and Atmospheric Control
Table 22.6. Twenty-four-hour minimum oxygen limits for the Inter-
national Space Station.
Ambient pressure Partial pressure of oxygen Oxygen concentration
760 mmHg (14.7 psia) 108 mmHg (2.09 psia) 14.2%
527 mmHg (10.2 psia) 111 mmHg (2.14 psia) 20.1%
490 mmHg (9.5 psia) 111 mmHg (2.14 psia) 22.5%
400 mmHg (7.7 psia) 114 mmHg (2.19 psia) 28.4%
hypoxic breathing mixtures. Because of the global nature of
the long- and short-term adaptations to chronic hypoxia, few,
if any, of the bodys organ systems are unaffected. The effect
that such changes could have on the pursuit of aerospace oper-
ations depends on the operational scenario. ISS flight rules
strictly limit the conditions under which crewmembers can
be exposed to a hypoxic environment in a habitation module
during a contingency situation. ISS crewmembers cannot be
exposed to the environments shown in Table 22.6 for more
than 24 h. If these minimum pressure and concentration levels
cannot be maintained, appropriate action (from donning por-
table breathing apparatuses up to and including evacuation of
the station) must be taken.
An operational environment that intentionally exposes the
crew to chronic hypoxic conditions may be useful but must be
designed carefully. The potential operational benefits (lower
ambient pressure, diminished fire risk) must be weighed against
the resultant physiologic changes and the as-yet unstudied rela-
tionships between hypoxic acclimatization and adaptation to
microgravity. Many questions still require answers, including
how the composition of the blood would change in light of the
increase in hemoglobin from hypoxia and the decreased red
cell mass characteristic of microgravity adaptation and how
the right heart would respond to the increase in pulmonary
pressures. Finally, basic assumptions regarding long-duration
space flight often ignore the effect that the inevitable minor
illnesses and the possible major acute medical events that
could have on such missions.
Hyperoxia
Like hypoxia, hyperoxia does not depend on the concentra-
tion of oxygen to which the body is exposed, but rather its
partial pressure. This is why at hypobaric pressures, a pure
oxygen atmosphere will not cause oxygen toxicity but at a
suitably hyperbaric pressure, even a concentration of oxygen
well below the 21% normal for sea level will lead to oxy-
gen toxicity syndromes. Breathing a gas mix with an FIO2
greater than 0.4 at sea level for an extended period can result
in toxic side effects in less than a day. Hyperoxia should thus
be thought of as elevated oxygen tensions, i.e., when the ppO2
is higher than 160 mmHg (3.1 psi) (the ppO2 at sea level) and
corresponds to a PAO2 level above 100 mmHg. Other groups
have defined hyperoxia in more operational terms, noting con-
cerns for pulmonary oxygen toxicity at oxygen pressures from
457
0.5 to 2.5 ATM and central nervous system toxicity at oxygen
pressures above 2.5 ATM [30]. Malkin assigned ppO2 ranges
on the basis of target tissue effects: central nervous system
effects at ppO2 1,500 to 2,000 mmHg; pulmonary effects at
400 to 1,500 mmHg; and effects on the respiratory, blood, and
lymphatic systems at 280 to 400 mmHg [2].
Oxygen toxicity has also been categorized in broader terms
as a pulmonary syndrome seen after long-term, moderate
exposures (the Lorraine Smith effect) and a central nervous
system syndrome associated with short-term, high-level expo-
sures (the Paul Bert effect). The latter syndrome results from
hyperbaric exposures, which are infrequent in normal space
operations. The pulmonary syndrome, by contrast, can be
seen with nominal therapeutic and operational oxygen levels
that are simply maintained beyond appropriate durations.
Cells generally require an intracellular oxygen tension of
only 3 to 5 mmHg to convert adenosine diphosphate (ADP)
to adenosine triphosphate (ATP), which the cells then use as
the basic substrate for creating cellular energy. Local tissue
oxygen levels are the result of numerous factors, including
arterial oxygen tension, local arteriolar and capillary flow,
metabolic requirements of the tissue, and the diffusion distance
from the capillary. Exposing the cells to additional oxygen
beyond what is required for cellular respiration can lead to
the formation of reactive oxygen molecules such as free radi-
cals (superoxide, hydroxyl radicals) and activated molecular
oxygen in the form of hydrogen peroxide or singlet oxygen
molecules. These radicals can then alter cell membranes and
inhibit the activity of intracellular enzymes, type I alveolar
cells, neurotransmitters and the pyridine nucleotide system,
leading to destruction of type I alveolar cells and proliferation
of type II cells [31].
In aerospace operations, hyperoxia could be encountered
through the use of different gas mixtures during the various
phases of a space mission. The nominal atmospheres of the
Space Shuttle, the Soyuz, and the ISS are dual-gas oxygen-
nitrogen (21% oxygen and the balance nitrogen). However,
numerous contingencies can lead to higher oxygen concentra-
tions. In environmental contingencies such as fire, atmospheric
contamination, or loss of cabin pressure, the crewmembers
are to don portable breathing apparatuses, which supply
100% oxygen. An illness or injury might require an afflicted
crewmember to breathe supplemental oxygen for an extended
period, and that supplemental oxygen will be 100% oxygen
unless an atmospheric entrainment or gas-blending system is
available.
Before routine EVAs, crewmembers breathe pure oxygen
at cabin pressure to eliminate nitrogen from the tissues and
thereby prevent decompression sickness. During the EVAs,
crews continue to breathe 100% oxygen in the low-pressure,
single-gas EMU (space suit) environment. In the event of
decompression sickness, modest hyperbaric treatment pres-
sures can be provided on orbit by overpressurizing the EMU
to levels above its normal 222 mmHg (4.3 psig); such suit
pressures would be in addition to the cabins ambient
458
pressure and would provide a total pressure on the crewmem-
ber of ~1,140 mmHg (22 psia) of 100% oxygen.
With time and increased partial pressure, no tissues are
immune to the toxic effects of oxygen. As described below, the
physiologic ramifications of oxygen toxicity can be classified
according to whether the exposures take place at hypobaric,
normobaric, or hyperbaric pressures relative to the sea-level
equivalent.
Hypobaric Hyperoxia
At reduced barometric pressures, healthy humans can breathe
100% oxygen, corresponding to a PAO2 of 171 mmHg, for as
long as 4 weeks continuously without incurring ill effects [32].
Subjects in these early U.S. Air Force-NASA experiments did
not develop atelectasis, underscoring the importance of partial
pressure over oxygen concentration. These findings suggested
that the pure oxygen atmospheres planned for U.S. spacecraft
through Apollo would not be harmful to the crew. A project
investigating high-pressure EVA suits also demonstrated that
a pure oxygen environment at 429 mmHg (8.3 psia) for 8 h per
day caused no physiologic decrements [30].
Normobaric Hyperoxia
Although hypobaric hyperoxia can be relatively benign,
breathing high concentrations of oxygen at sea-level pressure
results in an initial decrease in ventilation and heart rate within
a few minutes. As the hemoglobin becomes saturated with
oxygen, the bloods ability to carry CO2 is decreased (the Hal-
dane effect). As CO2 is retained, hydrogen ion levels increase,
leading to an increase in ventilation that depends directly on
the PIO2 [33]. The increased oxygen tension produces cerebral
vasoconstriction and dilation of the pulmonary vasculature.
The eye is also affected by oxygen exposures lasting longer
than 24 h, as evidenced by depression on electroretinography.
In normobaric hyperoxia, the available oxygen has
increased but the metabolic requirements for oxygen have not,
and as a result pathologic oxygen species are formed. Cells
have a finite ability to mitigate the toxic effects of oxygen
through the use of free-radical scavengers and other protec-
tive mechanisms; prolonged (>12 h) exposure to 100% oxygen
at sea level results in numerous deleterious effects in most
individuals. The first reported symptom is often irritation of
the trachea and bronchi, resulting in a dry cough and pain on
deep inhalation [34]. Caldwell and colleagues documented
progressive decreases in pulmonary function, vital capacity,
alveolar-arterial differences, and diffusion capacity over a 6-day
exposure [35]. By comparing studies of humans to studies of
animals that included necropsies, Caldwell concluded that the
observed decreases in vital capacity and diffusion capacity
were probably caused by alveolar edema.
Operationally, a hyperoxic exposure would likely arise from
the use of supplemental oxygen because of atmospheric con-
tamination or a medical contingency. Thus the flight surgeon,
K. Bacal et al.
in addition to remaining vigilant about the toxicity associated
with the operational uses of high oxygen pressures, should
also be diligent in directing the administration of oxygen in
clinical contingencies.
The aim of the NASA exposure limits for normobaric
oxygen breathing is to prevent pulmonary oxygen toxicity.
Six hours of breathing pure oxygen in a sea-level environment
is considered the minimum exposure needed to cause the
physiologic changes typical of oxygen toxicity. As a result,
crewmembers are not permitted to breathe 100% oxygen
via quick-don masks or in a launch-and-entry suit for more
than 6 h at pressures above 620 mmHg (12 psia), or for more
than 12 h at pressures between 526 and 620 mmHg (10.2 to
12 psia). The same rules are used for both the Space Shuttle
and the ISS, with the following exception: ISS rules also
limit the monthly exposure to enriched cabin atmospheres
to no more than 10 days per month when the ppO2 is 200 to
250 mmHg and no more than 1 day per month when the ppO2
is 250 to 300 mmHg.
On both the ISS and the Shuttle, the current medical ventilator
equipment, like field transport ventilators, can only deliver
100% oxygen to the patient. In subjects breathing 100% oxygen,
the alveolar gas is a mixture of oxygen, CO2, and water vapor
that readily diffuses into the surrounding tissue. This diffusion
facilitates atelectasis and, in combination with hyperoxia-
induced reduction in surfactant levels, promotes complete
alveolar collapse. Pulmonary oxygen toxicity may also be asso-
ciated with increased secretions. Any condition that requires
mechanical ventilation (which presumably will take place at
a nominal cabin pressure [760 mmHg or 14.7 psia]) for more
than 12 h can be expected to incur some degree of pulmonary
toxicity. It will thus be necessary to aggressively maintain
pulmonary toilet and prevent the build-up of secretions in the
airway. Retained secretions will block the flow of gas into
and out of the alveoli, resulting in absorption atelectasis. The
accumulation of secretions could be substantial depending on
the underlying pathology. Inhalation of toxic gas and thermal
pulmonary injuries are associated with significant production
of secretions and require regular suctioning just to maintain
the patency of the airway [36,37].
Although potentially lethal, the toxic effects of normobaric
hyperoxia resolve quickly when normoxic gas is breathed,
unless the exposure is long enough to lead to irreversible
pathologic changes such as the induction of fibrosis.
Hyperbaric Hyperoxia
Operational exposure to hyperbaric oxygen breathing during
space flight missions is currently limited to short-term prep-
arations for EVA before airlock depressurization, when the
additive pressure of suit and cabin is 982 mmHg (19 psi) and
to contingency treatment of decompression sickness, when the
space suit is overpressurized to 1,140 mmHg (22 psi). Given
the potential risk of decompression sickness, some clinicians
argue that the ISS and any spacecraft to be flown beyond low
22. Hypoxia, Hypercarbia, and Atmospheric Control
Earth orbit should have definitive hyperbaric capability on
board. The original design for Space Station Freedom included
a chamber capable of pressures up to 6 ATA; however, these
plans were not carried over to the ISS, in part because no
decompression sickness events associated with EVA had ever
been reported. However, aside from normal EVA-related
pressure excursions, mishaps are also possible.
As noted elsewhere in this chapter, oxygen pressure during
hyperbaric operations is typically quantified in terms of ATAs;
for example, an occupant of a hyperbaric chamber pressurized
to 14.7 psig (29.4 psia) who is breathing 100% oxygen is actu-
ally breathing 2 ATA oxygen, and individuals at sea level are
breathing 0.21 ATA oxygen. As ppO2 is increased above that
at sea level conditions, the rate of onset and the severity of
pulmonary symptoms increase. Visual effects become more
pronounced, with significant decreases in electroretinogram
activity and visual fields apparent after as few as 8 h at 2 ATA
oxygen [30]. Operationally, the most significant toxicity occurs
within the central nervous system and includes symptoms
ranging from seizures to nausea, tinnitus, dizziness, lightheaded-
ness, retching, paresthesias, and poor concentration.
Treatment includes removal from the hyperbaric oxygen
exposure and palliative care. Acute central nervous system
effects of oxygen toxicity are generally reversible once the
subject is returned to a normoxic environment.
Constituent Gases: Carbon Dioxide
Production and Control
On Earth, CO2 accounts for 0.03% of the air, at a partial
pressure of about 0.228 mmHg at sea level, but even tenfold
increases in environmental CO2 levels are not associated with
physiologic decrements. However, if CO2 levels rise well
beyond this, changes in acid-base balance, respiration, circu-
lation, and central nervous system activity are noted [2]. In
an attempt to balance operational realities with crew safety,
NASA has identified 15 mmHg (i.e., 65 times the normal
terrestrial levels) as the upper limit for off-nominal ppCO2
level and 20 mmHg as the emergency level.
The average human produces 0.4 L of CO2 per min
(600 L/day), although this rate varies widely with metabolic
production and can range from 0.2 L/min at rest to 5 L/min
during heavy physical activity. Most of the CO2 produced is
excreted from the body in gaseous form through the lungs dur-
ing respiration (1 kg/day), and a smaller amount is excreted
as bicarbonate ions in the urine [5]. CO2 levels, as a product
of respiration, will naturally increase in a closed system. The
detrimental physiologic effects first became noticeable when
levels exceed about 12 mmHg.
Accordingly, the cabin environment of a spacecraft must
be designed not only to support the demands for metabolic
oxygen but also to remove the CO2 that is the product of
respiration. In a closed environment, CO2 can be removed by
459
use of a continuous purge (in which small amounts of gas are
continually vented overboard) or a closed-loop removal system.
For routine space operations, resource limitations make it
impossible for crews to rely on atmospheric purging, so CO2
must be actively removed from the spacecraft environment.
Scrubbing of the spacecraft air is usually accomplished by
chemical means as the air is recirculated through the cabin.
Space presents a further challenge to a CO2 removal system
because of the lack of convection associated with microgravity.
CO2 is heavier than air; in a gravitational field it will fall away
from the face as it is exhaled, and gravitationally driven
convective forces, local airflows and winds serve to further
disperse it. In microgravity, a ventilation system is required to
carry the CO2 away from the mouth and nose and to move air
continuously through the cabin or space suit. As a result, the
efficiency of CO2 scrubbers in a microgravity environment is
highly dependent upon the ventilation system.
Forced ventilation in a spacecraft is essential to ensure good
mixing of the atmosphere components. Without well-blended
air, CO2, water, heat, and trace contaminants cannot be efficiently
removed. Circulation minimizes temperature variation, ensures a
homogeneous gaseous composition, and facilitates early smoke
detection [38]. Ventilation, as is true of other atmospheric
parameters, is also closely tied to atmospheric pressurization.
Less dense atmospheres require increased ventilation to achieve
the same cooling capacity, a phenomenon related to mass
flow of a surrounding gas. Ventilation systems for habitable
modules generally operate with a flow velocity between 0.08
and 0.2 m/s to control the CO2 level [39].
If ventilation is poor, as it is behind a rack or within a
closed space, atmospheric pockets of uneven gas distribution
can develop. CO2 bubbles, for example, may form around
the heads of stationary space crewmembers in such areas. If
they are intent upon their task, crewmembers may not realize
the problem until physiologic symptoms appear. In addition to
unventilated areas, cramped or highly populated spaces also
pose problems for the CO2 removal system. For example, if
several crewmembers were to gather in a single module, the
ventilation and CO2 removal systems would be more heav-
ily burdened. As a result, systems must be flexible enough to
accommodate changing crew operations.
Although CO2, unlike CO, is not odorless, its characteristic
scent and taste is undetectable to most people until it is present
at fairly high concentrations. Most people, for example, will
not choose to leave an area until the ppCO2 is above 23 mmHg,
by which time work capacity has already decreased and ven-
tilation increased [2]. For this reason, regulations regarding
elevated CO2 rely more heavily on measured levels than on
crew symptoms.
The maximum length of time permitted in a station module
that has lost ventilation either between or within modules
depends on the number of crewmembers present, the volume
of the affected module, and the assumption that the crew-
members will be performing no more than moderate work
in the unventilated area. According to ISS flight rules, the
460
ppCO2 is allowed to reach an average of 6 mmHg in an ISS
module during the ventilation repair process. At ppCO2 levels of
10 to 15 mmHg, actions must be taken to reduce the CO2 level,
e.g., increasing the atmospheric scrubbing. At levels above
20 mmHg, these tasks assume the highest priority because of
the unacceptably high risk of adverse effects (e.g., headaches,
tachypnea, or dyspnea). Flight rules also require oxygen
masks be donned as protection against hypercarbia should
crewmembers exhibit symptoms or if repairs require more
time in the module than is permitted by the flight rule.
Assuming that the ventilation is adequate, however, CO2
can be removed from the cabin air by any of several methods
including absorption (a chemical reaction that uses a sorbent,
such as lithium hydroxide [LiOH]), adsorption (physical
attraction to a sorbent, such as zeolite), membrane separation,
or biological consumption [1] from plant mass. Submarine
life support systems, which are faced with this same problem,
have made use of organic amines (e.g., monoethanol amine) to
combine with CO2. Hydrogen-depolarized devices that use an
electrochemical reaction to remove CO2 from the atmosphere
can also be used, as can molecular sieves that make use of
synthetic silicates to collect the gas.
Earths ecology relies heavily on biological consumption, as
plant life draws CO2 from the atmosphere and exchanges it for
oxygen. In future long-duration missions and extraterrestrial
colonies, plants may also have a critical role in CO2 removal. Up
to this point, however, long-duration platforms such as Skylab,
Mir, and the ISS have successfully used active, regenerable
sorbent beds and short-duration spacecraft with missions on the
order of several days have tended to use absorption reactions
with LiOH. The latter method relies on the exothermic reaction
of LiOH with CO2 to create Li2CO3 and water:
2LiOH + CO2 Li2CO3 + H2O (5)
The theoretical CO2 binding capacity of LiOH is 0.92 kg CO2
per kg of LiOH, or, stated another way, 2 kg of LiOH can remove
one persons daily CO2 from the cabin environment [39].
LiOH is an attractive choice for space flight because of
its high absorption capacity and the small amount of heat
produced in the reaction. Disadvantages to the use of LiOH
include the irreversibility of the chemical reaction, which
requires periodic replacement of the canisters and thus
represents a potential limit on the duration of a mission, and
its considerable toxicity. For these reasons, plans for longer-
term missions rely on other means to remove CO2 from the
spacecraft environments.
To avoid the need for resupplying LiOH, Skylab used a
molecular sieve technology for CO2 removal. Its regenerable
zeolite matrix had a crystalline structure with a very large surface
area. The U.S. orbital segment of the ISS also uses a zeolite
molecular sieve. ISS space suits use silver oxide (also known as
metal oxide or metox) in the form of regenerable canisters to
remove CO2, while the Shuttle space suits use LiOH.
Future spacecraft environmental control systems may also
regenerate oxygen from recaptured CO2first through reduction
K. Bacal et al.
of the CO2 and then through electrolysis of the resultant water
into hydrogen and oxygen. The Sabatier process, for example,
involves the following reactions:
CO2 + H2 CO + H2O (6)
CO + 3H2 CH4 + H2O (7)
CO2 + H2O CO + O2 + H2 (8)
Hypercarbia
Unlike hypoxia, the onset of which is either gradual or
immediate, hypercarbia is primarily insidious because of the
steady metabolic production of CO2. (An exception would
involve discharge of a CO2 fire extinguisher, but those circum-
stances would be obvious to all.) As a result, in microgravity,
hypercarbia should be anticipated in any circumstance where
ventilation is compromised, such as when active ventilation
systems fail or are blocked, e.g., in enclosed spaces.
During their mission to recover the Salyut 7 space station
in 1985, cosmonauts Dzhanibekov and Savinikh were forced
to work in a cold, unpowered platform with no active
ventilation. They reported having headaches, lethargy, and
sluggishness associated with the CO2 from their exhalations
and that providing active ventilation as soon as possible miti-
gated this effect. Crew time in an unpowered module whether
in the ISS or some other spacecraft is initially limited by lack
of ventilation; moving air with portable fans extends the time
crewmembers can remain in such modules for repair and
recovery activities by dispersing exhaled CO2 and circulating
whatever oxygen is available.
Enclosed spaces and local decreases in ventilation typically
lead to mild symptoms of hypercarbia during space flight.
Often crewmembers must work behind panels or in tight
quarters where multiple stowed items compromise airflow
(Figure 22.4). Crewmembers sleeping in small, enclosed sta-
tions on the Space Shuttle have occasionally been awakened
from sleep by headaches that can be mitigated by opening the
compartment door to allow ventilation.
As is true for hypoxia, hypercarbia is best prevented rather
than treated. If the potential for hypercarbia is recognized,
symptoms during work in confined spaces can be mitigated by
taking frequent breaks in an actively ventilated area, by using
small portable fans, or by routing flexible ventilation ducting
into the space. Measures as simple as periodically fanning the
area with procedure books have also been used.
The relationship between the decrease in O2 and the
buildup of CO2 for an individual at rest in an enclosed area
is shown as a function of volume in Figure 22.5. In a volume
of 100 L (3.5 ft3), CO2 levels can exceed the symptomatic
threshold in less than 20 min. In the absence of gravitational
convection forces and forced ventilation, such volume can
be a virtual enclosed space; physical activity, of course,
increases CO2 production and accelerates the development
of symptoms.
22. Hypoxia, Hypercarbia, and Atmospheric Control
Figure 22.4. Working in an enclosed, poorly ventilated area in
microgravity can lead to symptomatic hypercarbia. (Photo courtesy
of NASA)
Figure 22.5. Oxygen decrease and carbon dioxide buildup associated
with an individual breathing in an enclosed area. In microgravity, a
virtual enclosed space of low equivalent volume may exist around
a stationary crewmember without active ventilation.
Source: Rahn H and Fenn WO [40] and Billings [5]
For these reasons, space flight crewmembers are taught to
recognize symptoms of CO2 exposure. In a controlled training exercise,
crewmembers are exposed by means of a rebreathing apparatus
to CO2 beginning at ambient sea-level partial pressures and
increasing gradually to a partial pressure of (~60 mmHg. Exposure
is limited to several minutes, but participants are to take note
of physiologic symptoms corresponding to specific CO2 lev-
els. A portable CO2 detector developed to assess CO2 levels in
local environments aboard ISS provides another level of safety in
potentially unventilated areas and can help distinguish symptoms
of hypercarbia from those of exposure to other toxins that could
accumulate locally, such as pyrolysis products from an electrical
fire, which could also be associated with the malfunction precipi-
tating loss of ventilation.
461
Exposure to atmospheres enriched in CO2 has predictable
physiologic effects. The effects of CO2, like any drug, depend
on the dose and duration of exposure and include respiratory
stimulation and vasodilation, mediated through stimulation of
the respiratory chemoreceptors in the carotid bodies and
central receptors.
In the blood, carbonic anhydrase catalyzes the hydration of
CO2 and the dehydration of bicarbonate as follows:
CO2 + H2O HCO3 + H+ (9)
In this way, increased CO2 levels lead to the formation of
additional hydrogen ions, thereby decreasing pH.
Thus when hypercarbic gas mixtures are inhaled, the
increased level of CO2 in the tissues and blood generates
an acidosis, which prompts substantial increases in ventilation.
Hypercarbia also influences hyperoxic effects. During
hyperbaric oxygen exposures, hypercarbia has been asso-
ciated with decreases in the seizure threshold thought to
result from CO2-induced vasodilation and increased blood
flow to the brain [41].
Signs and Symptoms of Hypercarbia
Initial symptoms of hypercarbia vary somewhat among
individuals, but generally include air hunger, shortness of
breath, tachycardia, increased blood pressure, sweating,
headache, lethargy, anxiety, dizziness, and nausea. Prolonged
exposure to higher CO2 levels results in difficulty breathing,
muscle spasms, tremors, visual effects, convulsions, loss of
consciousness, respiratory failure, and death. These signs and
symptoms, and their effects on physical and mental performance
are summarized in Table 22.7.
Chronic Hypercapnia
Although CO2 levels in spacecraft are significantly (20 to 50
times) higher than the levels on Earth, no evidence exists to
suggest that such high CO2 levels lead to any short- or long-
term deficits. Studies in healthy subjects have demonstrated
no residual effects from breathing low to moderate CO2 levels
(<11 mmHg) for extended periods (30 to 40 days), although
the consequences of exposure to higher levels, on either a
sustained or an episodic basis, remain unclear [2]. Prolonged
exposure to CO2 results in several physiological adaptations,
including a compensatory metabolic alkalosis arising from the
metabolic buffering with hydrogen carbonate (HCO3) and a
respiratory acidosis that leads in turn to various electrolyte
and metabolic alterations. Changes in calcium levels in blood
and bone in particular can raise the risk of forming renal
calculi [2], a particular concern for space operations.
Three different syndromes, corresponding to different levels
of hypercapnia, have been described. A ppCO2 between 4 to
6 mmHg produces few, if any, adaptational changes. Beginning at
about 11 mmHg CO2, subtle changes in acid-base equilibrium,
462 K. Bacal et al.

Table 22.7. Symptoms and performance effects of increased atmospheric CO2.

PCO2 (mmHg) Exposure Duration Symptoms Exercise performance Mental performance
7.5 34 months No unpleasant sensations, Possible (all levels) Possible
no functional impairments
<15 Up to 30 days No perceived symptoms; Light and moderate; Possible
some increase in respiratory heavy is difficult
minute volume; slight acidosis
2530 Up to 7 days Discomfort; dyspnea, especially on Light possible; Possible, if well learned
exertion; respiratory minute volume moderate limited;
elevated by 22.5 at rest; exposure up heavy extremely difficult
to 3 days leads to easily reversible changes
in metabolism due to acidosis
3540 up to 15 h Dyspnea, even at rest, heaviness Light limited; moderate Limited, even for
of head, vertigo; respiratory minute volume extremely difficult familiar tasks
elevated by a factor of 34; parameters if
cardiovascular function relatively stable;
respiratory acidosis; impaired cerebral
functioning; sleep disorders
< 50 up to 34 h Dyspnea, headache, vertigo, visual Light limited; moderate Difficult
impairments, sleep disorders; respiratory and heavy impossible
minute volume increased by a factor
of 45, respiratory acidosis; marked
changes in cardiovascular function;
tachycardia, elevated blood pressure;
disruption of central nervous
system function
< 60 Up to 1 h Drastic worsening of symptoms All types impossible Impossible
> 60, < 75 None acceptable Drastic worsening of symptoms Precluded Precluded

Source: Malkin [2]. Used with permission.

ventilation, and electrolyte balance are seen that although
minor may become deleterious over times. Above 22 mmHg
ppCO2, obvious abnormalities are noted, including decreased
performance and subjective complaints. These findings have
lead several groups to suggest that the ppCO2 in enclosed ves-
selswhether submarines, biospheres, or space stationsbe
maintained at levels below 4 mmHg and permitted to rise only
for transient episodes [2]. NASA and its international part-
ners have chosen to accept slightly higher levels than this for
nominal operations, but flight rules described below ensure
that potentially harmful levels are avoided.
Operational Limits
The CO2 levels that are considered normal in space opera-
tions are surprisingly close to the threshold for toxic effects on
Earth. On the Space Shuttle, for example, the current upper limit
for normal CO2 levels is 7.6 mmHg (i.e., 33 times Earth-normal
levels). If the atmospheric revitalization system cannot maintain
the cabin ppCO2 below 15 mmHg, the shuttle crew must don
portable oxygen masks and the Space Shuttle must deorbit at the
next opportunity to arrive at a primary landing site.
The ISS, like the Space Shuttle, also sets 7.6 mmHg as a level
above which corrective actions must be taken. Above a ppCO2
of 20 mmHg, these actions take on high priority for a crew.
Specifically, the procedure for managing abnormally high CO2
levels calls for recovering ventilation, followed by increas-
ing atmospheric gas flow through the CO2 absorption bed.
If scrubbing is inadequate, procedures then require the use of
personal breathing apparatus and evacuation of the affected area.
Although early crewed U.S. missions made extensive use
of pure oxygen environments, single-gas environments are
currently limited to operations in EVA suits and launch and
landing suits. Rules regarding CO2 limits for EVA suits differ
somewhat from those of habitable modules because of the more
significant isolation and lower failure tolerance associated with
EVA and because the suit sensor system is less redundant than
the spacecraft CO2 transducers. In addition, telemetered values
of CO2 levels around the face may not be accurate owing to
sensor placement in the helmet. As a result, self-recognition
of hypercarbia symptoms takes on an even greater importance
for EVA operations. ppCO2, along with heart rate, electrocar-
diogram, and temperature, are monitored in the current U.S.
EVA suits. In the U.S. program, when ppCO2 levels reach 3 to
8 mmHg hypercarbic symptoms are present, the crewmember
must return to the airlock, connect to the umbilical, and purge
the suit with oxygen. When ppCO2 levels exceed 8 mmHg, the
EVA must be terminated, even in the absence of symptoms.
In the Russian Orlan space suit, however, operations
are permitted for ppCO2 levels up to 10 mmHg while the
22. Hypoxia, Hypercarbia, and Atmospheric Control
crewmember is at rest or is not displaying any symptoms of
hypercarbia. If that resting limit is exceeded, if symptoms are
present, or if the ppCO2 rises above 20 mmHg upon exertion,
the crewmember is to terminate the EVA and return to the
airlock. These differences in CO2 limits reflect techno-
logic variations between the Russian and U.S. space suits.
Although the goal in both programs is to prevent crewmem-
bers from being exposed to CO2 levels above 15 mmHg, the
sensors used in the two space suits are slightly different.
The placement and response time of the U.S. EMU sensor
are such that a measured value of 8 mmHg likely means
that the concentration in the helmet is closer to 15 mmHg.
The Russian Orlan sensor is configured differently, and
its measured value is closer to the actual helmet ppCO2,
thereby allowing 10 mmHg (0.2 psi), rather than 8 mmHg,
to be used as the threshold value.
Treatment of Hypercapnia
Therapy for hypercapnia is similar to that for environmental
exposures to other toxins, and starts with the removal of the
exposed individual to a safe environment. Exposure to hypoxia
is often associated with significant exposure to CO2, although
hypercarbic symptoms typically appear first because of the
exquisite sensitivity of the chemoreceptors.
After prolonged exposure to elevated CO2 levels, nausea and
vomiting often occur immediately after removal to a normoxic,
normocarbic region. This CO2 withdrawal syndrome is not
dangerous in itself and will resolve spontaneously with continued
exposure to a normal atmosphere. However, the occurrence
of this reaction within the close confines of an EVA suit could
pose significant problems, as emesis in an EVA helmet could
easily lead to aspiration or other complications.
Other Factors: Temperature, Humidity,
and Trace Contaminants
In addition to atmospheric pressure and gaseous composition,
other factors play a role in creating and maintaining an accept-
able artificial atmosphere. Temperature, humidity, and trace
contaminants can also create challenges for environmental
system designers.
Temperature
Spacecraft must be designed to protect their occupants not only
from the extreme temperatures outside the vehicle but also
from the buildup of heat within it. Avionics and other equip-
ment can produce high thermal loads, and task performance is
known to decrease with uncomfortable ambient temperatures.
Given the coldness of the surrounding space, it would not be
unreasonable to assume that astronauts are at greater risk of
exposure to cold than to heat; however, the reverse is generally
463
true, although the risk depends on the attitude of the spacecraft
with respect to the Sun. Notable exceptions have included
the return of the crippled Apollo 13 spacecraft, where cabin
temperatures fell to 9 to 13C (49 to 55F) because of low
electrical power levels, and the salvage of the Salyut 7 space
station, during which crewmembers conducted repair opera-
tions in subfreezing temperatures.
Spacecraft must have a way of rejecting the heat from
solar incident radiation and from onboard systems [6];
flight rules specifically address the issue of heat buildup.
Crew cabin temperature limits on the Space Shuttle are
specifically defined and must be kept below 24 to 27C
(75 to 80F) depending on the phase of flight. Tempera-
ture limits during entry and landing are 3C (5F) cooler
than other times because of uncomfortable increases in
orthostatic hypotension associated with thermal stresses
upon return to Earth. On the ISS, crewmembers must take
actions, such as fluid loading (to avoid dehydration) and
donning supplemental oxygen masks (to facilitate respira-
tory cooling) should the temperature and humidity through-
out the entire station rise beyond 32C (90F) and 90%,
respectively. As described below, life support designers
have used different methods to control cabin temperature
depending on spacecraft and mission parameters. In all
cases, however, temperature control relies heavily upon
circulation of cabin air, as does CO2 removal.
Humidity
Humidity or water vapor is another atmospheric component
of physiologic relevance. Humidity varies with tempera-
ture and the availability of free water. It can play a critical
role in heat balance and the personal comfort of crewmem-
bers. As temperature rises, humidity must fall to promote
evaporative cooling, whereas at lower temperatures, higher
humidity reduces evaporation and facilitates heat retention.
Generally, humidity is less noticeable in comfortable ambi-
ent temperatures, but when ambient temperature strays out-
side normal ranges, relative humidity can play an important
role in ensuring crew comfort. An example is the difference
between desert heat and jungle heat: at equivalent tempera-
tures, the humid, tropical heat will be more oppressive than
the dry desert air.
Humidity can be removed from cabin air either by use of
a desiccant material or through condensation of atmospheric
water vapor followed by the phase separation of moisture from
air. The latter method has been more widely used in spacecraft
because it permits the reclamation and further use of water.
As warm cabin air is processed, it is cooled below its dew
point on heat exchangers and the water is condensed from the
humid air. The water droplets thus created are then separated
from the air flow through either a wick condenser separator,
which uses capillary action and surface tension to transfer the
water, or a hydrophobic-hydrophilic separator, which deflects
and directs droplets through use of hydrophobic and hydrophilic
464
Figure 22.6. Atmospheric gas flow requirement and heat load for
humidity control.
Source: Rousseau J [42] and Jones [1].
surfaces. The reclaimed water is then sent to the water man-
agement equipment [1]. Desiccant materials are more widely
used in space suits, the short-term use of which makes recla-
mation unnecessary.
To maintain lower relative humidity levels requires rela-
tively higher airflow and cooling load (Figure 22.6), and
thus from an engineering perspective a relatively high cabin
humidity is preferable and a water vapor pressure of 10 to
14 mmHg (0.2 to 0.27 psi) is considered optimum. Higher (>
70%) humidity levels promote condensation and produce con-
ditions that favor the growth of microorganisms and adverse
physical effects such as corrosion. Low humidity (<25%)
leads to chapped lips, dry eyes, and increased incidence of
upper respiratory infections [8]. The comfort zone for humans
in terms of relative humidity and ambient temperature is
illustrated in Figure 22.7.
An example of the difficulties created by the failure to con-
trol humidity was reported on the Russian space station Mir
shortly after the cosmonauts began using the on-orbit shower.
Complaints of insufficient water were attributed at first to less
condensate being collected than predicted, but it was eventually
determined that the materials in the habitable volume were
K. Bacal et al.
Figure 22.7. Relationship between temperature and humidity ratio,
showing an optimal comfort box for sustaining human occupants.
RH, relative humidity.
Source: Wieland P [43].
themselves absorbing water (in the form of humidity) from the
atmosphere before the water reclamation system could do so.
These conditions led to a temporary water shortage, affected
temperature control (wet insulation cannot function properly),
and promoted bacterial growth in the wet materials. Some of
the microorganisms produced in turn created a green slime that
contaminated the environment, while other microorganisms
consumed the adhesive material used in the station construc-
tion, loosening materials and creating particulate debris [44].
This experience underscores the need not only to set temperature
and humidity limits but also to select materials that will function
properly and be compatible with other systems.
Trace Contaminants
On Earth, gravity and weather remove most of the trace
contaminants from the air, which are generally in the form
of particles and gases. Because neither gravity nor weather
exists on orbiting spacecraft, the environmental system is
responsible for removing both particulate matter (such as
dust) and gases (including CO, sulfur dioxide, ethanol, and
butanol) [1] before they can become a source of irritation or
toxicity. Sources of such contaminants in a spacecraft include
their off-gassing from habitat materials, leaks or spills, food
preparation, combustion products, crew metabolism (feces,
urine, sweat), scientific experiments, and cleaning supplies.
By the early 1970s, results from studies of closed-loop
environments such as submarines and ground-based test chambers
showed that trace contaminants could build up to significant
levels over time. Before the Skylab Program, spacecraft had
measured only CO levels and used LiOH canisters, filters,
and absorbents in a somewhat blind approach to removing any
and all possible contaminants [45]. No capability for on-orbit
monitoring and analysis of trace contaminants aside from CO
was included on Mercury, Gemini, Apollo, or the post-Skylab era
Space Shuttle, in part because of the relatively short duration
of those flights. Samples of the spacecraft atmospheres were
obtained and archived for study after landing, but no on-orbit
22. Hypoxia, Hypercarbia, and Atmospheric Control
analyses were performed. For contingency events, chemical
colorimetric tests have been available on the Space Shuttle
for certain targeted substances; hydrazine, for example, can
be detected by a gold salt method involving a color change
on a coupon.
Skylab, which supported the first long-duration U.S. missions,
monitored a variety of contaminants through the use of vari-
ous sensors. Since the Skylab era, researchers have used gas
chromatography, mass spectrometry, ultraviolet and infrared
spectroscopy, and sensors for individual contaminants (such as
CO or hydrogen cyanide) to examine atmospheric samples for
the presence of trace contaminants. Such substances are usually
removed through the use of various physical barriers.
Although careful selection of component material and other
preventive measures by environmental control system design-
ers can minimize off-gassing hazards, some contaminants are
unavoidable, and the biological implications of such expo-
sures remain unclear. Although classical consideration of
trace contaminants have typically studied the accumulation of a
single substance to high levels, attention has recently turned to
the potential interactive effects of multiple substances at lower
concentrations [4].
Some trace contamination can be expected as part of the
normal life of a spacecraft, but off-nominal situations can
greatly increase these levels. For example, when the Skylab
micrometeoroid shield was lost during launch of the vehi-
cle, the interior wall of the orbital workshop overheated,
causing concern that its polyurethane foam insulation
would off-gas unacceptable levels of toluene diisocyanate
[46]. Activated charcoal filters were used to remove the
contaminants from the cabin before the first crew entered,
and subsequent investigation found no danger to crew
health and safety.
The most severe spacecraft event that generates toxic prod-
ucts is fire, as occurred on both the Salyut 1 and Mir space
stations [7]. During and after a fire, the number and amounts
of trace contaminants from pyrolysis rise exponentially. In
addition to the smoke itself, combustion products such as
hydrogen cyanide, hydrogen sulfide, and CO are likely to be
generated, as well as particulate matter. Not all toxins after a
fire will be airborne; surfaces will also be contaminated and
will require careful cleanup.
The fire suppression system can also contaminate the envi-
ronment by introducing Halon or CO2 into the atmosphere.
Although the Halon 1301 agent used as a fire suppressant on
the Space Shuttle is highly effective and not overtly toxic,
when combusted it produces cardiotoxic byproducts that
are difficult to scrub from the atmosphere. CO2 requires a
higher concentration than Halon to suppress a fire, but it is
also more readily removed from the atmosphere. Russian fire-
suppressant systems use water in a foam or spray form that
complicates the clean-up process after the fire but essentially
eliminates any additive toxic constituents. A further option,
depending on the severity of the fire and the damage it caused,
is to seal off and vent the affected part of the spacecraft.
465
Future missions may include time on other planetary bod-
ies and thus will have to consider contamination of the atmo-
sphere by unknown substances such as Martian soil or lunar
dust. Toxicity hazards will remain high for the foreseeable
future and will continue to pose a challenge for life support
system designers and medical care providers alike.
Environment Control Systems
The three major acute environmental threats to humans
aboard a spacecraft or planetary habitat are loss of pressure
(as occurred in the Soyuz 11 mission), fire (as occurred on the
Apollo 1 ground test), and atmospheric toxicity from sudden
contamination (as occurred during landing of the Apollo cap-
sule after the joint Apollo-Soyuz mission). These threats can
occur singly or in combination and constitute the three major
atmospheric emergencies of space flight. All require not only
immediate, focused action by the crew but also a supplemental
breathing supply for the crew to protect them from diminished
oxygen levels or dangerous atmospheric contaminants where
they carry out the activities necessary to salvage the vehicle.
As a result, emergency oxygen ports and portable oxygen bot-
tles must be placed strategically throughout every space habi-
tat to ensure crew protection and enable corrective actions.
Simultaneously, scrubbing and other atmospheric purification
systems must be highly redundant and sufficiently robust as
to clean a contaminated environment. The provision of such
multiple, interactive, reliable, and complex systems forms
the foundation necessary for establishing and maintaining a
human presence in space.
In brief, the goals of a life support system (Table 22.8) are
to maintain acceptable cabin pressure and atmospheric
composition; to circulate the cabin air; to remove humidity,
CO2, and contaminants from the air; and to return cooled,
purified air to the cabin. CO2 can be processed or dumped
Table 22.8. Goals of a life support system.
Variable Goal
Adequate pressure Minimum of about 210 mmHg
(for a pure O2 atmosphere)
Adequate pO2 About 160 mmHg
Acceptable fire risk FiO2 < 0.3
Structural mass constraint Decreased P = Decreased Mass
Availability of replenishment gases Tanked, Generated, etc.
Atmospheric composition Single gas (O2) versus dual gas
(O2 + N2)
Acceptable relative humidity 2570%
Acceptable temperature 2224C (7275F)
Acceptable ventilation 0.080.2 m/s
Trace contaminant and odor Maintain levels below SMACs
removal system
CO2 removal system Maintain levels below 15 mmHg
Risk of decompression sickness cabinsuit P to DCS risk
Abbreviations: SMAC spacecraft maximum allowable concentration, DP pres-
sure differential, FiO2 inspired oxygen fraction.
466
overboard depending upon the scrubbing system used; atmo-
spheric water vapor can be recycled for drinking or technical
use. Sufficient supplies of the atmospheric gas or gases must
be available during the course of the mission to compensate
for depressurizations, both mission-related, such as use of an
airlock during EVAs, expected, such as nominal gas leakage,
or unintentional, such as a hull breach. Last, the vehicle itself
must be constructed with sufficient structural integrity to
contain the pressurized atmosphere within it.
These goals can be achieved in a variety of ways and
the methods selected will naturally differ based on mission
parameters, budget, weight constraints, acceptable levels of
risk, safety, and reliability. Physiologic factors often compete
with engineering or technical considerations. Atmospheric
pressures, for example, must be chosen to ensure that gases
are sufficiently dense to provide cooling to crewmembers
and electronics while maintaining an acceptably low medi-
cal risk in the transition to lower pressures during EVAs.
Previous spacecraft have used atmospheres pressurized
from 259 to 760 mmHg (5 to 14.7 psi), with ppO2 as high as
260 mmHg (5 psi).
The earliest space missions were brief, on the order of a few
days, and involved only one crewmember, thus necessitating
minimal reclamation systems. The long-duration missions
supported by the ISS, by contrast, are vastly more complex.
The number of people aboard the station fluctuates over time,
as the ISS crew is joined by astronauts and cosmonauts from
the Space Shuttle and Soyuz vehicles that dock for joint opera-
tions with combined crews and then leave again. ISS missions
last several months, and the stations mandateto perform
scientific researchoften necessitates maintaining an atmo-
sphere as close to Earth-normal as possible. For short-duration
missions, spacecraft designers may find it more economical to
carry only what the crew needs and to vent wastes as needed
rather than investing resources in developing and maintaining
a complex recycling system. The ISS does not have that luxury
and must rely on reclamation systems whenever possible.
To maintain a breathable atmosphere, a life support system
must provide pressure and oxygen, remove CO2, and control
trace contaminants. A more complex closed-loop environ-
ment also requires systems for recovering oxygen from CO2
(CO2 reduction) and for generating (not supplying) oxygen.
To maximize crew comfort, temperature and humidity must
be controlled and means provided to remove trace contaminants,
particulates, and odors.
Atmospheric composition can be controlled manually,
automatically, or by a combination of both. Some form of
on-demand method is usually available to counter leakage
with the periodic injection of gas. The amount of such gas
needed is calculated from measurements of cabin pressure and
(in a two-gas system) of ppO2. Similarly, if the total pressure
becomes too great on board, for example because of leakage
of stored gas into the cabin, a means must be available for
dumping or reducing pressure before structural integrity of
the spacecraft is compromised.
K. Bacal et al.
The gases needed to repressurize the spacecraft can be
stored in high-pressure tanks (as was done on all U.S. space-
craft from Mercury through the Space Shuttle), as liquids in
cryogenic storage (as on Gemini, Apollo, Shuttle, and ISS),
or in other more novel forms. Nitrogen, for example, can
be stored as hydrazine (N2H2), which also serves the more
customary role as spacecraft propellant [47]. For long-term
habitation, some gases (e.g., oxygen) may need to be regener-
ated to the extent possible rather than totally resupplied.
In a dual-gas storage system, care must be taken to adequately
diffuse and distribute the gas constituents to avoid pockets
of enriched nitrogen, which may create local asphyxiation
hazards, or of oxygen, which may be a fire hazard. Systems are
generally designed to circumvent such situations, but objects
may be inadvertently placed in the path of gas flow, thereby
thwarting the expected diffusion. In addition to the introduction
and diffusion of respirable gases, continued ventilation is vital
to maintaining atmospheric homogeneity.
Temperature and humidity control are closely tied to
pressure control. If the pressures dip too low, the ability to cool
the spacecraft is impaired. Temperature is also affected by the
multiple heat sources within the vehicle, including electronics,
lighting, solar heating, and metabolic heat (as produced by
exercise). The Russian experience has suggested that the ideal
temperatures for a working environment are from 22.2C to
23.9C (72F to 75F), whereas temperatures below 18.9C
(66F) and relative humidity greater than 70% are perceived
by crews as unpleasantly cold [48]. The atmospheric control
systems used in past and present spacecraft are discussed in
the remainder of this section.
Mercury
Missions in Project Mercury were relatively brief, lasting
from 15 min to 34 h, and involved only one astronaut in a
bell-shaped volume of 1.56 m3 (55 ft3) [44]. Accordingly, the
life support system could be relatively simple. A single sys-
tem provided atmospheric control to both the cabin and the
astronauts pressure suit. Requirements called for a 28-h flight
capability, based on an oxygen consumption of 500 ml/min
and a standard cabin leakage rate of 300 ml/min [49].
The Mercury spacecraft used a low cabin pressure
(258 mmHg [5 psi]) and a single-gas atmosphere. The cabin
pressure was chosen because it provided the needed PAO2,
a small pressure differential with the ambient atmosphere
in case of vessel decompression, and a low potential risk
of decompression sickness [49]. NASA mission designers
decided that the spacecraft environment would be closed to
conserve oxygen and thus to diminish the necessary amount
and weight. Four pounds of oxygen were required, but a sup-
ply of 8 lb of oxygen was flown to ensure sufficient amounts
in case of emergency.
A store of pressurized oxygen provided both ambient
pressure and adequate ppO2. From an engineering standpoint,
NASA decided to use a single-gas atmosphere because it was
22. Hypoxia, Hypercarbia, and Atmospheric Control
simple and reliable and required minimal weight. The pressure
suit was designed to operate at 238 mmHg (4.6 psi) after a
cabin depressurization.
The environmental control system originally called for
a pure oxygen environment in the pressure suit, but a cabin
atmosphere consisting of 33% nitrogen and 66% oxygen
(obtained by enriching the cabin atmosphere at launch with
pure oxygen) was chosen because of concerns about the fire
hazard. In early ground tests, problems were experienced with
nitrogen concentrating in the pressure suit, and so the pure
oxygen environment was extended to the cabin. Additional
emphasis was then placed on the selection of fire-retardant
materials to combat the increased risk.
LiOH removed CO2, and a sublimate heat exchanger cooled
the cabin based on an estimated metabolic heat production of
126 kcal/h (500 Btu/h) by the astronaut. In a foreshadowing of
future closed-loop systems, the heat exchanger used condensate
derived from the vehicles humidity-removal system.
The pressure suit was considered a backup to the cabin
environment. A battery-powered blower drove oxygen into
the suit torso, providing cooling and producing a mixture of
oxygen, CO2, and water vapor. This mixed gas then left the
suit through a helmet connection and was processed by the
suits environmental subsystem. Activated charcoal filtered
odors, LiOH absorbed the CO2, and a water-evaporative heat
exchanger cooled the air. Additional oxygen was fed into the
suit by a demand regulator. The suit subsystem was designed
to work with a CO2 production rate of up to 400 ml/min.
Gemini
The Gemini spacecraft supported two crewmembers simul-
taneously in a larger capsule (volume 2.26 m3 [80 ft3]) during
missions lasting nearly 10 times longer than the Mercury
missions (i.e., 5 h to 14 days) [44]. The capability of the envi-
ronmental control system had to advance accordingly. At the
same time, the desire on the part of NASA engineers was to
retain as much of Mercurys technology as possible because
of its proven record of success.
As was true for Mercury, a 260 mmHg (5 psi) single-gas atmo-
sphere was used in Gemini, although its primary oxygen source was
liquid oxygen rather than gaseous oxygen. Initially, concerns were
expressed about the effect of a pure oxygen environment for the
duration of the planned missions, but ground-based research docu-
mented that exposure to the Gemini atmosphere for up to 2 weeks
had no negative physiologic effects on test subjects, and the
pure-oxygen system went ahead as planned [50].
Liquid oxygen was heated to gaseous form by a heat
exchanger and passed through a pressure-reducing regulator
before being delivered to the cabin through a cabin pressure
regulator. As was true in the Mercury program, the astronauts
pressure suit served as a backup in the event of cabin decom-
pression. A LiOH canister removed CO2 and associated odors.
The longer missions and the larger crew (two crewmem-
bers rather than the single-crewmember Mercury missions)
467
made the rudimentary temperature control system of Mer-
cury insufficient to support Gemini, and a new fluid cool-
ant and radiator system was used to control temperature.
The suit heat exchanger transferred heat and moisture from
the suit circuit oxygen to vehicle coolant flow. The cool-
ant (a silicon ester fluid) then went to the adapter module
skin and transmitted the heat into space [51]. As much as
375 kcal/h (1,500 BTU/h) could be handled in this fashion,
with control provided by the amount of coolant flow to the
radiator. A backup system also permitted additional cool-
ing through the use of sublimated water.
The Gemini spacecraft was also the first U.S. design to pro-
vide environmental control to an astronaut outside the vehicle.
Life support was controlled through an umbilical connection
that tethered the astronaut to the spacecraft.
Apollo
Apollo life support systems were necessarily more complex
than previous ones, as they involved separate systems for the
command module and the lunar excursion module. Once again,
however, technology from proven environmental control systems
of Projects Mercury and Gemini was extensively used.
The command module was a pressurized conical capsule
(5.9 m3 [210 ft3]) suitable for a three-person crew. The life
support system took up 0.25 m3 (9 ft3) and could operate for
up to 14 days; the service module supplied potable water
and oxygen. The lunar excursion module, by contrast, was
designed to serve two astronauts in a pressurized vessel of
4.5 m3 (158.9 ft3) [44]. Missions in the Apollo Program lasted
from 6 days (Apollo 13) to 12.5 days.
In the original plans for the Apollo Program, concerns about
oxygen toxicity and pulmonary atelectasis led to the call for
a spacecraft atmosphere of 50% nitrogen and 50% oxygen at
362 mmHg (7 psi). However, because Project Gemini had suc-
cessfully used a 100% oxygen atmosphere for up to 14 days,
NASA engineers elected to continue with the single-gas envi-
ronment at 260 mmHg.
Apollo preflight checkout initially called for overpressur-
izing the command module to 827 mmHg (16 psia) before
launch, which unfortunately contributed to the fire that killed
the Apollo 1 crew during a launch pad simulation. After this
tragedy, an atmosphere of 60% nitrogen and 40% oxygen was
used at launch. Over the course of the Apollo missions, the
cabin environment eventually became nearly pure oxygen, as
leakage was exclusively replaced by oxygen during flight.
A cryogenic store in the service module supplied oxygen,
which remained the only gas available during flight to main-
tain pressurization. During lunar surface activities, astro-
nauts wore suits that were pressurized to 200 mmHg (3.9 psi)
and breathed 100% oxygen. In his memoir, Michael Collins
described a probable decompression sickness event dur-
ing Apollo 11. Although this was reported retrospectively, it
remains the only such event known during the Apollo
Program [52].
468 K. Bacal et al.

Again, LiOH removed CO2 and humidity from the space- Thermal control was generally provided with passive sys-
craft atmosphere, and the ppCO2 was designed to remain near tems. One such system involved the use of surface paints of
3.8 mmHg, with maximum levels of 7.6 mmHg and an emer- various reflectivities and emission patterns, thereby allowing
gency limit of 15 mmHg [50]. Sensors located in the command solar heat to be reflected or absorbed according to regional
and lunar modules recorded CO2 levels, which remained within heat requirements. After repairs were made to the surface pan-
design specifications at all times other than during the return of els that had been damaged at launch, the use of radiators or
Apollo 13. On that mission, the CO2 absorption capability of evaporators was rarely necessary [10].
the lunar modules LiOH canister became exhausted after 83 h, As did Apollo crewmembers, Skylab astronauts used liq-
and CO2 levels rose to 14.9 mmHg until the command modules uid-cooled garments and space suits pressurized to 200 mmHg
LiOH canisters could be retrofitted for use. Once the modifica- (3.9 psi) during EVAs. Also like the Apollo crew, the Skylab
tions were made and the new canisters were deployed, CO2 levels crews were transported to Skylab in an Apollo spacecraft so
again fell to between 0.1 and 1.8 mmHg. that additional nitrogen washout occurred even before they
A space radiator similar to that used on Gemini maintained reached Skylabs 70/30 ATM.
the vehicle temperature between 21.1C and 26.7C (70F
and 80F), with a relative humidity of 40% to 70% [10]. Cold-
plate wall radiators were used to control the temperature in the Space Shuttle
command module after a cabin gas heat exchanger proved to
The Space Shuttle required the next generation in life support
be too noisy and inefficient.
systems. Although the durations of its missions were simi-
lar to those in the Apollo program, the crew complement was
Skylab significantly larger at up to eight astronauts. Other significant
changes were also made in the composition and volume of the
In contrast to previous vehicles, the Skylab station was the first
spacecraft atmosphere.
U.S. long-duration space habitat and accordingly required a
The environmental control and life support system on the
more elaborate environmental control system. Three separate
Space Shuttle contains several interlinked systems, including
crews supported missions of 28, 59, and 84 days in a volume
systems for atmospheric revitalization, pressure control, active
of 361 m3 (12,750 ft3). Trace contaminant buildup, which was
previously less of a concern because of the relatively short thermal control, and water supply, and waste water manage-
duration of the missions, became a major consideration, as ment (Figure 22.8).
did the need for recyclable and renewable consumables. In Unlike previous U.S. vehicles, the pressure of the Space
the end, however, Skylabs life support system did not recycle Shuttles 74 m3, (2,615 ft3) cabin is maintained at sea level
(760 mmHg [14.7 psi]) and consists of a mixture of 80%
all compounds, which greatly simplified the system design,
albeit at the cost of requiring larger supplies of consumables.
The Skylab atmosphere also differed from that of previous
programs. In response to concerns about the possible toxic
effects of chronic hyperoxic environments, a two-gas environ-
ment was used for the first time. The atmospheric pressure
remained at 260 mmHg (5 psi), but the atmosphere was altered
to a 30% nitrogen +70% oxygen mix. This system resulted in
an inspired oxygen tension of 182 mmHg, which was slightly
higher than on Earth. The mixture of the gases was controlled
both automatically and manually. Between the crewed mis-
sions, the atmosphere was depressurized to 103 mmHg (2 psi)
and allowed to deteriorate as far as 26 mmHg (0.5 psi) as a
means of preventing fire and removing trace contaminants.
CO2 was removed from the atmosphere not by the LiOH
canisters used previously but rather by regenerable molecular
sieves. These sieves trapped CO2 in pores but allowed oxygen
and nitrogen to pass through. The zeolite matrix was periodi-
cally heated and exposed to vacuum to remove the trapped
CO2 and regenerate the bed for further use. Two alternating
beds were usually used. The sieve operated at a slightly higher
CO2 level (5 mmHg) than did the LiOH canisters, with the end
result that Skylab astronauts were exposed to greater CO2 ten- Figure 22.8. Schematic overview of Space Shuttle environmental
sions than were previous crews. The upper limit of 7.6 mmHg control and life support system. (ARS = atmosphere revitalization
was maintained, however. system; ATCS = active thermal control system.)
22. Hypoxia, Hypercarbia, and Atmospheric Control
nitrogen and 20% oxygen. Oxygen is supplied to the system
through cryogenic storage tanks. The Space Shuttle is unique
among U.S. spacecraft in that it also has nitrogen supply tanks.
This dual-gas system is significantly more advanced than the
single-gas system used through the Apollo era.
Gaseous nitrogen provides atmospheric pressurization to
sea level and also pressurizes the water tanks to 879 mmHg
(17 psi). Oxygen, derived from the same source as that of the
orbiter fuel cells, also provides pressurization to sea level.
Supplies of both gases, as well as positive- and negative-pres-
sure relief valves, are regulated at a nitrogen/oxygen control
panel. Normal daily losses of crew cabin gas from metabolism
and leakage are calculated as up to 3.5 kg (7.7 lbs) of nitrogen
and 4.1 kg (9 lbs) of oxygen. Caution and warning lights are
activated whenever the following ranges are violated: cabin
pressure 724 to 796 mmHg (14.0 to 15.4 psi), ppO2 145 to
186 mmHg (2.8 to 3.6 psi), or oxygen or nitrogen flow rates
in excess of 2.27 kg/h (5 lbs/h). Caution and warning limits
can be changed to reflect different cabin pressures such as the
intermediate pressures to support EVA.
A complex active thermal control system provides temperature
control by means of Freon-21 coolant loops, cold plate
networks, heat exchangers, and heat sinks. Different heat
rejection systems are used at different stages of flight. For
example, once the Space Shuttle has reached orbit, its pay-
load bay doors are opened so that the radiator panels on the
undersides of the doors can begin to radiate heat. A water
flash evaporator serves as a backup during flight and as the
primary system when the payload bay doors are closed during
launch and landing.
The atmosphere revitalization subsystem maintains cabin
humidity levels between 30% and 75%, removes CO2 and
CO, and provides ventilation and temperature control for
both avionics and crew areas. The atmosphere revitalization
subsystem circulates cabin air while picking up CO2, odors,
heat, and moisture; debris is then removed by using one of two
fans to draw cabin air through a 300-m filter. The air is sent
through two LiOH-activated charcoal canisters to absorb CO2
and odors. The canisters have a lifespan of 24 h, requiring that
one canister be changed every 12 h. Cabin air then travels to
the heat exchanger and is cooled by the water coolant loops.
Humidity condensate is removed and separated from the air.
Up to 1.8 kg (4 lbs) of water is removed per hour and sent to
the waste water tank. Most of the revitalized air is meanwhile
ducted back into the cabin, with a small fraction of the air
sent to the CO removal unit. That unit converts CO into CO2,
which the LiOH canisters can then remove. The entire volume
of cabin air travels through the atmosphere revitalization
subsystem 8.5 times every hour (330 ft3/min).
Some cabin air bypasses the heat exchanger and mixes
with the revitalized air to maintain the cabin temperature
between 18.3C and 27C (65F to 80F). The same system between the Russian and U.S. space agencies, and much
cools the avionics units and the three inertial measurement
units, although this air is carried on independent loops from
the cabin air.
469
The life support system on the Space Shuttle can also be
extended to pressurized modules in the payload bay, such as
Spacehab, and can partially depressurize and repressurize for
EVAs. Because U.S. space suits operate at 222 mmHg (4.3 psi)
during EVAs, concerns have been raised that the pressure dif-
ferential between the vehicle and suit might lead to the devel-
opment of decompression sickness. On previous missions
with pure oxygen atmospheres, the risk of decompression
sickness was greatest at launch, when cabin pressure changed
from 760 mmHg to 260 mmHg (14.7 psi to 5 psi). Gemini and
Apollo crews minimized this risk by breathing 100% oxy-
gen for 3 h before launch. By the time the crews exited the
vehicle, the risk of forming nitrogen bubbles was extremely
low. Even Apollo astronauts, whose space suits were pressur-
ized to 200 mmHg (3.9 psi), had been breathing a high-oxygen
environment for several days before engaging in EVAs on the
lunar surface, so the small change between the cabin pressure
and space suit pressure reduced the risk even further.
Space Shuttle crews, by contrast, are at the greater risk dur-
ing the transition from their sea-level-equivalent cabin to their
single-gas, 222-mmHg (4.3-psi) EMU. As a result, 12 to
24 h before performing an EVA, the entire crew compartment
is depressurized from sea level to 527 mmHg (10.2 psi). The
crewmembers who will actually be outside the vehicle in
the EMUs also breathe 100% oxygen to purge their tissues of
dissolved nitrogen. After these actions, they enter the 100%-oxygen,
222-mmHg (4.3-psi) EMU and exit the Space Shuttle.
The EMU space suit is essentially a single-person space-
ship that is suitable for missions lasting up to 8 h. As such,
it has its own independent life support system. LiOH
canisters are used to regulate CO2 levels below 0.15 psi
(7.75 mmHg) or at 0.29 psi (15 mmHg) at metabolic rates
that exceed 400 kcal/h (1,600 Btu/h) [13]. (For station-
based EVA, the LiOH canisters are replaced by regener-
able metal oxide cartridges) A liquid cooling garment helps
to combat thermal stresses caused by heat released by the
suit machinery, the exothermic CO2 absorbing reaction, and
metabolic workloads. As is true for the cabin environment,
the EMU atmosphere must be adequately ventilated and
rigorously monitored.
Although the Space Shuttle is the first U.S. spacecraft to offer
an Earth-normal atmosphere on orbit, Russian spacecraft have
done so for many years. The next section constitutes a review of
Russian contributions to environmental control systems.
The Russian Experience
Although the early years of space exploration were
influenced by Cold War competition, the last decades
have seen an increasing number of joint space operations.
The ISS Program has greatly increased cooperation
knowledge has been shared with regard to previous joint
missions on the Shuttle and Mir station as well. The Russian Space
Agency is quite experienced, particularly in the realm
470
of long-duration space flight. Since 1971, eight Soviet/
Russian space stations have been flown (seven Salyut sta-
tions and Mir); other Russian spacecraft include the Vostok,
Voskhod, and Soyuz vehicles.
Both the Russian and U.S. space programs began with small
vehicles with open-loop environmental support systems. The
Vostok, which carried cosmonaut Yuri Gagarin into history as
the first human in space, was a spherical craft with a volume
of 2 to 3 m3 (71 to 106 ft3). Unlike NASAs early spacecraft,
the early on the Russian spacecraft involved use of an Earth-
like atmosphere (80% nitrogen and 20% oxygen at 760 mmHg
[14.7 psi]) [53].
The Vostoks life support system was similar to those of
early U.S. spacecraft. The Voskhod was an improved Vostok
that housed three seated crewmembers in a shirtsleeve envi-
ronment (i.e., pressure suits were not required). The Soyuz
spacecraft, upgraded versions of which are still in use as
transport and escape vehicles for the ISS, was first flown in
1967. It contains two pressurized compartments for three
crewmembers, again in shirtsleeves. After all three cosmonauts
aboard Soyuz 11 died in a spacecraft depressurization, the
Soyuz crews were limited to two people in pressure suits. The
vehicle was later modified into the Soyuz T to accommodate
three suited crewmembers. In contrast to U.S. vehicles, the
Soyuz was designed to allow no gas leakage. Its sea-level
atmosphere is a mixture of oxygen and nitrogen, maintained
at an ambient pressure of 708 to 847 mmHg (13.7 to 16.4 psi)
with partial pressures of oxygen between 140 and 202 mmHg
(2.7 to 3.9 psi).
These differences between vehicle design in the Russian
and U.S. programs led to some concerns during the Apollo-
Soyuz Test Program, during which the two spacecraft were
to dock and allow contact between crewmembers. Russian
engineers were concerned about the Apollo capsules normal
leakage rate of 1 kg/day, and U.S. flight surgeons were con-
cerned about the development of decompression sickness. In
the Apollo-Soyuz Test Program, the atmosphere of the Apollo
vehicle was 100% oxygen at 260 mmHg (5-psi) atmosphere
and the Soyuz environment was a mixture of oxygen and
nitrogen at 517 mmHg (10 psi). Despite these concerns, no
episodes of decompression sickness were reported.
The Soviet spacecraft also stored oxygen in solid form, as
alkali metal superoxides, rather than the liquid and gaseous forms
used by NASA. As these solid compounds absorb moisture, they
liberate oxygen and form alkalis, which in turn absorb CO2.
Life support systems planned for space stations were revised
to accommodate the longer-term functionality required for
weeks- or months-long missions. The first space station was
the Salyut, designed to house up to five crewmembers in three
modules with a total volume of 100 m3 (3,530 ft3). Seven
Salyut stations were launched between 1971 and 1982. Oxy-
gen was created on board by means of a potassium superoxide
system, and both LiOH canisters and the oxygen regenerators
removed CO2. The life support system on Salyut 6 was modi-
fied to include a water reclamation system.
K. Bacal et al.
The Mir space station was the next generation beyond the
Salyut 7 station. Mir was designed to house up to six crew-
members in a volume of 150 m3 (5,300 ft3) and, like its suc-
cessor the ISS, modules could be added to its core structure.
In addition to tanked stores and a hypochlorite generator sys-
tem, oxygen on Mir was produced by water electrolysis. As
was the case on Skylab, CO2 on Mir was removed through an
absorbable system that vented to space.
International Space Station
The ISS is international not only in name but also in components.
Many of the station systems were created by partnerships
between two or more countries; the Russian and U.S. orbital
segments of the ISS often use different methods, even in the
environmental control and life support system.
The atmosphere control and supply system onboard the ISS
is responsible for maintaining the pressure and composition
of the station atmosphere, providing oxygen and nitrogen,
and allowing pressure equalization and depressurization. The
ISS, like the Russian space stations that preceded it, uses a
760 mmHg (14.7 psi), 80% nitrogen and 20% oxygen atmo-
sphere. The Russian orbital segment is primarily responsible
for atmosphere control and supply during the initial years of
station operations. Progress resupply vehicles, equipped with
tanks that can be filled with nitrogen, oxygen, or mixed air,
can be accessed by ISS crews in the event of a drop in cabin
pressure. Although the ISS was initially supplied with all
respirable gases, oxygen can also be generated through the
electrolysis of waste water with the Russian Elektron device.
An oxygen generator is eventually planned for the U.S. orbital
segment as well. As a backup, a solid fuel oxygen generator
is present that relies on the exothermic production of oxygen
from chemical cartridges.
The atmosphere control and supply subsystem in the U.S.
orbital segment (Figure 22.9) makes use of four high-pressure
gas tanks, two oxygen and two nitrogen, located on the airlock
exterior and connected by a system of pipes. The tanks can be
refilled by the Space Shuttle, although a pressure differential
between the Space Shuttle tanks and the ISS tanks mandates
use of a transfer pump to ensure that the ISS tanks can be
fully recharged. The external location was chosen to allow the
tanks to be replaced by full ones if refilling is unavailable. A
pressure control assembly is responsible for introducing gas
or gases into the cabin environment, monitoring the station
pressure, and permitting depressurization as needed. Manual
pressure equalization values are provided to equalize pressure
between closed modules.
The atmosphere revitalization subsystem on the ISS
maintains the safety of the breathing air by removing CO2 and
other contaminants and by monitoring air quality with a mass
spectrometer. The U.S. CO2 removal assembly and the Russian
Vozdukh system use a series of reusable sorbent beds to remove
CO2, which is then vented to space. For maximal efficiency, the
22. Hypoxia, Hypercarbia, and Atmospheric Control
Figure 22.9. Atmospheric control and supply subsystem for the U.S. orbital segment of the International Space Station
systems require cool, dry air and are linked directly to the tem-
perature and humidity control subsystem to receive processed
air. LiOH canisters are also available as backup. Trace contami-
nants are controlled in both the Russian and U.S. segments by
high-efficiency particulate air filters and catalyzation.
When the ISS is completely assembled, CO2 scrubbing will
allow reclamation of oxygen that would otherwise be lost. The
Russian Sabatier reactor will eventually be used to conserve
resources by combining hydrogen from the Elektron and CO2
from the atmosphere revitalization subsystem at relatively
high temperatures (480C to 650C [900F to 1,200F]) to
create water and then oxygen by hydrolysis.
As is true for other spacecraft, ventilation is critical for
temperature and humidity control on ISS. Air circulation
takes place at three levels: within an individual rack, within an
471
individual module, and between two or more modules. Rack
ventilation makes use of the avionics air assembly, cooling
the air within a rack by using fans and noncondensing heat
exchangers. The system is also linked with smoke detectors
from the fire detection and suppression subsystem.
Intramodule ventilation in contrast, is provided by the cabin
air assembly. That assembly draws cabin air through a high-
efficiency particulate air filter and then removes moisture
through a condensing heat exchanger. The water thus produced
is sent to the water recovery and management subsystem, and
the cool, dry air goes first to the CO2 removal assembly and
then back into the cabin. In the Russian orbital segment, drag-
through flexible ducting and open hatches provides ventilation
between modules, and the U.S. segment uses a series of fans,
valves, and hard-plumbed ducts.
472
Both the 222-mmHg (4.3-psi) U.S. space suit and the
higher-pressure Russian Orlan suit (295 mmHg [5.7 psi]) are
used for EVAs from the ISS. Although flight surgeons con-
tinue to be concerned about the risk of decompression sick-
ness from the pressure differential between vessel and suit, to
depress the entire ISS to an intermediate pressure stage before
an EVA, as the Space Shuttle does, is not practical. The Space
Shuttles smaller volume and shorter mission duration allow it
to depressurize and repressurize its entire crew compartment.
The ISS airlock can serve this function by being isolated from
the remainder of the station and being partially decompressed,
although new concerns have been raised about prolonged iso-
lation of crewmembers. To mitigate this concern and further
conserve ISS gas resources, a new EVA prebreathe procedure
in which exercise is used to enhance nitrogen elimination and
decrease the amount of oxygen prebreathe time has recently
been developed and utilized from the ISS joint airlock.
Future Directions
As the duration of orbital missions and the size of the crews
increase and as plans are made for explorations beyond
Earths orbit, the ability to provide space crews with a healthy
and comfortable living environment grows ever more com-
plex. Advanced environmental control systems will be needed
for both planetary exploration missions and permanent settle-
ments beyond Earths atmosphere. New technologies will be
needed to enhance water reclamation, produce oxygen, and
remove CO2. The primary requirements for such a system
will be minimal power usage and volume, robust autonomous
operation, and a closed-loop design that minimizes reliance
on stored consumables. Once we venture beyond low-Earth
orbit, the risks associated with radiation increase, the capabil-
ity for frequent resupply diminishes, and medical assistance
and evacuation become less available. Life support systems
must become more closed loop, more robust, more efficient,
more operationally simplified, more automated, and more
reliablewhile simultaneously requiring less energy-inten-
sive, less massive, and less expensive technology.
Although the ISS currently uses electrolysis of waste water
to produce oxygen, oxygen can be generated by other means,
such as electrolysis of CO2 or water vapor or use of plants. Not
only waste water but solid wastes will be recycled in future
habitats, and plants, grown from these recycled solids may
come to form a critical link in the life support loop. Just as
Earth is a spacecraft with a planetary ecology that forms its
life support system, extraterrestrial human habitations will
need to create their own ecologies, complete with biological
air revitalization and water reclamation systems.
It is also critical to point out that the location of any
future missions will influence the design of the environ-
mental control system. For example, hazards associated
with lunar or Mars missions (dust, falls, potential micro-
organisms) do not exist in long-duration space station mis-
K. Bacal et al.
sions in microgravity; however, additional resources may
be available on lunar or Mars missions that may range from
oxygen-containing soil to potential heat sinks or radiation
barriers. All of these factors must be considered in the
development of future life support systems.
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206956.
23
Radiation Disorders
Jeffrey A. Jones and Fathi Karouia
Space presents a unique radiation environment to the intrud-
ing human; from a different viewpoint, Earth is a unique
radiation haven in which humans live and flourish. Radiation
exposure remains perhaps the single most important limiting
factor for human exploration of space beyond low Earth orbit
(LEO), primarily because of difficulties in providing adequate
protection for the crew. Protection that would limit exposures
to anywhere near terrestrial normal values would involve
shielding of substantial mass. Moreover, considerable variet-
ies of radiation types and energies are associated with space
flight, many of which can have potentially adverse effects on
biological and physical systems. Unlike Earth-based radia-
tion exposures, space flight involves exposures from outside
sources such as solar particle events or galactic cosmic rays
rather than radioactive contamination, and most such expo-
sures affect the entire body.
The effects of radiation on the cell, the fundamental unit of
a biological system, can be compared with its effects on the
electronic system equivalent, the integrated circuit. In the ter-
minology of electronics, incident radiation could cause a sin-
gle event upset that might go completely unnoticed but could
also trigger an undesirable software response, shut down that
component, or devastate the hardware through a short circuit
or power surge, depending on the location and activity of the
component that was hit. The same is true of ionizing radiation
events in the cell. The ionized molecule could be immediately
neutralized by a cytoplasmic antioxidant molecule, or it could
produce a nuclear DNA point mutation in a non-coding region
of the genome. It could trigger a chain reaction of ionization
events or a DNA single-strand break (SSB) that might lead to
mutation or a double-strand break (DSB) leading to cell death.
The uncertainties associated with the effects of ionizing radia-
tion and its risks to human health are still quite high.
This chapter will review how the space environment differs
from that on the surface of Earth and review current knowledge
of space radiation. Also included are descriptions of the key
areas of research needed to reduce the level of uncertainty asso-
ciated with space travel and strategies to mitigate the inherent
risks associated with human exposure to space radiation.
Radiation Physics: A Brief Overview
Definition of Terms
Definitions of terms used to describe radiation quantity and
quality are provided below.
The electron volt (eV) is the common unit of measure for
energy present in radiation and is often expressed in multiples
of thousands (keV) or millions (MeV). One eV is the kinetic
energy acquired by an electron accelerated in a vacuum
through a potential difference of 1 v; 1eV = 1.6 10 12
ergs = 1.6 1019 joules.
The radiation absorbed dose (rad) is the amount of energy
that is absorbed from radiation per unit mass of material. The
System International unit (SI) unit for absorbed dose is the
gray (Gy); 1 Gy = 100 rad = 10,000 ergs/g. Relative biological
effectiveness (RBE) is the ratio of a standard X-ray dose to
that of another type of ionizing radiation that results in the
same risk of a biological event. The RBE, as its name implies,
is used to compare the biological effectiveness of different
types of ionizing radiation.
The dose-equivalent or biologically equivalent dose is
expressed as roentgen-equivalents man (rem) and represents
the absorbed dose adjusted for the biological effectiveness
of the particular type of radiation. The SI unit for dose-
equivalent is the sievert (Sv); 100 rem = 1 Sv. Dose-equivalents
are calculated as the product of the absorbed dose and a quality
factor Q (see below).
The quality factor (Q) is a function of a particles linear
energy transfer (LET) (see below), which in turn is determined
by the charge and energy of the radiation particles. Quality
factors account for differences in the biological effectiveness
of different particles and, as noted in the previous paragraph,
they are used to convert absorbed doses into dose-equiva-
lents. In terms of the traditional units, rem = rad x Q; in SI
units, sievert = Gy x Q. Current values for Q range from 1 (for
X rays) to 20 (Table 23.1) [1,2]. Quality factor values as high
as 100 for certain highly damaging particles may be deemed
appropriate as additional research continues.
475
476 J.A. Jones and F. Karouia

Linear energy transfer (LET) quantifies the amount of event) and chronic exposures (i.e., an exposure fractionated
energy deposited by a radiation particle per unit length of over time) of the same type of radiation at the same total dose.
the particles track. This factor increases with the square Like RBE, the DREF is expressed as a ratio and is a way of
of the charge and is inversely proportional to the energy understanding the influence of dose rate on the biological
of the radiation particle. The influence of the electric force effect. Practically, this term becomes a scaling factor whereby
field depends on the velocity of the particle. Slower moving meaningful comparisons can be made between acute expo-
charged particles will produce more ionizations per unit path sure events for which there is historical evidence linking dose
length than faster moving ones. LET accounts for all energy and outcome, such as those experienced by atomic bomb
transfers along the particles path, regardless of the mecha- survivors, and events such as long duration space flight that
nism of those transfers. involve low dose rates.
The biologically weighted dose-equivalent value (H) is the Flux is the density at which particles are incoming, measured
product of the absorbed dose, Q, and other dose-modifying in number of particles/cm2. Fluence is the rate at which particles
factors. H is expressed in rem or Sv and is intended to encom- are incoming, measured in number of particles/second.
pass all aspects of a certain radiation exposure influencing a Stochastic or probabilistic effects are defined as effects that
biological effect. have some probability of occurring; that probability is a function
The dose rate effectiveness factor (DREF) measures the of dose. Some somatic effects, particularly carcinogenesis, are
differences between acute exposures (i.e., a single large exposure regarded as being stochastic, as are hereditary effects.
Deterministic or nonstochastic effects, on the other hand,
Table 23.1. Quality factors associated with various types of are effects considered to be inevitable; deterministic effects
radiation. are associated with some threshold dose above which the
Radiation type and energy range Quality factor (Q)
probability of their occurrence is expected to be 100%. In bio-
logical terms, most of the deterministic effects of radiation
Photons, all energies 1
Electrons and muons, all energiesa 1
involve cell killing and can occur soon after (early effects) or
Neutrons, energy < 10 keV 5 later after the radiation exposure (late effects).
10 keV to 100 keV 10 An overview of types of radiation of interest, with their
100 keV to 2 MeV 20 sources, penetration, and principal types of interactions, is
2 MeV to 20 MeV 10 given in Table 23.2 [3].
20 MeV 5
Protons (other than recoil protons) of energy > 2 MeV 2b
Alpha particles, fission fragments, heavy nuclei 20 Electromagnetic Radiation
NOTE: All values relate to the radiation incident on the body or (for internal The electromagnetic radiation environment aboard a space
sources) emitted from the source.
a
Excluding auger electrons emitted from nuclei bound to DNA.
vehicle in LEO is determined by the contributions of electric
b
The Q value recommended by the International Commission on Radiological fields, magnetic fields, and electromagnetic radiation from
Protection for this type of radiation is 5. onboard sources; other contributors include extremely low
Sources: Adapted from National Council on Radiation Protection and Mea- frequency variations in the electromagnetic radiation from the
surements [1] and Prasad [2]. motion of the spacecraft within the geomagnetic field.

Table 23.2. Types of radiation and the possible extent of hazard.

Type of radiation Symbol Usual source
X rays X-ray machines and accelerators
Gamma rays Most radioisotopes emit rays
after decay
Neutrons Generally produced by critical
assemblies, nuclear reactors, or
accelerators
Beta particles Most radioisotopes decay by
emitting particles, usually
followed by emission of rays
Alpha particles Many heavy radioactive elements
(e.g., plutonium) decay by
emitting particles
Protons Energetic protons are found only
near particle accelerators
Source: Andrews and Cloutier[3]. Used with permission, Heldref Publications.
Penetration of external radiation
X and rays penetrate deeply, for only Ejected electron loses energy by causing
a fraction of the rays interact with
each layer of tissue
Neutrons penetrate deeply, for only
a fraction of the neutrons interact
with each layer of tissue
Penetration depends on the energy of
the particle but is usually limited
to less than 8 mm in tissue
Penetration is limited to about
the thickness of the epidermis
Penetration depends on the energy
of the proton
Principal types of interaction
additional ionization; deflected X or
ray may interact again some distance away
Deflected neutrons may interact some
distance away; recoil proton loses energy
by causing ionization
Ejected electron loses energy by causing
additional ionization; deflected electron
or particle causes additional ionization
Ejected electron loses energy by causing
additional ionization; deflected goes
on to cause additional ionization
Deflected proton causes additional
ionization; ejected electron loses energy
by causing additional ionization.
23. Radiation Disorders
Spans of interest in the electromagnetic spectrum (Figure
23.1) include the radiofrequency range, the microwave range
(300 MHz to 300 GHz), and the ultraviolet light range (750 THz
to 3 PHz). An electromagnetic wave is emitted any time elec-
trical charges (i.e., electrons) are made to accelerate. Once an
electromagnetic wave is underway, a changing electric field
creates a changing magnetic field. The electric field and magnetic
field point in directions perpendicular to one another, and the
electromagnetic wave propagates in a direction perpendicular
to both. The separation between adjacent peaks or valleys
of the wave is called the wavelength () and the number of
peaks or valleys observed per second at a fixed point in space
is called the frequency (f ), expressed in Hertz (Hz; 1 Hz = 1
Figure 23.1. The electromagnetic spectrum
477
cycle per second). Because the peaks are apart and pass a
point at the rate of f per second, the velocity v of the wave
must be f = v. This general expression is valid for any
kind of wave. However, the speed of electromagnetic waves
is so central to modern physical theory that it has its own sym-
bol, c. Thus, for electromagnetic radiation, f = c, where
c = 3.00 108 m/second. The energy of an electromagnetic
wave is proportional to its frequency; therefore long low-frequency
waves have low energy, and short high-frequency waves have
high energy.
Ionizing Electromagnetic Radiation
X rays. At the atomic level, two processes produce X rays.
One process involves the collision of accelerated electrons
with orbital electrons in target atoms. If the energy imparted
to the orbital electron is greater than the binding energy of
the specific electron shell, the orbital electron is ejected
and the atom becomes ionized. As other electrons move to
replace the ejected electron (from the outer to the inner
shells), characteristic X rays will be emitted and their energy
will be the difference of the binding energies of the two
different shells. X rays are given a quality factor of 1 and are
the benchmark by which all other bioeffects of radiation
are measured.
In the other process, a continuous spectrum is produced
when high-speed electrons encounter nuclei in target atoms.
If an electron passes close to the atomic nucleus, it will be
attracted by the strong positive charge of the nucleus and
its direction of travel will be changed. This process causes
a reduction in electron energy in which the energy is dis-
sipated as X rays (the Bremsstrahlung effect). The greatest
X ray energy is produced when the high-speed electrons occa-
sionally collide with an atomic nucleus. In such cases, all of
the electron energy is given up as X rays. Because any amount
of energy may be lost by the electron (up to the maximum
electron energy) and converted to X rays, the X rays produced
in this process are not of a specific energy but rather are
distributed in the form of a continuous spectrum.
Gamma rays. Atoms can also be unstable and therefore
radioactive because they possess an excess of energy. Gamma
() rays are produced during the radioactive decay of an
excited nucleus just after a beta decay has occurred. Gamma
rays belong to the electromagnetic spectrum and have a char-
acteristic wavelike nature; they are highly penetrating into
matter and they interact briefly with material (e.g., tissues)
that they encounter. Their reactions are more readily under-
stood if gamma rays are considered as small bundles of energy
traveling at the speed of light. A bundle of such energy is
called a quantum or a photon.
Nonionizing Electromagnetic Radiation
Because the energy of nonionizing radiation dissipates mainly
in the form of heat, the chief effect of nonionizing radia-
tion on its target is thermal. The thermal effect depends on
478 J.A. Jones and F. Karouia

the intensity of the source, the distance between the source
and the target, and the duration of exposure. Another factor
is the composition of the target material, as different types of
material can absorb incident nonionizing radiation to different
extents. The major types of nonionizing radiation are ultraviolet
radiation, visible light, and longer wavelength electromagnetic
radiation.
Ultraviolet (UV) radiation ranges in wavelength from
about 100400 nm. UV radiation of wavelengths shorter
than 180 nm, the most biologically active component of
UV radiation from the sun, is absorbed almost completely
by Earths atmosphere. Most of the long-wave component
of UV radiation (320400 nm, known as UV-A) reaches
the surface of the Earth and penetrates air, quartz, glass,
and water; until recently, its biological effects were thought
to be slight [4]. UV radiation of intermediate wavelengths
(280320 nm; UV-B) is completely transmitted through
air and quartz but is partially absorbed by the atmospheric
ozone layer and is completely absorbed by ordinary window
(lime) glass. UV-B significantly influences both the bio-
sphere and human tissues by producing actinic changes, free
radicals, and dimerization. Short-wavelength UV radiation
(100280 nm; UV-C) is poorly transmitted through air and
quartz and is not thought to be important in terrestrial human
disease, although it is bactericidal and fungicidal. UV radia-
tion of wavelengths shorter than 240 nm reacts with oxygen
and nitrogen oxides to produce ozone; UV radiation of
wavelengths less than 180 nm can, in the presence of oxygen,
oxidize hydrocarbons.
Visible light (400780 nm wavelength) is extremely important
for life on Earth. Plants convert visible light to energy via photo-
synthesis by their chloroplasts. Visible light also constitutes the
range of wavelengths that mammalian eyes can detect.
Electromagnetic radiation of longer wavelengths is found
throughout the universe and is detectable on Earth from all
directions. Radiofrequency energies are used extensively on
Earth for communications and other purposes such as radar
and microwave heating.
Particulate Radiation
In the several known atomic and subatomic particle species,
the fundamental particles are classed broadly as photons,
leptons, and hadrons (Table 23.3) [5]. A photon comprises a
single quantum of energy; X and gamma rays are short-wave-
length forms of photon or electromagnetic radiation. As noted
previously, gamma rays originate from nuclear interactions,
whereas X rays originate from electron or charged particle col-
lisions. Photons move at the speed of light (c), are electrically
neutral and have no mass, but do have momentum. Leptons
consist of three families of particles and their antiparticles,
including the electron and electron neutrino (e, e, e, and e);

Table 23.3. Classification and occurrences of fundamental [particle] elements relevant to space radiation.
Class Charge Rest energy (MeV) Lifetime Typical reaction Quality factor Occurrence
Photons
X-rays 0 0 stable e + e+ 1 Van Allen belts, solar radiation, electro
5 MeV rays 0 0 stable H2O+ H+OH 0.5 magnetic cascade (pair production, Brems
strahlung), scattered photons (Compton and
photoelectric effect), annihilation photons
Leptons
Electron/positron +/e0 0.511 stable e +H2O H2O 1.0 Van Allen belts, GCR, solar particle events,
induced radioactivity, primary and
secondary beams, forward shielding
Positive/negative +/e0 105.66 2.2.106 s + e+ + e + 1.0 GCR, radiation belts, atmosphere
muon
Hadrons
Baryons
Proton +e0 938.28 Stable p n + e+ + e 2.010.0 Van Allen belts, GCR, solar particle events,
primary and secondary (-ray) beams,
radiation therapy
Neutron 0 939.57 925 s n + 16O 4 He 2.010.0 Van Allen Belts, solar radiation, atmosphere,
shielding leakage, radiation therapy
Mesons
Positive/ +/e0 139.57 2.6 108 s GCR + N, O 1.0 Atmosphere, secondary beams
negative pion
Atmospheric n,
,
HZE
Z > 2 elements Z.e0 A931.5 stable Fe + DNA DSB
56
>10.0 GCR, solar radiation
With elementary charge e0 = 1.6021019C and the atomic mass number A.
Abbreviations: GCR, galactic cosmic radiation; DSB, double-stranded [DNA] break.
Source: Modified from ICRP 28, 1978.
23. Radiation Disorders
the muon and muon neutrino (, , , and ); and the tau Pions
and tau neutrino (, , , and ). Hadrons are particles that
can interact with each other by strong (nuclear) interaction or,
at longer distances, through the electromagnetic interaction;
two examples include the scattering of protons in traversing
matter and energy loss by ionization. Weak interactions can
also affect unstable hadrons, causing various relatively slow
decay processes such as the beta-decay of radioactive nuclei.
Hadrons can be divided into two subgroups, the baryons and
the mesons. Baryons such as neutrons, protons, and hyperons
are particles with a half spin and a rest mass equal to or greater
than the proton. Mesons are a rather large group consisting
of eight elements that are distinguished on the basis of their
composition of quarks. Mesons consist of strongly interact-
ing particles, e.g. pions, which have integral spin; particles
of dosimetric significance have rest masses lower than that
of protons.
The following sections focus on particle species with bio-
logical effects and their dosimetric significance associated
with human spaceflight exposures.
Photons
The energy of a photon is related to its wavelength as follows:
E = (hc) / l, where h = Plancks constant
= 6.6 107 joule seconds
For example, X-ray photons have energy of 1 keV, and gamma
rays have energy of 1 MeV. Photons can interact only through
electromagnetic interaction. In interactions with matter, the
energy of the photon is transferred by collision, usually with
an orbital electron in an atom of the absorbing medium. Photons
are lightly ionizing and highly penetrating and leave no per-
sisting radioactivity in the irradiated material.
Protons
The proton is the nucleus of a hydrogen (H) atom and carries a
charge of 1 unit. The mass of a proton is 1,825 times that of an
electron. The ionizing track of a proton is straight, as they are
not deflected by the less-massive electrons with which they
interact, but their direction can be radically altered by occa-
sional interaction with atomic nuclei. The ionization density
of protons, for equal energies, is somewhere between that of
electrons and that of alpha particles. Photons typically penetrate
to several centimeters in air and to tens of micrometers in
aluminum at energies in the MeV range [6].
Neutrons
Neutrons are of similar mass to protons, but neutrons have no
charge (and thus no electromagnetic interaction) and consequently
are difficult to stop. Neutrons are classified according to their
energy as thermal (< 1 eV), intermediate, or fast (> 100 keV).
Neutrons in equilibrium with the environment are called
thermal neutrons.
479
The most important mesons in dosimetry are the pions. These
key hadrons are produced copiously in high-energy interactions.
Depending on the medium, pions can decay into muons (e.g.,
in air and in a vacuum) or simply come to rest (while interacting
in condensed matter).
Beta Particles: Electrons and Positrons
Beta particles are electrons and their antiparticles, the positrons.
With their small size and charge, beta particles penetrate
matter more easily than do alpha particles, but they are more
easily deflected. Their high velocity (normally approaching
that of light) means they are lightly ionizing. Incoming
electrons approaching a target atom can interact with either
the orbital electrons or the atomic nucleus. They can directly
collide with or exert their electrical force on orbital electrons
(usually displacing them from the orbit), lose energy, and
undergo a change in their direction of flight. Interactions
with the atomic nucleus are possible when the electron is
near the nucleus; slowing of the electron represents a loss of
energy from it, which is produced as X-ray photons. This
X radiation has great penetration in tissue and can produce
biological damage distant from the track of the electron. This
process, in which radiation is emitted by an electron through
its collision with an atomic nucleus (the Bremsstrahlung effect)
is most important with high-speed electrons and absorbers
with high atomic (Z) numbers. Because living tissues consist
of mostly elements of low atomic number (hydrogen [H],
oxygen [O], nitrogen [N], and carbon [C]), this process is not
common in organisms. However, Bremsstrahlung is important
in the space environment, where high-energy electrons collide
and interact with spacecraft structural elements, which could
include materials of higher atomic numbers.
Because of the tortuous nature of the electron track, the actual
penetration of the electron in matter will be less than the total
track length. The distance penetrated is called the range and is
measured as the linear distance of a charged particle from the
point of origin to its extinction as a charged particle. Ranges
in tissue vary from about 6 m for the beta particle emitted
by the 3H radionuclide to about 0.8 cm for the beta particle
emitted by 32P.
Alpha Particles
Alpha particles are helium (He) nuclei with an atomic mass of
4 and a charge of +2. Alpha particles are the product of radio-
active decay of very heavy radionuclides such as radium.
Normally of high energy (in the MeV range), alpha particles
interact strongly with matter and are heavily ionizing. They give up
all their energy in short, straight tracks of exceedingly high ion
density. Their penetrance ranges from a few to several microns
in soft tissue, and they deposit large amounts of energy over the
short distances that they travel. Alpha particles are highly damaging
to living cells, and thus their quality factor (Q) is 20.
480
Heavy Nuclei
So-called heavy nuclei are the nuclei of ordinary atoms of
high atomic number whose electrons have been stripped
away, thereby yielding a heavy, highly charged particle. Inter-
action of these nuclei with any absorbing material produces
absorber nucleus fragments and secondary particles that are
highly damaging to biological systems. In space, the major
source of such high-Z, high-energy (HZE) particles is galactic
cosmic rays, which produce particles of a charge greater than
2 and can penetrate at least 1 mm of aluminum shielding (the
density of which is = 2.6997 grams per cubic centimeter). Iron
is the most important of the HZE particles because of its rela-
tive contribution to the dose from galactic cosmic rays and
because of its high LET value.
Interaction of Radiation with Target Atoms
Incoming (incident) radiation can interact with the elements
of the components of the space vehicle or the crewmembers
body parts in several ways. It can pass through unperturbed; it
can interact with one of the atomic components (nucleus, elec-
tron cloud, or other) so as to destroy the incident radiation, the
target, or both, which usually produces secondary radiation;
or it can interact with atomic components so as to change the
target atoms and lose energy as the first step in a chain reaction
of radiation events. The processes important in energy deposi-
tion can involve three of the four known types of fundamen-
tal interactions: nuclear (strong); weak; electromagnetic; and
gravitational. (The fourth type, gravitational interactions, has
no significant role in ionizing radiation events.)
Nuclear (strong) interactions occur only between hadrons.
The strongest of the fundamental interactions, nuclear interactions
are of extremely short range (1013 cm) and are responsible for
the binding of protons and neutrons in atomic nuclei. Particles
decaying through strong interactions are usually the shortest-
lived, normally decaying in less than 1020 s. Because of the
huge amount of energy used to keep the core stable, nuclear
interactions are an important aspect of the biological effects
from space radiation.
Weak interactions are most important in the decay of particles
that have been produced in strong hadronic interactions.
Decays caused by weak interactions are the slowest of the
three interactions, generally being longer than 1010 s. Weak
interactions do not participate in the various processes resulting
in biological damage.
Electromagnetic interactions are somewhat better under-
stood than either the nuclear or weak interactions. In the first
type of electromagnetic interaction, direct interactions occur
between particles with charge or magnetic moment and are
of long range. The most important of such direct interactions
results from the electromagnetic force between electrostatically
charged particles (the Coulomb force). Sequential electro-
magnetic interactions of a moving charged particle with electrons
and atoms in a medium result in the important process of
J.A. Jones and F. Karouia
ionization and excitation loss, in which the largest part of
the incident energy is transferred to the absorber. The second
type of electromagnetic interaction consists of interactions
in which photons are emitted or absorbed. Decays caused by
electromagnetic interactions are intermediate between those
of strong and weak interactions and are generally on the order
of 1016 s. Details of the interaction of photons with matter are
described below.
Photon Interactions
In the interactions of photons with matter, the energy of the
photons is transferred by collision, usually with orbital electrons
in an atom of the absorbing medium. Of the 12 possible pro-
cesses by which the electromagnetic field of a photon can
interact with matter, the processes most relevant to space
radiation are the photoelectric process, the Compton process,
and the pair-production process.
The photoelectric effect involves the collision of a low-
energy photon with an orbital electron. In the most likely
event, the photon transfers all its energy to the electron and
the photon disappears entirely or is absorbed by the elec-
tron. As the photon gives up its energy to the electron, some
is used to overcome the binding energy of the electron and
release it from the orbit and the remainder is imparted to the
electron as kinetic energy of motion. As outer electrons fill the
vacancy, this energy is released as X-rays. This energy change
is balanced by the emission of a photon. In tissue, this type of
photon emission has a low energy, typically 0.5 kV, and is of
little biological consequence. The process cannot occur with
the electron of a particular orbit if the photon energy is less
than the binding energy of the orbit.
In Compton scattering, in which photons of higher energy
interact with matter, only a portion of the energy of the photon
is absorbed in interacting with orbital electrons, and the pho-
ton is confined, for the most part, to interactions with outer,
loosely bound electrons. Part of the energy of the photon is
given to the electron as kinetic energy, and the lower energy
photon is deflected from its original path. Hence the products
of Compton interactions are a scattered, less energetic photon
of reduced wavelength; a high-speed electron; and an ionized
atom. The ejected electron will travel some distance in matter,
producing ionizations along its track; in the course of this travel,
the photon may undergo additional Compton collisions before
finally expending all of its energy. Thus, photons in this energy
range have their energy distributed through repeated Compton
interactions (chain reaction) over a relatively large volume of
matter and therefore may have significant biological effects.
Photon energy can also be exchanged into matter by pair
production, which differs from the other two processes in that
it occurs exclusively with high-energy photons and in that the
interactions are with the atomic nucleus and do not involve the
ejection of orbital electrons. Photons with energy higher than
1.02 MeV may interact with the electric field of the highly
charged nucleus so that the photons energy is converted to
23. Radiation Disorders
mass. The photon changes into two particles, a positron and an
electron. Photon energy in excess of the threshold value will
be shared as kinetic energy between the two newly formed
particles. If no excess energy is present, then the two particles
recombine (or annihilate each other) and are converted back
to energy. When the threshold energy is exceeded, the posi-
tron-electron pair moves away from the point of formation
and moves through matter while interacting with and ionizing
other atoms in the substance until the excess kinetic energy is
exhausted. In this way, energy is ultimately transferred from
the photon to matter. Finally, the positrons interact with elec-
trons from the target matter to annihilate and produce two
photons, which generate further scattering processes before
they leave the system.
Which of these three ionization events (photoelectric
effect, Compton scattering, or pair production) occurs is a
function of the Z of the target nucleus and the energy of
the incident photon [7]. In general, the photoelectric effect
is dominant for low-energy photons, and pair production is
more likely for high-energy photons. Compton scattering is
the predominant mechanism for intermediate photon ener-
gies of all absorbers [8].
Track Structure
Details regarding track structures remain a subject of intense
research; agreed-upon conventions include the concepts of
tracks having a core and a penumbra (Figure 23.2). Energy
from a heavy ion is deposited along the core of the track,
where the ionization events produced in glancing collisions
are quite dense. The core can be as wide as a few nanometers.
Surrounding the core is a penumbra of delta rays (electrons),
where the density of ionization events is much less than that in
the core but extends for considerable distances. These features
allow even a single heavy ion particle to affect many cells
in an irradiated tissue, which make the biological effects of
Figure 23.2. Track and energy deposition pattern representative of an
HZE particle, such as may be associated with galactic cosmic radiation,
compared with an equivalent dose of ionizing electromagnetic radiation
481
heavy ions different from those of other radiation phenom-
ena. Deterministic models for calculating the probability of
a molecular hit along an HZE track, based on frequency
distributions of the imparted energy, have been developed for
DNA-sized molecules [9].
Neutron Interactions
Interactions of neutrons, given their small and uncharged
nature, depend on chance collisions with atoms in the materials
through which they traverse. Neutrons can penetrate great dis-
tances into matter of all types. Fast neutrons lose their energy
mainly through colliding with atomic nuclei, which results in
ejection of a high-speed proton that is highly ionizing and has
high LET. From the viewpoint of shielding, neutrons can be
slowed most effectively by materials that include many hydro-
gen molecules, because fast neutrons transfer more of their
energy to hydrogen nuclei than to any other nuclei. Water is
an especially effective shield for neutrons [10]. Slow neutrons, in
contrast, interact with matter chiefly through capture. Specifi-
cally, slow neutrons lose half their energy upon collision with
hydrogen, eventually reaching thermal status (i.e., of energy
< 1 eV). Thermal neutrons continue to scatter until they are
captured by a hydrogen nucleus, forming a deuteron.
Natural Sources of Ionizing Radiation
Natural sources of radiation exposures for space crewmembers
can be of terrestrial or space-related origin. Natural terrestrial
exposures include the background radiation that penetrates
from space to the surface of the planet and the radioactive decay
of unstable isotopes present in Earths crust (e.g., uranium, thorium,
radium, and others). These exposures vary geographically and
by altitude. Radon and its radioactive daughter products are
a common source of radiation that can affect health [11,12].
High radon concentrations appear in clusters throughout Earth,
tending to become concentrated in the air in enclosed spaces
(e.g., those of basements in buildings with closed circula-
tion). Although radon is not a significant source of radiation
exposure in Houston, Texas, where U.S. crewmembers train,
radon accounts for more than half the general populations
annual radiation exposure ( 2 mSv/year), with the remainder
coming from cosmic, artificial, and other terrestrial sources.
Radiation exposures are also higher among members of air-
crews in high-altitude flights; the exposure amounts depend
on altitude and routes flown. (Exposures from high-altitude
terrestrial flight are included in the annual dose monitoring
of space crewmembers.) Representative terrestrial radiation
exposures and those associated with space flight are shown
in Table 23.4.
Space radiation sources consist of a variety of particles that
have a wide range of energies and both temporal and spatial
variations. These variations result from complex phenomena
and interactions such as solar particle events and the existence
482 J.A. Jones and F. Karouia

Table 23.4. Typical terrestrial and spaceflightrelated radiation exposures.

Event or limit Radiation dose level
Exposure from a typical chest X ray 0.0001 Sv (0.01 rem)/exposure
Exposure during a typical trans-Atlantic airline flight 0.00012 Sv (0.012 rem)/exposure
Skin dose aboard the ISS during solar maximum 0.0005 Sv (0.050 rem)/day
Skin dose aboard the ISS during solar mininum 0.001 Sv (0.100 rem)/day
Exposure from living in Houston, Texas (sea level) 0.001 Sv (0.100 rem)/year
Exposure from living in Denver, Colorado 0.002 Sv (0.200 rem)/year
(1,524 m [5,000 ft] above sea level)
Exposure for an average U.S. radiation worker 0.0021 Sv (0.210 rem)/year
Exposure from a mammogram 0.0035 Sv (0.350 rem)/year
Exposure during EVA with excessive South Atlantic 0.0045 Sv (0.450 rem)/event
Anomaly passes
Exposure limit for the U.S. general public 0.005 Sv (0.500 rem)/year
Skin dose to a Space Shuttle crewmember during 0.01 Sv (1.0 rem)/event
the October 1989 SPE (no magnetic storm, no EVA)
Exposure limit for Russian terrestrial radiation workers 0.02 Sv (2.0 rem)/year
Dose estimated during the October 1989 magnetic storm, 0.03 Sv (3.0+ rem)/event
from crew dosimeters aboard Mir
Exposure limit for U.S. terrestrial radiation workers 0.05 Sv (5.0 rem)/year
Exposure limit for U.S. astronaut in any 1-month period 0.25 Sv (25 rem)/month
Skin exposure during an EVA during a radiation 0.4 Sv (40.0 rem)/event
belt enhancement
Annual exposure limit for U.S. astronauts 0.5 Sv (50 rem)/year
Values indicate approximate dose to the blood-forming organs unless otherwise noted.
Abbreviation: ISS, International Space Station; SPE, solar particle event; EVA, extravehicular activity.

of planetary magnetic fields. For practical purposes, the space

radiation environment can be considered in two distinct cat-
egories: LEO and deep space. For missions in LEO, such as
those on the Space Shuttle, Mir, and the International Space
Station (ISS), the two main sources of radiation exposure
are galactic cosmic rays and geomagnetospheric (trapped
belt) radiation, bands of geomagnetically trapped particles
(the Van Allen belts) consisting of mostly protons and elec-
trons. Earths geomagnetic field lines protect the planetary
surface from incident cosmic and solar radiation by deflect-
ing charged particles, but the belts themselves also create a
local hazard for LEO missions. Deep space missions, such as Figure 23.3. The Van Allen radiation belts, showing the distribution
lunar or interplanetary space flights, extend beyond the rela- of trapped protons and electrons along Earths geomagnetic field.
tive protection of the geomagnetic fields; the primary sources
of exposure in deep space missions include galactic cosmic
radiation and potential exposures from solar particle events.
measurements on Explorer III and first reported by Van Allen
Secondary radiation can also be produced when the primary
in 1960. The trapped radiation particles in the ionosphere have
particles interact with the materials of the spacecraft, those of
been used for years to transmit amplitude-modulated and ham
its human occupants, or the constituents of the rarefied upper
radiowaves by reflection over great distances on the planetary
atmosphere in LEO.
surface. The Van Allen belts span two broad regionsthe inner
belt and the outer belt (Figure 23.3). The inner Van Allen belt
The Radiation Environment in Low Earth Orbit begins at an altitude of roughly 3001,200 km (about 1.5 Earth
radii) depending on latitude. The outer belt begins at about
Geomagnetically Trapped (Van Allen Belt) Radiation 10,000 km (about 5.0 Earth radii) and the upper boundary
The trapped radiation belts surrounding Earth were first mea- depends on the activity of the sun; the cap for the main compo-
sured in 1958 by large Geiger counters flown aboard Explorer I, nents is about 55,000 km, but trapped belt effects can be evident
the first U.S. satellite; their existence was confirmed by later at altitudes as high as 75,000 km. The slot region between the
23. Radiation Disorders
belts is thought to be devoid of high-energy trapped particles
and is filled with lower energy protons.
The trapped particles consist mainly of protons and electrons,
but other species (helium, carbon, oxygen) have been observed
as well. The most plausible sources of high-energy protons
and electrons at lower altitudes are the decay of albedo neu-
trons produced by nuclear reactions between galactic cosmic
rays and constituents of Earths atmosphere, particles from the
ionosphere, or solar wind. Neutrons that are freed from the
nucleus of atoms are unstable and decay with a half-life of
10.6 min (rest) into a proton p, an electron e, and an antineu-
trino n :
np+e+n
These protons and electrons are then trapped by Earths magnetic
field and oscillate back and forth along the magnetic lines of
force (Figure 23.4). In each zone, the particles spiral around
the geomagnetic field lines, moving towards and away from
the magnetic poles, i.e., bouncing between mirror points in the
Northern and Southern hemispheres. At the same time, their
charge leads the electrons to drift eastward and the protons
and heavy ions to drift westward.
Interactions of the inner belt with Earths upper atmosphere
produce colorful aurorae that can be observed in high north-
ern or southern latitudes where the horns of the geomagneto-
sphere converge. Diffuse luminous forms over large areas of
the sky have been observed since ancient times in northern
regions, between 15 and 30 from the magnetic pole; astro-
nauts in LEO have also witnessed spectacular auroral phe-
nomena. Auroral emissions result when low-energy electrons
precipitate out of the inner radiation zone and, through colli-
sions, excite and ionize atmospheric gases. Solar flares and
geomagnetic storms can influence the occurrence and inten-
sity of aurorae.
Geomagnetic storms arising from solar events can cause
surges in the trapped belts, with the bowshock from the
solar radiation distorting the magnetosphere; the latitude of
the geomagnetic cut-off changes with enhancement of the
electron belts associated with these storms. Thus the geo-
magnetosphere is now known to be highly dynamic. Unfor-
Figure 23.4. The motion of a trapped charged particle along
geomagnetic field lines [18]. Used with permission by IEEE
483
tunately, current means of estimating radiation doses from
trapped radiation rely on static models of the geomagneto-
sphere; because the geomagnetosphere is now known to be
highly dynamic, new models for predicting doses are needed
to account for the frequent changes in geomagnetic field par-
ticle density.
Both the altitude and the direction of orbital flight with
respect to geomagnetic field lines affect the radiation
exposure to vehicles in LEO. An east-west anisotropy of
trapped particle fluxes results from particle motion along
magnetic field lines. At the bottom of a helical path of a
trapped proton, the proton is traveling eastward; at the top
of the helix, it is traveling westward. Thus on a spacecraft
traveling east, its trailing edge is struck by particles traveling
east and its leading edge is struck by particles traveling west.
Particles traveling west are emerging from a region where
the atmospheric density is greater (lower altitude); the inter-
action of westward particles with the atmosphere results in a
reduction in their flux. The differences in the flux of particles
striking the leading vs trailing edges of a spacecraft can be
considerable; for example, the doses to the Long-Duration
Exposure Facility, an experimental platform that remained in
orbit from April 1984 through January 1990, were 2.5 times
higher on the trailing edge than those on the leading edge
[13].
The bulk of radiation exposure from the Van Allen belts
during activities in LEO (e.g., those aboard the Space Shuttle)
occurs as the vehicle passes through a region called the South
Atlantic anomaly. This region represents a discontinuity in
geomagnetic field lines resulting from the roughly 500-km
offset between Earths geomagnetic center and its geographic
center (center of mass). This offset shifts the magnetic axis
from the spin axis by 11, and the subsequent offset of the
magnetic field results in trapped particles dipping to lower
altitudes relative to the Earth surface. At this mid-latitude
location, which extends from about 0 to 60 west longitude
(Figure 23.5) [14], the intensity of trapped protons of energies
higher than 30 MeV at 161322 km altitude is equivalent to
the intensity found at 1,287 km altitude elsewhere. Measure-
ments made aboard the Space Shuttle indicate that the loca-
tion of the South Atlantic Anomaly is moving westward at
300 km, or about 0.32, per year and northward drift by 0.16
degrees per year [15].
Spacecraft in LEO make anywhere from 5 to 7 passes
through the South Atlantic anomaly during a 24-h period,
with each pass lasting 1520 min. By far the greatest part
of the radiation dose received by crewmembers on LEO
missions occurs during passage through this region, even
though the total time spent there is only about 10% of total
orbital flight time [16] (Figure 23.6). The trajectories of
low-altitude Shuttle flights generally do not pass through
the zone of maximal intensity within the anomaly; high alti-
tude flights do, but they usually spend less overall time in
the anomaly [17].
484
Figure 23.5. The South Atlantic anomaly (SAA) is shown, along
with the track of an orbiting spacecraft. The actual shape and area
vary with altitude. Passage through the SAA accounts for a large
fraction of the total radiation exposure in low earth orbit
Figure 23.6. Three dimensional graphic showing radiation absorbed
dose as a function of position for 28.5 shuttle flight (STS-31). The
effect of transit through the South Atlantic anomaly is clearly seen
Galactic Cosmic Rays
In 1912, Hess was the first to identify galactic cosmic rays
(GCR). The cosmic rays are present isotropically in space
and provide a continuous, low flux component of the radia-
tion environment. In spite of their common name, GCR are
not rays per se, but high-energy charged particles moving at
near-light speed with large kinetic energies. GCR consists of
ions of all elements of the periodic table and are composed of
9798% baryons and 23% electrons. The baryons consist of
83% protons, 13% alphas (4He ions), and 1% heavier particles
with energies extending to several GeV (1020 eV) [18,16].).
Figure 23.7 shows the abundance and the distribution in
J.A. Jones and F. Karouia
Figure 23.7. Relative abundance and ionizing power of some of the
more biologically important HZE nuclei comprising galactic cosmic
radiation. As the atomic number increases, it is seen that the rela-
tive abundance decreases considerably as compared to hydrogen (H)
and helium (He). However, the relative ionizing power increases by
several orders of magnitude, giving iron (Fe) a composite biological
effect approaching that of the much more abundant H
energy of several important HZE nuclei. GCR originates from
sources outside the solar system, most likely associated with
supernovae remnants and galactic nuclear events, and consists
of charged particles ranging in energy from around 10 MeV to
10 GeV per nucleon.
Most of the dose from GCR can be accounted for by the
contributions from hydrogen, helium, carbon, neon, oxygen,
silicon, and iron. Iron is usually considered the most impor-
tant of the heavier ions for biological effects because of its
abundance and high LET. Iron ions are one thousandth as
abundant as protons but have equal dose contribution owing
to the Z2 dependence. The HZE particles have very high ener-
gies and charges, sufficient to penetrate many centimeters of
tissue or other materials to contribute to significant biologi-
cal or electronic damage. HZE particles are characterized by
marked spatial and temporal concentrations of energy deposi-
tion around and along their tracks, thereby making the term
mean absorbed dose inadequate to describe their biological
effects [19].
The incoming GCR in our solar system is modulated by the
suns magnetic field and varies with the solar cycle. The inter-
planetary (solar) magnetic field strength increases as solar
activity increases and typically extends radially outward from
the sun to a distance in excess of 10.5 billion kilometers (6.5
billion miles) or 70 times the mean distance between Earth
and the sun. GCR entering the solar system are deflected by
the more intense interplanetary magnetic fields, an effect that
reduces the GCR intensities in the inner heliosphere, where
the terrestrial planets like Earth and Mars orbit. The greatest
effects are observed for ions of lowest energies. The difference
between the extremes of the solar minimum and maximum
fluence levels is approximately a factor 2 to 10 depending
on the ion energy. For example, intensities of ions with ener-
23. Radiation Disorders
gies < 100 MeV/nucleon can vary by as much as a factor of
10, but those with energies > 10 GeV/nucleon typically
vary less than 20%. In the inner heliosphere, GCR fluence
is at its peak level during solar minimum and at its lowest
level during solar maximum. The length of the GCR modula-
tion cycle is now considered by many to be 22 years and not
11 years as previously thought [18]. The solar cycle is driven
by changes in the solar dipole movement, which reverses
every 1011 years. The orientation of the solar dipole has a
22-year cycle but results in a bimodal modulation of the GCR
(every 11 years).
GCR are also deflected by Earths magnetic field, which
reduces the intensity of galactic cosmic radiation inside the
geomagnetosphere. The galactic cosmic radiation received on
Earth varies substantially as a function of the level of solar
activity and the location on Earths surface, with less protec-
tion being provided by the geomagnetosphere at the poles
and higher altitudes. Figure 23.8 shows the galactic radia-
tion received at varying altitudes up to 36,750 m (120,000 ft)
during periods of solar maximum and minimum. This figure
illustrates the modulating effect of the suns magnetic field
on GCR dose. The two curves are based on estimated whole-
body dose to an unshielded human at about 40 degrees north
latitude. Measurements obtained by deep space probes show
similar intensity, suggesting that the GCR component would
be similar at other planets, such as Mars.
The rigidity threshold for each point inside the magneto-
sphere, below which cosmic rays cannot penetrate, is called
the geomagnetic cut-off. The value is lower for high inclination
(high latitude) than for low inclination (low latitude) orbits,
which means that space crews are protected more by the geo-
magnetosphere at the low inclination orbits [16].
Figure 23.8. Measured and calculated radiation dose rate vs altitude
for solar minimum and maximum phases
485
Solar Flares and Solar Particle Events
Solar flares are a major source of radiation concern, possi-
bly the most potent of the radiation hazards encountered in
space flight beyond the geomagnetosphere. As noted above,
the sun follows approximately an 11-year cycle of variance of
emission (the solar cycle) as part of an overall 22-year cycle
of solar magnetic activity. Studies of recent solar cycles have
determined that the length of the solar cycle over the past
40 years has ranged from 9 to 13 years (mean, 11.5 years).
For modeling purposes and for defining the environment for
spacecraft missions, the solar cycle can be divided into a 7-
year maximum phase of high levels of activity and a relatively
quiet 4-year minimum phase. The charged particle environ-
ment in near-Earth regions is dominated by the activity of the
sun, which acts as both a source and a modulator. When solar
activity approaches maximum, spectacular disturbances can
occur on the solar surface.
A solar flare is actually a solar magnetic storm. These
storms build up over several hours and can last for several
days. The most dramatic and energetic solar particle event
(SPE) is called a coronal mass ejection (CME), which occurs
in the layer of the sun outside of the photosphere, known as
the chromosphere. CMEs are observed as large bubbles of gas
and magnetic field, releasing large quantities of plasma into
interplanetary space. CMEs lead to large increases in solar
wind velocity. The shock wave of the plasma release is asso-
ciated with particle acceleration and magnetic storms at the
Earth. CMEs are poorly associated with flares but, in very
large CMEs, both CMEs and flares occur together [20].
Although solar flares cannot be forecast, the physical evi-
dence for an impending flare can be observed on the solar
disc. As the flare builds, an increase in visible light first
takes place, accompanied by disturbances in Earths iono-
sphere, which are probably due to solar X rays. The princi-
pal problem, though, arises from the high-energy particles
(mostly protons) that are produced during the flare, which
may generate an SPE. The energy of these protons can range
from about 10 MeV500 MeV per nucleon. The flux can be
quite high, resulting in a potentially lethal dose for unpro-
tected space crews outside LEO. The size of an SPE can vary
by many orders of magnitude. The location of an SPE flare
on the sun relative to the position of Earth or space vehi-
cle is one factor that affects the magnitude of the exposure.
Another factor is association of an SPE with a CME that will
affect the particle distribution zone and thus the likelihood of
interaction with the space vehicle trajectory. The mean rise
time of the six largest SPEs in solar cycle 21 (19711987)
was 40 h for particle energies 10 MeV; the minimum rise
time was 10.5 h. One of the largest SPEs ever measured,
that of August 4, 1972, had a time-integrated intensity of
5 109 particles/cm2 with energies 30 MeV and 1.1 1010
particles/cm2 with energies 10 MeV.
SPEs can affect orbiting satellites, including telecommuni-
cations, navigation, and military assets, as well as the commu-
nications network for crew operations in LEO. Disruption of
486
satellite services as well as hardware failures can be expected
in extreme cases.
Energy spectra of SPE can also vary considerably. In
addition to protons and alpha particles (helium nuclei), ions
with higher atomic numbers have been observed during SPEs.
Their spectra are relatively soft and their intensities significantly
lower. Some SPEs have protons with energies high enough
to penetrate to the ground where they (or their secondar-
ies) can be measured. The largest event ever observed by
ground measurements took place on February 23, 1956, in
which levels measured were 3600% above background [21].
The anomalously large solar flare of August 1972 occurred
within the initial launch window considerations of Apollo
16 and 17. Calculations indicate that astronauts exposed
to such a flare during flight might receive a depth dose-
equivalent of around 50 rem (0.5 Sv)a dose sufficiently
close to clinical thresholds for acute radiation exposures to
raise major concern.
On October 19, 1989, a solar event occurred at the end of
Space Shuttle mission STS-34. Monitoring equipment aboard
the shuttle confirmed an enhanced radiation environment and
led to the discovery of a secondary belt formed by effects on
Earths geomagnetosphere. Dose calculation from models in
use at the time demonstrated the shortcomings inherent in
these older tools; efforts are underway to improve the accu-
racy of models used for dose projection calculations. Esti-
mates of organ doses from these events conclude that either
could have been life-threatening to crews in interplanetary
space (i.e., outside of the protective geomagnetic fields [22].
Four anomalously large events have taken place during the last
three solar cycles that could have produced lethal exposures
to crews in interplanetary space. In the worst-case scenario,
doses as high as 10 Gy could have been received over a few
days, which would result in death in a short interval [16].
These events underscore the need for careful monitoring of
the space radiation environment during all aspects of crewed
operations in LEO and beyond, and demonstrate the need to
account for the influence of solar activity on mission plan-
ning. Exploration-class missions such as those to Mars will
require that the spacecraft have monitoring equipment on
board that can determine radiation exposure risks from solar
activity autonomously from Earth because particles from the
sun will travel in spiral trajectories along solar magnetic field
lines and may impact the spacecraft without affecting Earth
or vice versa. The detection and warning system should be
robust enough to provide adequate warning to the crew for
their protection and safety, allowing them to take refuge in a
radiation-hardened storm shelter.
The Radiation Environment Outside Low
Earth Orbit
For crewed missions to the Moon, Mars, and Earth-moon and
Earth-sun Lagrangian points, all beyond the protection of the
geomagnetosphere, the major radiation component is exposure to
J.A. Jones and F. Karouia
the highly damaging GCR. Additional radiation beyond the
normal background dose could be received during SPEs, which
pose a greater threat further away from LEO. For the first time
in the U.S. human space program, crewmembers on an explora-
tion-class mission will be approaching a significant portion of
their established career exposure limits during a single mission.
Factors to consider when evaluating radiation exposure on
other planetary surfaces during exploration-class missions
include secondary shielding resulting from the planets mass,
atmosphere, and geomagnetosphere as well as the incident
radiations interaction with planetary regolith. In the case of
the moons of the giants Jupiter and Saturn, the trapped par-
ticle radiation field produced by the planet itself can be even
more important than the local geomagnetosphere around the
individual moon.
Secondary Radiation
One of the principal problems in developing effective shield-
ing for the occupants of space vehicles concerns secondary
radiation. Whenever primary particles strike a spacecrafts
shielding and structural material, secondary radiation is pro-
duced. Incident electrons and positrons are stopped by the
vehicle wall, which subsequently emits secondary gamma
rays (Bremsstrahlung). Protons and heavy ions may hit a tar-
get in the wall or within the cabin, or they may pass through
the structures. Wherever a target is hit, these particles pro-
duce characteristic showers of secondary particles. When a
primary particle with an energy of 300 meV or more hits a
nucleus of target material, secondary particles and electro-
magnetic radiation are generated in great variety. Second-
ary radiation, most importantly neutrons, is also produced
when the primary incident radiation strikes components of
the human body directly. The secondaries produced from
these interactions may have the greater contribution to the
total dose owing to their significant biological effect, where
Q ranges from 2 to 20.
Neutrons
Neutrons, inherently unstable entities with a half-life of roughly
11 min, arise locally from interactions of charged particles
with matter within the spacecraft or Earths atmosphere. The
concern for crewed space flight is high-energy GCR interacting
with spacecraft structural elements and producing secondary
neutrons. As described above, neutrons are uncharged particles
that affect nuclei by direct collision, with significant bio-
medical implications. Neutrons can penetrate deeply into
matter, including biological tissues. Fast (high-energy) neutrons
lose energy mainly via collisions, whereas slow (low energy)
neutrons lose energy mainly via capture.
In early human space flight programs, neutrons were not
considered a significant component of the overall dose to
crews. The passive detectors flown during previous crewed
missions were relatively insensitive to high-energy neutrons,
23. Radiation Disorders
providing data only on low-LET charged particles. More
recent calculations and occasional measurements onboard
the Space Shuttle and Mir indicate that the contribution
of secondary neutrons could be significant and should be
included in assessing the radiation risk to astronauts. Badh-
war and others [2326] measured neutrons on several Space
Shuttle and Mir missions with the use of metal foils, nuclear
emulsions, thermal means, Bonner spheres, and bubble
detectors.
Estimates by Reitz and others of fast neutrons on the Space
Shuttle and Mir [2729] have since been confirmed by mea-
surements from Japanese and European investigators using
a variety of different instruments and form the basis for the
belief that neutrons contribute 1540% of the dose equivalent
from charged particles. Because standard thermoluminescent
detectors are inefficient for detecting high-energy neutrons,
up to half of the dose may be unmeasured, making the true
neutron contribution 3085%. Tissue-equivalent proportion-
ate counters efficiently measure low-energy neutrons. High-
energy (>1 MeV) neutrons account for most of the H, with
almost 50% coming from > 10 MeV neutrons. Neutron H
increases by a factor of 2 as shielding increases from 20 to
40 g/cm2 aluminum equivalent. Notably, the 1- to 14-MeV
neutron-to-charged-particle ratio in the least shielded area
of Mir at the height of the last solar maximum, occurring at
the end of the 1990s, was 58%, whereas at solar minimum
it varied from 14% to 60%. These findings again reflect the
influence of increased GCR associated with solar minimum
on overall radiation fluence [30].
New evidence regarding the relative contribution of sec-
ondary neutrons to astronaut equivalent dose rates has led
to the development of new detectors and dosimetry meth-
ods to support ISS operations. Crew dosimeters sensitive to
secondary neutrons in the 0.1 to 200 MeV energy range are
being provided; CR-39 plastic track nuclear detectors are
currently the best candidate for this task. Radiation trans-
port models for estimating organ doses from secondary
neutrons in complex spacecraft are also being developed
and validated.
Nonionizing Radiation
The entire electromagnetic spectrum emanates from the sun
and is minimally filtered when encountering objects in LEO.
Ultraviolet, other low-energy-spectra visible light, and infra-
red will strike the vehicle and crew for at least 45 min of each
90-min orbit. Heating from infrared requires that cooling
systems be included in the vehicle and in the extravehicular
activity (EVA) suits. Crewmembers can be exposed to ultra-
violet light during EVAs through the visor assembly of the
helmet or from solar rays penetrating the vehicle windows.
A 1997 study [31] in which dosimeters were used to quantify
the exposure of a Mir crew to ultraviolet light showed that
the dose to the crewmembers was negligibleexcept when
they passed by one of the windows, as the dosimeter behind
487
the quartz window received significant ultraviolet doses, pre-
dominantly from UVB and C.
Artificial Sources of Radiation in Space
Low-level ionizing radiation may arise from medical, inves-
tigational, and operational sources. Astronauts are required to
undergo certain radiographic procedures to rule out disease
states as part of the routine monitoring of their health (e.g.,
mammography, dental bite wing X rays). Crewmembers may
also undergo radiographic evaluation for medical conditions
that arise during training. The doses associated with these
procedures are tracked and maintained as part of the crew-
members medical records.
Astronauts may also participate in science experiments that
involve exposure to radioactive agents. Strict flight rules
dictate that such agents be contained and shielded to the extent
required to minimize possible exposures. Although some in-
flight studies of animal and plant physiology may involve use
of radioactive tracers, studies of human physiology mostly use
stable (nonemitting) isotopes.
Several on-board instruments can contain small amounts
of radiaoactive materials; examples include smoke detectors
(61.2 Ci of 241Am) and hydrazine monitors (10 mCi of 63Ni).
The Soyuz descent module uses a gamma ray altimeter with
8 Ci of 137Cesium for calculating altitudes and triggering the
braking rockets during the final landing phase. Exposure to crew
is minimal, at 0.001 Gy (0.1 rad)/day at the source, 0.0005 Gy
(0.05 rad)/day at 1 m from the source, and < 0.0001 Gy
(0.01 rad)/day at 2 m from the source; the average extra dose to
Soyuz crewmembers is about 0.0005 Gy (0.05 rad)/day when
they occupy that vehicle. Despite this low dose rate, crews are
advised not to sleep in the Soyuz vehicle during normal opera-
tions, when the ISS is docked to the Soyuz. Finally, because
astronauts actively participate in high-performance aircraft
flights during their training, the time spent above 7,620 meters
(25,000 ft) is also tracked.
At present no crewed space vehicles use nuclear power
for propulsion or for power generation. However, future
exploration-class missions may require a nuclear power
source for propulsion as well as for generating power on
a planetary surface. The inclusion of nuclear power aboard
spacecraft will require meticulous attention to shielding,
crew dosimetry, and mission planning to maintain and
operate such a system, as is the case for nuclear naval ves-
sels. Although explosions from nuclear weapons at orbital
altitudes are thought to be unlikely in the post Cold War
era, this possibility has driven the inclusion of high-rate
dosimeters aboard spacecraft since the early years of
crewed space flights.
Artificial sources of nonionizing radiation, e.g., from
radiowaves and microwaves, are also a concern in current
operations. Spacecraft use much of the electromagnetic
radiation spectrum for communication, spacecraft navigation,
488
reconnaissance, and scientific experimentation. The Space
Shuttle and ISS use ultrahigh frequency systems for
communications between vehicles or between EVA crew-
members and the vehicle. The main operating frequency
of such systems is in the vicinity of 400 MHz, and their
maximum power output is 6.76 W. The wireless instrumenta-
tion system transmits at 915 MHz, with a peak output of
0.316 W (25 dBm). S-band and Ku-band antennae are used
in Space Shuttle and ISS communications by means of the
Tracking Data and Relay Satellites network. The S-band
antennae typically broadcast and receive in the range of
2,2002,300 MHz, with peak power output of 40 W and
power density of 10 mW/cm2; the Ku-band transmits and
receives in the range from 15.25 to 17.25 GHz, with a power
output of 20 W and power density of 10 mW/cm2 (240 V/
m). The possible consequences of exposure to these forms
of nonionizing radiation are unknown at this time owing to
the scarcity of high-quality dosimetry and the complexity
of isolating and identifying environmental factors.
Sources of artificial ultraviolet radiation that may be present
aboard spacecraft include antibacterial lamps and forms of
radiation treatments that might be used to compensate for
vitamin D3 deficiencies. The chief concern in ensuring the
safe use of ultraviolet radiation involves selecting radiation of
spectral energy that maximizes the putative therapeutic effect
while minimizing the risk of dangerous side effects. Finally,
laser light sources are flown on space vehicles as components
of scientific instruments and range-finding equipment. The
relative danger of these radiation sources is a function of
the power and energy densities of the laser source as well as
the wavelength and frequency of the laser light, because dif-
ferent human tissues absorb various wavelengths to different
extents. The main hazard from the kinds of lower-level laser
radiation likely to be used onboard a space vehicle is to ocular
structures.
Space Weather
Space weather describes the processes, influences, and effects
of the space radiation environment and is largely driven by
solar activity. Space weather is every bit as dynamic and
potentially violent as its atmospheric analog and is on a much
more massive scale of distance and energy. Understanding the
suns inherent activity as well as its influence on GCR and
Earths trapped radiation belts is crucial for developing use-
ful methods of space weather forecasting and prediction. The
need to do so pertains to both human space flight and to the
sensitive electronics aboard unmanned spacecraft.
NASA flight rules define a geomagnetic storm as a change
from normal levels in the horizontal component of the magnetic
field at Earths surface, as measured by magnetometers at
Boulder, Colorado. Space weather monitoring personnel sta-
tioned at Mission Control during crewed space flights notify
the Crew Surgeon and Flight Director if defined thresholds for
J.A. Jones and F. Karouia
major X-ray flares, SPE, or geomagnetic storms are exceeded.
Actions to be taken in the event of the ensuing radiation alert
or contingency condition might include terminating or
replanning an EVA, changing the flight orientation of the
vehicle or platform, or, in a major event, directing the crew to
take shelter in the most heavily shielded structural elements.
The alert is terminated when three consecutive readings show
a downward trend [18].
Biological Effects of Ionizing Radiation
Most of the current knowledge of the biological effects of
radiation on humans has been derived from four sources
occupational exposures in industry and research settings,
exposures from the detonation of nuclear weapons, exposures
from use of radiation as medical treatment, and studies of ani-
mal models. Both the Russian and U.S. space programs have
undertaken long-term assessment of space crewmembers for
evidence of stochastic and deterministic effects of space radia-
tion, but relatively few findings have been obtained and the
data are far from mature. The epidemiologic data from the
first three of these sources have served as a starting point for
assessing the risks associated with of space flightacquired
radiation exposure.
Occupational Exposures
Both standard occupational exposures and mishaps have
resulted in a wide range of doses and dose rates. During
the early part of the 20th century, radium dial workers, who
tipped brushes on their tongues and ingested 226Ra to a dose
equivalent of 0.5 rem (0.005 Sv) per week, showed increased
incidence of bone cancer. Uranium miners were shown to
have increased mortality from pulmonary neoplasms and
fibrosis from chronic inhalation of radon and radon daughter
molecules [32]. The excess relative risk of leukemia per
Sievert of exposure in U.S. and U.K. nuclear workers averages
1.7 (95% confidence interval [CI], 0.59.0) as compared with
6.2 (95% CI, 2.713.8) for male atomic-bomb survivors over
the age of 20 [33]. Nuclear power accidents, such as those
at JCO Tokaimura, Japan in September 1999 and Chernobyl,
Ukraine in 1986 have resulted in population exposures that
are being carefully followed. One study has concluded, for
example, that the radioactive iodine generated in the Chernobyl
accident has resulted in an increase in thyroid cancer among
children in neighboring Belarus [34]. Major epidemiologic
studies of large numbers of people exposed to radiation from
various sources are ongoing and provide data that may be
extrapolated to the space flight environment. Typically, how-
ever, such exposures involve radiation of a single type and
energy spectrum; the space flight environment, by contrast,
involves multiple types of radiation and a wide range of
energy spectra.
23. Radiation Disorders
Nuclear Weapons
Although the use of atomic weapons constitutes a grim war-
time event, the information available should be used to benefit
those in radiation occupations or with inadvertent exposures.
The Radiation Effects Research Foundation (formerly the
Atomic Bomb Casualty Commission) is a binational organi-
zation formed to evaluate the medical effects of radiation on
humans and on diseases affected by radiation. Laboratories in
Hiroshima and Nagasaki are dedicated to studying the acute
and chronic effects of the atomic detonations in those cities.
Epidemiologic tracking of the survivors has allowed the rela-
tionship between estimated radiation dose and development of
leukemias and solid tumors to be studied. The acute, annual, and
career radiation exposure limits recommended by organizations
such as the International Commission on Radiological Protection
(ICRP) and the National Council for Radiation Protection and
Measurement (NCRP) are largely based on findings from this
cohort of acutely exposed individuals. Weapon-related expo-
sures represent large single-point events and thus do not cor-
relate directly with the more protracted exposures encountered
in space flight. However, scaling factors and other corrective
methods can be applied to make meaningful inferences with
regard to spaceflight risk.
The characteristic spectrum of symptoms after acute irradi-
ation has been ascertained largely through interviewing more
than 100,000 atomic-bomb survivors. The highly subjective
nature of survivor recollections may have biased the recorded
data regarding early effects. Nevertheless, among the acute
radiation symptoms recalled by survivors, epilation (hair loss)
is regarded as the most reliably reported as compared with
other symptoms such as vomiting, bleeding from the gums,
diarrhea, and purpura. In general, acute radiation symptoms
do not appear at low-dose radiation exposures, giving support
to a threshold dose concept (i.e., that of deterministic effects);
that is, below a certain radiation dose, no acute symptoms
occur. This is in contrast to the linear dose-response relation-
ship demonstrated by malignant diseases, one of the most
well-established late effects of radiation exposure.
By examining the fate of family members who were in
the same houses during atomic bomb explosions, it has been
estimated that doses of 2.73.1 Gy (270310 rad) to the bone
marrow caused death within 2 months in some 50% of cases.
Estimates of the LD50/60 (death of 50% of the exposed population
within 60 days) generated by the United Nations Scientific
Committee from information on atomic bomb survivors, acci-
dental radiation exposure cases, and radiation therapy studies
suggest that the LD50/60 is 2.53.2 Gy (250320 rad) to the bone
marrow when little medical assistance is available, and about
5 Gy (500 rad) when extensive medical care is provided. Animal
studies have shown that administering various growth factors to
stimulate surviving blood-forming stem cells in bone marrow
facilitates more rapid recovery from radiation injury, and the
lives of 100% of the exposed population can be saved after a
whole-body dose of up to about 10 Gy (1000 rad).
489
Exposure to radiation in utero causes developmental impair-
ment. In addition to noted reductions in head growth, height,
and body weight, radiation causes a dose-dependent decline in
intelligence quotient of at least 5 points, with the most severe
effects noted if the fetuses were irradiated between 8 and 15
weeks menstrual age. Otake and Schull [35] reported mental
retardation rates of 4050% per Gy (100 rad) among fetuses
irradiated during this period, although they could not exclude
a threshold in the 0.1- to 0.2-Gy (10- to 20-rad) range. The
ICRP has taken the position that irradiation during this partic-
ularly sensitive period causes a linear reduction in intelligence
quotient of 30 points per Gy [36].
Radiation-induced (excess) cancer risks for crewed space
activities can be estimated based in part on results of follow-
up studies of atomic bomb survivors [37]. Projected risks
based on the Japanese data are appropriate for the fraction of
total risk attributable to low-LET geomagnetically trapped
protons because the Japanese experience primarily involved
low-LET radiation exposure. An excess risk of leukemia was
one of the earliest delayed effects of radiation exposure seen
in the victims of the atomic bombs dropped on Hiroshima and
Nagasaki in August 1945. Now, more than 50 years after these
events, this excess is widely seen as the most apparent long-
term effect of radiation. As of 1990, 176 of the 50,113 survi-
vors in the Life Span Study who had had significant exposures
(> 0.005 Gy [0.5 rad]) had died of leukemia, and about 90 of
these deaths were attributable to radiation exposure. This
excess was especially apparent because much of it occurred
during the first 1015 years after the exposures. Unlike the
dose-response curves for other types of cancer, the leukemia
dose-response curve seems to be nonlinear, with low doses
being less effective than would be predicted by a simple linear
dose response. With regard to other types of cancer, 4,687
people in the Life Span study had died of nonleukemic forms
of cancer by 1990, which represents an excess of 381 deaths
as compared with an estimated of 4,306 deaths in a popula-
tion that had not been exposed [38]. A comparison of excess
deaths in the Life Span Study population between 1950 and
1990 according to radiation dose is shown in Table 23.5; the
numbers of deaths sorted by type of cancer are shown in
Table 23.6 [38].
Medical Exposures
Radiation has been used for diagnostic and therapeutic purposes
for many years, mostly in the form of 60Cobalt, linear accelerators,
and injected and ingested radionuclides. Some of these
therapeutic modalities turned out to be more hazardous than
efficacious. As an example, patients with ankylosing spon-
dylitis treated with external beam x rays were found to be at
slightly increased risk (relative risk, 1.51.8) of developing
lung cancer or other solid tumors between 8 and 20 years after
therapy; surprisingly, the relative risk declined thereafter.
Women given pelvic irradiation for metropathia hemorrhagica
showed a greatly increased risk of developing bladder cancer
490 J.A. Jones and F. Karouia

Table 23.5. Cancer deaths between 1950 and 1990 among life span have an RBE of 1.01.1, similar to that of 2-MeV x- and
study survivors according to dose. - rays. In long-term follow-up (at 2024 years), these animals
0.0050.2 Sv 0.20.5 Sv 0.51Sv >1 Sv showed significant numbers of lenticular opacities from 55-
No. deaths from leukemia 70 27 23 56 MeV protons at 1.25 Gy (125 rad), but these findings were
Estimated excess deaths 10 13 17 47 consistent with other studies of low-LET radiation. The same
Percent attributable to radiation 14% 48% 74% 84% is true of the induction of solid tumors and leukemia, where the
No. deaths from all other cancers 3,391 646 342 308 observed extent of life-shortening was similar to that resulting
Estimated excess deaths 63 76 79 121
Percent attributable to radiation 2% 12% 23% 39%
from similar doses of low-LET radiation and the extent of life-
shortening and cancer induction depended on dose and not on
Source: Modified from Pierce et al. [38]. Used with permission.
proton energy level. Other animal studies indicate that long-
term exposures to penetrating low-LET radiation result in less
risk of cancer than acute exposures. Animal studies have also
Table 23.6. Cancer deaths between 1950 and 1990 among life span
been useful for determining the RBE of various heavy ions
study survivors according to cancer site. for producing deterministic effects such as cell killing in the
Estimated
gut, testis, and bone marrow. Such values range from 2 to 3
Type of cancer Total No. deaths excess deaths Evidence for effect for cell killing, peaking at an LET of 100 to 200 keV/nucleon.
Stomach 2,529 65 Strong Data on the peak RBE for inducing Harderian gland tumors in
Lung 939 67 Strong mice was 30 at 100 keV/nucleon, but no decline in effect was
Liver 753 30 Strong noted beyond an LET of 100. The RBE for cataract induction
Uterus 476 9 Moderate by heavy ions in rats may be much higher than for cell killing,
Colon 347 23 Strong
Rectum 298 7 Weak
perhaps as high as 4050 [4143]. Significant uncertainty still
Pancreas 297 3 Weak exists in the accuracy of extrapolating results of animal studies
Esophagus 234 14 Strong to humans.
Gallbladder 228 12 Moderate
Breast (female) 211 37 Strong
Ovary 120 10 Strong Acute Cellular and Molecular Effects of Ionizing
Bladder 118 10 Strong Radiation
Prostate 80 2 Weak
Bone 32 3 Moderate Cellular responses to radiation involve a broad spectrum of
Other solid tumors 948 47 Strong structural and biochemical changes. Cytoplasmic responses to
Lymphoma 162 1 Weak radiation include swelling (increased free water), vacuoliza-
Myeloma 51 6 Strong
tion, and disintegration of the mitochondria and endoplasmic
Source: Modified from Pierce et al. [38]. Used with permission. reticulum. Nuclear changes include swelling and distortion of
the nuclear membrane and disruption of the chromatin materials.
Factors that that can influence the response of a cell to exog-
(relative risk, 3.02), but the vast majority of these cancers were enous radiation exposure include the cellular environment, the
not observed until more than 20 years after treatment [39]. presence or absence of radiation sensitizers or protectors, and
The more recent use of conformal radiation treatment for the cells natural defense systems.
malignancies has tipped the balance of the risk-benefit com- A cells sensitivity to radiation is influenced by its stage in
parison to favor benefit; however, the risk of developing the cell cycle, its state, and the component of the cell that was
certain radiation-induced malignancies may be increased in exposed. With regard to cell-cycle stage, cells are generally
long-term survivors. most sensitive to reproductive death when irradiated during
M phase (mitosis); to chromosomal damage and division delay
when irradiated during G2; and to problems with DNA synthe-
Studies of Animal Models sis during early G1. The most resistant stages are during late
The response to radiation differs among species, as it does among S phase and during G0. The timing of the irradiation also affects
cell types. Animal models used for studying the bioeffects of the progression of the cell through the cell cycle in a way that
radiation have included rabbits, mice, rats, and other mammalian reflects the normal rate of cell division; for example, low-dose
and nonmammalian species, including dogs and monkeys flown radiation stops slowly dividing cellsbut not rapidly divid-
aboard the Russian Bion satellites. Many of the bioeffects are ing onesin G1. With regard to cell state, cells irradiated in
thought to be universal responses to radiation, whereas others vitro are more radiosensitive than those irradiated in vivo [2].
are thought to be specific to cell type or species. Amplification of the expression of specific oncogenes (e.g., ras,
Studies conducted jointly by the U.S. Air Force and NASA especially when myc is co-expressed, or raf) or the presence
from 1963 to 1969 looked at the RBE of various types of of radiosensitive or radioprotective genes can confer radiore-
space-associated radiation exposures on rhesus monkeys and sistance to cells [44]. With regard to cellular components, the
mice [40]. High-energy protons (>138 MeV) were found to nucleus is more sensitive to both low- and high-LET radiation
23. Radiation Disorders
than the cytoplasm. Redundancy in numbers of mitochondria
may confer radioresistance; lymphocytes, for example, contain
few mitochondria and are exquisitely sensitive to irradiation.
Another factor affecting cell death or inactivation from radiation
is the oxygen tension in the cellular environment; many cells
are more sensitive to irradiation under normoxic conditions as
compared with hypoxic environments [32].
Mechanisms of Damage from Ionizing Radiation
The main cellular effects of ionizing radiation relate to specific
ionization events that produce molecular alterations. Space
radiation, as opposed to typical terrestrial sources, contains
a much greater proportion of particulate radiation. Of most
concern are HZE, high-LET radiation particles, which produce
dense ionization tracks. Cells exposed to radiation have one
of four fates: (1) complete recovery to the preradiation state;
(2) partial recovery with repair of injury but with diminished
functionality; (3) mutations caused by incomplete or errone-
ous repair; or (4) cell death.
Incident radiation injures cells both directly and indirectly.
Approximately one third of biological damage from low-LET
radiation is thought to be from direct ionization, with the
remainder incurred from indirect damage. The vast majority
of damage from high-LET radiation results from direct ioniza-
tion [2]. The following sections outline mechanisms by which
radiation directly and indirectly induces genetic damage (i.e.,
damage to a cells DNA), followed by a brief review of mech-
anisms of additional, epigenetic damage.
Direct DNA Damage
Ionizing radiation can penetrate the cytoplasm of a cell and
interact with the molecularly rich cell nucleus, which is packed
with DNA, histone proteins, and nuclear matrix. The severity
of the injury depends on the track, the cross-section, and the
LET of the particle. When electromagnetic or particle radiation
strikes DNA and other macromolecules directly, molecular
damage occurs in the form of ionization and possibly breaks.
The hydrogen bonds (including hydrogen-hydrogen [H-H]
and sulfhydryl [S-H]) are the weakest in the macromolecular
structure and are therefore the most vulnerable to disruption
by ionizing radiation. Breaks in these bonds lead to changes
in secondary and tertiary structure of proteins and enzymes,
which lead in turn to decreases or loss of functional activity.
Cellular proteins may express alterations in their viscosity,
conductivity, and other physical properties. The side chains of
amino acids are the most radiosensitive portions of proteins.
Large macromolecules with repeated identical units often
show disruption in the same bond, suggesting that the energy
absorbed in the molecule can be transmitted down the molecu-
lar chain to the weakest bond. Histone proteins may lose their
associations with DNA, and the secondary and tertiary DNA
structure may be altered with disruption of the hydrogen bond
linkage between base pairs; both effects can lead to errors in
transcription and translation.
491
Molecular disruptions in the DNA molecule are characterized
as strand breaks (single or double), apurination, or deamina-
tion. Strand breaks often occur between a sugar (ribose) and a
phosphate, although these breaks often will rejoin if the broken
end is not peroxidized by a reactive oxygen species. Radiation
of energy as low as 3040 eV can produce a break in one of
the two strands of DNA (a single-strand break [SSB]), and an
exposure of a cell to 0.01 Sv (1 rem) can be expected to produce
1020 SSBs. Double-strand breaks (DSBs) can occur when two
SSBs are juxtaposed or when a single densely ionizing particle
(HZE with > 500 eV) produces a cluster of ionization within
a span of about 20 . High-LET radiation, at a given energy,
will induce more nonrejoining strand breaks than will low-LET
radiation, and nonrejoining strand breaks are more likely to lead
to cell death. Another mechanism of DNA damage is cross-
linking, irreversible binding between chemically active loci
produced in adjacent molecules or within the same molecule.
Base-pair dimerization, a type of cross-linking from an ionizing
exposure, can easily produce a downstream mutation.
Radiation-induced SSBs between a sugar and the phosphate
group of the nucleotide can readily be repaired with high fidelity,
since the template for the nucleotide is preserved. Occasionally,
if SSBs occur in adjacent sister chromatid regions, the nicked
DNA segments undergo a process called sister chromatid
exchange. However, when an ionization event leads to a DSB,
the template is lost and errors in repair are much more likely,
producing a point or segmental mutation. Such injuries or
mutations can be lethal if the DNA damage is severe enough
to cause the loss of function of one or several key proteins, or
if repair is not possible and the chromosomal elements beyond
the break are lost. Sometimes DSBs can be removed by a pro-
cess similar to sister chromatid exchange that preserves the
broken chromosome, but such repair may place genes under
different control mechanisms (as can happen with genetic
recombination), which also can lead to changes in cellular
activity and phenotype.
Single hits within chromosomes are more likely to be
repairable by normal cellular mechanisms, but multiple hits in
the same region of a chromosome may require more complex
repair mechanisms or may not be repairable at all. Depending
on the path of the ionizing particle, multiple damage sites can
occur in proximity to one another. If the sites are located less
than 20 apart, the ionization event is usually lethal to the
cell, whereas sites separated by more than 80 are usually
survivable but are likely to lead to mutations.
HZE exposure tends to produce more complex nuclear bio-
chemical events than those produced by low-LET radiation. The
complex events can lead to unfaithful or nonrejoining strand
breaks and clusters of injury (e.g., base damage, SSBs, DSBs).
Specific postexposure chromosomal aberrations observed in
cytogenetic analysis of lymphocytes include inversions, dicen-
trics, fragments, rings, and translocations (Figure 23.9).
If the cell survives the damage event, several downstream
effects may occur. Translation errors can be seen if a DSB
occurred in a coding region of the DNA, leading to mutated
492 J.A. Jones and F. Karouia

Figure 23.9. Chromosomal aberrations resulting from radiation

damage to DNA. Such changes are representative of lymphocyte
gene anomalies assessed for radiation dosimetry

Figure 23.10. Molecular pathology associated with oxidizing

or truncated proteins with aberrant or lost function and sub- species production
sequent alterations in phenotype. Mutations can also result
in replication errors during mitosis. Errors in replication, if
varies from 1:5 to less than 1:1 depending on the lineage of the
they occur in a sensitive region of the genome, can cause fur-
cell. For the vast majority of cells, the probability of radiation
ther mutations in daughter cells through rearrangements; such
interacting with cytoplasmic organelles and molecular species
errors are the root of potential carcinogenesis in these cells.
is statistically much larger than with nuclear species. Damage
In addition to overt injury, incidental radiation exposure can
to either the cytoplasm or the nucleus from ionizing radiation
induce genomic instability. This can be produced with as little
can result not only from direct damage but also from second-
as 0.20.3 Gy (2030 rem) of high-LET radiation in mammary
ary reactive species. Radiation exposure results in energy
and other cell lines. [44,45] In one experiment, transplanted
being released into cellular materials, causing excitation of
bronchial epithelial cells that were irradiated with 0.3 Gy of
56
electrons or secondary ionization. In addition to the forma-
Fe (< 1 particle/cell) and 6 months later irradiated with 1 Gy
tion of ions, radiation can cause the loss of an electron from
of X rays developed tumors upon implantation in 3 of 7 ani-
an atom or molecule resulting in an unstable, highly reactive
mals; no tumors formed when cells had been irradiated with
entity called a free radical. The unpaired outer shell electron
either 0.3 Gy of 56Fe or 1 Gy of X rays immediately before
of these electrically neutral radicals causes them to react very
transplantation [46]. These results imply that exposure to as
quickly with one another or with stable molecules. Because
little as a single HZE particle may render a cell genetically
the human body consists of about 70% water, such events
more sensitive or unstable for months and thus at greater risk
primarily involve aqueous products, particularly the highly
for subsequent initiation events. The mechanism for high-
reactive hydroxyl (OH*) and peroxy (HO2*) radicals.
LETinduced genomic instability is unknown, but genetic
Reactive species such as the oxidizing agents OH* and HO2*
instability may account for the carcinogenic side effect of
and the reducing agent H* generated anywhere in the cell can
such irradiation. This condition seems to persist for several
propagate and disseminate, interacting with various parts of
generations of cellular offspring after exposure. However,
the cell such as cytosolic proteins and other macromolecules,
cells transformed by high-LET radiation cannot be distin-
membrane constituents such as lipids, and nuclear contents,
guished phenotypically from those transformed by low-LET
including DNA (Figure 23.10). The base structures are particu-
radiation.
larly susceptible to direct damage by hydroxyl radicals, and
the pyrimidine bases are almost twice as radiosensitive as are
Indirect DNA Damage the purines. In macromolecules, radicals can cause hydrogen
Ionizing radiation can interact with other parts of the cell bond breakage, molecular degradation or breakage, and intra- and
besides the nucleus. The nucleus-to-cytoplasm ratio of cells inter-molecular cross-linking [8]. Hydroxyl species produced
23. Radiation Disorders
by -irradiation can induce DNAprotein cross-links, which
tend to occur mostly in areas of the genome that are being
actively transcribed [47]. Components of these links, known
as DNA adducts, can be quantified as an indication of DNA
damage from chemical or radiation exposure.
Epigenetic Effects
As noted above, reactive species can be generated anywhere
in the cell and can propagate and disseminate, eventually
interacting with chromosomal elements, including the DNA
itself. Such interactions can create DNA adducts and meth-
ylation (hypo- or hyper-) events, which do not mutate the
structure of the DNA but change the pattern of expression of
the affected genes. Epigenetic effects arise from one of three
mechanisms: (1) from modifications of nongenetic nuclear
proteins (histones or nonhistones) that affect transcriptional
or translational activities or prolong the activity of protein
kinases; (2) from binding between carcinogens and tRNA,
which can change amino acid codons, or between carcinogens
and RNA polymerases, which can increase the expression of
enzymatic proteins; and (3) from the action of cocarcinogens
such as hormonal transcription factors.
Membrane Damage
Another source of cell damage from radiation is its effects
on cell membranes, chiefly through lipid peroxidation. Reactive
oxygen species and other radicals can attack the carboxyl,
ester, amide and phosphate ends of membrane phospholipids,
producing lipid peroxides and their by-products. Peroxidation
reactions can induce lipidlipid, lipidprotein, and protein
protein cross-linking in the membrane [8]. These molecular-
level effects can affect membrane permeability and ultimately,
if the damage is severe enough, loss of membrane function and
integrity. Peroxidation reactions can also activate phospholi-
pase A2, which results in the release of arachidonic acid from
the membrane and the production of prostaglandins, leukotri-
enes, and thromboxanes via cyclo- and lipoxygenases [48].
Lipid peroxidation probably does not result in significant
cell killing, but perturbations in membrane function unques-
tionably affect cell physiology and reproduction. Studies
have shown that lipid peroxidation can eventually lead to
DNA damage through the formation of etheno-, propane- and
malondialdehyde DNA adducts [49]. Empirical findings that
support the importance of membrane damage in cell radiobio-
logical effects include the following observations: membrane-
associated enzymes are not directly inactivated by ionizing
radiation but rather are indirectly inactivated through lipid
peroxidation; DNA function is intimately associated with
membrane connectivity; oxygen enhances radiation damage to
membranes; and even sublethal doses of radiation can induce
structural and functional changes in membranes.
With regard to the timing of these effects, biochemical
changes resulting from radiation exposure can be observed
within seconds after the exposure. Depending on the mitotic
493
and metabolic rate of the cell, cell division can be affected
within hours of the exposure. Tissue-specific effects can be
seen within hours to days, depending on the exposure dose
and dose rate, as well as the relative radioresistance of the
tissue. Dysfunction of the organ and fibrotic reactions such as
occurs in the lung will be observed over days to weeks. The
appearance of other tissue pathology such as neoplasms and
cataracts, plus any birth defects attributable to lesions pro-
duced in the genetic material of the gonadal cells, will take
years to be seen after the exposure.
DNA Repair Mechanisms
DNA repair processes have been studied extensively in pro-
karyotic and eukaryotic cells, and much of the processes for
mammalian cells has been inferred from the study of lower
organisms. A human syndrome, ataxia telangiectasia, which
is characterized by increased sensitivity to radiation-induced
mutations and cell killing because of a defect in cell cycle
control and defective activation of damage-inducible DNA
repair, has also provided significant amounts of information
on the repair process. Eukaryotes have developed complex
repair processes, with specialized enzymes that become acti-
vated depending on the mechanism of damage (oxidative vs.
nonoxidative) and the degree of injury (SSB vs DSB). The
timing of the repair effort is critical to subsequent cellular
downstream events. If the repair occurs before the cell enters
S-phase, during which DNA is synthesized in preparation for
cell division, then the chances of point mutations or errors in
replication would be greatly reduced relative to repairs that
occur after DNA synthesis or chromosomal separation.
Simple base and sugar damage, such as that which occurs
in SSBs, is repaired by DNA excision repair via two main
mechanisms. In base excision repair, the damaged base is
recognized and removed by DNA glycosolase; after that, an
endonuclease removes the baseless sugar, and the gap is filled
by DNA polymerase and sealed by DNA ligase. In nucleotide
excision repair, an incision nuclease cuts the DNA phospho-
diester backbone near the damaged nucleotide (unless the
radiation break had already involved the backbone). A second
endonuclease or an excision exonuclease then removes the
damaged material, and the resultant gap is filled by and then
sealed by DNA polymerase and DNA ligase.
More complex damage, e.g., DSBs and DNA cross-
links, is repaired by other mechanisms including global and
transcription-coupled repair, recombinatorial repair, and
postreplication repair. Many of these repair processes involve
proteins that are normally involved in cellular transcription or
housekeeping activities such as cell cycle regulation. Com-
plexes of specific proteins that first recognize damaged DNA
and then recruit repair enzymes seem to be more efficient in
the recognition and repair process in regions of the genome
that are actively transcribed [50].
The time required to initiate and complete DNA repair
depends on the type of cell, the phase of the cell cycle, the type
494
and dose of radiation, and the timing of the repeated exposure,
if any. Sufficient time must be allowed between exposures to
allow repair to be completed, if the cell is to survive. Exposures
can be categorized as sublethal, potentially lethal, and supra-
lethal based on the quantity of radiation and the above factors.
Some evidence exists to refute the original postulate that dam-
age by high-LET radiation cannot be repaired, but the time
required and the mechanisms underlying that type of repair may
be different from repair of damage by low-LET radiation [2].
Acute Tissue- and Organ-Specific Effects from
Whole-Body Irradiation
The likelihood of a significant acute exposure that would lead
to acute radiation symptoms while a crew is in LEO is very
low. Such an exposure would require either an exoatmospheric
detonation of a nuclear weapon (which has not occurred since
1964) or a very large SPE while the vehicle is in a high-altitude
polar orbit or in combination with a geomagnetic storm that
would significantly distort the magnetosphere shielding. The
likelihood of an acute high-dose radiation exposure is higher
for a crew traveling in interplanetary space in a minimally
shielded vehicle. As previously mentioned, SPEs of sufficient
intensity to breach clinical thresholds outside the geomagne-
tosphere (e.g., for travel to Mars) have been recorded in the
recent past. Mishaps with a nuclear power system used for
propulsion or for surface electricity could also lead to such an
event. This section examines the effects of ionizing radiation
on specific tissues; the section that follows considers whole-
body exposures and clinical presentation.
Tissue sensitivity depends on the cellular, extracellular, and
stromal composition of the tissue. The number of stem cells
and stem cell dependence of the tissue, the dividing transits,
the transit pool, and the closed (static) cell populations will
also influence a tissues resistance to radiation injury. In general,
tissues that have large numbers of active stem cells, such as
the bone marrow and intestinal crypts, are highly sensitive to
radiation. Those tissues with mainly terminally differentiated,
static cells (such as neurons) or with large amounts of sup-
porting stroma and noncellular elements (such as cartilage and
connective tissue) are relatively radioresistant.
Cardiovascular Effects
Cardiovascular tissue is generally resistant to radiation damage,
in part because of the large numbers of mitochondria in cardiac
muscle. The main effects of high doses of ionizing radiation
include intimal fibrosis, endothelial swelling, vascular sclerosis,
pericarditis, and pericardial effusion. The aorta can rupture
after exposure to doses of 50 Gy (5000 rad) experienced over
less than a 2-month period. Arterioles and capillaries are much
more sensitive to radiation and account for many of the effects
seen in other tissues.
Doses larger than 50 Gy (5000 rad) can affect myocardial
cells directly, inducing loss of cross striations, homogeniza-
tion of the sarcolemma, intimal thickening, and nuclear lysis.
J.A. Jones and F. Karouia
Respiratory Effects
Respiratory tissue exhibits mixed sensitivity to ionizing radia-
tion. The pulmonary cartilage and pleura are radioresistant, but
the rich network of small vessels and lymphatics are sensitive.
Early changes in hyaline membranes are evident after 20 Gy
(2000 rad). Radiation pneumonitis, an acute inflammatory
reaction characterized by alveolar fibrinous exudates, septal
thickening, leukocyte infiltration, and cellular proliferation,
results after doses between 30 and 40 Gy (3000 to 4000 rad).
Recovery from doses less than 50 Gy is possible, but interstitial
fibrosis can result from exposure to higher doses over a period
of several months.
Gastrointestinal Effects
Exposures as low as 1 Gy (100 rad) can diminish gastric motility
(with delayed gastric emptying) and sometimes induce sphincter
incompetence, and the duration of the change in motility depends
on dose. Delayed suppression of gastric acid secretion and
release of neurohumoral factors are also possible. The normally
high turnover of intestinal mucosal cells renders the intestinal
lining quite susceptible to massive injury; dividing intes-
tinal mucosal cells are extremely vulnerable. Nondividing
cells can survive and may resume mitosis after an exposure to
less than 10 Gy (1000 rad). Histamine released within minutes
after exposure contributes to diarrhea. Fluid and electrolyte
loss manifests within 12 h of exposure from impaired absorption
of sodium and water, possibly because of damage to the tight
junctions at the apical epithelium, with subsequent net secretion
of both water and electrolytes from the gastrointestinal tract.
The entire epithelial lining becomes denuded by 4 days after
a 5-Gy (500-rad) dose. Increased permeability to enteric
microorganisms has a key role in gastrointestinal syndrome
mortality [8].
Hepatic Effects
The liver is relatively radioresistant except for regenerating liver
cells, which are very sensitive. Doses of up to 30 Gy (3000 rad)
do not damage mature liver tissue, but doses exceeding 40 Gy
(4000 rad) cause damage in 75% of cases. Radiation hepatitis
is characterized by sinusoidal congestion, hyperemia, central
venous dilation, and central lobar cellular atrophy.
Skin Effects
Skin sensitivity to direct ionizing radiation varies with the
anatomic location and type of radiation. Radiosensitivity is
roughly associated with level of keratinization; the anterior
aspect of the neck, for example, is more sensitive than the
palms and soles. Mucous membranes are particularly sensi-
tive. Integumental substructures, including hair follicles and
apocrine sweat glands, are also quite sensitive. Skin injury
associated with space flight could take place even in LEO
operations if crewmembers were outside the space vehicle
performing an EVA during a large SPE or geomagnetic storm.
23. Radiation Disorders
Although the penetration capability of protons or electrons
into the vehicle is low because of structural shielding, pen-
etration through the relatively thin layers of EVA spacesuits,
particularly to the skin, renders the occupants significantly
more vulnerable.
Skin erythema and possibly transient depilation are observed
at acute doses of 720 Gy (7002000 rad). A dose of 30 Gy
(3000 rad) produces dry desquamation, but moist desquama-
tion of the epidermis does not appear until acute doses of 40 Gy
(4000 rad) [2]. In rodents, the doses required to impair wound
healing are about 5 Gy (500 rad), but whether the impairment
results from loss of tensile strength or extension of healing
time and increased incidence of infection remains uncertain
[51]. Because other factors may be operative that could impair
wound healing (e.g., stress, microgravity) in addition to radia-
tion exposures, vigorous treatment of radiation-associated
skin injury in astronauts is warranted.
The response of mucous membranes to radiation is similar
to that of the skin, except that the mucosal effects appear more
quickly and tend to resolve (or progress) more quickly as well.
With regard to acute effects on the oral mucosa, doses of 20
24 Gy produce patchy mucositis, dysphagia, impaired masti-
cation, and diminished taste by the end of the second week.
Doses of 3036 Gy lead to edema of the tongue and throat,
confluent mucositis, and thickened saliva by the end of the
third week; doses of 4048 Gy produce mucositis that extends
onto the buccal mucosa by the end of the fourth week. Doses
of 5060 Gy result in severe mucositis with the appearance of
pseudomembranes and superficial ulceration; the tongue may
finally show injury by the end of the fifth week, and regenera-
tion begins after 6 weeks.
The radiosensitivity of mucous membranes in the head and
neck region varies depending on their location; those in the
soft palate and pillars are the most sensitive, followed in order
of decreasing sensitivity by membranes in the posterior phar-
ynx, tonsils, floor of mouth, anterior buccal mucosa, lower
alveolar mucosa, epiglottis, tongue, and vocal cords.
Eye Effects
The lens is quite sensitive to radiation; the threshold for the
formation of cataracts is 25 Gy (200500 rad) for a single
dose or 510 Gy (5001000 rad) fractionated over time.
The average latency period is 23 years but can range from
10 months to 35 years. The cornea and conjunctiva are par-
ticularly sensitive, but the optic nerve and sclera are resistant.
The blood-aqueous barrier is highly radioresistant, requiring
20 Gy (2000 rad) to produce a breakdown. The main effects of
radiation on the eye, aside from the lens, involve the micro-
vasculature. The lens is devoid of vasculature and depends on
the aqueous humor to receive nutrients and metabolic support.
The proliferative cells in the germinal epithelium are radio-
sensitive. Irradiation produces initial mitotic arrest followed
by production of fragmented nuclei and degenerated cells.
As the LET of the incident radiation increases, the number of
abnormal mitoses, micronuclei, and disordered meridional rows
495
increases; therefore the threshold dose for cataract induc-
tion is lower for high-LET radiation than for low-LET radi-
ation [43].
An interesting phenomenon, initially reported by Edwin
Buzz Aldrin, the pilot of the Lunar Excursion Module on
Apollo 11 and reported on all subsequent Apollo missions, is
the perception of transient light flashes during space flight.
Light flashes apparently are not noticed by the observer
unless the eyes are dark-adapted and the observers attention
is not distracted by other visual stimuli. The exact mech-
anism underlying the flashes has not been elucidated, but
some theories implicate particle interaction with the retina
or elsewhere along the optic pathway. Direct interaction
between retinal or nerve cells and relativistic particles or
their Cherenkov (secondary) radiation has also been postu-
lated. Either way, the loss of ionization energy as the particle
traverses the cell is thought to produce the perceived flash.
Whether the affected cells survive the incident is not clear.
Flashes observed during Skylab 4 are believed to have origi-
nated both from GCR sources as well as trapped radiation in
the Van Allen belts. Crewmembers aboard Skylab reported
increased frequency of flashes during transit through the
SAA (Figure 23.11) [52], prompting the question of whether
the proportion of heavy (Z > 2) particles in the trapped inner
belt is higher than the originally posited 0.1% [52]. Crews
aboard the ISS sleeping behind shielding of water bags and
high-density polyethylene brick have not reported seeing
any light flashes.
Figure 23.11. Distribution of perceived light flash phenomena
relative to orbital position and passage through the South Atlantic
anomaly (SAA), correlated with objective dosimetry. A striking
increase is noted in the SAA
496 J.A. Jones and F. Karouia

Endocrine/Exocrine Effects and convoluted tubule ischemia produces chronic nephritis

6 months after exposure.
Endocrine glands are relatively radioresistant. Moderate radi-
Other changes include epithelial degeneration or desquama-
ation doses produce inflammation, and higher doses cause
tion, and damage to connective tissue, especially elastin fibers.
glandular dysfunction. In the salivary glands, for example,
Large doses can cause necrosis, which can lead to obstruction
25 Gy (2500 rad) causes swelling of acini and loss of secre-
of the ureters and formation of fistulae. Infection increases
tion. In the pancreas, the islet cells are the most sensitive,
the likelihood of fistulae. The bladder and ureters are more
with a threshold dose of 2550 Gy. The LD50 for alpha cells is
resistant, but injury to the bladder mucosa can produce radia-
50 Gy, and the LD50 for the beta cells is 20 Gy.
tion cystitis, which may further lead to hemorrhage, fibrosis,
Steroidogenesis occurring in the adrenals can remain normal
and fistula formation. Radiation cystitis is characterized by
after exposure doses of up to 35 Gy (3500 rad). In the thyroid,
irritative voiding symptoms (dysuria, urgency, and frequency)
moderate doses may produce hypofunction years after expo-
and is caused by primary and secondary edema in the bladder
sure, but it has been estimated that 500 Gy (50,000 rad) is
mucosa 34 weeks after exposure.
required to completely destroy all thyroid tissue [2].
Reproductive System Effects
Immune System and Bone Marrow Effects
In males, the testis is extremely radiosensitive, whereas the
The bone marrow stem cells, which are actively dividing, are
accessory reproductive organs such as the prostate, seminal
extremely radiosensitive; mature peripheral white cells are
vesicles, penis, and urethra are radioresistant. A single dose
more resistant. Radiation-induced immune dysfunctions can
of 0.15 Gy (15 rad) has been been reported to reduce sperm
arise through several mechanisms. Loss of innate resistance
counts in some healthy men. In men, transient sterility occurs
results from breakdown of the natural mechanical barriers to
after doses of 0.54.0 Gy (50400 rad), but generally a dose of
infection, impaired cellular defense, impaired clearance of
at least 2 Gy (200 rad) is required to produce effects that last a
infectious organisms from decreased respiratory cilia func-
year (Table 23.7). Susceptibility of spermatogonia to radiation
tion, increased bowel permeability to microbes, and dimin-
may be enhanced by chronic low-dose exposures because of
ished bactericidal properties of serum.
the cyclic nature of meiotic division in these stem cells. Human
Antibody production may be diminished after as little as
testes have a finite number of stem spermotagonia. Radiation
3 Gy (300 rad), thereby curtailing normal antibody responses.
above threshold doses impairs and disrupts stem cell mitosis
Progenitor cells may be lost; marrow pluripotential stem cells
and meiotic division and can be lethal to the stem cells, result-
are highly sensitive to radiation-induced mutation and cell
ing in temporary or permanent oligospermia or azoospermia
death. Marrow stem cell depletion can lead to pancytopenia,
as well as spermatic dysfunction. Sublethal levels of radiation
which without vigorous medical support can be fatal. In fact,
can induce a state of dormancy in the spermatogonia that can
radiation injury to the bone marrow may be the most important
last 78 years, after which sperm counts and function may
acute biological effect of whole body radiation influencing
improve. The effects of radiation on testicular stem cells can
survival of the organism.
be reduced by administering gonadotropin-releasing hormone
(GnRH) for several weeks beginning at the time of radiation
Muscle and Bone Effects
Morphologically, muscle is highly radioresistant, tolerating up
Table 23.7. Radiation effects on reproductive function.
to 45 Gy (4,500 rad) with only mild changes in histology. Bone
Sex Dose, Gy (rad) Effect
and cartilage are resistant if they are mature; growing bones
and cartilage are more sensitive. For low-energy photons, bone Male 2.5 (250) Temporary sterility lasting about
12 months
absorbs five to six times as much energy per gram as soft tissue;
56 (500600) Permanent sterility
for medium-energy photons, bone absorbs the same energy per Femalea
gram as soft tissue; and for high-energy photons, bone absorbs All ages 1.7 (170) Temporary sterility lasting 13
twice as much energy as soft tissue. Doses exceeding 50 Gy years
(5,000 rad) may produce delayed necrosis in bone and cartilage, 1.251.5 (125150) Amenorrhea in 50%
presumably through injury to the small vasculature. 3.26.25 (320625) Permanent sterility
Ages 1540 1.52.5 (150250) Temporary amenorrhea
2.55 (250500) Ovulatory suppression in
Genitourinary Effects 40100%
The kidney is moderately radiosensitive, manifesting nephri- (permanent in 60%)
58 (500800) Permament ovulatory suppression
tis as the predominant clinical entity. Most of the radiation in 40100%
effects on the kidney result from vascular injury. The first >8 (>800) Permament ovulatory suppression
signs are hyperemia, increased permeability and interstitial in 100%
edema; later findings may include slow vascular occlusion a
Dose needed to induce ovarian failure is age-dependent, with lower doses
due to endothelial swelling, fibrosis, and thrombosis. Cortical needed for women older than 40 years.
23. Radiation Disorders
exposure [53]. Radiation damage is not cumulative for males
because gametogenesis continues into later years of life, and
damaged cells can be eliminated.
In females, the ovary is extremely radiosensitive. Radiation-
induced cessation of hormone production (premature menopause)
can lead to temporary or permanent infertility. The vagina is
similar to other mucous membranes in terms of radio-
sensitivity, but the vulva, labia, and clitoris are more sensitive.
The uterus is radioresistant. Transient sterility can occur after
doses as low as 1.25 Gy (125 rad), although most report the
threshold dose for temporary sterility as being 1.7 Gy (170 rad)
[2]. The dose required for permanent sterility in women ranges
from 3.5 to 20 Gy (3502000 rad) (Table 23.7) [54]. Radiation
damage to the female gonads is cumulative because gameto-
genesis essentially stops at the time of birth.
Central Nervous System Effects
Mature neurons are highly radioresistant; glia and support
cells are also resistant, with astrocytes being somewhat more
sensitive. Neuroblasts are very radiosensitive, and exposure
to radiation has significant negative effects on the learning
capacity of a developing fetal or infant brain. White matter is
more sensitive than gray matter, presumably because of injury
to oligodendrocytes and subsequent demyelination. Doses of
40 Gy (4000 rad) to the brains of monkeys have produced
demyelination at 18 weeks after exposure. Peripheral nerves
are more resistant than central (CNS) neurons.
If radiation doses are high, symptoms and signs in the
acute clinical period (i.e., within the first 6 months after
exposure) include headache, lethargy, nausea, vomiting, and
papilledema, progressing to convulsions and coma. The acute
response in the cerebrovascular system includes endolethial
injury, capillary circulation impairment and increased perme-
ability, interstitial edema, leukocytic infiltration, loosening
of perivascular astrocytes and weakening of the blood-brain
barrier, petechial hemorrhages, vasculitis, meningitis, and
choroid plexitis. Neurons show no acute morphologic response
other than some delayed cellular disorganization, pyknosis,
and dendritic process reduction at 12 weeks. Oligodenrocytes
show edema with the acute inflammatory reaction. In the sub-
acute period (612 months), recovery may be complete or can
be characterized by episodic partial or grand-mal seizures,
ataxia, or impaired motor coordination caused by slow neural
degeneration and progression of vascular lesions that can lead
to necrosis [2].
Doses of less than 5 Gy (500 rad) increase levels of
neurotransmitters such as acetylcholine and 5-hydroxytryp-
tamine, whereas doses greater than 500 rad tend to decrease
neurotransmitter levels [2]. Several investigations of rodents
showed impaired regulation of dopamine-controlling motor
function and CNS performance impairments after only 0.5 Gy
(50 rad) from 0.6-GeV 56Fe particles, which persisted for at
least 6 months. Specifically, the rat striatum was depleted of
dopamine when exposed to 0.6 GeV 56Fe particles but not when
exposed to 1.54.0 Gy (150400 rad) of 0.25-GeV protons
497
[55]. Nerve signal transduction is also affected because of
uncoupling of membrane receptors and G-protein signal mol-
ecules [56]. Adult humans undergoing radiation therapy for
cancer have shown no impairments in higher mental function,
motor coordination, or strength, but this may not be true for
children. However, doses of 6 Gy (300600 rad) to adult rat
brains resulted in diminution of complex task performance
scores and behavior decrements in these animals [57]. Spatial
learning and memory were impaired in rats exposed to 1.5 Gy
(150 rad) of 0.6-GeV 56Fe but not to 4 Gy (400 rad) of 250-
MeV protons [58].
Chronic and Long-Term Effects of Ionizing Radiation
Cancer
Types of cancer observed after exposure to ionizing radia-
tion include leukemias (primarily acute lymphoblastic and
myeloblastic and chronic granulocytic), which arise 715
years after exposure, and solid tumors of the breast, lung,
gastrointestinal tract, lymphoid system, and various sarco-
mas, which can appear several decades after exposure. Given
these long latency periods, neoplasms such as these would
not be expected to appear de novo during any crewed space
mission within the foreseeable future. However, cancers that
arise after exposure to ionizing radiation are morphologically
indistinct from cancers that are not associated with radiation.
What is known is that limiting the radiation dose to which
one is exposed will mitigate the occurrence of such neoplasms
later in life. Attempts to maintain delayed effects at an accept-
able incidence are made by setting and following strict career
exposure limits.
Knowledge of the carcinogenic process is still somewhat
limited and that process almost certainly varies according to
the type of cancer. However, it seems clear that several steps
are required to induce neoplasia in a cell. Cell and tissue culture
models have yielded useful information as to the mechanisms
of radiation-induced damage, but such models have been less
helpful in predicting oncogenesis in humans. Animal studies
have provided the bulk of knowledge regarding the bioeffects
of HZE particles on tissues and have allowed some testing of
the complex interaction of radiation with co-carcinogens and
tumor promoters. However such studies are expensive, time-
consuming and opposed by numerous organizations. Questions
have also been raised regarding variability in radiation sensitiv-
ity between species and the validity of extrapolating risks of
cancer and other stochastic effects from rodents to humans.
As noted earlier, human data have been derived primarily from
accidental and therapeutic radiation exposures. Although
diagnostic doses of radiation may induce tumors in the
breast, thyroid, and bone marrow, other solid organs require
therapeutic levels of radiation to induce tumors. Table 23.8
shows the risk of cancer after a single radiation exposure at
the indicated threshold doses; Table 23.9 shows estimates of
probability of excess cancer deaths associated with an expo-
sure to 0.1 Sv (10 rem) over a 1-year period [59].
498 J.A. Jones and F. Karouia

Table 23.8. Relative risk of developing leukemia, breast, or thyroid at this stage, healing is poor because of the inadequate vascu-
cancer after a single exposure to a threshold dose. lar supply. Over the long term, chronic dermatitis may ensue,
Relative risk (Cases per associated with increased incidence of neoplasia, especially
Type of cancer Threshold dose, Gy (rad) million/year/rad) squamous cell carcinoma [2].
Leukemia 0.2 (20) 3.1
Breast <0.01 (<1) 6.68.7
Thyroid 0.060.07 (67) 1.99.3
Cataracts
Radiation exposure is well known to cause cataract forma-
tion in humans and animals. However, cataracts are a com-
Table 23.9. Estimated excess cancer incidence and mortality, in mon clinical entity seen with aging, and it becomes important
percent, after an exposure to 0.1 Sv over a period of 1 year. to track radiation as an attributable risk factor. Radiation
Mortality Morbidity exposure to the eye causes partial opacity in the crystalline
All All lens. Symptoms are usually observed after several months of
Solid tumors Leukemia cancers Solid tumors Leukemia cancers latency after radiation exposure, with 23 years being aver-
Age at exposure 35 years age. Unlike senile cataract common in old age, few radiation
Male 0.19 0.666 0.26 0.39 0.044 0.44 cataracts advance, and visual impairment is infrequent. One
Female 0.34 0.023 0.36 0.71 0.031 0.74 aspect of radiation cataract that sets it apart from radiation-
45 years related cancer is the possible existence of a threshold, a cer-
Male 0.13 0.039 0.17 0.21 0.049 0.26
Female 0.24 0.032 0.27 0.60 0.061 0.66
tain low-dose value below which no effect is observed.
55 years Characteristically, radiation-induced cataracts occur most
Male 0.10 0.028 0.13 0.16 0.041 0.20 commonly in the posterior subcapsular area [61]. They can
Female 0.16 0.021 0.18 0.38 0.03 0.41 progress to full cortical and even nuclear opacities. Energy
Risks to women are higher because of breast and ovarian cancer and higher deposition from GCR, gamma rays, or neutrons causes ioniza-
incidence of lung cancer. tion of lens constituents, mainly water, which in turn leads to
Source: (Modified from NCRP, 1997). production of free hydroxyl and other radicals. This process
may be compounded by decreases in antioxidant concentra-
tions associated with age, which further increases vulnerabil-
Many cocarcinogens, immune system modulators, and
ity to oxidative damage. Opacities of the lens are typified
antitumor agents can influence the development of tumors
by multiple vacuoles, a feathery appearance, and web-like
in humans. Current theories of carcinogenesis postulate that
fringes. Glare is a common initial complaint of posterior sub-
cancer arises only after the accumulation of a certain level of
capsular cataracts [62].
abnormally expressed cellular oncogenes (amplified) or tumor
The risk for humans of forming cataracts from space radia-
suppressor genes (deleted or mutated). Normal cells have
tion exposure is difficult to extrapolate from animal experi-
multiple growth-control points that must be circumvented to
ments, in part because species vary in their sensitivity to
allow a cell to become immortalized, and additional changes
radiation. In humans, acute single doses are known to be more
in gene expression are required before a cell can become inva-
cataractogenic than multiple protracted doses. The single-
sive and subsequently metastatic. Even low-dose radiation
dose threshold is 2 Gy (200 rad) for photons in humans, 4 Gy
can induce genetic instability in the progeny of cells, and that
(400 rad) if the dose is delivered over 3 months, and 5.5 Gy
instability can persist for up to 50 generations. Mutation rates
(550 rad) if delivered over 3 years [63]. Findings from several
are elevated in the progeny, producing increasing numbers of
investigators suggest that because lens epithelial activity even-
transformed descendents. Cells that have sustained radiation
tually returns to normal despite HZE particulate exposure, the
to their cytoplasm are at increased risk of undergoing subse-
differences in cataract dose threshold from high-LET radia-
quent mutational events; the existence of a bystander effect
tion is quantitative and not qualitative. Protons over a broad
can even lead to mutations in nearby (nonirradiated) cells,
range of energies do not seem to be more cataractogenic than
presumably through the production of a soluble radiation
photons. However, the threshold for mixed gamma-ray and
by-product molecule [60].
neutron radiation may be lower than 1 Gy (100 rad). The RBE
of neutron exposure in atomic bomb victims has been calcu-
Skin
lated to be 32 and may even be higher at lower doses [64].
Late effects of radiation skin damage include dermal atrophy The RBE of heavy ions is by most accounts similar to that of
and telangiectasia, occuring a minimum of 612 months after neutrons, but may possibly be as high as 200.
exposure [61]. In the 1- to 5-year period thereafter, atrophy, The practical applicability of using objective classification
ulceration, and deep fibrosis can appear after high-dose exposure. methods for assessing the presence and progression of clinical
Repeated exposures may produce epidermal hyperplasia and cataracts is being demonstrated by several studies. The LOCS
hyperkeratosis. Atrophic skin is smooth, thin and scaly, and II and III subjective classification systems have been com-
is more susceptible to traumatic injury. If ulceration occurs pared to objective techniques, including digital camera image
23. Radiation Disorders
analysis of Scheimpflug and retroillumination images [65,66].
Several studies have demonstrated the value of this approach
for posterior subcapsular cataracts [67]. These methods are
currently being used to evaluate cataract incidence and char-
acter in astronauts as part of the Longitudinal Study of Astro-
naut Health at the Johnson Space Center. Preliminary findings
indicate a trend toward a higher incidence of cataracts among
crewmembers who have flown outside the geomagnetosphere
(to the moon) or on high-altitude flights, thereby incurring
higher HZE exposures (Figure 23.12) [68].
Nervous System
Curtis and others [69] estimated that during interplanetary
space flight, every nucleus in the CNS (estimated area 100 m2
per nucleus) would be hit by a proton once every 3 days, by
an alpha particle once a month, and by higher weight particles
once a year. The National Academy of Sciences has expressed
concern regarding damage to nonrenewable cell systems,
especially the CNS, from HZE ions. Considerable uncertainty
Figure 23.12. Probability and standard error of cataract formation
versus time in NASA astronauts following first space mission for
low dose group (lens doses below 8 mSv, average 4.7) and high dose
group (lens doses above 8 mSv, average 45). A depicts data for all
cataracts; B depicts data for non-trace cataracts only. Trace cataracts
are defined as a small opacification with no apparent loss of visual
acuity
499
exists as to the long-term effects of radiation on neurons, but
studies by Lett and others with rabbit retinas suggest that
initial radiation-induced DNA lesions can be repaired, but
DNA degeneration will accumulate with age because of the
long-term effects of irradiation in the DNA repair processes
[63]. Such degeneration, in extreme forms, could conceivably
give rise to premature dementia and cerebellar dysfunction.
Late degenerative damage to neurons and behavioral changes
including accelerated aging has been seen in animal models.
Over the medium term of 15 years, CNS radionecrosis
can still occur through progression of vascular lesions, which
can continue for up to 15 years after exposure. Seizures have
been observed 7 years after irradiation. Diminished cognitive
capacity and motor performance may follow the progression
of vascular changes. Radiation myelitis of the brainstem and
spinal cord has been observed 1120 months after exposure to
4560 Gy (45006000 rad). Malignant intracranial neoplasia
has also been noted 5 or more years after exposure.
Interaction of Ionizing Radiation with Other Space
Flight Health Factors
Cellular and Immune Function
Assessments of immune function during long-term stays in
microgravity indicate that both cellular and humoral immune
functions are affected (see Chapter 15). Isolation, stress, and
diminished sleep may all contribute to these functional dec-
rements [70]. However, the microgravity environment itself
seems to induce a unique pattern of cellular genetic expres-
sion, at least as evaluated in in vitro conditions. During a
Space Shuttle investigation, human renal cells were grown for
6 days in microgravity and were then fixed during flight and
analyzed for changes in gene expression. The expression pat-
terns of 914 genes had changed as a result of microgravity
exposure; these included heat shock proteins and shear stress
response genes. Increased expression of specific transcription
factors, such as the Wilms tumor gene zinc-finger protein and
the vitamin D receptor, was also noted [71]. These findings
contrast with conclusions drawn from experiments flown
on Gemini 11, from which the investigators concluded that
microgravity had no synergistic effects with radiation during
orbital space flight [72], and Skylab, which showed no sig-
nificant differences in the growth curves of cultured Wistar-
38 human embryonic lung cells. Analysis techniques in the
Skylab experiments included microspectrophotometry, phase
microscopy, scanning and transmission electron microscopy,
and chromosomal C- or G-banding between space flight and
ground-based controls [73].
Several mechanisms have been postulated to explain
microgravity-induced changes in function at the molecular,
cellular, and tissue or organ levels. Changes in genetic expres-
sion, especially in terms of DNA repair and hormonal and
cytokine production, are thought to be particularly important
in the potential synergy between microgravity and ionizing
500
radiation exposure [7476]. Investigators on the European
Space Agencys Biorack experiments found more anomalies
in fetal insect tissues exposed to an onboard ionizing radia-
tion source than onboard controls that were not exposed; the
conclusion from these experiments was that microgravity has
synergistic effects with GCR [77]. In the late 1970s, Grigoriev
and colleagues [78,79] reported a synergistic effect of radia-
tion and microgravity in the production of chromosomal
aberrations in lettuce seeds and in Artemia (brine shrimp)
larvae; work on the Biosatellite II mission demonstrated
time-dependent effects of space radiation on pupal and larval
development of a beetle (Tribolium), a wasp (Habrobracon
juglandis), and a fly (Drosophila melanogaster) [80].
If the differences in genetic expression noted during these
inflight investigations are valid, they could significantly affect
the cellular response and repair mechanisms normally acti-
vated by exposure to ionizing radiation. This presumption
would be contrary to opinions on radiation sensitivity during
early crewed space flight, in which microgravity was thought
to have no significant role [81].
Toxic Vehicular Agents
Many chemicals associated wih space flight have potentially
injurious effects. Hypergolic fuels such as hydrazine and
nitrogen tetroxide as well as their combustion by-products are
quite toxic to human tissues as well as being carcinogenic;
their effects may be additive in combination with ionizing
radiation. Components of the interior vehicular structure will
emit volatile compounds into the contained atmosphere (listed
in Chapter 21. Control levels for many of these agents have
been established in attempts to prevent their potentially toxic
effects from overtly affecting the crew. However, some of these
agents can produce cellular injury by increasing oxidative stress
or diminishing the cells natural defense mechanisms to oxi-
dative stress. Therefore coincident ionizing radiation may act
synergistically with inhaled or absorbed airborne chemicals to
produce cellular injury in target organs.
Acceleration and Vibration
Exposure of space crews to acceleration forces is usually brief,
lasting on the order of minutes during the launch and landing
periods, and thus is not thought to be a major modifier of radiation-
induced bioeffects. Only limited studies have been conducted
to date on acceleration in combination with radiation exposure.
Animal studies by Bender and colleagues focused on cellular-
level responses; those by Antipov and colleagues looked at
whole-organism effects. Both modest synergy and antagonism
were observed, depending on the timing and intensity of exposure.
Slight increases in radiation resistance seen during the accel-
erated state were attributed to acceleration-induced hypoxia
resulting in reduced oxidative stress [82].
Exposure to vibration during space flight is also brief, expe-
rienced mainly during launch and landing, and is not believed
to modify radiation-induced bioeffects. Limited previous
J.A. Jones and F. Karouia
studies have shown vibration to have either synergistic or
antagonistic effects depending on the timing and intensity of
the exposure [82].
Planetary Surface Dust
On lunar and Mars missions, crewmembers may be exposed
to planetary surface dust particles. Presumably surface habitats
will have an air scrubbing system for particulate matter, and
that system will be aided by planetary gravity. However, such
gravity fields will be lower than those of Earth and particles thus
will be suspended for longer periods before settling, thereby
increasing the chance of aspiration. Lunar regolith was found to
be chemically inert, composed mainly of silica, but its angular
shape and hardness made regolith particles abrasive, particu-
larly to space suit components. Chronic inhalation of these dust
particles could produce inflammatory changes in the alveoli.
Remote measurements and analysis suggest that the Mars regolith
is chemically reactive [83]. Oxidizing or reducing soil when
inhaled into the pulmonary system carries its own risk of
pulmonary injury, but the localized reaction, along with an
induced chronic inflammatory reaction, may be synergistic to
coincident ionizing radiation exposure to the lung.
Clinical Aspects of Acute Ionizing
Radiation Exposure
Manifestations of Exposure
Although the most common acute radiation incident in indus-
trial settings involves local skin exposure, acute events in the
spaceflight environment will most likely involve whole body
exposures from SPEs. For a LEO platform in a low incli-
nation orbit, radiation from even a significant SPE may be
barely detectable. However, a geosynchronous platform or
a transplanetary spacecraft outside the geomagnetic field is
highly exposed, and the dose to the crew will depend entirely
on shielding. For an SPE such as the one that took place on
4 August 1972, which involved the largest particle fluence
ever recorded, the annual and career exposure limits for the
skin would be rapidly exceeded. During the peak intensity
period, the average dose-equivalent behind 2 g/cm2 equivalent
of aluminum shielding would have been 1.5 Sv/hour (150 rem/
h) [84]. The radiation dose to a crewmember conducting an
EVA during this time would certainly have exceeded the
threshold for deterministic clinical effects.
Exposure to even a few Sieverts (several hundred rem) may
go unnoticed; exposed individuals may be completely unaware
and without symptoms for several hours afterward. In the very
early phase of exposure, the diagnosis of radiation exposure
equates to dosimetry. Specific responses to measured doses of
ionizing radiation have been characterized according to total
dose and time and are influenced by individual variability,
level of treatment, and other factors. Preexisting illness, stress,
immune compromise, infections, and dietary deficiencies all
23. Radiation Disorders 501

Table 23.10. Selected features of acute radiation syndromes after whole-body exposure.
Characteristic signs and
Principal cause of death Lethal dose symptoms prodromal Time of death
(latency period) range, Gy Underlying cellular event phase Principal phase (after exposure)
Hematopoietic 2.510 Necrosis of bone marrow cells Anorexia, nausea, Petechia and purpura, bleed 23 weeks
(23 weeks) vomiting ing from mucous membranes,
infection
Gastrointestinal 1050 Necrosis and mitotic arrest of mucosal Anorexia, nausea, Fever, bloody diarrhea, loss of 512 days
(37 days) stem cells vomiting fluids and electrolytes
Acute incapacitation 50+ Unknown; perhaps direct injury of Anorexia, nausea, Apathy, lethargy. 1036 h
(15 min3 h) endothelial cells, death of neurons vomiting, confusion, somnolence, tremors,
and vasculitis at very high doses ataxia, anxiety convulsions, coma
Source: From Fajardo et al.[61].

correlate negatively with survival. A combined injury scenario Table 23.11. Expected acute radiation effects for doses acquired
involving major trauma and acute radiation syndrome could be over 24 h or less.
particularly severe. The radiation impairment of immune and Effective doses, rad (Gy)a
fibroblastic cellular reponse will significantly delay trauma- Symptoms ED10 ED50 ED90
induced wound healing as well. Anorexia 40 (0.4) 100 (1) 240 (2.4)
Nausea 50 (0.5) 170 (1.7) 320 (3.2)
Vomiting 60 (0.6) 215 (2.15) 380 (3.8)
Acute Radiation Syndromes
Diarrhea 90 (0.9) 240 (2.4) 390 (3.9)
The predominant symptoms resulting from acute radiation Erythema 400 (4) 575 (5.75) 750 (7.5)
exposures are predictable and depend on the dose received; Desquamation 1,400 (14) 2,000 (20) 2,600 (26)
a
exposure to 15 Gy (100500 rad) produces the so-called hema- Effective doses are those at which a specified dose would produce the effect
topoietic syndrome; 520 Gy (5002,000 rad), the gastrointes- in question in various percentages of the exposed population; ED10, for
example, is the dose that would cause the given effect in 10% of the popula-
tinal syndrome; and exposure to more than 20 Gy (2,000 rad) tion exposed to that dose.
evokes the CNS syndrome. Table 23.10 summarizes the char-
acteristic signs and symptoms based on the pathophysiologic
mechanisms underlying each of these three syndromes [61].
with coronary artery disease. Oral ulcerations appear at 34
days after exposure and are often associated with fungal over-
Temporal Sequence of Acute Reponses to Whole-Body
growth. Erythema of the skin becomes apparent 13 days after
Radiation Exposure exposure. The predicted acute effects of radiation exposure
The transient prodromal phase generally lasts 4872 h and is acquired over less than 24 h, according to dose, are summa-
seen after low to moderate doses of acute ionizing radiation. rized in Table 23.11.
For doses larger than 10 Gy (1,000 rad), the prodromal phase The latency phase is relatively free of symptoms, represent-
is almost nonexistent. During this phase, chemical mediators ing the time between initial injury to cells and the manifesta-
are released from damaged cells in the marrow, lymphoid tis- tions of impaired cell repair and renewal; it typically lasts 320
sues, and possibly the gastrointestinal tract. Release of these days. At 710 days after exposure, loss of mitotic activity results
mediators peaks at 812 h; they are usually cleared by mac- in incomplete, temporary hair loss. The number of surviving
rophages by 48 h after exposure. Doses of less than 10 Gy stem cells determines the duration and magnitude of compli-
(1,000) typically produce fatigue, malaise, listlessness, apa- cations such as pancytopenia and infectious disorders, since
thy, and weakness. Neuromuscular symptoms include head- these cells are the only source of renewal [damage repair] in
ache, insomnia, difficulty concentrating, occasional dizziness, mitotically active tissues.
or vertigo. Psychological symptoms can include depression, The recovery phase is characterized by stem-cell renewal
despair, and hopelessness. Gastrointestinal manifestations of depleted and damaged cell populations in the bone marrow
may include abnormal tastes and smells, stomach upset within and the gastrointestinal crypts. Whether recovery occurs at all
2 h, anorexia, and nausea leading to emesis by 58 h, which depends on the radiation dose and the availability of medical treat-
usually subsides by 12 h. Painful edema of the parotid glands ment (Table 23.12). At a minimum, treatment should include
is typical. Diarrhea, intestinal cramps, dehydration, and fluid and electrolyte support and palliative care. Hematopoietic
weight loss may develop within 37 days. Doses of 7.510 Gy syndromes will require more vigorous supportive care, includ-
(7501,000 rad) are often associated with a drop in blood ing blood products, infectious isolation, and carefully targeted
pressure and an increase in pulse rate because of circulatory antibiotic therapy. Gastrointestinal syndromes may require
hypovolemia; these effects can lead to early death in individuals oral or parenteral nutritional support. Advanced treatment may
502
Table 23.12. Whole-body radiation dose lethal to half of the popula-
tion (LD50) without and with treatment.
Expected response in healthy adults Dose
Blood count changes 50
Effective threshold for vomiting 100
Effective threshold for mortality 2 Gy (200 rad)a
LD50 with minimal medical treatment 3.5 Gy (350 rad)
LD50 with supportive medical treatment 5 Gy (500 rad; range, 4.85.4 Gy)
LD50 with advanced medical treatment 10 Gy (1,000 rad)
a
(ED10 = 2 Gy; ED50 = 2.85 Gy; ED90 = 3.5 Gy).
Source: (Victor Bond NCRP SC75 report).
Table 23.13. Correlation of lymphocyte counts with radia-
tion dose level and clinical effects at 24 hafter an acute radiation
exposure.
Lymphocyte counts Dose level and expected clinical effects
>1500/mm3 Insignificant dose; no treatment necessary
10001500/mm3 Low dose; treatment may be necessary for moder
ately suppressed polymorphonucleocyte and
platelet counts at 34 weeks after exposure
5001000/mm3 Moderate dose; treatment for moderate to severe
injury will be required; hemorrhage or infection
can develop at 23 weeks after exposure
<500/mm3 High dose; treatment for severe injury will be
required; exposure can be lethal, pancytopenia
will ensue at 2 weeks
Undetectable Very high dose; palliative treatment as needed;
survival unlikely beyond 2 weeks
involve compatible bone marrow transplantation or immune
cell stimulants such as granulocyte-macrophage colony stimu-
lating factor. Differential diagnosis of a crewmember present-
ing with acute whole-body radiation exposure should not be
problematic if the radiation detection equipment is function-
ing properly. However, if real-time dosimetery equipment is
not located near the individual during exposure (e.g., during
an EVA that takes place during an SPE), the clinical signs
can give a rough indication of exposure. Vomiting within 3 h
of exposure suggests a high dose. Prompt, explosive bloody
diarrhea suggests a lethal exposure. An early drop in the lym-
phocyte count indicates injury to the blood-forming organs, but
levels of platelets and polymorphonucleocytes (PMNs) later
after exposure are the most important guides for therapy. The
PMN count will initially increase as a result of inflammatory
release from the marrow; PMNs are not as vulnerable as stem
cells. Neutropenia develops 34 weeks after sublethal expo-
sures as the granulocyte reserves become depleted. Lympho-
cyte counts 24 h after exposure are a rough indicator of overall
dose and expected clinical sequelae (see Table 23.13); means
of measuring lymphocyte counts during space flight are under
development.
Given the wide-ranging physiological changes induced by
the weightless environment, including diminished red blood
cell mass and immune function, it remains to be seen whether
J.A. Jones and F. Karouia
the symptomatic thresholds and dose-response relationships
are the same for long-duration space crewmembers as for the
terrestrially exposed. The net physiological effects of space
flight would not seem to be favorable; however, further inves-
tigation is clearly needed.
Clinical Case Management
Adequate therapy for even one victim of whole-body radia-
tion will require significant medical care resources, and con-
sumables such as antibiotics and blood products in any remote
medical facility will be rapidly depleted. Treatment modalities
and adjuncts for acute radiation syndromes stretch any foresee-
able spacecrafts logistics, storage, and shelf-life constraints to
extreme limits. Plans for equipping a space vehicles medical
facility must account for the likelihood of whole-body exposure
syndromes, the possibility of rendering aid onsite vs the need to
return a patient or patients to Earth, and the level of risk deemed
acceptable from an operations standpoint. The level of training
for the crew medical officer will be a vital element; expecting
an individual who is not a physician to administer the level of
care required to support even a minor acute radiation exposure
during space flight is hardly justifiable. Classifying the radia-
tion injury broadly in terms of exposure may be useful for mak-
ing triage decisions. In such a classification, an exposure to up
to 2 Sv (200 rem) would be considered mild, with survival
deemed probable; exposure to 27 Sv (200700 rem) would be
moderate, with survival possible; and exposure to more than
7 Sv (>700 rem) would be severe, with survival improbable.
The primary determinant of survival for individuals sustain-
ing significant radiation exposures will be the ability to manage
the sequelae of pancytopenia, with attendant decreased antibody
production and phagocytosis. Clinical problems include sus-
ceptibility to infection and sepsis from skin or mucosal injury
and loss of gastrointestinal epithelial tight-junction integrity, as
well as hemorrhage from thrombocytopenia. Survival to 56
weeks indicates that marrow recovery is underway.
Initial Treatment
Until the bone marrow recovers, the greatest concern for initial
treatment strategies is infection. The main endogenous bacterial
flora to cover will be Escherichia coli, Klebsiella pneumonia,
Pseudomonas aeruginosa, Staphylococcus aureus, and fungi
such as Candida albicans. Synergistic antibiotic combinations
such as late-generation -lactams with clavulanic acid or mono-
bactam agents with an aminoglycoside should be given at the
onset of granulocytopenic fever and continued for about 2 weeks
or until the leukocyte counts exceed 5,000/L. Antifungal agents
such as fluconazole or amphotericin should be given to patients
whose blood cultures test positive for fungi or whose fevers do
not respond to antibacterial agents. Support of septic shock will
also require parenteral steroids such as methylprednisolone.
Platelet transfusions, if available, are indicated for patients
with platelet counts of less than 50,000/L who are actively
23. Radiation Disorders
bleeding; platelets should be given prophylactically when
counts are less than 20,000/L. Erythrocytes and plasma may
be required as well.
Nausea should be treated symptomatically with anti-
emetics such as prochlorperazine and promethazine. Treat-
ment of gastrointestinal manifestations may require large
amounts of intravenous fluids in addition to blood products,
and possibly nutrition via peripheral or central intravenous
lines. Radiation-induced skin injury would be treated as a
thermal burn based on the degree and percentage surface
area burned. Ringers lactate solution, topical antibacterial
creams, and petrolatum gauze dressings to the areas of
skin damage constitute an initial response like that in the
terrestrial setting. Because a transplanetary spacecraft is
unlikely to have room to carry sufficient intravenous fluids
to support treatment in such a scenario, parenteral support
will rely on the on-site manufacture of sterile fluids from
potable water sources.
Advanced and Definitive Care
The advanced therapies described here are at present far
beyond the scope of any spacecraft medical facility that
has been flown thus far. For patients exposed to more than
4 Gy (400 rad), bone marrow transplantation may be the only
chance for survival and should be begun between 1 and 2
weeks after exposure. Autologous marrow is greatly preferred
to heterologous marrow to avoid inducing graft-vs-host reac-
tions. Preparations for missions in deep space should require
collection of autologous marrow from all crewmembers
before flight, and that marrow should be stored in a refrigerated,
radiation-protected facility on board. Marrow stimulants such
as recombinant erythropoietin for erythrocyte precursors, and
granulocyte and granulocyte-macrophage colony-stimulating
factors for leukocyte precursors, may be used. Immune modu-
lators such as interleukin-2 and interleukin-3 may be also
useful for stimulating granulopoiesis and immune function.
Current Spacecraft Medical Capabilities
Currently operating crewed spacecraft are limited to LEO,
where the chance of an acute clinical radiation syndrome is
highly unlikely, as it would have to entail an EVA taking place
during a major SPE. However, procedures are in place for
dealing with such an event. The ambulatory and emergency
medical packs on the Space Shuttle enable the crew medical
officers to provide basic initial supportive care for an acute
radiation injury (described in Chapter 5). These kits include
limited supplies of intravenous fluids, parenteral antiemetic
agents, containers for vomitus, and oral antidiarrheal agents.
Also included are first aid supplies for skin injury, including
ointments and bandages to protect erythematous regions and
to prevent breakdown of injured epidermis. Actual desqua-
mation ulcers will be treated like thermal burns with topical
antibiotics and dressings. The selection of oral and parenteral
antibiotics for infection management will be limited. The ISS
503
medical kits include all of the drugs found in the Shuttle kit in
greater amounts, as well as an expanded advanced life support
capability that includes respiratory support and cardiac moni-
toring, defibrillation, and pacing. The current stock of medical
supplies onboard the ISS allows medical stabilization of an
acute significant illness, but it does not allow that support to
be maintained for longer than about 48 h.
A mainstay of medical decision-making in LEO involves
evacuation to definitive care on Earth. A significant radiation
exposure requiring medical treatment would prompt return
of the crew as soon as is practical, depending on vehicle safing
requirements (e.g., configuring the station to continue opera-
tion in an untended mode if required) and landing site opportu-
nities, to facilitate definitive care. Under most circumstances,
return to an Earth-based tertiary care facility from LEO may
be expected within 24 h. This would not be true for exploratory
missions. A lunar base may require more extensive safing, or
the injury may require more local care before the crew could
safely endure the 2- to 3-day return to Earth. Crews outbound
for Mars may not have any abort option that would allow
return to Earth in time to positively influence treatment of
radiation syndromes. Treatment capabilities for exploration-
class missions will necessarily be more robust than those for
LEO missions.
Radiosensitizing and Radioprotective
Agents
Radiation sensitizers (factors that have synergistic effects
with radiation) can include chemicals such as polycyclic
aromatic hydrocarbons, aromatic amines, hydrazine/azo com-
pounds, metals, butyric acid [which is produced naturally in
the colon]), drugs (such as psoralens, purine and pyrimidine
analogs, paclitaxel, actinomycin D, hydroxyurea, raxozane,
and electroaffinic agents such as misonidazole), endogenous
factors (hormones, epidermal growth factor, or the presence of
infection, endotoxins, or hyperthermia), or space flightrelated
factors such as vibration, noise, nonionizing radiation, and
possibly acceleration forces [16].
On the other hand, the presence of radioprotective agents
at the time of exposure may lessen the initial ionizing events
from radiation such as cell death and induction of mutations.
Radioprotective agents have been studied in the context of
military (nuclear warfare) and medical (radiation oncology)
applications. In terms of effectiveness, the ideal radioprotec-
tive agent must be present at the time of exposure, close by the
site of damage (and remain there until the damaging actions
have stopped), and able to protect against injury or damage
arising from multiple pathways [8588]. In practical terms,
the ideal agent would be deliverable orally or parenterally;
it would be effective for days to weeks (or could be given
repeatedly); it would have minimal effects on performance; it
would have no cumulative toxicity and minimal side effects;
it would be compatible with other drugs; and it must have a
504
long (2- to 5-year) shelf life. Although hundreds of potential
radioprotectants have been studied to date, the ideal agent has
yet to be identified.
Many chemoprotective compounds are present in natural
sources (Table 23.14). Indeed, it is preferable to derive these
agents from natural sources, both for palatability and for the
quality of their biological activity. However, it is not always
possible to provide fresh foods and vegetables for an entire
mission (especially long-duration missions), and therefore
other means of accessing these nutrients, particularly with
regard to their chemoprotective qualities, must be developed.
Many potentially chemoprotective agents have undergone
extensive testing in preclinical and clinical trials for their
anticancer or cancer-prevention properties; indeed, much of
the clinical experience with radioprotective agents has come
from radiation oncology [89,48]. Of the chemical agents,
amifostine (WR-2721) has been relatively well studied in this
context, [48,9093,] as has misoprostol [48,94]. Antioxidant
agents such as vitamin C, vitamin E, beta-carotene, selenium,
N-acetyl cystine, and alpha-lipoic acid may be recommended
as prophylactic agents for deep space missions. Because radi-
ation causes damage at many levels, a combination of agents
representing the major classes of prevention molecules may
be added to a daily prophylactic regimen. Such a regimen
might include one or more of the following agents: retinyl
acetate, allylic sulfide, ellagic acid, tea polyphenols, terpenes,
isoflavones, isothiocyanate, indoles, flavonoids, phytoestro-
gens, anti-inflammatories, and protease inhibitors. Several
other radioprotective agents have also been studied for their
anticataractogenic effects [66,95,96]. Tests of agents used to
protect against the effects of HZE radiation have been more
limited; the few studies conducted have focused on reducing
the frequency of mutations in cells [97] or reducing the num-
ber of cancers in exposed animals [98100].
Table 23.14. Natural sources of chemical radioprotective agents in
plants.
Compounds Sources
Allium and N-acetyl cysteine [diallyl Onions, garlic, chives, scallions
sulfide]
Sulphoranes, indoles, and isothio Cruciferous vegetables (e.g., broccoli,
cyanates [dithiolthiones, indole- cauliflower, kale, cabbage)
3-carbinol]
Isoflavones and phytoestrogens Soybeans (e.g., tofu, soy milk)
Terpenes and ascorbic acid [perillyl Citrus fruits (esp. lemon peels),
alcohol, limonene] cherries, tomatoes
Curcumins Tumeric
Carotinoids, lycopene, lutein, Yellow vegetables, fruits (e.g.,
antioxidants carrots, tomatoes, squash)
Polyphenols and flavonoids Green and black teas, fruits, wine
[epigallocatechin gallate,
thearubigens, theaflavins]
[Phenolic acids- ellagic acid, Whole grains, nuts, tomatoes, carrots,
ferulic acid] citrus fruits
J.A. Jones and F. Karouia
Biological Effects of Nonionizing
Radiation
Higher organisms have developed effective shielding mecha-
nisms for UV radiation, e.g., the stratum corneum and mel-
anin skin layers, to protect their DNA from the biological
effects of shorter wavelength UV radiation. The risk of bio-
logical damage is tied to the specific spectral region and the
effective irradiance incident upon the exposed tissue [101].
Short-wavelength UV radiation does not penetrate into the
cell nucleus but does damage the cell membrane. Longer
wavelength (240400 nm) UV radiation penetrates into the
cell, where it causes protein photodestruction and dimeriza-
tion of nucleic acids [102]. UV cell killing results mainly
from nucleic acid alterations rather than protein inactivation,
as originally suspected. The main UV-photo product, cyclobu-
tane pyrimidine dimers, is highly disruptive to the normal pro-
cesses of replication and transcription. UV has a particular
propensity to produce cross-linking between identical DNA
bases (dimerization) either within or between DNA molecules
[8]. Cyclobutane pyrimidine dimers can be repaired by pho-
toreactivation with light of 300600 nm, which costs the cell
no energy and is error-free; or excision repair, which requires
cellular energy and can be inaccurate.
Eye Effects
Unlike the skin, the outer layer of the cornea of the eye is com-
posed of living cells. All three types of UV radiation can dam-
age the cornea. This is one of the more significant concerns of
space flight and deserves specific mention here. Photokerati-
tis and photoconjunctivitis, also known as snowblindness,
can result within as few as 90 min, but usually occur after a
4- to 12-h symptom-free period after exposure without eye
protection. In terms of photokeratitis, the eye is most sensitive
to wavelengths of 270 nm. The action spectrum threshold for
corneal reaction is 414 mJ/cm2. Symptoms include the sensa-
tion of sand in the eyes, photophobia, blurred vision, edema
of the eyelids, lacrimation, and blepharospasm. Horizontal
staining bands may be seen on fluorescein staining, and acute
corneal ulcers can be seen on magnification. Acute symptoms
last 24 h, and the discomfort usually disappears by 3648 h
after exposure.
Treatment of photokeratitis involves examination and
removal of any ocular foreign bodies, including contact lenses.
An ocular anesthetic can be instilled to relieve pain, but dos-
ing and repeat installation should be limited. If ciliary spasm
is severe, a cycloplegic-mydriatic agent should be instilled.
Antibiotic ointment should be applied, followed by an eye
patch and shield, taped into position. The patch should be left
in position for 12 h before re-examination and reapplication
of antibiotic. Oral pain medications should be used if pain
is severe and cannot be controlled with the above measures.
Generally topical steroids are not indicated and may interfere
23. Radiation Disorders 505

with re-epithelialization. Except for full-thickness injury, the the wavelength of incident light and the spectral weighting
corneal epithelium will heal and regenerate within days to a functions for retinal light hazards [106].
week; full-thickness injuries may produce scarring. Evaluating a given exposure requires consideration of several
UV-A exposure (350380 nm) can produce lenticular fluores- points. First, the ACGIH values are not to be taken as a fine
cence that is not damaging but can produce an unusual haze sen- line between safe and unsafe conditions. Rather, they should
sation on the retina in the absence of visual light. Chronic or very be used as a guide, bearing in mind that the error associated
high-dose exposures can result in lenticular opacities, especially with the available statistics is large enough so that case-by-
in the posterior subcapsular region of the lens. [95,103105] case analyses are necessary. Second, because of the statistical
Cataracts in experimental rodents are produced by exposures to inadequacies in the available exposure database, a margin of
light of 295320 nm wavelengths, at a threshold of 0.1512.6 J/ error is taken into account in the limits. For the retinal thermal
cm2 depending on the incident wavelength. (visible) hazard, a safety factor of 10 is associated with the
The eye possesses two focusing (refracting) mechanisms for source term in the calculation; a safety factor also applies to
incident lightthe convex surface of the cornea and the dual permissible exposure limits for blue light exposure. For IR,
convexity of the lens. The ocular media (aqueous and vitreous there is at least this margin of safety because of the conditions
humor) are transparent and transmit the focused light to the retina implied by the hazard. For UV exposure to the skin or the eye,
such that the irradiance (radiant exposure) is greatly enhanced at there is no safety margin, and the limits given are the levels
the level of the retinal pigment epithelium. The nonregenerative at which molecular rearrangement would be expected. Third,
properties of this epithelial layer increase the potential conse- it should be noted that the limits given are levels at which
quences of overexposure to nonionizing radiation. The retinal molecular damage is expected, and these levels are often well
pigment epithelium is where the first histologic and probably below clinically detectable damage. Finally, the calculated
ophthalmoscopic damage is detectable. Higher levels of expo- times should be weighed against the bodys own natural aver-
sure can also damage the choroids and neural retina, which can sion response. For example, if a look time of 5 s is calculated
result in permanent visual field defects. Such defects can be with regard to the retinal thermal injury pathway for exposure
especially serious if the fovea and macula are involved. to the sun, then the reality of directly viewing the solar disk
for 5 s should be evaluated. In this case, the pain associated
Estimating Risks Associated with Viewing Activities with direct viewing of the sun would probably cause an indi-
vidual to look away before the limit was reached, even though
A favorite crew activity, both for Earth observation and for
the time itself may seem to be short. These considerations
recreation, is looking out spacecraft windows. On an orbiting
should be borne in mind in evaluating risks associated with
spacecraft, the solar spectrum is not attenuated by the Earth
each pathway.
atmosphere and thus the hazards associated with exposure to
In evaluating a particular viewing condition, the risk of
direct solar irradiance are greater than exposure to atmospheri-
retinal thermal injury associated with viewing a visible light
cally screened irradiance on Earth. Thus the light transmittance
source should be evaluated in terms of look time, window
properties of spacecraft windows and protective eyewear for
space crews require careful analysis to avoid exposing crews
to harmful levels of electromagnetic radiation.
The best current source of information on human exposure
to nonionizing radiation is found in the American Conference
of Governmental Industrial Hygienists (ACGIH) Threshold
Limit Values and Biological Exposure Indices, which outlines
a method for evaluating the effects of exposures according
to four pathways: retinal thermal injury from exposure to a
visible light source (region of interest, 4001400 nm), reti-
nal photochemical injury from chronic exposure to blue-light
(region of interest, 400700 nm), exposure of the unprotected
skin or eye to ultraviolet radiation (region of interest, 180
400 nm); and corneal or lenticular injury from exposure to
an IR source (region of interest, 7703000 nm). The ACGIH
method involves evaluating a known spectral distribution and
provides a method for calculating the amount of time that
the source may be directly viewed, or the amount of time for
direct exposure in the case of skin UV exposure, before mea-
surable molecular effects accrue. This look time can be used Figure 23.13. Retinal thermal injury potential from the solar out-
to guide crewmembers as to appropriate exposure durations. put spectrum, based on the American Conference of Governmental
Figure 23.13 illustrates the peaks in injury potential based on Industrial Hygienists (ACGIH) blue light hazard function [106]
506
Table 23.15. Permissible ISS window observation time to avoid eye
injury.
Time to injury Time to injury
Light and damage Light without approved with approved
pathway wavelength sunglasses sunglasses
Ultraviolet 180400 nm 36 min >8 h
Blue light (direct 400700 nm 4.41 s 30.35 s
continuous vision)
Retinal thermal 4001400 nm 1.71 s >1 h
Infrared (corneal) 7703000 nnm 27 min >8 h
transmittance, sun angle, and sun spectral irradiance. For
exposures longer than 1,000 s (about 16 min), the exposure
to humans should be limited to 10 mW/cm2. The calculated
exposure from this portion of the solar spectrum is 5.9 mW/
cm2; thus the exposure is roughly half of the long-exposure
limit and therefore is acceptable. Analysis of transmittance
through the ISS windows reveals an ocular hazard to the ret-
ina and other elements of the eye such that damage to these
elements may occur within a matter of seconds of exposure if
appropriate eye protection is not used. The window materials
(magnesium fluoride and borosilicate) provide some protec-
tion from UV and IR wavelengths but not other wavelengths.
Various types of sunglasses have been tested for their ability
to block or filter transmission of light in the wavelengths of
greatest concern; those that provide adequate protection and
have been approved allow less than 2% transmittance of light
shorter than 400 nm, less than 10% of light in the 400- to 700-
nm range, and less than 30% of light longer than 700 nm. The
permissible look times while wearing these sunglasses thus
can be extended from seconds to minutes or hours of constant
viewing through windows from which the scratch pane has
been removed (Table 23.15).
The VIPOR study
A hazard analysis conducted for the Visual Investigation Pro-
gram on Orbiter Operations (VIPOR) specifically addressed
non-ionizing radiation hazards associated with window obser-
vations during space flight. According to this study, unpro-
tected viewing of the sun through the side hatch window of
the Space Shuttle (or, for an EVA crewmember, through the
EMU helmet without the sun visor protection being in place)
should be limited to less than 2 s because of potential injury
from light at several wavelengths. The exposure time limit
for blue light (Lblue) is 1.23 s, and that for exposure to actinic
UV (200315 nm) is 3.36 s. The time limits for exposure to
visible to infrared (IR) light is 11.7 s, 2.6 s, and 0.4 s based
on a respective pupillary size of 5, 6, and 7 mm. Because the
human blink reflex occurs within 0.150.2 s, the risk of thermal
injury to the retina is thought to be low. However, given the
collective risk from all nonionizing-wavelength radiation,
crewmembers are advised to wear additional eye protection
(in the form of blue-blocking polarizing sunglasses) when the
protective shroud is removed from the side hatch window of
the Space Shuttle during times of direct sunlight exposure.
J.A. Jones and F. Karouia
Skin Effects
Exposure to UV-B and UV-C wavelengths produces a
photochemical effect that depends on the wavelength and
duration of the exposure as well as the presence of melanin or
photosensitizers. Agents that sensitize skin to UV irradiation
include antimicrobial agents such as topical fungicides, hexa-
chlorophene, oral sulfa drugs and tetracycline; chlorproma-
zine; salicylate; psoralin; and oral contraceptive pills. Melanin
can increase the minimal erythema dose (typically 630 mJ/
cm2) by an order of magnitude. Observed effects resemble
those of terrestrial sunburn and include erythema (with a 4- to
8-h latency period), blistering (after 848 h) and desquamation
(more than 48 h after exposure). Exposure to a combination
of UV-A and UV-B intensifies the erythema response. Skin
sensitivity is maximal at 295 nm, and longer-wavelength UV
(295315 nm) produces a more severe and persistent erythema
response. Chronic exposure to UV radiation produces tough,
wrinkled, darkened skin (farmers skin or sailors skin)
characterized by thickening of the epidermis and actinic
changes such as actinic and seborrheic keratoses.
Exposure to UV radiation, especially UV-B, at early ages
predisposes the skin to basal cell and squamous cell carcinoma
and melanoma [107]. Individuals with defects in DNA repair
(e.g., those with xeroderma pigmentosum) are particularly
susceptible to skin cancer because of the inefficient repair
of UV-induced cross-links. Epidemiologic studies have also
shown higher rates of skin cancer among populations living at
low latitudes or those living at high altitudes and those with
low melanin content in the skin (e.g., individuals of Northern
European origin).
The main biological effect of IR radiation is thermal. High
levels of IR-induced tissue excitation produce increased tem-
perature in the tissue. Generally slight, short-lived increases
in temperature are well tolerated and rapidly dissipated by
the circulation. Prolonged continuous exposure to IR or other
nonionizing radiation, however, can overwhelm heat dissi-
pation mechanisms and elevate cellular temperatures, which
in turn can lead to the release of heat shock proteins and the
induction of apoptosis.
The strategy for controlling skin effects of exposure to non-
ionizing radiation is to use topical sunblock creams (those
with a sun protection factor [SPF] rating of 30). Crewmembers
are required to use such skin creams when the exposure of
uncovered skin through the windows in the Lab Module, the
Japanese Experiment Module, or the Cupola is anticipated to
exceed 45 min over the course of a 24-h period.
Whole-Body Effects from Electromagnetic
Radiation
When the human body is exposed to electromagnetic radiation
in the radiofrequency wavelengths, some of the radiation is
absorbed and some passes through depending on the frequency.
Both the type of tissue and the frequency of the radiation affect
23. Radiation Disorders
the depth of energy penetration and degree of absorption. For
frequencies below 150 MHz, the body acts like a cylindrical
antenna. For a typical 1.7-meter human, the resonance fre-
quency is 44 MHz on the ground and 88 MHz in free space;
this means that humans in the path of 88 MHz electromagnetic
radiation can incur significant heating and tissue effects.
The carcinogenic potential of electromagnetic radiation is
controversial. Despite highly sensationalized anecdotal reports
of brain cancer in individuals who use cell telephones, or tes-
ticular cancer in policemen who use radar to monitor the speed
of motorists, no clear evidence of any increase in risk, or any
possible mechanism of induction, has ever been found. In a 1997
meta-analysis of 70 studies to examine whether electromag-
netic radiation was associated with cancer incidence [108], the
authors concluded that a very small elevation in cancer risk was
associated with exposure to electromagnetic radiation exposure
in the workplace (relative risks of 1.10 for brain cancer and 1.18
for leukemia). However biases may have affected conclusions
drawn in the studies analyzed that could have influenced their
results and the results of the meta-analysis.
Space Radiation Monitoring and Dosimetry
As is true for any occupational radiation exposure, the radia-
tion doses incurred during space flight must be meticulously
measured and tracked to ensure that identified health limits
are not exceeded. Space radiation dosimetry differs from other
branches of radiation physics in that the energies of the radia-
tion to be measured can extend over many orders of magnitude
and the radiation can include particles of many different species,
thus mandating the measurement of several types of variables.
A variety of techniques and instruments have been developed
for measuring absorbed dose, dose equivalents, particle flux
and fluence, and linear energy transfer spectra as well as particle
charge, mass, and energy distribution. Most of these variables
vary temporally as well as spatially. The detectors used in
space-based dosimetry include thermoluminescent dosimeters
(TLDs), plastic nuclear track detectors, tissue equivalent pro-
portional counters (TEPCs), and charged particle directional
spectrometers. After each space mission, an integrated report
detailing the radiation dose for each crewmember is developed
and becomes part of that crewmembers medical record.
Space radiation dosimetry can be accomplished through
the use of active or passive measurement systems. Active sys-
tems involve dosimeters whose data can be read during flight,
either on board or after telemetry to Earth and near-real time
processing. Passive systems, in contrast, are dosimeters that
are read and analyzed after landing; two examples used in
space radiation dosimetry are TLDs and plastic nuclear track
detectors. In the absence of active monitoring and telemetry,
the crew and flight control team must rely on exposure data
collected from orbiting satellites and the use of models to
calculate the projected dose to the crew at altitudes that are
different from those of the detection satellites. One such satellite,
507
the TIROS, orbits at 830850 km from Earth; by comparison,
the ISS orbits at 400 km from Earth.
Passive Dosimetry
Several types of passive dosimeters are used to track radiation
doses to the crew and to the space vehicle over time. The crew
personal dosimeter devices are small (5.5 3 0.5 cm) Lexan
badges containing TLD chips that are to be worn at all times;
these devices track an individuals accumulated dose throughout
a mission. Crewmembers are asked to wear the dosimeters dur-
ing launch and entry and EVAs, which necessitates transferring
the devices from clothing to the space suits. Personal dosimeters
are returned with the crewmembers, and their data are processed
after landing. Another type of passive dosimeter are the area
monitors, which also incorporate TLD chips and are deployed
throughout the Space Shuttle and the ISS to measure radia-
tion that accumulates over the course of a mission. Devices on
board the ISS are retrieved and exchanged at each crew rotation.
Doses to the area monitors vary according to their location on
the spacecraft (and the associated structural shielding) and the
spacecraft attitude; as such, they are strategically deployed so as
to best characterize the radiation environment of the habitable
volumes and to correlate with personal dosimetry. High-rate
dosimeters are carried for contingency scenarios involving large
radiation exposures, such as those arising from a massive SPE or
the detonation of a nuclear weapon in space. These dosimeters
consist of small, easily visualized ionization chambers that are
designed to give rough estimates of radiation doses between 0
and 6 Gy (600 rad).
Active Dosimetry
Real-time measurement of radiation exposures during space
mission require the use of active dosimeters. A suite of such
dosimeters is currently on board the ISS, and others are being
developed to enable real-time insights into radiation doses
that might prompt immediate crew action. Two types of active
dosimeters, those focused on microdosimetry and measure-
ment of particle types and spectra, are described below.
Microdosimetry: Tissue Equivalent Proportional
Counters
Microdosimetry is based on the principle of measuring the
energy deposited in microscopic (1-m3) volumes of simulated
tissue. For measuring energy loss from charged particles, tis-
sue volumes of about 0.3 m3 to several m3 can be replicated
by using gas at low pressure. Since the physical basis of the
RBE of different types of radiation is thought to result from
differences in the spatial distribution of ionization along the
particle track, physical quantities can be measured and related
to biologically relevant quantities. Radiation experts now rec-
ommend that the quality factor Q be expressed in terms of
LET, which can be measured directly by microdosimeters.
508
The tissue-equivalent proportional counter (TEPC) is the
microdosimeter currently flown in the U.S. space program. It
has flown on the space shuttle, the Mir space station, and is
flying aboard the International Space Station (ISS) with data
continually fed to the ground via telemetry link.
Tissue equivalent proportional counter devices are character-
ized by small, nearly spherical chambers filled with a low-
pressure gas such as propane. The gain of such devices, created
by applying a potential of 600800 v to a wire that passes
through the chamber, has been demonstrated to be stable for
more than a year, and calibration tests using ion beams at a
particle accelerator have verified the ability of such instruments
to measure LET distribution accurately. The TEPC is relocated
periodically to map the dose in various parts of the station.
LET-Spectrum Measurement: Particle Spectrometry
Microdosimetry instruments such as the TEPC cannot distin-
guish among particle types, nor can they provide information
on the arrival direction of the particles. Detecting the arrival
direction of GCR is not crucial since their fluence is isotropic.
However, trapped-belt protons are highly directional and
energy dependent. Radiologic studies [9] indicate that inacti-
vation or transformation cross-sections for cells are not a func-
tion of LET but rather of the nuclear charge Z and the velocity
of the particle, where = v/c (velocity v is expressed in
units of the velocity of light, c). The restricted energy-loss
model predicts a dependence of these cross-sections on Z2/
2. Knowing the particle charge and velocity thus provides
a means of computing the relevant energy loss parameter in
any medium. When a nonrelativistic particle of charge Z and
velocity comes to rest in a stack of detectors, the amount of
energy that it deposits in a top thin layer of thickness x is
DE ~ (Z2 / b 2) Dx
Detectors in a charged particle spectrometer can be stacked
to allow discrimination of energies over a broad range. If the
particle of mass m is stopped in the bottom detector, its residual
kinetic energy E is
E = mb 2/2
and thus
EDE ~ mZ2
Every isotope can be represented by a unique hyperbola pro-
portional to the mass of the particle and the square of its nuclear
charge. The measurement, therefore, of E and E yields a mea-
sure of the kinetic energy per nucleon, particle charge, and iso-
topic mass. Care must be taken with such detector systems to
limit the acceptance angle of the spectrometer so that the varia-
tions in the particle path length are minimized. One option is
to use position-sensitive detectors that can provide the arrival
direction of the particle and avoid these path length variations.
As particle energy increases, it becomes impractical to increase
the depth of total E detectors because of possible interactions
of the particle in the detector material. The charge, mass, or
J.A. Jones and F. Karouia
energy of these high-energy particles cannot be calculated.
However, a different arrangement can be used that replaces the
total E detector with a Cerenkov detector. The light output L,
which can be measured with a photomultiplier tube, is
L = KZ2 (1b 20 / b 2)
where K is a constant and o is the cutoff velocity below which
no Cerenkov light is generated. o is related to the real part of
the index of refraction n by o = 1/n. UV-transparent Ceren-
kov materials provide cut-off energies as low as 160 MeV/
nucleon for solids and up to several tens of GeV/nucleon for
gases. The charge and velocity of the particle can be deter-
mined from measurements of E and L. Both the technique
that measures EE and the one that measures LE can yield
energies and nuclear charges of particles over a wide range.
For the ISS, one such single-axis, charged particle directional
spectrometer will be kept inside the vehicle and relocated
about every 2 weeks to map the radiation levels in the entire
station. A triple-axis device with three directed telescopes will
be mounted outside the habitable volume on the truss struc-
ture. Differences between the spectrometer readings outside
and inside the spacecraft can be used to calculate transport of
charged particles into the vehicle.
Russian Active Monitors
The active R-16 monitor system, manufactured by Moscow
State University Scientific Research Institute for Nuclear Phys-
ics, measures the dose of cosmic radiation and depth dose. The
radiation detector consists of an integrated pulse ion chamber
with two independent chambers. One chamber is filled with
only air and provides the physical dose. The other chamber
has a piece of glass across the ostium, simulating a tissue-like
equivalence. Real-time data are provided via 16-bit binary code
telemetry. The anticipated lifetime of the R-16 system is 8 years
(20,000 h of use.) A similar instrument was flown aboard Mir.
Two other Russian devices are the DB-8, a large monitor that
is hard-mounted aboard the ISS that measures energy deposited
into silicon, and the Lyulin, a smaller portable silicon detector.
Active Personal Dosimetry
The current suite of instruments onboard the ISS does not include
an active personal dosimeter, which would be used to character-
ize the local environment during intravehicular or extravehicular
operations. However a prototype has been built that would pro-
vide instantaneous readings of absorbed dose rate, cumulative
dose, dose equivalent rate, and cumulative dose equivalent, plus
an alarm for high dose rates, to the crewmember. The current
compact prototype, designed not to exceed 100 grams, would
allow crewmembers to know immediately, in the case of lost
communication to the ground from a SPE or geomagnetic storm,
when their exposure is increasing and let them know if the area
of the vehicle provides adequate shielding protection to reduce
the dose rate to acceptably safe levels.
23. Radiation Disorders 509

Organ Dose Models Analyses of aberrations in metaphase chromosomes in

crewmembers aboard the MIR and EUROMIR missions
Newer organ-dose models and detector assemblies have (flown in 19941996) showed increased numbers of aberrations
been designed in an attempt to better replicate the exposure a in chromosomes, but not in chromatids, after space flight, sug-
human body would receive from space radiation sources. One gesting that the detected lesions had been radiation-induced.
such model, the Computational Anatomic Male, developed The numbers of dicentric chromosomes were doubled after
by P. Kase, uses anthropometric and anatomic data to better flight compared with before in crewmembers exposed to >
quantify incoming radiation effects based on organ and body 2.5 mGy from HZE particles of LET > 2.0 GeV/cm; the
weight and different tissue types. The model is constructed pooled frequencies of dicentrics were 35 times greater after
of 1500 quadratic surfaces in a Cartesian coordinate system flight. Estimates of total flux of HZE particles with LET >
yielding about 2500 closed volumes. This modeling system 2.0 GeV/cm was 510/cm2. Given that the geometric cross section
can be translated into a three-dimensional detector array to of lymphocytes is 16 m2, the fraction of cell nuclei hit was
better simulate human body exposures. Such an anatomically calculated to be 8.2 105. Rogue cells containing multiple
correct array of detectors co-located with an on-orbit crew discrete aberrations within the same nucleus have also been
would give more mature estimates of whole body dose equiva- reported after exposure to HZE radiation [19]. Other biological
lent or effective dose. The Phantom Torso experiment, which measures that might be used to quantify the effects of radia-
features just such an array, has been flown on the Shuttle and tion on the human body are being investigated as well.
ISS. Russians investigators have flown a water-filled phantom
on the Mir, from which they reported exposures of 29 Sv/
hour, with 3 Sv/hour coming from neutrons. Phantom Torso Radiation Exposures Measured Aboard Crewed
measurements have helped to confirm calculated dose to spe- Spacecraft
cific organs during space flight.
The U.S. space program has involved missions at diverse alti-
tudes and inclinations in Earth orbit and in lunar space.
Biodosimetry
Mercury/Gemini
Use of principles from biodosimetry allows a better understand-
ing of how radiation, measured by physical dosimetry, affects Project Mercury flights were both brief and flown at low
space crewmembers. Because the RBE of space radiation is altitudes, and thus the radiation exposure to the crews was
largely unknown, biodosimetry provides means of measuring inconsequential. Data from Gemini 4 (duration 4.05 days
of the biologically relevant adsorbed dose by examining actual at 32.5 degrees inclination) resulted in a mission dose of
end point damage. The biologically relevant dose obtained by 0.46 mGy, whereas Gemini 6 (1.05 days at 28.9 degrees
biodosimetric analysis should correlate better with actual health inclination) resulted in a mission dose of 0.25 mGy.
risk than physical measurements of radiation. Quantification of
chromosomal aberrations found in peripheral blood lymphocytes
is currently the most widely used method for biodosimetry. In its
standard application, metaphase chromosomes are analyzed for
physical and chemical evidence of damage. However, this tech-
nique requires some degree of cell-cycle synchronization, which
is complicated by microgravity and by delays in the cell cycle
induced by high-LET radiation. Thus, an interphase method is
used for space radiation biodosimetry. Assaying cells that are in
interphase rather than metaphase greatly increases the number of
cells available for analysis. Use of premature chromosomal con-
densation by fluorescence in-situ hybridization (FISH) has also
helped to overcome the problems with metaphase cytogenetics
and has lowered the dose-detection threshold [109].
Chromosomal translocations are particularly informative
for biodosimetry because they are easily identified by FISH
chromosome painting techniques, they often remain stable
in the body for years, and because they are associated with
genomic instability they can serve as a marker for cancer risk. Figure 23.14. Chromosomal translocations measured in peripheral
Background levels of translocations must be controlled for by blood lymphocytes as an index of radiation exposure in a group of
using preflight measurements to develop a calibration curve; longduration flight crewmembers, with missions ranging between
examples of such curves for a group of long-duration crew- four and six months. A calibration curve is shown along with actual
members are shown in Figure 23.14 [110]. astronaut data [109]
510 J.A. Jones and F. Karouia

Apollo Shuttle/Mir Program

The highest dose received during an Apollo flight occurred
on Apollo 14, with a mission dose of 11.40 mGy. Most of the
total radiation exposure during Apollo missions 7 through 17
took place while the vehicle was within the Van Allen belts.
The Apollo 14 trajectory, particularly the outbound portion,
also took the spacecraft close to the heart of the trapped radia-
tion belts. Because the mission took place during solar mini-
mum, the cosmic ray flux was relatively higher than it had
been during previous missions. The dose rate of 0.13 mGy
[0.127 rad] per day (total dose of 1.14 mGy [1.14 rad] over the
216-h mission) was the highest measured in the space pro-
gram until high-altitude LEO flights were undertaken in the
Space Shuttle program.
The Apollo missions also represented the first crewed
flights outside the protective geomagnetosphere. A major
flare such as that of October 1989 may have imparted a
few to several tens of rems to blood-forming elements over
a 2-day period in areas shielded to 510 g/cm2 aluminum
equivalent. An unshielded crewmember, i.e., one outside
the vehicle during the flare, would have been exposed to
doses of a few Sieverts (or a few hundred rem) [111].
A worst-case exposure scenario would involve a lengthy
EVA during such an event; given the minimal structural
shielding of the space suit, such a dose, experienced over
13 days, would eventually be fatal to a significant percentage
of crewmembers.
Data collected and analyzed over the life of the Mir station,
which orbited at a 51-degree inclination, have been invaluable
for radiation monitoring, modeling, and dosimetry. Scientists
from the European Space Agency and NASA have flown radi-
ation-monitoring devices on the MIR during its operational
lifetime, and in conjunction with the data from the Russian
R16 ionization chambers, the results from these devices have
been helpful for predicting exposures to crews onboard the
ISS. Absorbed doses and dose rates for cosmonauts aboard
Mir from 1986 to 1997 are shown in Table 23.16[23]. Because
the length of the missions varied, the best comparator is prob-
ably dose rate, which varied from 182 to 397 Gy/d.
The quality factors (Q) of radiation assessed during solar
minimum, as measured with a TEPC during the NASA/Mir
program, were found to be 3.18 from GCR, 1.88 from trapped-
belt radiation (2.51 total) within the Service Module vs. 3.38
from GCR and 1.66 from trapped-belt radiation (2.14 total)
in the Kristal module [23]. These differences are assumed to
have been due to variations in shielding and east-west asym-
metry. Assuming an average Q of 2.5, the dose-equivalent rate
for the cosmonauts ranged from 0.457 to 0.996 Sv/d. Factor-
ing in inefficiencies inherent in TLDs for high-LET charged
particles and contributions from high-energy neutrons (which
could not be detected by TLDs or the TEPC), the true dose
may have been as much as 25% higher.

Skylab
Radiation doses received during each Skylab mission ranged Table 23.16. Average cosmonaut absorbed dose and dose rates
from 15.96 mGy for the 28-day Skylab 2 mission to 77.40 mGy aboard mir.
for the 84-day Skylab 4 mission. Altitude Dose rate
Mission Launch Date Duration (d) (km) Dose (cGy) (Gy/d)
Space Shuttle Mir-01 3-13-86 123 4.53 368
Mir-02 2-06-87 217 3.95 182
Space Shuttle flights to date have involved relatively low Mir-03 12-26-87 366 8.18 223
radiation doses because of their limited duration (13 Mir-04 11-26-88 152 3.70 243
weeks). Mission altitude has a significant influence on Mir-05 9-06-89 225 403.8 4.73 210
exposures received by Shuttle crews. The lowest dose rate Mir-06 2-11-90 179 396.7 3.74 209
Mir-07 8-01-90 131 397.7 2.89 220
encountered during Space Shuttle missions was on STS-38,
Mir-08 12-02-90 176 390.2 4.63 263
which was flown at low altitude (110 nautical miles) at 28.5 Mir-09 5-18-90 145 398.0
inclination (about 0.0002 Sv [0.02 rem] per day for a total Mir-10 10-02-91 175 402.2
dose of about 0.001 Sv [0.1 rem]). The enhancing effect of Mir-11 3-17-92 146 405.8 3.71 254
altitude at the same 28.5-degree inclination was notable Mir-12 7-27-92 190 414.5 4.96 261
on the STS-31 mission (during which the Hubble Space Mir-13 1-26-93 180 405.0 4.61 256
Mir-14 7-01-93 197 403.7 4.38 222
Telescope was deployed); at an altitude of about 300 km,
Mir-15 1-08-94 183 405.6 4.81 263
the total dose-equivalent was about 0.01 Sv (1.1 rem), with Mir-16 7-01-94 126 410.0 2.90 230
a dose rate of 0.016 Gy (1.642 rad) per day. The largest Mir-17 10-04-94 169 406.6 4.11 243
total exposure to date during a Space Shuttle mission has Mir-18 3-15-95 115 393.7 3.32 288
been 0.043 Gy (4.3 rad); the smallest has been 0.00006 Gy Mir-19 6-27-95 76 394.9 2.43 320
(0.006 rad) (mean, 0.00235 Gy [0.235 rad] per mission; Mir-20 9-03-95 179 393.3 7.10 397
Mir-21 2-21-96 195 389.8 6.62 339
median, 0.0012 Gy [0.122 rad] per mission). The highest
Mir-22 8-17-96 198 382.3 7.50 379
dose rate ever observed in on a Space Shuttle at high altitude Mir-23 2-10-97 187 386.8 6.15 329
was 3.211 mGy/d.
Source: Data from Table 23.2, Badhwar [23].
23. Radiation Disorders 511

International Space Station

The ISS orbits in a 51-degree inclination, and its external
radiation milieu is much like that of Mir. The altitude varies
with boost phases between about 320 and 385 km (200 and 240
nautical miles). As is true for other LEO platforms, the major
radiation components contributing to the total dose on the ISS
are trapped protons from the SAA and GCR. The radiation
experienced at a given point within the ISS depends strongly
on the external radiation impinging on the structures of the
spacecraft and on the amount and composition of the materials
of those structures (e.g., spacecraft walls, furnishings, stowage,
electronics) in the radiation path. Structural materials both atten-
uate the incident radiation and serve as a source of complex
secondary radiation. Because of these manifold interactions,
the radiation environment within ISS will be considerably
more complex than the primary radiation incident upon it, and
it will vary substantially over time because of the changing
orientation of the structural materials and the varying incident
radiation field. This complex multicomponent radiation field
presents a unique and difficult measurement problem for any
space radiation protection program.
Estimates of the radiation exposure for crewmembers onboard
the ISS are based on historic dose measurements of cosmonauts
onboard Mir along with modeling of exposure based on current
knowledge of ISS vehicle components, shielding, attitude, and
altitude, as shown in Figure 23.15 [112].

Radiation Monitoring during Extravehicular

Activities
Doses likely to be experienced from radiation exposures dur-
ing specific EVA sorties are estimated and analyzed before
flight and during each mission by a space radiation analysis
group. This group also provides recommendations as to the
timing of the EVA relative to the orbital trajectory so as to
minimize the dose to the EVA crewmembers. Dose penalties
associated with beginning an EVA before the scheduled start
time or extending beyond the scheduled terminate time are
also calculated. Depending on the altitude and inclination of
the vehicle as well as the state of the geomagnetosphere at
the time of the EVA, the dose penalties for suboptimal and
extended timing of EVAs can be substantial. Other consid-
erations for timing EVAs include avoiding the SAA and the
electron horn (low cut-off zone) regions. Contingency EVAs
that must be done during an SPE with electron belt enhance-
ment are assessed with the goal of avoiding the periods of
peak flux. The attitude of the Shuttle vehicle can be adjusted
so as to afford maximum structural protection to crewmem-
bers outside the vehicle. Doses during EVAs that take place in
LEO come mainly from trapped particle radiation. The radia-
tion analysis group also provides recommendations to the
flight surgeon and the flight director to prematurely terminate
or delay an EVA on the basis of current space weather and
projected dose rate during the EVA. Projected organ dose and
Figure 23.15. Predicted radiation dose rates to International Space
Station (ISS) crewmembers relative to altitude. Figure A shows pre-
dicted altitude-dependent dose rates to the skin and to the blood
forming organs (BFO) as a function of solar cycle extremes [112].
Figure B shows the annual BFO dose vs altitude for varying levels
of shielding.
the cumulative projected dose to date for each crewmember
are also taken into account.
Limits and Medicolegal Aspects of
Radiation Exposure
Space flight unavoidably exposes crewmembers to ionizing
radiation from natural sources, and any increase in radiation
exposure increases the risk of cancer or genetic mutations.
Because risk avoidance is equivalent to dose avoidance and
because complete dose avoidance in space is not possible,
levels of acceptable risk must be established. Research over
the past decade has led to the cancer risk per dose-equivalent
being revised upward, and the relative carcinogenic effective-
ness of certain types of space radiation may be much higher
than previously thought. Current U.S. and international annual
512
limits for ISS crewmembers dictate that a space crewmember
may not receive more than a depth-dose equivalent of 0.5 Sv
(50 rem) per year. Calculations indicate that a 180-day stay
aboard the ISS could result in a worst-case depth-dose of
roughly 0.3 Sv (30 rem). A 180-day mission in a spacecraft
more heavily shielded than the ISS (e.g., one shielded to 20 g/
cm2) in a nominal, constant atmospheric density orbit with a
varying altitude would result in a depth-dose equivalent of
roughly 0.1 Sv (10 rem), which is still twice the annual allow-
able dose-equivalent of 0.05 Sv (5 rem) for terrestrial radiation
workers. Astronauts thus work under an annual limit that is
ten times the allowed limit for terrestrial radiation workers.
Crewmembers on long-duration missions thus normally incur
a much greater absolute dose, and a much higher fraction of
their allowable limits, than do their terrestrial counterparts.
Uncertainties abound in many of the variables influencing
radiation dose, including the initial charged-particle spectra,
radiation transport calculation, risk coefficients for low-LET
radiation (most of which reflect uncertainty in the dose and
dose rate effectiveness factor), and the risk cross section for
exposure to high-LET radiation. The overall uncertainty in the
risk of radiation-induced cancer, at our present state of knowl-
edge, has been estimated as being between 4 and 15 for a space
crew in the galactic cosmic ray environment [69]. Additional
experiments with phantom torsos combined with the suite of
instruments planned for ISS may improve the organ-specific
quality factor and dose estimations of the risk models [113].
During this time, a rigorous occupational health approach is
being developed and implemented. Although limits for non-
ionizing electromagnetic radiation, based on frequency spectra
and field strength, have been established for space operations,
the remainder of this section focuses on ionizing radiation and
cumulative exposure aspects.
Occupational Health Aspects
In the United States, astronauts have been classified as radia-
tion workers, and thus the U.S. Code of Federal Regulations
dictates that a program must be in place to protect them from
excessive radiation exposure. This program and its regulations
are the responsibility of the Occupational Safety and Health
Administration (OSHA) under the Department of Labor.
OSHA established limits for the exposure of workers and
the general public to ionizing radiation in 1971. Presidential
Executive Order 12196 (Feb. 26, 1980) requires that all fed-
eral agencies, including NASA, comply with OSHA regula-
tions related to ionizing radiation exposure. Although NASA
is required to follow OSHA regulations, no OSHA standards
exist for space flight. Terrestrial radiation exposure guidelines
provided in the Code of Federal Regulations (29 CFR 1910.96)
are too restrictive for space activities and therefore have been
judged inappropriate. For these reasons, NASA is allowed to
establish supplementary standards for appropriate control of
radiation for astronauts in accordance with 29 CFR 1960.18,
Basic Program Elements for Federal Employees Occupational
J.A. Jones and F. Karouia
Health and Related Matters. This regulation was updated by
the Presidential document Radiation Protection Guidance for
Occupational Exposure: Recommendations Approved by the
President (Vol. 52 Jan. 1987). The following NASA require-
ments serve as a basis for implementation of this supplemen-
tary standard: that it be used only for a limited population
(i.e., space crewmembers), that detailed exposure records are
kept for flight crews, that hazards are assessed before every
mission, that planned exposures are kept as low as reasonably
achievable (the ALARA principle), that operational pro-
cedures and flight rules are maintained so as to minimize the
chance of excessive exposure, and that any exposure to artifi-
cial onboard radiation sources complies with 29 CFR 1910.96,
except where the NASA mission objectives cannot be accom-
plished otherwise.
NASA has adopted the recommendations of the National
Council on Radiation Protection and Measurements as pre-
sented in its Report 98, Guidance on Radiation Received
in Space Activities [114], as the basis for its supplementary
standard for spaceflight crew radiation exposures. Values are
defined for maximum (career), 1-year, and monthly exposure
limits. Whereas monthly and annual limits primarily exist
to prevent the short-term physiological effects of exposure,
career limits exist to contain radiation risk at a maximum of
3% increased lifetime cancer mortality. The defined limit of
3% excess cancer deaths originates from comparisons to other
occupational injuries. In a subsequent report (Report 132) [112],
the National Council on Radiation Protection recommended
that a new radiation measurement unit, the Gy-equivalent, be
used for calculating short-term limits. The Gy-equivalent is
based on RBE instead of Qf, the factor used for estimating late
effects and the calculation of career limits. Short-term limits
have been established for three organ-specific sites: eye, skin,
and blood-forming organs. The recommendations of the NCRP
reports 98 [114] and 132 [115] apply to activities in LEO, such
as those aboard the Shuttle or space stations.
In addition to the revision of units for radiation risk assess-
ment information from recent reevaluations of atomic bomb
survivor data and other sources and has provided the impetus
for further examination of the acceptable limits of astronaut
radiation exposure. Recommendations from the NCRP based
on evaluation of the new data suggest that even lower career
limits for astronauts may be warranted, and the NCRP 132
report cites lower doses associated with 3% excess cancer
mortality career limits. The new recommended space flight
exposure limits from NCRP 132 are presented in Table 23.17.
These recommendations were being considered for adoption
by NASA when this chapter was written.
NASA is also developing flight rules that account for action
levels (which are one third the levels of acute and annual dose
limits) to assist in operational implementation of the ALARA
principle. As noted above, sufficient uncertainty exists in pre-
dicting the risk of cancer from a certain dose that a further
degree of conservatism may be warranted. The current agency
approach is to work toward a radiation dose associated with a
23. Radiation Disorders
Table 23.17. Recommended organ dose-equivalent limits from
ionizing radiation for space crewmembers in low earth orbit.
Skin (Sv or Ocular Lens Blood-Forming
Limits Gy-Eq) (Sv of Gy-Eq) Organs (Sv)
30-Day 1.5 1.0 0.25
1-Yeara 3.0 2.0 0.50
Career 6.0 4.0 1.04.0b
Abbreviations: Gy-Eq, Gray-equivalent.
a
1-year limits are not to be considered annual limits, i.e., not repeated year
after year.
b
The limit for the dose to the blood-forming organs varies according to age
and sex.
Source: NCRP Report No. 98 and 132.
3% excess lifetime cancer mortality within a 95% confidence
interval. This level will vary with radiation type, and crew-
member age and sex; for individuals at higher risk, i.e. young
female crewmembers, the level may approach that of a dose
associated with a 1% excess mortality. For doses projected to
breach the 95% confidence interval range, further risk/ben-
efit analyses and informed consent procedures will be under-
taken. Depending on the astronauts age and sex, two or three
180-day ISS missions may complete his or her long-duration
career under this new limit.
At NASA, radiation health officers are responsible for gen-
erating reports that summarize each astronauts occupational
radiation exposure, including both terrestrial and spaceflight
exposures. These reports include physical absorbed space-
flight doses, as measured by the personal passive dosimeters;
estimates of whole body effective dose, which are based on the
average quality factor measured by TEPC or similar devices;
and modeled estimates of individual organ exposure. Expo-
sure from medical procedures and experiments are also deter-
mined for each crewmember. Exposure calculations and the
age and sex of the crewmember are used to generate estimates
of the risk of developing fatal cancer. Crew flight surgeons
review these reports with each crewmember once a year and
before every flight.
Radiation Issues for Exploration
and Habitation Missions
Radiation Assessment for Lunar and Mars
Missions
Many variables must be considered in assessing the radiation
profile associated with travel beyond Earth and its protective
geomagnetic fields. This section considers aspects of human
lunar and Mars exploration efforts, in which the spacecraft tra-
verses the Van Allen belts and their trapped radiation, exiting
the geomagnetic shield and becoming exposed to isotropic GCR
and unencumbered SPEs. With current propulsion technologies,
transit to Mars will involve very long periods in this deep space
environment. The increasing remoteness of travel through deep
513
space renders medical return for in the event of acute radiation
syndromes much less likely. As such, missions must be care-
fully planned to minimize the chances of exposures that might
approach the threshold levels for deterministic effects.
This elaborate planning process begins with analysis of
celestial mechanics to minimize transit time and synchrony
with the solar cycle. Notably, a 36-month mission beginning
4 years after solar minimum would result in a total incurred
dose 45% lower than would be received on a mission begin-
ning at solar minimum [116]. In addition, the acceptable risk
for stochastic effects may differ from current NASA limits,
which were designed for routine LEO operations rather than
exploration efforts.
The Storm Shelter
To optimize crewmember protection from the most dangerous
aspects of SPEs, the concept of a radiation haven within the
spacecraft has been proposed. Such a storm shelter would pro-
vide a radiation-hardened volume within which all crew-
members could take refuge during these unpredictable but
short-lived events. One scenario for a 500-day Mars mission
includes the assumptions that the vehicle has been designed
to include a 20 g/cm2 aluminum storm shelter and that the
crew will occupy the sleep station, which could be a modified
storm shelter, for 8 h a day [117]. Calculations generated with
an anatomical model and assuming exposure to two types of
environments (GCR and solar flares) yield estimated cumu-
lative dose equivalents for a 500-day mission of 0.6621 Sv
(66.21 rem) to the skin, 0.6695 Sv (66.95 rem) to the eye, and
0.4892 Sv (48.92 rem) to the blood-forming organs. All pre-
dicted dose-equivalents in this calculation would be below
the annual exposure limit for astronauts as currently defined
for LEO activities. The storm shelter concept would apply
for lunar and Mars transit as well as for surface activities, as
described in the following paragraphs.
Lunar Mission
The overall radiation dose for a 12-month mission on the lunar
surface has been estimated as follows. Days are divided into
three 8-h periods, the first of which is used for research and
exploration activities on the surface. During that time, crew-
members would wear a Space Shuttle-type EVA suit consid-
ered to have shielding equivalent to 0.3 g/cm2 of aluminum
(i.e., a suit that lacks the hard upper torso and portable life
support system of the current Shuttle suit). During the second
8-h period, crewmembers would be in a pressurized habitat,
the worst-case areal density of which will be equivalent to
5 g/cm2 of aluminum. Several meters of lunar regolith will
cover the habitat to minimize the dose exposure. During the
third 8-h period, crewmembers would be inside a storm shel-
ter sleep station, equivalent to 10 g/cm2 aluminum, to reduce
radiation exposure. This scenario also includes an additional
three EVAs outside the habitat per week.
514
The dose exposure from a 3-day round trip to the Moon
inside a 2 g/cm2 aluminum-shielded vehicle will be 0.05 Sv
(5 rem) [118]. The overall dose exposure for the mission,
calculated considering the 1977 GCR, will be 0.42 Sv
(42 rem) to the skin, 0.41 Sv (41 rem) to the eyes, and
0.32 Sv (32 rem) to the blood-forming organs [85]. The
addition of one 1972-class SPE during the 1-year mission,
with the crewmembers inside a 10 g/cm2 storm shelter,
contributes another 0.11 Sv (110 rem) to the skin and eyes
and another 0.24 Sv (24.3 rem) to the blood-forming organs
[85]. Hence the total dose exposure during a 12-month
mission on the Moon plus a 6-day round trip flight plus one
1972 class SPE while the crewmembers are on the surface
will be 1.57 Sv (157 rem) to the skin and eyes and 0.71 Sv
(71 rem) to the blood-forming organs.
Mars Mission
In a similar calculation, a mission to Mars (using conventional
chemical rocket propulsion systems) would involve two 6-month
transit periods. The overall dose-equivalent exposure, assum-
ing a 1977 level of GCR, can be calculated by dividing the day
into two parts: a 16-h period spent inside a 5 g/cm2-equipped
room and an 8-h period spent inside a 10 g/cm2 sleeping area
storm shelter. The corresponding doses for that 1-year mission will
be 0.82 Sv (82 rem) to the skin, 0.81 Sv (81 rem) to the eyes,
and 0.63 Sv (63 rem) to the blood-forming organs [119,120].
Notably, this dose-equivalent is twice that of a similar period
spent on the lunar surface. Estimated annual dose equivalents
from GCR at solar minimum during long-duration stays on
the surface of Mars, considering protection from the 16 g/
cm2 CO2 atmosphere, will be 0.12 Sv (12 rem) to the skin and
0.11 Sv (11 rem) to the blood-forming organs [121]. Adding an
event of 10 times the scale of the 1989 SPE, while crewmem-
bers are inside a 10 g/cm2 storm shelter, results in additional
dose equivalents of 0.33 Sv (33 rem) to the skin and eyes and
0.25 Sv (25 rem) to the blood-forming organs for crewmembers
on the Martian surface [122]. Thus the overall dose during a
2-year mission to Mars from GCR plus two SPEs, one 10
times the intensity of the 1989 event on the Martian surface
and one equal to the 1972 event during the transit phase, will
be 2.4 Sv (237 rem) to the skin and 1.2 Sv (123 rem) to the
blood-forming organs.
As a point of reference, Letaw [16] calculated that in the
absence of SPEs and with a vehicle and habitat shielding of
4 g/cm2, the dose equivalent during solar maximum would be
0.18 Sv (18 rem) per year and 0.45 Sv (45 rem) per year during
solar minimum.
Planetary Surface Shielding
Martian Atmosphere
In contrast to the Moon, which has essentially no atmosphere,
Mars has a rarefied atmosphere composed mainly of car-
bon dioxide (95.3% by volume), nitrogen (2.7%), and argon
J.A. Jones and F. Karouia
(1.6%). Although the pressure at ground level is less than 1%
of that of Earths atmosphere, the Mars CO2 atmosphere will
have a substantial protective effect from space radiation, with
some studies estimating that at ground level, the density of
the CO2 would be equivalent to 1622 g/cm2 aluminum [122].
Hence the shielding effectiveness per unit of CO2 is greater
than that of either aluminum or Martian regolith [123]. At
ground level, assuming a 100% CO2 atmosphere and a 1-year
exposure to GCR at solar minimum, the contribution to the
dose to the blood-forming organs from elements with atomic
number between 10 and 38 (HZE particles) drops to 50%.
However, secondary radiation, assuming a 100% CO2 atmo-
sphere, increases the contribution from neutrons by a factor of
3 and that from protons by a factor of 1.5 [124].
Martian and Lunar Regolith
The Martian and Lunar regolith are composed mainly of
silicate and iron. The shielding properties of the lunar
regolith are similar to those of aluminum because the mean
molecular weight of all its components is comparable to
the atomic weight of aluminum [123]. At 30 g/cm2, add-
ing a layer of lunar regolith to any kind of habitation
will decrease the dose to the blood-forming organs from
atomic particles higher than 10 by a factor of 2 for a 1-year
exposure (considering GCR at solar minimum). However,
because of secondary interactions, the dose exposure from
protons will increase by a factor of 2 and that from nucle-
ons will increase by a factor of 4 [125]. In other words, for
a regolith thickness of 30 g/cm2, 70% of the dose would
result from nucleons (mostly from secondary radiation
from protons and neutrons). However, because regolith
shields primary radiation quite effectively, the dose to
the blood-forming organs would be kept below the cur-
rent NASA annual limits [114], even assuming one or two
SPEs (a dose-equivalent of about 0.3 Sv); the maximum
dose per SPE is estimated not to exceed 0.12 Sv (12 rem) to
the blood-forming organs [126]. The density of the Martian
regolith, on the other hand, is lower than that of aluminum,
and thus it provides less primary protection from SPEs and
from the incident GCR. However, it will result in fewer
secondary radiation particles being produced than in the
case of lunar regolith [127].
The location of the habitat will also affect the amount
of radiation the crew receives while inside. Given the rela-
tively smooth surface of the Moon, a lunar habitation module
will offer at least full 2 steradian protection of the volume
because of the planets mass. For a Mars habitat, the dose can
be decreased by taking advantage of the surface features, for
example by embedding a module in the side of a cliff. The
reduction in dose exposure would correlate directly with the
dimension of the terrain overhanging the habitat; for a habitat
under a 10-m cliff, the dose to the blood-forming organs
during a 1-year surface stay, from GCR and from one solar
flare, will decrease by 0.045 Sv (4.5 rem) per year [127].
23. Radiation Disorders
Conclusions
With current technologies, radiation doses associated with
exploration and habitation missions to the moon and Mars
may well exceed the limits currently defined for LEO opera-
tions. Assessment of the radiation protection needed during
interplanetary and remote planetary missions should include
consideration of several key technologies, such as integrat-
ing structural radiation shielding into vehicle design. Mission
planning should, of course, account for solar cycles in consid-
ering vehicular trajectories. Vehicle designs could maximize
shielding of crew compartments by considering fuel and water
storage tanks as components of that shielding. Development
of advanced propulsion systems are expected to shorten the
required transit time. Advanced warning systems for SPEs
might be possible through the use of solar orbiting satel-
lites. Shielding strategies for surface habitats should include
consideration of materials (e.g., regolith) that would reduce
exposure to primary radiation and not evoke significant doses
from secondary radiation. Geographic variations in the natural
terrain can be exploited to enhance habitat shielding. Devel-
opment and use of personalized active dosimeters deserves
particular attention, as does selection of EVA suit materials.
Other important areas of development, applicable to all
aspects of human space travel and operations, include the
following:
Radiation shielding and storm shelters that use improved,
easy to implement shielding strategies
Active dosimetry and monitoring with real-time alarm
capability
Improved SPE forecasting
High-energy neutron monitoring
Study of HZE-specific mechanism of genomic instability
and carcinogenesis
Study of HZE effects on CNS, fertility, spermatogenesis,
teratogenesis, and heritable lesions
Means of monitoring radiation bioeffects during missions,
including biomarkers and cytogenetics
Further study of radioprotective molecules and chemopre-
vention agents
For remote exploration missions, a multifaceted radiation
management program must assume autonomous operations.
Many techniques currently available for Earth-based laboratory
analysis for assessing cytogenetics, genetic polymorphisms,
point mutations, apoptosis, and the like could be modified for
in-flight use. Such technologies would best be tested on the
ISS and validated before attempting to embark on transplane-
tary missions. ISS research should also include vigorous efforts
to reduce the uncertainties associated with risk assessment for
stochastic events. Our ability to understand the biological result
of a given dose of space radiation would be greatly enhanced
by development of the following capabilities: a standardized
scoring system for fluorescence in-situ hybridizidation (FISH)
techniques to detect aberrations, to allow development of
515
calibration curves, and thereby to standardize estimates of
relative risk; assays to define hot spots in the genome that
are particularly prone to injury or cross-linking as the site of
carcinogenesis or oncogene activation; and assays for evalu-
ating epigenetic mechanisms of carcinogenesis instead of
focusing only on stable events occurring after irradiation.
Our ability to develop improved countermeasures and
treatments for radiation-induced bioeffects [128] would
also be enhanced by the development of animal models
for testing chemoprevention agents, which would facilitate
translation of findings from both low-LET and high-LET
radiation from cell cultures to organ systems to animals and
to humans. Another useful tool would be nontoxic, easily
administered radioprotectant agents of high bioavailability
that could be given alone or in combination to ameliorate
or prevent radiation damage. The pharmacokinetics and
pharmacodynamics of such agents would need to be thor-
oughly characterized both under Earth-based conditions
and in microgravity. Genetic engineering may be useful for
rendering astronauts more radioresistant in the future. Stem
cells might be genetically engineered for radioresistance;
key genes in molecular-level protection from HZE radiation
might be inserted into cells, which would then be introduced
into gastrointestinal and bone marrow stem cells.
Radiation was one of the first aspects of the spaceflight
environment to be characterized as humans ventured away
from Earth in the mid-20th century, and it remains the
most limiting factor with regard to stay time and enduring
health risk. GCR make space radiation a ubiquitous back-
ground entity and acute clinical syndromes may result from
unpredictable solar flares. Radiation will always be a promi-
nent factor in human spaceflight planning and operations,
as it drives both vehicle design and mission architecture.
Technological leaps may someday allow the generation
of electrical power levels great enough to create artificial
magnetic fields sufficient to deflect charged solar parti-
cles from spacecraft crew cabins, and advanced materials
may afford better shielding-to-mass capabilities. For now,
vigorous research continues in ground and Earth-orbiting
laboratories to better characterize radiation bioeffects and
monitoring technologies.
Acknowledgments. The author would like to note the follow-
ing individuals for contributions to the field of space radia-
tion and to this chapter: Michael Stanford, Ph.D., University
of Houston; Frank Cucinotta, Ph.D., NASA/JSC; Lief Peter-
son, Ph.D., Baylor College of Medicine; and [the late]
Gautam Badhwar, Ph.D., NASA/JSC. Acknowledgments
to: Mark Weyland. Mike Golightly, Steve Johnson, Ph.D.,
Ed Semones, M.S., Neal Zapp, M.S., S. Vlahovich, M.D.,
Canadian Space Agency, Prem Seganti Ph.D., John Wilson,
Ph.D., Mike Moyers, Ph.D., Linda Hewes, Ed Stasinopo-
lous, Ph.D., Vincent Witt, Jennifer Jadwyck, and Francois
Becker, Ph.D.
516
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24
Acoustics Issues
Jonathan B. Clark and Christopher S. Allen
Omnipresent with human habitation in artificial environments
is background and operational noise. Inherent in almost any
platform or craft that maintains a human crew in an enclosed
cabin is the need for circulation of air to remove metabolic
and other adverse waste products and to replenish consumed
oxygen. Water and fluid coolants of thermal control systems
may also require circulation, typically provided by motor-
ized fans and pumps. Noise generated by such systems is an
expected consequence for surface ships, submarines, aircraft,
and spacecraft and adds to noise that may be produced by pro-
pulsion systems and other operational equipment. Noise in
low Earth orbit spacecraft operations has been identified as a
significant environmental hazard for human crews. This chap-
ter examines the sources and character of background noise
on board orbiting spacecraft, the morbidity and pathophysiol-
ogy associated with such noise, and aspects of remediation
and crew protection.
Mechanics of Hearing
Hearing is the transduction of sound (mechanical energy) into
neural impulses and the interpretation of those impulses by the
central nervous system. Hearing loss can result from a defect
at any point in this system. Loudness is quantified as sound
pressure level (SPL) determined by the amplitude of pressure
changes in the alternating compression and rarefaction of air
and is expressed in decibels (dB) with a reference pressure
fluctuation of 20 Pa, which is accepted as the threshold of
hearing for a typical 18-year old human male. Pitch is quan-
tified as frequency, determined by the number of pressure
peaks encountered per second and is expressed in cycles per
second or Hertz (Hz). The frequency of sound is often pre-
sented on a logarithmic frequency scale that is divided into
standard octave or 1/3 octave bands [1].
In order to relate sound pressure levels to human physiol-
ogy, it is necessary to take into account the response of the
human auditory system. One of the most frequently used
methods for this incorporates the A-weighted scale, which
approximates the response of human hearing to high noise
levels. When applying the A-weighted scale, adjustments are
made to the SPL of each frequency band and the SPL units are
changed to dBA, referenced to 20 Pa. While the A-weighted
SPL values of individual frequency bands are rarely stated, the
most commonly used acoustic metric is the A-weighted over-
all sound pressure level, referred to as the noise level, in dBA.
This noise level is the combination of A-weighted SPL bands
over the frequency range of human hearing (typically 63 to
20,000 Hz). This metric is the standard output of sound level
meters and is also used when calculating or measuring noise
exposure. The subsequent discussion will relate exclusively to
the A-weighted scale.
The noise criterion, or NC, family of curves also takes into
account the human response to noise and is typically used
when designing working or living spaces by specifying a
curve for the octave band SPLs to satisfy, e.g., NC-50. The
NC curves are a function of SPL and frequency in octave-
bands from 63 to 8000 Hz [1]. The relationship between the
NC curves and A-weighted scale is shown in Table 24.1,
where the A-weighted scale has been applied to the specified
NC curve, and the corresponding noise level of the curve has
been calculated and is shown.
Noise is unwanted, unpleasant, or bothersome sound that
often interferes with tasks and may be perceived as harmful
[2,3]. Even at the high noise level extreme, the energy suf-
ficient to cause permanent hearing loss resulting from a single
acute exposure is low, equivalent to 1/10,000 of a watt, which
equates to 120 dB SPL. In addition, chronic health effects
(physiological) and performance effects (psychological) may
result from long-term exposure to continuous noise sources at
even lower levels. Physiologic effects of noise include tempo-
rary and permanent hearing loss, cardiovascular system fluc-
tuations, digestive changes, and immune system suppression
[2]. Threshold shift, a change in hearing sensitivity (expressed
in dB or dB for a given frequency) usually induced by noise
exposure, occurs as a function of sound pressure level and
duration and may occur after exposure to acute high inten-
sity noise or long term continuous noise at lower levels. Krebs
521
522
Table 24.1. A-Weighted overall sound pressure
level as related to the NC (noise criterion) curve.
NC curve Sound level, dBA of NC curve
70 78
65 71
60 66
55 61
50 56
45 52
40 47
35 42
30 38
25 34
20 30
15 25
reported a greater than 10 dB average threshold shift across
frequencies in subjects exposed for four days to 60 dBA con-
tinuous noise and 77 to 89 dBA intermittent noise. Exposure to
levels of up to 75 dBA noise for 30 days resulted in a threshold
shift that recovered after 50 h of noise rest. Occupational noise
exposure assumes a rest period at reduced noise levels (e.g. at
the end of the work day) to allow critical recovery time; this
understanding is incorporated into industry regulations. Expo-
sure to prolonged noise as low as 58 dBA in combination with
ototoxic drugs (e.g., neomycin and streptomycin) has been
proven to cause permanent hearing loss.
Analogous scenarios may be found in industrial and aviation
settings; however, the spacecraft environment adds a further
factor in that the measure of noise exposure is not limited by the
workday or sortie. Crew exposure to spacecraft cabin noise is
continuous; although some regional distribution is expected,
there is literally no place to go for complete ear rest.
High noise levels can cause headaches, irritation, fatigue,
impaired sleep, and tinnitus. High noise levels disrupt commu-
nication in the spacecraft environment and on occasion have
resulted in an inability to hear alarms at a distance. Speech
intelligibility may be more impaired for crew understanding,
especially with regard to non-native language use in a noisy
environment, a factor of particular relevance to international
space efforts. Speech reception will be further compromised
when crew are not aligned upright with respect to each other,
which will limit ability to interpret nonauditory cues such as
facial expressions and lip movement [4]. Crews communicat-
ing in noisy environments often complain of sore throat from
talking loudly. Community based studies of high levels of
environmental noise suggest associated mental health symp-
toms (depression and anxiety) but not impaired psychological
functioning [5].
NASA is particularly concerned about crew health effects
of sound on the International Space Station (ISS), the larg-
est and most complex spacecraft to date. Acoustic specialists
have been tasked with providing guidance for safe permis-
sible sound exposure on the ISS, developing strategies to
assess and reduce acute effect of sound on crew performance,
and coordinating the approach to study acute, chronic, and
J.B. Clark and C.S. Allen
delayed effects of sound on ISS crewmembers. The medical
guidance provided to spaceflight crew and management con-
cerning biological effects of acoustic energy will be used to
optimize crew performance and reduce or eliminate adverse
health effects. Specific objectives include characterizing
the sound environment in habitable areas using onboard noise
measurement equipment, tracking of crew hearing including
inflight via onboard hearing assessments, providing medi-
cal guidance for safe permissible exposure levels on ISS,
and identifying loud systems and payloads that may be ame-
nable to engineering mitigation procedures. The operational
approach is to identify issues based on known crew impact
and priorities, develop workaround options, obtain supporting
data, review the weight of evidence, and establish recommen-
dations. Four levels of impact and priority have been estab-
lished in this approach. Flight safety is the highest priority
impact. The next level is mission accomplishment, which is
given a high priority; impact on mission effectiveness is given
a medium priority. The lowest priority is assigned to the effect
on longitudinal health. All are of concern from the perspective
of human health.
Pathophysiology of Noise
Acoustic damage to the cochlea depends on the type, frequency,
level, and duration of noise and the potential presence of other
auditory toxins. Noise type is characterized as continuous
(engine noise), impulsive (rifle shot/hammer blow), or kur-
totic (impulsive noise superimposed upon continuous noise).
For a given energy level, kurtotic noise is the most damaging,
impulse noise is moderately damaging, and continuous noise
is the least damaging [6,7]. Acoustic energy damages auditory
tissue in several ways. At high energy levels, delicate cochlear
structures are physically disrupted [8]. Metabolic exhaustion,
the most common mechanism, occurs when increased meta-
bolic activity from acoustic energy results in glycogen deple-
tion induced by cochlear ischemia [9]. Excessive stimulation
overdrives the auditory system, generating reactive oxygen
species and free radicals, which initiate protein oxidation and
disrupt cell membrane phospholipid integrity and the actin
filaments of hair cell stereocilia [10]. Oxidation of the cell
membrane results in release of toxins, such as 4-hydroxy
2,3-nonenal (HNE), which disrupts cellular processes such
as sodium/potassium pumping, glucose and excitatory neu-
rotransmitter (glutamate) transport, and ion homeostasis, and
can lead to accelerated programmed cell death (apoptosis).
Minor damage may be repaired and is initially manifested as a
temporary threshold shift (TTS), while more significant injury
can result in permanent noise-induced sensorineural hearing
loss or permanent threshold shift (PTS).
Typical antioxidant defenses include vitamins C and E, and
reduced glutathione (GSH). Enhancing inner ear antioxidants
by increasing antioxidant enzyme activity, increasing inner
ear GSH, or adding exogenous antioxidants can reduce
24. Acoustics Issues
permanent noise induced hearing loss (NIHL) [10]. Perma-
nent damage to hair cells may occur days or weeks follow-
ing noise exposure, and this critical interval allows a potential
therapeutic window that could be initiated after noise expo-
sure but before cell death [6]. The generation of reactive oxy-
gen species may be an early event, followed by the generation
of lipid peroxidation products, then mitochondrial injury and
activation of cell termination programs.
The onset of TTS may be asymptotic, meaning a maximum
threshold shift or plateau is reached at a given sound level
exposure and duration and remains constant regardless of fur-
ther length of noise exposure. The concern is that repeated
TTS could produce NIHL. In animals, noise sufficient to
cause a reversible behavioral threshold shift is known to pro-
duce histologic damage to the outer hair cells. Intracellular
metabolic exhaustion of the hair cells, swelling of the auditory
nerve endings, and spiral artery vasoconstriction with resul-
tant hair cell ischemia have been demonstrated [11]. Noise
at 70 dB SPL at 1000 Hz may induce peripheral vasoconstric-
tion, minor changes in heart rate, and increased cerebral blood
flow. Finkleman demonstrated increased heart rate with the
combination of physical activity and noise [12]. Exposure to
continuous noise may produce changes in skeletal muscle ten-
sion, depth of breathing, galvanic skin response, and a decrease
in gastrointestinal mobility. Falk investigated the noise effects
on the adrenal medulla, observing changes in blood and urine
concentrations of cortisol [11]. Stimulation of the pituitary
adrenal axis by 68 to 70 dB at 1000 Hz resulted in a release of
adrenocorticosteroids, epinephrine, and norepinephrine that
showed no adaptation and persisted as long as noise was pres-
ent [13]. Falk showed that noise stress lowered resistance to
disease, presumably from a suppressed immune system [11].
The use of ototoxic drugs such as salicylates, diuretics, and
antibiotics (streptomycin and neomycin) combined with con-
tinuous exposure in the 50 to 60 dBA range may result in per-
manent hearing loss [13].
It should be stated that the difference in effects between
response to tonal and random broadband noise with the same
energy has not yet been determined. It is intuitive that the
tonal noise would cause more damage as the total energy is
concentrated at a single frequency. However, this effect is
expected to be highly frequency dependant and related to
physical dimensions of an individuals sensing organs.
Vorobiov and Skrebnev studied the effects of continuous
noise exposure on jet aircraft maintenance workers living near
the airport and reported 69% of maintenance engineers had hear-
ing problems, 20% being significant, especially in the 1 to 8 kHz
range [14,15]. The National Institute of Health (NIH) consensus
development conference of 1990 stated levels of less than 75 dBA
were unlikely to cause NIHL and levels greater than 85 dBA
for longer than 8 h will cause hearing loss over time [16]. The
American Society for Testing and Materials (ASTM 1166) and
Department of Defense military criteria standard (MIL-STD-1472)
provides similar acceptable upper noise limits for human indoor
environments [17,18]. The Environmental Protection Agency in
523
1971 recommended 70 dBA as the acceptable outdoor exposure
for 24 h, 45 dBA during the day and 35 dBA during the night for
indoor exposure. The NATO Advisory Group for Aerospace
Research and Development (AGARD) in 1975 recommended
avoiding levels greater than 90 dBA and noted that exposures
between 80 to 90 dBA are potentially hazardous, and asymptotic
TTS greater that 40 dB may cause permanent hearing loss [19].
The US Coast Guard (USCG) stated the minimum goal of any
noise program is to ensure that an exposure is not so great that
any Temporary Threshold Shift cannot be recovered during the
following rest period. The USCG limit for intermittent noise is
82 dBA for existing vessels and 77 dBA for new ships [20].
Noise and Performance
The acoustic environment on board the International Space
Station (ISS) is expected to contribute to negative psycho-
logical effects, which may be exacerbated by high workloads,
diminished sleep, stress from family separation, and other
aspects of environmental habitability. The acoustic environ-
ment may be acceptable from an operational standpoint if
permanent hearing loss and negative communication and per-
formance impacts are unlikely. The continuous noise levels
anticipated on ISS for the duration of typical crewed missions
(up to six months) are not expected to cause PTS. However,
the psychological effect of continuous noise exposure at levels
likely to be encountered on long-duration space station mis-
sions could result in performance degradation during critical
tasks and emergency situations.
The level of performance degradation is dependent on the
level, variability, duration, intermittency, and periodicity of the
source noise, as well as the type of task undertaken by a crew-
member. Annoyance from noise depends on the source, meaning,
level of disruption, and ability to control the noise [13]. Driskell
and Salas reported that long term continuous noise results in nar-
rowed attention, decreased search behavior, longer reaction time
to peripheral cues, decreased vigilance and motivation, degraded
problem solving, performance rigidity, and decreased ability to
scan alternatives. Noise exposure was associated with loss of the
team perspective, decreases in helping behavior, decreases in
team performance, attention narrowing, negative affective state, a
threefold increase in operational procedure errors, and a twofold
increase in time necessary to complete manual tasks [2]. Con-
tinuous noise exposure may have a greater negative impact on
tasks requiring a faster work pace, and individual variability may
be a function of personality [21]. The ambient background noise
level may create performance decrements for repetitive tasks
[22]. Tasks requiring multiple information sources, information
processing, and vigilance all show degradation under noise expo-
sure while repetitive or practiced tasks or tasks that provide clear
warnings or use visual stimuli are unaffected by noise [22].
NASA developed a standard battery of performance tests
for the assessment of noise stress effects [23]. Fifty percent of
people in an open office area where the ambient background
524
sound levels ranged from 53 to 62 dBA found the noise to
be extremely annoying or unbearable [24]. Continuous tus. If persistent STS is documented in the medical record, the
noise (50.0 to 86.6 dBA, mean 56.3 dBA) for 24 h resulted in
decreased rapid eye movement (REM) sleep, reduced sleep
efficiency (time asleep/time in bed), and sleep deprivation
[25]. Kawada reported a decrease in REM sleep at 45 dBA and
subjective degradation of sleep quality and awakening [26].
Clinical Hearing Assessment
The standard hearing test performed annually and before and
after space flight on all astronauts is the pure tone thresh-
old audiogram. The test is administered in an acoustically
isolated chamber where a series of low intensity tones are
sent to either ear via headphones at frequencies between 500
and 8000 Hz (0.5 to 8 kHz). The threshold intensity, defined
as the lowest intensity sound at which the patient consis-
tently hears the tone, is determined for each frequency and
each ear. Pure tone thresholds in the NASA Flight Medicine
Clinic are typically measured by automated testing, where
a change in intensity is marked by a push button switch in
the astronauts hand. The tone begins at a normally audible
intensity, and the subject presses the button until the tone
falls off into the inaudible range. When the button is released,
the intensity begins to increase until the astronaut presses the
switch again. This series continues for several cycles; then
the signal frequency is changed. The process continues for
all frequencies in both ears.
The advantage of automated testing is that multiple tests can
be done simultaneously. The disadvantage is that automated
testing can be overcome by pressing the button in a cyclic
pattern. However, newer testing machines present the tones
in a random non-rhythmic fashion and the subject presses
and releases the button for each tone heard. Audiometer out-
puts are set to comply with the American National Standards
Institute (ANSI) 1969 standards to allow comparison of audi-
ometry data to facilitate longitudinal follow-up. Audiometer
calibration is accomplished annually.
A standard threshold shift (STS) is defined as a change in
hearing threshold over the baseline audiogram of an average
of 10 dBA or more at 2000, 3000, and 4000 Hz in either ear. If
an STS is identified on the annual examination, the crewmem-
ber will be scheduled for a repeat exam within 30 days. The
second exam is preceded by at least 14 h in a relatively noise-
free environment (<72 dBA). If the STS is resolved on the first
or second repeat audiogram, the individual is counseled on
effects of excessive noise; methods of conservation and hear-
ing protection devices (HPD) are discussed. If the STS is per-
sistent, a PTS is documented in the medical record. A PTS
of >25 dBA is considered an OSHA-reportable loss. Referral
to an otolaryngologist is indicated for significant audiogram
changes consistent with noise-induced hearing loss, such as
an STS, accompanied by clinical signs or symptoms of other
otologic pathology, or changes of a magnitude that result in
J.B. Clark and C.S. Allen
hearing acuity below the standards for retention of flight sta-
baseline is reset to the values reflected in the audiogram, per-
mitting increased specificity of the STS. If data in the annual
audiogram which suggest an auditory acuity better than that
seen in the baseline audiogram, the baseline will be adjusted
upwards to increase the sensitivity for detecting significant
threshold shifts.
Unaided hearing loss in either ear of less than 25 dB for
500, 1000 and 2000 Hz, 35 dB for 3000 Hz, and 45 dB for
4000 and 6000 Hz is considered normal over time. Unaided
hearing loss in either ear greater than 30 dB average over
500, 1000, and 2000 Hz and/or with a single value greater
than 35 dB for 500, 1000, and 2000 Hz and 45 dB for 3000
and 4000 Hz requires audiologic and ear, nose, and throat
(ENT) evaluation, as does an asymmetric hearing loss
(greater than 15 dB difference between the two ears at any
frequency). Restriction from flying is not required during
workup and the evaluation may be deferred until the first
long flight physical for individuals with longstanding hear-
ing loss in this range. Unaided hearing loss in either ear
greater than or equal to 35 dB averaged over 500, 1000, and
2000 Hz requires ENT evaluation for continued flying and
audiologic evaluation of fitness for continued active duty,
during which time disqualification from flying is appropri-
ate. Hearing loss sufficient to preclude safe and effective
performance of duty regardless of level of pure tone hear-
ing loss and despite use of hearing aids requires the inter-
vention of the Aerospace Medical Board for waiver.
LongDuration Noise Exposure
In an animal model of exposure to moderate sound levels for
nine days, PTS occurred in animals exposed to 85 dBA SPL or
greater [27]. But in a study of human subjects, 72 h exposures
of 72 to 74 dBA resulted in raised hearing thresholds of 15 to
20 dB that recovered to normal thresholds in 2 to 3 h [28]. In a
second set of experiments, Yuganov et al. reported that 10- and
30-day exposures (using the same levels of noise exposure)
resulted in threshold shifts of 20 to 25 and 25 to 30 dB with
recovery taking place in 818 h and 48 to 50 h after exposure,
respectively [28]. These threshold shifts and recovery times
are summarized in Table 24.2. A characteristic feature dis-
tinguishing these investigations was the constant complaints
throughout the experiment of the irritant and fatiguing action
Table 24.2. Threshold shift and recovery time for high-frequency
noise (<3 kHz) exposures lasting 330 days.
Duration Level Threshold shift Recovery time
3 day 7274 dBA 1520 dB 23 h
10 day 7274 dBA 2025 dB 818 h
30 day 7274 dBA 2530 dB 4850 h
Adapted from Yuganov et al. [28].
24. Acoustics Issues
of the noise. Ward indicated that a 150-day continuous expo-
sure of 82 dBA SPL caused permanent hearing loss as well
as quantifiable hair cell loss in the chinchilla. Intermittent
rest prevented permanent hearing loss and cochlear damage
due to noise [29]. Rest periods longer than 18 h were no more
effective in preventing hearing loss than the 18-h rest periods
[3033]. Little data were found for rest periods shorter than
8 h although one duty/rest cycle used for 144 days involved
15 min of rest for every 45 min of exposure.
Space Shuttle Experience
The U.S. Space Transportation System specification for noise
on the Space Shuttle during development was the noise crite-
rion curve NC-50, corresponding to 56 dBA. This requirement
was increased to 68 dBA due to hardware constraints in 1986.
Space shuttle flight rules stipulate that when noise levels are
at or above 74 dBA when measured over a 24-h period, the
crew is required to wear hearing protection during sleep and
to adjust the time line and equipment usage to reduce noise.
Shuttle noise exposure limits are 76 to 80 dBA for five min,
81 to 85 dBA for 1 min, and noise at or above 86 dBA is not
allowed. Acoustic dosimetry, which measures noise exposure,
on one Shuttle mission (STS-40), revealed background levels
of 73 dBA, with a maximum of 80 to 85 dBA during ergom-
eter operations. There were significant effects on crew per-
formance and communication [34]. For short-duration shuttle
flights, standard hearing tests pre- and postflight have been
adequate to measure changes in hearing. Neither temporary
nor permanent threshold shifts have been observed in the U.S.
Space Shuttle program.
During the nine-day STS-40 mission, six of seven crew-
members reported that noise interfered with their ability to
concentrate and relax and the six crewmembers who wore
earplugs still had sleep disruptions [35]. The average back-
ground noise levels were 70 dBA in the SpaceLab module,
64 dBA on the shuttle middeck, and 62 dBA on the flight deck.
The STS-40 crew reported that speech intelligibility was ham-
pered by noise and that an acoustic level equivalent to NC-50
would only allow 80% of key words to be understood. The
crew reported increased vocal effort was necessary to com-
municate with fellow crew if they were more than 2 ft apart
on the flight deck, 1.6 ft apart on the middeck, and 0.65 ft
apart in the SpaceLab and that this contributed to fatigue.
No clinically significant hearing loss was documented, but
average postflight thresholds increased 4 dB, from 9 dB pre-
flight to 13 dB postflight, which was statistically significant
(see Figure 24.1). The entire crew agreed that the noise levels
experienced during that mission, would be unacceptable for
long-duration missions. On the 13-day STS-50 mission 67%
of the crew (four astronauts) expressed difficulty concentrat-
ing or relaxing with background noise levels of 64 dBA on
the flight deck, 60 dBA on the middeck, and 61 dBA in the
SpaceLab [36]. The same report also indicated that 60% of
525
Figure 24.1. Average preflight and postflight audiometry results for
the STS-40 crew. Increased hearing thresholds were noted in all fre-
quencies
33 flown astronauts reported disturbed sleep, annoyance, or
trouble with relaxation and speech intelligibility as a result of
noise on orbit. Half of the STS-57 crew felt that noise levels
during that mission would be unacceptable for a six month
stay [37]. The sampling interval of acoustic data may also be
a factor. On the STS-74 mission to the Mir space station, a
1 h and 50 min audio dosimetry measurement extrapolated to
a 24 h exposure was not felt to be a reliable estimate of the
noise environment [38]. In a ground-based study involving
a Lunar-Mars habitat test chamber, participants reported that
noise exposure could result in communication difficulties
and cause hearing damage; they could also be annoying or
stressful and cause degradation in work performance. [39]
Russian Space Experience
Temporary and, in some cases, permanent hearing loss has
been a demonstrated consequence of long-duration space
flight [40]. Reports from the Salyut 6 space station note the
highest postflight threshold shifts were at 4 to 6 kHz. A Rus-
sian summary of Salyut 6, Salyut 7, and Mir station data found
changes in cosmonaut hearing in high frequencies (2 kHz and
higher) on flights of seven days to one year. In one study, TTS
has been reported in 100% of cosmonauts, and PTS has been
identified in 27 of 33 cosmonauts. In 30 years of Russian
long-duration space flight, 33 Soyuz, Salyut, and Mir civilian
cosmonauts, (excluding military aviators) with normal hearing
initially were followed. Five cosmonauts were disqualified
from further space flight because of extreme NIHL (50 dB
loss at 4 to 6 kHz), and 12 had 30 dB loss. The noise environ-
ment on Mir caused permanent hearing damage in one third
of the long-duration crewmembers, and five cosmonauts were
medically disqualified from subsequent flights as a result. The
measured sound pressure levels on the Mir from expeditions
26 and 27 were 71 to 77 dBA during work periods. One Mir
cosmonaut had a threshold shift 71 days after a 365-day space
flight [40].
Hearing loss incurred during space flight typically affects
the high frequency range (1 to 6 kHz) [41]. Nefedova in 1990
summarized that while there are individual differences,
changes in cosmonaut hearing may be described as involving
526 J.B. Clark and C.S. Allen

Table 24.3. Postflight threshold shift (dB) of either ear compared

to preflight audiometry in cosmonauts who consistently did or did
not use hearing protection.
Flight
duration Hearing
(days) 0.5 kHz 1 kHz 2 kHz 3 kHz 4 kHz 6 kHz protection
7 6 19 8 1 0 6 No
7 19 4 4 11 5 11 No
25 0 0 1520 No
150 0 0 0 0 0 1020 Yes
150 0 0 0 0 0 0 Yes
241 0 0 0 0 0 0 Yes
365 0 0 2040 No Figure 24.2. Hearing acuity (dBA) as measured in left ear at 4 kHz
365 2045 0 2045 No in Skylab astronauts compared with non-Skylab astronauts and con-
Actual audiograms available for seven-day missions only; other data derived
trols (LSAH comparisons) vs. age. (LSAH = longitudinal study of
from compiled data and presented as ranges in merged cells. astronaut health.)

changes in auditory sensitivity in the area of high frequen-

cies (2 kHz and higher) for flights of seven days to one year.
[42] Table 24.3 summarizes published Russian studies from
Salyut 6, Salyut 7, and Mir missions on hearing assessments
performed after space flight. Unresolved questions include
what the background noise levels were and type of and com-
pliance with hearing protection. These data suggest that aside
from bone and muscle loss and radiation accumulation, hear-
ing loss may also be a significant medical problem associated
with long-duration space flight.

U.S. LongDuration Spaceflight

Experience
The Skylab series of long-duration space flight included
the 28-day Skylab 2 mission, the 59-day Skylab-3 mission,
and the 84-day Skylab-4 mission, each of which involved a
three-person crew. No changes in pure tone audiograms were
observed on postflight testing after the 28-, 59-, and 84-day
Skylab missions. Differences between the Skylab and Russian
experiences could be attributed to larger habitable volumes
in the Skylab with increased crew distance from noise-pro-
ducing equipment and the fact that the cabin atmosphere was
maintained at lower than sea level pressure (5 psi rather than
14.7 psi), which may have resulted in acoustic effects such
as reduced radiation efficiency of noise sources, and pos-
sible changes in the hearing response of the crew. Hearing
protection was not used on Skylab. Follow-up audiograms
have shown decline in high frequency hearing function as the
crewmembers have aged. At 20-year follow up examinations,
Skylab crewmembers had 40 to 70 dB loss at 6 to 8 kHz and
30 to 50 dB loss at 3 to 4 kHz. Comparing Skylab audiograms
to those of age-matched controls in the Longitudinal Study of
Astronaut Health, the Skylab astronauts showed 5 to 10 dB
more loss at 2 to 4 kHz after age 55, which parallels the non-
Skylab astronauts hearing decline with age (see Figures 24.2
and 24.3). These changes may be related to jet noise exposure
and not necessarily to the spaceflight experience.
Figure 24.3. Mean hearing acuity (dBA) measured in left ear for
Skylab astronauts vs. age. Flight experience includes three missions
of 28, 59, and 84 days duration shared among nine crewmembers
One of seven NASA-Mir astronauts experienced a TTS as
a result of long-duration space flight without hearing protec-
tion, with subsequent resolution (no PTS). On the Mir space
station the measured sound was a maximum of 73 dBA. One
NASA-Mir astronaut gave his perspective of noise on long-
duration space flight. During his stay on Mir, he slept in the
Priroda module near a massive fan. Using this structure for
added radiation protection, the sound level in this location was
58 dBA. His acoustic dosimetry readings averaged from 62
to 68 dBA. The muff headsets were found to be too uncom-
fortable after 30 min. However, foam earplugs were used as
protection against high frequency noise, and an active noise
reduction headset was worn for low-frequency noise for his
entire 8-h sleep shift. The active noise reduction headset did
not interfere with hearing alarms. The high noise levels inter-
fered with communications, and this crewmember had to press
the headset to his ears to hear. Noise levels of 68 to 70 dBA
caused headaches in the crew. The operational impact of high
noise levels resulted in an inability to hear alarms more than
20 ft away. The treadmill operation was also noted to be very
noisy, and the continuous noise was noted to be worse than
intermittent noise.
24. Acoustics Issues
International Space Station Experience
The International Space Station (ISS) is comprised primarily
of components built by the United States and Russia, which
together with other international partners establish specifica-
tions for habitation. The Russian Space Agency (RSA) speci-
fication for continuous noise on board spacecraft is 60 dBA,
in addition to SPL requirements given in each octave band,
when the crew is awake, and correspondingly 50 dBA when
the crew is asleep. The U.S. Space Station Program (SSP)
specification for continuous noise in ISS modules is the noise
criterion curve NC-50 when the crew is awake and NC-40
when the crew is asleep (see Figure 24.4). In U.S. modules
with payloads (science experiments), the complement of pay-
loads is also allowed an allocation equivalent to NC-48 so
that the total module plus payloads requirement is NC-48 +
NC-50, which is approximately equivalent to the NC-52 noise
criterion curve.
In addition to continuous noise requirements, there are also
intermittent noise requirements, which are based on the dura-
tion of the increased levels. These intermittent requirements
are implemented differently in the Russian and U.S. seg-
ments. Finally, an impulsive noise limit of 140 dB (not dBA)
for a noise with duration less than 1 s, and a hazard limit of
85 dBA (for noise durations longer than 1 s) are established.
Caution and warning alarms, which project acoustic tones at
0.5 and 2 kHz, are required to be 20 dB louder than ambient
noise levels. Detailed acoustics analyses and application of
countermeasures have been described by Goodman and Allen
[43,44].
In order to ensure a safe acoustic environment for the crew,
noise levels in the ISS modules are routinely monitored. In the
Service Module, the primary residence for ISS crews, noise
levels have been measured at 69 dBA during ground testing,
and 67 to 72 dBA on orbit. These noise levels in the Service
Figure 24.4. Noise criterion (NC) curves and Russian specification
for spacecraft. Limits are expressed in octave frequency bands
527
Module exceed specifications substantially, and work is cur-
rently underway to reduce these levels.
The U.S. Lab module produces levels up to 60 to 64 dBA
depending on location. In addition, the Node 1 module has
been measured to produce levels of 50 to 57 dBA, and the
Functional Cargo Block (Russian Acronym FGB) produces up
to 58 to 66 dBA. Crew noise exposure levels on ISS, measured
over a 24-h period, range typically from 65 to 71 dBA. These
exposure levels are highly dependant on where the crew spent
most of their time, what type of work was being performed,
and where the crewmembers slept.
Among the significant noise sources throughout the ISS
are the life support system ventilation fans. The most sig-
nificant acoustic contributions on the Service Module are
the Vozdukh carbon dioxide removal system (+70 dBA),
the refrigerators (70 dBA), air conditioning and ventilation
fans (69 to 52 dBA), and the Thermal Control System pump
(57 dBA). The U.S. supplied Treadmill and Vibration Isola-
tion System (TVIS) is an intermittent noise contributor with
measured levels of 77 dBA during ground assessments (see
Figure 24.5).
The ISS Safety Review Panel (SRP) reviews hazard reports
and endorses them as approved, approved with modifications,
or disapproved. Failure of the functional cargo block (Rus-
sian acronym FGB) and Service Module, for example, to meet
the Russian acoustic requirements necessitated the submittal
of a non-compliance report (NCR) for the Russian Segment,
which outlined a staged risk mitigation implementation plan.
The SRP conditionally accepted the NCR with the provision
that additional controls be identified and implemented for 24-
h ISS occupation. The ISS Russian Segment acoustic require-
ments were modified from 60 to 73 dBA for the FGB work
environment. Maximum noise levels on the FGB module were
measured at 74 dBA on the first Shuttle mission to visit the
ISS (STS-88). Acoustic hardware modifications, including air
Figure 24.5. International Space Station Service Module sound
pressure levels (SPL) as a function of frequency with and without
treadmill operations (from ground test data) at one location com-
pared with Russian spacecraft continuous noise specifications
528
vent louvers, air duct mufflers, and fan base isolators, were
made to the FGB in May to June 1999 during the STS-96 mis-
sion. These modifications reduced noise 0.5 to 5 dBA in the
FGB but failed to reduce noise levels enough to meet require-
ments and contributed to negative air quality experienced by
the STS 96 flight crew [45].
The SRP granted approval of the NCR concerning the FGB
and Service Module acoustic hazards, conditional upon crew
hearing protection availability and implementation of acoustic
mitigation hardware modifications. The Implementation Plan
was divided into high priority measures, measures imple-
mented during Service Module habitation for Expedition 1,
logistics issues, and operational modifications to crew sched-
ule. High priority measures included noise-dampening covers
for the carbon dioxide removal system, installation of sound-
absorbing material on circulation fans, modification to refrig-
erator components, and gap closures, as well as the addition
of noise abatement material to the Service Module inte-
rior. Lower priority measures after Service Module habitation
included redesign of fans and thermal control pump compo-
nents. Logistic items included noise level assessment and use
of active noise cancellation headsets by the crew. Modifica-
tions to crew schedule included identification of equipment
that could be operated intermittently or in sequence to mini-
mize cumulative noise. Finally, flight rules for operation of
noise producing hardware and for the wearing of hearing pro-
tection were developed.
Individual hearing protection hardware is provided to all ISS
crewmembers and must permit caution and warning (C&W)
tones to be audible. Comfort, anthropometric accommoda-
tion, and ease of cleaning were considered in the certification
and selection of hearing protection equipment. Guidelines for
the applicability of Active Noise Reduction (ANR) headsets
include noise attenuation as a function of frequency of the
passive components, overall noise attenuation of the system
including active components, and individual factors. ANR
headsets are generally effective from 125 to 2000 Hz and most
effective up to 800 Hz, while other passive hearing protection
(foam plugs, plastic plugs, and molded plastic plugs) are effec-
tive at all ranges tested, particularly above 2000 Hz. ANR and
passive hearing protection may also be used simultaneously.
In a study of ANR headset effectiveness in helicopters, sub-
stantial low frequency noise attenuation was demonstrated, but
when white noise from the communication system was intro-
duced there was an increase in middle frequency noise [46].
Assessment of the acoustic environment aboard the ISS is
made possible with on-orbit equipment capable of making
real-time measurements of sound pressure levels [47]. Two
devices are available; the ISS Sound Level Meter (SLM) and
ISS Acoustic Dosimeter. The ISS SLM measures the equiva-
lent SPL in each 1/3 octave band from 50 Hz through 10 kHz,
averaged over a short time, nominally 15 s. Measurements
are performed at many locations on the ISS as part of a sur-
vey with only the continuously operating hardware activated.
Octave band SPLs are then calculated from the 1/3 octave
J.B. Clark and C.S. Allen
bands to compare with ISS continuous noise requirements.
The ISS Acoustic Dosimeter measures equivalent A-weighted
overall sound pressure levels, averaged over an extended
time, typically 24 h. These measurements capture the intermit-
tent noise in addition to the continuous noise, including noise
from speech, and are either worn by the crew or placed at a
specified location. Both types of measurements are performed
approximately once every two months as well as at the crews
discretion.
Hearing Assessment in Space
Conventional pure tone audiometry requires a personal head-
set and heavy soundproof booth, which is impractical for
space flight. Audiometry was performed as a flight experiment
on Space Shuttle flights STS-6, 7, and 8 by astronauts under
the direction of investigator Dr. Bill Thornton, who designed
and built an audiometer that delivered sound by a headset.
Although the procedures worked well in this experiment,
results were questionable due to differences in background
noise levels between the missions confounding the findings
and causing apparent threshold shifts during the testing. Pure
tone audiometry has also been performed in space as part of
a joint Russian-German cooperative project. The audiometer,
Elbe 2, was flown on a seven day Salyut 6 docking mission
and was also used on Mir. Complete data have been published
from the seven-day flight [48]. The in-flight data show clear
threshold shifts, particularly at the lower frequencies, that are
not present on the day following landing. These data suggest
that ambient noise in the station may have interfered with
the measurements, but the details on how the testing was
performed were not provided in the published reports. An
in-flight hearing test could monitor effectiveness of standard
hearing protection countermeasures and provide the crew with
a new capability to tailor hearing protection countermeasures
to individual crewmembers.
Otoacoustic emissions (OAE) measurement offers an
attractive alternative to standard pure tone audiography for
the spaceflight environment. OAE are physiologic signals that
arise from vibration of outer hair cells (OHC) in the cochlea
[49]. Mechanical energy travels from the OHC via the middle
ear ossicles and tympanic membrane, where it is measured
by a microphone in the ear canal. Outer hair cells are highly
metabolically active and are damaged by ototoxic medica-
tions and agents, vascular disease, hypoxia, and high-energy
noise exposure. OAE signals have been used extensively in
screening neonatal hearing and in assessing cochlear function
in infants and children [50].
Otoacoustic emissions may be spontaneously generated or
evoked by various stimuli. Two types of evoked OAEs are the
transient evoked otoacoustic emissions (TEOAE) and distor-
tion-product otoacoustic emissions (DPOAE). Evoked OAEs
are generated by using a small speaker to excite a mechanical
response from the eardrum and use a microphone to detect
24. Acoustics Issues
the response of the OHC to the sound stimulus [51]. The
approaches used to acquire evoked OAE signals include (1)
keeping stimulus intensity constant while varying frequencies
or (2) varying stimulus intensity while keeping frequency con-
stant. Transient-evoked otoacoustic emissions are evoked by
brief click stimuli and may be detected in people with hearing
thresholds of 30 dB or better [52]. DPOAEs are elicited after
the presentation of two pure tones closely spaced in frequency
(f1 and f2, where f1 = 1.2f2) and amplitude (where L1 =
55 dB and L2 = 65 dB). The cochlea produces distortion prod-
uct harmonics of these tones, the most prominent of which is
at 2f1-f2. DPOAE is more frequency specific and is detected
in people with hearing thresholds of 50 dB or better [53].
Otoacoustic emissions are entering clinical use for the moni-
toring of noise-induced hearing loss [51]. Otoacoustic emissions
provide insight into potential damage before changes in pure
tone audiometry thresholds can be detected, and can be used to
identify noise-susceptible individuals [54]. High-energy noise
decreases emission amplitude and narrows the spectral band.
The DPOAE in noise-induced hearing loss shows a character-
istic notch around 4 kHz [55]. Reduction of DPOAE amplitude
has been observed with short (hour) and long-term (years) noise
exposure [56]. Middle-ear abnormalities such as otosclerosis or
external ear blockage from cerumen can interfere with OAE sig-
nals, although it is not entirely understood how such abnormali-
ties affect OAE transmission [57]. Although DPOAE performed
on normal hearing subjects can predict normal or sensory-
impaired hearing with a high degree of accuracy, threshold
estimation is still marginal [58].
OAEs have several advantages for space flight operations;
they may be performed quickly by unskilled personnel, do
not require a subjective or conscious response, and may be
done in a noisy environment. The DPOAE signal has been
recorded in high-noise environments using a standard passive
hearing protection headset placed over the otoacoustic probe,
but the signal is usually not detectable in a noisy environment
without hearing protection as the increased background noise
decreases the signal-to-noise ratio (Figure 24.6). The noise
environment used in the testing was sound-recorded from the
ISS Service Module in May 2000 while it was operating dur-
ing ground tests prior to the 12 July 2000 launch. The noise
was played at the sound level of 70 dBA measured in the Ser-
vice Module at the time of recording. DPOAE were recorded
on six subjects using the Etymotic EroScan ER-34 with and
without the headsets while seated in a quiet environment or
subjected to Space Station noise. The passive hearing protection
headset has attenuation better than 20 dB above 200 Hz, which
was adequate to shield ambient background noise and gener-
ate reliable otoacoustic emission signal to noise ratios, as seen
in Figure 24.6. DPOAE were not adequate in a noisy environ-
ment without the use of a hearing protection headset but were
adequate in the noise environment with hearing protection. A
similar test under identical conditions was conducted on the
Grason Stradler GSI 70 OAE screening device, which yielded
similar results.
529
Figure 24.6. Distortion product otoacoustic emission (DPOAE) under
quiet and noise conditions with and without hearing protection. Noise
source used for testing is representative of International Space Station
background noise
The clinical utility of OAEs lies in screening, monitoring,
and quantifying hearing loss and aiding in differential diag-
nosis. OAE may be practical for on-orbit hearing assessment
because it is objective (no subject response required), self-
calibrating, and functional in the presence of background
noise. DPOAEs have been performed in noise fields beyond
65 dBA. DPOAEs are consistently and reproducibly able to
detect smaller differences than audiometry. A 3 dB change in
OAEs is considered clinically meaningful, and a 6 dB change
is very significant, whereas with conventional audiometry
5 dBA is significant. Drawbacks of OAEs include difficulty
recording with middle ear pathology (stimulus and OAE
response transmit energy via the middle ear), signal limitations
due to cochlear hearing loss (30 dBA for TEOAE, 50 dBA for
DPOAE), and inability to assess retrocochlear function. In
addition, OAEs represent a young technology without ANSI
standards in place; as such, inter-manufacturer variability
exists in available equipment.
Physiologic changes in the auditory system associated with
microgravity may affect evoked stimulus propagation and
OAE detection. More global physiologic changes associ-
ated with microgravity may alter OAEs, particularly headward
fluid shifts. Intracranial pressure is increased in weightlessness
compared with ground valves in seated and standing postures
[59]. Although some studies show no effect on otoacoustic
emissions with changes in body position and the accompany-
ing changes in CSF pressure [60], others do show changes
[61]. Future flight experiments will hopefully evaluate OAEs
to evaluate this procedure in the space environment and estab-
lish this method as a useful onboard clinical tool.
To assess hearing of the initial ISS increment crewmembers,
a Minimum Audibility Test (EarQ Software) with modified
off-the-shelf software used by musicians and professional
divers was flight certified for on-orbit hearing assessment.
The software uses a laptop computer sound card to deliver
tones of varying frequencies and calibrated intensities through
high fidelity custom molded earphones which are part of the
Acoustic Countermeasures Hardware. The Medical Equipment
530
Computer (MEC) is part of the Crew Health Care Systems
(CHeCS) on board the ISS. The MECs primary purpose is
to provide the user with information services for CHeCS.
The MEC is an off-the-shelf, flight-certified portable com-
puter that has the ability to display physiological data, main-
tain medical records, assess crew health, and permit two-way
data exchange through the command and data handling sys-
tem of ISS. Volume in the Minimum Audibility Test may be
increased in 1 dB increments using the MEC keyboard. The
subject increases the volume level until a hearing threshold is
reached at each frequency (0.25, 0.5, 1, 2, 4, 6, 8, 10 kHz) in
each ear. The results are sent to the ground during scheduled
MEC downlink periods for assessment by the ground medical
team. The program is small (~500 kB), the user interface very
intuitive, involving limited procedures and training, and testing
may be completed in under 10 min. Each session is displayed
with regard to frequency intensity and compared to baseline
or other prior sessions to provide immediate feedback to crew-
members. Session data files are archived and downlinked for
further interpretation. Based on the results of the EarQ tests,
the flight surgeon may ask that the crewmember take addi-
tional precautions such as donning ear plugs for a certain
amount of time each day or minimizing time in proximity to
noise-producing systems to help conserve the crewmembers
hearing. Other methods for monitoring hearing include crews
subjective reports during periodic medical debriefs as well as
quantitative tools for measuring actual on-orbit noise expo-
sure (audio dosimeter and sound level meter).
Space Environment Interactions
The combined effects of environmental factors (vibration,
temperature, continuous noise, and physical exertion) associ-
ated with long-duration space flight are relatively unknown. A
number of ototoxic agents such as carbon monoxide and sol-
vents may synergistically interact with noise to produce hear-
ing loss [62]. Exposure to simultaneous noise and vibration
results in temporary and permanent threshold shifts and hair
cell loss greater than with noise alone [63,64]. A human study
examined combinations of noise (two categories: no noise and
stable broadband A-weighted noise of 90 dBA), whole body
vibration (three categories: no vibration, sinusoidal whole body
vibration of 5 Hz, z-axis and stochastic whole body vibration
of 2.8 to 11.2 Hz) and dynamic muscular work (three levels:
2W, 4W, 8W). Noise was the greatest single contributing
factor for TTS. TTS increased further as a result of the combi-
nations of noise plus vibration and noise plus muscular work.
The combined effect of all three factors (noise, vibration, and
work) on the TTS results was greatest when the vibration was
stochastic and the dynamic muscular work was light (2W);
by increasing the workload the measured TTS levels were
attenuated. Light dynamic muscular work and cardiovascular
activity may have enabled the interaction of noise and vibra-
tion, while strenuous muscular and cardiovascular activity in
J.B. Clark and C.S. Allen
some way negated the effects of noise and vibration [65]. Heat
stress also appears to play a role; a 10C ambient tempera-
ture increase resulted in 5 to 10 dB greater TTS when subjects
were exposed to noise and whole body vibration [66].
The microgravity environment, dynamic workload, stress,
continuous 24-h-a-day moderate noise exposure, electromag-
netic radiation, and potential for toxic exposure all may lead
to cochlear hair cell damage and greater than expected noise-
induced hearing loss. Electromagnetic energy may be trans-
duced to acoustic energy by thermal expansion, electrostriction
(volume contraction in protein solution due to formation of
electrically charged particles), and surface radiation pressure.
Microwave energy such as from radiating communications
antennae can result in audible clicks and annoyance [67].
Such emitters are present on the ISS, although radiating zones
exclude habitable areas and outside emission zones are avoided
during extravehicular activities (EVAs). Carbon monoxide, a
byproduct of combustion that has been detected in spacecraft
combustion events, can increase high frequency noise-induced
hearing loss [68]. High intensity low frequency noise may ema-
nate from such sources as the life support system ventilation
fans. The use of the A-weighted scale of sound measurement
for assessing spacecraft noise levels may under-emphasize the
intensity of low frequency noise, where the maximum energy
is often found [32]. By A-weighting sound pressure levels, the
low frequency levels are reduced by 0.8 dB at 800 Hz, 26 dB
at 63 Hz, and 39 dB at 31.5 Hz. Burdick demonstrated that low
frequency noise exposures (below 500 Hz) in animal models
consistently produced their greatest threshold shifts and hair
cell damage 3 to 7 octaves above the characteristic frequency,
and above 500 Hz noise produced its maximum effects one-
half to one octave above the center frequency of the noise
band [69]. Burdick further demonstrated that humans exposed
to tones from 2 to 22 Hz at intensity levels of 119 to 144 dB
SPL developed threshold shifts in the frequencies from 3000
to 8000 Hz. Exposure to 63 Hz at 110 and 120 dB SPL (84
and 94 dBA) resulted in the highest threshold shifts occurring
between 1000 to 3000 Hz.
Countermeasures
Countermeasures against spacecraft noise include design engi-
neering controls, sound insulation materials, and hearing pro-
tection. Engineering and design controls to reduce noise should
be the primary focus of any hearing conservation program, but
this is not possible in all situations. Quiet fan technology exists
but may exact a penalty in weight, power consumption. and
circulation efficiency, all of which are crucial factors in space-
craft environmental controls. Advanced composite materials
with excellent low frequency attenuation properties could be
applied as a barrier protection around noisy equipment or used
on personal protective equipment worn by the crew. Hearing
protection countermeasures include foam ear inserts, passive
muff headsets, and active noise reduction headsets. Hearing
24. Acoustics Issues
protection is recommended when the crewmembers 24-h
equivalent noise exposure exceeds 65 dBA or when they are
exposed to high levels of noise such as when exercising on
the treadmill (TVIS). However, wearing hearing protection
for long periods of time is not an optimal solution because
of discomfort, increased risk of ear infections, difficulty with
communications, and reduced effectiveness when removed fre-
quently to communicate. Crewmembers should also be aware
that playing music over personal headphones or speakers in an
attempt to mask noise only increases risk of hearing loss.
While noise levels on spacecraft are far below the 110 dBA
SPL levels considered necessary for mechanical damage, the
continuous nature of this sound environment may cause long-
term metabolic exhaustion of the inner ear cochlear tissue.
Periods of quiet rest are needed to allow the cochlea to recover
from hearing fatigue [70]. Although most people are able to
experience relatively long periods of quiet while sleeping, this
was not possible in the environment found on the Mir, and
even hearing protection offers only slight attenuation of low
frequency noise due to persistent bone conduction, of which
the levels were unknown. The standard occupational exposure
to environmental noise assumes an 8-h exposure with 16 h of
acoustic rest. Periods of relative quiet (less than 70 dB) have
been suggested for treatment of very high levels of noise
exposure, to allow hair cells to repair themselves [71]. The
recovery time for TTS, a biological repair process, is roughly
proportional to exposure time and intensity and seems to
depend on frequency as well [72]. The time needed for repair
of the damage may be as long as 24 to 48 h for an 8 to 24 h
exposure. In the Yuganov study, 50 h of recovery was needed
for a 75 dBA exposure, but animal data at 80 dBA suggests
TTS recovery took five days after a 48 h exposure and was
still incomplete after a 90 day exposure at 150 days after noise
exposure [28,73]. Noise capable of causing a TTS is propor-
tional to the intensity and time of exposure and is also fre-
quency dependent. A general formula for TTS four minutes
post-exposure (TTS4 min) is:
TTS4 min = 1.7(SPL A),
where A = 47 dB for 4 kHz octave band noise and A = 65 dB
for 0.5 kHz octave band noise [73,74]. This formula implies
that noise rest should occur in an environment with an octave
band background of less than 47 dB for high frequency noise
and below 65 dB for low frequency noise. Reestablishing a
rest period through engineering methods, e.g. as with
sufficiently quiet sleep quarters or provision of pharmacologi-
cal protection or repair enhancement may constitute effective
countermeasures.
In many pathological conditions, such as injury, aging,
inflammation, and ischemia and subsequent reperfusion,
excessive production of reactive oxygen species has been
postulated to occur and cause cell damage. Evidence has
been accumulating that indicates that reactive oxygen species
play a substantial role in damaging the inner ear secondary
to various toxins and noise. Continuous high-level noise is
531
associated with cochlear production of superoxide anion and
the hydroxyl radical, both of which are capable of inducing
cochlear damage and loss of function. Noise modulates the
level and activity of key antioxidant compounds in the inner
ear such as glutathione (GSH) and a variety of antioxidant
enzymes. Supplanting or reducing inner ear GSH either ame-
liorates or intensifies noise induced permanent threshold shift
(NIPTS), and a variety of strategies to augment cochlear anti-
oxidant defenses have been shown experimentally to reduce
noise related hearing loss. It has recently been shown that an
antioxidant combination of L-N- acetyl cysteine and low dose
salicylate was effective in reducing permanent hearing loss
as well as hair cell loss in a chinchilla model, opening up the
very real and exciting possibility of utilizing pharmacological
agents to prevent NIPTS [10]. Future work includes under-
standing the role oxidative stress plays in NIHL and develop-
ing an effective pharmacological strategy to reduce cochlear
damage in the spacecraft environment associated with moderate
continuous noise.
Conclusions
NASA is concerned about acute effects of spacecraft acous-
tic noise on crew performance and is developing strategies to
assess and reduce the acute, chronic, and delayed effects of
this noise. High noise levels can cause headaches, irritation,
fatigue, impaired sleep, and tinnitus, all of which can impair
performance. High noise levels have resulted in an inability to
hear alarms, and speech intelligibility may be more impaired
for crew hearing a non-native language in a noisy environ-
ment. Countermeasures include hearing protection and
designengineering controls. Advanced composite materials
with excellent low frequency attenuation properties could be
applied as a protective barrier around noisy equipment or used
on personal protective equipment worn by the crew. Hearing
protection countermeasures include foam ear inserts, passive
muff headsets, and active noise reduction headsets, though
wearing hearing protection for long periods may be prob-
lematic. Microgravity, vibration, toxic fumes, air quality and
composition, stress, temperature, physical exertion or some
combination of these may interact with moderate long-term
noise exposure to cause significant hearing loss. Crewmem-
bers should be aware that playing music over personal head-
phones in an attempt to mask noise increases risk of hearing
loss. Future work includes determination of whether the dBA
scale is adequate for estimating acoustic bioeffects and what
sound level and duration are adequate for noise rest (quiet).
The ability to perform hearing assessments in the noise
environment of spacecraft is highly desirable but leaves other
unanswered questions. If a threshold shift occurs in flight,
what treatment is adequate, and what agents can be used for
NIHL prevention or treatment in space? A significant concern
is the interaction between noise, vibration, workload, and co-
morbidity factors, such as radiation, toxicology, microgravity
532
effects (e.g. thoracic fluid shift), and aging, which may be
involved with NIHL. Longitudinal studies will need to address
which of these co-morbid factors might be involved with hear-
ing loss. The basic science of noise induced hearing loss (NIHL)
is essential in developing strategies for protection, rescue, and
regeneration. Pharmacological modalities may prove useful in
countering cell damage. Space medicine practitioners should
remain active in formulating and enforcing noise standards in
all aspects of human space flight; this includes hardware design
and production, mission design, and activities planning. New
technology such as OAE may well prove useful for in-flight
acoustic monitoring and longitudinal baseline screening.
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25
Ophthalmologic Concerns
F. Keith Manuel and Thomas H. Mader
This chapter reviews ophthalmic issues associated with space-
flight operations. Current vision standards for space flight,
methods of vision correction for spaceflight crewmembers,
and vision demographics are discussed, followed by clinical
conditions that could affect spaceflight duties and common
ocular emergencies that could occur during space opera-
tions. The current medical selection and retention standards
ensure that space crewmembers are generally healthy, free of
significant chronic disease, and are not taking medication on
a long-term basis. This chapter focuses primarily on ocular
abnormalities that might be expected in healthy subjects dur-
ing exposure to microgravity.
Vision Standards and Selection Testing
Since 1959, more than 300 men and women have been
selected for service in the U.S. space program as pilots, mis-
sion specialists, or payload specialists. In the early years of
NASAs history, all astronauts were military test pilots and as
such were required to meet the rigorous vision standards of
the military. As the effects of space flight on vision became
better understood and as more astronauts became needed in
the post-Apollo era, vision standards were relaxed.
The current NASA selection process begins with an initial
screening of several thousand applications. Information on the
physical health of these applicants is provided by examiners
from the Federal Aviation Administration (for civilian appli-
cants) or by military flight surgeons (for military applicants).
Between 120 and 140 astronaut candidates are selected from
this pool and personally examined by NASA flight surgeons
to further evaluate their medical status. Because vision is criti-
cal for astronaut function and survival, the eyes of astronaut
candidates are evaluated in a detailed and systematic fash-
ion, with standard and specialized ophthalmic equipment, in
accordance with NASA directives [13].
Unaided and best-corrected distant visual acuity is mea-
sured by using a Landolt C system, in which the letter C is
presented in various sizes and orientations. The test consists
of a random, timed presentation of single letters starting at a
visual acuity level of 20/300 and ending at the 20/20 level,
with 10 letters presented at each acuity level. The target, a
high-contrast letter C, is presented on a standard video moni-
tor (Mentor B-VAT system) for ~1 s followed by a 1.5-s pause
until the next presentation. Each eye is tested separately at a
distance of 20 ft (6 m) under controlled lighting. Selection and
retention standards dictate that for pilot astronauts, unaided
distant visual acuity must not exceed 20/100; the corresponding
value for mission-specialist astronauts is 20/200 in either eye.
Selection and retention standards for both pilots and mission
specialists also require that vision be correctable to 20/20 in
each eye. Standards for uncorrected distant vision have not
been established for payload specialists, but vision in these
individuals must be correctable to 20/30 in the better eye. No
standard has been established for uncorrected near visual
acuity in any applicant group, but near visual acuity must be
correctable to 20/20 in each eye.
Extraocular muscle function and range of motion are evaluated
by gross observation, alternating cover-uncover testing,
phorometry, and prism and red-lens testing. The results must
indicate no evidence of microtropia or macrotropia, suppres-
sion, or diplopia. The presence of any tropia is disqualifying.
Measurements exceeding 10 prism diopters of lateral phoria
or 1.5 prism diopters of vertical phoria are disqualifying.
Stereopsis is assessed at distance with a telebinocular instru-
ment (Optec 2300, Stereo Optical, Chicago, IL). A series of
3-dimensional circles consisting of 6 groups (3 rows of 5 cir-
cles per group) are presented with various levels of stereoacuity
down to 15 arc-seconds. Inability to achieve stereopsis at 25
arc-seconds is disqualifying. No alternative tests are allowed.
Color vision is assessed in each eye with a 14-plate Dvorine
pseudoisochromatic test under recommended lighting. A quali-
fying score is the correct identification of 10 of 14 plates, with
no more than 5 s viewing time allowed per plate. Subjects who
fail the pseudoisochromatic test can be retested with the Farn-
sworth Lantern Test, which consists of 9 paired presentations
of red, green, or white light. A successful score on this test is
the proper color identification of all 9 paired presentations.
535
536 F.K. Manuel and T.H. Mader

Manifest refractions are performed in standard fashion

at 20 ft (6 m) with and without cycloplegia. End points are estab-
lished for minimum correction to achieve 20/20 vision in each
eye. Notably, a candidates refraction is not maximized in an
attempt to achieve 20/15 or better during selection examina-
tions. Refractive error exceeding 5.5 D, 3.0 D of cylinder in
any meridian, or 2.0 D anisometropia (between the 2 eyes) is
disqualifying.
Intraocular pressure, measured by Goldmann applanation
tonometry, cannot exceed 24 mmHg in each eye. A difference
of 4 mmHg between eyes is also disqualifying. The cornea,
anterior chamber, iris, and lens are examined by slit lamp bio-
microscopy. Corneal topography is mapped by videokeratogra-
phy. Binocular indirect ophthalmoscopy is used to examine the
fundus while the pupil is dilated, and the fundus is photographed
as well. Central and peripheral visual fields are assessed with
computerized techniques. Listing all of the disqualifying find-
ings is beyond the scope of this chapter; however, in general
terms, any active or potentially debilitating finding in any
ocular tissue would disqualify a candidate for selection. How- Figure 25.1. Mean spherical-equivalent refraction values for 44
ever, many findings that are disqualifying for selection may be pilots and 88 mission specialists in the U.S. Astronaut Corps
considered acceptable for retention purposes.

Vision Correction
Space crewmembers must contend with demanding visual
environments during space missions and during training for
those missions. In space, these environments include rapid
lighting changes from sunrise and sunset occurring every
45 min, vibration, head-movement limitations caused by the
space suit helmet, and possibly changes in visual acuity related
to microgravity exposure. Challenges during training involve
positional constraints and need to wear specialized headgear
during flights aboard the T-38 aircraft and during underwa-
ter training activities. Environmental demands such as these,
especially for individuals who require visual correction for
presbyopia or other conditions, necessitate a vision support
system that incorporates many forms of correction. Experience Figure 25.2. Vision-correction modalities used by 135 pilots and
has demonstrated a need not only for standard-design bifocals, mission specialists in the U.S. Astronaut Corps
trifocals, double bifocals, and progressive addition lenses but
for many other specialty lenses and frames as well. The follow-
ing paragraphs give a brief overview of the vision demograph- with no refractive error) probably reflects the age of the popu-
ics among the current active U.S. Astronaut Corps is given, lation. According to the ongoing Longitudinal Study of Astro-
followed by descriptions of special visual correction systems naut Health at Johnson Space Center, currently 59% of pilot
designed for use during training and space flight activities. astronauts and 77% of mission specialist astronauts require
some form of visual correction (Figure 25.2). Among those
who wear visual corrective devices, 15% of the pilots and
Vision Demographics 33% of the mission specialists elect to wear contact lenses.
The distribution and extent of refractive error among a current Among those with ametropia (nearsightedness, farsightedness,
group of pilots and mission specialists in the U.S. Astronaut or astigmatism), a multifocal correction is required for 50% of
Corps are shown in Figure 25.1. The magnitude of refractive the pilots and 53% of the mission specialists (Figure 25.3). Inter-
error reflects the stringent vision standards described previously. estingly, in the multifocal-correction group, progressive addition
As the figure indicates, the data are distributed normally; the lenses are preferred over bifocals by 42% of the pilots and
notable absence of individuals with emmetropia (i.e., those 49% of the mission specialist astronauts.
25. Ophthalmologic Concerns
Figure 25.3. Spectacle types used by 96 pilots and mission special-
ists in the U.S. Astronaut Corps
Spectacles
Many modifications have been made to standard spectacles to
meet the unique demands of training for space flight and the activ-
ities in that environment. One such modification is the insertion of
vertical bifocal lenses in the temporal aspect of the spectacle lens;
these lenses allow the wearer to see small nearby objects located
in the extreme lateral viewing area while wearing the extrave-
hicular-activity helmet. Many presbyopic astronauts have found
such lenses extremely useful in this confined environment.
Another vision system that has proven useful in space is the
FD trifocal (Vision Ease, Azusa, CA), an executive-style trifo-
cal lens with a line traversing the width of the lens and a flat-
top 28-mm bifocal inset. The vertical separation of bifocal and
trifocal lines in these lenses is 11 mm rather than the standard
7-mm separation. The exceptional amount of lateral viewing
area provided by the wide intermediate lens area has proven
practical in the operational space flight environment.
Another type of multifocal corrective lens, the Access pro-
gressive addition lens (Sola Optical USA, Petaluma, CA),
was designed for near and intermediate-distance work. The
designated reading area of the lens has a centrally located 10-mm
transition zone of +0.75 or +1.25 D (depending on the pre-
scription required) and an upper segment of uniform inter-
mediate power. This lens has been used successfully during
underwater training sessions for extravehicular activities, in
which the interface between the water and the helmet mask
produces a 2.57-D myopic effect. Because many space crew-
members are presbyopic and a vital control panel on the chest
of the suit is located ~10 in. (25 cm) from the crewmembers
eyes, a compensatory spectacle prescription is often needed to
meet this increased demand for accommodation. The Access
lens design, with +2.50 D added to the normal calculated
prescription, has been successful for this purpose.
537
Slight modifications to traditional bifocal or trifocal line set-
tings are also useful during T-38 missions. This aircraft, which
NASA pilots and mission specialists are required to fly to
maintain flight proficiency, includes a tilted seat that mandates
the lines on bifocals or trifocals be set lower than standard lev-
els. Experience has shown that in standard aviator frames, seg-
ment lines 10 mm above the lower eye-wire are successful. A
slightly longer bifocal focal length calculation of 20 in. (51 cm)
works well for individuals with early presbyopia and can help
avoid the need for trifocals for older presbyopic individuals.
Other ocular challenges associated with orbital flight
include glare from extreme sun intensity and the potential for
exposure to UVA, UVB, and UVC electromagnetic radiation.
The Adidas model A125 wrap-around sunglass frame (Silhou-
ette Ltd, Northvale, NJ) design has been found to be effective
for this purpose. This product fits comfortably, blocks 100%
of electromagnetic radiation at less than 400-nm wavelengths,
limits visible blue light to 5%, limits all visible light to 7%,
and restricts infrared light to less than 31%. A mirror-coated
front surface lens wraps around, giving excellent peripheral
vision protection. A prescription spectacle insert is easily
added behind the tinted carrier lens if necessary.
Suspension frames, a specialty frame from Suspension Eye-
wear Enterprises (Fountain Valley, CA), have proven useful
in situations requiring long-term use of helmets during T-38
flights and communication gear during space flights. Wearing
such headgear for long periods frequently causes hot spots
where the temple of standard spectacle frames is pressed
against the temporal aspects of the crewmembers head. In the
unique suspension frame design, each temple portion of the
glasses frame is replaced with 2 monofilament nylon lines that
originate from 2 drilled holes in the temporal aspects of
the spectacle lens. The strings are then tied into a small earpiece
when the glasses are fit, thus allowing a customized fit. The
monofilament lines preclude any compression hot spots.
After manufacture of the suspension frame was discon-
tinued, a titanium-frame product has been used in its stead.
Manufactured by Silhouette Optical, these frames are thin,
lightweight, and highly durable. The temple wires are thin
enough to avoid causing hot spots around the temples, and
their low mass helps stabilize the frames during head move-
ments made in microgravity. The absence of screws in this
eyewear design further reduces risk to the crewmembers from
product failure. If a screw in a typical spectacle design were
to back out, the corresponding release of the spectacle lens
poses potential hazards, particularly during extravehicular
activities. A free-floating lens could become lodged between
the astronaut and a firm area of the suit, possibly cutting the
inside suit bladders and causing suit depressurization. Free-
floating screws could be drawn into the suit-cooling impeller,
resulting in mechanical malfunction, or could be accidentally
ingested or aspirated as well as becoming lodged in the eye of
a crewmember. For these reasons, the titanium-frame design is
recommended for crewmembers who elect to wear spectacles
during space flight.
538
Contact Lenses
Approximately one-third of U.S. astronauts who wear spec-
tacles prefer to wear contact lenses during space missions.
NASA has evaluated a variety of soft and hard contact lenses
aboard the parabolic-flight aircraft. In these studies, alternating
exposure to simulated hypergravity conditions and simulated
microgravity (free fall of 30 s duration) did not affect the
performance of spherical or toric soft contact lens. Rigid gas-
permeable lenses, however, tended to be displaced superiorly.
As a result of these assessments, nearly all types of contact
lenses are approved for all phases of orbital flight. However,
segmented or progressive power rigid gas-permeable multifo-
cal lenses are not recommended because of their tendency for
superior displacement on the cornea. Our clinical experience
since 1990 has supported these findings, with no reports to
date of poor visual performance or permanent corneal insults
as a result of wearing contact lenses during space flight.
Nevertheless, caution is required when contact lenses are
used during space flight because of limited on-board diagnos-
tic and treatment capabilities in the event of ocular complica-
tions. Altered fluid dynamics in microgravity and the limited
hand-washing capability aboard spacecraft require some
changes in the procedures for cleaning and handling contact
lenses in microgravity. Hand cleaning is best accomplished
with evaporating finger wipes; however, alcohol-based prod-
ucts should be avoided because of the potential for ocular irri-
tation if residual alcohol is transferred from the fingers to the
contact lenses. An alternative hand-cleaning agent approved
for use in space flight is a benzalkonium chloride-based
product. The risks of ocular contamination make the use of
single-day, disposable contact lenses prudent. When reusable
lenses are necessary, AMCONs SoftMate hydromat cleaner
has proven useful for both cleaning and rinsing in micrograv-
ity, with the added benefit of fluid containment. No hydrogen-
based disinfection systems that require venting of gases are
used, as their function depends on fluids remaining in the bottom
of a container and off-gassing through a vent in the container
lid. Because fluids do not settle in microgravity, such gravity-
dependent systems have proven suboptimal for use in space.
Ophthalmic Medications:
Microgravity Considerations
Ophthalmic medications are available in several forms, includ-
ing ointments and solutions. The effects of microgravity on
fluid dynamics make some of these formulations more advan-
tageous than others. Ointments can be applied effectively
in microgravity; however, the reduction in minimum force
required to move objects in microgravity dictates that caution
be used to avoid a conjunctival or corneal abrasion from the
applicator tip. Solutions continue to be the most common for-
mulation used in U.S. space programs; however, several challenges
remain. Because drops do not drop in microgravity, the normal
F.K. Manuel and T.H. Mader
delivery mode must be modified. If a medicine vial is squeezed
slowly, a globule of medication forms on the dropper tip. This
globule can then be gently touched to the inferior conjunctival
cul de sac or to the lateral canthus while the eye is directed
away; surface tension quickly wicks the solution to the ocular
surface. However, use of the globule technique is problematic
with regard to dose control. Experience from past flights sug-
gests that each globule contains 3 to 6 drops; thus, dispensing
medications as globules can result in overdoses in addition
to wasting limited medication resources. Medication should
not be applied to the central palpebral fissure area because of
the risk of corneal or conjunctival abrasions. Ocular medica-
tions must not be shared among crew members because of the
potential for cross contamination. Finally, given the limited
refrigerated storage capacity aboard spacecraft, ophthalmic
drugs that require refrigeration should be avoided and alternate
selections made if possible.
Preflight Surgical Treatment of Refractive
Error: Microgravity Considerations
Over the past few decades, numerous surgical procedures have
become available for correcting myopia. Many of these procedures
have been accompanied by huge and occasionally misleading
marketing campaigns. The rapid technologic changes in this
field have made objective analysis of the sequelae of these
procedures difficult. This section briefly reviews the surgi-
cal options currently available for correcting myopia and
the possible effects of these procedures in the environmental
conditions encountered during preflight training and orbital
space flight.
Radial Keratotomy
Radial keratotomy has been performed on millions of active
young myopic individuals. The procedure usually involves
making 4 to 8 radial incisions at a depth of 90% in the periph-
ery of the cornea. These incisions are normally made with
a diamond blade, and the visual axis of the cornea remains
untouched. These wounds may never heal completely and can
remain weak even years after the surgery. Diurnal changes
in vision at sea level after radial keratotomy have been well
documented [4]. Several reports have also documented visual
changes after this procedure at altitudes in excess of 9,000 ft
(2,743 m) [59]. Any cornea exposed to hypoxia will thicken
[10]. However, research suggests that when the normal corneal
architecture is weakened by radial incisions, the hypoxic cornea
may preferentially expand circumferentially in the periphery,
leading to flattening of the central cornea and a resultant hyper-
opic (farsighted) shift [8,10]. Such changes normally require
overnight exposure to hypoxia to become manifest [11,12].
Conversely, exposures to increased oxygen concentrations
result in a myopic (nearsighted) shift [8,12]. The environ-
ments of flight training, underwater training, extravehicular
25. Ophthalmologic Concerns
activities, and space flight all subject the cornea to varying
oxygen concentrations. Because such variations may affect
corneal curvature and result in visual alterations, radial kera-
totomy is not suitable for astronauts.
Photorefractive Keratectomy
Photorefractive keratectomy (PRK), another surgical proce-
dure designed to correct myopia, involves a laser ablation of
the anterior cornea resulting in a resculpturing of the corneal
surface. This procedure ablates the central 6 mm or so of
the cornea to a maximum depth of about 100 m. Although
PRK has been used to correct very high degrees of myopia, it
has been most successful for low to moderate myopia (up to
6.0 D). Mild optical aberrations may be present after PRK if
the entire corneal surface is not uniformly ablated [13]. When
a corneal surface irregularity persists after PRK, the image
produced may lack edge definition and contrast [1417].
Numerous studies have documented glare and ghost images
after PRK that may become more prominent with increased
pupil size [1822]. This effect was particularly true of early
PRK procedures, which ablated only 4 to 5.5 mm of the cen-
tral cornea. Optical zone diameters must be at least as large
as the entrance pupil to preclude glare at the fovea and larger
than the entrance pupil to preclude perifoveal glare [23]. More
modern lasers that ablate the optical zone to 6 mm or more
have greatly decreased the incidence of these complaints.
Temporary corneal haze within the optical zone can also occur
after PRK; this effect is more prominent when deeper abla-
tions are used for more severe myopia [2429]. On the posi-
tive side, the visual results from PRK have been well accepted
by most patients, and PRK produces no diurnal variations in
refraction. In one study, subjects who had undergone PRK
were exposed to simulated altitudes of 14,000 ft (4,267 m)
for 72 h and demonstrated no significant change in refractive
error [8]. Thus, those individuals who have undergone PRK
for myopia do not seem to be susceptible to altitude-related
refractive shifts. PRK is currently disqualifying. In the future,
because of possible visual aberrations, PRK may not be suit-
able for pilots but may be considered for mission or payload
specialists.
Laser in Situ Keratomileusis
A newer procedure for the correction of myopia is laser in situ
keratomileusis (LASIK). This procedure involves creating a
planolamellar corneal flap by incising the anterior stroma with
a microkeratome. Refractive ablation with an excimer laser is
then performed in the anterior corneal stromal bed, and the
flap is replaced without sutures or adhesives. The LASIK pro-
cedure preserves the central epithelium, basement membrane,
and Bowmans membrane and is frequently used to correct
myopia of up to about 12 D. Although long-term studies have
yet to be conducted, early reports suggest that LASIK can
result in predictable and stable visual acuity [30,31]. Findings
539
from high-altitude studies of patients who had undergone
LASIK, however, have been controversial. In one case report,
refraction and near point of accommodation were found to be
stable at 16,000 ft (4,877 m) in a 29-year-old climber who had
previously undergone LASIK [32]. However, no cycloplegic
refraction was performed at high altitude [33]. Three other
reports have documented various degrees of myopic shifts in
refraction upon exposure to high altitude [3436]. Sea-level
laboratory studies in which the corneas of 10 healthy subjects
were subjected to total surface hypoxia for 2 h documented a
statistically significant myopic shift in refraction in subjects
who had undergone LASIK [37]. The clinical significance of
this myopic shift for aviators is unknown. To date, no long-
term studies after LASIK have been done, and the potential of
LASIK for use in astronauts is promising but largely speculative.
Intrastromal Corneal Ring
Another new device for the surgical correction of myopia is
the intrastromal corneal ring. This ring device, made of a clear
polymer, is surgically inserted through a single small radial
incision in the peripheral stroma of the cornea, outside the
central optical zone [38]. The intracorneal inlay mechanically
flattens the central cornea and can correct myopia in the range
of 1.0 to 3.5 D. Unlike other procedures for correcting
myopia, the intracorneal ring technique does not involve dis-
ruption of the optical zone, multiple incisions, or the removal
of large amounts of corneal tissue. Exchanging the implanted
rings for others of different sizes allows surgical outcome to
be adjusted as necessary; moreover, the refractive effect theo-
retically can be reversed by removing the ring. Neither long-
term nor altitude studies of patients who have undergone this
procedure have been conducted.
Intraocular Lenses
Perhaps the most common ocular surgical procedure performed
worldwide is removal of a cataractous lens and replacement
with an intraocular lens. This is also a refractive procedure.
Before performing the procedure, the surgeon calculates the
power of the intraocular lens from measurements of the cur-
vature of the cornea and the axial length of the eye. With this
information, the surgeon can choose a lens power that cor-
rects existing refractive error. For example, a patient with a
history of severe myopia or hyperopia can be made emme-
tropic (i.e., no longer needing glasses for distant vision) by
inserting an intraocular lens of the appropriate power. Modern
intraocular lens surgery has successfully withstood the
test of time. A variety of intraocular lenses, most with ultra-
violet protection, can be inserted through incisions as small
as 2.5 mm. The success of this procedure for aviators is well
documented [3942], and this procedure is now considered
acceptable in all three U.S. military services and the Federal Avia-
tion Administration. A 64-year-old NASA astronaut who had
undergone bilateral intraocular lens implantation was found to
540
have stable vision during a 2-week space flight [43]. As is true
for any surgical procedure, intraocular lens implantation can
be associated with intraoperative and postoperative complica-
tions such as infection, lens dislocation, or macular edema.
Moreover, because accommodation is no longer possible after
this procedure, the focal length becomes fixed. Nevertheless,
this procedure has been extremely successful and will no
doubt continue to play a major role in the visual rehabilitation
of astronauts. The aging of the astronaut population as well as
the possible effects of space radiation on the human lens may
increase the need for this procedure in the future [44].
Clinical Conditions That May Affect
Astronaut Duty
Elevated Intraocular Pressure
Intraocular pressure (IOP) has been observed to increase dur-
ing parabolic flight and during microgravity exposure
[4548]. Specific evidence for IOP elevation in microgravity,
the possible mechanism by which this occurs, and the potential
significance of such an increase for astronauts are discussed
briefly in this section. Also discussed are the clinical presenta-
tion of a rise in IOP and methods for treating this condition
during space flight.
Several sources of information indicate that IOP rises in
microgravity. Draeger and colleagues documented a mean
5-mm increase in IOP during the free-fall phase of parabolic
flight by using a hand-held applanation tonometer [45,46]. A
later study, also performed during parabolic flight, documented
a 58% increase in IOP measured with TonoPen tonometry [47].
Draeger reported measurements of IOP made with a hand-held
applanation tonometer during a Space Shuttle flight [45,46].
An initial 20% to 25% increase in IOP was noted 44 min into
the mission. Several years later, the same group documented
a 92% increase in IOP in cosmonauts bound for Mir ~16 min
after reaching microgravity [48]. These studies suggest that in
healthy subjects, the initial rise in IOP after reaching micro-
gravity declines to roughly normal values after several hours.
IOP has not been measured during extended space flight.
The specific mechanism by which IOP rises in micrograv-
ity is open to speculation. The microgravity environment is
thought to affect ocular physiology through the cephalad
shift in intravascular and extravascular body fluids resulting
from the absence of the 1-G hydrostatic gradient [49]. The
effects of this fluid shift have been documented by changes in
leg girth, photographic evidence of facial edema, and verbal
reports of head fullness and nasal stuffiness [4951]. These
shifts occur within 20 s of microgravity exposure. Whole-body
head-down tilt studies suggest that a sudden elevation in IOP
may be due to vascular engorgement of the choroid brought
about by the cephalad fluid shift [52]. Since the rigid sclera
does not expand as ocular volume increases, the IOP may rise.
Previous experiments noted that a 20-l increase in choroi-
F.K. Manuel and T.H. Mader
dal volume produced a 20-mm increase in IOP [53]. Thus,
a very small increase in choroidal volume may produce an
immediate and prominent increase in IOP. Other investigators
have hypothesized that the change in IOP is caused mainly by
increased intracranial blood pressure [45,46,48], which may
lead to increased perfusion of the ciliary body and increased
production of aqueous humor. Congestion in the venous sys-
tem and a concomitant rise in pressure in the episcleral vessels
may increase the resistance to aqueous-humor outflow, lead-
ing to a rise in IOP.
The clinical significance of a rise in IOP in microgravity is
unknown but merits discussion [54]. A prolonged increase in
IOP during space flight could put astronauts at risk for optic
nerve damage. Those at risk for glaucomatous optic nerve
damage would most likely be those who are exposed to micro-
gravity for months to years. Glaucomatous damage would
present clinically as a slow, painless loss of vision. Astronauts
with moderate increases in IOP for brief periods, as may occur
with relatively short space shuttle operations, would not be
expected to develop measurable optic nerve damage.
Astronauts with elevated IOP or frank glaucoma at baseline
may be at risk during extended space operations because their
ability to adapt to elevated IOPs may be impaired. In the past,
strict screening programs have excluded individuals with ocular
anomalies from space flight. Most of the subjects whose IOP was
monitored in the bed-rest, parabolic flight, Space Shuttle, and Mir
studies described in the previous paragraphs had low to normal
baseline IOP at 1-G. Individuals with higher baseline IOP may
be particularly vulnerable to a rise in IOP associated with micro-
gravity exposure. For this high-risk subgroup, it may be prudent
to measure visual fields and obtain stereo-optic nerve photos
before and after the space missions and to measure IOP during
the missions. Pressure-lowering medications should be continued
on patients already taking such medications and should be made
available for others in the event of a pressure rise.
Theoretically, acute angle closure glaucoma would also be
possible in some predisposed individuals. Two mechanisms
could produce angle closure in microgravity. First, if the cho-
roid were to expand in microgravity, this could lead to a slight
anterior displacement of the vitreous, lens, and ciliary body.
The lens-iris diaphragm thus could be pushed forward suffi-
ciently to narrow or close the anterior chamber angle, which in
turn could obstruct the aqueous drainage from the eye and lead
to a rise in IOP over a period of several hours. Alternatively,
swelling of the ciliary body associated with cephalad fluid
shifts may rotate the ciliary body and iris root further into the
angle, worsening angle closure. Subjects with normal anterior
chamber angles would not be expected to be affected by such
shifts. However, subjects with preexisting narrow angles may
be predisposed to angle closure. The actual effect of such fluid
shifts on anterior chamber depth, if any, is unknown since ante-
rior chamber depth has never been measured in microgravity.
The treatment for an acute rise in IOP would include oral acet-
azolimide as well as topical medications such as pilocarpine
to promote reopening of the chamber angle.
25. Ophthalmologic Concerns
Assuming that IOP does rise significantly in the micrograv-
ity environment, how could it be controlled? If increased cho-
roidal volume is responsible for the rise in IOP, no direct means
of pharmacologic control would exist since choroidal blood
flow is not autoregulated [55]. A more practical approach
may be to control aqueous production. Moreover, if a rise in
episcleral venous pressure or increased ciliary perfusion were
the cause of elevated IOP, then decreasing aqueous production
pharmacologically would also be advantageous. Several sys-
temic and many topical antiglaucoma medications decrease
aqueous production and thus reduce IOP. Topical beta block-
ers would be a logical first choice because they effectively
decrease aqueous production, are easy to administer, and have
few side effects. Preliminary studies performed with patients
transiently exposed to simulated microgravity have demon-
strated the effectiveness of these agents [56]. Unfortunately,
the long-term effectiveness of pressure-lowering medications
in microgravity is thus far unknown. Also, since most anti-
glaucoma medications are given topically, they may be dif-
ficult to administer in microgravity. As noted earlier in this
chapter, giving an eye drop in microgravity requires touching
the tip of the dropper bottle to the conjunctival cul de sac so
that capillary action draws the medication to the eye. Such
direct contact with the eye could contaminate the medication
container. Therefore, a unit-dose container of the antiglau-
coma medications, one that could be used for a maximum of
24 h and then discarded, may be a practical alternative.
In summary, data from parabolic flight, bed-rest, and
orbital flight studies suggest that IOP may be significantly
elevated immediately after exposure to microgravity. This
rise in IOP may result from increased choroidal volume or
increased ciliary-body perfusion caused by cephalad fluid
shifts. Astronauts with low to normal IOP seem to undergo a
pressure-lowering adaptation phase lasting several hours. We
hypothesize that individuals with ocular hypertension or clin-
ical glaucoma may be at risk for a prolonged increase in IOP.
Chronic exposure to an elevated IOP could cause glaucoma-
tous optic nerve damage. Should a long-term increase in IOP
occur, topical pressure-lowering medications would probably
be the best means of controlling it. Although unlikely, the
potential does exist for acute glaucoma in a small number of
individuals upon exposure to microgravity. Means of measur-
ing intraocular pressure during prolonged space flight should
be available, both for monitoring individuals at high risk and
for diagnostic purposes should suggestive symptoms arise.
Although several intraocular pressure-measuring devices
have been used in microgravity, the optimal device for use in
prolonged space flight remains unclear [4548,57].
Ophthalmic Emergencies
Although a wide variety of ocular emergencies are possible
in the microgravity environment, the following discussion is
limited to those most commonly anticipated. Our goal is to
541
concentrate on realistic diagnostic and treatment measures
that are practical in the current microgravity environment.
Bacterial Corneal Ulcers
The unique environment in which space operations take place
poses challenges for the diagnosis and treatment of corneal
ulcers. The term corneal ulcer (bacterial ulcerative keratitis)
refers to the breakdown of the corneal epithelium from an under-
lying bacterial infection of the corneal stroma. These ulcers can
be extremely painful and can profoundly and sometimes perma-
nently impair vision. Their occurrence during a space mission
could be catastrophic. It is imperative that clinicians be familiar
with the diagnosis and treatment of this condition.
The first line of defense against ulcerative keratitis is an
intact corneal epithelial barrier. A corneal abrasion, foreign
body, or any condition leading to an epithelial defect could
precipitate the development of bacterial keratitis. The risk of
injury from a foreign body in particular is heightened in micro-
gravity because particulates that would normally settle out in
1-G float freely in the cabin and follow prevailing air currents.
Even seemingly trivial trauma that causes microabrasions to
the corneal epithelium may set the stage for bacterial adher-
ence and subsequent invasion of the cornea by microorgan-
isms. Thus, any ocular injury that causes a corneal epithelial
defect should be treated promptly with topical antibiotics and
followed up appropriately.
The use of contact lenses during space flight is a risk factor
for the development of corneal ulcers. As noted previously,
contact lenses are commonly used by astronauts, particularly
mission specialists and payload specialists. Contact lenses
provide excellent vision for myopic individuals and are an
appealing alternative to glasses. However, the use of any type
of contact lens, including rigid gas-permeable lenses as well as
disposable or conventional soft lenses, predisposes the wearer
to corneal ulcers [5860]. Furthermore, the overnight use of
conventional or disposable soft extended-wear contact lenses
confers at least a 10-fold higher risk of ulcerative keratitis than
does strict daily-wear use [5860]. Eye pain in a contact lens
user on a space mission should be assumed to be a bacterial
corneal ulcer until proven otherwise.
The most common symptoms of a corneal ulcer are pain,
photophobia, tearing, and blepharospasm. Signs may include
conjunctival hyperemia, lid edema, and discharge. The degree
of visual incapacitation varies depending on the extent and
location of the ulcer. Because prompt clinical recognition is
essential to successful treatment, the index of suspicion must
be kept high for any patient presenting with eye pain.
Microscopic examination of the cornea usually reveals
definitive clinical signs of infection. The distinguishing char-
acteristics of bacterial ulcerative keratitis are epithelial
ulceration and underlying suppurative stromal inflamma-
tion. The inflammatory reaction in the anterior chamber
can vary from mild cells to obvious hypopyon. Objective
quantification of both the extent of corneal involvement
542
and visual acuity is very important. If possible, corneal
photos or clinical drawings (as detailed as possible) should
be recorded by the crew medical officer as a means of fol-
lowing corneal changes after the initiation of therapy. Live
downlinked images should be reviewed daily in a private
medical conference with the mission crew surgeon.
Although a large number of pathogenic bacteria have been
implicated in bacterial ulcerative keratitis, no definite clini-
cal sign exists to identify a specific bacterial pathogen. Thus,
corneal scrapings should be obtained for staining and micro-
scopic examination if such facilities are available. Additional
corneal scrapings can be plated on culture media for definitive
identification of pathogenic bacteria. Normally, in a medical
center setting, initial selection of antimicrobial agents is based
on the results of gram staining. If gram-positive cocci are seen,
then topical concentrated cephalosporin is the standard treat-
ment; for gram-negative bacilli, topical concentrated genta-
mycin or tobramycin is indicated. Subsequent culture results
may modify the initial antibiotic treatment. However, because
such facilities and medications would not normally be avail-
able during current space operations, an alternative approach
may be prudent.
Recent evidence suggests that topical fluoroquinolone
preparations are extremely effective against a wide variety of
bacterial pathogens and are gaining acceptance as single-agent
therapy for bacterial keratitis [61]. Fluoroquinolones are effec-
tive against most strains of staphylococci as well as P. aeru-
ginosa, the most common etiologic agent in corneal ulcers
caused by contact lenses. Fluoroquinolones require neither
refrigeration nor special mixing and are usually well tolerated.
Thus although fluoroquinolones are not universally effective
against all bacterial pathogens, they may be the most practical
empiric treatment for corneal ulcers encountered during space
operations. Therefore, if the diagnosis of corneal ulcer is made,
0.3% ciprofloxacin, a commonly available fluoroquinolone,
could be used for treatment. Specifically, a loading dose of one
or two drops every 15 min for 2 h can be initiated, followed by
a drop every 2 h for a day or more. Subsequent dosage can be
titrated over time depending on the clinical response.
Corneal Abrasions
Corneal abrasion refers to the loss of corneal epithelial tissue,
most commonly through direct trauma. Fortunately, since the
cornea is well endowed with nerves, even the slightest corneal
epithelial injury will not go unnoticed. As nearly all corneal
abrasions are accompanied by photosensitivity, examining the
eye in a dimly lit area is usually advantageous. The use of 0.5%
proparacaine (a topical ophthalmic anesthetic) may allow a
more complete examination. In the event of blepharospasm, a
drop of proparacaine can be instilled by having the patient
look up while the examiner gently pulls down on the lower
lid to expose the lower conjunctival cul de sac into which a
drop is placed. This single drop will quickly anesthetize the
entire cornea and conjunctiva and allow a more comfortable
F.K. Manuel and T.H. Mader
examination. Biomicroscopic examination of the cornea with
the aid of a fluorescein strip usually vividly demonstrates an
epithelial defect. The best technique is to wet the tip of the
fluorescein strip with a drop of proparacaine and then to touch
the wet tip to the inferior conjunctival cul de sac while the eye
is looking up. Fluorescein should not be applied directly to
the cornea, as it may abrade the corneal epithelium and cause
diagnostic confusion.
Treatment and follow-up of a corneal abrasion vary accord-
ing to the extent of the injury. Most superficial abrasions can
be treated with a drop of antibiotic applied 4 times a day. A
cycloplegic topical medication such as cyclopentolate, used
twice daily, may also be given to reduce ciliary spasm and
thus alleviate discomfort. Use of an eye patch is normally not
necessary and should be avoided. Patching the eye produces a
natural culture medium that may predispose the cornea to bac-
terial infection. Occasionally, an extensive corneal abrasion
may require antibiotic application with patching for comfort.
Regardless of the extent of injury, the patient should always
be examined daily and reports made to ground specialists until
the epithelium heals.
Corneal Foreign Body
Persistent sensations of a foreign body in the eye and ocular
discomfort strongly suggest the presence of a corneal foreign
body. Although a slit lamp or other magnification device is
optimal for visualization, corneal foreign bodies can also be
visualized by shining a penlight on the eye from the temporal
periphery. This technique retroilluminates the cornea, and a
foreign body presents as a dark spot on the bright background
of the iris. The conjunctiva of the upper and lower lids should
also be examined any time a foreign body is suspected. Diag-
nostic examination and treatment of corneal foreign bodies
is heavily emphasized in preflight training for crew medical
officers.
Most superficial corneal foreign bodies can be removed
with the tip of a 25- to 27-gauge sterile needle; removal is usu-
ally accomplished with the aid of a slit lamp but may be done
with a magnifying lens or even the naked eye if necessary. The
very tip of the needle is placed under the foreign body, which
is then gently lifted from the cornea. Although a sharp needle
near the eye may seem a bit intimidating, this technique is
actually quite precise and only rarely causes iatrogenic injury
to the tough cornea. The use of cotton swabs is best avoided,
because the swab only rarely dislodges the foreign body and
may damage the surrounding epithelial tissue. Multiple super-
ficial corneal foreign bodies can be removed by irrigation.
Means of accomplishing bilateral and unilateral irrigation in
a closed system in which effluent is not lost into the cabin
atmosphere are provided aboard the U.S. Space Shuttle and
the International Space Station. As is true for any epithelial
defect, mandatory treatment includes the use of antibiotic
drops such as ciprofloxacin 4 times per day and daily ocular
examinations until the epithelium is healed.
25. Ophthalmologic Concerns
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Results from Skylab. Washington, DC: US Government Printing
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26
Dental Concerns
Michael H. Hodapp
Dental emergencies have occurred only rarely in space flight;
they are prevented through the use of comprehensive preflight
examinations and preventive measures while the crew is in
training. As the duration of space flights increases and as
exploration-class missions are planned for travel to the Moon,
Mars, and beyond, the likelihood of a dental emergency occur-
ring in space flight also increases. Although space crews live
and work in a weightless environment, the forces produced
from the mass and velocity of moving objects nevertheless
produce impact forces that can cause tooth fracture and other
significant injuries to the face and jaws. Also possible during
a long-duration flight are the development of cracked teeth,
inflammation or infections of the tooth pulp, temporomandib-
ular disorders, periodontal abscesses, and dental caries.
This chapter was prepared to provide a brief for flight sur-
geons and chief medical officers who will be diagnosing and
treating the dental emergencies of long-duration spaceflight
crews. Basic information has been included to help man-
age a potential emergency situation. A summary of the basic
approach to differential diagnosis of dental problems is given
in Table 26.1. Although some of the procedures may seem to
be below the standard of care advocated by dental healthcare
professionals, these procedures will bring the afflicted crew-
members to a stable condition with the least risk of iatrogenic
injury, so that they can perform their duties comfortably.
Visiting a dentist during an extended-duration space flight is
not an option. X rays, root canals, and definitive dental care are
luxuries that are not available in space. Moreover, since in-flight
equipment and supplies carried into space are limited by con-
straints on weight and storage space in addition to the require-
ment that they operate well in microgravity, the dental care-related
equipment that can be provided is currently restricted. This
restriction, however, should be all but eliminated by the advent
of new technologies and the expansion of current technologies.
Thus with the construction of long-term space habitats such as
the International Space Station already being realized and plans
for exploration-class missions maturing, the provision of com-
prehensive dental treatment to crews during space flights will
become not only possible but practicable in the near future.
Preventive Strategies, Standards,
and Screening
Although the primary goal of clinical space dentistry is to
return an astronaut or a cosmonaut who has a dental emer-
gency to optimal functioning capacity as soon as possible, our
focus in this chapter is prevention. NASA has established strict
standards for astronaut selection, retention, and preflight den-
tal examinations. Currently all U.S. astronauts undergo annual
dental cleanings and examinations to identify any underlying
problems.
For astronauts who have been chosen for a specific space
flight, a strict clinical schedule is followed. At 6 months before
launch, crewmembers undergo an examination. If dental treat-
ment is deemed necessary, all such treatment is completed by
3 months before launch so as to minimize potential problems
in flight. The crew medical officers attend a preflight brief-
ing that prepares them to handle the dental emergencies that
might occur during a flight. Finally and most important from
our perspective, all astronautswhether assigned to a crew
or notare expected to maintain optimal physical and oral
health and to follow good oral hygiene practices.
Dental Caries
Presentation and Diagnosis
Although astronauts are unlikely to develop dental caries
because of the strict dental standards they must follow, dental
caries remain the most common cause of odontalgia. Indeed,
despite regularly scheduled examinations and radiography,
dental caries can often remain undetected under preexisting
restorations or within the pits and fissures of teeth. Caries should
therefore be viewed as the likely cause whenever odontog-
enous pain presents itself. In most cases, the patient can localize the
pain to the specific tooth involved, but in other cases
the pain can be so generalized that the patient is unable to determine
its true source.
545
 546
Table 26.1. Differential diagnosis of dental problems.
Percussion test (tap- Hyperosmotic chal-
Hot/cold stimulus Bite pressure (load) Tooth feels high ping) Palpation of roots lenge (salt, sugar) Visible signs
Gum Fractured
Pain: but Com- Pimple inflamed tooth or
Spontane- does not Painful Relieves Recent No recent Uncom- Comfort- Uncom- fort- Immediate Delayed or boil on around missing
Diagnosis ous pain linger and lingers pain Dull ache Sharp pain restoration treatment fortable able fortable able pain pain gum tissue tooth restoration
Cracked tooth + + +
Bite prematurity + + * + * + +
Gap between tooth + + * + * + + + + *
and restoration
Dental caries * + * * + + * * * *
Hyperalgesia + + + * * +
(exposed dentin)
Reversible pulpitis * + + * * + *
Irreversible pulpitis + + * * * * * + *
Pulpal necrosis + * * * * * * * * * *
Partial necrosis + * * * * * * * * * * * *
(multirooted teeth)
Apical periodontitis + + * * * + * * *
Periodontal abscess + + + + + *
Temporomandibular + (usually * * + +
joint disorder a dull
head-
ache)
+ = likely to be present; * = may be present; = usually not present.

M.H. Hodapp
26. Dental Concerns
Dental caries are most commonly found, in descending order
of frequency, in the pits and fissures, the proximal surfaces,
and the smooth surfaces of the teeth. Caries can be detected by
direct examination with a mirror and an explorer, by bite-wing
radiography, or by transillumination with a fiber-optic light.
Understanding the mode by which a carious lesion spreads helps
when detecting caries. Pit-and-fissure caries spread in the shape
of a cone with the tip facing the outer surface of the enamel and
the base at the dentoenamel junction. As the caries progresses
into the dentin, it re-assumes the shape of a conethis time
with the base at the dentoenamel junction and the tip progress-
ing toward the pulp. Smooth-surface caries, which includes the
proximal surfaces, also presents in the shape of a cone, but here
the base is at the outer surface of the tooth and the tip progresses
toward the dentoenamel junction. As the caries progresses into
the dentin, the base of the cone again forms at the dentoenamel
junction and the tip progresses toward the pulp.
Diagnosis begins with a visual examination performed with
a mirror and an explorer and a recent set of bite-wing radio-
graphs. The mirror allows the examiner to view all exposed
surfaces of the teeth, the explorer is used to feel for caries and
to aid in the diagnostic process, and the bite-wing radiographs
allow detection of caries between the teeth. Since radiogra-
phy is unavailable on space flights, some difficulties are thus
imposed in the diagnostic process. Caries are not always read-
ily visible. In fact, caries that have a dark color are usually a
slow-growing form of the disease and have become stained
over time. (Some dark areas in the pits and fissures of teeth
are only stains and not caries at all.) Caries that are the color
of dentin typically are produced by a more vigorous type of
bacteria and are usually detected with an explorer. That is why
the use of an explorer is critical in the detection process.
To the explorer, the carious surface is soft, allowing the
explorer to sink and stick in the dentin or the enamel. In a
normal state, the dentin and the enamel are both hard; the
explorer will neither sink in nor have a sticky feel.
Treatment and Management
Treatment of dental caries during space flight depends on the
extent of the carious lesion and the type of symptoms the patient is
experiencing. Whatever the case, the key to appropriate treatment
is making a good diagnosis, a process that can be either simple or
quite difficult depending on the presenting signs and symptoms. In
the case of a carious tooth that is symptomatic, the first objective
would be to make a diagnosis based on the signs and symptoms a
patient is experiencing. Once a diagnosis is made, treatment can
proceed accordingly. (Additional information on diagnosis can be
found in the section of this chapter devoted to diagnostic testing.)
Caries can present in many ways and can produce a variety
of symptoms. The remainder of this section describes three
classifications of the carious process: simple caries; moder-
ate caries; and advanced caries. Each classification will be
described briefly, followed by our recommendations with
regard to treatment and medical disposition.
547
Simple Caries
Simple caries is asymptomatic. The carious lesion has
destroyed a small portion of the patients enamel or some of
the underlying dentin, sometimes causing the brittle enamel to
fracture. Treatment consists of administering local anesthesia,
removing the decayed structure, and placing a sedative filling.
The diagnosis and treatment are straightforward.
In simple caries, the carious material will feel soft or leath-
ery and should be removed with a spoon excavator or similar
dental instrument down to the hard dentinal structure. The
cavity is then filled with Cavit, a temporary filling material
composed of a mixture of zinc oxide and eugenol, or with
another similar temporary filling material. After the filling is
in place, the patient should be told to bite down before the
material sets to optimize surface occlusion. If the filling is too
high, it should be adjusted before the filling material hardens.
The medical disposition of a patient who requires a filling
in an asymptomatic tooth is good. After treatment, the patient
should be able to resume assigned duties.
Moderate Caries
Moderate caries destroys a moderate portion of the underlying
dentin without communication with the pulp chamber. The
affected tooth is either asymptomatic or exhibits symptoms
of a reversible pulpitis. Symptoms in this case usually mani-
fest while the patient eats or drinks. The treatment in most
cases consists of administering local anesthesia, removing the
decayed structure with a spoon excavator or similar dental
instrument, and placing a sedative filling.
In moderate caries, the carious material will feel soft or leath-
ery and should be removed to the hard dentinal structure. (Care
must be taken to determine that the pulp chamber of the tooth
has not been exposed during removal of the carious material.) A
mirror and an explorer are used to check the floor of the tooth to
verify that the floor is hard dentin and that no holes leading into
the pulp chamber are present. After verification that the pulp
chamber has not been exposed, the cavity can be filled with
Cavit or another similar temporary filling material. Once the
filling is in place, the patient should be told to bite down before
the material sets to optimize surface occlusion. If the filling is
too high, it should be adjusted before the filling hardens.
The medical disposition of a patient who needs a filling in
an asymptomatic tooth or who initially had a reversible pul-
pitis is good. After treatment, the patient should be able to
perform assigned duties.
Advanced Caries
Advanced caries destroys so much dentinal structure that it
affects the pulp chamber and causes spontaneous symptoms
from the tooth. These symptoms are classified as an irrevers-
ible pulpitis or a pulpal necrosis depending on the type of pre-
senting symptoms. A tooth with multiple roots can have both
an irreversible pulpitis and a partial necrosis at the same time.
548 M.H. Hodapp

When a tooth presents with symptoms of irreversible pulpitis

or pulpal necrosis, the decision regarding the type of treatment
to be provided should be based on the severity of the present-
ing symptoms.
The first course of treatment for advanced caries is to apply
anesthesia and remove all of the carious material. Then a mir-
ror and an explorer are used to check the floor of the tooth to
determine whether the cavity has exposed the pulp chamber.
If the pulp chamber has been exposed (regardless of whether
the pulp is bleeding or not), the best strategy is to cover the
area with a cotton pellet moistened with Red Cross Medica-
tion, a mixture of eugenol and oil of cloves. Care must be
taken to keep the cotton pellet in place so that it acts as a
vent and also keeps the area free of food debris. Sealing an
exposed vital or necrotic pulp chamber with a temporary fill-
ing could lead to infection, which could cause severe facial
swelling and pain. If the treated area becomes sensitive again,
additional medicament can be applied by repeating the proce-
dure described. Subsequent applications usually can be placed
without recourse to a local anesthetic.
Medical disposition of a case of advanced caries is guarded.
The patient should be monitored daily for any evidence of
swelling. In the event of infection (which will manifest as
swelling), the patient must be treated immediately with anti-
biotics. Depending on the time remaining in the mission, the
next step may be to extract the offending tooth. It is important
to note that prescribing a course of antibiotics will not elimi-
nate the bacteria present in an infected tooth. Antibiotics serve
only to control the bacteria around the bony area underneath
the tooth until definitive care can be given.

Figure 26.1. Tooth anatomy and Ellis fracture classification.

Traumatic Dental Emergencies
Traumatic dental injuries can and do occur in space flight.
Although space crews live in a weightless environment, the
combined forces of mass and velocity can significantly injure
the face and jaws. For example, a force directed to the face can
fracture, subluxate, or avulse the anterior teeth, fracture either
or both of the condyles, or cause other significant injuries. A
force directed vertically to the lower jaw could fracture the pre-
molar or molar teeth as a result of the wedging effect of the cusp
of one tooth being forced into the fossa of an opposing tooth.
However the fracture occurs, whenever teeth are fractured
and tooth fragments are missing, it is always wise to palpate
the patients lips and tongue to determine whether any frag-
ments have lodged there. All fragments that have lodged in
tissue must be removed promptly to prevent infection [1].
Fractures of Anterior Teeth
Fractures of the anterior teeth are managed on the basis of
fracture type. The Ellis classification, traditionally used to
describe fractures of anterior teeth, includes class I, class II,
and class III fractures (Figure 26.1).
The simplest and most common type of fracture is the Ellis
class I fracture, which involves only the enamel portion of
the tooth. Managing this type of fracture usually involves no
more than smoothing the rough edge with an emery board.
The medical disposition of an Ellis class I fracture is good;
after treatment, the patient should be able to perform assigned
duties.
An Ellis class II fracture involves both the enamel and
the dentin but does not expose the pulpal tissue. When den-
tinal tissue is exposed, the tooth enamel portion will appear
chalky-white, and the dentin will usually appear ivory-yellow.
Management of an Ellis class II fracture typically requires
applying anesthesia and placing a temporary filling that cov-
ers the exposed dentin. The medical disposition of an Ellis
class II fracture is good; after treatment, the patient should be
able to perform assigned duties.
An Ellis class III fracture involves the enamel, dentin, and
pulp tissue. The injury is frequently accompanied by serious
fractures of not only the crown but the root of the tooth as well
[2,3]. This fracture is the most serious type, not only because
of the immediate emergency but also because of the ensu-
26. Dental Concerns
ing problem of the tooth eventually becoming necrotic and
infected. Managing an Ellis class III fracture involves admin-
istering anesthesia before removing as much of the pulp tissue
as can be accessed. Once the pulp tissue has been removed, a
cotton pellet moistened with Red Cross Medication is placed
over the exposed area and left in place. No temporary filling
should be applied over the area, since doing so could seal off
the area and result in unnecessary facial swelling and pain.
A thin layer of foil may be used to cover the cotton pellet to
keep the area free of food debris. The medical disposition of
an Ellis class III fracture is guarded, and the patient should be
monitored carefully. If facial swelling occurs from infection,
antibiotics are the first line of defense. Depending on the time
remaining in the mission, the second line of defense is tooth
extraction to prevent chronic infection, which can progress to
life-threatening sepsis.
Cracked Tooth
A cracked tooth can present in several ways. The tooth may be
totally asymptomatic or can be quite painful during chewing.
The classic symptom of a cracked posterior tooth is a sharp,
stabbing pain either upon biting into something or immedi-
ately upon release. Usually these symptoms occur when a
food that distributes force vertically as well as laterally (such
as chicken) is being eaten, causing the cusps to separate on
closure. Cracks occur most often in the maxillary premolars
because of the V-shaped nature of the biting surface and the
wedging effect of the mandibular cusp.
Management of a cracked tooth is based on the presenting
signs and symptoms and the time remaining in the mission.
In most cases, all that is necessary is that the patient avoid
using the affected tooth until return to Earth. If the tooth is
cracked to the point of a true split, depending on the nature
of the split, the only method of treatment may be extraction.
This would be the case when a tooth has split down the cen-
ter and essentially separates into two halves. When the tooth
splits at an angle and only the cusp breaks off, the recom-
mended treatment is to apply anesthetic and, if the pulp is not
exposed, to place a temporary filling. If the pulp is exposed,
we recommend that a cotton pellet moistened with Red Cross
Medication be placed over the exposed area and the tooth
covered with a thin sheet of foil to keep food debris out of
the exposed area.
Subluxation
In dentistry, the term subluxation (dislocation) is used to
describe a tooth that has loosened because of a traumatic
injury. Because subluxation may be related to fracture of
the jaws or teeth, the patient should be checked carefully. If
the injury caused only slight mobility of the affected tooth,
the condition will respond well to restricting food intake to
soft foods for about 1 week. If the injury displaces the tooth
549
to the point of causing a traumatic occlusion (bite) with the
opposing teeth, the treatment involves physically moving
the tooth into a more acceptable bite position, a procedure
that might require local anesthesia. Once the tooth has been
moved into a more acceptable position, food intake should
be restricted to soft foods.
Avulsion
Avulsion, the complete displacement of a tooth from the
socket, constitutes a true dental emergency. When a tooth has
been avulsed after a traumatic injury, the first priority is to
locate the tooth. The possibility of aspiration or entrapment
in soft tissue must always be considered whenever a patient
sustains a traumatic injury to the face [1]. This is especially
true in microgravity, where an avulsed tooth could float freely
into the oropharynx or elsewhere. Once the avulsed tooth has
been found, it should be stored for examination upon return to
Earth. Reimplantation, although possible, is too risky a pro-
cedure to attempt during space flight because of the pulpal
infection that inevitably ensues.
Necrosis
Presentation and Diagnosis
Pulpal necrosis involves death of a portion of the pulp or the
entire pulpal tissue of a tooth. This condition can manifest
in many different forms, and the tooth itself may present as
symptomatic or asymptomatic. In teeth with multiple roots,
the pulp may be partially or fully necrotic.
Partial Necrosis
Necrosis of a tooth with multiple canals (e.g., a molar or
premolar) fully tests the clinicians diagnostic skill, as the
results can be confusing even when vital testing is available.
For example, a maxillary molar with three roots can have one
root that is necrotic, another root that is vital, and a third root
that has gone through various stages of inflammation depend-
ing on the activity of the necrotic root next to it. With regard
to the dental pulp, no natural dichotomy exists between vital
and necrotic tissue. When a tooth that has multiple roots
exhibits symptoms that vary from day to day, partial necrosis
should be suspected. However, if the symptoms are not exten-
sive, it is best to leave the tooth untreated until the patient
returns to Earth.
Total Necrosis
Total necrosis is asymptomatic until it affects the periapical
tissue of the tooth. Thermal tests will not produce a response
in a totally necrotic tooth. In fact, until the infection has spread
to the periapical tissues, percussion will produce responses
550
similar to those of the teeth around the affected tooth. Once
the infection has spread to the periapical tissue, however, bit-
ing pressure will produce pain. Sometimes the affected tooth
is said to feel high as the infection spreads out the apex of
the tooth and into the periapical space below, forcing the tooth
upward.
Total necrosis can be dangerous, and the affected tooth may
have to be extracted. An infected tooth, unlike other areas of
the body, does not have a blood supply that can deliver anti-
biotics to the source of an infection. The tooth therefore acts
as a protective chamber in which bacteria multiply freely, and
the infection remains until either a root canal is performed or
the necrotic tooth is extracted. Antibiotics only temporarily
fight the bony infection at the tooth apex, the area in which
the patient feels pain. Without definitive treatment, the infec-
tion can spread after the antibiotics are discontinued; such
spreading frequently produces resistant strains of the infec-
tious agent.I
Acute Apical Periodontitis
Acute apical periodontitis is a local painful inflammation
around the apex of a tooth that may be associated with a vital
tooth, a partially necrotic tooth, or a totally necrotic tooth. It
can be caused by trauma, a recent high restoration, bruxism,
or infection. Given the range of possible causes, it is important
for the clinician to run a series of pulp tests before initiating
treatment.
For a patient with necrotic pulp, antibiotic therapy is the
initial course of treatment. The time remaining in the mission
will determine the next course of treatment. If the patient is
to return to Earth in less than a month, the tooth should be
treated with root canal therapy immediately upon return. If the
mission is to last more than a month longer, it might be best to
extract the offending tooth. If the tooth is found to be vital, the
treatment consists of removing the cause of the trauma, such
as making a minor adjustment in the patients bite.
Acute Apical Abscess
An acute apical abscess manifests with pain and a purulent
exudate around the apex of a tooth. It is caused by an advanced
case of acute apical periodontitis, which itself results from
pulpal necrosis and extensive suppurative inflammation. An
acute apical abscess is a serious condition that can quickly
incapacitate a patient. It presents with a rapid onset of slight
to severe swelling and pain. The tooth will be painful to per-
cussion, bite pressure, and palpation, and it may be mobile. In
severe cases, the patient may become febrile.
Once an acute apical abscess is diagnosed, a course of anti-
biotics should be started immediately. The time remaining in
the mission will determine the next course of treatment. If
the patient is returning to Earth in less than a month and the
infection can be controlled with antibiotics, the tooth should
be treated with root canal therapy immediately upon return.
M.H. Hodapp
However, if the mission is to last more than a month longer, the
best course of treatment may be to extract the offending tooth.
Diagnostic Testing
Determining the source of dental pain can be simple or, in
cases involving multirooted teeth or temporomandibular dis-
orders, complex. The source of the pain is usually revealed
in the course of a thorough dental history, examination, and
testing. The vast majority of cases in which pain is reported
encompass conditions of irreversible pulpitis, with or with-
out partial necrosis [4]. Since pain can be described in several
ways, an accurate description of pain plays a significant role
in the diagnosis of dental disorders.
Some common terms used for odontogenous pain are sharp,
dull, intermittent, spontaneous, continuous, mild, moderate,
and severe. Since the neural portion of the tooth contains only
afferent pain fibers, inflammation that is limited to the pulp
tissue can produce pain that is quite difficult for a patient to
localize. Once the inflammation progresses beyond the apical
foramen to include the periodontal ligament, which contains
proprioceptive fibers, the source of pain becomes clearer and
the patient can usually locate the offending tooth.
Whether the source of the pain is clear or not, diagnostic
procedures should be performed systematically, with the examiner
making note of the patients presenting signs and symptoms and
analyzing the results of clinical testing. Usually the diagnosis is
straightforward once the examination process is complete.
When a patient reports pain, the examination should begin
with a brief dental history while the examiner observes the
patient for any facial asymmetry or distensions that might
indicate facial swelling of systemic or odontogenous origin.
Examination of the inside of the mouth should then proceed
with the aid of a mouth mirror and light source.
Intraoral screening begins with an examination of the soft
tissue, with the examiner looking for changes in tissue color
or contour and for the presence of a raised bump with either a
head resembling a pimple or a small opening (sinus tract) on
the buccal or palatal mucosa. This type of lesion could signify
a necrotic root or necrotic tooth next to the lesion. Once the
soft tissue and teeth have been evaluated visually for any obvi-
ous lesions, a series of tests-palpation, percussion, bite test,
periodontal probing, thermal tests, and transilluminationcan
aid in the diagnosis.
Palpation Test
When pulpal necrosis has extended to involve periapical
inflammation, the inflammatory reaction may involve burrow-
ing through the cortical bone to affect the mucoperiosteum.
Before incipient swelling is clinically evident, it can be
detected through gentle palpation.
The palpation test entails placing a finger along the gingiva
at about the height of the root tip and gently palpating the
26. Dental Concerns
tissue on both the palatal and facial aspects of the teeth. A
painful response over the root apex of a tooth should raise
suspicion of pulpal necrosis. Another area to palpate to deter-
mine whether an infection is arising from the oral cavity is
at the submandibular nodes, located just below the border of
the mandible and the cervical nodes on each side of the neck
[5]. Raised, tender nodes can be the first noticeable sign of an
intraoral infection.
Percussion Test
The percussion test consists of gentle tapping on the biting
surface of the teeth and can help detect apical abnormalities.
It should be performed initially with a finger in the event the
questionable tooth is highly inflamed and painful. The handle
of a mouth mirror can then be used to help identify the tooth
in question.
The diagnostic value of the percussion test is in determin-
ing whether the apical tissues of a tooth are inflamed. The
test does not reveal whether a tooth is vital or necrotic; apical
tissue can be irritated in either situation depending on the cir-
cumstances. In the case of a vital tooth, the irritation is usually
caused by a recently placed restoration or by bruxism (grinding
of the teeth). This irritation can cause the periodontal ligament
to become irritated, and thus the tooth will be painful upon
application of biting pressure. In the case of a necrotic tooth,
the necrotic tissue within the tooth multiplies and pushes out
through the apical foramen into the bone beneath the tooth,
causing a painful response to biting pressure. Any time a pain-
ful response to the percussion test presents itself, further tests
and questioning should follow.
Bite Test
The percussion test helps to determine whether a tooth has
inflammation in the apical tissues; the bite test, in contrast, is
done to check for a split in the tooth.
The bite test is performed by placing the head of a cotton-
tipped applicator or an orangewood stick at different positions
on the tooth or teeth under suspicion at different angles to
determine whether the patient experiences a painful response.
A patient with a cracked tooth will respond to this test with
a sharp stabbing pain, either upon biting the applicator or
immediately upon release of it.
Periodontal Probing Test
The periodontal probe is a valuable diagnostic aid that is used
to distinguish between dental or periodontal pain. The probe
is inserted between the patients gum and tooth, using only
very light pressure, and then is walked gently along the side of
the tooth between the gum and the tooth, sounding the height
and contour of the tissue. This sounding should not be painful,
and the measured depth of the probe should range from about
13 mm, with no bleeding in the absence of disease.
551
If the patient feels some pain when the probe is being used,
either the examiner is putting too much force on the instrument
or the area is inflamed. If the patient experiences a great deal
of pain in an area of a tooth, this suggests the presence of a
periodontal abscess due to a retained popcorn hull (this would
be highly unlikely during space flight) or similar substance, a
tooth with a cracked root that is causing pulpal inflammation,
a tooth with a failing root canal or pulpal necrosis, or some
other form of periodontal disease.
Thermal Tests
One of the most common symptoms associated with an inflamed
pulp is pain that is triggered by a hot or cold stimulus. In this
case, thermal testing is a valuable diagnostic aid because it can
help determine whether a pulp is healthy, inflamed, or necrotic.
Testing several teeth in a quadrant by the application of cold,
heat, or both also can identify the offending tooth.
Cold Test
Before the cold test is performed, the patient should be
informed of the nature of the test and what to expect. The
nerve fibers in the tooth can sense only pain. The proper method
of performing the test is to dry the teeth in the quadrant with
2 2-in. gauze. The teeth are then tested individually, starting
with the last tooth in the quadrant and proceeding anteriorly. The
cold test is performed most commonly with ice sticks, ethyl chlo-
ride, CO2 snow (dry ice), 1,1,1,2-tetrafluoroethane, or Freon
[6]. Of these five methods, all of which are generally accepted,
ethyl chloride and 1,1,1,2 tetrafluoroethane are the methods of
choice on Earth. However, given the risk of contaminating the
spacecraft cabin atmosphere, a moistened and frozen cotton-
tipped applicator is the preferred means of applying the cold
stimulus in space.
The moistened and frozen cotton-tipped applicator is first
placed on a tooth on the other side of the arch being tested to
check the response of the patients healthy pulp. The patient is
asked to respond by raising a hand the moment the cold stimu-
lus is felt. Once the patient responds, the cotton-tipped appli-
cator is removed from the tooth and the number of seconds
are counted until the stimulus subsides. (The patient may not
always respond if the tooth has had a previous root canal or
porcelain crown.) Once the patient has felt the cold stimulus
on a healthy tooth and understands how to properly respond,
the test is performed on the tooth in question. All teeth in the
quadrant should be tested if there is any question of which
tooth is affected.
Heat Test
The heat test, although it can aid in the diagnostic process,
is too difficult to perform in weightlessness, especially by inexperi-
enced examiners. Since the neural fibers in the pulp of a tooth
transmit only the sensation of pain, the patients response to
552
both types of thermal testing is essentially the same, and thus
the heat test is of little use in these circumstances.
Evaluating Results of a Thermal Test
The pulp usually responds to a thermal test in one of four ways:
with a mild transient response; with no response at all; with a pain-
ful response that subsides quickly after the stimulus is removed; or
with a painful response that lingers after removal of the stimulus.
A mild and transient response is typically considered normal,
and any other response usually signifies some type of pulpal
abnormality. If the pulp does not respond at all, the tooth may
be either nonvital or the result may be a false-negative. A false
negative may occur with excessive calcification of pulp, a previ-
ous root canal, an insulated restoration (e.g., a porcelain crown
or large composite filling), an immature apex, recent trauma,
or secondary to some medications that may have been taken
before pulp testing. A painful response that subsides quickly
after removal of the stimulus usually indicates a reversible pul-
pitis. This type of inflammation will often heal itself once the
traumatic stimulus is removed. Finally, a painful response that
lingers even after the stimulus is removed indicates a symptom-
atic, irreversible pulpitis. The disease process in this case gener-
ally requires treatment to alleviate the symptoms.
Transillumination
A strong fiber-optic light is an excellent adjunct for identify-
ing an offending tooth. Transillumination of the anterior teeth
can help detect interproximal caries and determine whether
the tooth is vital or necrotic. A vital anterior tooth, when trans-
illuminated, appears clear and slightly pink. A necrotic tooth
appears opaque and darker than the surrounding teeth because
of the breakdown of blood in the pulp chamber.
Transillumination can also help in the diagnosis of cracked
teeth in the posterior region of the mouth. Normally, a light
source placed against the outside surface of a tooth will trans-
mit light through the tooth, illuminating the whole tooth. If
the light source is placed against the side of a tooth and the
light goes through the tooth only to the point of a crack before
stopping and the patient has shown symptoms of a cracked
tooth, it is safe to assume that the tooth is cracked. If light goes
all the way through the tooth, even if crack lines are showing
on the outer surface of the tooth, it could be that the cracks
only go through the enamel surface and this tooth should not
be suspect. This test is invalid if a restoration is present that
prevents the transmission of light.
Anesthesia Tests
Tests involving selective local anesthesia are used when pain
is diffuse and of vague origin and the results of all other tests
are inconclusive. Anesthesia testing is based on the fact that
pulpal pain, even when it is referred, is almost invariably
unilateral. The anesthesia test can be given by one of three
M.H. Hodapp
methods, the first of which involves use of block anesthesia,
the second infiltration, and the third intraligamentary anesthesia.
Block anesthesia is used for the mandibular teeth if, for
example, the pain is diffuse over the right side of the face, all
pulp tests have been exhausted, and the source of pain is inde-
terminate. Block anesthesia is used on the mandible because
infiltration alone usually does not work for mandibular teeth
owing to the dense nature of the mandibular bone. If the pain
subsides 35 min after a mandibular block is administered, it
can be surmised that a mandibular tooth is causing the pain.
However, if the pain continues despite achievement of pro-
found anesthesia of the mandibular teeth, then each maxillary
tooth can be infiltrated until the pain subsides. It is important
to wait 35 min between each injection to allow the anesthetic
to take effect in order to determine which tooth is the culprit.
If a mandibular tooth has been demonstrated to be the cul-
prit, intraligamentary anesthesia can then be administered
after the block anesthetic has worn off to permit definitive
treatment. (To administer intraligamentary anesthesia, a short,
preferably 30-gauge needle is placed into the sulcus at an
angle 30 degrees from the perpendicular, with the bevel fac-
ing away from the tooth and very firm pressure placed on the
plunger of the syringe for several seconds. Approximately
0.2 ml of local anesthetic is used.) When the offending tooth
has been anesthetized with this intraligamentary technique,
the pain will immediately disappear [7].
On rare occasions, the pain does not disappear despite the
correct administration of an anesthetic. If it is determined that
all tests have been performed correctly and a definitive diagno-
sis could not be made, the differential diagnosis must include
the possibility of a temporomandibular disorder or some form
of organic disease of nonodontogenic origin.
Classification of Tooth Disorders
Normal
A tooth that is considered normal is asymptomatic. During
pulp testing, percussion or palpation of the tooth and its sur-
rounding attachment does not elicit a painful response. Ther-
mal or electrical stimulation, on the other hand, does produce
a mild to moderate transient response. On radiography, no
evidence of internal calcification of the canal space or root
resorption is present, the lamina dura (the bony outline around
the surface of the tooth) is intact, and the periodontal ligament
is viewed as a thin, equally spaced dark line between the root
surface and the lamina dura without interruption or widening.
Reversible Pulpitis
In the case of reversible pulpitis, the pulp is not diseased but
rather is only symptomatic. The pulpal tissue is inflamed to the
point where a thermal stimulus causes a sharp hypersensitive
response that subsides as soon as the stimulus is removed.
26. Dental Concerns
Potential causes of reversible pulpitis are essentially anything
that can affect the pulp tissue. These include caries, abfractive
(wedge-shaped) lesions causing gingival recession, a recent
restoration that was left high, a filling without a good bond,
and bruxism. The symptoms usually subside once the irritat-
ing stimulus is removed.
Treatment consists of removing the irritating stimulus. If the
cause of irritation is bruxism, then removing the interference is
the only treatment necessary. If reversible pulpitis is due to a car-
ious lesion, the carious material should be removed and a seda-
tive dressing (e.g., Cavit) should be placed. Abfractive lesions
sometimes can also be covered with a sedative dressing.
Irreversible Pulpitis
Irreversible pulpitis can be described as acute, subacute, or
chronic. It can occasionally be detected radiographically in
forms such as canal calcification and internal resorption.
Affected pulp can be partially or totally inflamed. The pulp
can also be partially infected or sterile. Irreversible pulpitis
can present as a lingering sensitivity to hot or cold, or it may
be relieved by either of the same stimuli.
The pulp of a tooth is always in a dynamic state, and a
change in pulpitis from quiescent chronicity to acute sympto-
mology can occur over several years or in a matter of hours.
When a tooth is in the acute symptomatic stage, it requires
treatment (e.g., root canal therapy or extraction), particularly
when the individual has symptomatic irreversible pulpitis, as
described in the following paragraph.
Symptomatic irreversible pulpitis is characterized by spon-
taneous intermittent or continuous paroxysms of pain that
can range from moderate to severe depending on the extent
of the inflammation. The pain may present as sharp or dull,
and it may be localized or referred. A mandibular molar, for
example, commonly refers pain to the ear or temporal area.
This referral occurs because of the protective nature of the
neuromuscular system, which can be compounded by muscle
splinting and spasms. The treatment of choice for irreversible
pulpitisroot canal therapyis unfortunately not feasible at
this time in space flight. Thus, if pain cannot be controlled
with analgesic medication, the only in-flight alternative is
extraction. (The technique for tooth extraction in flight is
described in further detail later in this chapter.)
Asymptomatic irreversible pulpitis is a condition in which
inflammatory exudates are present but are quickly vented.
This condition sometimes develops during the conversion of
acute irreversible pulpitis to a chronic state. In the chronic
state, the patient usually has no symptoms and can function
normally. If the tooth is left untreated, however, it will usu-
ally become necrotic. The treatment to be taken will depend
on the duration of the mission, at what point the condition
manifests itself within the mission, and the symptoms that the
patient may be experiencing. In most cases, immediate care
is not necessary, but treatment should be given immediately
upon return to Earth. However, if the tooth becomes necrotic
553
and the patient begins to experience symptoms of pain and
swelling during flight, treatment for a necrotic tooth should
then proceed.
Other Dental Emergencies
Temporomandibular Joint Disorders
Temporomandibular joint disorders are quite common and are
expressed in many different forms. Typically, most temporo-
mandibular disorders go undiagnosed and untreated because
the disease is not in an acute phase or form. During periods
of unusual stress, an asymptomatic condition can become
symptomatic. Under normal conditions, the disorder usually
presents itself during the third through fifth decades of life and
most often occurs in women. Since temporomandibular dis-
orders are often multifaceted in nature, their diagnosis can be
quite complex. The important point to note is that when dental
pain is expressed but the pain cannot readily be pinpointed to
a specific tooth, the patient should be evaluated for the possi-
bility of a temporomandibular disorder. Several types of such
disorders are described below.
Myofascial Pain Dysfunction
Myofascial pain dysfunction, also known as trigger-point
myalgia, is the most common form of temporomandibular
joint disorder. In one study [8], myofascial pain dysfunction
was diagnosed in more than 50% of the patients reporting to a
university pain center. Although the exact cause of the disorder
is not fully understood, myofascial pain dysfunction is thought
to arise from trauma, stress, and discrepancies between the
temporomandibular joints and the occlusion of teeth.
Myofascial pain arises from hypersensitive localized areas
within the muscles known as trigger points. These trigger
points, which are either within the muscles or their fibrous
attachments, are often felt as tight bands or knots that are
painful upon palpation of the area. However, since only a
select group of motor units is firing, no overall shortening of
the muscle like that in myospasm is observed. Uniquely, since
trigger points can be a source of deep, constant pain, they can
produce central excitatory effects.
Trigger-point pain is often reported as a headache, and in
many instances the patient is aware of only the referred pain
they may not even acknowledge the actual trigger point. This
situation can be confusing to the clinician who is attempting a
differential diagnosis of dental pain, because the trigger points
have been known to refer pain to areas of the oral cavity. Sev-
eral cases have been reported cases of in which pain that was
originally thought to be of dental origin was later found to
be myofascial pain dysfunction or some other temporoman-
dibular disorder. This is why pulp testing and questioning the
patient is so critical before any form of dental treatment is
administered.
554 M.H. Hodapp

Myofascial pain dysfunction is treated with warm and cold
compresses over the trigger-point area to break up the trig-
ger points and to increase circulation to the muscle tissue.
Since the trigger point is usually in a different location than
the referred source of pain, it can be identified only by pal-
pating the muscle tissue of the face and neck [9]. Treatment
is relatively straightforward in that rest, a soft food diet, and
nonsteroidal anti-inflammatory drugs (e.g., aspirin or ibupro-
fen) have been shown to be helpful in alleviating discomfort.
The medical disposition of individuals diagnosed as having
myofascial pain dysfunction is directly related to their pain
level. In most cases, patients should be able to perform their
normal duties after treatment.
Trigeminal Neuralgia
Trigeminal neuralgia or tic douloureux presents as parox-
ysmal pain of neuropathic origin. Fortunately, this painful
disorder is not very common. When it does occur, the pain
is described as being excruciating, sharp, and stabbing. Tri-
geminal neuralgia can be aggravated by brushing the teeth,
chewing, or even talking [10]. Pain can also be induced by
touching a specific area of the face. The slightest touch on
such trigger zones can produce several excruciatingly painful
shocks. The difference between these trigger zones and the
trigger point commonly found in myofascial pain dysfunc-
tion is that a trigger zone requires only a light touch on the
outer skin to elicit paroxysms of pain, whereas trigger points
require pressure to elicit pain within the muscle tissue.
Trigeminal neuralgia is usually caused by compression
of a blood vessel where the trigeminal nerve root enters
and exits the base of the skull. The features that distinguish
trigeminal neuralgia from myofascial pain dysfunction are
the dystonic paroxysm, grimace, or tic. [11] Trigeminal
neuralgia is treated with anticonvulsant drugs such as car-
bamazepine. Medical disposition depends on the severity of
symptoms. In most cases, patients can perform their duties
as long as the trigger area is not touched or disturbed.
mouth, as occurs during yawning. Anterior dislocation takes
place when the condyle of the lower jaw extends beyond the
articular eminence of the temporal bone, after which the ele-
vator muscles of the mandible go into spasm. Trismus results,
and the condyle cannot return to its proper location within
the mandibular fossa. Mandibular dislocation can be fright-
ening and painful. However, in most cases the mandible can
be physically manipulated (reduced) into its original position
without recourse to sedatives. Occasionally, a sedative such as
diazepam may be needed to allow the muscles to release.
Reduction is performed by grasping the patients mandible
intraorally, with the thumbs of both hands placed on the bony
ridge adjacent to the molars and the fingers wrapped around
the underside of the jaw (Figure 26.2). Downward pressure
is then applied to the bony ridge of the mandible while an
upward force is applied to the anterior region of the mouth.
The effect is to free the condyles from the anterior portion
of the articular eminence of the temporal bone. Care must be
taken to keep the thumbs away from the biting surfaces of the
teeth, since the elevator muscles of the mandible tend to con-
tract with intense force once reduction has occurred. Under
no circumstances should the mandible be forced back or the
mouth forced closed.

Arthralgia
Pain in any joint structure that includes the temporomandibular
joint is known as arthralgia. Arthralgia can be caused by discrep-
ancies between occlusion of teeth and joint position, rheumatoid
arthritis, inflammation, or trauma. The patient usually complains
of sharp, sudden, intense pain in the joint area when moving the
lower jaw. When the joint area is rested, the pain usually resolves
quickly. Patients with arthralgia typically also suffer with myo-
fascial pain dysfunction that can be controlled by nonsteroidal
anti-inflammatory drugs and warm and cold compresses.

Dislocation of the Temporomandibular Joint

Although trauma can cause temporomandibular dislocation,
its most common cause is excessively wide opening of the Figure 26.2. Reduction of a dislocated temporomandibular joint
26. Dental Concerns
Dental Techniques for Use in Space Flight
Dental Injection
Anesthetizing the upper teeth for most procedures usually
requires injecting a small amount of anesthetic proximate to the
offending tooth. If a tooth extraction is involved, however, the
palatal portion of the tissue will also require anesthetization.
To anesthetize the desired tooth the needle is placed at the
height of the moveable membrane (mucobuccal fold) above the
fixed gum tissue and the needle inserted, with the tip directed
upward towards the root apex of the tooth to be anesthetized.
Once the needle is in position, the plunger should be gently
drawn back to aspirate and determine whether the needle has
entered a blood vessel. If the aspirant is clear, about one-third
of a carpule of anesthetic is delivered and the syringe with-
drawn. The patients pain should subside within 35 min; if it
does not subside after 5 min, reinjection may be necessary.
Since the mandible is dense, anesthetizing the lower teeth
requires block anesthesia, a technique in which an entire sec-
tion of the mandibular nerve and usually the lingual nerve are
anesthetized. A successful block of the mandibular and lingual
nerve will produce a numbing sensation on half of the tongue
and on the lower lip on the side into which the anesthetic was
delivered. This method requires careful attention to technique
in order to achieve profound anesthesia. To anesthetize the
lower teeth, the syringe is first loaded with a long needle and
the yellow needle cap removed as described above. Next, the
thumb of the examiners nondominant hand is positioned in
the deepest portion of the coronoid notch of the mandibular
ramus. The centerline of the thumb is used as a guide for the
height at which the needle is to be inserted (Figure 26.3).
While the patient holds his or her mouth open wide, the
examiner, holding the syringe in the dominant hand, places
the barrel of the syringe so that it is resting over the man-
dibular teeth between the canine and first premolar (the third
and fourth teeth back from the midline). The needle is then
inserted, at this angle, where the seam between the cheek and
Figure 26.3. Administration of block anesthesia to the mandibular
and lingual nerve
555
throat (the pterygomandibular raphe) turns upward towards
the maxilla until the jawbone is contacted.
At the point where the jawbone is contacted, only about
510 mm of needle should be left exposed from the tissue. If
the angle of the patients jaw is such that bone was not con-
tacted and the needle hub is pressed against the tissue, the
needle should be withdrawn halfway and reinserted with
the syringe barrel resting over the 2 premolars (the fourth and
fifth teeth back from the midline). If, on the other hand, the
needle contacts bone before reaching the proper depth (i.e.,
more than 510 mm of needle is left exposed from the tissue),
the needle should be withdrawn halfway and reinserted with
the syringe barrel resting over the lateral incisor and canine
(the second and third teeth back from the midline).
Once the proper depth is achieved and the patients jawbone
has been contacted at the same time, the plunger of the syringe
is drawn back gently to check for aspiration of blood. If no
blood is aspirated, the entire contents of the syringe are slowly
injected over a 1- to 2-min period. Once the contents of the
carpule have been delivered, the syringe is withdrawn. Pro-
found anesthesia should be obtained within 35 min; if not,
then reinjection will be necessary.
Temporary Filling
A temporary filling is a means of covering sensitive, exposed
dentin. Dentin can be exposed as a result of caries, trauma,
or wear. Covering a sensitive dentinal surface ensures that
the patient can continue to function comfortably. If a tempo-
rary filling is to be placed, the tooth should be anesthetized
and all carious material and any food debris removed with
a spoon excavator or similar instrument. However, before a
temporary filling is considered, it must be determined with
absolute certainty that the pulp chamber is not exposedeven
if the pulp is nonvital. An easy way of determining whether
pulp has been exposed is to use a good light source, a dental
mirror, and an explorer to sound the floor of the tooth. If the
floor of the tooth is oozing blood, the pulp of a vital tooth has
been exposed. If no blood is present, the next step is to rub
the explorer along the floor of the tooth to feel for a pinhole-
type opening. If an opening is found, the pulp chamber can be
assumed to have been exposed, and the area should be treated
as exposed pulp. (When in doubt, it is always best to assume
that the pulp chamber has been exposed.)
If the dentinal surface is intact (it is assumed at this point
that the tooth has been anesthetized, the dentinal surface is
clean, and pulpal exposure has not occurred), a temporary res-
toration can be placed as follows. First, a small amount of
Cavit or similar filling material is squeezed onto a small work
surface, such as a wooden tongue blade, and the material is
rolled into a ball. Next, with the aid of the spoon excavator, the
filling material is placed into the exposed cavity and the material
condensed into the dentinal surface. Once the material is in
place, 2 2-in. gauze pads are used to wipe off and contain
the excess filling material. To determine whether the bite is
556
correct, the patient is asked to close his or her teeth together.
If the filling is too high, it should be adjusted immediately. (It
is better for the filling to be a little low than a little high.) The
filling material should set for approximately 20 min before the
patient is allowed to eat.
Exposed Pulp
When the pulp chamber is exposed, regardless of whether
bleeding is present after the carious material has been removed
or whether the tooth is necrotic with an access hole into the
pulp chamber, the best practice is to leave the area open and
keep it clean. Covering an exposed vital or necrotic pulp
chamber could lead to an infection that could cause severe
facial swelling and pain.
In the case of a carious exposure of the pulp when remov-
ing decay, the initial strategy is to remove all carious material
first before removing as much of the pulpal tissue as possible.
Next, Red Cross Medication should be placed on a cotton pel-
let. Because the eugenol in this medication can be an eye irri-
tant, we recommend that the medication be dispensed from
the tubex syringe directly onto the cotton pellet. Once the cot-
ton pellet has been moistened with medication, the pellet is
squeezed onto the 2 2-in. gauze to remove any excess med-
ication. Finally, the cotton pellet is placed into the exposed
area of the tooth and left there.
Should the area become sensitive again, additional medica-
tion can be placed as needed by repeating the above procedure.
Typically, subsequent applications can be placed without the
use of a local anesthetic. The area should not be covered with
a temporary filling, since doing so could cause facial swelling
and pain. It is important to leave the exposed area covered only
by the cotton pellet and to remove any food debris that might
get into the exposed area. The medical disposition in the case
of an individual with exposed pulp would be guarded, and
the patient should be monitored daily for swelling. If swell-
ing appears, immediate treatment with antibiotics would be in
order, and then, depending on the proposed time remaining in
flight, the next protocol may be to extract the offending tooth.
As noted earlier in this chapter, a course of antibiotics will
not eliminate the bacteria present in an infected tooth. Rather,
antibiotics are a means of controlling the bacteria escaping
into the bony area underneath the tooth until definitive care
can be obtained.
Recementing a Crown
When a crown becomes dislodged during space flight, the rec-
ommended procedure if the tooth is asymptomatic is to stow
the crown in a secure location until the individual returns to
Earth. The risk of discomfort as a result of incorrect replace-
ment of the crown or the risk of the crown becoming dislodged
and aspirated is too great to consider replacing the crown of an
asymptomatic tooth. However, if the tooth is sensitive and loss
M.H. Hodapp
of the crown interferes with the performance of the afflicted
crewmember, the correct protocol is to recement the crown
with temporary cement. When temporarily recementing a
crown, it is imperative that all cement be removed from the
internal aspect of the crown and tooth and the bite be checked
with the crown in and out of the mouth. If the bite is changed
after the crown is placed, it is better to stow the crown than to
cement it in place.
If the bite does not change, the following steps should be
taken. First, all residual cement is removed from the inside
crown surface and from around the tooth with a dental
carver or spoon excavator. Next, the fit of the crown should
be checked carefully by placing the crown on the tooth and
asking the patient to bite down while keeping a finger on the
side of the crown to prevent it from dislodging. The patient
is asked whether his or her teeth feel as if they are hitting
correctly (the teeth should hit the same with the crown in or
out of the mouth.) If the bite feels different with the crown in
the mouth, the crown should be removed and the crown and
tooth should be cleaned again, since this feeling of difference
is usually caused by residual cement. Once the bite feels the
same when the crown is in and when it is out, the crown and
tooth should be dried off and the tooth isolated with gauze
or cotton rolls. Next, the luting cement is mixed on a tongue
depressor and placed into the inside of the crown, after which
the crown is seated on the tooth by using a positive pressure
rocking force.
Once the crown is in place, the patient should be told to bite
down and the crown should be checked to see whether it is
fully seated. If the crown is not fully seated, the crown should
be carefully removed by using the spoon excavator to pry it
up at different locations around the margin until it is loose.
The crown is then removed and the process is begun again. If the
crown is fully seated, the tip end of a cotton swab is placed
over the crown and the patient is asked to bite down gently for
35 min, after which the remaining cement is gently cleaned
from around the gum tissue with a dental carver or explorer
and dental floss. To floss the cement from between the teeth, a
knot is placed in the center of an 18-in. (46-cm) piece of den-
tal floss and the floss is gently glided back and forth between
the crown and the adjacent tooth.
Dental Extraction
In space flight, tooth extraction should be considered only as a
last resort because of the possibility of complications such as
loss of a root tip, sinus exposure, jaw breakage, dry socket, or
infection. Extraction should be performed only after all other
treatment options have been exhausted.
Understanding the physiology underlying a properly per-
formed extraction is important when a tooth extraction is
deemed necessary. The most important point that must be
understood before an instrument is ever placed on a tooth
is that a tooth is not pulled out. The roots of a tooth have a
26. Dental Concerns
natural conical shape, a shape that gives the tooth its natu-
ral tendency to erupt. The only force keeping a tooth in its
socket is the fibrous periodontal ligament. In other words,
the tooth has a natural tendency to come out on its own but
is essentially held in place by connective tissue. Also impor-
tant to remember is that both the tooth and the underlying
bone are brittle.
So the question is: How can two brittle objects that are held
together by fibers be safely separated? The answer is patiently,
and with light force. If a gentle-to-moderate force is placed on
a ligament for a long time, the ligaments will stretch and the
tooth will, by its physiological nature, extract itself. The key
to extraction is light-to-moderate force and time. The moment
an extraction is rushed, the tooth will break.
Also important to note is that a properly performed
extraction involves no vertical pulling force on the for-
ceps. To get the maximum benefit from forceps, the crown
of the tooth is held in the forceps as close to the gum tissue
as possible, and the tooth is rotated clockwise and held in
that position so as to maximize the number of fibers being
stretched at the same time. As the tooth is held in this
position, an ensuing inflammatory reaction also causes
the ligament fibers to weaken. This position is to be held
for at least 2 min, after which the tooth is slowly rotated
counterclockwise and that position again held for at least
2 min. This procedure may need to be repeated several
times before the tooth comes out on its own. The points to
remember are to be patient and to be gentle. Persuasion is
easier than force.
The recommended procedure for extraction is as follows:
The tooth to be extracted should be anesthetized, using proper
dental injection techniques. If the tooth to be extracted is an
upper tooth, the palatal tissue next to the tooth to be extracted
must be anesthetized; if a lower tooth is to be extracted, the
tissue on the cheek side of the tooth may have to be anesthe-
tized before extraction. Next, the explorer is used to disengage
the attached tissue from the tooth at the base of the crown.
The forceps are then placed on the tooth to be extracted, and the
examiners other hand is used to either grasp both sides of
the gum tissue of the tooth to be extracted (if an upper tooth)
or stabilize the lower jaw (if a lower tooth). The crown of the
tooth is held in the forceps as close to the gum tissue as pos-
sible. The tooth in the forceps is rotated clockwise and held in
this position for at least 2 min. The tooth is then slowly rotated
counterclockwise and again held in position for at least 2 min.
This procedure should be repeated several times until the tooth
comes out on its own. If after several minutes the mobility of
the tooth has not increased, dental elevators can be used as
described below.
Use of Elevators
From the cheek side, a small elevator (#301) is placed between
the tooth to be extracted and the adjacent tooth, with the lower
557
edge of the elevator against the tooth that is to be extracted.
Moderate rotational force is applied to the elevator (as if turn-
ing a screwdriver), thereby creating a lifting force on the tooth
to be extracted, and the position is held for 60 s. This force
is to be applied sequentially on both the front and back side
of the tooth. Once the tooth is slightly elevated, the proce-
dure can be repeated with a large (#34S) elevator if adequate
room exists. Finally, the tooth is extracted with the forceps as
described above.
Conclusions
In the future, space travel will entail human travel and colo-
nization of distant planets. The crews of these exploration-
class missions must be versatile, and must be well trained in
all phases of medical and dental emergency situations. Dental
emergencies in space can become true medical emergencies.
Infections in this area can be serious, since veins in areas of
the face do not have valves to prevent backflow into the cav-
ernous sinus area of the brain. Research into space dentistry
must continue to help provide the most effective and simpli-
fied care for the crews of these missions, helping guarantee
our survival in space.
References
1. Houck JR, Klingensmith MR. The tooth as a foreign body
in soft tissue after head and neck trauma. Head Neck 1989;
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2. Laskin DM, Steinberg B. Diagnosis and treatment of common
dental emergencies. Alpha Omegan 1984; 77:4152.
3. Amsterdam JT, Hendler BH, Rose LF. Emergency dental proce-
dures. In: Roberts JR, Hedges J (eds.), Clinical Procedures in
Emergency Medicine. Philadelphia, PA: WB Saunders; 1985:
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4. Seltzer S, Bender IB. The Dental Pulp: Biologic Considerations
in Dental Procedures. 3rd edn. Philadelphia, PA: JB Lippincott
Company; 1984.
5. Rose LF, Kaye D. Internal Medicine for Dentistry. St Louis, MO:
CV Mosby Co.; 1983.
6. Trowbridge HO. Changing concepts in endodontic therapy.
J Am Dent Assoc 1985; 110:470480.
7. Littner MM, Tamse A, Kaffe I. A new technique of selective
anesthesia for diagnosing acute pulpitis in the mandible.
J Endod 1983; 9:116119.
8. Travell JG, Rinzter SH. The myofascial genesis of pain. Postgrad
Med 1952; 11:425.
9. Travell JG, Simons DG. The upper extremities. In: Myofascial
Pain and Dysfunction: The Trigger Point Manual. Vol 1. Balti-
more, MD: Williams & Wilkins; 1982:5963.
10. Gilroy J, Meyer JS. Medical Neurology. London: Macmillan;
1969: 8081, 280288, 547549, 612615.
11. Travell J. Identification of myofascial trigger point syndromes:
A case of atypical facial neuralgia. Arch Phys Med Rehabil 1981;
62:100106.
27
Spaceflight Metabolism and Nutritional Support
Scott M. Smith and Helen W. Lane
Adequate nutritional status is critical to maintaining crew
health during extended-duration space flight and post-
flight rehabilitation. Nutrition issues relate to intake of
required nutrients, physiological adaptation to microgravity,
psychological adaptation to extreme environments, and
countermeasures to ameliorate the negative effects of space
flight. Our ability to define the nutrient requirements for
space flight and to ensure the provision and intake of those
nutrients by spaceflight crews is thus critical for crew health
and mission success.
Specialized nutritional requirements have only been
considered for extended-duration flightsthose lasting longer
than 30 days. Although adequate nutrition is important on the
1- to 3-week Space Shuttle flights, intake of specific nutrients
above or below space-specific requirements for such periods
is not thought to be cause for concern. Thus, planning menus
for Space Shuttle flights has always used recognized nutri-
tional requirements for adult males and females [1,2]. In this
chapter, we will further classify nutritional requirements for
long-duration space flight into those for orbital missions, such
as on the International Space Station, and those for explora-
tion-class missions.
Nutritional and Physiologic Effects
of Space Flight
Nutrition is closely, if not directly, related to many of the
physiologic consequences of space flight. Specific examples
of these consequences include loss of weight in the form
of both lean and adipose tissue, loss of bone, hematologic
changes, and increased risk of renal stone formation. Issues
that should be considered related to nutrition in the weight-
lessness of space include dietary intake, specific nutrient
deficiencies or excesses, stress, environmental features,
and the influence of exercise and other countermeasures
[312]. This chapter focuses on the clinical aspects of
nutrition in space.
Dietary Intake
Although the overall percentage of calories derived from
protein, carbohydrate, and fat ingested by spaceflight crews
has been acceptable (Figure 27.1), the total intake of food and
energy (Figure 27.2) is nonetheless generally less during space
flight than before flight [5,1319]despite data indicating
that in-flight and preflight energy requirements are similar
[14]. World Health Organization estimates of the energy
required for moderately active individuals [2], which reflect
current in-flight requirements, have been used as the standards
by which spaceflight menus are planned (Table 27.1). Yet from
the Apollo program onwards, crewmembers have typically
consumed only about 70% of predicted requirements (Figure
27.2). The obvious and immediate reason for concern about
this reduction in dietary intake is the associated risk of body
mass loss and dehydration.
The gap between energy intake and expenditure is widened
further by the exercise associated with physical countermea-
sures. Results from metabolic experiments conducted during
the U.S. Skylab missions showed that simply ingesting the
prescribed amount of calories did not maintain astronaut body
mass (Figure 27.2) [2022]. Inadequate energy intake clearly
ensures loss of body mass. Preliminary data also suggest that
the lesser energy intake during space flight is associated with
a decrease in protein synthesis [23]. This finding is significant
not only from the point of view of crew health but also for
medical and research studies, in which clear interpretation of
other physiological data from malnourished subjects becomes
impossible.
The cause of reduced dietary intake during space flight is
unknown, although anecdotal information provides potential
explanations [5,17,24]. Food palatability has been identified
occasionally as a cause of reduced in-flight intake. Anecdotal
reports suggest that food taste and aroma change during
space flight, and the fluid shifts and congestion associated
with microgravity, especially during the first few days, have
been hypothesized to affect taste and odor perception. Nev-
ertheless, spaceflight studies have not demonstrated changes
559
560
Figure 27.1. Diet composition before and during flight for Skylab
and Shuttle missions. Data are expressed as percentage of calories
Figure 27.2. Energy intake during flight for four different space pro-
grams. Intake is expressed as percentage of WHO requirement as cal-
culated for each individual crewmember (see Table 27.1 for equation)
Table 27.1. Recommended macronutrient intake levels for crew-
members on missions lasting from 30 days to 1 year.
Nutrient Recommendation
Energy From the World Health Organization (1985) equation:
Men: (1830 years): 1.7 (15.3W + 679) = kcal/day
required
(3060 years): 1.7 (11.6W + 879) = kcal/day required
Women: (1830 years): 1.6 (14.7W + 496) = kcal/day
required
(3060 years): 1.6 (8.7W + 829) = kcal/day required
W = weight in kg. These figures are for moderate
levels of activity. An additional 500 kcal/day is
supplied on days when extravehicular activities are
to take place or when end-of-mission counter
measures are being conducted.
Protein 1215% of calories
Carbohydrate 5055% of calories
Fiber 1025 g/day
Fat 3035% of calories
Fluid 1.5 ml/kcal (>2 L/day)
S.M. Smith and H.W. Lane
Figure 27.3. Examples of Space Shuttle foods. (Photo courtesy of
NASA)
in taste or olfaction [25,26], and results from ground-
based studies have been equivocal. Tongue taste perception
measured before, during, and after 30 days of 6-degree
head-down bed rest produced reports of decreased appetite
and lack of taste early in the bed-rest phase, but by day 13 the
threshold for sensitivity to all tastes (sweet, salt, acidic, and
bitter) had increased [27,28]. In contrast, a more recent study
found no changes in odor or taste perception after 14 days of
head-down bed rest [29], suggesting that multiple factors are
involved in the process.
A common cause of reduced dietary intake during the first
days of a mission [16] is space motion sickness [30]. However,
the effects of space motion sickness typically pass after the
first several days of space flight, and the decrease in dietary
intake often extends far beyond this time [5]. Moreover, anec-
dotal reports of appetite vary significantly, as indicated in a
Russian study in which 40% of the Mir crewmembers reported
decreased appetite, 40% reported no change in their appe-
tite, and 20% reported experiencing increased appetite [31].
Other spaceflight-related changes in gastrointestinal func-
tion are also possible. Fluid shifts, combined with reduced
fluid intake, would tend to decrease gastrointestinal motility.
Although transit time has not been systematically studied in
space flight, 10 days of 6-degree head-down bed rest signifi-
cantly extended the mouth-to-cecum transit time relative to the
transit time during ambulatory control periods [9]. Additional
information regarding gastrointestinal function can be derived
from Russian studies of humans and animals conducted dur-
ing actual and simulated space flight [32].
Developing foods for space flight has proven a significant
challenge from the earliest days of the crewed space program
[3335], yet the design criteria have changed little [36]. The
food systems used on the Space Shuttle and those that were
used on the Russian Mir station are entirely shelf stable and
are composed mainly of rehydratable or thermostabilized
food items [37]. Although these foods are known to be less
palatable than fresh or frozen foods, ground-based studies
have shown that the Space Shuttle food system (Figure 27.3)
can adequately support nutritional requirements [38]. Skylab
was the only U.S. space program that included frozen foods
[37]; Skylab crewmembers ate essentially 100% of their pre-
dicted [2] energy requirements (Figure 27.2) [5]. Although the
Skylab crews were involved in metabolic studies that required
27. Spaceflight Metabolism and Nutritional Support
Figure 27.4. Examples of International Space Station foods. (Photo
courtesy of NASA)
complete consumption of a prescribed diet [22,39], this finding
nevertheless demonstrates that crews can, when required, con-
sume the recommended amounts of food during space flight.
Hypotheses regarding a crews inability to consume the req-
uisite amount of food because of a sense of stomach fullness
or other factors are therefore not likely to fully explain the
decrease in in-flight dietary intake.
Although we are unlikely to determine whether food con-
sumption on Skylab was related more to the requirement that
the crew consume the food or to the fact that the food was more
palatable, it is difficult to argue against the benefit of palatability.
Clearly, it is imperative that adequate resources to support food
consumption be provided to long-duration spaceflight crews.
A reliable food system must include a variety of palatable
foods and the means to prepare themincluding rehydration,
heating, and cooling. Time for meal preparation, consumption,
and cleanup is another limited resource that often hinders
dietary intake. Plans for the International Space Station food
system (Figure 27.4) at assembly complete should include the
use of freezers and refrigerators for food storage. These items
would provide a more palatable food system, which would
likely increase dietary intake as well as provide the crew
additional psychological support.
Freezers for food are not typically flown in space because
they represent a significant drain on crew resources, on-orbit
volume, and vehicle power. Moreover, frozen food requires
the additional launch mass of frozen food resupply, which
also consumes power, volume, and conditioned stowage on
the resupply vehicle. It is often difficult to balance the intangible
potential increase in dietary intake and psychological support
against tangible dollar and power allocations, both of which
are typically, if not always, constrained.
Body Mass and Composition
Losses of 15% of preflight body mass have been a consistent
finding in the history of space flight (Figure 27.5), with losses
documented on short- and long-duration flights from the U.S.
and the Russian space programs [17,18,35,40,41]. Indeed, all
561
Figure 27.5. Body mass loss after spaceflight. Data are expressed
as percent change from preflight values for each individual. Data are
included from several Shuttle and Mir flights, as well as the three
Skylab missions
crewmembers from the Gemini, Apollo, Skylab, and Apollo-
Soyuz Test Project missions lost body mass [20,21,22,4244].
In a study of 13 male Space Shuttle crewmembers, body
weight losses ranged from 0.0 to 3.9 kg [14]. Body mass loss
also reached 1015% of preflight body mass on the longer
Mir missions [45]. Although a 1% body weight loss can be
explained by loss of body water [13], most of the observed
loss of body weight comes from loss of muscle and adipose
tissue [5,17].
A change in energy expenditure is a commonly proposed
explanation for the loss of body mass in space. According to
early hypotheses, energy expenditure during space flight would
be lower than that on the ground because of relative hypokine-
sia [24]. Lower energy expenditure was observed during extra-
vehicular activities on the lunar surface compared with similar
activities performed at Earth gravity [46]. However, studies
of in-flight, intravehicular energy expenditure demonstrated
that in-flight energy expenditure is unchanged from preflight
levels [14]. More recent studies have even shown an increase
in energy expenditure during space flight relative to preflight
levels, most likely as a result of increased exercise [47]. These
studies, which involved Space Shuttle astronauts, determined
total energy expenditure before and during space flight by
using the doubly labeled water (2H218O) technique [48]. This
noninvasive technique takes into account the energy cost of all
activities over several days. Unfortunately, it does not provide
information about the individual components of total energy
expenditure, including resting, sleeping, and exercising.
Although we can safely assume that less energy is expended
in moving ones body mass around the cabin during space
flight, energy requirements for other metabolic activities
including resting metabolic rate and stressmay increase,
resulting in unchanged total energy expenditure. Bed-rest
studies have shown decreased total energy expenditure with
no change in resting energy expenditure [49]. Since total
energy expenditure during space flight is either unchanged
[14] or increased [47], a bed-rest model may not be appropriate for
562
studies of energy metabolism in space flight, possibly because
of a lack of stress or metabolic response during bed rest. Love-
joy, Smith, Zachwieja, and others have suggested that exog-
enous addition of a metabolic stressor (e.g., triiodothyronine)
provides a better ground-based model for the metabolic effects
of space flight on energy and fuel metabolism than does bed
rest [50].
Fluid and Electrolyte Homeostasis
Fluid and electrolyte homeostasis changes significantly during
space flight [5157]. The hypothesis originally proposed was
that the human body, upon entering weightlessness, would
experience a headward shift of fluids, with subsequent diuresis
and dehydration. A series of experiments has been conducted
to assess fluid and electrolyte homeostasis during space flight.
The most comprehensive stemmed from the two Spacelab
Life Sciences missions flown in the early 1990s [13].
Within hours of experiencing weightlessness, which is
the earliest available data point, crewmembers experience
reductions in plasma and extracellular fluid volume [13], and
fluid redistribution, which produce the puffy faces typically
observed early in space flight [58]. Initially, the decrement
in plasma volume (17%) [13] is larger than the decrement
in extracellular fluid volume (10%) [13]. This suggests that
interstitial fluid volume, the other 80% of extracellular fluid,
is conserved proportionally more than is plasma volume.
Conservation of interstitial fluid volume is supported by rapid
decreases in total circulating protein (specifically, albumin)
[13]. This shift of protein and associated oncotic pressure
from the intravascular to the extravascular space would also
facilitate initial changes in plasma volume [53].
After initial adaptation to weightlessness, the crews extra-
cellular fluid volume decreases (between the first days of
flight and 8 to 12 days of flight) from the initial 10% below
preflight levels to 15% below preflight levels [13]. Plasma
volume is partially restored during this period, from the ini-
tial 17% below preflight levels to 11% below preflight levels
[13], and it remains 10% to 15% below preflight levels even
for extended-duration missions [59].
Huntoon, Cintrn, Whitson, and Smith have hypothesized
that the shift in extravascular protein and fluid is caused by
adapting to weightlessness and that, after several days, some
of the extravascular albumin is metabolized, with a loss of
oncotic force and a resulting decreased extracellular fluid
volume and increased plasma volume [53]. This intravascular
or extravascular loss of extracellular protein and associated
decreased oncotic potential probably plays a role in postflight
orthostatic intolerance, which may result partly from reduced
plasma volume at landing [60]. Further, the loss of protein
may explain why fluid loadinga technique in which space-
flight crews ingest large quantities of fluids before landing to
counter the effects of returning to 1 Galone does not restore
circulatory volume [61,62], since no additional solute load
exists to maintain fluid volume.
S.M. Smith and H.W. Lane
The effect of space flight on total body water has also been
evaluated to assess dehydration. Studies with Space Shuttle
and Skylab astronauts showed an approximately 1% decrease
in total body water during space flight [13,63,64]; the percent
of body mass represented by water did not change. Thus, the
often-proposed weightlessness-induced dehydration does not
exist in spaceflight crews.
Diuresis is typically not observed during space flight
[17,51,52,6568]. Although operational constraints make it
difficult to document urine volumes accurately on the first day
of space flight, on the Spacelab Life Sciences missions urine
volume was significantly lower on the first 3 days of space
flight and tended to be lower than preflight values throughout
the mission [13]. Urine volumes on a week-long mission to Mir
were also less than preflight volumes [67]. On the 59-day and
84-day Skylab missions [39], urine volume decreased during
the first week, and remained unchanged from preflight levels
for the remainder of the missions. Decreased fluid intake most
likely accounts for the decrease in urine volume accompanied
by little or no change in total body water. Diuresis has been
documented in bed-rest studies [69], again suggesting differ-
ences between analog studies and actual space flight.
As mentioned earlier in this chapter, the percent of body mass
represented by total body water remains relatively unchanged
during space flight [13]. On a volume basis, however, the
change in extracellular fluid volume is greater than either the
change or lack of change in total body water. Thus, intracel-
lular fluid volume increases by this difference during space
flight [13]. This fact, which was previously hypothesized from
ground-based studies [70], was observed in postflight studies of
Apollo crews [17]. The mechanism by which space flight would
induce an increase in intracellular fluid volume is unknown.
It is possible that a shift in fuel use results in altered glycogen
storage, a condition known to increase cellular water content.
In summary, available information indicates that the fluid shift
in crews during weightlessness is in fact a shift from extracellu-
lar to intracellular, or from vascular to extravascular. Clearly, a
cephalad shift of fluid occurs, but it does not produce diuresis and
dehydration as was originally hypothesized. The implications
of either an extracellular-to-intracellular or an intravascular-to-
extravascular shift are unknown, but this shift may explain many
of the physiologic phenomena associated with space flight.
Hematology
Decreases in red blood cell mass (Figure 27.6) are consistently
found after short- and long-term space flights [59,7174]. This
spaceflight anemia was observed as early as the Gemini mis-
sions of the 1960s [75]. Although this decrease in red blood
cell mass is significant (i.e., it reaches from 10% to 15% below
preflight levels within 10 to 14 days of space flight), it seems
to be an adaptation to space flight that has no documented
functional consequences. Several theories about the origin of
the phenomenon have been advanced over the years, some of
which have been eliminated and others expanded upon.
27. Spaceflight Metabolism and Nutritional Support
Figure 27.6. Red blood cell mass loss after space flight. Data are
expressed as percent change from preflight values for each individ-
ual. Data are included from Shuttle, Mir, and Skylab missions
A confounding factor in the U.S. space flights conducted
before the Skylab program was the increased cabin partial
pressure of O2 [74]. The possibility of hyperoxia-induced
red blood cell membrane peroxidation was considered [59].
This possibility was ruled out when changes in erythropoiesis
were also observed during Skylab [59,76] and Space Shuttle
missions [72,73], during which the partial pressure of O2 was
similar to that of Earths atmosphere [5,17].
The decrease in the release of mature red blood cells into the
circulation is associated with a decrease in circulating eryth-
ropoietin concentrations. An early hypothesis for the cause of
decreased red blood cell mass was that red blood cell synthesis
was understimulated relative to synthesis on the ground [74].
However, since iron turnover is unchanged during space flight
[72,73], this would seem to indicate that synthesis of hemo-
globin and red blood cells is also unchanged.
During the first several days of space flight, hematocrit is
either unchanged [77] or slightly elevated [7173]. When it is
elevated, the elevation is not as great as would be predicted
in relation to the decrease in plasma volume [13]. The initial
decrease in red blood cell mass occurs at a rate of slightly more
than 1% per day, with an eventual loss of 1015% [7173,78].
Although removal of mature red blood cells from the circula-
tion is unchanged during space flight [72,79,80], the release
of new red blood cells stops on entry into weightlessness
[72,73,78]. In addition, newly released red blood cells, which
are larger than the more mature circulating red blood cells, are
selectively removed from the circulation and destroyed [78].
In-flight changes in body fluid volumes and red blood cell
mass seem to be adaptive and to reach a new plateau after the
first weeks of space flight, as shown by findings from long-term
space flights [5,20,81,82]. The triggering mechanism for these
changes is unknown. The body somehow senses a decreased
requirement for blood volume and adapts accordingly.
563
This adaptation may be related to changes in fluid (circulatory)
dynamics and to reduced gravitational strain on the circulatory
system during space flight.
One consequence of a decrease in red blood cell mass is
that the iron released when red blood cells are destroyed is
processed for storage. This interpretation is based on find-
ings of increased serum ferritin concentrations during and
after both short- and long-duration space flights. Serum iron
concentrations are also normal to elevated during and after
space flight [72,73]. The implications of excess iron storage
during extended-duration space flights are not known. Current
space food systems provide excessive amounts of dietary iron
(20 mg per day) [5], which could lead to deleterious effects
during extended-duration space missions. Absorption of
dietary iron in space has not been studied, but such studies
could alleviate concern about iron overload during extended-
duration space flights. Until such studies are undertaken, a
panel of experts has recommended that the iron intake of male
and female crewmembers be reduced to less than 10 mg per
day during space flight [5,83]. Future studies will allow us to
estimate dietary iron absorption and provide insight into the
nature and extent of the problem.
Another consequence of reduced blood volume and red
blood cell mass occurs after crews return to Earth gravity. It is
at this time that dilutional anemia often occurs [77], with a
disproportionate return of plasma volume before repletion of
red blood cells. For example, a 35% decrease in hematocrit
levels between R + 0 and R + 3 is common after short- or
long-duration space flights [77].
Bed-rest studies have not proven to be suitable models for
studying the hematologic changes of space flight. In bed rest,
red blood cell mass decreases, but erythropoietin is unchanged
and hematocrit increases [84]. This difference suggests that
different mechanisms are operating in space flight and analog
studies. If the reduction in red blood cell mass during space
flight is a result of reduced gravitational load on the circulatory
system, it is reasonable to assume that bed rest alone would
not alleviate these forces but would only reposition them.
Indices of iron metabolism and erythropoiesis return towards
normal within days after landing, although red blood cell mass
replenishment may take several weeks. Efficient postflight
recovery suggests that in-flight anemia represents an adapta-
tion to weightlessness, probably in response to either the easier
delivery of O2 to tissues that are not influenced by gravity or to
the decrease in plasma volume and increase in concentration of
red blood cells during the first few days of space flight.
Protein and Muscle
Exposure to microgravity reduces muscle mass, volume, and
performance, especially in the legs, on long- [20,21] and
short-duration [85] space flights. Muscle biopsy studies
demonstrated postflight decreases in cross-sectional area only
in type II (fast-twitch) myofibers, the fiber type that responds
to resistive exercise [86].
564
In the Skylab missions, potassium and nitrogen balances
became increasingly negative throughout the flights, but uri-
nary creatinine did not change [39,87] despite losses of leg
volume [20,88]. Disuse atrophy of muscles in space flight
may be related to changes in whole-body protein turnover.
A ground-based study [89] demonstrated that whole-body
protein synthesis decreased by approximately 13% during
2 weeks of bed rest and that 50% of this decrease could be
accounted for by the leg muscles. This bed-rest study did not
include exercise but did involve maintenance of body weight
during the bed-rest period. In the same study, excretion of 4-
pyridoxic acid (a vitamin B6 metabolite) increased during bed
rest [90], suggesting that metabolically active muscle tissue
was being lost.
During short-term space flight, studies of stable-iso-
tope turnover indicate that turnover of whole-body protein
increases, with elevations in protein synthesis and even
greater increases in protein breakdown [91,92]. This synthesis
increase was hypothesized by Stein and others to be related to
physiologic stress, as indicated by increased urinary cortisol
levels during space flight [13,93]. These findings are similar
to those found in a catabolic state. Decreased prostaglandin
secretion has also been implicated in muscle tissue loss dur-
ing space flight because of decreases in the mechanical stress
on muscles in weightlessness [93]. On long-duration Mir
flights, on the other hand, investigators noted decreased rates
of protein synthesis [23]. Because protein synthesis correlates
directly with energy intake, the reduced protein synthesis was
probably related to inadequate energy intake [23].
Although evaluation of plasma and urinary amino acids does
not provide a clear index of muscle metabolism, an increase in
plasma amino acids has been noted in cosmonauts after land-
ing [94]. Limited Space Shuttle flight data indicate a tendency
for plasma levels of branched-chain amino acids to increase
during space flight as compared with preflight levels [95] with
little or no change in urinary amino acid profiles [16]. Increases
in the excretion of three amino acid metabolitescreatinine,
sarcosine, and 3-methylhistidine [96] were noted in Skylab
studies, a finding that suggests that the contractile proteins of
skeletal muscle are degraded in weightlessness.
Differences between findings from space flight and ground
studies may result from other variables in addition to the
potential shortcomings of the analog studies. Dietary intake
is greatly different in space flight versus that in ground-based
studies. On the Space Life Sciences missions, consumption
of protein and energy during flight was about 20% less than
levels consumed before flight, which resulted in crewmembers
losing 11.5% of their body mass [92]. Ground-based studies
typically involved prescribed and controlled dietary intakes or
are designed to maintain body mass. Fluctuating stress levels
might explain some of the variability in results from this type of
study, both spaceflight- and ground-based. Spaceflight studies
are often associated with increased stress; although ground-
based studies also have the potential for increased stress, this
is not an entirely consistent finding. As shown in studies of
S.M. Smith and H.W. Lane
energy metabolism, the administration of exogenous thyroid
hormone provides a metabolic stress that in turn produces a
more accurate ground-based model of protein metabolism
during space flight [50].
The exercise protocols used to date have not succeeded in
maintaining muscle mass and strength or bone mass of crews
during space flight. Indeed, on a Mir mission, despite signifi-
cant differences in in-flight exercise frequency and intensity
among crewmembers (owing to mission requirements and
personal habits), losses of leg muscle volume, which were
detected immediately after landing by magnetic resonance
imaging, were almost 20% in all subjects [97]. By comparison,
bed-rest subjects given exogenous testosterone have main-
tained muscle mass and protein balance but muscle strength
remained unchanged [98]. Resistive exercise protocols have
been proposed to help maintain both muscle and bone during
space flight. These protocols have proven effective for main-
taining muscle [99] in short-term bed-rest studies; long-term
studies of bone maintenance have not yet been completed.
Calcium and Bone
The ability to counteract weightlessness-induced bone loss is
critical for crew health and safety during and after extended-
duration space station and exploration-class missions [100
104]. Bone mineral is lost during space flight as a result of
skeletal unloading [105112], thereby increasing the excre-
tion of calcium in the urine [87,108,110]. The loss of bone
and the increased risk of renal-stone formation during and
after space flight [113,114] present significant risks to crew-
member health and safety. In-flight and ground-based analog
studies have shown that the loss of calcium from bones varies
between sites within a subject, and that the nature and degree
of loss over time also varies among subjects [105,115,116].
Long-term follow-up data on bone recovery are lacking, but
as astronauts return from ISS, this data will become available
Negative calcium balance has been observed during Skylab
[39,87,108,110,112,117] and Mir [45] missions. Increased
urinary and fecal calcium excretion accounted for most of
the deficit [39,45,87,108,110,114,118]. During the Skylab-4
mission, calcium losses roughly correlated with loss of cal-
caneal mineral [119] and with increases in the excretion of
hydroxyproline [96].
If the rate at which bone calcium is lost remains constant
throughout a space flight, which is a reasonable assumption
based on collagen cross-link excretion data [45,120],250 mg
of bone calcium are lost per day [45,87,121]. The rate of
postflight recovery, if it is assumed to be constant (which is
a reasonable assumption, based on ground-based [115] and
spaceflight [45] data), is approximately +100 mg/day [45]. By
these estimates, on space flights lasting as long as approxi-
mately 6 months, it will take 2 to 3 times the length of the
mission flown to recover lost bone. The validity of these
assumptions is questionable for longer space flights because
spaceflight data are not available. Nonetheless, this hypothesis,
27. Spaceflight Metabolism and Nutritional Support
which needs data to validate it, has significant implications
as mission durations increase. For exploration-class missions,
the potential for discovering a terrestrial partial gravity force
(e.g., Mars = 0.38 G) that would reduce bone loss, or even
begin recovery, is unknown. Although no data on responses
to partial gravity forces are available, some investigators think
that forces less than 0.5 G are likely to be of little value in
recovering lost bone.
Bone loss is a function of changes in the balance between
formation and resorption. Bone formation, as indicated by
serum concentrations of bone-specific alkaline phosphatase
and osteocalcin, was unchanged during one Mir mission but
was increased at 2 to 3 months after landing [45]. Apparent
decreases in bone formation markers have been noted in some
Mir studies [122,123]. Studies of bone formation in three
Mir crewmembers using calcium-tracer techniques produced
equivocal results [45]. (Formation reportedly decreased in
one crewmember and was unchanged in the other two crew-
members.)
Bone resorption increases during space flight. Urinary
hydroxyproline levels were elevated by 33% over preflight
values after 84 days of space flight [87,96]. Urinary levels
of collagen cross-links, another marker of bone resorption,
are elevated by more than 100% over preflight levels during
space flight [45,120]. Data on the kinetics of calcium tracers
also indicate that bone resorption increases by approximately
50% during space flight [45].
Analog (bed-rest) studies of humans have shown quali-
tative effects on bone and calcium homeostasis that are
similar to those in spaceflight studies, with generally lesser
quantitative effects. These effects include loss of bone mass
[115,124], decreases in calcium absorption [125], increases
in calcium excretion [110,125130], increases in renal stone
risk [128,129], and decreases in serum concentrations of
parathyroid hormone [126] and 1,25-dihydroxyvitamin D
[125,126,131].
According to histomorphometric analysis of bone biopsy
samples, bone formation during bed rest was decreased
[115,120,121], but no changes were found according to
biochemical markers [124,125]. This difference likely reflects
the difference between site-specific biopsy samples versus
systemic biochemical markers as indices of bone formation.
Ambulation after bed rest tends to increase bone formation
[124,125]. With regard to bone resorption, both histomor-
phometric [132,133] and biochemical markers of bone
metabolism indicate an increase in resorption during bed rest
[120,125,134]. Hydroxyproline excretion is elevated during
bed rest [125]. Excretion of collagen cross-links during bed
rest [120,125] is elevated approximately 50% above con-
trol levels; this increase reaches more than 100% during
space flight [45,120]. These data suggest that bed rest may
not produce the same magnitude of bone changes as does
space flight.
The loss of bone and the change in calcium metabolism
in paralyzed individuals, as reviewed by Elias and Gwinup
565
[135], share several similarities with the changes associated
with space flight. In both conditions, serum calcium is either
unchanged [136] or elevated [137] relative to levels in ambu-
latory controls. Concentrations of parathyroid hormone and
1,25-dihydroxyvitamin D are reduced in patients immobilized
because of spinal cord trauma [136], which likely leads to
increased excretion of calcium in the feces [136] and decreased
absorption of calcium from the intestines. Urinary levels of
calcium and hydroxyproline are also elevated [136,138,139].
Although bone loss after spinal cord injury seems to stabilize
after approximately 25 weeks [140], the same cannot be said
for bone loss in space flight, because studies of bone metabo-
lism have not been possible during 25-week missions, and the
limited postflight bone assessments to date do not allow rates
of loss to be calculated.
Circulating levels of 25-hydroxyvitamin D reflect body stores
of vitamin D. The absence of ultraviolet light during space flight,
coupled with the crews decreased consumption of vitamin D,
diminish body stores of vitamin D, as observed during the 84-day
Skylab mission [39] and the 115-day Mir mission [45]. How-
ever, the slight decrease noted in the Skylab mission occurred
despite dietary supplements of 500 international units of vitamin
D per day [39]. Decreases in levels of 1,25-dihydroxyvitamin
D, the active form of vitamin D, were also observed during the
Mir mission [45], but these decreases occurred before signifi-
cant changes were made in vitamin D stores. The decrease in
1,25-dihydroxyvitamin D is believed to be related to decreased
production secondary to decreased parathyroid hormone concen-
trations rather than to increased disposal. Circulating vitamin D
metabolites were investigated on the Spacelab-2 mission aboard
the Space Shuttle and found to be unchanged, although consid-
erable variability was present before flight [141].
Observed changes in the endocrine regulation of bone
metabolism seem to reflect adaptation to the weightless envi-
ronment. Decreases in calcium absorption and decreases in
plasma levels of parathyroid hormone and 1,25-dihydroxy
vitamin D would be the expected physiologic responses to the
presumed increase in bone resorption that occurs as the body
adapts to an environment in which bones bear less weight.
This evidence, as well as the lack of improvement in earlier
dietary countermeasure studies, indicates that supplemental
nutrients (e.g., calcium and vitamin D) will not correct the
problem. However, adequate nutrition is a required compo-
nent in the success of the countermeasures currently being
identified and implemented.
Several nutrients are known to affect bone and calcium
homeostasis, including calcium, vitamin D, vitamin K, protein,
sodium, and phosphorus. The importance of calcium and vita-
min D are obvious, as described in this chapter. Vitamin K
is responsible for carboxylation reactions in osteocalcin. Its
importance during space flight has been the subject of pre-
liminary reports [142], but further study is clearly required.
Sodium also poses a concern during space flight, because
space diets tend to be relatively high in sodium and increased
consumption of sodium is typically associated with hypercalciuria
566 S.M. Smith and H.W. Lane

[11,143,144]. Dietary sodium also seems to exacerbate the cal- Table 27.3. Recommended mineral intake levels for crewmembers
ciuric responses to physical unloading. In one bed-rest study, on missions lasting from 30 days to 1 year.
subjects consuming a low-sodium diet (100 mmol/day) had no Nutrient Recommendation
change in urinary calcium, but subjects on a high-sodium diet Calcium 1,0001,200 mg/day
(190 mmol/day) exhibited hypercalciuria [145]. More detailed Phosphorus 1,0001,200 mg/day
studies of this phenomenon are required to better understand Magnesium 350 mg/day for men
280 mg/day for women
the interaction between dietary sodium and bone loss experi-
Sodium < 3,500 mg
enced during weightlessness. Potassium 3,500 mg
The effect of these and other nutrients in preserving bone Iron 10 mg
during space flight highlights the importance of understand- Copper 1.53.0 mg
ing and maintaining adequate dietary intake. This point will Manganese 2.05.0 mg
Fluoride 4.0 mg
be especially critical, because at this time, the most promis-
Zinc 15 mg
ing countermeasures for bone loss are not nutrients but rather Selenium 70 g
focus on exercise and pharmacologic agents. Iodine 150 g
Chromium 100200 g

Nutrient Requirements
on Mir that food becomes a supportive psychological factor
Nutritional requirements for crewmembers during space for humans in an isolated environment far from home.
flight have been developed and reviewed by several panels Although the question of whether to provide dietary supple-
of experts [5,83]. Planners developed an initial set of nutrient ments to crews is raised often, NASA currently does not rec-
requirements for use on missions aboard the Mir and Interna- ommend the use of nutritional supplements during space flight
tional Space Station lasting from 30 to 120 days [146]. These for several reasons. Experience indicates that crewmembers
requirements were revised when the range of mission dura- do not consume the recommended number of calories, and
tions was extended to include missions lasting from 30 days hence the intake of many individual nutrients is inadequate as
to 1 year [147]. The nutrient requirements for missions lasting well. Unfortunately, the concept of using a vitamin or mineral
up to 1 year are shown in Tables 27.127.3. supplement to remedy this problem is unwarranted, because
It has generally been agreed that crewmembers should the primary probleminadequate food consumptioncan-
obtain nutrients from standard foods as opposed to supple- not be resolved by taking a supplement. This situation can
ments [4,5,77,83]. This is a critical point, as natural foods be exacerbated further if crewmembers conclude that taking a
provide non-nutritive substances such as fiber and carotenoids supplement reduces their need to consume adequate amounts
and are palatable and psychologically satisfying, consider- of food, which may lead to their eating even less. Moreover,
ations that will be important for long-duration missions. The many nutrients, when provided as oral supplements, are not
need for more detailed information about the psychophysiol- metabolized in the same way as are nutrients from food,
ogy of hunger and eating was noted decades ago during the and changes in nutrient bioavailability and metabolism can
early space programs [24], but it has yet to be studied in detail. increase the risk of malnutrition. Vitamin or mineral supple-
It is clear from the experience of astronauts and cosmonauts ments should be used only when the nutrient content of the
nominal food system does not meet the requirements for a
given nutrient, or when sufficient evidence indicates that the
Table 27.2. Recommended vitamin intake levels for crewmembers efficacy of single- or multiple-nutrient supplementation is
on missions lasting from 30 days to 1 year. advantageous.
Nutrient Recommendation
Nutritional requirements for crews in space will need to be
evaluated throughout the evolution of the International Space
Vitamin A 1,000 g of retinol equivalents
Vitamin D 10 g
Station Program. The current requirements have been defined
Vitamin E 20 mg of -tocopherol equivalents largely by extrapolation from ground-based data and from limited
Vitamin K 80 g for men spaceflight studies. As more knowledge is gained from space-
65 g for women flight experience, requirements will be periodically reviewed
Vitamin C 100 mg to assure confidence in their definition. Further, as countermea-
Vitamin B12 2.0 g
Vitamin B6 2.0 mg
sures to the negative effects of space flight are developed and
Thiamin 1.5 mg implemented, assurances will be needed that countermeasures
Riboflavin 2.0 mg do not have secondary effects on nutrient requirements. A simple
Folate 400 g example of such an effect is the implementation of an exercise
Niacin 20 mg protocol that would alter energy requirements. More complex
Biotin 100 g
Pantothenic Acid 5.0 mg
examples include the use pharmacologic agents to alter cardio-
vascular system function or bone metabolism.
27. Spaceflight Metabolism and Nutritional Support 567

The nutrient requirements for exploration-class missions,
when defined, will be still harder to implement in terms of
the need to find a balance among a stored food system, a
regenerative food system, and requests for supplements to
be used instead of food [4]. Conferences have been con-
ducted recently [148] to begin integrating horticultural and
nutritional issues with the initial understanding that neither
a 100% regenerative nor a 100% supplied food system will
be successful. Melding the two systems is a critical, albeit
difficult task. Meeting or supplementing the nutritional
requirements of long-duration spaceflight crews with the
consumption of fresh foods would have several advantages,
including improved palatability as well as the provision of
sufficient potassium, fiber, and antioxidants.
Nutritional Assessment and Implications
of Malnutrition
Maintaining adequate nutrition in spaceflight crews during
long-duration missions requires that healthcare profession-
als periodically assess nutritional status to identify areas of
concern. Assessment procedures should provide information
about crew health and nutritional status during three periods,
namely before, during, and after flight. The purpose of the
assessments is to evaluate the adequacy of each crewmem-
bers physiological nutrient stores before flight, their health
and nutritional status during flight, and the recovery of their
nutrient stores to normal levels after landing. If these proce-
dures are to be effective, means of making real-time corrective
changes to crew diet must be available. These procedures will
also clarify the physiological changes that occur in micrograv-
ity and will be helpful in defining and evaluating countermea-
sures and in developing space food systems.
The nutritional status assessment profile used during
Phase I of the Shuttle-Mir Program included anthropometric,
biochemical, clinical, and dietary assessment components
(Table 27.4) [149]. The biochemical markers are indicators
of protein, bone, mineral, vitamin, and antioxidant status.
Each component contributes valuable information to the total
picture of nutritional status. Assessments of dietary intake
allow possible nutrient deficiencies to be identified from
typical patterns of individual food intake; in this way we may
be able to detect potential concerns through diet evaluation
before biochemical or clinical manifestations of the deficien-
cies present themselves. Early detection allows appropriate
modifications to the diet to be made to correct the deficiency
before impairment or loss of function occurs.
Typically, most research samples are collected during space
flight and stored for analysis after return. This restriction not
only eliminates the possibility of some analyses because of
problems with sample stability and storage, but more impor-
tantly it also delays the ability to identify a problem until, in
many cases, long after the mission has ended. Limited bio-
chemical assessments can be performed during space flight
Table 27.4. Components of nutritional status assessment.
Body mass and composition
Body mass
Body composition
Bone mineral density
Protein status
Total protein (serum)
Retinol binding protein, transthyretin, albumin (serum)
-1 globulin, -2 globulin, -globulin, -globulin (serum)
3-methylhistidine (urine)
Calcium/bone status
25-hydroxyvitamin D, 1,25-dihydroxyvitamin D (serum)
Parathyroid hormone, osteocalcin (serum, total and undercarboxylated)
Calcium (serum total and ionized, urine)
Alkaline phosphatase (serum, total and bone-specific)
Collagen crosslinks (urine n-telopeptide, pyridinoline, deoxypyridinoline)
Antioxidant status
Total antioxidant capacity (serum)
Superoxide dismutase (serum)
Glutathione peroxidase (serum)
Malondialdehyde (urine)
4-hydroxy-alkenal (urine)
8-hydroxy-deoxyguanosine (urine)
Iron status
Hemoglobin, hematocrit (whole blood)
Mean corpuscular volume (whole blood)
Transferrin, transferrin receptors (serum)
Ferritin, ferritin iron (serum)
Mineral status
Mineral profile
Serum: iron, zinc, selenium, iodine
Urine: iron, zinc, selenium, iodine, phosphorus, magnesium)
Ceruloplasmin (serum)
Fat-soluble vitamins status
Vitamin A (serum; retinol, retinyl palmitate, -carotene, -carotene)
Vitamin K (serum; phylloquinone, urinary -carboxyglutamic acid)
Vitamin E (serum; -tocopherol, -tocopherol, tocopherol:lipid ratio)
Water-soluble vitamin status
Transketolase stimulation (erythrocyte)
Glutathione reductase activity (erythrocyte)
Nicotinamide adenine dinucleotide (erythrocyte)
N-methyl nicotinamide (urine)
2-pyridone (urine)
Transaminase activity (erythrocyte)
4-pyridoxic acid (urine)
Folate (erythrocyte)
Vitamin C (serum)
General chemistry
Aspartate aminotransferase (serum)
Alanine aminotransferase (serum)
Sodium, potassium, chloride (serum)
Cholesterol, triglycerides (serum)
Creatinine (serum and urine)
with modified portable bedside blood analyzers or urine dip-
stick technologies [150]. A portable clinical blood analyzer
has been successful in measuring a panel of clinical variables
during space flight [77]. Development of techniques and tech-
nology that would allow more routine on-site testing would
greatly benefit clinical assessments during a mission [150].
Obviously, this type of testing would be even more critical on
planetary missions.
568
Weight loss is a only a gross indicator of inadequate intake
and ill health. Although virtually all crewmembers lose some
weight during space flight [20,21,22,42,43,44], this loss needs
to be monitored carefully to ensure that it does not become
excessive. Since a weight loss of more than 10% of a crew-
members preflight weight is considered clinically significant,
we should attempt to control the situation before a crewmem-
ber reaches that point. By devising a means of determining
body composition, we will be able to distinguish types of tis-
sue loss during space flight so that we can better understand
human adaptation to weightlessness.
Assessment of in-flight dietary intake is critical and
must be done as easily and unobtrusively as possible. The
reliability of such assessments depends on the technique
and the measurement tool. For spaceflight research studies,
detailed records are currently kept using a barcode reader or
related tool [5,13,45]. This method is very accurate, but it is
also very time-consuming. Clinical nutritional assessments,
on the other hand, do not require such detail, but their reli-
ability is a significant concern. As a compromise, we and
others developed a food frequency questionnaire that allows
easy, yet reasonably accurate monitoring of in-flight dietary
intake [151]. The food frequency questionnaire provides reli-
able estimates of the consumption of six key nutrients (water,
energy [calories], protein, iron, calcium, and sodium) that
have been validated in ground-based, closed-system studies
[151]. Crews can complete the food frequency questionnaire
in 10 to 15 min once a week and then telemeter the infor-
mation to the ground. Results are provided to ground-based
medical support personnel, who then make near-real-time
suggestions for altering dietary intake as necessary.
Undernutrition results in the metabolic overuse of body com-
ponents, primarily adipose tissue and muscle, to provide energy
for essential metabolic processes. Inadequate food intake has
consequences for both macronutrient and micronutrient sta-
tus. Adipose tissue is initially mobilized to meet most of the
bodys energy needs, but it cannot be metabolized to glucose
for use by the brain. Instead, visceral and somatic proteins are
metabolized to supply glucose to sustain the brains vital func-
tions. Because the body has no expendable protein reserves,
the depletion of skeletal and vital organ protein mass is sig-
nificant [152]. The consequences of body protein depletion
include impaired performance, increased risk of infections,
and depression [153]. Markers of protein status include serum
protein levels and urinary analytes that reflect the condition of
visceral and skeletal proteins. Suboptimal nutrient consump-
tion has been documented among individuals in confined envi-
ronments, including hospitals, military field operations, and
nursing homes [154157]. As discussed earlier in this chapter,
loss of body mass has occurred during space flight despite con-
sumption of adequate protein and calories [20,40]. Deficits in
aspects of immune system function have also been observed
during space flight [158,159] and may be exacerbated by the
effects of altered protein status. However, clinical manifesta-
tions of such deficits have not been documented.
S.M. Smith and H.W. Lane
Bone loss, as described earlier in this chapter, contributes
to the increased risk of renal-stone formation during and after
space flight [113,114,160]. Measuring urinary levels of col-
lagen cross-links provides the opportunity to monitor bone
resorption easily, without invasive and costly procedures
such as bone biopsies and tracer kinetics studies. Cross-link
excretion also provides information on bone metabolism far
in advance of the changes that can be measured by absorp-
tiometry techniques. Moreover, measurements of collagen
cross-links have several advantages over other bone markers
(hydroxyproline and calcium, for example) in that pyridin-
ium cross-links are formed only in mature collagen and their
excretion reflects the breakdown of the extracellular matrix.
Therefore, the use of cross-links as markers is not confounded
by dietary intake of collagen products [161]. Markers such as
these thus provide tools with which we can assess the efficacy
of treatments intended to reduce bone loss [162,163].
Space flight exposes crewmembers to greater amounts of
radiation, with equivalent doses potentially up to 0.3 Sv [5],
than they would be exposed to on Earth [164]. Radiation causes
cell death, mutation, and oncogenic transformation in mam-
malian cells, either directly by interacting with nuclear DNA
or indirectly by producing free radicals [165]. Free radicals are
generated both from normal metabolism and from exposure to
certain drugs, ultraviolet radiation, cigarette smoke, and envi-
ronmental pollutants. They are highly reactive and can damage
membranes, DNA, and enzymes. Free radicals can also form
in response to increased atmospheric O2 concentrations such
as those encountered during N2 washout (O2 prebreathe) pro-
cedures conducted before extravehicular activities. If the free
radicals are not converted by antioxidants, these compounds
will react with the closest molecule (lipid, protein, carbohy-
drate, or nucleic acid) and alter that molecules structure and
function [166].
Antioxidants, which include -carotene, vitamins A, C,
and E, and antioxidant enzyme systems (e.g., superoxide dis-
mutase, glutathione peroxidases, and catalase), act together
as the bodys defense against free radical damage [167]. The
most effective antioxidants are specific for the molecules that
cause oxidative stress. When resisting oxidants attack cell
membranes, vitamin E reacts with peroxyl and hydroxyl radi-
cals, whereas carotenoids react with singlet oxygen. Vitamin
E radicals can be reduced by vitamin C or glutathione, and
vitamin C is reduced by glutathione [168]. The mechanisms
of cell injury by oxidative stress and the protection of cells
from this injury potentially involve many dietary constituents.
Diets rich in antioxidants (i.e., vitamins A, C, and E and -
carotene) have also been recommended for individuals at high
risk for cardiovascular disease [169]. Evidence is increasing
in support of a role for nutrition in reducing the mortality and
morbidity from diseases linked to oxidative stress, such as
cardiovascular disease and cancer [170].
The fat-soluble vitamins (A, D, E, and K) have many
functions in the body, including serving as antioxidants and
coenzymes. Vitamin D takes part in the absorption of dietary
27. Spaceflight Metabolism and Nutritional Support
calcium and general bone metabolism; vitamin A and its pre-
cursor, -carotene, and vitamin E function as antioxidants;
and vitamin K is required for blood clotting and bone metabo-
lism. The body absorbs and transports these vitamins in the
same manner as other lipids and can store them in the liver
and adipose tissue. Although day-to-day consumption of fat-
soluble vitamins is not as critical as the consumption of other
nutrients, those vitamins are a matter of concern on long-dura-
tion space flights, and excessive intake can lead to toxicity.
Attempts to monitor the status of fat-soluble vitamins dur-
ing space flight should take into account the metabolism of
the individual vitamins. For example, microgravity dampens
endogenous production of vitamin D because the spacecraft
cabin is shielded from ultraviolet light. No information about
in-flight production of vitamin K by the gastrointestinal flora
is available, but consumption of this vitamin in space could be
more important than it is in Earths gravity [5,146,147].
The water-soluble vitamins (thiamin, riboflavin, niacin,
folate, B6, B12, pantothenic acid, and C) act as coenzymes
in many metabolic pathways throughout the body. Although
these vitamins have vastly different functions, they are clas-
sified together because of their solubility in water and their
participation in reactions in the fluid-based compartments of
the body. These vitamins are transported in the bloodstream
and excreted in the urine. In general, since they are not stored
in the body and insufficient intake quickly lead to deficien-
cies, all of these vitamins must be taken daily to maintain
health. Little is known regarding the requirement for these
vitamins during space flight, however [5,11], so monitoring
the status of water-soluble vitamins during extended-dura-
tion space flight is essential.
The food systems used to support space flight are semi
closed systems with a limited number of foods, most of which
are highly processed to extend shelf life. Since water-soluble
vitamins and minerals are frequently degraded, destroyed, or
otherwise removed during food-processing procedures, the
vitamin content of many spaceflight foods may differ signifi-
cantly from that of the raw foods from which they are made.
In a food-processing study, however, no significant degrada-
tion was found when the folate content of freeze-dried food
was evaluated to assess process-related degradation [171].
It is critical that the iron status of crewmembers be assessed
before, during, and after space flight because both iron defi-
ciency and iron excess can lead to clinical problems. Iron
deficiency not only reduces work capacity but also impairs
temperature regulation, behavior, intellectual performance,
and immune system function [172174]. Excessive iron
stores have been associated with ascorbic acid deficiency,
and reductions in ascorbic acid, vitamin A, and selenium tend
to exacerbate iron-induced peroxidation processes [175].
Specific clinical conditions characterized by iron overload
have been well documented, including Bantu siderosis, idio-
pathic hemochromatosis, congenital atransferrinemia, and
variants of thalassemia [176,177]. These pathologic condi-
tions result in severe tissue damage and, frequently, death.
569
The role of iron in several subclinical circumstances in
human disease has also been described. Iron is reported to
be involved in the formation of potentially toxic free radicals
[177180]. Also suspected of involving iron-related radicals
and of specific relevance to space flight are ionizing radiation
and inflammatory immune injury [177]. Free radical involve-
ment subsequent to elevations in iron stores has been linked
to cardiovascular disease and to cancer. Associations between
cardiovascular disease and iron status have been described
in several recent studies [181185]. Although the evidence
is contradictory [186,187], an association has been observed
between increased iron stores (as measured by serum ferritin)
and increased incidence of myocardial infarction [183,185]. In
a prospective Finnish study, increased risk of all types of can-
cer combinedand risk of colorectal cancer in particularwas
associated with high iron stores [188]. A relationship has also
been indicated between lowering iron stores through phlebot-
omy and a subsequent increase in oxidative resistance [189].
These findings suggest that changes that occur in erythro-
poiesis and ferrokinetics in microgravity may have significant
implications for crew health.
In the U.S. and Russian space programs, exercise is used
to counter bone and muscle loss and to maintain cardiovascu-
lar health. Exercise has been implicated in the pathogenesis
of anemias in trained and untrained individuals [190,191].
Relationships among serum iron and ferritin levels and physi-
cal activity have been linked to adaptation to sustained stress
[192196]. Howeverr, the effects of space flight on iron
metabolism and stress are not fully understood, nor are the
effects of space flight-induced changes in iron metabolism or
stress on other physiologic systems. Further, these effects are
likely to be confounded and exacerbated by exercise.
Minerals play important roles in several life processes by
serving as coenzymes, components of hormones, antioxidants,
and components of O2 transport systems. It is essential that
we monitor the status of minerals during extended-duration
missions. A particularly important concern during space flight
is the release of minerals into the circulation coincident with
bone demineralization. Although the release of calcium is
well known, other minerals such as zinc and even lead may
also be released from a relatively quiescent state, with potential
implications for human health.
The foregoing discussion illustrates the fundamental impor-
tance of monitoring the nutritional status of crews to prevent
ill effects from a closed or semi closed food system and from
physiologic adaptation to weightlessness. To this end, NASA
is in the process of identifying potentially problematic issues
associated with food and nutrition for extended-duration
space flight [197]. This project involves identifying risks
associated with the nature of space missions (e.g., isolation,
closed or semi closed food system, and mission duration),
the spaceflight environment (including radiation and micro-
gravity), and the consequences of a lack of countermeasures
and known points of intervention where mitigating factors
can be implemented to avoid outcomes such as malnutrition
570
and unsafe foods. Physiologic changes that may affect nutri-
ent requirements are also to be identified. Inadequacies in the
food systemwhether they arise from technical limitations,
nutritional shortcomings, or inadequate intake by crewmem-
berscan produce serious consequences [197]. Microbial and
chemical food contamination or psychological factors such as
depression can also lead to insufficient food intake. Finally,
more catastrophic events also pose a concern, among them
being food becoming inaccessible after a module depressur-
ization or crop failure on planetary missions. A major goal of
this project is to identify critical questions that define areas in
which further research is required to eliminate or ameliorate
these risks, thereby enabling exploration-class missions.
Countermeasures
Nutrition is often considered a convenient means of counter-
acting the negative effects of space flight on human physi-
ology. Providing additional calcium to prevent bone loss, or
providing protein to prevent muscle loss, has been proposed
as a means of protection; however, this approach generally
has not proven successful. Clearly, adequate nutritional sup-
port is required to provide biochemical building blocks when
effective countermeasures are established. Nutritional require-
ments will also need to be assessed in light of countermeasure
effects to ensure that the solution to one problem does not
create another.
Many countermeasures to ameliorate space flight-induced
bone loss have been tested. However, those tested to date,
including exercise, increased intake of calcium or phosphate,
vitamin D supplementation, exposure to ultraviolet light, and
the administration of early-generation bisphosphonates, have
not proven effective during space flight or bed rest [198202].
Recent studies of resistive exercise paradigms, new anti-
resorptive therapies [203205], and other treatments with
bone-regulating proteins show promise for preventing bone
loss. Ensuring adequate intake or, in some cases, adequate
synthesis of calcium, vitamin D, and other bone-related nutrients
will be necessary; however, this strategy does not seem to be
sufficient to solve the problem of bone loss. Other factors that
may contribute to the degree of calcium loss are age, sex,
fitness, genetic background, and dietary history.
Nutritional means of preventing muscle disuse atrophy
have been evaluated. Oral doses of branched-chain amino
acids had little effect on leg-muscle protein kinetics [206],
whereas feeding a bed-rest group adequate energy with
excess protein reversed loss of N2 [207]. However, feeding
Skylab crewmembers energy and protein at levels equivalent
to those given the bed-rest group did not prevent negative N2
balance and loss of leg muscle strength during space flight
[21,87,88]. It is unclear whether nutritional means beyond
consuming adequate energy and protein would be beneficial
in reducing muscle atrophy. The effect of exercise counter-
measures on energy requirements also needs to be considered
S.M. Smith and H.W. Lane
so that energy balance is not compromised in a futile attempt
to maintain crew health.
Since maintaining adequate intake of all nutrients and
non-nutritive compounds such as fiber is so important, the
use of dietary supplements is discouraged unless absolutely
necessary. At this time, vitamin D seems to be a candidate
for supplementation, because the adequacy of the amount
of vitamin D provided by the International Space Station
food system remains unclear. Antioxidant supplements may
play a role in ameliorating radiation effects on the human
body during space flight, but no hard evidence exists to
substantiate this idea. Concern has been expressed, how-
ever, that use of multivitamin supplements may counteract
a deficiency of one nutrient and simultaneously create an
excess of another (e.g., iron).
Multivitamins are provided to cosmonauts in the Russian
space program, but no information is available on the
frequency of their use. U.S. astronauts can elect to bring dietary
supplements aboard, but they are not required to take any sup-
plement. Under special circumstances, recommendations have
been made to take dietary supplements; for example, crew-
members and support staff who worked in Russia through-
out the winter were advised to take vitamin D supplements to
counteract their limited exposure to ultraviolet light.
Nutrition in Future Missions
The role of nutrition in future space programs will depend on
mission duration and the limitations imposed by available food
systems. The main goal of food-system development from a
nutritional viewpoint is to deliver all of the required nutrients
in palatable foods. Space-based food systems also must meet
the design criteria of the space vehicle or habitat. Using regen-
erative systems for food production will require careful study
to ensure that crewmembers will receive a palatable, nutritious
diet within an acceptable mission risk scenario.
The prospect of interplanetary space flights and surface
settlement missions raises significant issues with respect to
space food systems. The required 3- to 5-year shelf life that
is typical of food types today obviously constrains selection.
Degradation of many nutrients, particularly vitamins, and
oxidation of lipids occur over time and need to be taken into
account. How to balance normally hydrated food and dehy-
drated food stores is an issue that also needs to be addressed
because dehydrated foods are known to be less palatable than
fresh foods. Although the desired ratio of transported to pro-
duced food is also subject to debate, feasibility, palatability,
and mission risk are likely to drive the ultimate decision;
resource requirements and nutritional yield must be balanced.
In-situ-produced food will likely supplement, but not replace,
the stored food system.
Crew interactions during mealtimes are difficult to quantify;
however, mealtimes can provide important periods of relax-
ation and camaraderie. These benefits will become critical on
27. Spaceflight Metabolism and Nutritional Support
extended-duration missions, during which the sense of con-
finement and heavy workloads will probably increase psycho-
logical stress. Various foods that the crew will find palatable
will be needed. Schedules for mealtimes must include time
for food preparation and cleanup activities, as well as for food
consumption. On exploration-class missions, a significant
amount of time will be needed for food processing.
During the International Space Station era, multicultural
issues may arise. Foods from different cultures should be
included in the food system to provide all individuals with a
sense of ownership while also taking into account occasional
food dislikes. Familiarization with the food system before
flight will help mitigate some of these risks, but only within
the constraints of the food system.
A thorough understanding of the effect of countermeasures
on nutritional requirements will be required before flight to
ensure that the station food system will support the crew.
Countermeasures often fall into categories of exercise, phar-
macologic, or dietary manipulations. These will clearly affect
energy requirements, and they may also affect individual
nutrient requirements.
Extended-duration space flights will require nutritional sta-
tus assessments to ensure optimal missions. In-flight monitor-
ing of dietary intake and nutritional status will also be critical
to allow near-real-time mitigation of problems.
Conclusions
Nutrition plays a multifaceted role during space flight.
Although its most obvious function is general health maintenance
through the consumption of required nutrients, the particular
importance of proper nutrition lies in maintaining endocrine
and immune system function, skeletal and muscle integrity,
and hydration status of space flight crews. In addition, inter-
personal interactions during mealtimes build team morale and
enhance productivity. Providing high quality, palatable foods is
imperative for ensuring adequate nutritional intake, and care-
ful assessment is required to monitor the success or failure of
the food system and to ensure crew health. We believe that
acknowledging the full role of nutrition will be critical to the
success of extended-duration space missions.
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Index

A associated infectious disease, 265

Abdominal distress, from expansion of trapped gases within GI biochemical markers, 264
tract, 255 cerebral blood flow, 264
Abdominal sweep, for detecting blood collections in terrestrially Environmental Symptoms Questionnaire (ESQ), 261, 262
atypical locations, 200 high altitude cerebral edema (HACE), 266
Abdominal trauma management, in spaceflight, 134 high altitude pulmonary edema (HAPE), 265, 266
ABV. See Alternobaric vertigo hypoxia and simulated microgravity, 263
Acceleration forces Longitudinal Study of Astronaut Health (LSAH) database, 267
Earth launch and landing loads, 12 medication management, 268
in space flight pathophysiology of, 261
angular acceleration, 1415 physical conditioning, 262, 263
linear acceleration, 1214 respiratory and diurnal effects, 264
radial acceleration, 14 susceptibility, 263
and spaceflight deconditioning, 15 treatment
Acclimatization calcium channel blockers, 267
to environmental hypoxia, 265 carbonic anhydrase inhibitors, 266
for preventing symptoms of high-altitude illness, 261 glucocorticosteroids, 266, 267
for space operations, 456 hyperbaric recompression, 267
strategies to prevent AMS, 262 Acute myocardial infarction, 344
ACESs. See Advanced crew-escape suits Acute radiation syndromes, 501
Acetaminophen drug, 110 ADH. See Antidiuretic hormone
Acetazolamide, 266 Adjustment disorders, 406
ACGIH. See American Conference of Governmental Industrial Adrenal corticotropic hormone, 212
Hygienists Advanced cardiac life support, 117, 118, 145, 345
ACLS. See Advanced cardiac life support Advanced Communications Technology Satellite Program,
ACRV. See Assured Crew Return Vehicle program NASA, 171
ACS. See Acute coronary syndrome Advanced crew-escape suits, 329
ACTH. See Adrenal corticotropic hormone Advanced life support (ALS) pack, 89, 145
Actigraphs, 414 Advanced Trauma Life Support program, 145
Active noise reduction, 526, 528, 530, 531 Advisory Group for Aerospace Research and Development, 523
ACTS. See Advanced communications technology satellite Aeromedical transport and evacuation, risks in, 149152
Acute angle closure glaucoma, 540, 541 AGARD. See Advisory Group for Aerospace Research and
Acute appendicitis, treatment of, 126 Development
Acute care, definition of, 101 Airborne particles and dust
Acute coronary syndrome, 318 Apollo program, 439
Acute hypoxia environment, decontamination, 440441
hyperventilation, 454, 455 lint particles, 440
physiological effects of, 452, 453 properties of, 440
recognition and treatment of, 454, 455 protection and treatment of, 440
symptoms of, 453 smoke detectors, 440
types of, 451 smoke particles, 439
Acute mountain sickness (AMS) sources of, 439
acclimatization, 262 toxicity, mechanism of, 440

577
578 Index

Air contamination, 427 Artemia, 500

Air revitalization system, 437 Arterial gas embolism (AGE), 254
ALARA principle, 512 clinical picture and disposition, 239
Alert somnotype, 414 pathophysiology, 238, 239
Allergic reactions, in crewmembers, 115 Arthralgia, 554
Alpha particles, 479 Artificial atmosphere control system, 446
Alternobaric vertigo, 257 Artificial gravity, 10, 377
Altitude DCS. See Hyperbaric DCS and bioelectric activity, 19
Alveolar gas equation, 448, 449 provisions of, 17
Ambient cabin pressure, 343 Aspirin drug, 110
Ambulatory medical pack, 8994 Assisted reproductive technology, 384
American College of Radiology, 164 Assured Crew Return Vehicle program, 151
American Conference of Governmental Industrial Hygienists, 505 Asthenia, 395, 402
American Heart Association ASTM. See American Society for Testing and Materials
Advanced Cardiac Life Support program, 145 Astronauts
Cardiopulmonary Resuscitation program, 145 flying to low Earth orbit (LEO), 4
American National Standards Institute, 524 genitourinary tract examination, 285
American Red Cross, ATS-3 provision by NASA, 170 hospitalizations, categories for, 144
American Society for Testing and Materials, 523 medical event analysis from, 140142
Amikacin drug, 108 medical screening of
Ammonia Mercury, 61
environment, decontamination, 439 population bias in, 6566
sampling and analysis, 439 selection and requalification examinations, requirements
sources of, 438 for, 64
susceptibility, 439 Ataxia telangiectasia, 493
toxicity, mechanisms and properties of, 438 ATLS. See Advanced Trauma Life Support
Analog populations, medical event analysis from, 140142 Atmosphere revitalization pressure control system, 248, 249
Analog remote medical care systems, 125, 126 Atmospheric functions, 4
Anemic hypoxia. See Hypemic hypoxia Atmospheric pressure, 339
Anesthesia administration, in spaceflight, 134135 Atomic Bomb Casualty Commission. See Radiation Effects
Anesthesia tests, 552 Research Foundation
Angular acceleration, 1415 Automated ventilation, 70
ANR. See Active Noise Reduction Aviation medicine, 3
ANSI. See American National Standards Institute Aviation safety board, 414
Antarctic stations, importance of, 142 Avogadros law, 446
Anterior teeth, fractures, 548549 Avulsion, 549
Anthropometric changes
limb volume changes, 32 B
trunk, changes in, 32, 33 Back pain, in crewmembers, 104
Antidiuretic hormone, 212 Bacterial ulcerative keratitis. See Corneal ulcer
Antiemetics drug, 103 Ballistic vehicles, designing, 151152
Anti-motion-sickness drugs, 362363 Bandwidth influence, on telemedicine program, 165
Antioxidants, 568 Barodontalgia, 255
Apollo mission Barotitis, 255. See also Ear barotrauma
biomedical observations in, 28 Baryons, 479, 484
fractional gravity, 50 Beance Tubaire Voluntaire (BTV) maneuver, 260
gastrointestinal problems during, 112 Bed rest and space flight
human spaceflight activity during, 22 bone mineral loss
lunar dust during, 23 difference in degree, 301
medical kit, 7274 similarity in pattern, 273, 274, 301
Apollo program (U.S.), crew members of, 167 muscle cell decrements, 295
Apollo-Soyuz mission, 182 redistribution of body fluids, 273
Apollo-Soyuz Test Project (U.S.), 168 Behavioral health problems
Apollo spacecraft adjustment disorders, 406
environment control system in, 467, 468 anxiety disorders, 405
radiation exposure in, 510 asthenia, 402
Applications technology satellite-1 (ATS-1), 170 behavioral illness
Armenia project, 171 four-factor concept, diagnosis, 401
ARPCS. See Atmosphere revitalization pressure control system mental status examination, components, 402
ART. See Assisted reproductive technology monitoring, 400
Index
prevention of, 400401
circadian health problems, 398
euphoria, 402404
human-system interface problems
prevention of, 400
work effectiveness, 399
workplace environment, 399
medical disposition, 406407
monitoring of, 396
prevention of
mission training events, 397
psychological tests, Selecting-In, 397
psychosocial support, 397
psychiatric emergencies, 406407
psychotic disorders
hallucinations, 404
organic mental disorders and delirium, 404
treatment for, 405
Benzodiazepines, 405406
Benzoin, 104
Betadine drug, 127
Beta particles, electrons and positrons, 479
Biologically equivalent dose, 475
Biologically weighted dose-equivalent, 476
Biosound genesis II scanner (AERIS) development, by
NASA, 182
Biphasic sleepiness, 414
Bite test, for determining inflammation in apical
tissues, 551
Body mass density (BMD), 297, 298
Body weight, space flight effects on, 32
Bohr effect, 450
Bone anatomy and structure
axial division, 294
cancellous or trabecular bone, 294
compact or cortical bone, 294
Bone density measurements
DEXA and QCT, comparative study for, 296
Gemini and Apollo missions, 296
Bone mineral density (BMD)
calcium balance studies, countermeasures, 298
changes in, during space flight, 38
in-flight countermeasures
astronaut/cosmonaut comparison, 302
challenges for Mars mission, 302
ergonomic spacecraft design, 303
in-flight treatment
exercise devices evolution, 300
resistance exercise, benefits of, 301
postflight treatment, 298
renal stone formation, 298
Bone physiology
remodeling regulation, 295
resorption and formation, 294
Bowel activity, space flight, 4445
Boyles law, 446
Bromotrifluoromethane, 435
Bupavicaine drug, 106
Burkholdera cepacia, 105
Burns, in crewmembers, 108
579
C
Cabin pressure loss rate, 249
Cabin pressurization, 247, 248
Cabin telemetry, 217
CAD. See Coronary artery disease
CAF. See Coronary artery fluoroscopy
Caffeine, in headache treatment, 109
Calcium channel blockers, 267
Canadian astronaut selection, medical disqualification reasons in, 63
Canadian Space Agency, 143, 188
Candida albicans, 502
Carbonic anhydrase inhibitors, 266
Carbon monoxide
clinical presentation
effects of hypoxia, 430
space motion sickness, symptom of, 429
environment decontamination
catalytic oxidizer, 430
palladium catalyst canister, 431
protection and treatment
after exposure, 430
inhalation treatment, 430
sampling and analysis, 430
sources of
catalytic oxidizers, 428
most hazardous, 427
Oxygen generator, 427, 428
Symptoms of Co poisoning, 428
toxicity, effects of
airborne concentration, 429
Coburn-Foster-Kane, 429
CoHb, 428
effects on hemoglobin, 428
lack of warning properties, 429
properties of, 432
Stewart equation, 429
Carbon monoxide and headache, 109
Carboxy hemoglobin, 428
Cardiac abnormalities, 318
flight surgeons, 319
Cardiac and trauma life support, in parabolic flight, 129130
Cardiac defibrillation, 71
Cardiac disease
in military aviators, 318
occurrence of, 321
prevalence of, 317
risk of, 317
mitigation strategies, spaceflight crews, 322, 323
in space flight, 317
treatment of
on exploration-class missions, 346348
in low Earth orbit, 344
Cardiac disorders, in crewmembers, 116118
Cardiac events, prevalence of, 319
Cardiac imaging, phased-array probe for, 194
Cardiac pressure pulses, monitored by, 337
Cardiac rhythms, military aviators, 334
Cardiac sympathetic modulation, 414
Cardiomyopathy, 320
Cardiopulmonary resuscitation, 71, 145
580 Index

Cardiovascular abnormalities, 344 melatonin measurement, 418

Cardiovascular evaluations, periodically, 334 physiological and biochemical markers, 417
Cardiovascular medical care, 322 pineal hormone, 417
Cardiovascular physiology, 317 periodicity spectrum
Cardiovascular risk mitigation, 323 biological functions of, 417
Cardiovascular screening tests photo-period, 417
electrocardiography, 325 sleep and performance in space
electron-beam computed tomography, 328 light therapy, 420
exercise testing, 326 pharmacologic counter measures, 420
nuclide and coronary artery calcium imaging, 327 strategies for, 420
Cardiovascular selection standards, 325 in space
Cardiovascular system, 331 acrophase, 418
baroreceptor reflex, 34 cosinor methods, 418
disqualification standards for astronauts and cosmonauts, 63 Closed head injuries management, in spaceflight, 134
limitations, in crewmembers, 147148 CME. See Coronal mass ejection
volume status and central venous pressure, 332 CMO. See Crew medical officer
in weightlessness CMRS. See Crew medical restraint system
plasma volume loss, 36 CNS. See Central nervous system
short-term and long-term response, 35 CNS syndrome, 501
-Carotene, 568, 569 Coburn-Foster-Kane equation, 429
Carotid baroreceptors, 338 CO2 contamination, in spacecraft, 109
Cefoxitin drug, 126 Colony forming units (CFU), 105
Central nervous system, 310, 365, 430 Colorimetric analysis, for quantifying formaldehyde, 433
Central venous pressure (CVP), 330 Commercial-off-the-shelf (COTS), 168, 176177
microgravity measurements of, 333 Compton scattering, 480
Cephalosporins drug, 114 Congestive heart failure, 338
Cerebral arterial gas embolism, 254 Conjunctivitis, 111
Cerebral DCS, 229, 230 Constipation, in crewmembers, 112
Cerenkov detector, 508 Contingency depressurization, 249
CEV. See Crew Exploration Vehicle Coriolis acceleration effects, 18
Charless law, 446 Corneal abrasion, 542
CHeCS. See Crew Health Care System; Crew health Corneal ulcer
care system diagnosis and treatment, 542
Chemical rockets risk factor for, 541
lofting force, 4 Coronal mass ejection, 485
payload mass and, 9 Coronary angiography, 327
Chemoprotective agents, 504 Coronary artery disease
Chest trauma management, in spaceflight, 134 EBCT for, 184
CHF. See Congestive heart failure mortality rate, 318
Chromosphere, 485. See also Coronal mass ejection predictive value of, 327
Chronic hypercapnia in spaceflight crews, 321
syndromes corresponding to, 461 Coronary artery fluoroscopy, 327
treatment for, 463 Coronary atherosclerosis, 318, 320
Chronic hypoxia Cosmonaut, medical event analysis from, 140142
acclimatization, 455 CPR. See Cardiopulmonary Resuscitation
complex adaptation to, 456 CPTD. See Cumulative pulmonary toxicity dose
Ciprofloxacin drug, 111 C-reactive protein (CRP)
Circadian health problems biochemical markers for, 264
monitoring of, 397 utility of measuring, 318
prevention of, 398 Creatinine, 564
psychotropic medications for, 398 Crew behavioral health
Circadian rhythms crews adaptation, 396
in light environment family stability, role, 392
aboard spacecraft, 419 flight surgeon role, 392
actillume devices, 420 human systems interface issues, 394
digital monitioring system, 420 medical disposition, 406
light illumination, 419 monitoring of, 396
markers of, prevention of, 397
core body temperature, 417 simple model approach, 393
cortisol level, 418 Crew Exploration Vehicle, 139
Index 581

Crew health care system, 82, 143 physiological effects

components of, 89 evolved and trapped gas disorders, 253, 254
crew training on, 98 gastrointestinal (GI) tract barotrauma, 254, 255
onboard diagnostic and therapeutic capabilities, 99 hypoxia and hypothermia, 253
Crew medical officer, 69, 123, 139, 323, 345 sinus barotrauma, 255
cardiac defibrillation, 70 Decompression sickness, 117, 156, 201
training, 98 bubble formation, 224
Crew medical restraint system, 146, 196 cerebral, 229, 230
Crewmembers clinical course of, 231, 232
allergic reactions in, 115 differential diagnosis, 231
biomedical training of, 90 evolved gas disorder, 253
burns in, 108 inert gas uptake and elimination, 225, 226
cardiac disorders in, 116118 intravascular and extravascular bubbles, 224, 225
cross-coupling effects and neurovestibular dysfunction, 18 otologic manifestations of, 259
dental disorders in, 115116 pathophysiology
eye disorders in, 111112 blood, 228
facial fullness, complains of, 31 bubble formation time course, 227
gastrointestinal disorders in, 112113 hyperbaric vs. hypobaric, 226
hand injuries in, 108 musculoskeletal system, 228
headache in, 108110 of peripheral nerves, 230, 231
lacerations in, 104106 of skin bends, 230
medical care of, 69 spacewalkers pressure profile, 226
medicines intake by, 103 spinal, 228, 229
muscular strain syndromes and, 104 treatment
musculoskeletal trauma in, 106108 ground-level oxygen (GLO) breathing, 232, 233
on-orbit medical resources usage by, 101102 hyperbaric oxygen (HBO) therapy, 233
preflight training, 29 neurologic oxygen toxicity, 234
psychological tolerance and mission performance, 10 pulmonary oxygen toxicity, 233, 234
pulmonary disorders in, 114115 treatment table 5 (TT5), 237
radiation exposure and bone mineral loss, 10 treatment table 6 (TT6), 235, 236
respiratory irritation in, lunar dust, 23 type I and type II, 223
selection standards and operational considerations, 5960 Deep vein thrombosis (DVT), in space, 182
skin disorders in, 110 Definitive medical care facility, 139
sleep disorders in, 110 Delirium, 404
space motion sickness, 3132 Dental diagnosis, testing procedures for, 550551
superficial trauma and, 103104 Dental disorders
upper respiratory disorders in, 113114 about traumatic emergencies, 548549
urologic disorders in, 116 advanced caries, 547548
Crew rescue, treaties for, 157158 in crewmembers, 115116
Crew return vehicle, 140 iatrogenic injury, 542, 545
crew compartment design for, 155156 moderate caries, 547
development of, 150151 odontalgia in, 545
environment control and life support system in, 156157 simple caries, 547
limitations in designing, 148149 techniques, use in space flight
Crohns disease, 201 dental extraction, 556557
CRV. See Crew return vehicle dental injection, 555
CSA. See Canadian Space Agency exposed pulp, 556
Cumulative pulmonary toxicity dose, 233 recementing a crown, 556
Cytokines temporary filling, 555
bi-directional interplay with CNS, 310 use of elevators, 557
role in immune function, 309 treatment and management of, 547
Dentin, 560562, 569
D Deoxyribonucleic acid, 417
Daltons law, 446 Department of Defense military criteria standard
DCS. See Decompression sickness (MIL-STD-1472), 523
Decompression Design Reference Missions, 140
orbital debris objects, 249252 Device for orientation and motion environments, 219
physical factors DEXA. See Dual energy X-ray absorptiometry
pressure of stabilization (POS), 253 Dexamethasone, 266, 267
rapid cabin depressurization consequences, 252 Dextroamphetamine drug, 103, 420
582 Index

Diagnostic peritoneal lavage (DPL), 200 Electromagnetic radiation

Dichlorofluoromethane, 436 effects of, 506, 507
DICOM. See Digital Imaging and Communications in Medicine ionizing, 477
Digital Imaging and Communications in Medicine, 164 non-ionizing, 477, 478
Digital radiography, in spaceflight, 135 Electromyography, 413
Distortion-product otoacoustic emissions, 528, 529 Electron-beam computed tomography, 184
Diving medicine, 3 Electrooculography, 413
DMCF. See Definitive medical care facility Emergency medical technician (EMT), 146, 147, 165
DNA. See Deoxyribonucleic acid EMUs. See Extravehicular mobility units
DOME. See Device for orientation and motion environments EMU space suit, 469
Doppler sonography, 329 EMV. See Extravehicular mobility units
Dorsogluteal IM injection, 103 Endeavour, space shuttle, 169
Dose equivalent. See Biologically equivalent dose Endocrine systems
Dose rate effectiveness factor, 476 fluid regulation in weightlessness, 43
Dosimetry. See Space radiation dosimetry monitoring norepinephrine levels, 44
DPOAE. See Distortion-product otoacoustic emissions Endometrial ablation, 386, 387
DREF. See Dose rate effectiveness factor Endometriosis, 382, 384386
DRM. See Design Reference Missions Endometriosis, risk of, 382
Drosophila melanogaster, 500 Endothelial cell, 318
Dual adaptation, 218 Entry motion sickness (EMS)
Dual energy X-ray absorptiometry, 296 clinical and differential diagnosis, 217
Duraprep drug, 127 definition, 211
Dvorine pseudoisochromatic test, 535 epidemiology
Dynamic Soaring Vehicle (DynaSoar) X-20 program, 151 influencing and precipitating factors, 214
time course, 215
E U.S. and Russian space programs, 213, 214
Ear barotrauma in-flight treatment for, 219, 220
eustachian tube (ET) dysfunction laboratory interpretation, electrolytes and harmones, 212
causes and symptoms, 255 microgravity environment of, 212
evaluation techniques, 256 preflight adaptation training, 218, 219
syndromes prognosis, 220
alternobaric facial paralysis, 257 prophylaxis, 218
inner ear barotrauma (IEBT), 257259 Russian cosmonaut Gherman Titov, 212
middle ear barotrauma (MEBT), 259, 260 symptoms of, 212, 214, 215
post-oxygen exposure ear block, 257 Environmental control and life support systems, 154
pressure-related ear block, 256, 257 Environmental health system, 89, 98
EarQ Software, 529 Environmental Symptoms Questionnaire (ESQ), 261, 262
Earth atmosphere, composed of, 445 Erythromycin drug, 111
Earth gravity, 361 Erythropoietin, 563
Earths atmosphere ESA. See European Space Agency
acceleration forces, 27 Escherichia coli, 116, 502
Van Allen radiation belts and external field lines, 21 ESS. See European Space Station
EASI electrode system, 335 Ethylene glycol
EBCT. See Electron-beam computed tomography Apollo space vehicle, 433
Ebullism syndrome CNS effects, 434
clinical picture, 240, 241 environment, decontamination of, 435
description, 239 heat-exchange loops, 433
disposition, 241 oxalic acid, 434
pathophysiology, 240 properties of, 434
ECG. See Electrocardiography protection and treatment of, 435
Echocardiography, LV end-diastolic dimension measured sampling and analysis of, 435
by, 333 sources of, 433
ECLSS. See Environmental control and life toxicity, mechanisms of, 434
support systems triol, 433
E. coli. See Escherichia coli Euphoria
Effective performance time (EPT), 453454 and mania, 402
EHS. See Environmental health system symptoms of, 403
Electrocardiography, 414 treatment for, 403
analysis, 326 European Commission Biomedicine & Health Research Program
monitoring, 322, 334 (U.K.), 187
Index 583

European Space Agency, 152 Focused assessment by sonography in trauma, 199

European Space Station, 152 Formaldehyde
Eustachian tube (ET) dysfunction environment, decontamination, 433
causes and symptoms, 255 irritating compound, 431
evaluation techniques, 256 payload experiments, 431
Exercise treadmill tests (ETT), 325 polymer delrin, 431
Exploration-class missions protection and treatment, 433
cardiovascular illness treatment on, 346 sources of, 431
surgical challenges in, 124125 toxicity, mechanism of,
Extravehicular activity (EVA), 101, 103, 274, 308, 321, 362, 446, 530 airborne concentration, 432
crew members training, 383 molecular mechanism, 432
radiation monitoring, 511 properties of, 432
training, 383 sampling and analysis, 433
Extravehicular mobility units, 252, 340, 383, 451 ultraviolet spectrophotometry, 433
Eye disorders, in crewmembers, 111112 Fracture management, in spaceflight, 134
Framingham risk scores (FRS), 324
F Frenzel maneuver, 259
Farnsworth Lantern Test, 535 Freons and halocarbons
FAST. See Focused assessment by sonography in trauma environment, decontamination of, 436
Fatigue freon leak detection and quantification, 436
anecdotal information, 417 properties of, 436
circadian rhythms, 416 sources of, 435
indication of drowsiness, 417 toxicity, mechanisms of, 435
protective mechanism of, 416
during space flight, 417 G
stress, responses to, 416 Galactic cosmic radiation, 20
Federal Aviation Administration, 449 Galactic cosmic rays, 484
Female astronaut Gamma-scintillation cameras, 184
for long-duration space flights Gastrointestinal disorders, in crewmembers, 112113
avoiding surgery, 387 Gastrointestinal syndrome, 501
KC-135E and DC-9, porcine models, 388 Gastrointestinal tract barotrauma, 254, 255
menstrual cycle, 385 GCR. See Galactic cosmic radiation; Galactic cosmic rays
osteoporosis risk, neurovestibular problems, 385 Gemini spacecraft
preventive concepts, 386 environment control system in, 467
maternal age of, 384 radiation exposure, 509
medical selection criteria, 381382 Gemini VII medical kit, 72, 73
menstruation and hygiene, 384 Gemini VII mission, 419
operational gynecologic considerations, 383 Genitourinary (GU) issues
contraception, 384 glomerular disease, occurrence and prevalence, 286
pregnancy, 383 in-flight management
preflight medical examinations, pregnancy test, 383 Bartholins gland infection, 289
reproductive considerations, 383 epididymitis, 289
selection and disqualification criteria for, 383 prostatitis, 289
space flight considerations pyelonephritis, 288289
endometriosis risks, 384385 testicular torsion, 290
menstrual cycling, 385 urethritis/cystitis infections 287288
prevention concepts, 386387 urinary obstruction/retention, 290
reproductive function and osteoporosis risk, 385386 nephrolithiasis or stone formation
surgical conditions, mitigating, 387 classic signs and symptoms, 278
training, reproductive considerations during, 383 in-flight history and significance, 279
Final transfer protocol (FTP) server, at JSC center, 174 inhibitory factors, 277
Fitzsimons Army Medical Center, 171 physical examination, 279
Flight surgeon, 317, 319, 323 prevalence and recurrence rates, 276
diagnosis and treatment of crewmember, 102 sites of occurrence, 278
ground-based, role of, 101 space flight history of, 279
sleep disorders and, 110 urinary calculi, types of, 276, 277
Fluid shift theory, in motion sickness, 216, 217 spaceflight factors
Flumazenil, 420 body fluid balance, 273
Fluorescein strip test, cornea, 542 bone mineral loss, 273, 274
Fluoroquinolones, 542 Gentamicin drug, 111
584 Index

Gentamycin drug, 126 chronic stress and isolation

Geomagnetically bound radiation, 21 closed chamber studies, 310, 311
Geomagnetically trapped radiation, 482 cytokines, dysregulation effects, 309, 310
Glomerular filtration rate (GFR), 273 delayed-type hypersensitivity (DTH) tests, 311
Glucocorticosteroids, 266, 267 risk of immune alterations, 309
Glutathione, 568 defects in function and impact, 307
Gold salt method, for contaminant monitoring, 465 dysregulation during spaceflight
Goldstone Deep Space Network radars, 249 alterations in cell-mediated immunity, 311
Gravito-inertial acceleration vector, 378 Epstein Barr virus, reactivation analysis, 313
Gravity suit protocol, 342 Health Stabilization Program (HSP) implementation, 311, 314
GT-7 mission. See Project Gemini hypothalamic-pituitary-adrenal (HPA) axis, 313
Gynecologic medical standards, for female astronaut selection, viral reactivation, 313
381382 extravehicular activities (EVAs), 308
Gynecologic selection standards infectious disease development
endometriosis, risk of, 382 adverse effects, 313
mission-specific training, 383 minimization strategies, 314
operational gynecologic considerations inflight vs. postflight changes, 312
menstruation and hygiene, 384 long duration spacecraft problems
pregnancy after space flight, 384 exposure to radiation, 309
pregnancy and contraception, 383 microbial colonies establishment, 308
spacecraft-related risks
H air and water system limitations, 308
Habrobracon juglandis, 500 atmospheric restrictions, 308
HACE. See High altitude cerebral edema life support equipment malfunction, 308
Hadrons, 479 microgravity and particulates, 308
Haldane effect, 450 physical constraints, 307
Hand injuries, in crewmembers, 108 Human research facility (HRF) ultrasound on, ISS program,
HAPE. See High altitude pulmonary edema 186, 190
HBO therapy. See Hyperbaric oxygen (HBO) therapy Human space flight, general physics of, 3
HCN. See Hydrogen Cyanide absolute radiation dose, 10
HDL. See High-density lipoprotein acceleration forces, 11
Headache, in crewmembers, 108110 Earth launch and landing loads, 12
Health Maintenance Facility, for Mars expedition, 125 linear, radial, and angular, 1215
Health Maintenance System, 143 escape velocity, 9
Hearing landing loads, 15
assessment in space, 528530 lofting force, 4
clinical assessment, 524 microgravity and partial gravity, 1519
definition, 521 onboard power generation, technologies for, 11
mechanics, 521523 orbital debris, collision potential with, 89
Heimlich valve, uses of, 129 planetary surface factors, 22
Hematopoietic syndrome, 501 radiation sources, 19
Hemorrhage controlling, methods of, 131 galactic cosmic radiation, 20
Henrys law, 446 geomagnetically bound radiation, 2122
High altitude cerebral edema, 266 solar radiation and solar cosmic particles, 2021
High altitude pulmonary edema surface dust, 2325
periodic breathing (PB), 265 Human-system interface problems, 399, 400
treatment of, 266 Hydrogen cyanide
High-density lipoprotein, 324 chemical and infrared sensors for monitoring, 115
High-energy particles, 480 symptoms on exposure to, 429
Histotoxic hypoxia, 451 use of various physical barriers for removing, 465
HMS. See Health Maintenance System Hydrostatic pressure and weightlessness, 1617
HNE. See 4-Hydroxy 2,3-nonenal 4-Hydroxy 2,3-nonenal, 522
Holter analysis, 321 Hydroxyproline, 565
Hormone replacement therapy, 385 1, 2-Hydroxyvitamin D, 565
Human immune system Hypemic hypoxia, 451
allergic and hypersensitive reactions Hyperbaric DCS, 223, 226, 227, 234
experience and need for research, 315 Hyperbaric hyperoxia, 458, 459
prevention strategies, 314 Hyperbaric oxygen (HBO) therapy, 233
alteration in cytokine production, 312 Hypercalciuria, 565, 566
CD4:CD8 ratio increase, 312 Hypercapnia. See Chronic hypercapnia
Index 585

Hypercarbia International Council on Radiation Protection, 386

causes and prevention of, 460 International Space Station (ISS), 102, 123, 249, 251, 319, 362,
effects of, 461 382, 415, 428, 523, 527, 528
signs and symptoms of, 461, 462 air circulation in, 471
symptoms for, 375 atmosphere control and supply system, 470
Hyperoxia contingency plans for, 66
in aerospace operations, 457 crew health care system (CHeCS) for, 82, 89, 98
oxygen toxicity, 457 crews, medical selection and evaluation standards for, 6265
toxic effects of, 458 EASI lead system, for cardiac monitoring, 335
Hyperuricemia, 268 evacuation estimates for, 145
Hypobaric DCS, 231. See also Decompression sickness exercise countermeasures, 340
Hypobaric hyperoxia, 458 food system in, 561
Hypokinesia, 418, 561 health maintenance system, 8990
Hypothermia, 253 launch window, 7
Hypoxia medical checklist, 72
acute, 451455 medical event classification of, 142143
in acute mountain sickness (AMS), 263, 264 medical requirements for, 154
chronic, 455, 456 medical restraint system, 70
in decompression, 253 minimum care standards, medical capabilities for, 146
normobaric vs. hypobaric, 263, 264 orbital inclination of, 6
Hypoxic acclimatization, for space operations, 456, 457 oxygen production in, 472
Hypoxic cornea, 538, 539 radiation exposure, 510
Hypoxic hypoxia, 451 surgical capability for, 125126
Hypoxic ventilatory response, 452 International Space Station program, 163, 566
crew medical restraint system (CMRS), 197
I HRF ultrasound on, 186, 190
Ibuprofen drug, 110 local area network, provision for, 173
ICRP. See International Commission on Radiological Protection L12-5 ultrasound probing, 193
Ideal gas laws, 446 medical data communication systems, 174
IE-DCS. See Inner ear decompression sickness medical data management in, 172
Imipenem drug, 108, 113 preflight imaging study, 188
Immune system. See Human immune system Russian segment of, 174
Impedance threshold device (ITD), 343 S-band system use, 173
In-flight exercise, 341 video baseband signal processor (VBSP), 185
In-flight imaging (1982), 181 Internet, in telemedicine program, 163
In-flight management of GU problems Interplanetary transit times, operational factors affecting, 10
Bartholins gland infection, 289 Intracorneal ring technique, 539
epididymitis, 289 Intracranial pressure measurements, 264
prostatitis, 289 Intramuscular (IM) injection, 103, 118
pyelonephritis, 289 Intraocular lens implantation, 539, 540
urethritis/cystitis infections Intraocular pressure, 540
community acquired organisms, 288 Intraocular pressure rise, microgravity
symptoms and signs, 287 clinical significance of, 540
treatment, 288 mechanism of, 540
urinalysis as clinical indicator, 287 treatment for, 540, 541
urinary obstruction/retention, symptoms, causes and treatment for, 290 Intrathoracic gas, 238
Inflight physical performance Intrathoracic trauma, 238
exercise tolerance, 41 Intravascular coronary ultrasound, 320
heart rate and stroke volume, 42 Intravenous catheterization, 118119
oxygen uptake, 4142 Intravenous fluid therapy, 71
Inner ear barotrauma (IEB) Ionizing radiation, spacecraft
composition, 257 acceleration and vibration, 500
implosive injury mechanism, 258 acute cellular and molecular effects of
irreversible hearing loss, 259 cell membrane damage, 493
Inner ear decompression sickness, 259 cell sensitivity, 490
Inspired Partial Pressure, 448 DNA damage, 491494
Integrated medical system (IMedS), 344 epigenetic effects, 493
Crew Health Care System, 345 acute response to, 501, 502
International Civil Aviation Organization, 445 acute tissue and organ specific effects of, 494497
International Commission on Radiological Protection, 489 biological effects of
586 Index

Ionizing radiation, spacecraft (Continued) Linear acceleration, 1214

animal model study, 490 detection thresholds for, 365
medical exposures, 489, 490 Linear energy transfer, 476
nuclear weapons, 489 Linear G field, for interplanetary flight, 18
occupational exposures, 488 Lithium-perchlorate, 108
chronic effects of Locomotor coordination test battery, 372
cancer, 497, 498 Locomotor oculomotor interaction, assessment of, 372
cataracts, 498, 499 Longitudinal Study of Astronaut Health, 143, 174
nervous system, 499 Low-density lipoprotein, 324
skin, 498 Low Earth Orbit (LEO), 106, 139, 181, 182, 475
clinical management, 502, 503 cardiovascular illness treatment, 344
clinical manifestations, 500, 501 ground track of spacecraft in, 8
immune function changes, 499, 500 medical capabilities for, 147
natural sources of, 481, 482 medical evacuation from, 157158
toxic vehicular agents, 500 orbital debris, 9
IOP. See Intraocular pressure Lower-body negative pressure, 321, 343
Ischemic hypoxia, 451 caudal fluid shift induced by, 343
Isobaric-differential pressurization system, 247, 248 termination criteria for, 344
Isobaric pressurization system, 247 LSAH. See Longitudinal Study of Astronaut Health
Isotonic fluid-loading, 342 Lunar dust, chronic pulmonary diseases due to, 23
Isotope-dilution technique, 332 Lunar Mars life support test, 431
ISS astronaut, 319 Lunar mission, radiation assessment, 513, 514
Lunar regolith, 23, 500, 513, 514
J Lung parenchyma, visualization of, 182
J2000 Inertial Reference Frame, 6
Johnson Space Center Aerospace Medicine Board, 382 M
Johnson Space Center (JSC), 102, 103, 167, 393, 396, Macrolides drug, 114
418, 431 Magnetic resonance imaging usage, for space medicine, 184
ACTS program use by, 171 Magnetoplasmadynamic engines, 10
space medicine development, by NASA, 174 Maneuverable Entry Research Vehicle, 151
Just-in-time concept, 164 Mania, euphoria and development of, 402403
Manned Orbital Laboratory, 151
K Mars
Klebsiella pneumonia, 502 atmosphere, 514
Ku-band system, for data communication, 169, 173 communication, 164
Kurtotic noise, 522 expedition
Kvant-1 module, 428 future perspective for surgical care in, 135
medical care system for, 124
L medical transport and evacuation, 158
Lacerations, in crewmembers, 104106 surgical capability for, 125126
Lactamase penicillins, 114 flight mission for, 9
Lagrangian points and payload, 9 gravitational effects on osteoporosis, 303
Laminar airflow device, in parabolic flight, 128129 microgravity and Martian gravity, 303, 304
Laparoscopic surgery, in space flight, 130131 radiation assessment for, 513, 514
Laparotomy, 387388 surface dust on, 24
Laser in situ keratomileusis (LASIK), 539 Marshall Space Flight Center (Huntsville), 174
Laser surgical techniques, 128 MASH. See Mobile Army Surgical Hospital
Launching to orbit McMurdo Station, medical evacuation in, 142
from higher latitude sites, 5 Medical assessment testing, for flight crews, 60
lofting force, 4 Medical care delivery, in space, 163
Launch window, 6 Medical equipment in space flight, lack of, 132
LBNP. See Lower-body negative pressure Medical imaging, in space
LBNP device, 343 altered gravity implication for, 189190
LDL. See Low-density lipoprotein application, 182
Left ventricular (LV) cardiac chamber volume, 332 endoscopy techniques for, 184185
Leptons, 478 history of
LET. See Linear energy transfer echocardiographic series development (U.S.), 182
Lidocaine drug, 106, 117 in-flight imaging, 181
Lifting body spacecraft, development, 151 Soviet-French research study, 181
Limb volume, space flight effects on, 32 limitations on, 197198
Index 587

magnetic resonance imaging (MRI), 184 Microbiology hardware, 89

nuclear imaging techniques, 184 Microgravity, 15
optical imaging, 185 body fluid redistribution, 273
patient positioning techniques, 197 bone mineral density loss
radiography for gastrointestinal pathology, 183 artificial loading of the bone, 300
ultrasound imaging use, 185186, 191194 exercise devices evolution, 300
Medical restraint systems ISS astronauts recovery, 297
cardiac defibrillation and cardiopulmonary resuscitation, 71 Mir cosmonauts recovery, 297
cardiac drug kit, 78, 82 cephalic fluid shift, 374
contingency respiratory capability, 71 comparative study of BMD, 297, 298
features of ideal, 70 effect on carotid baroreceptor, 338
injection fluids, 71 effect on venous vascular system, 331
microbiology and radiation hardware, 89 eye-head coordination, 361
pressure-driven ventilator, 70 functional loading, 293
Medical screening herniated nucleus pulposus (HNP), 299, 304
after crew selection, 5960 human response to, 16
mercury astronaut candidates, 61 influence on
mission-specific, 65 buoyancy and sedimentation, 16
NASA astronaut program and Canadian convection, 17
astronaut selection, 6265 hydrostatic pressure, 1617
operational considerations, 60 medical examination techniques under, 70
select-in vs. select-out concepts in, 6061 muscle loss, 299
Medical standards oculomotor effects, 367, 374
astronaut specific, 61 postural and gait effects of, 369, 370
for future space exploration sensory illusions in, 361
intensive medical evaluation, 67 space motion sickness, 363
onboard medical facilities, 66 spinal lengthening, 299
Russian and U.S. cardiovascular standards, 62, 63 surgical care in
for spaceflight candidates selection, 59 atmospheric contamination, 130
waiver process, 65 capabilities of, 125
Medical support system first aid equipment, 89, 9598 challenges in, 123
Medical systems future perspectives of, 135
of spacecraft, 7278 issues for, 124
of space shuttle, 73, 777982 limitations to, 132133
of space stations surgical researches, 126131
International Space Station, 82, 8990 surgical techniques for, 387
Mir space station, 78, 82, 8489 vestibular function, 373, 374
Medical transport and evacuation, in spaceflight, 139 Midazolam, 420
aeromedical transport, risk for, 149152 Middle ear barotrauma (MEBT)
anthropometric requirements in, 152153 pressure-related hearing loss, 259
crew return vehicle, medical requirements for, 154157 Tonybee and Edmonds maneuver, 260
deconditioned crewmembers, pathophysiology, 146148 treatment of, 260, 261
epidemiological risk analysis for, 140144 Valsalva and Frenzel maneuver, 259, 260
from LEO, 157158 Military pilots, screening for, 64
for Moon and Mars expedition, 158 Mir space station, 103, 168, 470
patient accessibility and treatment capabilities, 153154 cosmonaut, medical event analysis from, 140142
psychological deconditioning of crewmembers, 148 mission for, 525, 526
risk analysis based on evidences, 140 supplemental medical kit
standards of, 144146 components of, 82
Melatonin drug, 110, 398 training, 98
Mercury astronaut, medical screening tests of, 61 Mobile Army Surgical Hospital, 145
Mercury medical kits, 72 MOL. See Manned Orbital Laboratory
Mercury spacecraft Monophasic sleep pattern, 414
cabin pressure, 466 Moon expedition, medical care
environment control system in, 466, 467 systems for, 124, 140, 158
radiation exposure in, 509 Motion Picture Experts Group (MPEG), 165
MERV. See Maneuverable Entry Research Vehicle Motion sickness
Mesenteric ischemia, in crewmembers, 112 anatomy and physiology
Metronidazole drug, 113 central neural connections, 215, 216
Microbial content, in spacecraft, 105 vestibular system, 215
588
Motion sickness (Continued)
etiology
fluid shift theory, 216, 217
sensory conflict theory, 216
MRI. See Magnetic resonance imaging
MSMK. See Mir supplemental medical kit
Multicast backbone (MBONE), 170
Muscle loss countermeasures
pharmaceutical measures, advantages/disadvantages of, 303
physical measures
artificial gravity, 302
ergonomic spacecraft design, 303
resistive exercise developments, 302
Muscle strain and overuse syndromes, in crewmembers, 104
Musculoskeletal response
connective tissue changes, 299
in-flight muscle loss, 299
influence of mechanical forces, 293
Musculoskeletal system, 38
limitations, in crewmembers, 147
Musculoskeletal trauma, in crewmembers, 106108
Myofascial pain dysfunction, 553
Myopia, surgical procedures
intracorneal ring technique, 538, 539
intraocular lens implantation, 539, 540
LASIK, 539
photorefractive keratectomy, 539
radial keratotomy, 538, 539
N percutaneous nephrolithotripsy, 283
Nasopharyngeal congestion, in astronauts, 113
National Aeronautics and Space Administration (NASA), 418
Advanced Communications Technology Satellite (ACTS)
program, 171
astronaut selection procedure, 62, 65
biosound genesis II scanner (AERIS), development of, 182
crew return vehicle
development and capabilities, 150153
medical requirements for, 154157
database development by, 199
design reference missions of, 140
ground-based simulation program, 195
high-altitude physiologic training, 383
lifting body spacecraft, 151
longitudinal study of astronaut health, 66
medical devices communication system, 173174
medical operations risk study, 143, 144
microgravity program, 124, 126
Mir program, 213, 220, 428
heat stress, 274
Reduced Gravity Program, 387
remote guidance of, 197
Spacebridge to Russia project, 171
space medicine, 174
and NEDU, 201
strong angel humanitarian relief exercise, 172
terrestrial telemedicine project, 170
ultrasound imaging, 186
for pneumothorax treatment, 199
video baseband signal processor (VBSP) testing by, 185
Index
National Council on Radiation Protection and Measurements, 382,
386, 489
National Electrical Manufacturers Association, 164
National Institute of Health, 523
National Science Foundation, 140
National Sleep Foundation, 414
National Television Standards Committee (NTSC), 165
Navy experimental diving unit, 201
NCRP. See National Council on Radiation Protection and
Measurements
Necrosis
acute apical abscess, 550
acute apical periodontitis, 550
partial, 549
total, 549550
NEDU. See Navy experimental diving unit
Nephrolithiasis, 44
in astronauts
inflight management, 284
preflight management, 283, 284
preventive measures in flight, 284
risk profile and lifestyle, 281
space flight history of
factors for increased risk, 280
risk assessment and countermeasures, 280
Russian space programs, 279
space shuttle flights, 279
treatment of renal stones
extracorporeal shock wave lithotripsy (ESWL), 282
Neural integrator, 369
Neural plasticity, 368
Neural receptors, 331
Neurological countermeasures, 376
Neurologic dysfunction, 239
Neurologic function rating scale, 374
Neuromotor dysfunction and assessment, 366
Neurovestibular symptoms, 366
Neurovestibular system, 361
adaptation, operational concerns due
extravehicular activity, 362
spacecraft reentry and landing, 362
unaided vehicle egress, 363
dysfunction, spaceflight adaptation, 363
RMS operations, 362
visual vestibular ocular reflex, 361
Neurovestibular system limitations, in crewmembers, 147
Neutral buoyancy, surgery in, 126
NIH. See National Institute of Health
NIHL. See Noise induced hearing loss
NIPTS. See Noise induced permanent threshold shift
Nodal regression, 7
Noise induced hearing loss, 523, 524, 529, 530, 532
Noise induced permanent threshold shift, 531
Noise, spacecraft
countermeasures to, 530, 531
criterion for, 521
environmental factors, effects of, 530
hearing assessment, 524
level, 521
Index
pathophysiology of, 522, 523
and performance, 523, 524
physiologic effects of, 521
specification of, 525
threshold shift, 522, 523
types, 522
Nonionizing radiation effects
on eye
risks associated, estimation of, 505, 506
symptoms and treatment, 504, 505
VIPOR study, 506
on skin, 506
Non-rapid eye movement, 413
Normobaric hyperoxia, 458
Noxious compounds
environment, decontamination, 438
properties of, 438
sampling and analysis, 438
sulfurous compounds, sources of, 437
susceptibility, 438
NREM. See Non-rapid eye movement
NSF. See National Science Foundation
Nuclear thermal rocket engines, 10
Nutrient imbalance
bone resorption and endocrine regulation, 565
erythropoiesis and ferritin levels in, 563
fluid and electrolyte homeostasis, 562
in muscle and protein, 563564
O PEEP. See Positive end-expiratory pressure
Obsessivecompulsive disorder, 405
Occupational Safety and Health Administration, 512
Ocular abnormalities
acute angle closure glaucoma, 540, 541
bacterial corneal ulcers, 541, 542
cephalad fluid shift, effects, 540
corneal abrasions and foreign body, 542
myopia, surgical procedures, 538540
Oculomotor dysfunction, 368
OKN. See Optokinetic nystagmus
Onboard medical facilities, space expeditions, 66
On-orbit medical resources, 101102
Optokinetic nystagmus, 368
Optokinetic stimulation, 368
Oral rehydration, 341
Orbit
body in, basic elements of, 7
inclination of, 56
node of, 7
payload, 5
Orbital debris, 89
collision effects, 250
composition of, 249
from fragmentation, 249, 250
hypervelocity impact testing, 251
Orbital flight, cardiovascular issues for, 331
Orbital space flight, 344
Orbital space plane, 139
Orbiter communications adapter (OCA) system, 168
Organic mental disorders, 404405
589
Orthopedic injuries, treatment of, 134
Orthostatic intolerance, 212, 327, 336, 338
heart rate responses and plasma volume, 48
in postflight period, 47
OSHA. See Occupational Safety and Health Administration
OSP. See Orbital space plane
Otoacoustic emissions
advantages and clinical utility of, 529
Minimum Audibility Test, 529, 530
types of, 528
Otolith asymmetry hypothesis, 217
Otolith tilt-translation reinterpretation (OTTR) hypothesis, 216
Otoscope, 170
Ottawa ankle rules, 107108
Oxyhemoglobin dissociation curve, 449, 450
Oxymetazolone drug, 113
P
Pan American Health Organization, ATS-3 provision by NASA, 170
Panic disorder, 405
Parabolic Flight Program, surgical techniques and findings, 126
Parathyroid hormone, 565
Parenchymal blood flow, 337
Partial gravity
and linear G field, 18
locomotion in, 22
sustained, importance of, 17
Patent foramen ovale (PFO), preflight screening for, 202
PCWP. See Pulmonary capillary wedge pressure
Penicillins, 114
Periodic fitness examinations (PFE), 325
Periodontal probing test, 551
Permanent noise-induced sensorineural hearing loss. See Permanent
threshold shift
Permanent threshold shift, 522, 525, 530, 531
Perturbation forces, 8
Phased-array probe, for cardiac imaging, 194
PhenDex, 218
Photoconjunctivitis and photokeratitis. See Snowblindness,
causes of
Photoelectric effect, 480
Photons, 479
Photorefractive keratectomy, 539
Physical examination, in weightlessness, 3334
Pions, 479
Pittsburgh knee rules, 108
Planetary surface dust, 500
Plaque calcification, 318
Plasma aldosterone, 212
Plasma osmolality, 341
Plasma proteins, 332
Platelet glycoprotein, 344
Pleural fluid, on earth, 189, 190
PMC. See Private medical conference
Pneumopericardium, 254
Pneumoperitoneum diagnosis, by sonography, 200
Pneumothorax, 199
Politzerization, 260
Polysomnography, 413
590 Index

POS. See Pressure of stabilization Radiation environment, in low earth orbit

Posigrade launch, 5 galactic cosmic rays
Positive end-expiratory pressure, 114 consists of, 484
Positive predictive value, 317 magnetic field effect of sun on, 485
Positron emission tomography (PET), 186 geomagnetically trapped radiation
Positron-emitting isotopes, 184 particle consists of, 483
Post-bailout motion sickness, 362 regions of, 482
Postflight ataxia, 370 solar flares, 485
Postflight muscle pain syndrome treatment solar particle events
exercise countermeasures, 301 effects of, 485
exercise devices evolution, 300 energy spectra of, 486
low back pain, 299300 Radiation environment, outside low energy orbit, 486487
plantar fasciitis, 300 Radiation exposure, spacecraft
Postflight neurovestibular symptoms, 363 Gemini, 509
Postural equilibrium, postflight, 370, 371 ISS, 511
PPV. See Positive predictive value limits and medicolegal aspects, 511, 512
Preflight medical examinations, 383 Mercury, 509
Preflight screening, for patent foramen ovale (PFO), 202 occupational health aspects, 512, 513
Preflight vestibular-adaptation training, 218, 220 Shuttle/Mir program, 510
Premature ventricular contractions, 320 Skylab, 510
Pressure space shuttle, 510
alveolar gas exchange, 447 Radiation hardware, 89
change with altitude, 446 Radiation interaction, with target atoms
off-nominal event, 447 neutron interaction, 481
units of, 447, 448 photon interaction, 480, 481
Pressure-driven ventilator, 70 track structure on, 481
Pressure gradient, 331 Radiation sensitizers, 503
Pressure of stabilization, 253 Radiography for gastrointestinal pathology, in space, 183
Private medical conference, 101, 102 Radioprotective agents, 503, 504
PRK. See Photorefractive keratectomy Rapid eye movement sleep, 413
Probability of No Penetration (PNP), 251 RBE. See Relative biological effectiveness
Project Gemini, 167 RCS. See Reaction control system
Project Mercury (U.S.), 167 Reaction control system, 140
Promethazine drug, 103, 118, 218220 Red Cross Medication, 548
Propulsion concepts, relative performance characteristics of, 10 Reissners membrane, 258
Prostaglandin, 564 Rejection criteria, cardiovascular, 326
Prostate specific antigen (PSA), 286 Relative biological effectiveness, 475
Protein synthesis, 564 REM. See Rapid eye movement sleep
Pseudomonas aeruginosa, 502, 542 Remote manipulator system (RMS), 362
Psychological deconditioning, in crewmembers, 148 Remote sensing, for planets, 182
Psychosis, 404 Renal stone risk index assessment (RSRI), 281
Psychosocial stressors, long duration crews, 391 Renal system
PTS. See Permanent threshold shift fluid regulation in weightlessness, 43
Pulmonary artery pressures (PAP), 267 nephrolithiasis, 44
Pulmonary bullae, 254 Reserve time, acute hypoxia, 454
Pulmonary capillary wedge pressure, 339 Respiratory minute ventilation, 429
Pulmonary disorders, in crewmembers, 114115 Respiratory system
Pulmonary edema, 240 changes in, space flight, 37
Pulmonary emboli, 230 in weightlessness, 3738
Pulmonary over-inflation syndromes, 254 Right lower quadrant pain (RLQ), 200201
PVCs. See Premature ventricular contractions RMV. See Respiratory minute ventilation
Rotating crew module, gravity gradient in, 18
Q RSA. See Russian Space Agency
Quality factor (Q), 475 Russian crew return vehicle, capabilities of, 152153
Quantitative Computed Tomography (QCT), 296 Russian medical support system, 89
Quantum. See Photons Russian Orlan space suit, 462, 463
Russian Soyuz, 152
R Russian Space Agency, 188, 527
Radial keratotomy, 538, 539 Russian spaceflight program, 396
Radiation Effects Research Foundation, 489 Russian space station, 394, 419, 428
Index 591

Russia space program environment control system in, 468

ISS segment in, 174 radiation exposure, 510
telemedicine program, 163, 168 Sleep
Internet based, 171 autonomic functions, 414
disorders, in crewmembers, 110
S physiological function
SAA. See South Atlantic anomaly alpha rhythm, 413
Sabatier process, for reducing CO2, 460 EEG characteristics, 413
Sabatier reactor, 471 sleep spindle and K-complex, 413
Saccade slow-wave sleep, 413
for acquiring objects in peripheral visual field and scan REM sleep characterization, 414
instruments, 361 sleep-wake detection algorithms, 414
oculomotor effects of microgravity, 367 in space, 415
Salyut mission, 168, 525, 526 stress, 414
Salyut-6/7 orbital complex, 181 temporal structure of, 414
Salyut space station, 470 types of, 414
Salyut-T6 orbital complex, 181 Sleep-shift protocols, 420
Saturn V Apollo Lunar vehicle, 5 Sleepy somnotype, 414
S-band system SMAC. See Spacecraft maximum allowable concentration
space-to-ground communications capabilities, 173 Snowblindness, causes of, 504
used in Space Shuttle and ISS communications, 488 Solar cosmic rays, 20
for voice conferencing, 169 Solar flares, 485
ScopeDex, 218 biphasic solar cycle, correlation with, 21
Scopolamine drug, 103 blast wave, 20
SCR. See Solar cosmic rays Solar magnetic activity, effects of, 7
SCRAM. See Simplified Crew Rescue Alternative Module Solar particle events
Scuba-related gas embolism, 239 exposures affect on human body, 475
Seizure disorder, operational considerations for, 60 galactic cosmic radiation and potential exposures from, 482
Sensory conflict theory, in motion sickness, 216 radiation exposure rate during, 386
Sensory illusions, due to loss of spatial orientation, 361 Solar wind and GCR, 20
Sensory-motor systems, as mechanism used to recalibrate, 368 SOLUS-3D project (U.K.), 187
Sensory organization test, 371 Sonographic equipments, development pf, 135
Shift gaze, oculomotor control for, 361 Sorenson drainage system, 129, 130
Shuttle-Mir flights bone mineral loss, 274 SOT. See Sensory organization test
Shuttle-Mir Program, 567 Sound pressure level
radiation exposure, 510 on flight deck, 416
Shuttle mission (STS-40), 525 mechanics of hearing, 521
Shuttle Orbiter medical system real-time measurements of, 528
components of, 73, 7982 South Atlantic anomaly, 22, 483, 484, 495
space motion sickness kit, 78 Soyuz and Shuttle, differences of, 152153
Silver sulfadiazine drug, 108 Soyuz spacecraft, 112, 470
Simplified Crew Rescue Alternative Module, 152 designing of, 152
Sinus barotrauma, 255 Soyuz T10 orbital complex, 181
Sinusitis, in crewmembers, 113 Space adaptation syndrome, 102
Skeletal muscle Spacecraft
changes in, 39 Apollo, 467, 468
landing day vs. preflight, 41 artificial source of radiation in, 487, 488
postural muscles, 40 carbon dioxide
fiber types of, 40 LiOH binding capacity, 460
Skeletal muscle atrophy, 39 production and removal of, 459
Skin disorders, in crewmembers, 110 crew protection in, 465
Skylab In-Flight Medical Support System, 7577 disorders and care in
Skylab missions, 28, 526, 560, 561 allergic reactions, 115
biomedical crew training, 90, 9899 burns, 108
calcium balance studies in, 274 cardiac problems, 116118
crewmembers for, 362 dental disorders, 115116
surgical capabilities in, 125 eye disorders, 111112
Skylab Operational Bioinstrumentation System, 167 gastrointestinal disorders, 112113
Skylab program (U.S.), 167 hand injuries, 108
Skylab space station headache, 108110
592 Index

Spacecraft (Continued) transporting patients, 119

lacerations, 104106 Voskhod and Vostak, 470
microbial content, 105 Space flight
muscle strain and overuse syndromes, 104 anemia, 562
musculoskeletal trauma, 106108 back pain and nerve entrapment, 376
pulmonary disorders, 114115 balance function, recovery of, 370
skin disorders, 110 candidates for, medical screening of, 59
sleep disorders, 110 chronology of, 2829
SMS, 102103 conditions
trauma, 103104 urine collection devices, 275276
upper respiratory disorders, 113114 waste management systems, 275
urologic disorders, 116 crewmember
electromagnetic radiation balance assessment, 371
ionizing, 477 carotid sonography for, 328
non-ionizing, 477, 478 functional neurological assessment, 367
environment control systems video oculography (VOG), 375
life support system, goals of, 465, 466 data management system, capability of, 173
major threats, 465 deconditioning, 15
Gemini, 467, 509 diagnostic imaging
ground track of, in low Earth orbit, 8 in exploration-class mission, 198
humidity in issues in, 194
maintaining level of, 464 role in medical risk mitigation, 187188
removal of, 463 on transport spacecraft, 190
ionizing radiation female astronauts, maternal age of, 384
acceleration and vibration, 500 gynecologic malignancy, 382
acute radiation syndromes, 501 habitable volumes for, 149
clinical management, 502, 503 headache, 375
immune function changes, 499, 500 heart rate and blood pressure, 334
planetary surface dust, 500 human response to, clinico-physiological
toxic vehicular agents, 500 anthropometric changes, 32
ionizing radiation effects body posture changes, 33
acute cellular and molecular, 490494 body weight, 32
acute tissue and organ specific, 494497 bone integrity and calcium homeostasis, 3839
biological, 488490 cardiovascular system, 3436
chronic and long term, 497499 clinical laboratory values, 4950
ionizing radiation for, natural digestion, 4445
sources of, 481, 482 entry and landing, 4546
ISS, 511 functional fitness, 49
maneuvering inflight clinical laboratory findings, 45
acute performance effects, 363 inflight physical performance, 4142
engine circuit breakers, 364 limb volume, 32
maximum allowable concentration in, 428 neurological system, 4243
Mercury, 466, 467, 509 neurovestibular symptoms, 4849
methods of treatment, 118119 orthostatic intolerance, 47
nonionizing radiation effects, 504506 physical examination, 3334
operational limits in, 462, 463 plasma volume loss and diuresis, 36
orbit of, 78 postflight clinical disposition, 50
oxygen postlanding period, 4647
dissociation curve, 449, 450 pulmonary changes, 3738
sea level pressures, 449 renal function and hormonal regulation, 4344
transport of, 449, 450 skeletal muscle, 3941
performance capability of, 5 space motion sickness, 3132
pressurization, 248, 249 weightlessness, 3031
Shuttle/Mir Program, 510 imaging procedures, factors
Soyuz, 470 in interventional procedures, 204205
and space flight environment, 415 position and stability, operators, 195196
space shuttle, 510 training and responsibility, 194195
temperature in, 463 locomotor coordination test battery, 372
trace contaminants medical care delivery
fire suppression system and charcoal filters, 465 medical officers training, 163
off-gassing hazards, 464, 465 telemedicine use for, 163
Index 593

medical evacuation and transport, risks Space missions, behavioral problems

in, 150 health problems, 395396
medical imaging for human-to-system interface problems
application, 182 monitoring of, 399
EBCT (See Electron-beam computed tomography) prevention of, 400
history, 181182 psychological adaptation
limitations, 197198 cultural differences, 393
magnetic resonance imaging (MRI) usage in, 184 depressive symptoms, 394
radiography for gastrointestinal pathology, 183 sleep and circadian problems, 394
tomography use, 183184 Space motion sickness (SMS), 3132, 102103,
ultrasound imaging usage in, 185186, 191194 363, 395
medical systems clinical and differential diagnosis, 217
Apollo program, 72 definition of, 211
Mercury and Gemini (projects), 72 epidemiology
Skylab missions, 7273 influencing and precipitating factors, 214
morbidity and mortality in, 141, 143 time course, 214
neurological disorders, clinical implications of, 373 U.S. and Russian space programs, 213, 214
neurovestibular symptoms, 363 in-flight treatment for, 219, 220
nutritional and physiologic effects of laboratory interpretation for electrolytes and
body mass loss in, 561, 562 hormones, 212
bone resorption in, 565 microgravity environment of, 211, 214
countermeasures for, 570 preflight adaptation training, 218, 219
dietary intake and reduction in, 559 prognosis, 220
fluid and electrolyte homeostasis in, 562 prophylaxis, 218
future prospects in, 570571 Russian cosmonaut Gherman Titov, 212
hematocrit and anemia, 562, 563 symptoms of, 211, 212, 214
negative calcium balance in, 564 vs. terrestrial motion sickness, 211
skylab missions in, 560, 561 Space radiation dosimetry monitoring
space shuttle foods in, 560 active dosimetry, 507, 508
nutritional requirements and assessment in active personal dosimetry, 508
components of, 567 biodosimetry, 509
free radicals and antioxidants in, 568 organ dose models, 509
minerals and iron in, 569 passive dosimetry, 507
purpose of, 567 Space shuttle. See also Spacecraft
vitamins in, 568569 crewmembers
weight, bone loss in, 568 blood pressure, heart rate, 334
patient transport and resuscitation, 133 body water of, 332
perceptual effects and illusions, 364366 emergency egress, 330
physical challenges associated with, 41 entrainment strategies for, 421422
preflight and launch factors, 2930 heart rate response, 336
sensorimotor changes during, 42 isotonic solution, volume of, 342
skeletal muscle atrophy, 39 launch position, 329
surgery conditions, mitigating, 387 microgravity adaptation, 361
toxicology, 427 neurovestibular function, 361
vision orthostatic hypotension, 337
contact lenses and spectacles, 537, 538 phase delay and advanced, 421
correction, 536 role of, 101
demographics, 536 trans-thoracic acceleration for, 335
selection test for, 535, 536 engines
standards, 535 specific impulse of, 5
visual acuity level, 535 thrust generated by, 4
visual function, recovery of, 373 environment control system in, 468
weight loss, 340 food system in, 560
Space flight-induced change, 340 life support system in, 469
Spacelab life sciences (SLS), 332 medical system in, 125
Spacelab-1 mission, 365 orbital mechanics, 6, 7
Space medical practitioners, 69 power requirements, 11
Space medicine radiation exposure, 510
basic problems of, 3 STS-90 Neurolab mission, surgery in, 131132
historical aspects of, 2728 waste collection system in, 384
594 Index

Space Shuttle program patient monitoring, 130

Russia
electrocardiographic monitors during, 36
enzymes in blood samples, analysis of, 45
medical screening approaches in, 61
United States
electrocardiographic monitors during, 36
inflight clinical laboratory findings, 45
medical screening approaches in, 61
short-duration space flight, 29
Space sickness and weightlessness, 364
Space Technology Applied to Rural Papago Advanced Health
Care, 170
Spatial orientation, strategies for, 366
SPE. See Solar particle events
SPF. See Sun protection factor
Spinal cord trauma, 565
Spinal DCS. See also Decompression sickness
bubble formation, 229
etiology of, 228
SPL. See Sound pressure level
Stagnant hypoxia. See Ischemic hypoxia
Standard threshold shift (STS), 524
Staphylococcus aureus, 105, 108, 113, 502
STARPAHC. See Space Technology Applied to Rural Papago
Advanced Health Care
Stereopsis, telebinocular instrument for assessing, 535
Stewart equation, for predicting COHb concentrations
in blood, 429
Stone formation. See Nephrolithiasis
Storm shelter
for protection and safety of crewmembers, 486
for protection from most dangerous aspects of SPEs, 513
Streptococcus pyogenes, 108
Stress radionuclide imaging, 327
Strong Angel humanitarian relief exercise, Hawaii, 172
STS-50 mission (U.S.), 169
STS-89 mission (U.S.), 169, 185
Sun protection factor, 506
Superficial trauma, in crewmembers, 103104
Suprachiasmatic nucleus, 417
Supraventricular tachycardia, 320
Surface dust, 2324
Surgery in microgravity, issues of, 124
Surgical bleeding in weightlessness, control measures, 128129
Surgical care, in space
anesthesia administration in, 134135
atmospheric contamination in, 130
bleeding and hemostasis in, 128129
capabilities of, 125126
cardiac and trauma life support, 129130
challenges in performing, 123124
experiences of, 131132
in exploration-class missions, challenges, 124125
factors affecting, 124
future perspectives of, 135
limitations to, 132133
management and treatment of patients in, 134
in neutral buoyancy, 126
in Parabolic Flight Program, 126127
restraint system in, 127128
surgical endoscopy in, 130131
in weightlessness, 126128
Surgical overhead canopy, 128
Surgical resources, limitation of, 132
SVT. See Supraventricular tachycardia
T
TCP/IP. See Transmission control protocol/Internet protocol
TDRSS. See Tracking, data, and relay system satellites
Telemedicine instrumentation pack (TIP)
evaluation of different TIP embodiments, 171172
physical examinations using, 169
Telemedicine program, in space
applications for, 163
bandwidth influence, 165
clinical efficacy of, 165166
consultation in U.S.(1950), 163
definition of, 163
future, 177179
implications of, 175
interaction modalities of, 164
Internet applications, 163
Ku-band system, 169
Mars communication, 164
medical data management, in ISS program, 172
NASA
ACTS program, 171
terrestrial telemedicine project, 170
origin of, 163
real-time encounters involvement, 164
Russia, 168
United States
crewmembers, ECG monitoring of, 168
Project Mercury and Gemini, 167
verbal shorthand, development, 168
videoconferencing model for, 164, 165
video fundus camera, 169
Telepresence surgery, in space flight, 131
Telepsychiatry consultation, in U.S., 163
Telerobotics surgery, in space flight, 131
Temazepam drug, for sleep medications, 110
Temporary threshold shift, 522, 523
Temporomandibular joint dislocation, 554
Temporomandibular joint disorders, 553
Tenosynovitis, on long-duration space mission, 108
Tension headaches, endogenous causes of, 109
TEOAE. See Transient evoked otoacoustic emissions
TEPC. See Tissue equivalent proportional counter
Terrestrial telemedicine project, NASA, 170
Testosterone
impact of space flight on, 44
muscle mass and protein balance, 564
Thallium treadmills (TT), 325
Thermal loading, 329
caused by suit modifications, 335
effects of weightlessness, 30
performance under conditions of, 61
Thermal test, evaluation of, 552
Index
Thermoregulation mechanisms
circadian rhythms markers, 417
during flight, 44
Thorascopy, in space flight, 131
Threshold intensity, automated testing for measuring, 524
Threshold Limit Value Committee, 433
Thrust, for propelling rocket, 4
Tic douloureux. See Trigeminal neuralgia
Tilt-translation device, 219
Tissue equivalent proportional counter, 507, 508
Tooth disorders, classification of, 552553
Toxicology hardware, for International Space Station, 89
Toynbee maneuver, for unlocking ET, 260
Tracking, data, and relay system satellites, 173, 178
Transient evoked otoacoustic emissions, 528
Transillumination
aid in medical diagnosis, 550
with fiber-optic light, 547, 552
Transmission control protocol/Internet protocol, 168
Transportation Safety Board, 414
Trapped gas barotrauma, conditions for, 254
Trauma, in crewmembers, 103104
Trauma pod, in parabolic flight, 130
Treaty on Principles Governing the Activities of States in the
Exploration and Uses of Outer Space, 158
Tribolium, 500
Trigeminal neuralgia, 554
TTD. See Tilt-translation device
T-38 training aircraft, 383
TTS. See Temporary threshold shift
T-wave amplitude, due to changes in potassium
metabolism, 322
Tympanic membrane (TM), 256
U assessing, 371
Ultrasound biomicroscopy (UBM), 202
Ultrasound imaging, for space medicine, 185186, 191192
CMRS deployment, 197
RLQ pain evaluation, 201
Ultrasound probing, for space medicine, 193194
United Nations Space Treaty, 157
United States Armed Forces Institute of Pathology, 164
Unit of pulmonary toxic dose (UPTD), 233
Upper respiratory disorders, in crewmembers, 113114
Urologic disorders, in crewmembers, 116
US Coast Guard (USCG), 523
U.S. National Science Foundations Polar Medicine
Program, 140
U.S. Space Act, 157
U.S. Space Shuttle Program, 394, 397, 400
in admitting women, advantages of, 381
Apollo-Soyuz Test Project, 168
crew health care system (CHeCS), 172
ECG monitoring, crewmembers, 168
echocardiographic series performance, 182
intramuscular injection for in-flight medical procedure in, 118
medical selection criteria, 382
National Television Standards Committee (NTSC), 165
orbital segment of, 173
communication from, 174
595
radiation-exposure limits, 382
Skylab program, 167
space-to-ground communications, capability of, 173174
telemedicine program, 163
Apollo program crewmembers, 167
changes in, 168
Mercury and Gemini, Project, 167
UV keratitis, in crewmembers, 111112
V
Vagal autonaomic modulation, associated with shift-work of flight
crews, 414
Vagal-cardiac neural outflow, for flight crew after space mission, 337
Valsalva maneuver
alternobaric facial paralysis, 257
for clearing sinus block in flight crews, 255
influence on parasympathetic control of blood pressure, 36
for maintaining aortic root pressures and cerebral perfusion
during high +Gz maneuvers, 342
procedure for self-inflation of middle ear space, 259
vagal baroreflex gain in inflight measurements, 43
Van Allen belt radiation. See Geomagnetically trapped radiation
Van Allen radiation belts
flux, 22
inner and outer, 21
Variable specific-impulse magnetoplasma rocket (VASIMR), 11
Vascular abnormalities, in crewmembers, 112
Vectorcardiograph, 167
Ventricular tachycardia, 322
Verbal shorthand development (U.S.), by crewmembers, 168
Vestibular disorders
diagnosis and disposition of flight personnel with, 367
in humans, 373
Neurocom Equitest dynamic platform posturography for
Vestibular ocular reflex, 368
Vestibular spinal reflex, 361
Video baseband signal processor (VBSP), 185
Videoconferencing model, telemedicine, 164, 165
Video fundus camera investigation, for NASA program, 169
Virtual private network technology, 174
Visual Investigation Program on Orbiter Operations
(VIPOR), 506
Visual orientation memory, 364, 365
Visual spatial strategy, 366
Voice communications, air-to-ground, 341
Volutrauma, 238
VOR. See Vestibular ocular reflex
Voskhod spacecraft (Russia), 168, 470
Vostock 1 spacecraft, medical events in, 140
Vostok spacecraft (Russia), 168, 470
VPN. See Virtual private network
VT. See Ventricular tachycardia
W
Walter Reed Army Medical Center (U.S.), 166
Weightlessness, 15. See also Microgravity
clinical changes in physiological systems associated with
bone integrity and calcium homeostasis, 3839
cardiovascular system, 3436
596
Weightlessness (Continued)
clinical laboratory values, 4950
digestion, 4445
entry and landing, 4546
functional fitness, 49
inflight clinical laboratory findings, 45
inflight physical performance, 4142
neurological system, 4243
neurovestibular symptoms, 4849
orthostatic intolerance, 47
plasma volume loss and diuresis, 36
postflight clinical disposition, 50
Index
postlanding period, 4647
pulmonary changes, 3738
renal function and hormonal regulation, 4344
skeletal muscle, 3941
human response to, 3031
physical examination in, 3334
Z
Zero gravity flight, human surgical procedures for,
387388
Zolpidem drug, for assisting onset of sleep in space
crews, 110