Central Nervous System

2011
Dr. Mohammed Azam Danish

Consultant Anesthesiologist & Critical Care Specialist

Dr Azam's Notes in Anesthesiology
Second Edition
www.DrAzam.com
Central Nervous System
Dr Azam's Notes In Anesthesiology
-Second Edition
2011

2

www.DrAzam.com Central Nervous System

Dr Azams Notes in Anesthesiology
2nd Edition

CENTRAL NERVOUS SYSTEM
By
Dr. Azam
Consultant Anesthesiologist & Critical Care

-Second Edition
2011

3


PREFACE
This book grew from notes first written in 2003 - 2004 for the students at the J J M
Medical College in Davangere.

There are many textbooks to choose from when preparing for the Anesthesiology
examination. The candidate suffers not from the lack of information but rather from
being inundated with it. The candidate then has the task of information sorting and data
compression to memorize and utilize all this information.

Graphic representation of data is an excellent form of data compression; figures or
drawings are frequently asked about at the viva examination, particularly since the
candidates understanding of a problem comes across most clearly when drawing a
figure or a using a picture. Figures are also a good way of approaching a topic.

I constructed parts of Dr Azams Notes in Anesthesiology for Postgraduate students
when preparing for the Anesthesiology examination and later when preparing for
tutorials.

Dr Azams Notes is aimed primarily at trainees in Anesthesia though more experienced
practitioners may find it useful as a refresher in recent concepts and advances

Dr Azams Notes is not a substitute for the major anesthesiology text books but
concentrates on principles of management of the most challenging anesthetic cases.

The format is designed to provide easy access to information presented in a concise
manner. I have tried to eliminate all superfluous material. Selected important or
controversial references are presented as well as suggestions for further reading. Some
relate more to basic principles, physiology, pharmacology, etc. bookwork. Others are
more practical in nature, discussing the principles of anesthetic techniques for certain
high-risk situations.

Dr Azams Notes have been created keeping the Postgraduate needs while preparing
for the exams, and also help in his day to day practice. I am sure that Dr Azams Notes
will not only help him to secure highest marks but also help him to gain knowledge to
its full.

-Second Edition
2011

4


A NOTE TO THE READER

Anesthesiology is an ever-changing field. Standard safety precautions must be followed,
but as new research and clinical experience broaden our knowledge, changes in
treatment and drug therapy may become necessary or appropriate. Readers are advised
to check the most current product information provided by the manufacturer of each
drug to be administered to verify the recommended dose, the method and duration of
administration, and contraindications.

However, in view of the possibility of human error or changes in medical sciences,
neither the author nor the publisher nor any other party who has been involved in the
preparation or publication of this work warrants that the information contained herein
is in every respect accurate or complete, and they disclaim all responsibility for any
errors or omissions or for the results obtained from use of the information contained in
this work. Readers are encouraged to confirm the information contained herein with
other sources. It is the responsibility of the licensed prescriber, relying on experience
and knowledge of the patient, to determine dosages and the best treatment for each
individual patient. Neither the publisher nor the editor assumes any liability for any injury
and/or damage to persons or property arising from this publication.

-Second Edition
2011

5


DEDICATION

To Mohammed Shafiulla, my father, my oxygen,
companion, and best friend; for being my major pillar of
support and making this vision a reality. Thank you for your
continual sacrifices with boundless love and limitless
gratitude, for the sake of your children. I owe you a debt I can
never repay.

I also would like to thank my mom (Naaz Shafi), my wife
(Roohi Azam), my two lovely kids (Falaq Zohaa &
Mohammed Izaan),for their support, ideas, patience, and
encouragement during the many hours of writing this book.

I also thank my Colleagues Dr Rajshekar Reddy & Dr
Sachin for their support.

Finally, I would like to thank my teachers. The dream begins
with a teacher who believes in you, who tugs and pushes and
leads you to the next plateau, sometimes poking you with a
sharp stick called "truth."

-Second Edition
2011

6


Contributions
01. Dr. Rajshekar Reddy UAE
02. Dr. Surendra UAE
03. Dr. Nagaraj Chandy Hubli
04. Dr.Kusuma Bangalore
05. Dr Sachin Doijode London
06. Dr Chandrashekar Bangalore
07. Dr Sidhu Bangalore
08. Dr Ravindra B K Bangalore
09. Dr Harshavardhan Mangalore
10. Dr Anil Kumar Tamil Nadu
11. Dr Mashooda Kerla
12. Dr Anusuya Bangalore
13. Dr Sudhir Bangalore
14. Dr Uma Davangere
15. Dr Rajeev UAE
16. Dr Surendra UAE
17. Dr Shivananda Shimoga
18. Dr Soujanya Bangalore
19. Dr Aslam Faris Kerla
20. Dr Nandakumar Tamil Nadu
21. Dr Anuradha Bangalore
22. Dr Arun G Pai Kerla
23. Dr Geetha Bangalore

-Second Edition
2011

7


Table of Contents
PREFACE .......................................................................................................................................................... 3
DEDICATION .................................................................................................................................................... 5
CHAPTER 1 - ANATOMY AND PHYSIOLOGY OF THE AUTONOMIC NERVOUS SYSTEM ..................................... 15
SYMPATHETIC NERVOUS SYSTEM: ............................................................................................................................. 19
PARASYMPATHETIC NERVOUS SYSTEM: ..................................................................................................................... 24
Physiological effects of stimulation of the sympathetic and parasympathetic divisions of the autonomic
nervous system. ........................................................................................................................................... 27
CHAPTER 2 - AUTONOMIC NERVOUS SYSTEM DYSFUNCTION AND ANESTHETIC IMPLICATION ...................... 30
ANATOMY: .......................................................................................................................................................... 30
SYMPATHETIC SYSTEM: .......................................................................................................................................... 30
PARASYMPATHETIC NERVOUS SYSTEM: ..................................................................................................................... 32
PHYSIOLOGY AND PHARMACOLOGIC CONSIDERATIONS: ................................................................................................ 33
NEUROTRANSMITTERS: .......................................................................................................................................... 33
Neurotransmitters: ...................................................................................................................................... 33
CLINICAL FEATURES OF ANS DYSFUNCTION & HYPOFUNCTION ON ANS: EFFECTS OF VARIOUS SYSTEMS ...... 34
Treatment: .................................................................................................................................................. 34
HYPERFUNCTION OF ANS: ................................................................................................................................ 36
EVALUATION OF ANS DYSFUNCTION PRE ANESTHETIC CHECK UP ................................................................ 36
PHARMACOLOGICAL TESTS OF AUTONOMIC FUNCTION ................................................................................. 40
CLINICAL TESTS OF AUTONOMIC FUNCTION .................................................................................................... 42
Non-Invasive Bedside Tests: ........................................................................................................................ 42
DISEASES ASSOCIATED WITH PROGRESSIVE NEUROLOGICAL IMPAIRMENT OF AUTONOMIC NERVOUS
SYSTEM ............................................................................................................................................................ 43
MANAGEMENTOF ANESTHESIA: ................................................................................................................. 47
ANESTHETIC IMPLICATIONS IN AUTONOMIC DYSFUNCTION .................................................................... 47
CONDUCT OF ANESTHESIA IN PATIENTS WITH ANS DYSFUNCTION: ................................................................ 49
CHAPTER 3 - CEREBRAL BLOOD FLOW AND METABOLISM ............................................................................. 53
PHYSIOLOGICAL REGULATION OF CBF AND CMRO
2
: ................................................................................................... 53
Flow-Metabolism Coupling: ........................................................................................................................ 54
CHAPTER 4 - CEREBRAL FUNCTION MONITORING .......................................................................................... 70
MONITORING DEPTH OF ANESTHESIA ........................................................................................................................ 70
METHODS OF MEASURING DEPTH OF ANESTHESIA ........................................................................................................ 71
Factors affecting the EEG ............................................................................................................................ 76
Clinical Applications .................................................................................................................................... 77
Magneto-encephalography (MEG) ............................................................................................................. 77
SOMATOSENSORY EVOKED POTENTIALS (SSEP)........................................................................................................... 79
-Second Edition
2011

8


CLINICAL APPLICATIONS .......................................................................................................................................... 84
Special techniques to enhance motor evoked potential responses ............................................................. 84
CHAPTER 5 - SENSORY EVOKED POTENTIAL (SEP) .......................................................................................... 94
DEFINITION:......................................................................................................................................................... 94
CLASSIFICATION OF SENSORY EVOKED POTENTIALS: ..................................................................................................... 94
Post Stimulus Latencies: .............................................................................................................................. 94
Recording of Sensory Evoked Potentials: .................................................................................................... 95
Any System to adequately record SEP should contain: ............................................................................... 95
The sites of stimulation of the peripheral nerve are: .................................................................................. 96
Factors affecting SSEP: ................................................................................................................................ 97
AUDITORY EVOKED POTENTIALS: (AEP) .................................................................................................................... 97
Brain Stem Evoked Potentials: .................................................................................................................... 97
CHAPTER 6 - ELECTROCONVULSIVE THERAPY (ECT) ........................................................................................ 99
DEFINITION:......................................................................................................................................................... 99
Seizures duration depends on many factors like: ........................................................................................ 99
Physiological effects: ................................................................................................................................... 99
CHAPTER 7 - CEREBRAL STEAL ...................................................................................................................... 101
PACO
2
AND REGULATION OF CEREBRAL BLOOD FLOW: ............................................................................................... 101
CHAPTER 8 CECEREBRATE RIGIDITY ............................................................................................................. 103
CAUSE: ............................................................................................................................................................. 103
CHAPTER 9 - BRAIN-DEAD ORGAN DONOR .................................................................................................. 104
BRAIN STEM FUNCTION: ....................................................................................................................................... 104
AIRWAY CONSIDERATIONS AND MECHANICAL VENTILATION ........................................................................................ 106
Table 1. Indications for Intubation and Mechanical Ventilation ............................................................... 107
CHAPTER 10 - ANESTHESIA FOR INTRACRANIAL ANEURYSM SURGERY ........................................................ 113
CHAPTER 11 - ANESTHETIC MANAGEMENT OF POSTERIOR FOSSA SURGERY ............................................... 117
SURGICAL LESIONS: ............................................................................................................................................. 117
PREOPERATIVE ASSESSMENT: ................................................................................................................................ 117
COMPLICATIONS COMMON TO PATIENTS OPERATED UPON IN ALL POSITIONS ............................................ 123
CHAPTER 12 CEREBRAL PHYSIOLOGY ........................................................................................................... 127
CEREBRUM ..................................................................................................................................................... 128
CEREBRAL METABOLISM ........................................................................................................................... 128
Neurons require energy ............................................................................................................................. 128
NORMAL BRAIN OXYGEN REQUIREMENTS: ................................................................................................................ 129
Effect of anesthetic drugs & temperature on cerebral metabolic rate ..................................................... 130
CEREBRAL BLOOD FLOW ................................................................................................................................ 131
REGULATION OF CBF ...................................................................................................................................... 132
Factors affecting CMR ............................................................................................................................... 133
-Second Edition
2011

9


Precise mechanism of autoregulation is not defined. Proposed theories ................................................ 137
MEASUREMENT OF CEREBRAL BLOOD FLOW ................................................................................................ 140
TRANSCRANIAL DOPPLER (TCD) ULTRASONOGRAPHY: .................................................................................. 141
BLOOD BRAIN, BARRIER ................................................................................................................................. 144
SIGNIFICANCE OF BBB: ........................................................................................................................................ 144
BBB disrupted by ....................................................................................................................................... 146
CHAPTER 13 - INTRACRANIAL PRESSURE ...................................................................................................... 148
COMPENSATORY MECHANISMS: ............................................................................................................................. 148
ICP conventionally means supratentorial CSF pressure measured in the lateral ventricles or over the
cerebral cortex. ......................................................................................................................................... 148
INCRACRANIAL MEASUREMENT; ................................................................................................................... 149
SUBARACHNOID SCREW OR BOLT .................................................................................................................. 150
EPID URAL TRANSDUCERS: There are LADD, GAELTEC, ....................................................................... 151
LADD MONITOR ........................................................................................................................................ 151
ELECTROPHYSIOLOGICAL FUNCTIONS ........................................................................................................... 152
ELECTRO ENCEPHALOGRAM: ......................................................................................................................... 153
BISPECTRAL ANALYSIS (BIS) (BISPECTRAL INDEX SCALE): ....................................................................................... 154
EVOKED POTENTIAL: ...................................................................................................................................... 155
Commonly monitored EPs are: .................................................................................................................. 156
CHAPTER 14 - NEUROMUSCULAR JUNCTION PHYSIOLOGY AND ITS ANEASTHETIC IMPLICATIONS .............. 159
PHYSIOLOGY OF NEUROMUSCULAR TRANSMISSION ..................................................................................... 159
NEUROMUSCULAR JUNCTION: ............................................................................................................................... 160
ACETYLCHOLINE (SYNTHESIS, STORAGE, RELEASE): ..................................................................................................... 161
Acetylcholine receptors: ............................................................................................................................ 163
Post junctional receptors: .......................................................................................................................... 163
Prejunctional receptors: ............................................................................................................................ 166
Extra Junctional receptor: ......................................................................................................................... 166
Contractile apparatus: .............................................................................................................................. 166
Role of calcium: ......................................................................................................................................... 167
SEQUENCE OF EVENTS DURING NEUROMUSCULAR TRANSMISSION ................................................................................. 167
ACETYL CHOLINESTERASE: ..................................................................................................................................... 168
PHYSICAL CHANNEL BLOCKADE: .............................................................................................................................. 168
Characteristics of muscle relaxants: .......................................................................................................... 168
SEQUENCE OF MUSCLE BLOCKADE: ......................................................................................................................... 169
Mechanism of neuromuscular blockade: .................................................................................................. 169
DEPOLARIZING (NON COMPETITIVE) NEUROMUSCULAR BLOCK: .................................................................................... 169
RECEPTORS PHYSIOLOGY OF DEPOLARIZING BLOCKADE: ............................................................................................... 170
STRUCTURE: ...................................................................................................................................................... 170
Possible configuration of the Na
+
channel: ............................................................................................... 170
Desensitization block: ................................................................................................................................ 171
Mechanism: ............................................................................................................................................... 171
PROLONGED APNOEA AFTER SUCCINYLCHOLINE: ........................................................................................................ 171
Atypical pseudocholinesterase .................................................................................................................. 172
-Second Edition
2011

10


DIBUCAINE NUMBER: ........................................................................................................................................... 173
PHASE II BLOCK: ................................................................................................................................................. 173
Mechanism; ............................................................................................................................................... 173
FACTORS INFLUENCING THE DEVELOPMENT OF PHASE II BLOCK ..................................................................................... 174
FEATURES OF DEPOLARIZING NEUROMUSCULAR BLOCKADE: ......................................................................................... 174
NON DEPOLARIZING (COMPETITIVE) NEUROMUSCULAR BLOCK: .................................................................................... 174
Features of nondepolarizing muscle blockade: ......................................................................................... 175
FACTORS INFLUENCING NEUROMUSCULAR BLOCKADE ................................................................................................. 175
PHYSIOLOGICAL: ................................................................................................................................................. 175
NEUROMUSCULAR BLOCKING DRUGS: ..................................................................................................................... 177
b) Non-depolarizing - depolarizing interaction ......................................................................................... 177
c) Antibiotics .............................................................................................................................................. 177
d) Anticonvulsants ..................................................................................................................................... 177
MISCELLANEOUS ................................................................................................................................................. 177
2) Organ failure ......................................................................................................................................... 178
3) Electrolyte imbalance: ........................................................................................................................... 178
Antagonism of neuromuscular blockade: ................................................................................................. 180
In addition to the above the following drugs are used: ............................................................................ 182
NEUROMUSCULAR MONITORING .................................................................................................................. 182
Principle of peripheral nerve stimulation: ................................................................................................. 183
SUPRA MAXIMAL CURRENT: .................................................................................................................................. 184
Train of four (TOF stimulation) .................................................................................................................. 185
CHAPTER 15 - SUPRATENTORIAL TUMOUR AND ANESTHESIA ..................................................................... 193
CEREBRAL HEMODYNAMIC .................................................................................................................................... 193
Intracranial content: ................................................................................................................................. 193
CEREBRAL BLOOD FLOW ....................................................................................................................................... 193
INTRACRANIAL TUMOURS ..................................................................................................................................... 198
WHO CLASSIFICATION ......................................................................................................................................... 198
ETIOLOGY .......................................................................................................................................................... 198
Clinical features ......................................................................................................................................... 199
PRONE POSITION ................................................................................................................................................ 207
INDICATION ....................................................................................................................................................... 207
Semi lateral position .................................................................................................................................. 210
Lateral position ......................................................................................................................................... 211
AVOID THE FACTOR ICP SUCH AS ........................................................................................................................ 212
Treatment ................................................................................................................................................. 213
POST OPERATIVE CARE ......................................................................................................................................... 217
Pain ........................................................................................................................................................... 217
CHAPTER 16 - BRAIN PROTECTION ............................................................................................................... 220
NEUROPROTECTIVE AGENTS .......................................................................................................................... 222
NMDA AND AMPA/ KAINATE-RECEPTOR ANTAGONISTS: ......................................................................................... 222
CALCIUM-CHANNEL BLOCKERS: ............................................................................................................................. 222
FREE RADICALS AND LIPID ANTIOXIDANTS ................................................................................................................ 223
-Second Edition
2011

11


Hypothermia: ............................................................................................................................................ 225
CHAPTER 17 - PHARMACOLOGICAL NEUROPROTECTION ............................................................................. 229
MECHANISM OF ACTION OF NEURO PROTECTANT DRUGS: ........................................................................................... 238
ANESTHETIC AGENTS AS NEURO PROTECTANTS: ......................................................................................................... 239
PROBLEMS DURING BARBITURATE THERAPY: ............................................................................................................. 242
NON-ANESTHETIC AGENTS AS NEURO PROTECTANTS: ................................................................................................. 246
CHEMICAL BRAIN RETRACTOR CONCEPT: .................................................................................................................. 251
CHAPTER 18 - RECENT ADVANCES IN NEUROPROTECTION ........................................................................... 253
TECHNIQUES TO IMPROVE OXYGEN SUPPLY: .............................................................................................................. 253
TECHNIQUE TO REDUCE OXYGEN DEMAND: .............................................................................................................. 253
CHAPTER 19 - GLASGOW COMA SCALE ........................................................................................................ 257
CHAPTER 20 - SPINAL SHOCK ....................................................................................................................... 260
MANAGEMENT: .................................................................................................................................................. 261
Early care of acute injuries: ....................................................................................................................... 261
CHAPTER 21 - ELECTROENCEPHALOGRAM ................................................................................................... 262
DEFINITION:....................................................................................................................................................... 262
EEG SIGNAL: ...................................................................................................................................................... 262
NORMAL EEG: ................................................................................................................................................... 262
Abnormal EEG: .......................................................................................................................................... 263
USES OF EEG: .................................................................................................................................................... 263
ANESTHESIA AND EEG .................................................................................................................................... 263
EEG during cardiovascular surgery: .......................................................................................................... 264
EEG during carotid endarterectomy: ......................................................................................................... 264
PATHOPHYSIOLOGICAL EFFECTS ON EEG: ................................................................................................................. 265
Advantages of EEG: ................................................................................................................................... 265
Disadvantages of EEG: .............................................................................................................................. 265
NORMAL ALPHA AND SLEEP RHYTHM:...................................................................................................................... 266
CHAPTER 22 - CEREBRAL EDEMA .................................................................................................................. 267
CAUSES: ............................................................................................................................................................ 267
Fluid Restriction: ........................................................................................................................................ 267
Osmotic Agents: Mannitol......................................................................................................................... 267
Loop Diuretics: (Furosemide) ..................................................................................................................... 268
CHAPTER 23 BRAIN DEATH .......................................................................................................................... 269
DEFINITION OF DEATH: ......................................................................................................................................... 269
CRITERIA FOR DIAGNOSIS OF BRAIN DEATH .............................................................................................................. 271
CHAPTER 24 - ANESTHESIA FOR NEUROMUSCULAR DISORDERS .................................................................. 273
CLASSIFICATION OF NEUROMUSCULAR DISORDERS (NMD): ......................................................................... 273
MYASTHENIA GRAVIS (MG): ................................................................................................................................. 273
-Second Edition
2011

12


DEPENDING ON THE GROUP OF MUSCLES INVOLVED AND SEVERITY THEY ARE CLASSIFIED AS FOLLOWS: ADULT MYASTHENIA: ... 274
PEDIATRIC MYASTHENIA ....................................................................................................................................... 274
MECHANISM PROPOSED INCLUDES: ........................................................................................................................ 275
DIAGNOSIS: ....................................................................................................................................................... 276
DIFFERENTIAL DIAGNOSIS: .................................................................................................................................... 278
ANESTHETIC MANAGEMENT: ................................................................................................................................. 280
PREOPERATIVE EVALUATION: ................................................................................................................................. 281
PFTS: .............................................................................................................................................................. 281
Non-specific (bed side test) ....................................................................................................................... 281
Specific tests: ............................................................................................................................................. 281
PREOPERATIVE EVALUATION OF MG PATIENT INCLUDES.............................................................................................. 282
Preoperative Preparation: ......................................................................................................................... 282
INTRAOPERATIVE MONITORS: ................................................................................................................................ 284
STRATEGIES TO REDUCE POSTOPERATIVE PULMONARY COMPLICATIONS: ........................................................................ 285
MYASTHENIC SYNDROMES: ................................................................................................................................... 288
EATON LAMBERT SYNDROME (ELS): .................................................................................................................... 288
PATHOPHYSIOLOGY: ............................................................................................................................................ 288
Clinical features: ........................................................................................................................................ 288
COMPARISON OF MYASTHENIA GRAVIS AND MYASTHENIA SYNDROME: ......................................................................... 289
CLINICAL FEATURES ............................................................................................................................................. 289
MYASTHENIA GRAVIS .......................................................................................................................................... 289
EATONLAMBERT SYNDROME ............................................................................................................................... 289
DUCHENES MUSCULAR DYSTROPHY (DMD): .......................................................................................................... 291
DOSE OF DANTROLENE: ....................................................................................................................................... 293
Becker Muscular Dystrophy (BMD): .......................................................................................................... 293
Emery Dreifuss Dystrophy: ...................................................................................................................... 293
Treatment: ................................................................................................................................................ 295
CHAPTER 25 - TRAUMA SCALES .................................................................................................................... 299
I TRAUMA SCORE: ............................................................................................................................................... 299
II REVISED TRAUMA SCORE ................................................................................................................................... 299
PEDIATRIC TRAUMA SCORE: .................................................................................................................................. 300
CHAPTER 26 - HYPOXIC BRAIN DAMAGE DURING ANESTHESIA ................................................................... 302
CAUSES OF HYPOXIC BRAIN INJURY: .............................................................................................................. 302
CARDIAC ARREST: ............................................................................................................................................... 302
MECHANISMS OF INTRAOPERATIVE CARDIAC ARREST ................................................................................................. 302
CONTRIBUTING FACTORS FOR "LATENT" ERRORS ...................................................................................................... 305
PREVENTION AND MANAGEMENT OF ERRORS: ......................................................................................................... 306
CHAPTER 27 - ANESTHETIC MANAGEMENT OF INTRACRANIAL HYPERTENSION ........................................... 307
PATHOPHYSIOLOGY OF INTRACRANIAL HYPERTENSION................................................................................ 307
SECONDARY BRAIN INJURY ............................................................................................................................ 309
INTRACRANIAL HYPERTENSION IN THE PERIOPERATIVE PERIOD ................................................................... 309
THERAPEUTICAL APPROACH TO INTRAOPERATIVE TIGHT BRAIN .................................................................. 313
-Second Edition
2011

13


CHAPTER 28 - ICP MONITORING .................................................................................................................. 316
TYPE OF WAVES ................................................................................................................................................. 316
4 STAGES OF RAISED ICP: ..................................................................................................................................... 316
EXTRADURAL HEMORRHAGE: ................................................................................................................................. 316
C/F: ................................................................................................................................................................. 316
MANAGEMENT: .................................................................................................................................................. 317
SUBDURAL HAEMORRHAGE: .................................................................................................................................. 317
C/F: ................................................................................................................................................................. 318
COMMON PREDISPOSING FACTORS: ........................................................................................................................ 318
ASSESSMENT OF SEVERITY: .................................................................................................................................... 318
CHAPTER 29 - ICP AND ANESTHESIA ............................................................................................................. 319
FACTORY WHICH INCREASE ICP: ............................................................................................................................. 319
INDICATIONS FOR ICP MONITORING: ...................................................................................................................... 323
USES OF ICP MONITORING: .................................................................................................................................. 323
DIAGNOSTIC ...................................................................................................................................................... 323
TECHNIQUES OF ICP MONITORING: ....................................................................................................................... 323
ADVANTAGES: .................................................................................................................................................... 324
NON FLUID COUPLED DEVICES FOR SURFACE MONITORING OF ICP: ............................................................................. 324
CHAPTER 30 - NEUROGENIC PULMONARY EDEMA ....................................................................................... 326
CLINICAL SYNDROME ..................................................................................................................................... 326
PATHOGENESIS OF NPE: ................................................................................................................................. 328
HYDROSTATIC PULMONARY EDEMA ........................................................................................................................ 329
OTHER POSSIBLE MECHANISMS ............................................................................................................................. 330
MEDIATORS OF NPE ....................................................................................................................................... 330
CLINICAL MANAGEMENT OF NPE ................................................................................................................... 332
CHAPTER 31 - HEAD INJURY PATHOPHYSIOLOGY & ANESTHETIC MANAGEMENT ........................................ 336
HEAD INJURY DEFINITION AND STATISTICS: ........................................................................................................... 336
CEREBRAL AUTOREGULATION ....................................................................................................................... 337
MECHANISM OF BRAIN INJURY ...................................................................................................................... 338
PATHOPHYSIOLOGY: ...................................................................................................................................... 339
MAIN PATHOLOGICAL MANIFESTATIONS ...................................................................................................... 340
CLASSIFICATION OF HEAD INJURY: ................................................................................................................. 341
HEAD INJURY CLASSIFICATION: ............................................................................................................................... 341
SEVERITY OF INJURY: ...................................................................................................................................... 341
GLASGOW COMA SCALE: ...................................................................................................................................... 342
INTRA-CRANIAL LESIONS: ...................................................................................................................................... 344
THE SUBDURAL HEMATOMA: ........................................................................................................................ 344
EPIDURAL HEMATOMAS: ............................................................................................................................... 344
INTRA-CEREBRAL HEMATOMA....................................................................................................................... 344
Based on mechanism of injury: ................................................................................................................. 345
Based on CT scan: ...................................................................................................................................... 345
-Second Edition
2011

14


CHANGES IN CNS ....................................................................................................................................... 345
MULTISYSTEM SEQUELAE OF SEVERE HEAD INJURY: ..................................................................................... 347
PREHOSPITAL MANAGEMENT OF HEAD INJURY: ........................................................................................... 348
EMERGENCY ROOM MANAGEMENT OF HEAD INJURY ............................................................................. 349
DIAGNOSTIC EVALUATION .................................................................................................................................... 350
MEDICAL MANAGEMENT OF HEAD INJURY: TREATMENT OF INTRACRANIAL HYPERTENSION: ................................... 351
ANESTHETIC MANAGEMENT: ......................................................................................................................... 352
Practical Anesthesia .................................................................................................................................. 352
MONITORING DURING SURGERY ................................................................................................................... 356
Interpretation of ICP measurement .......................................................................................................... 358
INTERPRETATION ICP ........................................................................................................................................... 358
TABLE: EMERGENCY THERAPY FOR HERNIATION......................................................................................................... 360
Intraoperative fluid management ............................................................................................................. 360
FUTURE TRENDS IN THE MANAGEMENT OF HEAD INJURIES .......................................................................... 361
CHAPTER 32 - HEAD INJURY PATHOPHYSIOLOGY & ANESTHETIC MANAGEMENT ........................................ 364
PATHOPHYSIOLOGY OF HEAD INJURY ...................................................................................................................... 364
Anesthetic Management ........................................................................................................................... 364
TABLE 1. CEREBRAL EFFECTS OF ANESTHETIC DRUGS .................................................................................................. 372
HEAD INJURY & ITS EFFECTS ........................................................................................................................... 372
TABLE 1: LABORATORY EVALUATION OF DIC ............................................................................................................ 378
CHAPTER 33 RECENT ADVANCES RELEVANT TO NEUROANESTHESIA CARE OF TRAUMA PATIENT ............... 383
Hypertonic Solutions for Fluid Resuscitation ............................................................................................. 389

-Second Edition
2011

15


Chapter 1 - ANATOMY AND PHYSIOLOGY OF THE
AUTONOMIC NERVOUS SYSTEM
The nervous system can be divided into two-the cerebrospinal system made up
of the brain, spinal cord and peripheral nerves and the autonomic nervous
system (also called visceral or involuntary) formed by autonomic ganglia and
nerves. While the cerebrospinal system is concerned with reactions of the body
to the external environment, the autonomic system controls the internal
environment and the viscera.
The autonomic nervous system comprises of sensory and motor fibers
innervating the viscera. In addition, there are visceral centers within the brain
and spinal cord which integrate the afferent input and modulate efferent activity.
This motor system is so named because its activities are regulated automatically
and are not consciously controlled at will. They manifest primarily through
activity within reflex arcs and structures within the brain. Smooth musculature
of the organs within the head, thorax, abdomen and pelvis, and the blood vessels
and glands throughout the body are under the direct control of the autonomic
nervous system. It is described as a two-motor-neuron system comprising pre-
and postganglionic nerve cells. Structurally and functionally, the autonomic
nervous system is further divided into sympathetic and parasympathetic
nervous systems. The sympathetic preganglionic cells are located in the lateral
grey column of the spinal cord between the first thoracic and second lumbar
segments while the postganglionic sympathetic neurons lie within the
sympathetic ganglionated chains that run parallel to the spinal column and
within other outlying collateral ganglia. Preganglionic parasympathetic cells and
found within the brain-stem nuclei of cranial nerves III, VII, IX and X and in the
second, third and fourth sacral spinal segments. The preganglionic elements
emerge from these craniosacral sites to synapse with postganglionic
parasympathetic neurons are dually innervated, receiving fibers from each of the
divisions of the autonomic nervous system. Smooth musculature of blood vessels
sweat glands and hair follicles are exceptions to this arrangement.
Sympathetic discharge promotes activity in those viscera which are essential
during periods of stress and adversity. Flight, fright, fear and certain aspects of
mating behavior are accompanied by increased cardiac and respiratory rates and
an increased blood pressure. Parasympathetic activity, slowing of the heart,
lowering of blood pressure, and other visceral functions conducive to digestion,
growth and repair are promoted by the parasympathetic nervous system.
-Second Edition
2011

16


The great French Physiologist Claude Bernard brilliantly demonstrated the
physiological significance of the autonomic nervous system with his discovery of
the vasomotor responses to stimulation of sympathetic nerve trunks and slowing
of the heart by stimulation of the vagus. Claude Bernards description of the
sympathetic control of pupillarly, sudomotor and pilomotor functions as well as
vasomotor function was confirmed clinically by Johann F Horner who showed
that ptosis (as seen in Horners syndrome) is due to a lesion of cervical
sympathetic trunk.
The wide functional activity controlled by the autonomic nervous system is due
to the delicate balance of neurochemical regulation of sympathetic and
parasympathetic nervous systems. Together they regulate many aspects of
respiratory, cardiovascular, gastrointestinal and renal function as well as
secretary activity of the skin, salivary glands, stomach and pancreas.
This delicate balance of almost all body functions by the autonomic nervous
system led to the idea of homeostasis, a notion first mooted by Claude Bernard
as the milieu interieur or internal steady state. It is this homeostasis that all
anesthesiologists strive to preserve.
The autonomic nervous system regulates individual organ function and
homeostasis and for the most part is not subject to voluntary control. It is
predominantly efferent system transmitting impulses from the central nervous
system (CNS) to peripheral organ systems. Its effects include control of heart
rate and force of contraction, contraction and relaxation of smooth muscle in
blood vessels and various organs, constriction and dilatation of pupils, visual
accommodation, and secretions from exocrine and endocrine glands. Autonomic
nerves constitute all the efferents which leave the CNS except for those which
innervate skeletal muscle.
In addition, there are some afferent fibers (i.e., those that transmit information
from the periphery to the CNS) which control visceral sensation and vasomotor
and respiratory reflexes. Examples of these would be baroceptors and
chemoreceptor in the carotid sinus and aortic arch controlling the heart rate,
blood pressure and respiration. These afferent fibers usually reach the CNS via
the vagus, splanchnic or pelvic nerves, while afferent fibers usually reach the CNS
via the vagus, splanchnic or pelvic nerves, while afferent pain fibers from blood
vessels may be carried by somatic nerves. These afferent impulses often pain
fibers from blood vessels may be carried by somatic nerves. These afferent
-Second Edition
2011

17


impulses often do not reach our consciousness but elicit automatic or reflex
responses through efferent autonomic nerves. These, in turn, elicit appropriate
responses in all the organs of the body, especially the heart and blood vessels, to
variations in environmental temperature, positive food intake, stressful
experiences and other changes to which all individuals are exposed. Thus,
autonomic processing and innervations direct many homeostatic functions
necessary for basic life processes.
The autonomic nervous system (ANS) is primarily involved in reflex arcs, which
consist of either an autonomic or somatic afferent limb and an autonomic or
somatic efferent limb. For instance, afferent fibers convey stimuli from pain
receptors, mechanoreceptors or chemoreceptors in the heart, lungs or
gastrointestinal tract. As a result, reflex response is sent through autonomic
efferent fibers causing contraction in the smooth muscles of blood vessels, eyes,
lungs, bladder or gastrointestinal tract. The efferent limb of these reflexes may
also involve the somatic nerves and lead to cough; vomiting, etc. sympathetically-
mediated pain is an example of over activity of this reflex arc.
Simple reflexes are completed entirely within the organ concerned whereas
more complex reflexes are controlled by the higher autonomic centers in the
CNS, principally the hypothalamus.
The characteristic anatomic feature of the autonomic nervous system is that its
efferent nerves emerge as medullated fibers from the brain and spinal cord,
synapse in a peripheral ganglion and emerge as postganglionic unmyelinated
nerves. Thus, the myelinated preganglionic fibers synapse with unmyelinated
postganglionic fibers which innervate the effectors organ. Somatic reflex arcs are
bipolar i.e., a two-neuron chain from the CNS to the effector organ (Figure 1).
The autonomic nervous system is subdivided anatomically, functionally and
pharmacologically into sympathetic and parasympathetic nervous systems.

-Second Edition
2011

18


-Second Edition
2011

19


Sympathetic nervous system:
o The cell bodies of the sympathetic preganglionic fibers originate in the
lateral horns of the spinal segments T1-L2 and are thus called the thoraco
lumbar outflow. The preganglionic fibers travel a short distance in the
mixed spinal nerve and then branch off as white rami communicants
(myelinated) to enter the sympathetic ganglia. These are mainly arranged
in two
Paravertebral chains which lie anterolateral to the vertebral bodies and extend
from cervical to the sacral region. They constitute the sympathetic ganglion
chains (Figure 2). T1 short preganglionic fibers enter the chain and synapse with
a postsynaptic fibers either at same, higher or lower dermatome level. The
longer postganglionic fibers usually return to the adjacent spinal nerve via grey
rami communicants (unmyelinated) and are conveyed to the effector organ.
o Some preganglionic fibers do not synapse in the sympathetic chains but
terminate in separate cervical or abdominal ganglia, or travel in greater
splanchnic nerve and directly synapse with chromaffin cells in the adrenal
medulla (Figure 3).

Acetylcholine (Ach) is the neurotransmitter via a nicotinic receptor at the preganglionic
synapse. The adrenal medulla is innervated by preganglionic fibres and adrenaline
(epinephrine) is released from the gland by stimulation of nicotinic Ach receptors. At
most postganglionic sympathetic endings, the chemical transmitter is nor adrenaline
-Second Edition
2011

20


(nor epinephrine), which is present in the presynaptic terminal as well is in the adrenal
medulla. In sweat glands, however, postganglionic sympathetic fibres release Ach and
this transmission is nicotinic (Figure 4).

o The sympathetic system enables the body to be prepared for fear, flight or
fight. Sympathetic responses include an increase in heart rate, blood
pressure and cardiac output, a diversion of blood flow from the skin and
splanchnic vessels to those supplying skeletal muscle, increased papillary
size, bronchiolar dilation, contraction of sphincters and metabolic
changes such as mobilization of fat and glycogen. Classical examples of
this are responses to carbon dioxide retention or hypoglycemia under
anesthesia.
o Both adrenaline and nor adrenaline are catecholamines synthesized from
the essential amino acid phenylalanine by a series of steps which includes
-Second Edition
2011

21


the production of dopamine. The terminal branches of the sympathetic
postganglionic fibres have varicosities or swellings, giving them the
appearance of a string of beads. The swellings form the synaptic contact
with the effector organ. They are also the site of synthesis and storage of
nor adrenaline. On arrival of a nerve impulse, nor adrenaline is released
from granules in the presynaptic terminal into the synaptic cleft. The
action of nor adrenaline is terminated by diffusion from the site of action,
reuptake into the presynaptic nerve ending where it is inactivated by the
enzyme monoamine oxidase in mitochondria or by the enzyme catechol-
O-methyl-transferase locally.
o The synthesis and storage of catecholamines in adrenal medulla is similar
to that of sympathetic postganglionic nerve endings but due to the
presence of an additional enzyme, the majority of nor adrenaline is
converted to adrenaline. The adrenal medulla responds to nervous
impulses in the sympathetic cholinergic preganglionic fibres by
transforming neural impulses into hormonal secretion. In situations
involving physical or psychological stress, much larger quantities are
released.
o The actions of catecholamine are mediated by specific postsynaptic cell
surface receptors. Pharmacological subdivision of these receptors into
two groups ( and ) was first suggested by Ahlquist in 1948, based upon
the effects of adrenaline at peripheral sympathetic sites. These have since
been further subdivided on functional and anatomical grounds. Thus, 1
adrenoceptor mediated effects in the heart (increased force and rate of
contraction) have been differentiated from those producing smooth
muscle relaxation in the bronchi and blood vessels ( 2 effects). Similarly,
-adrenoceptor mediated effects such as vasoconstriction have been
termed 1-effects to differentiate them from the feedback inhibition by
nor-adrenaline of its own release from pre-synaptic terminals which is
mediated by 2- adrenoreceptors on the presynaptic membrane.

-Second Edition
2011

22


However, further research now shows that the classification is not as simple as
this. For instance, many organs have both 1 and 2 adrenoreceptors.(e.g., in the heart,
there is one 2 adrenoceptor for every three 1 adrenoreceptors). The receptors also
show differing responses to adrenaline and nor adrenaline. Adrenaline and nor
adrenaline appear to have an equal effect on the 1 adrenoreceptors in the heart
whereas the 2 adrenoreceptors in smooth muscle are more sensitive to circulating
adrenaline than nor adrenaline. The anatomic distribution of the various types of
adrenergic receptors and their actions at these sites is summarized in Table 1.

-Second Edition
2011

23


Table 1: Anatomic distribution of adrenergic receptors in the body and the
physiological effects of adrenergic stimulation.
Adrenergic Receptors
Recep
tor
Synaptic
Site
Anatomic Site Action
LV Function
and Stroke
Volume
1 Post
synaptic
Peripheral vascular smooth
muscle
Renal vascular smooth
muscle
Coronary arteries, epicardial
Myocardium

Renal tubules
Constriction

Constriction

Constriction
Positive
Inotropism
Antidiuresis
Decreased

Improved
2 Pre
synaptic

Post-
synaptic
Peripheral vascular smooth
muscle
Coronaries
CNS

Coronaries, endocardial
CNS

Renal tubule
Inhibit NE release
Secondary
vasodilation
Sedation
Decrease MAC
Constriction
Inhibition of
insulin release,
decreased bowel
motility.
Inhibition
antidiuretic
hormone
Analgesia
Promotes Na
+

and H2O
excretion
Improved

Decreased
1 Postsynap
tic NE
sensitive
Myocardium
Sinoatrial (SA) node
Ventricular conduction
Kidney
Coronaries
Positive
Inotropism and
chronotropism
Renin release
Relaxation
Improved
2 Pre
synaptic
Myocardium SA node

Accelerates NE
release
Improved

-Second Edition
2011

24


NE
sensitive
Post
synaptic
(extra
synaptic)
(EPI
sensitive)
Ventricular conduction

Vessels
Myocardium

Vascular smooth muscle
Bronchial smooth muscle
Renal vessels
Opposite action
to presynaptic
2 agonist
Constriction
Positive
Inotropism and
chronotropism
Relaxation
Relaxation
Relaxation

Improved
Improved
Improved
DA1 Postsynap
tic
Blood vessels (renal,
mesentery, coronary) Renal
tubules Juxta-glomerular
cells

Sympathetic ganglia
Vasodilation
Natriuresis/
Diuresis Renin
release
(modulates
dieresis)
Minor inhibition
Improved
DA2 Pre
synaptic
Post
synaptic
Postganglionic sympathetic
nerves
Renal and mesenteric
vasculature
Inhibit NE release
Secondary
vasodilation?
Vasoconstriction
Improved
NE= Norepinephrine EPI=Epinephrine DA1 and DA2 =Dopamine
Note: Though there are several other subtypes, their clinical relevance is unknown.
Parasympathetic Nervous System:
o The preganglionic outflow of the parasympathetic nervous system arises
from the cell both of the motor nuclei of the cranial nerves III, VII, IX and X
in the brain stem and from second, third and fourth sacral segments of the
spinal cord. It is therefore also known as craniosacral outflow.
o Preganglionic fibres run almost up to the organ which is innervated and
synapse in ganglia close to or within that organ, giving rise to
postganglionic fibres which then innervate relevant tissue. The ganglion
cells may be either well organized (as in the myenteric plexus the
intestine) or diffuse (as in bladder and blood vessels).
o The cranial nerves III, VII and IX affect the pupil and salivary gland
secretion while vagus (X) carries fibres to the heart, lungs, stomach, upper
intestine and ureter. The sacral fibres form pelvic plexuses which
innervate the distal colon, rectum, bladder and reproduction organs.
-Second Edition
2011

25


o In physiological terms, the parasympathetic system is concerned with
conservation and restoration of energy as it causes a reduction in heart
rate and blood pressure, facilitation digestion and absorption of nutrients,
and consequently the excretion of waste products.
o The chemical transmitter at both pre-and postganglionic synaptic in the
parasympathetic system is acetylcholine. Acetylcholine is also the
neurotransmitter at sympathetic preganglionic synapses, some
sympathetic postganglionic synapses, the neuromuscular junction
(somatic nervous system) and at some sites in the CNS. Nerve fibres that
release Ach from their endings are described as cholinergic fibres.
o Acetylcholine is synthesized in the cytoplasm of nerve endings and is
stored in vesicles in the presynaptic terminal. The arrival of a presynaptic
action potential causes an influx of calcium ions and release of the
contents of several hundred vesicles into the synaptic cleft. Acetylcholine
then binds to specific receptors on the postsynaptic membrane and
increase the membrane permeability to sodium, potassium and calcium
ions which results in excitatory postsynaptic potential. Acetylcholine is
hydrolyzed by the enzyme acetyl cholinesterase to bring about
termination of its action.
o Specific Ach receptors have been subdivided pharmacologically by the
actions of the alkaloids muscarine and nicotine. The actions of Ach at the
preganglionic synapses in both the parasympathetic and sympathetic
system are mimicked by nicotine and all autonomic ganglia are therefore
termed nicotinic. Nicotinic transmission also occurs at the neuromuscular
junction, in the CNS, the adrenal medulla and at some sympathetic
postganglionic sites. However, the actions of the Ach at the
parasympathetic postganglionic nerve ending in mimicked by muscarine.
Muscarinic transmission also occurs at certain site in the CNS.

-Second Edition
2011

26


-Second Edition
2011

27


Physiological effects of stimulation of the sympathetic and
parasympathetic divisions of the autonomic nervous system.
HOMEOSTATIC BALANCE BETWEEN ADRENERGIC AND CHOLINERGIC EFFECTS
Organ System Response
Adrenergic Cholinergic
Heart
Sinoatrial node
Atrioventricular node
His-Purkinje
Tachycardia
Increased conduction
Increased automaticity and
conduction velocity
Increased contractility,
conduction velocity Automaticity
Constriction ( 1)and dilation ( 1)
Bradycardia
Decreased conduction
Minimal

Minimal decrease in
contractility
Dilation and constriction
Blood vessels
Skin and mucosa
Skeletal muscle
Pulmonary

Constriction
Constriction ( 1) and dilation
( 1)
Constriction

Dilation
Dilation
? Dilation
Bronchial smooth
muscle
Relaxation Contraction
Gastrointestinal tract
Gallbladder and
ducts
Gut motility
Secretions
Sphincters
Relaxation
Decreased
Decreased
Constriction
Contraction
Increased
Increased
Relaxation
Bladder
Detrusor
Trigone
Relaxes
Contracts
Contracts
Relaxes
Glands
Nasal
Lacrimal
Parotid
Submandibular
Gastric
Pancreatic
Vasoconstriction and reduced
secretion
Stimulation of secretions
Sweat glands Diaphoresis (cholinergic) None
Apocrine glands Thick, odiferous secretion None
-Second Edition
2011

28


Eye
Pupil
Ciliary muscle

Mydriasis
Relaxation for far vision

Meiosis
Contraction for near
vision

-Second Edition
2011

29


This page intentionally left blank

-Second Edition
2011

30


Chapter 2 - AUTONOMIC NERVOUS SYSTEM DYSFUNCTION
AND ANESTHETIC IMPLICATION
Introduction:
Familiarity with the autonomic nervous system is important to the anesthetist:
In understanding the physiology of CVS
For skillful use of agonist and antagonist drugs acting on sympathetic and
parasympathetic nervous system.
In management of patients with impaired autonomic function.
In assessing anesthetic depth.
In performing diagnostic and therapeutic nerve blocks
Anatomy:
From a strictly anatomy point of view the autonomic nervous system is divided
into two parts.
Sympathetic part (Thoraco Lumbar)
Parasympathetic part (Cranio Sacral)
Sympathetic System:

-Second Edition
2011

31


Sympathetic system has connector cell bodies in the inferomedio lateral cell
column of the spinal grey matter in the thoraco lumbar region (T1-T2).their axons travel
of the sympathetic trunk where they may synapse with their affector cells. The
sympathetic trunk is ganglionated nerve chain extending from the base of the skull to
the coccyx lying about 1 inch from the midline of the vertebral column. As a result of
fusion there are approximately 3 cervical, 11 thoracic, 2-4 lumbar and 4 sacral ganglia.
The sympathetic innervation of adrenal medulla is peculiar in that its secretor cell
receives preganglionic fibres directly via the splanchnic nerves.

-Second Edition
2011

32


Parasympathetic Nervous System:
This division consists of special visceral nuclei in the brain stem from which
preganglionic fibres pass through cranial nerves III, VII, IX and X to reach effector
organs.

III Cranial Nerve through Ciliary ganglion
VII Cranial Nerve through Geniculate ganglion
IX Cranial Nerve through Otic ganglion
X Cranial Nerve to viscera
Sacral part of the parasympathetic system, originates in the lateral horn cells of
2,3 and 4 sacral segments. Preganglionic fibers traverse these sacral nerves and synapse
Fig. 3: Parasympathetic division of ANS
-Second Edition
2011

33


in the ganglia that lie within the walls of the distal colon, bladder and other pelvic
organs.
Physiology and Pharmacologic Considerations:
The function of the autonomic nervous system (ANS) is to regulate the activities
of the visceral organs that posses high degree of independence. Sympathetic system is
concerned with an often wide spread FIGHT OR FLIGHT response to the stress, while
the parasympathetic deals with the more discrete adjustments of relaxed homeostasis.
Some organs are stimulated by one division only e.g. Uterus, adrenal medulla and most
of the arterioles receive from sympathetic only. Glands of stomach and pancreas receive
from the parasympathetic only. Other has dual innervations which produce antagonistic
effect in the target organs.
Neurotransmitters:
All autonomic functions are mediated through neurotransmitters acetylcholine
(Ach) and nor-epinephrine (NE). Ach is released at the ends of all preganglionic fibers
(sympathetic and parasympathetic ganglia) as well as at the ends of all post-ganglionic
parasympathetic and a few post-ganglionic sympathetic fibers. Ach receptors are of two
types.
1. Muscarinic
2. Nicotinic
The post-ganglionic parasympathetic receptors are muscarinic, i.e. they are antagonized
by atropine drugs. Nicotinic receptors are blocked by tubocurarine. As a general rule
post ganglionic sympathetic fibers release NE at their terminals with few exceptions, eg:
sweat glands some blood vessels in the muscle are innervated by post-ganglionic
sympathetic fibers but release Ach.
Neurotransmitters:
Parasympathetic Sympathetic
Preganglionic Postganglionic Preganglionic Postganglionic
Ach Ach Ach NE

Adrenergic receptors are two types alpha and beta.
Alpha 1: Post synaptic mediate vasoconstriction, relaxation of gut and
Dilation of pupil.
Alpha 2: Pre synaptic when stimulated diminish the release of the
Transmitters
Beta 1: Limited to Heart-activation leads to increase in heart rate and
Contractility.
-Second Edition
2011

34


Beta2: When stimulated relax the smooth muscle of the bronchi and at most other sites.
CLINICAL FEATURES OF ANS DYSFUNCTION &
HYPOFUNCTION ON ANS: EFFECTS OF VARIOUS SYSTEMS
I Cardio vascular system: (CVS)
Resting Tachycardia:
An increased resting heart rate has frequently been observed. In advanced cases some
patients display a fixed heart rate which responds only minimally to physiologic stimuli.
The initial tachycardia is due to vagal cardiac neuropathy and fixed heart rate results
from the progression of dysfunction of cardiac sympathetic nervous system.
Orthostatic Hypotension:
This is defined as a fall in systolic blood pressure of 20 to 30mmHg or diastolic blood
pressure of 10 to 15 mmHg or during change of posture from lying to standing. Patients
typically present with lightheadedness and pre syncopal symptoms.
Treatment:
Non-Pharmacological:
Eating High Sodium Diet
Raising the head of the bed during sleep
Wearing supportive hose.
Pharmacological:
Mineralocorticoids e.g.: Fludrocortisone 0.1mg to 0.5mg
Sympathomimetic agents
Pressor agents
Prostaglandin synthesis inhibitors eg: Indomethacin, Ibuprofen.
Cardio-myopathy
This manifests as impaired myocardial contractility and decreased left ventricular
diastolic filing. Silent cardiac ischemia and prolongation of QT interval has also been
observed. Sudden death caused by cardio respiratory arrest and cardiac arrhythmias
has also been observed.
Gastrointestinal Tract:
Gastrointestinal Autonomic Neuropathy results in disordered gastrointestinal motility,
secretion and absorption.

-Second Edition
2011

35


Gastro paresis:
This may manifest as nausea, post prandial vomiting, bloating, belching, loss of
appetite, early satiety and delayed gastric emptying time.
Treatment:
Frequent small meals, Dopaminergic antagonists (Metoclopramide),
domperidone or Cisapride.
Nocturnal diarrhea which can last for hours or days frequently alternates with
constipations.
Urogenital system:
Bladder symptoms associated with autonomic neuropathy include hesitance, poor
stream, and sense of inadequate bladder emptying, urinary retention and overflow
incontinence. Sensory abnormality of Detrusor muscle producers impaired bladder
sensation and increase in threshold for initiation of micturition reflex.
Detrusor Areflexia:
A decrease in detrusor activity leads to incomplete bladder emptying, increased
post micturition residual volume, decreased peak urinary flow rate and urinary
retention.
Treatment:
Institution of regular voiding patterns, intermittent catheterization and use of
cholinergic agonists like carbachol and bethanechol.
Impotence:
Erectile function is mediated by parasympathetic nervous system.
Sympathetically mediated ejaculatory failure may precede the appearance of impotence.
IV. Others:
Sweating Abnormalities:
Unusual patterns of sweating abnormalities include focal loss of sweating and
gustatory sweating (an abnormal production of sweating after eating spicy food)
Neuroglycopenia and Hypoglycemic unawareness:
Unawareness of these symptoms is seen in ANS neuropathy. Neuroglycopenia
symptoms include cognitive dysfunction, encephalopathy, seizures, hemiplegia and
coma. Symptoms due to systemic epinephrine release are anxiety, hunger, restlessness,
diaphoresis and tachycardia.

-Second Edition
2011

36


HYPERFUNCTION OF ANS:
Phaeochromocytoma
Tetanus:
Sympatho-adrenal hyperactivity is a feature of tetanus as well the chief cause of death in
this condition. A direct effect to tetanus toxin on the sympathetic nervous system
produces high plasma catecholamine levels.
EVALUATION OF ANS DYSFUNCTION PRE ANESTHETIC
CHECK UP
History:
Routine information derived by careful history taking can raise suspicion
concerning autonomic nervous dysfunction.
History taking related to:
Orthostatic Tolerance:
a. Does the patient have the problems when arising in the morning?
b. Is there dizziness or faintness, nausea or diaphoresis while upright:
c. Has the patient fainted? Is fainting associated with emotional stress: Is it a
common occurrence: Is it related to meals intake (post prandial fainting)?
d. Bladder Sphincter disturbances and Impotence.
e. History of Night Blindness and Nasal stuffiness.
f. Impaired ability to sweat (Anhydrosis).
g. History of Drug intake: Antihypertensive, Antidepressants, Tranquilizers and
Diuretics.
h. History of Alcohol intake quantification.
i. History of diabetes mellitus, Chronic Alcoholism and Chronic renal failure.
If there is any doubt in history or in patients with diabetes mellitus etc., additional
bedside tests are to be done.

-Second Edition
2011

37


Bed side autonomic tests:
In patients with a positive history or disease processes associated with
autonomic dysfunction, a number of simple tests can be performed by anesthesiologist
during bedside visit. These can be divided into
I. Tests of Cardiac Vagal Function
II. Tests of Sympathetic Function
1. Tests of Cardiac Vagal Function:
Respiratory Sinus Arrhythmia (RSA)
Valsalva ratio (phase IV/II)
Bradycardia during phenylephrine challenge.
Absence of tachycardia with atropine.
2. Tests of Sympathetic Function:
a. Cardiac
Tachycardia during standing or head up tilt
Tachycardia during valsalva strain (phase II)
b. Peripheral
Blood pressure overshoot after valsalva release (phase IV)
Blood pressure increase with cold pressor test
Diastolic blood pressure increase with isometric hand grip exercise
Systolic and diastolic blood during response to upright posture.
Postural Stress: Supine to Standing
(Sympathetic Function)
The easiest and most commonly performed bed side test to evaluate autonomic function
is to record blood pressure and heart rate response to assumption of the upright
posture.
Procedure:
Heart rate and blood pressure should be recorded in the patient in supine
position after a resting period of 10 min. Then the patient is asked to stand up unaided
and after 50 seconds pulse rate and blood pressure are to be measured. When taking
blood pressure in a standing subject the cuff should be approximately at the
phlebostasis axis to eliminate the error due to gravity.
-Second Edition
2011

38


Result:
A decline in systolic blood pressure of greater than 20 mmHg is generally used as
a critical value suggestive of autonomic dysfunction. Similarly diastolic blood pressure
should not decrease by more than 10mm Hg during 1 min standing .Heart rate should
increase at least by 10beats/min in the upright position. The absence of tachycardia
during standing has also been interpreted as an impairment of sympathetic drive to the
heart.
Ratio of RR interval in ECG corresponding to 30
th
and 15
th
beats (30:15 ratios) is
a measure of integrity of vagal inhibition. A ratio in young adults of less than 1.04 is
abnormal.
Cold Pressor Test: (Sympathetic Function)
This is used to evaluate the peripheral sympathetic vasoconstrictor mechanism.
Procedure:
Record blood pressure response to a 1 min immersion of the hand in ice cold
water.
Result:
Both systolic and diastolic blood pressures at the end of 1 min of immersion
should increase at least by 10mm Hg.
Isometric Hand Grip Exercise (Sympathetic Function)
Procedure:
Record the blood pressure response to a sustained isometric contraction at 30%
of the patients maximum strength.
Result:
Diastolic blood pressure should increase at least by 10-15 mmHg at the end of
contraction. The failure to record a raise in diastolic blood pressure more than 10
mmHg is suggestive of deficient efferent sympathetic mechanisms.
Respiratory Sinus Arrhythmia: (RSA)
(Parasympathetic Function)
Perhaps the most sensitive test of cardiac vagal function is to determine the
maximum to minimum heart rate variation that occurs during forceful breathing.

-Second Edition
2011

39


Procedure:
Seated or lying subjects should breathe in at 6 breaths/min (5 sec. inspiration
and 5 sec. expiration). Maximum and minimum heart rate and RR interval variation are
recorded.
Result:
The average maximum to minimum heart rate variation during 3 consecutive
breaths should be greater than10 beats/min. The ratio of longest during inspiration
constitutes expiration and inspiration ratio. E:I less than 1.2 is abnormal in patients
upto 40 years of age.
Power spectral analysis of heart rate variability
There are slower periodic oscillations in heart period which can be decomposed into
series of sine waves with different amplitudes and frequencies. This frequency domain
approach reveals a consistent peak or power at the breathing frequency between 0.2 to
0.3 Hz (due to intact parasympathetic innervations of SA node) and another peak at low
frequencies between 0.05 to 0.15 Hz(due to changing levels of cardiac sympathetic
activity). Low frequency component is augmented by increased sympathetic drive eg.
head up tilt, mental arithmetic and reduced in quadriplegics with interrupted
sympathetic pathways.
The future in autonomic testing may be this quick determination of the relative power
in low and high frequency ranges by computer which will tell the status of autonomic
function.
Valsalvas Maneuver:
(Sympathetic and parasympathetic Function)
Instruments Required:
1. Pressure manometer connected to mouth piece.
2. Continuous recording of ECG or Intra arterial blood pressure.
Procedure:
The subject sits quietly or lies supine and blows into a mouth piece with an open
glottis and holds an airway pressure of 40mmHg for 15 seconds (Phase II) and is asked
to release the strain (Phase IV).
Result:
Heart rate normally increases during phase II of the maneuver i.e., 10 to 15
seconds after initiating the blowing but prior to release of the strain. This tachycardia is
due to baroreflex stimulation to the fall in blood pressure seen as result of raised
-Second Edition
2011

40


intrathoracic pressure (decreased venous return). On release of strain (Phase IV)
preload and cardiac output are restored and there is a blood pressure over shoot. This
hypertension stimulates baroreceptors initiating rapid reflex bradycardia.
The ratio of longest RR interval during phase IV to the shortest RR interval
during phase II has been used as an index of cardiac vagal function known as Valsalva
Ratio. A ratio of less than 1.2 is abnormal. Failure of heart rate increase during positive
intrathoracic pressure phase points to sympathetic dysfunction and failure of the heart
rate to slow during the period of BP overshoot points to a parasympathetic dysfunction.
Failure to observe BP overshoot flowing release of strain suggests that
peripheral sympathetic vasoconstriction has not occurred.
PHARMACOLOGICAL TESTS OF AUTONOMIC FUNCTION
Epinephrine Solution (1:1000) Instillation into Conjunctival Sac:
Procedure:
Instill 3 drops of the solution 3 times at 1 min interval. Pupillary size is checked
after 15, 30 and 45 min.
Result:
There is no effect on the normal pupil but is will cause the sympathetically
denervated pupil to dilate.
Cocaine (4 to 10%) Topical application:
Procedure: Some as above test.
Result: Normal response pupillary dilatation
In sympathetic enervation-no change in papillary size occurs because no
transmitter substance is available.
Histamine Test:
Procedure: Inject 0.05 ml of 1:1000 histamine phosphates intracutaneously.
Result: Normal response Triple response (1 cm wheal surrounded by narrow red
areola and this in turn by an erythematous flare)
In Familial Dysautonomia and peripheral neuropathies: Flare response is absent
Atropine Test:
Procedure: Inject 0.8mg of atropine intramuscularly.
Result: Normal response-There is an increase in heart rate caused by parasympathetic
block and unopposed sympathetic activity. No such change occurs in sympathetic
denervation of heart.
-Second Edition
2011

41


Ephedrine Test:
Procedure: Inject Ephedrine 25 mg intramuscularly.
Result: Heart rate increases normally.
In sympathetic denervation this response is absent.
Neostigmine Test:
Procedure: Inject Neostigmine 1 mg intramuscularly.
Result: Normal response-bradycardia in parasympathetic denervation no change
occurs.
OTHER TESTS:
Measurement of skin Temperature:
In sympathetic dysfunction there is a rise in temperature because of vasodilatation of
skin vessels caused by vasomotor paralysis.
Tests of Sudomotor Function:
Weight of the sweat Sweat can be weighed after it is absorbed by small squares of filter
paper.
Galvanic skin resistance test A string galvanometer indicates the resistance to the
passage of a weak galvanic current through the skin. An increase in sweating lowers the
resistance and anhydrosis raises it.
Tests of Lacrimal Function:
Schrimer test-tearing can be estimated by this test. Hypolacremia is suggestive of
autonomic dysfunction.
Tests of bladder and gastrointestinal function:
Bladder function is assessed by cystometrogram i.e., by measuring the intravesicular
pressure as a function of the volume of sterile saline solution permitted to flow by
gravity into the bladder.
Disorders of gastrointestinal motility can be demonstrated by radiological
examination like barium swallow and barium enema.

-Second Edition
2011

42


Laboratory Tests:
Measurements of plasma levels of catecholamines and other vasoactive
hormones such as renin, angiotensin and vasopressin. Levels of these hormones
are reduced in autonomic dysfunction.
Measurement of forearm blood flow with plethysmography.
Cerebral electroencephalography and blood flow studies.
CLINICAL TESTS OF AUTONOMIC FUNCTION
Non-Invasive Bedside Tests:
Test Normal response
Part of reflex ARC
tested
BP response to
Standing / Vertical
tilt
Fall in BP <30/15 mmHg- Afferent and efferent
limbs
HR response to
Standing
Increase 11-29 beat/min 30:15
ratio >1.04
Afferent and Efferent
limbs
Isometric Exercise Diastolic BP increase by 15mmHg Symp. Efferent limb
HR variation with
respiration
Max. Min. HR >15 beats/min Vagal Afferent and
Efferent limbs
Valsalva Ratio >1.4 Vagal Afferent and
Efferent
Sweat Tests Sweating all over body and limbs Symp. efferent limbs
Valsalva Maneuvers Phase I-Raise in BP
Phase II -Gradual reduction of BP
to plateau-Tachycardia. Phase III-
Fall in blood pressure
Phase IV-Overshoot of BP and
Bradycardia
Afferent and Efferent
limbs

-Second Edition
2011

43


DISEASES ASSOCIATED WITH PROGRESSIVE NEUROLOGICAL
IMPAIRMENT OF AUTONOMIC NERVOUS SYSTEM
They can be primary, idiopathic or due to secondary systemic disease or familial.
Primary:
1. Idiopathic Orthostatic Hypotension
2. Shy-Drager type of Orthostatic Hypotension
Familial:
1. Riley-Day Syndrome (Autonomic neuropathy in infants and children)
2. Lesch-Nyhan Syndrome
3. Gill Familial dysautonomia

Secondary to systemic diseases:
Aging
Diabetes Mellitus
Chronic Alcoholism
Chronic Renal Failure
Hypertension
Rheumatoid Arthritis
Carcinomatosis
Chagas disease
Tetanus
Spinal cord injury Transection
o Acute
o Chronic
Neurological diseases
o Tabes Dorsalis
o Syringomyelia
o Amyloidosis
Aging:
Approximately 20% of people over 65 years of age have postural hypotension. It
is estimated that one half of these patients are symptomatic that is they experience
dizziness, faintness, or loss of consciousness. It is well known that the reflex regulation
of heart rate which is mediated primarily by parasympathetic mechanisms declines
progressively with age. There will be a selective or earlier impairment of
-Second Edition
2011

44


parasympathetic function with aging with a minimal or a more gradual involvement of
the sympathetic nervous system.
Diabetes Mellitus:
Diabetic autonomic neuropathy is a well known clinical entity. It may result from
neuronal degeneration or metabolically related neuronal dysfunction. The afferent
central or efferent reflex pathways each can be involved. Diabetic autonomic
neuropathy may increase in frequency with the duration of the disease.
It has been suggested that the vagal neuropathy occurs earlier in the course of
DM than the sympathetic neuropathy. The most sensitive test of cardiac
parasympathetic impairment is that of determining RSA during forceful breathing.
Intolerance to upright posture is often evident. The presence of symptomatic postural
hypotension is associated with a poor prognosis. These patients are prone to sudden
cardiac death.
For those scheduled for surgery there are several implications that are important
to anesthesiologist.
1. Esophageal dysfunction and gastric hypotonia increase the risk of regurgitation
and aspiration.
2. Bradycardia, hypotension and cardiopulmonary arrest have been reported.
3. Abnormal blood pressure falls with induction and highest requirement for
intraoperative pressor agents to maintain stable hemodynamics.
4. ANS dysfunction may also interfere with control of ventilation, making diabetics
more susceptible to respiratory depressant effects of drugs.
5. Painless myocardial infarction and unexplained cardio respiratory arrest have
been reported.
Alcoholism:
Orthostatic intolerance occurs not only in chronic alcoholism but also after acute
alcohol ingestion and during acute withdrawal of alcohol.
Alcohol has direct effect on baroreceptors and poor nutrition associated with
alcoholism impairs the sympathetic nervous system at both central and peripheral
levels. Valsalva maneuver has been used to demonstrate the failure of sympathetic
vasoconstrictor mechanism. Valsalva ratio and cardiac acceleration following IV
atropine are shown to be diminished in alcoholics with neurologic deficits.
-Second Edition
2011

45


Spinal Cord Transection:
Spinal cord trisection in the description of damage to spinal cord manifested as
paraplegia or quadriplegia. The most common cause of spinal cord transection is
trauma and other causes being tumor, infection, vascular and developmental disorders.
Acute spinal cord transection manifests as spinal shock with features of flaccid
paralysis, loss of temperature regulation, loss of spinal reflexes, decrease in BP and
bradycardia. In chronic stages, spinal cord reflexes gradually return and patient exhibits
Autonomic hyper-reflexia or mass reflex.

-Second Edition
2011

46


Autonomic Hyperreflexia
Patients with spinal cord transection above T6 will exhibit this reflex. This reflex
response can be initiated by cutaneous or visceral stimulation below the level of
trisection. Distension of bladder, rectum or surgery is common stimulus.

Mechanism:
Stimulation below the level of spinal cord transection produces vasoconstriction
through activation produces vasoconstriction through activation of preganglionic
sympathetic fibers. In neurologically intact patients this outflow is modulated by
inhibitory impulses from higher centers in CNS. In the presence of trisection this
outflow is isolated from inhibitory impulses such that vasoconstriction persists below
the level of injury. This vasoconstriction results in hypertension which is perceived by
carotid sinuses producing bradycardia.
Symptoms and Signs:
Hypertension and bradycardia
Nasal stuffiness
Headache and blurred vision
Treatment:
Ganglion blocking drugs
Alpha adrenergic antagonists
Direct acting vasodilators
General or regional anesthesia
Stimulus below the level
Of spinal cord Transection
Activation of Pre-ganglionic
Sympathetic Nerves
Vasoconstriction
Vasodilatation
Bradycardia
Hypertension Carotid sinus
-Second Edition
2011

47


MANAGEMENTOF ANESTHESIA:
Acute Spinal cord transection:
The absence of compensatory responses of sympathetic nervous system makes
these patients show extreme decreases in blood pressure in response to acute changes
in posture, blood loss or IPPV.
Airway management
Liberal intravenous infusion of crystalloids
Blood loss should be replaced promptly
Hypothermia taken care of
Controlled ventilation
Chronic Spinal cord transaction:
The objective of management of anesthesia is the prevention of autonomic
hyperreflexia
General anesthesia which includes volatile drugs is effective in preventing this
response
Epidural and spinal anesthesia are also effective.
Block of afferent pathways with a topical local anesthetic applied to urethra may
not prevent this mass reflex.
Drugs used
o Sodium nitroprusside 1 to 2 g/kg/IV stat and IV infusion
o Nitroglycerine
o Clonidine
ANESTHETIC IMPLICATIONS IN AUTONOMIC DYSFUNCTION
Pharmacological Alteration:
Drugs may alter the autonomic transmission and thus interfere with the maintenance of
blood pressure, cardiac output under anesthesia. These drugs may form part of a
regular therapeutic regimen or might be administered by anesthesia. These drugs may
form part of a regular therapeutic regimen or might be administered by
anesthesiologist. Due attention must be paid to the various modes of action which
include.
1. Ganglion blockade e.g. Trimethaphan
2. Interference with noradrenaline synthesis E.g. Alpha Methyldopa, Carbidopa
3. Prevention of noradrenaline release e.g. Reserpine
4. Interference with noradrenaline uptake E.g. Guanithidine
5. Interference with not adrenaline breakdown E.g. MAO inhibitors
6. Agonists and Antagonists of autonomic receptors.
-Second Edition
2011

48


Receptor Agonists Antagonists
Alpha 1 Methoxamine Prazosin
Alpha 2 Clonidine Yohimbine
Beta 1 Adrenaline Metoprolol
Beta 2 Salbutamol Butoxamine
Dopaminergic 1 Dopamine Metoclopramide
Dopaminergic 2 Bromocriptine Haloperidol
Muscarinic Acetylcholine Atropine
Nicotinic Nicotine Curare

Effect of anesthetic agents on autonomic activity:
Opioids:
Morphine causes a biphasic response of circulation. The initial reduction in BP is
secondary to release of histamine and is followed by increase in BP which is due to
sympathetic stimulation. Plasma adrenaline increases upto 4 fold and Nor adrenaline 2
fold.
Agonists and antagonists:
Atropine Muscarinic antagonist
Metoclopramide Dopaminergic antagonist
Metoprolol Beta 1 antagonist
Clonidine Alpha 2 agonist
Some of these drugs may be used for premedication purpose.
IV Induction agents:
Intravenous Induction agents cause a reduction in arterial pressure associated
with baroreceptors mediated tachycardia except Ketamine. Plasma catecholamines are
usually reduced suggesting that central sympathetic activity is reduced inspite of
baroreceptor stimulation.
Etomidate, an Imidazole derivative is a potent inhibitor of adrenal
steroidogenesis regulating in inhibition of cortisol and aldosterone synthesis.
Ketamine produces sympathetic stimulation.
Volatile Anesthetics:
Halothane causes dose dependent reduction in preganglionic sympathetic
activity, resulting in the decrease of the release of noradrenaline by the adrenal medulla
and causes a reduction in plasma noradrenaline concentration. Halothane reduces
sympathetic activity by decreasing the release of noradrenaline.
-Second Edition
2011

49


Enflurane and Isoflurane decrease preganglionic sympathetic activity resulting
in the decrease of plasma catecholamine. Enflurane does not appear to modify
synthesis, metabolism or reuptake of catecholamines.
Cyclopropane and Diethyl ether increase sympathetic activity. Diethyl ether
increases pre-ganglionic sympathetic activity because of central action or an effect of
the vasomotor neurons in the spinal cord.
Muscle relaxants:
Pancuronium increases heart rate and blood pressure by way of stimulating
sympathetic system releasing adrenaline.
CONDUCT OF ANESTHESIA IN PATIENTS WITH ANS
DYSFUNCTION:
Management of anesthesia is based on understanding the impact of reduced
autonomic nervous system activity on the cardiovascular responses to such events as
changes in the body position, positive airway pressure and acute blood loss as well as
on the effects produced by administration of negative inotropic anesthetic agents.
Posture:
Since there is an exaggerated reduction in the blood pressure in the upright
posture it is advised to be cautious in shifting the patient to the operating theatre
preferably in supine position only. Induction in other than supine posture is better
avoided.
Premedication:
Narcotic analgesics and other drugs which depress respiratory centers are best
withheld because ANS dysfunction may interfere with control of respiration. Fentanyl
appears to be acceptable choice.
It is to be appreciated that atropine may fail to produce tachycardia.
Metoclopramide is advised to hasten gastric emptying since there will be gastroparesis.
Acid prophylaxis with ranitidine is recommended in view of possible regurgitation and
aspiration.
Monitoring:
Continuous measurement of arterial blood pressure by invasive technique or
NIBP.
CVP and / or PA Cather is useful in guiding the rate of intravenous fluid infusion
ECG- to monitor arrhythmias and ischemic changes
Pulse Oximeter for SaO2
-Second Edition
2011

50


Temperature recording
Urine output monitoring by catheterization of the bladder
Induction:
Thiopental as used for the induction of anesthesia might provoke an exaggerated
decrease in blood pressure if the rate of administration is rapid or if the intravascular
fluid volume is decreased.
Diazepam and Fentanyl are also advised. Ketamine may produce accentuated
blood pressure increase.
Intubation:
Rapid sequence induction intubation is advised because the patients often
exhibit gastroparesis.
Maintenance:
Spontaneous breathing with nitrous oxide and oxygen with minimal
concentration of halothane is advised. If muscle relaxants are to be used, cardio-stable
drug like vecuronium is chosen. Pancuronium produces hypertension and tachycardia.
IPPV produces exaggerated reduction in blood pressure since compensatory
mechanisms are not functioning. Hence low tidal volumes with minimal airway
pressure are to be used so that interference with venous filling is minimal.
Blood loss has to be meticulously assessed and blood has to be replaced
promptly otherwise exaggerated hypotension occurs since compensatory
vasoconstriction does not occur. Tachycardia as compensatory response to blood loss is
absent.
If a vasopressor is needed it should be appreciated that these patients can exhibit
exaggerated response to drugs that act by provoking the release of NE (denervation
hypersensitivity). Direct acting vasopressor like phenylephrine is used in infusion form
to maintain the blood pressure in the normal range in micro.gm/kg/min.
Volatile anesthetics produce exaggerated myocardial depression and
hypotension so caution is exercised in using them.
Fluid balance has to be maintained on the positive side to counter the
hypotension.
Hypothermia should be avoided as these patients tend to become poikilothermic
because of sympathetic dysfunction.
Regional anesthesia:
The risk of hypotension after the administration of spinal or
epidural anesthesia detracts from the use of these techniques in affected
patients. Post anesthetic (spinal) urinary retention may be problematic in these
-Second Edition
2011

51


patients who have already reduced genitourinary motility. The preoperative
presence of impotence must be brought to the notice before administering
regional anesthesia to avoid medico legal problems.

-Second Edition
2011

52



-Second Edition
2011

53


Chapter 3 - CEREBRAL BLOOD FLOW AND METABOLISM
The brain is one of the highly vascular and metabolically active organs of the human
body. Adult human brain weight 1350 gm (2% of the body weight) and the blood flow it
receives is 12-15% of the cardiac output. In absolute terms the normal cerebral blood
flow (CBF) is 45-55 ml/100 gm/minute (750 ml/minute in a 70 kg adult/). The regional
distribution of CBF is such that the cortical blood flow is four times the sub cortical
blood flow. At rest, the brain consumes 3-3.5 ml of O2/100 gm/minute which is
approximately 20% of whole body O2 consumption. This would explain the sensitivity of
the brain to O2 deprivation brain receives 12-15% of the cardiac output as the CBF but
consumes 20% of total body O2 utilization. The bulk of the energy consumed by the
brain (55-60%) goes towards maintaining the electrophysiological function of the brain
(EEG activity) and the remaining 40-45% is utilized for maintaining the integrity of the
neurons. The implication of this is that pharmacological interventions like barbiturate
therapy which decrease the CMRO2, influence only the functional component of energy
consumption, because they act by suppressing the electrical activity of the brain.
Given the important function of the brain, its demand for subtract has to be met
by adequate delivery of glucose and oxygen. However, the space constraint imposed by
the rigid cranium and meninges requires that the CBF cannot be excessive also, because
of the limitation of volume within the cranium. In view of this, there are elaborate
mechanisms in the brain for regulating the CBF in response to various physiological
factors. In order to understand the effect of anesthesia and anesthetic agents and allied
drugs on CBF and CMRO2 it is necessary to review the physiological regulation of CBF
and CMRO2 in the normal brain first. The discussion which is to follow will be covered
under the following headings:
1. Physiological regulation of CBF and CMRO2.
2. Effect of anesthesia on CBF and CMRO2.
3. Effect of anesthetic agents and allied drugs on CBF and CMRO2.
Physiological Regulation of CBF and CMRO2:
1. Flow-Metabolism coupling
2. Auto regulation of CBF
3. Effect of PaCO2 and PaO2 on CBF and CMRO2.
4. Neurogenic control of CBF
5. Effect of viscosity on CBF

-Second Edition
2011

54


Flow-Metabolism Coupling:
There is an intrinsic in mechanism in brain for maintaining the CBF proportionate to the
cerebral metabolic demand for O2 and substrates. In a non pathological and a
normocapnic brain, the CBF/CMRO2 ratio is closely maintained in the range of 14-18.
Any rise in CMRO2 is matched by a parallel increase in CBF, for example during
electroconvulsive therapy there is twofold rise in CMRO2 and a matching rise in CBF
also. This is referred to as flow-metabolism coupling. The proposed mechanisms for
coupling are:
a. Neurogenic control
b. Role of biochemical mediators, released in response to the rise in CMRO2
c. K
+
release by glial cells (glial foot processes directly about the cerebral
vasculature).
d. PaCO2 level.
Cerebral Auto regulation:

One of the features of a healthy normal cerebral vasculature is an intact auto-regulatory
response to variation in mean arterial pressure (MAP). Auto regulation is accounted for
by the myogenic response secondary to change in vessel wall tension. In a normotensive
individual over a range of cerebral perfusion pressure (CPP) of 50-150mmHg, a
constant CBF is maintained, by altering the (Figure 1) cerebrovascular resistance. But
auto regulation takes some times to set in. hence, if there is an abrupt change in CBF
also for a brief period (1-2 minutes) before auto regulation sets in and restores the CBF
back to the normal level. Thus, abrupt rise in MAP which occurs with maneuvers like
-Second Edition
2011

55


laryngoscopy; intubation etc. can still cause a rise in CBF and ICP (transiently) in a
patient with intact auto regulation. In a patient with chronic arterial hypertension, the
auto regulation curve is shifted to the right whereas in a patient with carotid stenosis
(CPP is decreased) auto regulation curve is shifted to the left. Certain other conditions
where there is an altered/abnormal auto regulation are: head injury, stroke, and intra
cranial tumors. Besides this, cerebral (CBL) vasodilators also impair or abolish auto
regulation.
Effect of PaCO2 and PaO2 on CMRO2
CBF-PaCO2 curve is a sigmoid shaped curve which plateaus at either end of the scale.
Over a range of PaCO2 of 20-80 mmHg there is a linear fourfold rise in CBF with no
change in CMRO2. A 1 mmHg drop in PaCO2 causes a 2% decrease in CBF
(approximately). CBF response to PaCO2 is driven by rapid change in H
+
ion
concentration in the cerebrospinal fluid (CSF). CO2 readily crosses the blood-brain
barrier and hence CBF response to CO2 is almost immediate. However with a chronic
change in PaCO2, CBF returns to baseline over a period of 24-36 hours. This is accounted
for by the gradual return of the CSF pH back to normal, secondary to the adjustment of
the CSF bicarbonate level. Bicarbonate does not cross the blood brain barrier readily.
Hence, CSF pH takes a much longer time to normalize as compared to the pH of plasma.
There is no other physiological/ pharmacological factor which can cause a similar
degree of change in CBF. Normal CO2 reactivity is one of the hallmarks of a health
cerebral vasculature. In presence of pathology CO2 response is the last to be abolished.
Once the CO2 response is abolished, the cerebral vasculature does not respond to any
other physiological or pharmacological factor.
Adaptation to hypocapnia: With prolonged hyperventilation, in normal individuals,
vascular pH normalizes in 4-6 hours while CSF pH takes 24-36 hours to normalize.
Hence, it is believed by some that prolonged hyperventilation is probably of no benefit
in decreasing the CBF. However this interpretation has to be viewed vis--vis the
following points:
I. In a normal individual CSF pH normalizes slowly with a half-life of 6 hours. It is
possible that it takes much longer in the presence of intracranial pathology.
II. In the presence of a cerebral pathology like tumor or head injury there is CSF
acidosis. In such cases, it is a matter of conjecture as to how long CSF pH would
take to normalize. If at all it occurs.
III. Once the CSF pH normalizes, raising the PaCO2 from 20 mmHg to 40 mmHg
abruptly amounts to the same as raising the PaCO2 from 40 mmHg to 80 mmHg
in a normal brain. From this point of view also it is advisable that hypocapnea be
continued, rather than discontinuing it suddenly.
-Second Edition
2011

56


Response to PaO2
CBF response to PaO2 is very sluggish. CBF change (rise) occurs only when PaO2
drops to less than 50 mmHg, because CBF starts rising only when the absolute O2
delivery to the brain decreases.
O2 delivery =CBF x (A-V)O2 difference:
Figure 2 shows the relationship between PaO2, cerebral O2 delivery and the CBF.
The break point of the curve is around 50 mmHg. Below this level there is an abrupt rise
in CBF. But O2 delivery to the brain is maintained up to a PaO2 of 30 mmHg. This
response is driven by the accumulation of acidic metabolites secondary to hypoxia. At
the other end of the scale, only at around 1 atmosphere PaO2 a slight decrease in CBF
can be demonstrated.
Neurogenic Regulation of CBF:
There is evidence of extensive innervations of the cerebral vasculature. The
density of the innervations decreases with vessel size. Hence, neurogenic regulation of
CBF acts mainly on the large size blood vessels, controlling the CBF in large areas the
brain. Cholinergic, adrenergic and serotonergic system has all been demonstrated in
both extra and intracranial vasculature. The central control for neurogenic regulation is
via the sympathetic system, through the superior cervical ganglion. There is some
evidence of innervations from the locus caerulus and dorsal raphae nucleus also. In
support of neurogenic regulation, it has been shown that in a situation where
sympathetic blockade is achieved and then hypotension is induced. CBF is maintained
up to a much lower level of MAP as compared to a situation of hypotension with intact
sympathetic activity. At the upper level of auto regulation, intense sympathetic activity
offers some protection against hypertension induced breakthrough of blood-brain
barrier.

-Second Edition
2011

57


Effect of Viscosity on CBF:
Viscosity influences CBF and the most important determinant of viscosity is
hematocrit. Variations of normal range (33%-45%) cause only modest change in CBF.
Beyond this range effect of viscosity is more apparent. In polycythemia, CBF decreases
and in anemia it rises. In presence of a focal cerebral chemical there is a rise in CBF due
to impaired O2 delivery. In such a condition if hematocrit is decreased from 34% to 30%
there is a further rise in CBF, thus optimizing the O2 delivery to the tissues.
Cerebral Metabolism:
Unlike CBF, which can vary considerably in a normal awake state, global cerebral
metabolism (CMRO2) is a remarkably stable parameter. The only factor varying CMRO2
is age-it decreases gradually by 10% with age in proportion to the progressive decrease
in the population of neurons in the brain. In children, CMRO2 is 25% higher as compared
to adults. This may be due to developmental factors, hormonal influences or the effect of
other unrecognized differences between these age groups. Although global CMRO2 is
remarkably constant, regional changes in CMRO2 do occur continually in the awake
brain and coupled changes in CBF also occur. Thus as CMRO2 increases in one area of
the brain, simultaneously or the effect of other unstimulated regions keeping the global
CMRO2 constant.
Effect of Anesthesia on CMRO2 and CBF:
When is the Brain Anaesthetized?
The clinical, electrophysiological, cerebrovascular and metabolic correlates of
anesthesia are still not very clear. From the clinical point of view, anaesthetized state
corresponds to loss of consciousness, suppression of unwanted reflexes, analgesia and
muscular relaxation. In a laboratory study CMRO2 and EEG were repeatedly studied
during the induction of anesthesia with a variety of anesthetics (halothane, enflurane,
isoflurane and thiopentone). All the anesthetics studied had similar effects on cerebral
physiology. Initially only a modest rate of decline in CMRO2 was observed at a stage
when EEG pattern was one of a stable awake state. Between 0.3-0.5 MAC EEG pattern
became a complex mixed type of high frequency low amplitude and low frequency high
amplitude activity. At this stage, rate of decline in CMRO2 increased until a stable EEG
pattern of low frequency high amplitude was established at 0.5-0.7 MAC. With this EEG
pattern, rate of decrease in CMRO2 slowed down to that observed initially. This change
in EEG pattern from a stable awake one to a stable anesthetic pattern reflects a major
functional change characteristic of induction of anesthesia. It seems likely that
anesthetic metabolic effects are produced by a generalized neuronal membrane effect
rather than a regional one. Further, it has been conclusively shown that any metabolic
changes during anesthesia are secondary to change in brain function. Anesthetics do
-Second Edition
2011

58


not, in anyway, interfere with neuronal oxygenation. Once EEG isoelectricity is achieved
with a large dose of any anesthetic, CMRO2 reaches a plateau. Any further increase in
dose of anesthetics does not decrease in CMRO2 any further .

Cerebrovascular effects of anesthesia: All anesthetics including N2O, as a group,
appear to uncouple the normally tight relationship between CBF and CMRO2. The only
other instance where this may happen is in the presence of CNS pathology. Thus, if BP is
maintained constant, in the face of an increasing anesthetic concentration CBF/CMRO2
ratio progressively increases. If sagittal sinus PO2 is recorded, it progressively increases
over a range of 0-2.5 MAC.

-Second Edition
2011

59


In fact, no matter which anesthetic is used, a progressively reproducible increase in
sagittal sinus PO2 (from 35 to 70 mmHg) can be observed with an increase in anesthetic
concentration. The cerebrovascular effects of inhalational anesthetics probably
represent the interaction of two independent mechanisms- a direct cerebral
vasodilatation effect tending to increase CBF and an indirect passive effect in response
to a decrease in CMRO2 which, by coupled effect, tends to cause cerebral
vasoconstriction and decrease CBF. E.g. halothane being a more potent cerebral
vasodilator and poor metabolic depressant causes considerable increase in CBF.
Isoflurane, on the other hand, is a potent depressor of CMRO2 and hence increase in CBF
with isoflurane is not all that high in clinically relevant concentrations. Because of their
cerebrovascular effects, inhalational anesthetics will attenuate or even abolish CBL auto
regulation. CO2 reactively appears to be exaggerated by them.
Intravenous anesthetics in general do not disturb the normal coupling between CBF and
CMRO2. They decrease the CMRO2 and a coupled decrease in CBF occurs. However by
themselves, IV anesthetics like barbiturates- in the absence of metabolic effects are
vasodilators, though hardly ever observed in clinical practice. This is because in clinical
concentration, the metabolic effects are potent enough to totally override the direct
vasodilator effect. Thus as is true for the awake brain, so too for the anesthetized brain,
function metabolism drives flow. Both auto regulation and CO2 reactivity are intact
during intravenous anesthesia. CO
2
response is blunted due to metabolism induced
vasoconstriction.
Effect of Anesthetic Agents and Allied Drugs on CBF CMRO2:
1. Inhalational Anesthetics
2. IV Anesthetics
Other Agents Local Anesthetics
Muscle Relaxants
Vasoactive Drugs.

-Second Edition
2011

60


Inhalational Anesthetics:
CBF, CMRO2 effects of all inhalational anesthetics are discussed together here because
leaving aside some of the earlier studies most of the recent studies are compressions of
the CBF, CMRO2 effects of halothane, enflurane and isoflurane - the three commonly
used inhalational anesthetics. Among these three drugs the order of vasodilating
potency halothane > enflurane > isoflurane. The general pattern of the effect of volatile
anesthetics on cerebral physiology is a dose related decrease in CMRO2 with a
simultaneous increase in CBF. Hence, it is commonly mentioned that volatile anesthetics
cause uncoupling of flow and metabolism. However, there is evidence now that coupling
persists under the influence of volatile anesthetics, that is, CBF changes paralleling
changes in CMRO2 do occur during volatile anesthetic anesthesia. However, the
CBF/CMRO2 ratio increases to a higher level (N- 14:18). There is a positive correlation
between MAC of different anesthetics and CBF / CMRO2 ratio.
A meaningful comparison between the effects of various volatile anesthetics on CBF and
CMRO2 is possible only if the various factors influencing these parameters are
controlled, viz.., background anesthesia, MAP, blood gas parameter, etc. In humans
when a MAP of 80 mmHg is maintained, equipment (1.1 MAC) concentration of
halothane, enflurane and isoflurane cause an increase CBF of 191%, 31% and 18%
respectively. The degree of CMRO2 reduction with halothane, enflurane and isoflurane
in humans has not been compared. In an experimental study it was shown that
halothane causes a 25% decrease in CMRO2 while enflurane and isoflurane decreased
CMRO2 by 50% with isoflurane, isoelectric EEG (maximum CMRO2 suppression 50%)
is achieved at clinically relevant concentrations (less than 3 MAC) and in animal studies,
further rise in inspired concentration of isoflurane up to 6% did not cause any
metabolic toxicity. However, with halothane a concentration of more than 4 MAC is
required for inducing an isoelectric EEG (much beyond clinically relevant
concentrations). At this concentration there is evidence of metabolic toxicity and
interference with oxidative phosphorylation. The cerebrovascular effects of volatile
anesthetics are the net result of two influences-a direct cerebral vasodilating effect
tending to increase CBF and an indirect cerebral vasoconstriction effect (coupled to
decrease in CMRO2) tending to decrease the CBF. Since the vasodilatory influence is
dominant, net effect is a rise in CBF with all the volatile anesthetics. The indirect effect
of decrease in CBF differs in potency form agent to agent and this is probably the basis
for the difference in the magnitude of rise in CBF with different agents. At equipotent
MAC concentration halothane has a minimal effect on CMRO2 and hence increase in CBF
is maximum with halothane and least with isoflurane (as isoflurane causes a 50%
decrease in CMRO2). Once the maximal suppression of CMRO2 has been achieved with
any agent, any additional dose of volatile anesthetic only causes direct vasodilating
-Second Edition
2011

61


effect resulting in a rise in CBF. The direct vasodilator effect of isoflurane is as much as
that of halothane hence if isoflurane is administered in the setting of a decrease in
CMRO2 induced either by drugs or cerebral pathology-this vasodilator effect is evident
causing a significant rise in CBF.
Regional distribution of CBF and CMRO2: If regional distribution of CBF and CMRO2 is
studied under the influence of volatile anesthetics then a difference in pattern is
observed between halothane and isoflurane. Halothane causes a homogenous change
throughout the brain and there is a global decrease in CMRO2 with a global increase in
CBF in neocortex and sub cortical areas. Isoflurane, on the other hand has a
heterogeneous effect CBF increases are greater in the sub cortical area and hind brain
than in the neocortex. This is probably because the suppression of CMRO2 with
isoflurane is predominantly in the neocortex. The net effect is, in neocortex, at equi
MAC-concentration, increase in CBF is more with halothane compared to isoflurane. In
sub cortical areas in some areas CBF with halothane and isoflurane are the same. In
certain other sub cortical areas, rise in CBF is more. In some studies though the increase
in CBF is found to be less with isoflurane, the increase in ICP has been found to be the
same with both. This is probably because the ICP is related to CBF changes in sub
cortical structures, which is about the same with halothane and isoflurane. The net
vasodilating effect of equi MAC concentration of isoflurane is less in human as compared
to halothane. Hence, in a setting of impaired intracranial compliance, isoflurane is
preferred to halothane. However; with the indication of hypocapnia, this vasodilating
influence of both halothane and isoflurane can be largely prevented or at least
attenuated. With isoflurane prior induction of hypocapnia is not necessary.
Simultaneous induction of hypocapnia is enough to neutralize the increase in CBF with
isoflurane.

-Second Edition
2011

62


CO2 response and auto regulation: CO2 response is well maintained under the
influence of volatile anesthetics. But Auto regulation of CBF is impaired. This is
maximum with halothane as halothane is a more potent vasodilator compared to
isoflurane. As mentioned earlier, CO2 response of cerebral vasculature is the last to be
abolished in presence of an intracranial pathology. Because of intact CO2 response, by
varying the PaCO2 level it is possible to modify the vascular effects of volatile
anesthetics.
Time course of CBF effects of inhalational anesthetics: As per some of the laboratory
studies, CBF effects of halothane and isoflurane are time dependent. Studies lasting for
long duration have shown that over the course of 3-5 hours CBF reaches the baseline
level thereby indicating that vasodilating influence does not last long. This has been
explained on the basis of prolonged immobilization or effect of controlled ventilation
etc, there is no clinical study to substantiate this. The only available clinical data is from
studies in patients for carotid endarterectomy. In these cases it was found that over the
course of 1-2 hours there is no decrease in CBF (that is, the increase in CBF with
halothane persisted for 1-2 hours).
Sevoflurane and Desflurane: These two are the new volatile anesthetic agents. Both of
them are more potent and have low blood-gas solubility coefficient (sevoflurane 0.6 and
desflurane 0.42). Hence, they have a quick onset and offset of action. CBF, CMRO2 and
EEG effects of sevoflurane are similar to those of isoflurane.
Effect of N2O on CBF: The first valid quantitative method CBF measurement, in man
introduced by Kety and Schmid utilized 15% N2O is an inert gas with no effect on
cerebral physiology. However, now we know that N2O is far from being inert in its
potential cerebral effects. As per the available data there is unequivocal proof that N2O
cause in increase in CBF and ICP. The magnitude of rise in CBF and ICP is however
variable depending on the background anesthetic (60%-100% rise in CBF). As per
studies, N2O is a patient CBL vasodilator. In the presence of a space occupying lesion the
rise in CBF and ICP is much more. Further, this vasodilator effect is attenuated or even
abolished by thiopentone, diazepam, narcotics and hyperventilation. Addition of N2O to
a background of volatile anesthetic causes a further rise in CBF. The data regarding the
-Second Edition
2011

63


effect of N2O on CMRO2 is contradictory. As per some of the studies,N2O causes a
minimal decrease in CMRO2. This would explain the commonly accepted clinical
assumption that N2O is an inert gas without any effect on cerebral physiology. Clinically
N2O is rarely ever administered alone. It is always given to a patient after induction of
anesthesia with thiopentone and hyperventilation is induced. In many of the patients
narcotic analgesics are also given. In fact, thiopentone in action with N2O and narcotic is
one of the commonly accepted anesthetics in neuro-anesthesia. In such a setting
cerebral vasodilator effect of N2O is either attenuated or abolished by the background
anesthetic. High dose barbiturate or narcotic analgesic administration abolishes N2O
induced vasodilatation. There are several experimental studies to show that N2O
narcotic anesthetic maintains CBF and CMRO2 at baseline levels. These above data
indicate that vasodilatation of N2O can be clinically significant in patients with poor
intracranial compliance, especially if N2O is used alone in presence or moderate levels
of hypocapnia.
Intravenous Anesthetics:
As a group, all IV anesthetic agents induce a decrease in CMRO2 and a parallel
decrease in CBF, the only exception being ketamine.
Barbiturates: Barbiturates are the most potent depressants of CMRO2, CBF, and ICP
and is dose dependent. With the onset of anesthesia, CMRO2 and CBF are decreased by
30%. With larger doses of thiopentone ECG suppression can be achieved to the point of
isoelectricity and CMRO2 and CBF are decreased by 50%. Further, it has been shown
that the primary effect of barbiturates is on brain function-they depress neuronal
function. This in turn, causes a coupled decrease in CMRO2 and CBF. Thus in vivo
because of their coupled effect on CBF vasoconstrictors. This is in contrast to the in vitro
effect; In vitro barbiturates are point cerebral vasodilators and can neutralize the
vasoconstriction induced by nor-epinephrine, K+, serotonin and PGF2 alpha. Further
increase in dose of barbiturates beyond the point of isoelectric EEG does not have any
effect on CMRO2 and CBF. This reinforces the concept that barbiturates (and for that
matter, all other anaesthetizes) can reduce/suppress that component of the CMRO2
linked to brain function (EEG activity) only. It has no effect on the component of CMRO2
-Second Edition
2011

64


(brain function and cellular homeostasis). At a temperature of 28 degree centigrade, we
can achieve a reduction in CMRO2 and CBF which occurs at normothermia with high
dose of thiopentone. Under the influence of barbiturates, CO2 response is attenuated
but not abolished and auto regulation is also maintained.
Clinical implications: The clinical implications of the effect of barbiturates on CMRO2
and CBF are in brain protection. In the presence of a complete global ischemia (cardiac
arrest). Since the basal metabolic state (isoelectric EEG) is immediately induced by the
insult. Further metabolic suppression (and hence protection) cannot be achieved by
barbiturates or other anesthetics. Hence, in cardiac arrest cases it is entirely predictable
that protection will not be demonstrable with barbiturates. In fact, such a prediction is
strongly supported by available studies reported in literature. In contrast to this, in
incomplete ischemia, there is an area of ischemic penumbra. The ischemic area may
continue to function at a CMRO2 higher than the basal level. Hence, a potentially
protective intervention like barbiturate therapy can decrease CMRO2 further to basal
level and thus might protect the brain. From a cerebrovascular point of view also blood
may get diverted from the normal area to ischemic area due to cerebral
vasoconstriction induced by barbiturates and thus improve the perfusion to the
ischemic zone.
Narcotics: A review of literature on the effect of narcotics on CBF and CMRO2 shows
that there is no consensus, but only an array contradiction. This is because the effect of
narcotics on CBF and CMRO2 is significantly influenced by the baseline anesthetic. The
general pattern observed with narcotics is one of modest decrease in CMRO2 and CBF.
When baseline anesthetic is N2O with minimal sedation and paralysis, narcotic
administration causes a substantial reduction in CBF and CMRO2 because the effect
observed here is that of reduction of arousal plus the basic effect of the narcotic. When
morphine is administered to patients anaesthetized with 70% N2O, there is no change
in CBF and CMRO2 compared to the baseline level; while compared to the CBF with 70%
N2O there is a substantial reduction in CBF, because N2O as such increases the CBF and
this is neutralized by morphine. Similarly, studies with fentanyl and sufentanyl also
show the evidence of modest decrease in CBF and CMRO2 or no change. However,
-Second Edition
2011

65


fentanyl can cause convulsions in some cases in high doses, in such cases significant
increases in CMRO2 and CBF is observed. There are a few studies showing a slight
cerebral vasodilatation with sufentanyl, causing an increase in ICP-this effect is
attenuated by hypocarbia.
Benzodiazepines: Benzodiazepines cause a parallel coupled decrease in CMRO2 and
CBF. The quantum of change is similar with equipment doses of diazepam, lorazepam
and midazolam. CO2 response is preserved. When compared to other drugs, the extent
of reduction in CMRO2 and CBF is somewhere between that of barbiturates and
narcotics. Similarly droperidol also induce only a modest decrease in CMRO2 and CBF.
Nonbarbiturate IV anesthetics: The effect of other IV anesthetics like etomidate,
althesin and propofol on CBF and CMRO2 is similar to that of barbiturates. There is
progressive EEG suppression and coupled to reduction in CMRO2 and CBF. However,
the quantum of decrease in CMRO2 and CBF with these drugs is not as much as with
barbiturates (etomidate-45% and 34% decrease in CMRO2 and CBF respectively). This
is probably due to a difference in the site of action- etomidate and althesin cause a more
profound decrease in CMRO2 of the forebrain while barbiturates have a global effect.
Etomidate and althesin are more cardio-stable as compared to barbiturates. Hence
cerebral perfusion pressure is maintained with these drugs. Propofol is a new IV
anesthetic and needs to be evaluated more. As per the available information, propofol
can cause 36% and 51% decreases in CMRO2 and CBF. However, in this dose propofol
also causes decrease in MAP; as a result, CPP decreases with propofol.
Ketamine: It is the only exception to the other IV anesthetics. It activates cerebral
function and thus increases CMRO2. It specifically activates the limbic system and
thalamus. In the only available human study 62% increase in CBF effect of ketamine. It
is also known that there is a species difference in the effect of ketamine on CMRO2
depending on the area of the brain activated.
Other agents:
Muscle relaxants.
Local anesthetics.
Vasoactive agents.
-Second Edition
2011

66


Muscle relaxants: Muscle relaxants, because of their chemical structure do not readily
cross the blood-brain barrier. Hence, they have no direct effect on CBF and CMRO2.
There are however, certain other mechanisms by which muscle relaxants influence CBL
physiology. These are:
Histamine release
Hemodynamic effects
Effect of metabolites
Systemic metabolic effects
Alteration in cerebral afferent activity.
D-tubocurarine is the most potent histamine releasing agent. Metocurine and
atracurium also release histamine but to a lesser extent. Histamine release causes
systemic and cerebral vasodilation resulting in a decrease in MAP, increase in CBF and
increase in ICP. The net result is a decrease in CPP.
Pancuronium: causes a 10-20% increase in heart rate and MAP following a standard
dose of 0.1mg/kg. This degree of hemodynamic response has no effect on normal
intracranial dynamics. But in the presence of an intracranial pathology with defective
auto regulation, this can cause an abrupt increase in CBF and ICP.
Atracurium also has a potential to release histamine but to a much lesser extent
compared to d-tubocurarine and it does not have any significant hemodynamic effect.
Hence, intracranial space occupying lesion. Atracurium has no significant effect on CBF
and ICP. Form theoretical point of view, one of the metabolites of atracurium,
Laudanosine crosses the blood brain barrier and can cause seizures in laboratory
animals. However, such an effect has not been reported clinically.
Vecuronium is the most inert of all muscle relaxants, from the cerebral physiology point
of view. It has no systemic hemodynamic effect, no histamine releasing potential and no
cerebrally active metabolites are produced. Clinical studies have also substantiated this.
Even in brain tumor patients vecuronium has no effect on CBF and CMRO2.
Succinylcholine (scoline).Since its introduction there have been a lot of conflicting
reports regarding the effect of succinylcholine on ICP. However, it has been clearly
established now that scoline administration causes a significant increase in muscle
spindle activity during scoline induced fasciculations. This causes increases in muscle
spindle afferent activity, which in turn increases the afferent input to the brain. As
expected, this increase in CBF and ICP is either attenuated or abolished by
defasiculating dose of non-depolarizing muscle relaxants. This effect can persist for as
long as 30 minutes after scoline administration. This would explain the conflicting
reports regarding effect of scoline on CBF and ICP. When scoline is administered after
-Second Edition
2011

67


thiopentone induction, then the afferent cerebral input, and hence the rise in CBF and
ICP is completely blocked by the depth of anesthesia. If the depth of anesthesia is
inadequate, then this effect can manifest.
Local Anesthetics: Though commonly used for nerve conduction blocks, lignocaine may
also be administered intravenously for its sedative, antiarrhythmic or ICP reducing
effect. It is used intravenously to suppress the hemodynamic response (and secondary
cerebrovascular response) to endotracheal intubation. Local anesthetics readily cross
the blood-brain barrier. They have a significant dose related cerebral effect. In subtoxic
doses a moderate decrease in CBF and CMRO2 occurs. With the onset of seizures, CBF
and increases proportionate to the increase in CMRO2. Dose beyond the seizure
threshold can cause CMRO2 depression and can induce an isoelectric EEG. But this is of
no clinical benefit as cardiovascular instability sets in at this stage. In clinical practice
sub-convulsant dose of lignocaine is used for lowering the ICP and CBF.
Effect of Vasoactive agents: Numerous drugs with agonist and antagonist activity at
catecholamine receptors and dopamine are in common use. There is a lot of
inconsistency in the available data on drugs, probably because of the several variables
involved such as species difference, difference in receptor population within a species,
baseline MAP level, and status of blood - brain barrier. Etc.
From the available data in clinical studies, it appears that alpha-1 agonist like or
epinephrine in dose that causes only a minimal increase in MAP has no effect on CBF,
due to CBL vasoconstriction (alpha-1 agonist effect). When blood brain barrier is
deranged, beta mimetic effect of nor-epinephrine manifests, causing an increase in
CMRO2 and CBF. Epinephrine also has only a minimal effect on CBF and CMRO2 unless
blood-brain barrier is opened up by any disease process, anesthetics or sudden
elevation in MAP. When blood-brain barrier is open, beta mimetic effects will cause
cerebral activation with increase in CMRO2 and CBF. This effect will be much greater
than that observed with nor-epinephrine. Dopamine in lower doses acts on
dopaminergic receptors causing cerebral vasodilatation and increase in CBF, while in
higher doses it acts on alpha-1 receptors causing cerebral vasoconstriction and
decrease in CBF.
Alpha-2 agonists: The role of alpha-2 agonists in anesthetic practice is still being
investigated. Clonidine has been found to cause a decrease in CBF in humans. In a study
in laboratory animals anaesthetized with isoflurane, alpha-1 agonist dexmedetomidine
revealed a potent cerebral vasoconstriction effect and decrease in CBF. If a similar effect
-Second Edition
2011

68


is demonstrated in humans, such a combination would help in neutralizing the only
adverse effect of isoflurane anesthesia. That is cerebral vasodilatation with increase in
CBF and increase in ICP. The mechanism involved is most probably something other
than a direct alpha-2 receptor effect, because alpha-2 receptor stimulation would be
expected to decrease in norepinephrine release and cause CBL vasodilatation is post
synaptic alpha-2 receptors and / or alpha-2 receptor site at a central level, example
locus caeruleus.
EFFECT OF CBF ON BRAIN:
CBF
ml/100gm/min
Effect Consequence
45 to 60 - Normal
20 to 30 Neurological function
impaired
EEG slow down
Neurological dysfunction
Altered mental status
16 to 20 Electrical failure
No spontaneous
electrical activity
Iso electric EEG, loss of evoked potential.
10-15 Ionic pump failure Na+, K+ pump fails, cytosolic edema, H2O
accumulates.
< 10 Metabolic failure. Complete failure, gross disturbance of
cellular energy and homeostasis.

-Second Edition
2011

69



-Second Edition
2011

70


Chapter 4 - CEREBRAL FUNCTION MONITORING
The goals of cerebral function monitoring from the anesthesiologists perspective, are:
Detect changes in cerebral hemodynamics
Monitor cerebral oxygenation
Monitor neuronal function
To monitor the depth of anesthesia
Monitoring depth of anesthesia
General anesthetics have a profound effect on conscious awareness and on explicit
recall of intraoperative events. When anesthetics are administered in gradually
increasing dose they cause a progressive impairment of central nervous system function
(CNS), the terms light and deep anesthesia are used to describe a small or large dose of
anesthetic. Depth of anesthesia is not just determined by the dose of the anesthetic but
instead is a state of analgesia and impaired cognitive function that results from the
depressant effects of anesthetics on the CNS and the stimulating effects of surgical and
other stimuli. This change of cognitive function is almost impossible to recognize in a
patient with complete neuromuscular blockade, episodes of awareness are not recalled
by patients due to the effect on explicit memory of tight anesthesia, on the other hand
prevents recognition by the anesthetist. Despite the wide range of monitoring devices
available to the anesthetist there is no single equipment that monitors depth of
anesthesia routinely.
Awareness is the single biggest complication with the advent of neuromuscular blocking
drugs. Patients who have conscious awareness during surgery with explicit recall of
intraoperative events. There has been a wide variation in the reported incidence of
conscious awareness, but there seems to be a higher incidence in obstetric anesthesia
(7- 28%), emergency anesthesia for major trauma (43%) cardiac anesthesia (23%) and
N2O opioid / relaxant technique.
General anesthesia is a continuous spectrum in which increasing depth of anesthesia
passes through three broad levels of awareness and on this basis four stages of
anesthesia have been proposed:
Conscious awareness with explicit recall
Conscious awareness without explicit recall
Subconscious awareness, implicit but no explicit recall
No awareness

-Second Edition
2011

71


Methods of measuring depth of anesthesia
The need for objectives techniques for measuring depth of anesthesia depends in part
on the need to avoid the dreaded complication of awareness, to standardize studies of
cognitive function during anesthesia and to enable deleterious effects of lack of oxygen
on the brain to be differentiated from the effects of general anesthetics.
The various methods available are:
Somatic responses - Isolated forearm technique.
Autonomic responses
Blood pressure
Heart Rate
Sweating
Tear production
Pupillary signs
Respiratory rate
Facial Electromyogram
Oesophageal contractions
Electroencephalogram Passive EEG Median frequency
Spectral edge

Stimulated EEG Median latency responses (MLR)
Auditory evoked Steady state
response
Responses Fourier analysis of MLR
Coherent frequency P300
Bispectral index
The need for a reliable monitor of anesthetic depth arises from the introduction of
neuromuscular blocking drugs. Changes in EEG are biphasic and often vary with
different anesthetic agents. By incorporating the phase coupling relationship (Bispectral
analysis) into a conventional power spectrum, the Bispectral index (BIS) is capable of
predicting loss o consciousness during anesthesia and appears to be promising in
determining the depth or anesthesia. BIS is rated from a scale of 0 (isoelectric EEG) to
100 (fully awake). The probability of awareness during anesthesia is extremely low
when BIS is < 50 conversely wakefulness is expected when BIS is > 90.

-Second Edition
2011

72


Auditory evoked potentials
Auditory evoked potentials (AEPs) are electro-physiological responses caused by
auditory stimulation of different areas of the brain. Anesthetic agents decrease the
amplitude and increase the latency of the early cortical AEPs in a dose dependant
manner. Since most patients with inadvertent awareness hear sounds or voices it is
logical to monitor AEPs intraoperatively.
Auditory steady state response (ASSR) is a sustained, sinusoidal electrical
response of the brain to rapidly delivered auditory stimuli. In the awake adult this
response is the largest when the stimulating frequency approaches 40 Hz. During
anesthesia there is a decrease in the 40 Hz -ASSR amplitude and a return to baseline as
the patient regains consciousness. A rapid rise in ASSR amplitude is strongly suggestive
of an awakening patient.
Alternatively, the auditory evoked potential index (AEP I) may be calculated,
which is the sum of the square root of the absolute difference between every two
consecutive 0.58 ms segments of AEP. An AEP index of 80 is generally associated with
wakefulness and a value of < 50 with unconsciousness .AEP is an appealing technology
to detect intraoperative awareness, but at present the cost may be prohibitive for it to
become a routine monitor for use in the operating rooms.
Somatic responses
Isolated forearm Technique (IFT)
The IFT provides a simple means of detecting whether a patient has conscious
awareness during surgery. Following induction of anesthesia a pneumatic tourniquet is
inflated to stop the circulation to one arm before administering neuromuscular blocking
drugs into the circulation via a vein in the opposite arm. One arm is thus isolated from
the effects of the relaxant and can be used by patients to respond to commands should
they enter a light stage of anesthesia Brekenridge and Aitkenhead suggested that the
IFT was of little benefit because when surgery started there were powerful movements
of the isolated forearm which interfered with the surgeon, they did not regard this as a
sign of light anesthesia since it was treated by deflating the tourniquet, without any
analgesic or anesthetic supplementation, so they concluded that IFT was less sensitive
than clinical signs to detect light planes of anesthesia .
Russell and others have challenged this saying that since the patient was not given any
supplement of drugs and the surgery was allowed to continue the clinical signs must
have been normal, and that purposeful movements of the arm were obvious signs of
light anesthesia. Indications for supplementation of anesthetic or analgesics are
frequent movement, rolling of the head or opening eyes, any or all these signs may be
present without any significant change in the blood pressure or heart rate.
-Second Edition
2011

73


As soon as signs of light anesthesia are noted, the tourniquet is inflated above the
systolic pressure and a dose of neuromuscular drug is administered. The tourniquet
should remain inflated for about 20minutes and then be released for several minutes to
allow the nerves and tissues to recover from ischemia. There is no limit to the duration
of surgery in using the technique, since the technique relies on using minimum doses of
neuromuscular drugs it is not advisable in those situations where movement may have
deleterious effects on surgery .One of the puzzling aspects of the IFT is the significance
to be attached to semi purposive movements in the absence of a response to a verbal
command: does this represent conscious awareness? The IFT is a simple monitor which
reveals the presence of conscious awareness and profound analgesia in patients who
subsequently demonstrate amnesia for intraoperative events, and is also a useful
method for further psychological study of cognitive function during light anesthesia.
Autonomic responses
The most widely used indices of depth of anesthesia are the clinical signs ranging from
body movement, breathing, lacrimation, pupil size, sweating, tachycardia or
hypertension. However all of them can be affected by drugs which have no anesthetic
effects .The concept of MAC is a useful guide to the anesthetic potency and is often used
by clinicians when using different volatile anesthetics. MAC multiples are often used to
describe anesthetic doses, but little is known about the relationship between the dose
and the effects on the CNS. MAC provides only one measure of anesthetic potency and
that the quantal dose-response relationships that define MAC are not the depth of
anesthesia dose-response curves because MAC represents one point in the presumed
continuum of anesthetic depth, Despite the fact that there is considerable evidence that
the usefulness of physical signs is a very limited guide to the depth of anesthesia, a
scoring system based on changes in blood pressure, pulse rate, sweating and tear
formation has recently been devised. This was developed by Evans and used for
computerized control anesthetic administration. The assumption was made that the
physical signs were a gold standard against which other tests could be compared

-Second Edition
2011

74


Method of calculation of the PRST score (Evans)
Variable Control Score
Systolic pressure (mm Hg) <Control+15 0
<Control + 30 1
>Control + 30 2
Heart rate (beats /min) <Control+15 0
<Control + 30 1
>Control + 30 2
Sweating Nil 0
Moist skin 1
Visible beads of sweat 2
Tears None in open eye 0
Excess in open eye 1
Tears overflow closed eye 2

Cerebral metabolism and markers of ischemia
The measurement of biochemical markers of hypoxic/ischemic cerebral cellular injury
is of increasing value in the acute clinical situation, providing information on the
ongoing state of the injured or necrotic tissue and offers a quantitative and objective
means with which to amplify clinically assessed cerebral function. Serial measurements
of specific markers may provide means of monitoring progress or observe the onset of
secondary changes which may cause further injury. Thus it may allow identification of
those patients who may benefit from a more aggressive approach to therapy. Further
the measurement of these markers provides a useful means of evaluating specific
treatments and the more general methods of cerebral protection, such as
hyperventilation, haemodilution, barbiturate therapy, calcium channel blocking drugs
and mannitol. To qualify as a biochemical marker of cerebral cellular injury, the
potential agent must display adequate tissue specificity and sensitivity. An ideal marker
is one where the detection of increased concentrations in either the CSF or blood can be
confidently linked to the tissue of origin and not derived from other tissues.
Cerebrospinal fluid markers
Biochemical markers of cerebral injury provide information as to the immediate
environment surrounding the brain, while measurements of cerebral markers in the
systemic circulation will reflect either a disruption of the protective blood-brain barrier,
with a consequent passage of agents in both directions. There are many markers in the
CSF but lack the specificity and hence limits the utility of these markers.
-Second Edition
2011

75


Cerebrospinal Fluid Markers
Aldolase S-100B protein
Glial fibrillary acid protein Adenylate cyclase
b-Endorphin Creatine kinase
Neuron specific enolase Myelin basic protein
Serum markers
Creatine kinase Neuron specific enolase
Myelin basic protein
At present the most valuable information that can be derived from plethora available
markers are only a few, the measurement of NSE, MBP, S-100B and GFAP make a
valuable contribution and act an adjunct to the clinical diagnosis.
Electroencephalography
The development of vacuum tube technology in the first decades of the century
permitted creation of amplifiers to record small signals. The detection and classification
of cortically derived electric currents on the human scalp and cataloguing of clinical
correlations with the EEG earned Hans Berger recognition as the father of
electroencephalography. Through decades of empirical observation the EEG has
emerged as a diagnostic tool to monitor cerebral ischemia, anesthetic depth and to as a
research tool to investigate new drugs.
Rational interpretation of the electrophysiological signals requires a basis in the genesis
of these signals. Many theories have been proposed one is a central pacemaker theory,
probably housed in the thalamus which drives the cortex rhythmically. Another
proposed by Nunez is that the brain is so interconnected that it functions as a volume
conductor, having an inherent resonance whose frequency depends in part on the
brain's physical dimensions. Nunez has in fact correlated inherent mu- rhythm
frequency with skull size.
Limitations
There is a need for expert professional interpretation.
Following a neuronal injury there is often a reduction of neuronal activity in the
corresponding area of the contralateral hemisphere, known as diaschisis. This is
probably due to extensive corticocortical pathways crossing the corpus callosum and it
may contribute to the inaccuracy of using the EEG to localize brain infarction.
Another anatomical and physiological constraint is that it is a cortical phenomenon;
consequently a substantial portion of the volume of the central nervous system neither
contributes nor significantly affects the scalp EEG.
-Second Edition
2011

76


Finally from its site of origin in the cortex, the electrical current associated with the EEG
must traverse three 'shells' of varying conductance, namely the cerebrospinal fluid, the
skull and the scalp. Following their genesis postsynaptic potential derived currents are
blended together in the highly conductive cerebrospinal fluid and forced through many
small and large foramina of the skull and further blended in the conductive scalp. The
effect of these intervening shells may attenuate and spatially blur any focal electrical
activity into neighboring areas of the scalp further reducing the resolving power of the
non-invasive EEG.
EEG measurement systems
Electrodes
To be useful to the clinician, the minute voltages traversing the scalp must be captured,
enhanced and displayed. The first step is transuding the scalp currents, converting them
from ionic form into currents carried by electrons in metal and thence into voltages; this
sequence is implemented by placing pairs of electrodes, using a standardized system of
sites that uses bony landmarks as reference points for placement. The international 10-
20' system provides intra and inter-patient repeatability of EEG recordings.
Factors affecting the EEG
Age
Carbon-dioxide
Electrolyte balance
Endocrine disease
Glucose
Oxygen
Temperature
Methods of Analysis
The raw EEG can represent an information overload, and subtle changes are difficult to
interpret without extensive experience. To overcome this various forms of processed or
automated EEG have been developed. Processed EEG refers to methods of converting
the raw EEG (a voltage v/s time plot) to a plot showing EEG frequency, voltage and time.
Two methods used to accomplish this are power spectrum analysis and spectral edge
frequency, both of which provide quantifiable and easily readable EEGs without loss of
information .In spectral analysis, the signal is processed via Fast Fourier transformation,
two to eight epochs of digitalized EEG are consecutively analyzed by breaking the
complex EEG waveform into its component frequencies. A histogram of EEG component
frequency versus voltage is then plotted. The time dimension is achieved by stacking
these histograms in a quasi-three dimensional manner:
-Second Edition
2011

77


Power spectrum analysis
CSA (Compressed spectral array) -
DSA (density modulated spectral array)
Spectral edge frequency
Frequency below which X% of the EEGs power lies. SEF of 95% is defined as that
frequency below which 95% of the EEG power lies.
Median power frequency is that frequency above and below which 50% of the EEG
power lies.
Clinical Applications
Monitoring for cerebral ischemia
Monitoring depth of anesthesia
Diagnosis of epilepsy
Herpes encephalitis
Metabolic encephalopathy
Focal cerebral lesions
Evaluation of altered states of consciousness
Aging and dementia
Brain death
Magneto-encephalography (MEG)
The magneto encephalography (MEG) is a measure of brain function equivalent to EEG.
The same neuronal sources that generate electrical activity also generate magnetic
fields. MEG has mainly been used to localize sources of evoked potentials and focal
epileptic form activity. It has also been used to investigate patients with psychiatric
disorders, stroke and migraine. MEG differs from EEG in several ways, EEG potentials
are volume conducted and are easily attenuated by the overlying CSF, dura and skull;
MEG is less affected by this. MEG more accurately measures tangential dipoles that are
parallel to the cortical surface, and also has a higher spatial resolution .MEG has to be
used taking into account their limitations and because of the shielding requirements
and the complex instrumentation necessary to measure neuro-magnetic fields this
technology is likely to remain limited to research applications
Intraoperative monitoring
Electrophysiological monitoring to assess the functional integrity of the brain and spinal
cord during neurosurgical and orthopedic procedures has become routinely available in
many centers. Such monitoring reduces neurologic morbidity by detecting adverse
effects at a time when prompt corrective action can prevent permanent neurologic
-Second Edition
2011

78


damage. Monitoring thus provides information about the mechanisms responsible for
neurologic abnormalities and sometimes lead to changes in surgical techniques.
Monitoring can be done by using EEG, evoked potentials, transcranial Doppler, Jugular
venous oxygen saturation, cerebral oximetry and infrared spectroscopy, depending on
the type of surgery and neural structures most likely to be at risk.
Evoked Potentials
Evoked potentials are those potentials evoked by sensory stimulation and recorded
either from electrodes placed over a nerve or scalp electrodes. They have proven to be a
useful diagnostic tool, and can be used to establish objective evidence of an abnormality
when clinical signs and symptoms are equivocal or when the patient is not able to
cooperate. Evidence can also be collected about silent or subclinical lesions, which are
electrical abnormalities in a pathway when clinical function may seem to be normal.
Evoked potentials can also help to define the anatomical level of the lesion and can be
used in the intensive care units for the prognostic evaluation of comatose patients. For
intraoperative monitoring four types of EP's are commonly used, somatosensory
evoked potentials for spinal cord monitoring, brain stem auditory evoked potentials for
posterior fossa lesions and neurovascular decompression surgery and visual evoked
potentials for monitoring lesions along the optic pathway and motor evoked potentials.
The main purpose of intraoperative monitoring is to reduce neurological complications.
According to this concept changed potentials should allow identification of both local
and systemic impairment. Unchanged potentials should provide reassurance to the
surgeon that complications are unlikely to occur. These are based on the assumptions
that alterations in the EP will occur before the lesion is irreversible, and that there will
not be any false positive or false negatives, will not harm the patient and finally the
warning or intervention criteria should be well defined.
EPs can be divided into near field and far field potentials, near field (cortical) responses
are affected to a major degree by anesthetics, whereas far field responses (sub cortical)
are not affected to the same degree. There are two measures which are commonly used
to describe EP morphology, latency- which represents the time taken from stimulus
until a particular feature appears and the amplitude.
There are several problems which confront the monitoring team in the operating room,
first the decision has to be made as to what is the technique to be adopted for a given
lesion, this includes the selection of the pathway to be monitored and of appropriate
stimulation, recording sites and parameters as well as a data acquisition and processing.
Another is anesthesia and collaboration with the anesthesiologist is essential to decide
upon an adequate anesthetic regime and to control physiologic and patient related
influences on EP such as body temperature, blood pressure and blood gases and decide
-Second Edition
2011

79


upon acceptable limits for changes in potentials, to define "warning criteria" or
"intervention criteria" and lastly the monitoring procedure itself should be safe.
Somatosensory evoked potentials (SSEP)
SSEP have now reached a stage of wide spread application in neurosurgery, orthopedic,
vascular surgery and interventional neuroradiology. Most experience is with the use of
SSEP in the assessment of spinal cord function. Many reports are described where SSEP
have been used in posterior fossa surgery carotid endarterectomy and aneurysm
surgery. When surgery is done below the neck it is appropriate to stimulate the
posterior tibial or peroneal nerves. For operations in the high cervical region median
nerve stimulation would be more appropriate. Direct spinal stimulation may also be
used.
Commonly cortical SSEPs are recorded from scalp electrodes, but these are
prone to the effects of anesthesia. Alternately electrodes may be placed in the extradural
space, where more stable EPs are obtained either by laminectomy or by inserting a
modified 15 gauge Touhy needle; when the dura is open subdural electrodes may be
placed.
Aortic surgery
SSEP monitoring may be useful in assessing the adequacy of spinal cord perfusion and
can alert the surgeon, loss of EPs can warn the surgeon of the need to implant critical
intercostal arteries or improve distal perfusion. In surgery of the descending thoracic
aorta following rupture or repair the incidence neurological deficits is high .It seems the
maintenance of a distal perfusion pressure of more than 60mm Hg, using either shunt or
bypass procedure results in the preservation of SSEPs. If the loss of EPs is limited to less
than 30 minutes no neurological deficit occurs, loss of ERs for more than 30 minutes
results in a 71% incidence of paraplegia.
Limitations
The main problem is that in these patients base line recordings are poor due to
preoperative neurological deficits. Therefore monitoring is unsuccessful in those
patients where it is required most. They are useful in other conditions where patients
do not have neurological deficits as in scoliosis, vascular surgery and interventional
neuroradiology. Impending neurological complications can be expected to be well
recognized by significant changes in SSEP. SSEP have been known to disappear rapidly
during intraoperative embolization on entry of dye or embolization material into the
anterior spinal artery.
The technical reliability both for cortical and spinal recordings is satisfactory, the
requirements of anesthesia are well known and monitoring has become possible with
-Second Edition
2011

80


hardly any anesthetic problems. The empirical criteria for warning the surgeon or
changing the procedure are have been used successfully to reverse potential
deteriorations with little or no neurological deficits. Minor deficits are occasionally seen
without any significant potential changes. Severe neurological deficits with unchanged
potentials are not impossible, but remain rare events. However the clinical relevance of
changed potentials needs further clarification in order to reduce the high number of
false positive recordings.
Brain stem auditory evoked potentials
The brain stem auditory evoked response (BAEP) has the most complex morphology
but at the same time is a robust monitor. Electrodes are placed on the scalp and along
the vertex and each ear lobe, stimuli are given in the form of click or tone bursts through
ear phones and the responses recorded on a graph. The response can be described in
three parts. The first part is the brain stem auditory response (BAEP) which is a short
latency potential, with seven waveforms being described in the first 10ms after
stimulation, the purported generators of these responses are shown in the figure .The
second, the middle latency response (MLR), comprises five waves, occurring between 8
and 50ms after stimulation, which are related to neural activity within the thalamus and
the primary auditory cortex and the late cortical response occurs between 50and
500msand reflects the activity of the frontal cortex.
Measurements: The normal BAEP has seven wave forms, but only five have proven
neuro-generators. These correspond to the following
Wave I - 8th nerve potential
Wave II - Cochlear nucleus or more proximal segment of the 8th nerve
Wave III - Superior Olivary complex
Wave IV - Lateral lemniscus
Wave V - Inferior colliculus or more recently still the lateral lemniscus
Wave VI - Medial geniculate body - (not proved)
Wave VII - Auditory radiation - (not proved)
Absolute latency: Measured from stimulus to peak of each wave
Inter peak latency: Measured from between the peaks of the two waves
Where a peak is not well defined, a midpoint of the wave is an estimate.
Amplitudes are measured from the positive peak of the wave to the following negative
one
Ratio of IV, VII is calculated, IV and V usually on the slope; choose the higher amplitude
Record the latencies of all identifiable waves (I through to VII) as well as the I-III, III-IV,
and
I-V inter peak latencies
-Second Edition
2011

81


It is considered abnormal if:
All or some of the waves are absent sequentially
The inter peak latencies are prolonged
The absolute latency of a particular wave, mainly V is prolonged
Decrease in the VII ratio is suspicious
Decrease in inter peak differences is suspicious
Clinical applications
Hearing loss
Multiple sclerosis
Stroke
Acoustic neuroma
Central pontine myelinolysis
Since BAEP represents signals traveling from the ear to the thalamo-cortical radiations,
during cerebellopontine angle surgery, monitoring the BAEP will test the integrity of the
pathway. When the auditory nerve was resected the BAEP was irreversibly obliterated,
other changes were associated with retraction, operative manipulation, head
positioning, hypocarbia and hypotension. If BAEP returned towards the end of surgery
hearing was preserved, irreversible loss occurred if the nerve was sacrificed. Retraction
was associated with marked increases in the latency and decrease in amplitude of
waves III -V, adjustment of retraction allowed return of the potentials
The use of BAEP and electrocochleogram (ECoG) has been recommended for the
preservation of hearing. It has been found that the preservation of potentials obtained
from the auditory nerve, wave I from the BAEP was indicative of preserved
postoperative hearing. BAEP not only tests the integrity of the 8th nerve but also the
function of the brain stem and may be useful during surgery of the posterior circulation,
especially when temporary occlusion of the basilar and vertebral arteries is required.
Visual evoked potentials
Visual evoked potentials (VEP) provide a qualitative and quantitative measure of the
optical pathway in that they indicate a degree of function of the optic nerve, optic
chiasma, lateral geniculate bodies, and geniculocalcarine projection to the visual cortex.
VEP is obtained by averaging the responses from occipital scalp electrodes generated by
100 or more sequential stimuli. Stimulus characteristics are critically important in
determining which portion of the visual system will be tested by the VEP and what the
sensitivity of the test will be to the presence of lesions.
Monocular stimulation is almost always employed so that the test is more sensitive to
lesions of the optic nerve anterior to the chiasma, it is possible to modify the stimulus so
that only selected portions of the visual field are stimulated, thus permitting detection
-Second Edition
2011

82


of post chiasmatic abnormalities also. VEP elicited by pattern reversal stimuli are much
more sensitive to lesions affecting the visual pathways. A few investigators have further
refined the pattern-reversal stimulus by using a black and white sinusoidal grating
rather than a checkerboard pattern; this appears to enhance test sensitivity by
permitting selective stimulation of the retinal elements responsive to specific spatial
frequencies and of cortical elements responsive to both spatial frequency and
orientation.
Stimulation:
Pattern reversal stimulation Hemifield stimulation Flash evoked response
Interpretation
- P100 is the most important peak to identify; it is often preceded by an N75 and
followed less reliably by N145.
- Hemifield studies
- Contralateral waves are measured (P75, N105, P135). The only secure
abnormalities are absence of waves or significantly delayed frequencies
- Flash evoked responses
- Alternating positive and negative waves appear
- Suprasellar tumors
- Posterior circulation aneurysms
- Optic neuritis
- Diagnosis of blindness
Causes of abnormal VEP
Ocular disease
- Major refractive error
- Lens and media opacities
- Glaucoma
- Rtinopathies
Compressive lesion
- Extrinsic tumours
- Optic nerve tumors
Non compressive lesions
- Demyelinating disease
- Ischemic optic neuritis
-Second Edition
2011

83


Nutritional and toxic amblyopia
- Leber's hereditary optic atrophy
- Diffuse CNS disease
- Adrenoleukodystrophy
- Spinocerebellar degeneration
- Parkinson's disease
Intraoperatively VEPs are difficult to record in the anaesthetized patient due to small
and changing pupil size as well as the extreme variability of VEPs with anesthetics. In
addition flash stimulation activates both temporal and nasal halves of the retina, making
it impossible to monitor retrochiasmatic lesions reliably. Clinical experience indicates a
high false positive rate. VEPs are therefore not widely used for intraoperative
monitoring.
Motor evoked potentials (MEP)
It is possible to study the functional integrity of the descending motor pathways by
stimulating the motor cortex directly by passing a brief high voltage electrical pulse
through the scalp or by using a time varying magnetic field to induce an electric current
within the brain. Stimulation can be accomplished at the level of the brain or the spinal
cord. Although the clinical utility of MEPs is not fully defined, they provide information
about the motor pathways. It also offers insight into the pathophysiology and evolution
of disorders affecting the motor system The evoked response is commonly recorded as
a muscle potential or from a peripheral nerve, a typical MEP waveform consists of an I
wave followed by several D waves.
Types of motor evoked responses and events recorded
Motor evoked response type Event
Transcranial electrical stimulation
(tcEMEP)
Direct activation of the corticospinal
pathway; D wave
Transcranial magnetic stimulation
(tcMMEP)
Also trans-synaptic activation ; D and I
waves
Direct cortical or spinal cord
stimulation
Muscle movement
(face and extremities)
Compound motor action potential
Nerve action potential
Spontaneous electromyogram activity Electromyography tracing; acoustic output

-Second Edition
2011

84


Intraoperative monitoring
- Multiple sclerosis
- Parkinson's disease
- Motor neuron disease
- Chronic spinal cord injury
- Localization of cortical lesions (epileptic foci, tumours)
Limitations
- Motor responses are extremely sensitive to anesthetics.
- Wave forms are of low amplitude and have large variability
- Requires avoidance of neuromuscular blockade
- Stimulation may result in potentially adverse effects like seizures,
- Arousal and hemodynamic activation
Special techniques to enhance motor evoked potential responses
- Timed peripheral nerve stimulation (spinal epidural recording)
- Dual stimuli to achieve temporal summation
- Train of stimuli with average responses
- Anesthetic techniques
- Rigidly controlled neuromuscular blockade
- Total intravenous anesthesia
It appears that the only method likely to become acceptable is that of magnetic
stimulation, which can be reliably recorded during surgery. Though data on the effect of
anesthetics on magnetic MEPs are limited. It appears logical that MEPs are more likely
to give information about motor function than SSEP, the clinical correlates at present
are currently lacking. The possibility that inducing electrical currents in the brain can be
dangerous, even though no adverse effects from magnetic stimulation have been
reported. This technology is still in its infancy; it may become useful with modifications
later.
Jugular Venous oxygen saturation
Cerebral venous oxygen saturation provides a global measure of the balance between
CBF and oxygen consumption (CMRO2). Based on anatomical venous drainage, mixed
venous blood can be studied in the jugular bulb. Under normal circumstances, CMRO2
matches with CBF and the ratio between the two variables can be described as

AVDO2=
CMRO2
CBF
-Second Edition
2011

85


AVDO2 is the arterio-jugular venous oxygen content difference. Assuming the
amount oxygen dissolved is negligible and the, hemoglobin, SaO2 remain unchanged
then

The normal values for AVDO2 and SjvO2 in healthy young men are 4.5-8.5 vol% and 55-
75%repectively .An increase in the SjvO2 indicate that the cerebral oxygen supply may
exceed metabolic demand, conversely a decrease in the SjvO2 implies that the CMRO2 is
increased, or there is insufficient oxygen delivery or both to the brain. The normal
values that are useful to adequacy of cerebral blood flow are given below
SjvO2 Normal
Hypoxia
Ischemia
55-75%
> 90%
<50%
AVDO2 Normal
Hypoxia
Ischemia
4.5- 8.5vol%
< 5vol%
> 7.5vol%
CEO2 Normal
Hypoxia
Ischemia
24-40%
< 24%
> 40%
In the absence of brain lesions the SjvO2 is similar in both the jugular bulbs. It is advised
now that in the presence of intracranial pathology the SjvO2 should be monitored on the
dominant side, however 13% of ischemic episodes could be missed if only one jugular
bulb is monitored. The dominant side of venous flow can be identified by the greater
increase in the ICP on unilateral jugular compression or on the CT by the size of the
larger jugular foramen.
Interpretation
Jugular venous oxygen saturation is a useful indicator of global cerebral blood flow,
however a number of factors make the interpretation difficult. Extracranial factors are
also important while interpreting SjvO2, apart from cerebral ischemia, jugular venous
bulb desaturation can be the consequence of systemic hypoxia, anemia,
dyshaemoglobinaemia and severe acidemia. Similarly polycythemia, cyanide poisoning
and hypothermia raise the SjvO2 regardless of changes in the CBF. Given the anatomical
variation and drainage of the venous system this becomes even more complicated.
A number of technical factors also affect SjvO2, a catheter situated low in the neck
usually overestimates cerebral venous oxygenation because of mixing of systemic blood.
On the contrary, a catheter high in the skull base often hinges on the vessel wall and
may produce abnormal readings with new fiber-optic oximetry catheters. The optimal
AVDO2=
1.39 x t Hb (SaO2 - SjVO2)
1- SjvO2
-Second Edition
2011

86


position of the catheter is still unknown; the generally catheter position accepted is
opposite to C2 vertebral body or 2.5 cm below the base of the skull. The rate of blood
withdrawal also changes SjvO2, compared with samples drawn at 2ml/min faster
withdrawal at 5 or 10 ml / min increases extracranial contamination and overestimates
SjvO2 by 8 to 17%. In addition when continuous fiber-optic catheters are used, base line
drift and light interference must also be considered, these catheters have to be
calibrated every 12 hours.
When extracranial causes are excluded, a low SjvO2 reliably indicates cerebral
hypoperfusion. The critical value for the ischemic threshold is still not clearly defined, a
SjvO2 value of 50% is considered as the ischemic threshold. It has been found that
during carotid endarterectomy neurological deficits are more likely when the SjvO2 is
less than 50%; similarly multiple episodes of SjvO2 are associated with a poor outcome
in patients with severe head injury.
Simultaneous measurement of jugular lactate concentration of > 1.5 mmol/lit will
confirm cerebral anaerobic metabolism. While jugular venous desaturation is definitely
harmful for Patients, an elevated SjvO2>75% is not necessarily favorable.
Despite its complexity in data interpretation SjvO2 has been widely used in the
management of patients with head injury, during cardiopulmonary bypass and
neurological procedures. SjvO2 is a useful tool in guiding therapy for intracranial
hypertension after head injury, and ventilation can be adjusted to prevent inadvertent
cerebral ischemia. Since SjvO2 is an invasive procedure, it carries a small risk of carotid
puncture of <5%. Non obstructive thrombosis of the ipsilateral jugular vein is detected
in about 40% of the patients even when the duration of monitoring is for less than
24hours.
Transcranial Doppler (TCD)
Transcranial Doppler is capable of providing real time information of cerebral
hemodynamics in beat to, beat fashion, something which was needed in the acute care
setting but till now not available. TCD measures blood flow velocity in the basal cerebral
arteries. Using arrange gated, directional sensitive ultrasound probe, the cerebral artery
is insonated by a low frequency 2MHz pulsed wave through one of the three acoustic
windows, transtemporal, transorbital and transforaminal. Basically an individual artery
is insonated and according to the window used, the depth of the sample flow and
direction of flow are identified.
TCD can be used to identify the following:
- Cerebral perfusion monitor
- To detect cerebral micro emboli
- Assessment of cerebrovascular reactivity
- Brain death
-Second Edition
2011

87


TCD as a cerebral perfusion monitor
The validity of flow velocity as a measure of volumetric cerebral blood flow (CBF) relies
heavily on the assumption that the vessel caliber remains unchanged. There is now
increasing evidence suggesting that diameters of the proximal arteries in the Circle of
Willis are constant during changes in perfusion pressure and carbon dioxide tension. An
elevated flow velocity could be due to either vessel narrowing or true hyperemia.
Lindegaard et al differentiated two opposing conditions by measuring the flow
velocities in the MCA and the distal segment of the extracranial portion of the ICA in the
neck. Since the flow in the two arteries is the same at a given point of time, an increase
in FV along the line of flow transmission must be result of narrowing, a ratio between
MGAFV and FV EICA was developed (MCAFV / FVECA) this is called the Lindegaard or
the hemispheric index, an index of < 3 suggests an absolute increase in the total CBF,
and a ratio > 6 indicates severe vasospasm using this criteria the sensitivity and
specificity of TCD to detect clinical and angiographic vasospasm after aneurysmal and
traumatic SAH are 60 and 78% A similar approach has been used to study the
vertebrobasilar system.
Vessel caliber can also be derived by the Goslings or the pulsatality index (PI), which is
ratio between the peak to peak amplitude of FV pulsation and the mean FV, a high PI >
1.2 suggests an increase in the distal cerebrovascular resistance. However PI cannot
distinguish the pathology of change either due to intrinsic vasospasm or external vessel
compression secondary to raised ICP. At the other extreme of the flow spectrum,
specific TCD changes during cerebral hypoperfusion are well documented. With
decreasing cerebral perfusion pressure, there is a progressive decrease in the diastolic
flow velocity. The flow direction becomes reversed in the diastolic phase as the ICP
exceeds the diastolic arterial pressure and finally ceases when the intracranial flow
arrest occurs. The flow velocity threshold for detection of cerebral ischemia is less
clearly defined
TCD for the detection of cerebral micro emboli
Micro emboli are a common cause of cerebral ischemia during CEA, CPB and coronary
angiography. Micro emboli produce transient signals from the back scatter of
ultrasound that is much higher than normal blood flow. TCD is capable of detecting
gaseous and solid material in the basal cerebral arteries. Micro emboli are usually brief
in duration (10-100ms) with a signal intensity >3 dB above the Doppler background
spectrum. New multigated TCD machines can enhance the identification micro emboli
as manual detection is quite a laborious process. Using this principle TCD can detect a
patent foramen ovale also.

-Second Edition
2011

88


TCD for the assessment of cerebral reactivity
Measurement of cerebrovascular response to different vasoactive stimuli indicates the
vasomotor reserve of the brain. CO2 reactivity is a very robust monitor, and an intact
cerebrovascular reactivity is very reassuring in the management of head injuries and a
persistent impairment in the CO2 reactivity indicates a poor outcome. Current
cerebrovascular reactivity tests require a sensitive measure of CBF and potent
vasoactive stimuli in the form of CO2, acetazolamide and perfusion pressure. Reactivity
tests done are of two types static and dynamic. Static reactivity testing measures CBF at
two steady states. Conventional clearance of radioactive isotopes (xenon) or inert gas
saturation (Kety-Schmidt techniques) measure absolute CBF at two separate time
intervals. This testing is time consuming, but they fulfill most of criteria for static
testing.
Dynamic reactivity assesses CBF response with respect to time; two tests that are
commonly employed are the leg cuff test and selective regional hypotension. The leg
cuff test measures the rate of change of CVR after a step decrease in the systemic
arterial pressure when a pair of leg cuffs is deflated. In a normal vascular bed, cerebral
vessels promptly dilate so as to maintain the baseline CBF; on the other hand prolonged
recovery > 5-6secs suggests vasoparalysis. Selective regional hypotension can also be
elicited by a brief > 15 sec carotid compression. In both the tests, a beat to beat monitor
of cerebral hemodynamics is crucial, TCD albeit indirect provides a continuous measure
of CBF with a high temporal resolution, and thus allows dynamic reactivity to be done
noninvasively Another form of reactivity testing is regional CBF changes.
Functional TCD is based on the principle that cerebral activation and therefore
metabolism and perfusion are normally coupled. It is possible to locate hemispheric
dominance of language and vision by recording the flow velocity in the middle and
posterior cerebral arteries of both sides. Functional TCD was able to predict language
dominance in all cases. Given the easy applicability of TCD, this will be a useful adjunct
during surgical planning.
Limitations
- Monitors flow velocity and not nutritive CBF
- Though easy to operate, accurate and reproducible, they are still operator
dependant. It may fail in about 20%of the subjects in whom the skull is too thick
to be penetrated
- Flow characteristics may be affected by anesthetics and other drugs

-Second Edition
2011

89


Near infrared spectroscopy
This technique employs principles of optical spectrophotometry which exploit the fact
that biological material is relatively transparent in the near infrared range. Light
transmission depends on a combination of reflectance scattering and absorption effects.
Reflectance is primarily a function of the angle of the light beam to the tissue surface,
while scattering decreases with increasing wavelength, favoring transmission of near-
infrared light (NIR) (650-1100nm). Absorption occurs at specific wavelengths,
determined by the molecular properties of the materials in the light path. Above
1300nm water absorbs all the photons over a path length of over a few millimeters,
while below 700nm increasing light scattering and intense absorption bands of
hemoglobin prevent transmission. In the 700-1300nm range NIR light penetrates
through several millimeters of tissue. The absorption spectra of oxyhaemoglobin (HbO2)
ranges from 800-850nm, that of deoxyhemoglobin ranges from 650-800nm and
cytochrome a3 has a broad peak at 820-840nm. Although the light absorption is small, it
is known that only three chromophore (hemoglobin myoglobin and cytochrome
oxidase) undergo characteristic oxygen dependant absorption. Therefore it is possible
to measure brain oxygenation by quantifying the relative absorption of Oxyhaemoglobin
(HbO2) and deoxyhemoglobin (Hb) in the cerebral tissue, and the sum of HbO2 and Hb
indicates cerebral blood volume. Extracranial contamination is a major concern in
interpreting NIRS.
In spite of the fact that there are concerns about its use in practice, clinical applications
are emerging. In patients undergoing carotid endarterectomy, a decrease in HbO2
(corrected for extracranial changes) > 6.8mmol/l after arterial cross clamp correlates
with slowing of EEG and a significant fall in MCAFV (> 60% from baseline). This
threshold value accurately predicts cerebral ischemia and allows a rational decision
regarding shunting. When compared with SjvO2, NIRS was more specific (97% vs 53%)
in detecting various critical events with a high temporal resolution. Given its rapid
response, NIRS can be used to assess cerebral perfusion. When patients are given CO2,
the percentage change in the HbO2 per mmHg increase in CO2 allows an assessment of
cerebral reactivity. Compared with TCD, NIRS is superior because it is less operator
dependant. NIRS has shown potential promise in quantifying changes of cerebral
oxygenation under a highly controlled environment. Extracranial contamination still
remains a continuous threat to its accuracy. Until the extracranial HbO2 content can be
easily eliminated, the clinical role of NIRS will remain uncertain.
Noninvasive cerebral optical spectroscopy
Invasive NIR Attempts have been made to reflectance NIR spectroscopy to measure
cortical oxygenation through the intact calvarium. A question arises regarding
validation of the technique, it appears that under some circumstances non perfused and
-Second Edition
2011

90


non biologic structures can yield regional oxygen saturation (rSO2) values that
correspond to those of normal healthy subjects. Another limitation is the fact that the
cerebral sample volume is very low of the order 1cc of cerebral tissue, thus rendering
non invasive cerebral spectroscopy highly regional.
Brain tissue oxygen tension
Cerebral oxygenation can be measured by direct brain tissue oxygen tension (PbtO2)
monitoring. A miniaturized polarographic Clark electrode and a thermocouple are
incorporated within the tip of a micro-catheter, 0.5mm in diameter for continuous
monitoring of tissue oxygenation and temperature. The catheter is placed in contact
with the cortical tissue through a standard burr hole or during craniotomy. Early
experience in head injured patients has shown that PbtO2 monitoring provides reliable
readings over a long period of time. During neurosurgical procedures at risk or
ischemia, PbtO2of < 20mmHg is suggestive of compromised cerebral circulation. A PbtO2
of <10mmHg for more than 15 min has been associated with an unfavorable outcome in
head injured patients. Thus a minimum PbtO2 of 15-20mmHg should be taken as the
target of therapy. It should be emphasized that PbtO2 is a focal measurement that may
not reflect regional oxygen gradients. In patients with unilateral lesions, PbtO2 is lower
around the lesion compared with the normal hemisphere. At present it is not clear
which hemisphere is to be monitored and further study is required to refine the
technique for clinical use.
Magnetic resonance spectroscopy (MRS)
Magnetic resonance spectroscopy provides spatial information of tissue metabolism in
the brain. MRS quantifies the weaker spectra derived from 1H and 31P in lactate and
high energy phosphates. Using new construction algorithms it is possible to visualize
the chemical composition of these metabolites in various parts of the brain. Compared
with MRS, positron emission tomography (PET) displays a map of cerebral metabolic
activity with better resolution. In PET, a smaller amount of radiotracer 18 F labeled
deoxyglucose is taken in parts of the brain that are metabolically active. The positron
emitted during tracer decay would then allow the scanner to quantify its concentration.
Since the chemical structure of the tracer is similar to its biologic counterpart, the
amount of metabolic activity can be estimated. The limitations of MRS and PET are that
they are expensive, time consuming and difficult to perform in ventilated patients. In
the case of PET, the added radiation hazard is also present.
Electrical Impedance Tomography
Electrical Impedance Tomography (EIT) of the brain is a computerized imaging system
which is based on reconstruction of multiple impedance measurements obtained with a
ring of electrodes for imaging physiological or pathological alterations in the brain. EIT
-Second Edition
2011

91


has been shown to be safe, inexpensive, and portable and allows rapid imaging. It might
be useful as a clinical tool for monitoring of various cerebral functions, and has been
shown to be capable of imaging experimental ischemia and spreading cortical
depression. This technology is still in an experimental stage.
Laser Doppler Flowmetry
Laser Doppler Flowmetry (LDF) focuses on a small volume of cerebral cortex and
measures relative change of microcirculatory blood flow. A small LDF probe is inserted
into subdural space through a burr hole or a craniotomy. Monochromatic light 600-800
nm wavelength emitted from a low power solid state laser diode is then delivered to the
cortical tissue by an optical fiber. A photo detector within the LDF probe receives light
scattered from the moving red cells. Red cell velocity is then calculated from the spectra
of laser shifts and the power of the signal indicates the red cell concentration. The
product of red cell velocity and concentration generates a new parameter called red cell
flux, which is proportional to the CBF.
LDF allows continuous assessment of focal cerebral perfusion with a high degree of
temporal resolution and its response is also rapid.
Detection of focal ischemia during excision of cerebral tumors, brain retraction, excision
of
AVM's.
Monitoring ischemic episodes in head injured patients
Real time index of auto regulation
The change in LDF follows that cerebral perfusion pressure is close to 1 when auto
regulation is impaired, whereas a correlation coefficient of 0 suggests intact reactivity
.LDF signal is not quantitative and is generally expressed as arbitrary units (AU).
Although red cell flux is directly proportional to C8F in animals the signal varies
considerably in individuals. A non pulsatile signal of < 5 AU implies microcirculatory
ischemia.
Limitations
Subject to movement artifacts
External light interference and fluctuation in hemoglobin concentration
Potential risk of infection as result of its invasive nature.
LDF though has shown promising results; further refinement in technology is
required for it to become a clinically useful monitor.

-Second Edition
2011

92


Future Developments
At present the best that can be offered to the patient with the available technology is
multimodality monitoring; the need of the hour is to identify the exact nature of the
underlying mechanisms that are responsible for the many subtle physiological changes
that manifest clinically as neurological deficits. Efforts are made to evolve new
strategies to treat abnormalities early so as to ensure normal function of the brain, after
the brain has suffered an insult which would have debilitated or disabled the patient
permanently.

-Second Edition
2011

93



-Second Edition
2011

94


Chapter 5 - SENSORY EVOKED POTENTIAL (SEP)
Definition:
Sensory Evoked Potentials are defined as the electrophysiological manifestation
of the Central Nervous System to Sensory Stimuli.
Sensory Evoked Potentials are gaining wide popularity because of the ability to
monitor the functional integrity of the Nervous System intra-operatively, of the
anaesthetized patients undergoing surgical procedures that would place the sensory
pathways at risk of injury.
Classification of Sensory Evoked Potentials:
Sensory evoked potentials can be classified in many ways:-
Depending upon distance between the neural generator and Recording
electrode, they are classified into Far Field Potentials and Near Field potentials.
Depending upon sensory between neural generator and Recording electrode:
Near field potentials: Evoked potentials recorded by Electrodes placed close to
the neurophysiological generator are called near field potential.
Example: Cortical potentials recorded by electrodes placed far from the
neurophysiological generator and are conducted to the recording electrodes
placed close to the scalp.
Far field potentials: These potentials are recorded by electrodes placed far
from the neurophysiological generator and are conducted to the recording
electrode through volume conduction of brain and CSF.
Example: Sub cortical potentials recorded from the spinal cord by electrodes
placed on the scalp.
Sensory evoked potentials can be classified depending upon the sensory
modality stimulated into.
Somato Sensory Evoked Potential (SSEP)
Visual Evoked Potential (VEP)
Auditory Evoked Potentials (AEP)
Post Stimulus Latencies:
The time interval between the stimulation of sensory pathway and recording of
evoked potential is known as post Stimulus Latency.
Post Stimulus Latency varies from 10 msec 120 msec depending upon the
pathway stimulated, short latency SEP are recorded from the sub-cortical region and
long Latency SEP are recorded from cortical area.
-Second Edition
2011

95


The conduction velocity and central conduction time (CCT) are measurements
derived from post stimulus latencies that help to assess and classify neurological from
cervical spinal cord and later from the evoked potentials arising from the primary
sensory cortex is called as central conduction time/which can be diagnostically
important in that they can indicate pathophysiological alterations in Brain function.
Recording of Sensory Evoked Potentials:
1. The Sensory. Evoked potentials occurs at a constant time after the sensory
stimulus where as the EEG occurs at random intervals after the stimulus.
2. SEP differs from EEG in that they are of low amplitude (0.1-20 microvolts) and
hence to distinguish from background brain wave activity computer signal
averaging or summation is required.
Any System to adequately record SEP should contain:
Sensory stimulation.
Amplification, acquisition and filtering of physiologic signals.
Signal processing.
Display, measurement and storage of SEP waveforms.
For all SEP monitoring recording electrodes are placed on the scalp using the
International 12-20 system and for recording the standard EEG.

Intra operative changes in evoked potentials such as
Decreased amplitude amplitude
Increased latencies or latencies
Complete loss of wave form and considered to be indications of surgical trespass
or ischemia.
-Second Edition
2011

96


When these changes are detected or considered to be significant the
anesthesiologist and / or surgeon can make changes to relive the insult to the
monitored pathway.
Interventions by anesthesiologist are directed at improving the perfusion to
nervous system and include increasing the arterial blood pressure especially of
controlled hypertensive technique is used. Alteration in evoked potentials may
warn the surgeon of excessive retractor pressure or surgical dissection of the
pathway at risk.
Somato sensory Evoked Potentials:
Somato Sensory Evoked Potentials are recorded after stimulation of a peripheral
sensory nerve with electrical stimulation via a surface electrode placed on the skin or by
fine needle electrodes.
The current strength used is 10 mA- 20 mA and duration of stimulus varies from
0.1-2 milli seconds.

The sites of stimulation of the peripheral nerve are:
Median nerve at wrist.
Posterior tibial nerve at ankle.
Peroneal nerve.
Clinical uses:
Somato sensory evoked potentials are used to assess the functional integrity of
the sensory pathways.
Intraoperative SSEP monitoring has been described for:
Scoliosis corrective surgery.
Stabilization and decompression after spinal cord surgery.
Spinal fusion surgery.
Brachial of acoustic neuroma.
Resection of acoustic neuroma.
Resection of thalamic tumor.
Abdominal and thoracic aortic aneurysm repair.
Decompressive laminectomies.
Spinal coral tumor (intra/extramedullary)

-Second Edition
2011

97


Factors affecting SSEP:
Apart from the anatomical disruption of the nervous pathway, certain factors can
decrease the amplitude and increase the latency of somato sensory evoked potential.
They are
Volatile anesthetic agents Halothane, Enflurane, Isoflurane
N2O
Diazepam
Hypothermia.
Auditory Evoked Potentials: (AEP)
Auditory evoked potentials are monitored when CRANIAL NERVE VIII or
Brainstem is at risk or Injury. The risk of hearing loss during resection of acoustic tumor
and other tumors of the cerebellopontine angle is substantial and hence the need for
Auditory Evoked potential monitoring.
Techniques:
There are three major techniques for monitoring Auditory Evoked potential.
Brainstem Auditory Evoked potential (BAEP).
Electrocochleography (ECOG)
Auditory Nerve Action Potential Recording (ANAP).
Brain Stem Evoked Potentials:
Brain stem evoked potentials are recorded after a brief auditory stimulus is
delivered to one ear that produces a sequential activation of the peripheral auditory
pathway.
BAEP are recorded be delivering clicks repeatedly (500-1000 stimuli) in one car
with frequency of 10 Hz and duration of 100 microseconds. Recording electrodes are
placed on the lobe of stimulated ear and on top of the head (vertex).
A normal BAEP shows 7 peaks or waves:
Wave Generator
Wave I
Wave II
Wave III
Wave IV
Wave V
Wave VI
Wave VII
Acoustic nerve I
Cochlear nucleus II
Superior olive (Pons) III
Lateral lemiscus IV
Inferior colliculus (midbrain) V
Medial geniculate (thalamus) VI
Thalamocortical radiations VII
A decrease in the recorded amplitude or increase in latency shows functional
derangement of the auditory.
-Second Edition
2011

98


Pathway:
I. Uses:
Micro vascular decompression of the cranial nerves
Resection of acoustic neuroma.
Posterior fossa exploration for vascular and neoplastic lesions.
Clipping of basilar artery aneurysm.
Section of the Nerve VIII for intractable tinnitus
II. ECOG - Electro- Cochleography:
With ECOG, a monopolar needle electrode is placed through the tympanic
membrane onto the soft tissue covering the bony promontory of the middle ear.
A reference needle electrode is placed over the mastoid. Thus near field action
potentials, can be recorded from the cochlear membrane and lateral segment of the
auditory nerve analogous to wave I of BAEP.
This technique affords the surgeon rapid feedback on the functional status of the
cochlea since ECOG requires only 20-50 stimuli.
III. Auditory Nerve Action Potential (ANAP):
The recording of ANAP involves placement of an electrode onto the auditory
nerve under direct vision after the cerebellopontine angle has been discovered. A click
or burst stimulus is delivered to the ipsilateral ear and a well defined 10-30 microvolt
potential can be recorded.
IV. Visual Evoked Potentials:
Visual evoked potentials are recorded after mono ocular stimulation with
recording electrodes placed over occipital, parietal and central scalp. The stimuli are
produced by light emitting diodes placed in a goggle or contact lens over a closed lid.
The flash rate is 1 to 3 Hz with duration of 3 to 5 milliseconds. Two positive peaks at
approximately 100 and 200 milliseconds are observed.
VEP are used in the following procedures:
Resection of pituitary tumors.
Resection of craniopharyngioma, optic glioma, orbital pseudo tumor, occipital
arterio-venous malformation.
Resection of meningioma impinging on optic chiasma.
Clipping of basilar artery aneurysm.
Correction of orbital fracture.

-Second Edition
2011

99


Chapter 6 - ELECTROCONVULSIVE THERAPY (ECT)
Definition:
Consists of programmed electrical stimuli (in progressively increasing strength of
stimuli till a seizure threshold is reached) of CNS to initiate seizure activity. Introduced
in 1930 as a treatment for schizophrenia.
Mechanism:
Exact mechanism is not known. It is believed that seizure duration of 25 sec is
ineffective.
Seizures duration depends on many factors like:
1. Patients age
2. Energy of stimuli
3. Medications and anesthesia
4. Electrode placement
5. Seizure threshold
It is done 2-3 times /wk which is continued till patient improves.
Indications Contraindications
Severe major depression
Acute mania
Acute schizophrenia
Catatonia
Failure of drug treatment
Where rapid response is required
Suicidal tendencies
Phaeochromocytoma
Increase ICP
Recent CVA
Cardiac conduction defects
High risk pregnancy
Aortic and cerebral aneurysms

Physiological effects:
ANS: It initially causes increased parasympathetic discharge leading to bradycardia,
hypotension, salivation, and asystole, followed by increased sympathetic discharge
HR, BP, VPB and VT.
CNS: headache, confusion, agitation and CBF, ICP, IOP, CMRO2
Endocrines: Increase in stress hormones like ACTH, GH, cortical ADH and prolactin.
Even the levels of epinephrine and norepinephrine are increased.
Anesthetic technique: anesthesia is required during ECT to prevent psychological and
physical trauma.
-Second Edition
2011

100


Preoperative: Look out for co-existing disease of CNS and CVS and osteoporosis and
other medication patient is receiving.
Premedication: with glycopyrrolate which does not cross BBB can prevent bradycardia
and decreases the oral secretion associated with ECT.
Monitors: ECG, BP, Pulse oximeter, EEG, and EMG.
Procedure: Patient is preoxygenated with 100% O2, and then induced with inj.
Methohexital or thiopentone or propofol or ketamine.
Ketamine: has been shown not to seizure duration or produce excessive post
procedure agitation.
Neuromuscular blocker: succinylcholine is preferred because of its quick onset and
rapid off set. A dose of 0.5mg/kg is sufficient as complete muscular block is not
required. Alternate is mivacurium but not effective as had prolonged duration of action
compared to sch.
Central seizure: are monitored by EEG.
Peripheral seizure: are monitored by electromyogram.
Manage airway patency, ventilation and oxygenate with mask or LMA.
Avoid tongue bite, fracture bone, dislocation, and fall from table due to tonic
clonic seizure.
Evaluate cardiac and respiratory system.
Seizure time > 25 sec to be effective.
Recovery: PONV, headache, cognition impaired, patient is left lateral position.
Cause of death: MI, arrhythmia and CVA

-Second Edition
2011

101


Chapter 7 - CEREBRAL STEAL
The adult brain weight about 1360 gm which is 2% of total body weight. It receives 12-
15% of cardiac output. At rest CMRO2 is 3.5 ml O2/100 gm of brain tissue.
Autoregulation refers to the intrinsic capacity of the cerebral circulation to adjust its
resistance to maintain CBF constant over a wide range of mean arterial pressure (MAP).
In normal subjects, the limits of autoregulation are approximately 50 and 150 mmHg.
Above and below this range, CBF is pressure dependent (pressure passive) and varies
linearly with cerebral perfusion pressure. Autoregulation is influenced by various
pathological processes and in addition by the time course over which CPP changes
occur. The precise mechanism by which autoregulation is accomplished is unknown. It
appears to be an intrinsic characteristic of cerebral vascular smooth muscle.
PaCO2 and regulation of cerebral blood flow:
CBF varies directly with PaCO2. The effect is greatest within the range of
physiologic PaCO2 variation. CBF changes 1-2 m1/100 gm/min for each 1 mmHg change
in PaCO2 around normal PaCO2 values. The response is attenuated below a PaCO2 of 25
mmHg.

Under normal circumstances, CBF sensitivity to changes in PaCO2 appears to be
positively, correlated with resting levels of CBF. Accordingly, anesthetics that alter
resting CBF cause change in the response of the cerebral circulation. The changes in CBF
caused by PaCO2 depend on pH alterations on the ECF of the brain. The changes in ECF,
pH and CBF occur rapidly after PaCO2 adjustment because CO2 diffuses freely across the
cerebrovascular endothelium. In contrast to a respiratory acidosis, acute systemic
metabolic acidosis has little immediate effect on CBF because BBB excludes H
+
ion from
-Second Edition
2011

102


the perivascular space. Although the CBF change in response to a PaCO2 alterations
occur rapidly, they are not sustained. CBF returns to normal over 6-8 hrs, because CSF
pH gradually normalizes as a result of the extrusion of bicarbonate.
As PaCO2 is reduced by hyperventilation, CBF is decreased by cerebral
vasoconstriction as a direct response to the reduction in H
+
ion concentration in CSF.
When PaCO2 is reduced below 30 mmHg, CBF continues to decrease but not so
markedly, at levels below 26 mmHg EEG slow wave actually increases and below 23
mmHg, the vasoconstriction may be so intense that cerebral hypoxia may follow.
Hypoxia may act as a greater stimulus and lead to vasodilatation.
Opposite effects occur when PaCO2 increases during hypoventilation with a
reduction in this response. When PaCO2 levels exceed 50 mmHg the cerebral blood
volume increases and formation of edema may occur.
Over the central part of the response graph, CBF increases or decreases by 10
ml/100g/min for each 1 ka (7.5 mmHg) change in PaCO2.
The normal responsiveness of cerebral vessel to PaCO2 is lost in areas of brain
where autoregulation has ceased. The vessels in these areas behave passively and so,
when vasoconstriction produced in normally responding cerebral vessels by
hyperventilation, the majority of the CBF is channeled through the unresponsive vessels
resulting in an increase of CBF through this area. This is known as the inverse steal
effect when blood is channeled from the healthy areas of brain to pathological zones.
The opposite effect occurs in hypoventilation, resulting in a decrease in CBF through
pathological areas of the brain cerebral steal syndrome.

-Second Edition
2011

103


Chapter 8 CECEREBRATE RIGIDITY
When the brain is sectioned between pons and the mesencephalon, leaving
pontine and medullary reticular system as well as the vestibular system intact, then the
patient develops a condition called decerebrate rigidity.
This occurs in the antigravity muscles and they are:
The muscles of the neck.
The muscle of the trunk.
Extensors of the legs.
Cause:
The cause of decerebrate rigidity is blockage of the normally strong excitatory input to
the medullary reticular nuclei from the cerebral cortex, red nuclei and basal ganglia.
As a result the medullary ventricular inhibitory system becomes non functional
because of loss of its usual excitatory drive, thus allowing full over activity of pontine
excitatory system.
The specific characteristic of decerebrate rigidity is that the antigravity muscles exhibit
the phenomenon called spasticity and rigidity. This means that any attempt to change
the position of a limb or any other part of the body especially attempts to stretch reflex.
This occurs because the pontine and vestibular antigravity signals to the cord selectivity
excite the gamma motor neurons in the spinal cord much more than they excite the
alpha motor neurons.
This tightens the interfused muscle fibers of the muscle spindles which in turn strongly
sensitizes the stretch reflex feedback loop.

-Second Edition
2011

104


Chapter 9 - BRAIN-DEAD ORGAN DONOR
Cadaveric Donors contribute to the majority of renal transplants done in the developed
countries and cadaveric transplantation is becoming common in India as well.
The donors should be heart beating with stable hemodynamics and adequate
respiratory support.
A protocol for Brain death certification should be in place in each institution and
followed mutinously so as to avoid medico legal problems.
Brain stem function:
Cerebro-cortical function
Unconsciousness
Loss of spontaneous movement
Unresponsive to external (noxious) stimuli
Brain stem function
Cranial reflexes absent
Corneal reflex
Papillary light reflex
Oculo cephalic reflex
Oculo vestibular reflex
Atropine resistance
Supporting clinical studies
Cerebral blood flow
o Cerebral Angiogram
o Transcranial Doppler
o Xenon enhanced CT scan.
EEG
Contra indication to organ harvesting:
Prolonged Hypotension and Hypothermia
Hepatitis B and C
HIV
Malignancy
Generalized Bacterial and viral infections
Relative contra indications
Age >70 yrs
Diabetes
Severe vascular disease
-Second Edition
2011

105


Elevated serum creatinine.
Pre terminal excessive requirement of vasopressors
Intraoperative Management
A guideline for care of Donor is satisfaction of the minimum hundred criteria.
1. Maintenance of systolic B.P at >100mmHg.
- With fluid infusion crystalloids, colloids or blood
- Inotropic support and urine production with Dopamine (5-10 mg/kg/min)
Dobutamine / Low dose Adrenaline
- High doses of vasopressors with a vasoconstriction effect.
2. PaCo2 at >100mmHg with Normocarbia with Mechanical ventilation
3. Urine output at >100ml/hr with adjuncts such as Mannitol, Dopamine and
Furosemide.
Heparin administration must precede organ harvesting
After organ harvesting ventilation is discontinued and anesthetic support in
ceased.
Anesthetic support consists of Muscle relation to suppress reflex motor response
to surgery.
All these measures are directed at having optimal functioning of the transplant kidney.
ANESTHETIC MANAGEMENT OF CERVICAL CORD INJURIES
Spinal injuries can have a devastating effect on their victims. The outcome depends not
only on the primary injury that occurs at the time of accident but also on the prevention
of secondary injury which results from improper management of the patient during the
phase of immediate resuscitation and in the perioperative period. Most often, the
resuscitative measures that have been started in the emergency room will have to
continue through the intraoperative period into the postoperative phase. The acute
multisystem sequelae of spinal injury persist during the postoperative period and a
careful attention to these derangements forms the essence of the management of these
patients. The following is a discussion on the optimization of the function of the various
organ systems in the perioperative period in a patient with a spinal injury.
Respiratory Function
Respiratory dysfunction in a patient with spinal cord lesion is related to the paralysis of
the muscles of respiration. The degree or respiratory dysfunction depends on the level
of the spinal lesion. If the spinal cord injury occurs at or immediately below C4 level,
voluntary respiratory control is possible, albeit, with a vital capacity which is 20-25% of
the normal. Injuries above this level are associated with severe respiratory inadequacy
-Second Edition
2011

106


requiring mechanical ventilation Cervical spinal injuries at C6 or below spare
diaphragmatic involvement, but may affect intercostal muscles to a varying extent.
Involvement of the intercostal muscles leads to paradoxical inward movement of the
upper chest during inspiration. Inadequate expansion of the chest during inspiration
and instability of the thoracic cage during expiration lead to poor cough, facilitating
retention of secretions. Pulmonary infection, pulmonary edema and pulmonary
embolism may further impair alveolar ventilation.
Body position markedly affects the alveolar ventilation in a quadriplegic patient. Supine
position improves ventilation compared to head-up position (1). In supine position,
descent of the diaphragm during inspiration pushes the abdominal contents downward
and the flaccid abdominal wall forward. At the end of inspiration, elastic recoil of the
abdominal wall along with an upward movement of the abdominal contents moves the
diaphragm cephalad decreasing the end-expiratory volume of the lungs and allowing for
greater descent of the diaphragm during the subsequent inspiration.
Pulmonary function testing in a patient with cervical spinal injury reveals a decrease in
forced vital capacity (FVC), forced expiratory volume in 1.0 s (FEV1.0) and expiratory
reserve volume (ERV) and a normal forced expiratory ratio (FER).
A progression the level of the lesion during the first 4-5 days is not uncommon, as a
result of extension of the edema or haemorrhage within the spinal cord.
Two other factors that can worsen the patient's alveolar ventilation are pulmonary
edema and pulmonary embolism. Pulmonary edema occurs as result of over-
enthusiastic fluid administration to correct the spinal shock. Excessive fluid
administration leads to pulmonary edema without increasing the blood pressure. This is
a result of myocardial depression that is associated with spinal cord injury. Pulmonary
embolism has been noted to occur in 15% of the cervical cord injuries. Most often, it
occurs in acute rather than chronic phase.
Airway Considerations and Mechanical Ventilation
Patients who reach the intensive care unit with an endotracheal tube in situ need to be
provided care to prevent complications related to endotracheal tube and mechanical
ventilation. In addition, they should be assessed carefully for neurological improvement
and the earliest' indications for extubation. Patients who arrive in the ICU without an
airway and those whose trachea has been extubated at the end of the surgery also pose
a great concern, as cord edema resulting in deterioration of pulmonary function is not
uncommon. Close observation should be maintained in these patients for any
indications for endotracheal intubation and mechanical ventilation (table 1).

-Second Edition
2011

107


Table 1. Indications for Intubation and Mechanical Ventilation
Parameter Indication
Maximal expiratory force
Maximal inspiratory force
Vital capacity
PaO2 / FiO2
Chest radiograph
< + 20 cmH2O
< - 20 cmH2O
< 15 ml/kg
< 250
Atelectasis / infiltrates

The technique of intubation and the choice of anesthetic for intubation in these patients
depend on a number of variables: the level of the lesion, its association with the injuries
of the skull base, the cooperation of the patient, the nature of equipment and the
expertise available. Orotracheal intubation under thiopentone and Suxamethonium
combination with manual in-line traction is recommended in most centers. If this
technique is used, hyperkalemic response to Suxamethonium should be anticipated
from 48 h onwards. The response is maximal between 4 weeks and 5 months. Provided
the patient does not have injuries of the skull base, awake nasotracheal intubation
under regional anesthesia is a good alternative. Unconscious patients with unstable
lesions and cardiovascular disturbances may be better managed by fibre optic
intubation which is least disturbing physiologically. But considerable expertise is
required to achieve this in an emergency situation. In a study of 150 patients with spinal
cord injury 85 patients were intubated under general anesthesia and the rest under
regional anesthesia. Seventy one percent of all the patients were intubated orally and
the rest nasally. The results of the study indicated no significant difference in the
neurological outcome between the two groups.
Alternatives to endotracheal intubation in case of difficult airway include
cricothyroidotomy and percutaneous or conventional tracheostomy. A recent surgery
on the cervical spine through anterior approach is a limitation for these procedures.
Apart from technical difficulties in performing the procedure, proximity of the
tracheostomy to the operative site may favor infection of the surgical wound.
Respiratory Care and Mechanical Ventilation: In recent years, there has been a marked
improvement in the mortality of spinal injuries due to the improvement in the
respiratory management of these patients. A spontaneously breathing patient with
cervical cord injury essentially has an acute restrictive lung disease. Further loss of lung
volume and reduction of functional residual capacity can occur as a result of atelectasis,
retention of secretions and pulmonary infection. The use of CPAP may avert
deterioration of the pulmonary function to some extent. If immediate intubation is not
necessary, aggressive chest physiotherapy is required to maintain pulmonary function.
Incentive spirometry, aerosol therapy, percussion and vibration chest physiotherapy,
-Second Edition
2011

108


frequent change of position, humidification of the inspired gases and avoidance of
anticholinergics are some of the measures to prevent deterioration of the pulmonary
function. Blind nasotracheal suctioning may be required to remove retained secretions.
Care should be taken to prevent life-threatening arrhythmias during these maneuvers.
Borderline hypoxia exaggerates the occurrence of such arrhythmias. Therefore, the
patient should be adequately oxygenated before attempting suction. During
physiotherapy, abdominal push and use of abdominal corset can assist the cough
mechanism. In spite of all the physiotherapeutic measures if the pulmonary function
deteriorates, endotracheal intubation should not be delayed for emotional reasons.
Once intubated, ventilatory support should be optimized for each patient. SIMV with
pressure support is an ideal mode to provide variable level of ventilatory support. The
choice between pressure and volume controlled strategies depends on the pulmonary
parenchymal pathology. Patients with extensive lung injury with risk of pulmonary
barotrauma may benefit from pressure-controlled rather than volume-controlled
modes. A PEEP of about 5cm H2O is required in most of the cases. But its effects on
hemodynamic function should be carefully monitored. Most patients who show
substantial improvement in respiratory function are ready for weaning in 2-3 weeks
time. The weaning process has to be gradual with progressive reduction of the SIMV
rate and pressure support. Rapid weaning with acute loading of the respiratory muscles
may not be tolerated well. The risk of aspiration in the immediate post-extubation
period should be kept in mind. Enteral feeding is better avoided for about a day or two
during this period.
Patients who require mechanical ventilation even at the end of 4-6 weeks tend to
remain ventilator-dependent in the long run. The need for long term ventilation in these
patients calls for exploring the possibilities of home-ventilation and diaphragmatic
pacing.
Cardiovascular System
In experimental animals, arterial hypertension, increased PCWP, lowered myocardial
contractility; raised ICP and brain edema were noticed transiently following spinal cord
injury. Such a response is not documented in clinical setting. Most often, the patients are
hypotensive due to spinal shock when they reach the intensive care unit. They may also
have bradycardia. The degree of hypotension and bradycardia are a function of the level
of the injury and the extent of the injury suffered by the spinal cord. In injuries above
mid-thoracic level, loss of sympathetic tone forms the basis of hypotension and
bradycardia. Tracheal suctioning and-change of body position may precipitate
bradycardia and supraventricular arrhythmias. These episodes may be treated with
vagolytic agents and increased ventilation and oxygenation. These patients may also be
at exaggerated risk of hypotension during positive pressure ventilation, as reflex
-Second Edition
2011

109


vasoconstriction does not compensate for the decreased venous return caused by
increased intrathoracic pressure. In addition, hyperventilation may aggravate the
myocardial depression that is associated with high spinal injuries.
Treatment of hypotension in these patients should comprise of a judicious combination
of intravascular volume replacement, inotropes and vasopressors. Though it is
commonly believed that peripheral vasodilatation is responsible for the hypotension,
myocardial depression also will have a significant contribution in many of these
patients. Attempts at restoration of normal blood pressure by excessive volume
replacement and/or peripheral vasoconstrictors could precipitate pulmonary edema.
Temperature Control
Loss of ability to contract the skeletal muscles and to vasoconstriction below the level of
the injury makes some of the patients poikilothermic and renders them vulnerable for
hypothermia. It has also been documented that spinal cord transection above C7
interferes with the sweating process and such patients are likely to become
hyperthermic under not environmental conditions. Close monitoring of the body
temperature and protection against such effects of environmental temperatures should
be provided.
Autonomic Dysreflexia
The early phase following spinal cord trauma is characterized by hypotonia and
hyporeflexia. Bladder and rectal sphincters are contracted. Retention with overflow of
urine occurs when the bladder pressure exceeds the sphincter pressure Urinary
catheterization becomes mandatory under these circumstances. Paralytic ileus results
from the loss of peristalsis and passive distension of the bowel. Attention should to be
paid to the fluid and electrolyte balance. Since enteral nutrition is not possible, in this
stage, parenteral nutrition has to be resorted.
After a period ranging from a few days UP to a few weeks the spinal shock subsides and
the reflex activity starts to reappear. In this phase, the patient exhibits autonomic
hyperreflexia characterized by flushing and diaphoresis in the head and neck, chest
pain, headache, hypertension and bradycardia. About 85% of patients with lesions
above TT are susceptible for this complication. Retinal hemorrhages and subarachnoid
haemorrhage have been reported as a consequence of severe hypertension. A wide
range of arrhythmias may accompany the episodes of autonomic hyperreflexia, which
include sinus bradycardia. P wave changes, prolongation of P-R interval, ectopic beats
and incomplete heart block. The stimuli that can trigger autoimmune hyperreflexia
include bowel or bladder distension and surgical stimuli. The mechanism of autonomic
hyperreflexia is as follows:-Dissociation of the thoracolumbar sympathetic outflow from
the central control results in uninhibited sympathetic activity in response to visceral or
-Second Edition
2011

110


somatic stimulation below the level of the lesion which explains the hypertension. As a
compensation for this, the blood vessels above the level of the lesion dilate and cause
symptoms such as flushing of the face, headache and diaphoresis in the head and neck. A
variety of vasoactive agents (centrally acting clonidine. peripherally acting alpha and
beta adrenergic blocking agents and direct vasodilators such as sodium nitroprusside)
have been used to treat the episodes of autonomic hyperreflexia.
Gastrointestinal Function:
Gastric stasis and intestinal atony may prevent enteral feeding in patients with spinal
shock. Abdominal distension, in turn, may interfere with pulmonary function by causing
diaphragmatic splinting and regurgitation and aspiration of the stomach contents.
Repeated aspiration of the gastric contents and usage of antacids and H2-receptor
blockers may lead to metabolic alkalosis. As a compensation for this metabolic alkalosis,
hypoventilation and respiratory acidosis may ensue. The hypoventilation may further
augment atelectasis. Acetazolamide has been suggested to stimulate ventilation under
these circumstances.
Renal Function
In the acute phase, spinal stock and hypotension may precipitate renal failure. In
chronic cases, renal failure is a major cause of death. The causes of renal failure in these
cases are recurrent urinary tract infections, pyelonephritis and hypercalcemia.
Skeletal System:
Demineralization of the bones leading to osteoporosis may cause pathological fractures.
Therefore, care should be exercised during movement and transfer of these patients.
Glucose and Spinal Cord Injury: In experimental studies, hyperglycemia has been
shown to worsen neurological outcome following spinal cord ischemia. Therefore,
normoglycemia should be aimed at while managing these patients in the postoperative
period.
Miscellaneous: Occurrence of pressure sores should be avoided with appropriate
nursing measures; Deep vein thrombosis should be prevented through active and
passive exercises, compression boots and prophylactic heparin. Adequate enteral
nutrition should be ensured from the beginning. If there is a prolonged need for tube
feeds, feeding jejunostomy should be considered.
Chronic pain is a long term complication in some of the patients with spinal cord
injuries. Three types of pain can be seen in these patients: Central pain characterized by
burning or stabbing pain or numbness, musculoskeletal pain characterized by aching
pain located at or distal to the level of paralysis and syringomyelic pain characterized by
pain above the level of injury.
-Second Edition
2011

111


Definitive Therapies in Spinal Cord Injuries: A wide range of agents and techniques
(anesthetic agents, calcium channel blockers, naloxone, local hypothermia,
hyperventilation etc.) have been investigated for their therapeutic potential, but till
today, steroids seem to be the only agents which have offered some demonstrable
clinical benefit.
The Role of Steroids: Steroids have been under experimental investigation for a number
of years. The first National Acute Spinal Cord Injury Study (NASCIS -1) compared methyl
prednisolone in low dose HOP mo IV loading followed by 100 mg daily for 10days) and
high dose of (1.0g IV lading followed by 1.0g daily for 10 days) regimens. With both the
schedules, no difference in outcome was shown in motor and sensory function. Later,
NASCIS-II study compared naloxone (574 mg/kg IV followed by 4.0 mg/kg/h for 23 h)
with methyl prednisolone (30 mg/kg IV followed by 5.4 mg/kg/h for 23 h). Both at 6
months and 1 year, the motor (unction was significantly better when methyl
prednisolone was administered within 8 h after injury. Patients who received either of
the two treatments after 8 hour fared poorly compared to the placebo group. Though
neurological examination revealed improvement in methyl prednisolone-treated group,
the improvement was not functionally significant.
In conclusion, cardio respiratory care remains the major consideration in the acute
management of patients with cervical spinal injuries. As there are no definitive
therapeutic modalities which can aid the recovery of the neurological function, the care
mainly remains supportive. A good general care goes a long way in preventing systemic
complications that could adversely affect the outcome.

-Second Edition
2011

112



-Second Edition
2011

113


Chapter 10 - ANESTHESIA FOR INTRACRANIAL ANEURYSM SURGERY
The aim of this review is to summarize the epidemiology, clinical presentation
and anesthetic management of intracranial aneurysms.
Intracranial aneurysms are saccular dilatations of blood vessels and are common
and the bifurcation of the major intracranial vessels. They may be either
congenital or acquired, may be associated with hypertension, and 21% of
patients have more than one aneurysm. The age-adjusted prevalence for this
condition in North America is 2000 per 100,000 populations and the annual
incidence of subarachnoid hemorrhage (SAH) secondary to the condition is 12
per 100,000. The age incidence varies from 40-60 years and the females' male
ratio is 1.6:1. Nearly a third of patients with this condition die or are severely
disabled at the time of the initial bleed. One-third of patients with this condition
are functional survivors, and the operative mortality for the condition is less
than 10%. The important risk factors for aneurysmal SAH are the size of the
aneurysm, age/gender of the patient history of hypertension, substance abuse,
systemic disease pregnancy and intracranial hemodynamic abnormalities.
Following rupture, the intracranial pressure (ICP) rises secondary to the
hematoma. The disturbance in the flow of cerebrospinal fluid (CSF) leads to
hydrocephalus and is associated with brain destruction, fluid and electrolyte
abnormality, cardiac irregularities and respiratory impairment. The clinical
presentation of this condition includes headache, loss or depressed level of
consciousness, focal neurological signs, seizures, nausea and vomiting, EKG
abnormalities, increased sympathetic activity with hypertension and fluid-
electrolyte abnormalities ranging from hypovolemia, hyponatremia and other
electrolyte abnormalities. CT scans are commonly used for the diagnosis of SAH
and can also reliably detect aneurysms greater than 1 cm in diameter. Four-
vessel angiography can determine the location of these lesions. With the
widespread adoption of these imaging modalities, lumbar puncture is used less
commonly. Various scoring systems are used to grade the severity of SAH, with
the Hunt-Hess classification and Fisher Grading systems being commonly
employed. Complications after SAH include vasospasm, re-bleeding,
hydrocephalus and medical complications. Importantly, the factors that
determine outcome after SAH are the admission neurological status of the
patient, age, the presence of vasospasm on admission, the size of the aneurysm
(with aneurysms less than 12 mm having better outcome), the distribution of the
subarachnoid clot, and the pre-existing medical condition of the patient;
hypertension and hyperglycemia are associated with poorer prognosis. The
advantages of early surgery for this condition are that it effectively eliminates
-Second Edition
2011

114


the risk of re-bleeding, allows treatment of the vasospasm and also results in clot
removal. On the other hand, late surgery has the advantage in that it is associated
with a lower incidence of vasospasm, allows better operative conditions and is
associated with a lower morbidity/mortality.
The anesthetic management of patients with this condition poses a formidable
challenge, and is based on the principles of maintenance of adequate cerebral
blood flow (CBF), optimal cerebral perfusion pressure (CPP), decreasing the risk
for intracranial hemorrhage and cerebral ischemia, and, finally, the avoidance of
cerebral hyperperfusion.
Anesthetic management can be conveniently divided into three main areas,
namely, preoperative evaluation, intra- and post-operative management.
The pre-operative evaluation of these high-risk patients should include a
thorough neurologic, radiologic and systemic evaluation. ECG changes are
frequently seen in nearly 50-70% of patients with this condition and include
inverted T-waves, ST-T changes, shortened PR interval, QTc prolongation,
peaked P waves, U waves and Q waves. Also, dysrhythmias are reported in up to
90% of patients with SAH secondary to ruptured aneurysms; the spectrum of
changes seen include Preventricular complexes (PVC) ventricular tachycardia,
ventricular fibrillation, supraventricular tachycardia, premature atrial
contractions, heart block, idioventricular rhythms and torsades de pointes.
Cardiac evaluation following aneurysmal SAH is performed by echocardiography,
angiography and thallium scintigraphy.
Important intra-operative considerations include premedication, the induction,
maintenance and monitoring of anesthesia and the risks of intraoperative
aneurysmal rupture. Patients on treatment with Ca channel blockers,
anticonvulsants or steroids should continue these medications and pre-operative
sedatives are generally avoided. The important goals of anesthetic management
include prevention of changes in transmural pressure (TMP); the TMP=MAP
(mean arterial pressure) - Intracranial pressure (ICP) and a low TMP is generally
preferred. Also, it is important to maintain adequate CPP to prevent cerebral
ischemia, and normal or high CPP are preferred. Aneurysm rupture may occur
during induction and smooth induction is achieved with intravenous thiopental
or propofol. Narcotics used include fentanyl and other rapidly active intravenous
agents include etomidate and thiopental; lidocaine may also be useful in blunting
the patients response to sympathetic stimulation. It is important to prevent
increases in blood pressure during laryngoscopy and the avoidance of the cough
reflex. Ventilation is controlled with 100% 02 to achieve an arterial PaCO2 of 35-
40 mm Hg when intracranial compliance is normal and 25-30 mm Hg when it is
-Second Edition
2011

115


impaired. Muscle relaxants used include Vecuronium and succinylcholine. It is
important to note that while hyperventilation is not required for Clinical Grade I
and II (Hunt-Hess classification) patients, moderate hyperventilation may be
required to reduce ICP and improve CPP for patients with Grades > II. Pre-
induction monitoring includes pulse oximeter, 5 lead EKG, blood pressure cuff
measurement and arterial waveform monitoring. Post-induction, monitoring is
performed with end tidal capnography, neuromuscular blockade monitor,
temperature monitoring, urinary catheter output measurement, central venous
line monitoring for central venous pressure (CVP), and. Pulmonary artery
catheter measurements in high risk patients. Special monitoring techniques
include transcutaneous Doppler ultrasonography, and electrophysiological
monitoring (EEG, somatosensory evoked potential). The important goals for the
maintenance of anesthesia include the provision of unconsciousness and
analgesia, appropriate to the level of surgical stimulation, the facilitation of
surgical exposure through optimal brain relaxation, the maintenance of optimal
CPP, reduction of TMP during exposure and clipping of the aneurysm, and the
prompt awakening and assessment of patients with good SAH grades; of
paramount importance is the ability of an anesthesiologist to effectively manage
an intra-operative aneurysm rupture. Vasoactive agents commonly employed
include esmolol, labetalol, propranolol, nitroglycerine, trimethaphan and
adenosine. Brain relaxation by reducing brain bulk is important for optimal
surgical exposure and also aids in brain retraction and facilitates clipping of
aneurysm. Intravenous mannitol is given 45 minutes before the dura is opened
and gradual CSF withdrawal via lumbar drains may also help, once the dura is
opened. A reduction in the TMP also decreases aneurysmal wall stress and may
facilitate surgical clipping; in the event that rupture occurs, control of the
bleeding is easier. Hypotension may also be induced with isoflurane,
nitroprusside or esmolol, but is associated with the complications of cerebral
thrombosis or ischemia, coronary artery thrombosis, renal insufficiency, hepatic
failure, post-operative pulmonary dysfunction and rebound hypertension.
Relative contraindication to the induction of hypotension includes ischemic
cerebrovascular disease, coronary artery disease, hypovolemia, anemia, severe
hypertension and extremes of age. Another important aspect of peri-operative
management includes cerebral protection where the goal is to improve the
ischemic tolerance. Barbiturates have been shown to reduce the magnitude of'
neurologic damage produced by focal ischemia.
A catastrophic occurrence during aneurysm surgery is rupture; the reported
incidence is 13% with an intraoperative leak rate of 6%. Rupture commonly
-Second Edition
2011

116


occurs during early surgical exposure and is associated with increased
neurological morbidity and mortality. Using modern anesthetic techniques, the
rupture rate for aneurysms should be less than 1%. If rupture occurs when the
skull is opened, it is associated with an abrupt increase in blood pressure; it is
important to realize that the ICP also increases and thiopental may be
administered along with blood pressure control. If aneurysm rupture occurs
during dissection, it is associated with hypotension.
Following aneurysmal surgery, the aim of anesthetic management is to allow
prompt recovery from anesthesia, so as to evaluate patients with Grades I and II
SAH and in those with an uncomplicated intra-operative course. To enhance
quick emergence inhalation anesthetic agents (desflurane. Sevoflurane) or
intravenous agents such as propofol or Remifentanyl may be safely used;
incremental doses of anti-hypertensive (labetalol, esmolol) may also be used.
Intravenous lidocaine may also be used to decrease airway reflexes due to
endotracheal tube movement. Delayed emergence from anesthesia lead to a
delay in the recognition of focal deficits. Thorough and repeated neurologic
examinations are required in the post-operative period. Vasospasm is
prevented by adequate volume expansion and moderate hypertension with a
mean arterial pressured between 80-120 mm Hg. Grades I and II patients with
no complications may be extubated immediately whereas those in Grades IV, V
and operative complications are returned to the intensive care unit intubated
and ventilated, till improvement in clinical status.

-Second Edition
2011

117


Chapter 11 - ANESTHETIC MANAGEMENT OF POSTERIOR
FOSSA SURGERY
Anesthetic management of patients during posterior cranial fossa surgery poses unique
challenges to the anesthesiologists because of the proximity of the surgical lesions to
vital cardio respiratory centers and cranial nerves. Complications associated with
surgical positioning demand specialized monitoring and meticulous intraoperative care.
Surgical Lesions:
A variety of congenital, inflammatory, neoplastic, traumatic and vascular lesions
in the posterior fossa may require surgical intervention. A list of some of the common
conditions is given in table 1.
Preoperative Assessment:
Patients requiring posterior fossa surgery range from small children to the
elderly. Apart from the general Preanesthetic assessment complication of mass lesions
in the posterior fossa. Headache vomiting, papilloma, enlarged lateral ventricles on CT
scan and presence of periventricular lucency.
Table 1. Common Surgical Lesions in Posterior Fossa
Congenital Arnold Chiari malformation

Neoplastic
Midline masses:
Medulloblastoma
Ependymoma
Brainstem glioma
Intraventricular papilloma
Cerebello- pontine angle tumours
Schwannoma of VIII, V or lower cranial nerves
Meningioma
Cerebellar tumours:
Astrocytoma
Meningioma
Inflammatory Cerebellar Abscess
Cerebellar Tuberculoma
Traumatic Extradural hematoma
Cerebellar contusion/hematoma
Vascular Aneurysms of vertebrobasilar system
Arteriovenous malformations
Miscellaneous Trigeminal neuralgia
Hemi facial spasms

-Second Edition
2011

118


Suggest raised ICP. History must be obtained about earlier CSF diversion procedures
(ventriculo-peritoneal or ventriculo-arterial shunt or endoscope third ventriculostomy).
A functioning preoperative shunt reduces the risk of intraoperative raised ICP (e.g.,
intraoperative swollen brain) are high in patients with untreated hydrocephalus.
Lower cranial nerve dysfunction is common in patients with cerebello-pontine
angle and brainstem tumors. Dysphagia, and impaired gag reflex my result in
preoperative pulmonary aspiration; the patient may have active pulmonary infection
when he presents for surgery.
Repeated vomiting and dysphagia may cause dehydration in these patients.
Preoperative hydration status must be evaluated to ensure intraoperative
hemodynamic stability.
Cardiac reserve must be evaluated in the elderly, hypertensive patients and
those with significant cardiac disease. Limited cardiorespiratory reserve may limit the
positioning options. The risk of orthostatic hypotension in sitting position is increased
in patients with uncontrolled hypertension, advanced age and hypovolemia. Preexisting
cardiac arrhythmia may interfere with interpretation of intraoperative cardiac changes
due to brainstem dysfunction.
In patients planned for surgery in sitting position. Information should be
obtained regarding the presence of patient foramen ovale (PFO) or any other right-to-
left intracardiac shunt. Autopsy studies have demonstrated a 27% incidence of PFO, but
preoperative testing has shown functional PFO only in 65.
Surgical Position:
Sitting position, which was most favored until about 15-20 years ago, is slowly
giving way to horizontal positions (prone, lateral and supine) because of concerns
relating to venous air embolism. Some centers however continue to practice it
frequently. Limited use of sitting position should remain in the neurosurgeons
armamentarium so that, where necessary, the patient is not denied the benefit of
individual cases is of great importance. The patient must be adequately informed of the
specific risks of venous air embolism, hypotension and neurological complications.
Preoperative echocardiography is recommended for identification of patient foramen
ovale.
Supine Position:
This position has a limited role in posterior fossa surgery. Its use is limited to
micro vascular decompressive procedures (for trigeminal neuralgia) and surgery on
acoustic neurinoma. The head is turned laterally and the ipsilateral shoulder is pulled
away from the operative site. Injury to brachial excessive. Supine position leads to a
-Second Edition
2011

119


progressive reduction of functional residual capacity and dependent atelectasis leading
to increased pulmonary shunt over a period of time.
Prone Position:
Prone position is commonly used for midline lesions and medial cerebellar
lesions. This position significantly reduces the risk of air embolism though it is possible
if the head is considerably elevated above the heart level. Reduction of functional
residual capacity in this position is less than that in supine position if pressure on the
abdomen is avoided. Postoperative blindness is a serious complication that may be
caused by central retinal arterial thrombosis. Depending positioning may lead to
massive face and tongue swelling. Special care must be taken to fix the endotracheal
tube securely so that it does not slip out during the course of surgery so that it does not
slip out during the course of surgery. Extreme flexion of the neck may cause a kink of
endotracheal tube. An armoured tube decreased this risk.
Lateral Position:
Cerebello-pontine lesions and lateral cerebellar lesions are operated upon in this
position. The lower arm is supported in a sling to allow proper fixation of the head in
the three-pin frame. Brachial plexus injury is prevented by using an axillary roll.
Respiratory compromise is less than in supine position, but may occur rarely due to
redistribution of ventilation perfusion rations. Park bench position is a modification of
lateral position used for cerebello-pontine angle surgery; the head is elevated above the
head and neck is rotated 30
0
to the opposite side.
Sitting Position:
Sitting position offers the advantages of excellent surgical access and decreased
blood loss. Despite a large volume of knowledge pertaining to the life-threatening
complications associated with sitting position. A 1994 British survey revealed that 34%
of the neurosurgical centers in Britain still use that position for infratentorial surgical
procedures in another German survey, sitting position was preferred for posterior fossa
surgery by 45% of the neurosurgeons. To decrease the risk of hemodynamic instability,
most often, a lounging position rather than a vertical sitting position is employed. A
recent study, reported very low incidence of complications in pediatric posterior fossa
surgery carried out in sitting position.
Some frequently encountered complications during posterior fossa surgery are
listed in table 2.

-Second Edition
2011

120


Table 2. Common Complications of Posterior Fossa surgery in Sitting Position
1. Hypotension
2. venous Air Embolism (VAE)
3. Airway problems
4. Tension Pneumocephalus
5. Neurological Complications
Peripheral Nerve Injuries
Upper Cervical Quadriplegia
Ischemia Cerebral Damage
Hypotension:
Peripheral pooling of the blood in the dependent areas due to vasodilatation
during anesthesia may result in hypotension at the time of positioning. The incidence of
this complication does not seem to be different between patients with and without
cardiac disease. Prevention of this complication depends on ensuring normovolemia
before positioning gradual positioning, usage of compressive stockings for legs and
adoption of a lounging position rather than a strict sitting position. Hypotension during
the course of surgery is related most often to surgical complications such as blood loss,
air embolism and brainstem disturbances than to the sitting position per se.
Acute hypotension at the time of positioning normally responds to intravenous
administration of fluids. If the hypotension persists despite adequate fluid
administration, the operating table should be tilted backwards to aid venous return to
the heart. If the hypotension is not corrected by these simple measures, it is advisable to
return the patient to supine position. Administration of vasopressors to treat the
hypotension during positioning is not recommended except in life-threatening
situations. Blood loss is very poorly tolerated in sitting position and it is essential to
ensure adequate intravascular volume throughout the procedure.
Venous Air Embolism (VAE):
Air embolism occurs during posterior fossa surgery in sitting position when
there is an open non-collapsible vein and the pressure at the site of opening is sub
atmospheric. The reported incidence of this complication varies with the sensitivity of
the monitoring device employed for its detection. With the advent of precardial
Doppler, most studies report an incidence varying between 30-45%. Microbubbles of air
appeared in the right atrium in all patients monitored by transesophageal
echocardiography in one study. Despite such high rate of detection, the actual risk of
clinically severe air embolism seems to be very low.
The clinical consequences of venous air embolism depend on the volume of air
entrained, the rate of entrainment of air and the presence of patent foramen ovale.
-Second Edition
2011

121


Continuous entrainment of air results in an increase in the pulmonary arterial pressure
as a result of mechanical blockade of the pulmonary vasculature and also reflex
pulmonary vasoconstriction. Micro bubbles in the pulmonary circulation may also
initiate pulmonary vascular endothelial injury leading to hypoxemia and hypercapnia.
Bronchoconstriction may occur in some patient. The consequences of massive air
embolism are cardiovascular collapse. Other complications of VAE include pulmonary
edema and ARDS.
Paradoxical air embolism (PAE) is a condition in which the air enters the
systemic circulation from the right heart through a patent defect. It is estimated that the
incidence to PFO in normal population is around 27% (Hagan 1984). Air may also be
forced through the pulmonary capillary bed, especially in the presence of pulmonary
vasodilatory drugs. Paradoxical air embolism is facilitated by hypovolemia, which
causes a reduction of both central venous pressure and systemic arterial pressure,
Embolization of coronary circulation due to PAE may lead to arrhythmia and cardiac
arrest; cerebral embolization may lead to cerebral infarction.
Emergency management of venous air embolism depends on accurate and
speedy detection of the complication. The rate of detection of air-embolism has
increased ever since the introduction of precordial Doppler. Detection of air embolism
has increased ever since the introduction of precordial Doppler. Detection of air
embolism based on clinical findings such as hypotension, hypoxia, cardiac arrhythmia,
mill-wheel murmur and gasping respiration is quite late. Increased airway pressure has
also been reported as an additional sign to detect VAE. Precordial Doppler can detect
even small quantities of air (0.5 ml/kg).
Spectral analysis of the precordial Doppler signal to obtain quantitative
information has been attempted. To date, transesophageal echo-cardiograph (TEE)
remains the most sensitive method to detect VAE. Using a 3.5-5.0 Hz esophageal probe,
it is possible to measure volumes as low as 0.02 ml/kg. One of the advantages that TEE
offers over precordial Doppler is that it can detect incidents of paradoxical air embolism
is a definite indication for the use of TEE. Routine use of TEE is limited by the cost and
the need for specialized training. Change in end tidal CO2 pressure (Pet CO2) occurs
later than Doppler change but earlier than cardiovascular changes. PetCO2 provides an
estimate of the physiologic derangement; the change, however, is not specific for VAE.
But both these methods are less sensitive than Doppler, TEE and PetCO2.
Prevention of VAE depends on attention to meticulous hemostasis at very stage
during surgery, especially during the dissection of muscle planes and craniotomy; VAE
may also occur during release of PEEP and repositioning of the patient into the4 supine
position. Therefore, continuous monitoring should be carried out until the patient is
returned to supine position. Appropriate placement of central venous catheter with the
-Second Edition
2011

122


tip at the junction of superior vena cava and right atrium aids recovery of air in the
event of air embolism. Preoperative TEE examination for PFO would forewarn the risk
for PAE.
When air embolism is detected, the operating surgeon must be informed about
the event; efforts must be made to secure hemostasis. If the bleeding point is not
evident immediately, applying Valsalva maneuver might help in its detection: Flooding
the operative field with saline prevents further entrainment of air. Discontinuation of
nitrous oxide from the anesthetic obviates the risk of enlargement of the air bubbles.
Application of PEEP is advocated by some authors to decrease air embolism. There is
not enough evidence to support the view that PEEP increases the intracranial venous
pressure so as to decrease the incidence of VAE. On the other hand, there are
suggestions that in susceptible individuals, it may enhance the risk of paradoxical air
embolism by reversing the pressure gradient between right and left atrium. Application
of the bleeding point; this maneuver may entail the risk of acute brain swelling. Though
military antishock trousers (MAST) have been shown to increase the venous pressure,
the elevation is not sustained for longer than 30 min and they do not seem to offer any
clinical benefit.
Airway Complications:
Acute flexion of the neck in sitting position may cause a kink of the endotracheal
tube. As the patients trachea is intubated in supine position with the neck in extension,
after assumption of the sitting position with acute neck flexion, there is a potential for
the endotracheal tube to migrate into one of the main bronchi or to slip out of the
larynx. Acute neck flexion in sitting position has also been associated with massive
swelling of the face and tongue and ischemic necrosis of the tongue necessitating
postoperative tracheostomy. Avoidance of extreme flexion and ensuring adequate space
between the chin and the sternum prevents kinking of the endotracheal tube. Avoiding
Guedels airway has been suggested to prevent swelling of the tongue. Repeated
auscultation of the chest during positioning and monitoring the airway pressure, end-
tidal carbon dioxide and oxygen saturation help to detect the airway problems at the
earliest before they lead serious consequences.
Tension Pneumocephalus:
Tension pneumocephalus is a complication reported more frequently in sitting
position, though it may occur in any craniotomy where a position, though it may occur
in any craniotomy where a large empty subdural space is created due to excessive
shrinkage of the brain or a large empty space is left after decompression of a big
tumour. During surgery in sitting position, a combination of hyperventilation, mannitol
and CSF drainage reduces the brain volume. The potential subdural space above the
-Second Edition
2011

123


brain surface is occupied by air when the dura is open. At the end of surgery after the
closure of the dura mater, re-expansion of the brain and restoration of normal PaCO2
(restoration of normal cerebral blood volume) increase the pressure within the trapped
air. The volume of air may increase if administration of nitrous oxide is continued after
dural closure. Irrigation of the subdural space with saline, discontinuation of nitrous
oxide and hyperventilation after dural closure may prevent this complication.
Delayed recovery is a common manifestation of tension pneumocephalus. In less
severe forms the patient may complain of persistent, headache. In more severe cases,
the patient may show signs of severe rise in intracranial pressure with imminent
herniation. A twist-drill aspiration of air rapidly improves the neurological state. Supine
position with administration of 100% oxygen may facilitate absorption of air in less
severe cases.
Neurological Complications:
Quadriplegia: Mid-cervical quadriplegia following operations in sitting position has
been described. Elderly spondylotic patients are prone for this complication. The
precipitating insult is not clear but may be related to prolonged flexion producing
stretch injury of the spinal cord. Attention to maintenance of adequate perfusion
pressure in sitting position and avoidance of excessive flexion prevent this
complication.
Subdural Hematoma: Supratentorial subdural hematoma occurs in less than 1% of
patients operated upon in sitting position. Subdural hematoma is caused by stretching
of the bridging veins due to excessive cerebral dehydration and effective CSF drainage
through a ventriculoperitoneal shunt. Management of this complication comprises of an
emergency CT scanning to confirm the diagnosis and prompt surgical evacuation of the
clot.
Ischemic Cerebral Damage: With an increased gradient between the heart and brain,
there is a potential risk of reduction of cerebral blood flow in the sitting position. A
number of studies examined this issue and it appears that the risk very low when the
intracranial pressure is normal. The cerebral blood flow values are the lowest in sitting
position when the intracranial pressure is high.
COMPLICATIONS COMMON TO PATIENTS OPERATED UPON IN
ALL POSITIONS
Cerebellar Swelling:
Slack cerebellum is one of the major advantages claimed for the sitting position.
However, it is not unusual, during surgery, to encounter cerebellar swelling as a result
of excessive retraction, deep-seated hematoma or dilated ventricles. The problem may
-Second Edition
2011

124


be further exaggerated by high concentrations of inhalational anesthetics, venous
obstruction due to excessive flexion or rotation of the neck and inappropriate control of
PaCO2. Management of this complication in sitting position is difficult as aggressive
measures such as controlled hyperventilation, and high-dose barbiturate therapy, that
can e applied with reasonable safety in supine position, are fraught with major risks of
cerebral ischemia in sitting position.
It the brain is tense at the time of dural opening, the position of the head and
neck should be verified. If the neck is rotated causing obstruction to jugular venous
outflow, appropriate correction should be carried out. Airway obstruction, hypoxia and
hypercapnia should be ruled out as the possible causes. Discontinuation of nitrous oxide
from anesthetic may be beneficial. Lowering the concentrations of inhalational agents
might help reduce the brain tension. Incipient straining could be avoided by ensuring
adequate muscle relaxation. If PaCO2 is not in the hypocapnic range, minute ventilation
could be increased to bring it down to around 25 mmHg. Caution should be exercised I
institution of hyperventilation as reduction of PaCO2 even to 25 mmHg could result in
cerebral hypoxia. Mannitol in a dose of o.5 1.0 g/kg in combination with furosemide
0.5 1.0 mg/kg reduces brain volume. As all these measures are being undertaken, it is
preferable not to open the dura until there are signs of laxity. After the dural opening, a
rapid initial decompression of the mass lesion would prevent the vicious cycle of venous
obstruction at the margins of craniotomy and further brain bulge. In patients with
evidence CSF drainage through a supratentorial burr-hole may be helpful to decrease
the brain-bulge.
Intraoperative Brainstem Dysfunction:
Integrity of the brainstem function may be jeopardized during the posterior
fossa surgery due to pressure, vascular compromise or mechanical distortion of the
brainstem. Such intraoperative ischemic episodes, when prolonged, may lead to
postoperative neurologic deficits, disturbances of spontaneous respiratory function and
cardiovascular instability. At present, in most of the institutions, intraoperative
monitoring of the integrity of the brain stem function relies on monitoring the heart
rate, rhythm and flood pressure. Sinus bradycardia, junctional bradycardia, sinus arrest
and ventricular tachycardia may occur during removal of medulloblastoma,
intraventricular ependymomas, and brainstem gliomas, dissection of acoustic
neurinoma and surgery on vertebrobasilar aneurysms. Manipulations in the root entry
zones of cranial nerves (surgery for trigeminal neuralgia, lower cranial nerve
Schwannoma) may cause hyper tension, bradycardia, and ventricular tachycardia and
ST segment changes.
Any unexplained change in the cardiac rate or rhythm or blood pressure,
irrespective of its magnitude, should be brought to the notice of the operating surgeon,
-Second Edition
2011

125


as it could be a potential indicator of a brain-stem insult. The surgeon, in turn, should
examine the possibility of the change being a result of the surgical procedure under
progress. It may be worthwhile to change the approach temporarily in order to avoid
any further insult to the brainstem. Usage of pharmacological agents to correct this
brainstem cardiovascular changes it to be discouraged unless the change is life-
threatening. Modification of these parameters by pharmacological agents prevents
utilization of these parameters for further monitoring of the brainstem function.
Evoked potential monitoring is a sensitive technique for detection of intra-
operative brainstem dysfunction; short latency somatosensory evoked potentials
(SSEP) can be helpful to monitor the cervical cord ischemia as well as the brainstem
function. Brainstem auditory evoked potentials (BAEP) are more robust and less
affected by anesthetics than SSEP. A 50% reduction in the height or a 1 ms increase in
the latency of N20 wave of SSEP or the fifth peak of BAER are considered clinically
significant. These two modalities of evoked potentials do not seem to differ in their
ability to predict postoperative neurological deficit. They are extensively used to
monitor eighth cranial nerve and brainstem function during resection of acoustic nerve
tumors and microvascular decompression of cranial nerves. The major limitation of
both SSEP and BAER is that they monitor only sensory pathways and damage to motor
tracts and cranial nerves can occur with a normal intraoperative SEP study. Secondly,
the recordings may be affected by anesthetics and changes in physiological parameters
such as mean arterial pressure; blood gases and body temperature. Motor evoked
potentials have been used to guide intraoperative compression and to predict
postoperative function in medullary tumors and Chiari malformation.
Neurological Complications
Cranial Nerve Dysfunction:
Surgical procedures on cerebellopontine angle lesions could result in
postoperative dysfunction of VII, VIII, IX and X cranial nerves. Involvement of IX and X
cranial nerves could lead to the risk of postoperative pulmonary aspiration and delay in
tracheal extubation. Significant obtundation of pharyngeal and laryngeal reflexes may
necessitate a tracheostomy.
Cerebellar Mutism:
Cerebellar mutism is a condition typically found only in children following
operations requiring entry into the cerebellum, especially the vermis. The cause is not
certain, but proposed to be due to injury to deep cerebellar nuclei. The mutism is
usually transient resolving in a few months.

-Second Edition
2011

126


Respiratory failure:
Some of the posterior fossa lesions like Arnold Chiari malformation and
cervicomedullary junction tumours may be associated with increased risk of
postoperative respiratory failure due to central sleep apnea and hypoventilation.
Anesthetic Technique:
The goals of anesthetic management in posterior fossa surgery are maintenance
of hemodynamic stability, cerebral perfusion pressure and oxygenation, facilitating
brain retraction, monitoring for air embolism, an choosing an anesthetic technique
compatible with electrophysiological monitoring, where it is used. No single anesthetic
technique meets all the requirements. Nitrous oxide is best avoided in situations
associated with increased risk of air embolism and tension pneumocephalus. Volatile
anesthetics may help to achieve smooth control of blood pressure; they may however,
increase the risk of hypotension and reduction of cerebral perfusion pressure in
patients with raised ICP and may interfere with interpretation of evoked potentials. Use
of controlled ventilation with narcotics, propofol and muscle relaxants provides slack
brain. Some reports have indicated the usefulness of an anesthetic technique with
spontaneous respiration to monitor brainstem function intraoperatively. Respiratory
changes seem to occur much earlier and more frequently than cardiovascular and even
evoked potential changes. But the technique may be associated with progressive
atelectasis, hypercapnia and hypoxia, all of which increase the risk of brain swelling.
Gasp response has been noticed during venous air embolism in awake individuals. A
similar response during surgery under spontaneous ventilation might increase the
volume of air entrained.
In conclusion, anesthetic management of posterior fossa lesions requires, in
addition to the general principles followed in any intracranial surgery, an
understanding of the primary pathology of the surgical lesion, institution of measures to
deal with the adverse consequences of the surgical positions and monitoring for and
prevention of intraoperative brainstem dysfunction.

-Second Edition
2011

127


Chapter 12 Cerebral Physiology
-Second Edition
2011

128


CEREBRUM
The cerebrum is made up of two cerebral hemispheres which are incompletely
separated from each other by the median longitudinal fissure.
The two hemispheres are connected to each other across the median plane by the
corpus callosum.
Each hemisphere contains a cavity, called the lateral ventricle
CEREBRAL METABOLISM
Brain consists of neurons and glia. .
Neurons are functional unit of central nervous system.
Neurons require energy to maintain their structure and internal function. The
main substance used for energy production in the brain is glucose.
Neurons require energy
1) For synaptic transmission.
2) Cell membranes, internal organelles and
l
cytoplasm which are made up of
carbohydrates, lipids and proteins require energy for their synthesis.
3) Ion channels, enzymes and cell structural components are important protein
molecules which are continuously formed which require ATP for synthesis.
4) Transport of molecules within the cells and across the cell membrane.
5) Pumping ions across the cell membrane Na, K, Ca against large electrochemical
differences with respect to the outside of the cell to maintain the neuronal activity uses
ATP as an energy source.
Neuronal cells utilize glucose as their primary energy source. When O2 levels are
sufficient, aerobic metabolism of glucose takes place. This process yields totally
38 ATP molecules for each glucose molecule metabolized.

-Second Edition
2011

129


Energy metabolism in the brain. Dotted lines indicate reactions that occur during
ischemia. The dotted line across the oxidative phosphorylation reaction indicates that
this reaction is blocked during ischemia.
There is glycolytic pathway then citric acid cycle and then oxidative phosphorylation in
a aerobic metabolism.
If oxygen is not present mitochondria can neither make ATP nor regenerate NAD from
NADPH. Aerobic metabolism requires NAD as cofactor and is blocked in the absence of
O2.Thus in the absence of O2Glycolysis proceeds by a modified pathway - anaerobic
glycolysis.
Disadvantage of anaerobic glycolysis:
1) There is net H
+
ion production which lowers the intracellular pH.
2) Only 2 ATPs molecules are formed for each molecule of glucose metabolized in
contrast to 38 ATPs from aerobic glycolysis. This level of ATP production is insufficient
to meet the brain's energy needs.
When O2 supply to a neuron is reduced, mechanisms that reduce and or slow the fall of
ATP levels include
a) Utilization of phospho-creatinine stores (a high energy phosphate that can donate its
energy to maintain ATP levels.)
b) The production of ATP at low levels by anaerobic glycolysis.
c) Rapid cessation of spontaneous electrophysiologic activity.
During starvation ketone bodies - acetoacetate and (3 hydroxyl butyrate become major
energy substrates.
Brain consumes 20% of total body O2.
60% of cerebral O2 consumption is used is generating ATP to support neuronal
electrical activity.
40% for cellular integrity.
Normal brain oxygen requirements:
Cerebral metabolic rate is expressed in terms of oxygen consumption -cerebral
metabolic rate for oxygen CMRO
2
.
CMRO2 averages 3-3.8ml/100 g/min- (50 ml/min) in adults represents 20% of
total body O2 utilization.
CMRO2 within the brain are heterogenous i.e. greatest in the gray matter of the
cerebral cortex, which parallels the cortical electrical activity.
Because of 2 reasons, interruption of cerebral perfusion results is
unconsciousness within 10sec as oxygen tension rapidly drops below 30 mm Hg.
If blood flow is not reestablished within 3-8 minutes, ATP stores are depleted
and irreversible cellular injury begins to occur. The reasons are
-Second Edition
2011

130


Relatively high oxygen consumption
Absence of significant oxygen reserve
Cerebral metabolic rate expressed
'
also in terms of glucose consumption. Brain
glucose consumption is approx 5mg/100 gm / min of which 90% is metabolized
aerobically.
Effect of anesthetic drugs & temperature on cerebral metabolic rate
Halothane, desflurane, sevoflurane and isoflurane produce dose dependent
decreases in CMR.
Barbiturate produce dose-dependent decrease in CMR until EEG becomes iso-
electrical. At that point, maximum reductions of nearly 50% are observed,
additional barbiturate does not further reduce metabolic rate.
1
0
of hypothermia (to 36
0
C) maintains ATP at normoxic levels during a hypoxia
insult that depletes ATP by half at normothermia (37
0
C) and 3
0
hypothermia to
(34
0
C) more than doubled preservation of phosphocreatine. Hypothermia is the
only one which causes reduction in CMR even after EEG becomes iso-electrical.
Opioids have minimal effects on CMR unless PCO2 rises secondarily to
respiratory depression.

-Second Edition
2011

131


Etomidate, propofol and benzodiazepines lower CMR.
Vasopressors: CMR is increased with normal cerebral blood flow autoregulation.
Adrenergic agents have greater effects on brain when blood brain barrier is
disrupted, central , receptor stimulation increases CMR.
Ketamine causes little or no change in CMR.
Intravenous lidocaine decreased CMR.
CEREBRAL BLOOD FLOW
Main source of blood supply:
Circle of Willis-polygonal anastomosis between ICA & Vertebral via Basilar artery.
Constituted by: FIG
Front- Anterior communicating artery
Anterolaterally- Anterior cerebral arteries
Laterally- Proximal segments of ICA
Posterolaterally- Posterior communicating arteries.
Behind- Posterior cerebral arteries.
ICA: Anterior cerebral- Medial and superolateral surface.
Middle Cerebral- Lateral surface (auditory).
Basilan Posterior Cerebral- Occipital (visual) & part of temporal.
Veins are thin walled and devoid of valves. They are arranged as superficial and deep
veins.
a. Superior cerebral vein drain the superolateral and medial surface of
cerebrum drains into superior sagittal sinus.
b. Superficial middle cerebral vein - drains from lateral surface drains into
cavernous sinus.
c. Inferior cerebral veins drains from inferior and ventral part of lateral
surface of hemisphere drains in to - cavernous, transverse and superior
petrosal an d sphenoparietal sinus.
Deep veins are - Internal cerebral
Basal veins of Rosenthal
Great arterial vein of Galen
The circle of Willis is thought to equalize the blood flow to different parts of the brain.
In case of occlusion of one of the arterial systems, the blood crosses the mid line
through the communicating branches and maintains nutrition of opposite brain by
-Second Edition
2011

132


contralateral flow thus acting as principal collateral channel to preserve the
independent cerebral blood flow.
Adult human brain approximately weighs 1350g represents total 2% of body weight.
Brain receives 12 15% of cardiac output.
Regional CBF parallels metabolic activity and can vary from 10 300ml/100g/min.
Average total global cerebral blood flow 45 55ml / 100g / min 50 ml / 100g / min.
Cortical (gray matter) 80 ml / 100g / min
subcortical (white matter) 20 ml / 100g / min
Total CBF in adults averages 750 ml / min.
Significance
CBF <20 - 25 ml / 100g / min associated with cerebral impairment as evidenced by
slowing on the EEG.
CBF 15 20 ml / 100g / min produce flat (isoelectric) EEG
CBF below 10ml / 100g / min associated with irreversible brain damage
REGULATION OF CBF
Chemical
Myogenic / autogenic
Neurogenic
Viscosity effect
Age
Drugs
Precise mechanism of these effects are not well understood but recent research indicate
that the modulation of Arginine nitric oxide cyclic guanosine monophosphate system
is central to changes in cerebral vascular tone.
1). CHEMICAL REGULATION
a). Cerebral metabolic rate (CMR)
b). Arterial CO2 TENSION (PaCO2)
c). Arterial O2 tension (PaO2)

-Second Edition
2011

133


a). CMR:
House keeping component i.e., cellular integrity maintenance
CMR

Neuronal function
Increase in neuronal activity

Increase in local brain metabolism

Proportional increase in CBF
This intrinsic mechanism is known as flow metabolism coupling.
Normal range of CBF / CMRO2 is 14 18.
Specific mechanism that mediate flow metabolism coupling has not been defined
available data implicate.
i). Increase in either potassium or hydrogen ion concentration in the ECF
surrounding arterioles lead to vasodilation and increase flow.
ii). Nitric oxide of neuronal origin contributes to the vasodilatation.
iii). Other agents like calcium, adenosine, prostaglandins. More than one or all of
them may contribute.
Factors affecting CMR
Decreased sleep, coma

Functional state
Increased sensory stimulation, mental tasks arousal, epilepsy
a). Anesthetics: In general all intravenous anesthetics decreases CMR except for
ketamine.
Increasing concentration of the drug cause progressive suppression of EEG
activity and a concomitant reduction in CMR however increasing plasma level
beyond that required first to suppress the EEG results in no further decrease in
suppression of CMR.
-Second Edition
2011

134


The component of CMR required for the maintenance of cellular integrity the
housekeeping components, is apparently unaltered by I.V. anesthetics and
anesthetics reduce only the component of CMR associated with neuronal
function.
CMR is depressed slightly more than CBF such that metabolic supply exceeds metabolic
demand as long as CPP is maintained.
Temperature: CMR decreases by 6 7% per degree centigrade of temperature
reduction.
Hyperthermia: Between 37 42o C CBF and CMR is increased, > 42o C oxygen activity
begins to decrease and may reflect cell damage as a result of enzyme degradation.
Hypothermia: CMR decreases by 50% if temperature of the brain falls by 10oC, at 20o C
EEG is iso-electrical.
Reduction in temperature beyond that at which EEG suppression first occurs does
produce a further decrease in CMR because:
Neuronal function
It affects both the components
Cellular integrity
B). PARTIAL PRESSURE OF CARBONDIOXIDE PACO2
Cerebral blood flow varies proportionally with PaCO2 and the effect is greatest within
range of physiologic PaCO2 variation.
CBF PaCO2 curve is sigmoid shaped, with plateaus at either end of the scale. Over a
range of 20 80mm Hg PaCO2 there is a linear 4 fold rise in CBF with no change in
CMRO2.
PaCO2< 20 mmHg shifts the O2-Hb curve to left and with changes in CBF, may result in
EEG suggestive of cerebral impairment even in normal individuals.
CBF changes approximately 1-2 ml / 100g / min per mm Hg change in PaCO2. It is
secondary to change in pH of CSF and cerebral tissue. High CO2level increases extra
cellular H
+
ion concentration hence increase blood flow. Low level of CO2H
+

concentration reduce blood flow.

-Second Edition
2011

135


CO2 readily crosses the BBB and hence cause vasodilation through nitric oxide
mediated. Hence CBF response to CO2 is almost immediate but are not sustained as CBF
returns to normal over a period of 6-8 hrs because CSF pH gradually normalize as a
result of extrusion of HCO3 which does not cross BBB readily. Hence CSF pH takes a
longer time to normalize as compared to pH of plasma.
Anesthetic implication
If the patient is hypoventilated

CO2 is increased

pH decreases

Vasodilatation

Blood flow increases throughout the brain

The arteriole could maximally becomes dilated throughout the brain

Impedes the ability to direct the flow to area of high metabolic demand

Thus, this luxury flow caused by high CO2 levels throughout the brain could steal blood
flow from area that require extra oxygen and produce metabolites

Thus, it steals the blood from the areas of focal ischemia

During hyperventilation

CO2 is decreased

Vasoconstriction

This decreases the blood flow to most areas of the brain but vessels in ischemic area would
maximally be dilated due to low pH.

This could maximize the blood flow to compromised (ischemic) areas

TERMED AS INVERSE STEAL OR ROBIN HOOD EFFECT
(Rob from a rich, give to the poor)

-Second Edition
2011

136


Acute normalization of PaCO2 after sustained hyperventilation will result in significant
CSF acidosis (after hypocapnia) results in raised CBF and intracranial pressure. Where
as after sustained hypoventilation results in CSF alkalosis (after hypercapnia) which
conveys the theoretical risk of ischemia.
In presence of pathology CO2 response is last to be abolished once the CO2 response is
abolished, cerebral vasculature does not respond to any other physiological /
pharmacological factor.
PARTIAL PRESSURE O2PAO2:
Within a range of 60 300 mmHg of PaO2 CBF variation is little. PaO2 < 60mmHg CBF
increases rapidly CO2 CBF starts rising only when absolute O2 delivery to brain
decreases.
< 50mmHg of PaO2 profoundly increases CBF
Probable mechanism:
1). Cerebral vasodilation initiated by peripheral and / or neuraxial chemoreceptors.
2). Local hormonal influences (nitric oxide)
At high PaCO2 CBF decreases modestly at atmosphere O2, CBF is reduced by 12%.
MYOGENIC / AUTOREGULATION
Autoregulation refers to the capacity of cerebral circulation to adjust its resistance so
that it can maintain CBF constant over a wide range of mean arterial pressure.
Its active vascular response is characterized by arterial constriction when BP is
increased and dilatation when BP is decreased.
Range of mean arterial pressure with in which autoregulation occurs 50 150mmHg.
Autoregulation takes 1-2 min to set in.
Above and below autoregulatory plateau, CBF is pressure dependent varies linearly
with cerebral perfusion pressure.
Decrease in CPP results in cerebral vasodilatation whereas elevation induces
vasoconstriction.
Relation between CPP and MAP
CPP = MAP ICP or CVP whichever is greater
Normal CPP is 80 100mm Hg
Normal ICP is 10 -1 5 mmHg
At MAP < 50mmHg symptoms of cerebral ischemia occurs and MAP > 150-160 mmHg
can disrupt the BBB and results in cerebral edema DNA haemorrhage.

-Second Edition
2011

137


Precise mechanism of autoregulation is not defined. Proposed theories
1. Myogenic theory according to this, cerebrovascular smooth muscle an intrinsic
ability to react (to the intraluminal pressure altering the tone) to changes in
MAP.
2. Metabolic theory cerebral metabolic demands determine arteriolar tone. When
tissue demands exceed cerebral blood flow, there is release of tissue metabolites
causing vasodilatation and increases CBF. Metabolites are probably nitric oxide,
prostaglandins, adenosine and perhaps electrolyte concentration gradients.
In chronic Hypertensives cerebral autoregulation curve is shifted to the right. (their
lower limit of autoregulation could be above 50mmHg, their upper limit of
autoregulation is also increased). This shift is due to hypertrophy of vessel wall.
In patients with carotid stenosis where cerebral perfusion pressure is decreased
autoregulation is shifted to left.
Factors causing loss of CBF autoregulation:
Head Injury
Trauma
Hypoxia
Intracranial tumor
Anesthetic agents
Severe hypertension
Marked hypercapnia
NEUROGENIC THEORY
Neurogenic factor have their greatest influence on the larger cerebral vessels. Cerebral
vasculature is extensively innervated.
The innervation includes cholinergic, adrenergic and serotoninergic systems.
Large cerebral blood vessel innervated by sympathetic fibres originating in the superior
cervical sympathetic ganglia.
High sympathetic tone leading to vasoconstriction decrease CBF as in hemorrhagic
shock.
EFFECT OF VISCOSITY ON CBF:
Hematocrit is the single most important determinant of blood viscosity. Hematocrit
variation within normal range 33 45% results in only trivial change in CBF.
In anemia cerebral vascular resistance is reduced and CBF increases which is a reduced
viscosity state and decrease O2 conveying capacity. In polycythemia, increase viscosity
leads to decreased CBF.

-Second Edition
2011

138


EFFECT OF AGING
Aging progressively reduce CBF and CMRO2 due to progressive neuronal loss.
ANESTHETIC DRUGS AND CEREBRAL BLOOD FLOW:
Robin Hood / reverse steal phenomenon
Barbiturate produce dose dependent decrease in CMR and CBF until EEG become iso-
electrical. CMR is depressed slightly more than CBF, such that metabolic supply exceeds
metabolic demands as long as CPP is maintained. Barbiturate induced cerebral
vasoconstriction occurs only in normal areas, these agents tend to redistribute blood
flow from normal to ischemic areas in the brain (cerebral vasculature in ischemic areas
remains maximally dilated and is unaffected by the ischemic areas remains maximally
dilated and is unaffected by the barbiturate because of ischemic vasomotor paralysis).
Thus blood flow to the brain can be manipulated to advantage during focal ischemia
Luxury perfusion
Volatile anesthetics alter but do not uncouple the normal relationship of CBF and CMR.
The combination of a decrease in cerebral metabolic demand with an increase in CBF
(metabolic supply) is termed as LUXURY PERFUSION.
This state is desirable during induced hypotension and supports the use of a volatile
agent, particularly isoflurane.
Circulatory steal phenomenon
In contrast to the above luxury perfusion, which is a potentially beneficial effect during
global ischemia, a detrimental circulatory steal phenomenon occurs with volatile
anesthetics in the setting of focal ischemia.
Volatile agents can increase the blood flow in normal areas of the brain but not in
ischemic areas, where arterioles are already maximally dilated. The end result may be a
redistribution of blood flow away from the ischemic to normal areas.
Volatile anesthetics and CBF
They dilate cerebral blood vessels and impair the auto-regulation in dose dependent
manner.
Halothane has the greatest affect on CBF at concentration greater than 1% it nearly
abolishes cerebral autoregulation.
The effect of volatile agents on CBF appears to be time dependent because, with
continuous administration (2-5 hr) blood flow begins to return to normal.
The response of the cerebral vasculature to CO2 is generally retained with all volatile
agents.
-Second Edition
2011

139


Increases in CBV (10 20%) generally parallel increases in CBF but relation is not
necessarily linear.
N2O on CBV and CBF:
Its effects are generally mild and easily overcome by other agents or changes in
CO2 tension.
Combined with intravenous agents, N2O has minimal effects on CBF, CMR and
ICP.
N2O with volatile agents can increase CBF.
Given alone N2O causes mild cerebral vasodilation.
Intravenous anesthetics on CBF and CBV
With exception of ketamine all I.V. anesthetic agents either have little effect on or
reduce CBF.
Cerebral autoregulation and CO2 responsiveness are preserved with all agents.
Propofol, Barbiturates, etomidate and then Benzodiazepines are in the
decreasing order of their ability to decrease CBF.
Vasopressors and vasodilators on CBF and CBV
With normal autoregulation and an intact blood brain barriers, vasopressors CBF alters
only when mean arterial blood pressure is below 50 60mm Hg or above 150 160 mm
Hg.
In absence of autoregulation, vasopressors increase CBF by their effect on CPP.
In the absence of hypotension, most of vasodilators induce cerebral vasodilatation and
increase CBF in dose related fashion.
Cerebral protection by thiopentone
Barbiturate have four major actions on the CNS
1). Hypnosis
2). Depression of CMR
3). Reduction of CBF due to increased cerebral vascular resistance
4). Anticonvulsant activity
5). Scavenging or suppression of free radical formation
6). Retardation of cerebral edema following ischemic brain injury.

Barbiturate produce dose dependent decrease in CMR and CBF until EEG becomes iso-
electrical. CMR is depressed slightly more than CBF, such that metabolic supply exceeds
metabolic demands as long as CPP is maintained.
-Second Edition
2011

140


MEASUREMENT OF CEREBRAL BLOOD FLOW
Methods that provide obsolete estimate of regional cerebral blood flow use one of two
principles.
Measurement of distribution of a tracer
Estimation of blood flow from the wash in or wash out curve of an indicator
COMPOSITION FO CEREBROSPINAL FLUID AND SERUM
CSF Serum
Sodium (mEq.1
-1
) 141 140
Potassium (mEq.1
-1
) 2.9 4.6
Calcium (mEq.1
-1
) 2.5 5.0
Magnesium (mEq.1
-1
) 2.4 1.7
Chloride (mEq.1
-1
) 124 101
Bicarbonate (mEq.1
-1
) 21 23
Glucose (mg. 100ml
-1
) 61 92
Protein (mg. 100ml
-1
) 28 7000
pH 7.31 7.41
Osmolality (mOsm.kg
-1
H2O) 289 289
Other technique make inferences about regional blood flow such as measurement of a
related flow variable (arterial flow velocity) or measurement of metabolic parameters.
1). KETY SCHMIDT TECHNIQUE:
2). XENON 133 washout
TOMOGRAPHY:
a. Dynamic CT scanning provides regional cerebral blood flow information by
quantitative studies of washout of a radio-dense contrast agent mostly xenon.
b. Single photon emission tomography (SPECT) and positron emission tomography
(PET) use remitting (e.g. Tc99) and positron emitting isotopes (e.g. O15, E18, C11,
N
13
) respectively to produce tomographic images of regional CBF.
c. Functional (fMRI) MRI is the use of MRI to map changes in brain hemodynamics
in response to brain neural activity. Images can be produced either using an
intravenous contrast agent or without eh use of contrast agents.
d. Magnetic resonance angiography (MRA) provides images of arterial & venous
sinus blood flow.

-Second Edition
2011

141


JUGULAR BULB VENOUS OXIMETRY
Global hemispheric measurements of cerebral oxygenation is achieved by means of a
catheter inserted up the internal jugular vein to jugular bulb. Normal jugular bulb
oxygen saturation tend to be 60 70%. In the absence of anemia, increase in SjVO2 to
above 75% indicative of absolute or relative hypoxia E.g: comatose, brain dead patient.
If <50% reflects increased oxygen extraction & indicates a potential ischemic injury.
Uses: intra and post operatively to diagnose cerebral ischemia from inadequate
perfusion pressure.
Limitation: regional cerebral ischemia cannot be detected.
TRANSCRANIAL DOPPLER (TCD) ULTRASONOGRAPHY:
TCD measures the velocity of RBC (flow velocity) flowing through the large vessels at
the base of brain using the Doppler shift principle. The middle cerebral artery is most
commonly isolated as it is easy to detect ; receives a substantial proportional of blood
flow from the internal carotid artery & allows easy probe fixation.
Can be used to detect cerebral ischemia, hyperemic, vasospasm & estimate of CPP.
CEREBROSPINAL FLUID DYNAMICS
CSF is found in cerebral ventricles and cisterns and subarachnoid space
surrounding the brain and spinal cord.
Major function of CSF is to 1). Cushion for CNS 2) as an excretory pathway 3)
protect the CNS against trauma.
CSF is formed by 1) the choroids plexus of the cerebral ventricles. (Mainly
lateral) 2) Smaller amounts are formed directly by the ventricles ependymal cell
linings and 3) yet smaller quantities from fluid leaking into perivascular spaces
surrounding cerebral vesicles (blood brain barrier leakage).
Approx 150ml of CSF in the adult human half with in the cranium and half in the
spinal CSF space.
Formed and reabsorbed at a rate of 0.3 0.4 ml / min (or 21 ml/hr ~ 500ml /
day). This allows the complete replacement of the CSF volume 3 or 4 times a day.
CSF formation involves active secretion of Na
+
, in the choroids plexus
Resultant CSF is isotonic with plasma despite lower K
+
, HCO3 and glucose conc.
CSF is primarily formed by the transport of Na
+
, chloride and bicarbonate with
the osmotic movement of water.
-Second Edition
2011

142


-Second Edition
2011

143


CSF Drainage:
CSF from lateral ventricles

Intra ventricular foramina of Monro

III Ventricle

Cerebral aqueduct of Sylvius

IV ventricle

Foramen of Megendie and foramen of Luschka

Cerebellomedullary cistern (cisterna magna)

Absorbed in arachnoid space circulating around the brain and spinal cord

Absorbed in arachnoid granulations over the cerebral hemispheres
into cerebral venous sinuses
CSF absorption appears to be directly proportional to ICP and inversely to
cerebral venous pressure.
Note: Arachnoid villi allows one way flow of CSF from SAS into venous sinuses
when CSF pressure is greater than pressure in these sinuses. If the foramina
connecting the ventricles or the arachnoid villi are blocked, pressure builds and
hydrocephalus develops.
Absorption of CSF into venous sinuses is the principal means by which
perivascular and interstitial proteins is returned to blood.
The two clinically used substances 1). Furosemide reduces CSF formation which
inhibits the combined transport of sodium and chloride.
2). Acetazolamide which reduces CSF formation by reducing bicarbonate
transport by inhibiting carbonic anhydrase.
The composition of the fluid surrounding the brain is tightly regulated and
distinct from ECF in the rest of the body. The two barriers.
1. Blood brain barrier and
2. Blood CSF barrier, maintain the difference between blood and CSF composition.
-Second Edition
2011

144


BLOOD BRAIN, BARRIER
The tight junction between vascular endothelial cells of cerebral blood vessels forms the
BBB contributed by low level of pinocytic activity. And processes of astrocyte glial cells
interposed between neurons of brain and capillaries involved in maintenance of barrier.
This is a lipid barrier
Significance of BBB:
This allows the passage of lipid soluble substances CO2, oxygen.
Restricts the movement of ionized or the large molecular weight molecules.
Impedes the flow of ions such as potassium, calcium, magnesium and sodium and
polar molecular such as glucose, amino-acids and mannitol and macromolecules
such as proteins.
Many substances that do not cross the BBB, are required for brain function, are
transported across capillary endothelial cell by a carrier mediated processes. Eg.
Glucose enters the brain by facilitated diffusion. (facilitated diffusion is a passive
-Second Edition
2011

145


transport where the molecules move into the brain only if their concentration in
blood is higher than their concentration in the brain and carrier mediated
without expenditure of energy.
Water moves freely across the BBB as a consequence of bulk flow.
How rapid changes in electrolyte i.e. tonicity of plasma influences movement of
water into or out of brain:
Rapid changes in plasma electrolyte concentration produce a transient osmotic
gradient between plasma and brain.

-Second Edition
2011

146


Acute hypertonicity of plasma

Net movement of water out o the brain
acute hypotonicity of the plasma

Net movement of water into the brain
These effects are short lived, as eventually equilibration occurs, but when marked, cause
rapid fluid shifts in the brain.
Implication: Marked abnormalities in serum sodium or glucose concentration should
generally be corrected slowly.
BBB disrupted by
Severe hypertension
Brain tumours
Trauma
Strokes
Infection
Marked hypercapnia
Hypoxia
Sustained seizure activity
BLOOD CSF BARRIER:
Endothelial cells of the capillaries of choroids plexus are surrounded by choroids plexus
epithelial cells which have tight junctions this forms the basis of blood CSF barrier.
Significance of BCB:
Allows the movement of water, gases and lipid soluble compounds, requires carrier
mediated active or passive transport process for glucose, amino acids and ions.
-Second Edition
2011

147


-Second Edition
2011

148


Chapter 13 - INTRACRANIAL PRESSURE
In humans ICP is less than 10mmHg.
The ICP is determined by the major components that occupy the spaces in the
skull.
The brain which includes neurons and glia (80%)
CSF and extracellular fluid (8%)
Blood vessels perfusing the brain (12%)
An increase in the volume of one of these components can increase ICP which results in
2 deleterious effects.
First reduce blood flow to the brain. Cerebral perfusion pressure is MAP minus
ICP. If ICP increases to a great extent than MAP, CPP is reduced. If ICP rises
sufficiently, the brain can become ischemic.
2nd effect of increased ICP is brain herniation. Herniation can rapidly lead to
neurologic degeneration. 4 sites herniation.
Intracranial compliance is determined by measuring the change in ICP is
response to a change in intracranial volume. Normal increase in volume is
initially well compensated.
Normal increases in volume are initially well compensated.
Compensatory mechanisms:
1) Initial displacement of CSF from cranial to the spinal component.
2) Increase in CSF absorption by arachnoid villi upto ICP limit of 30 mmHg.
3) Decrease in CSF production
4) Decrease in total cerebral blood volume (primarily venous)
ICP conventionally means supratentorial CSF pressure measured in
the lateral ventricles or over the cerebral cortex.
When isobaric spatial compensation is exhausted ICP begins to rise and pathologic
spatial compensation is achieved by decrease in cerebral volume by compression of low
pressure venous system followed by capillary collapse and ultimately cerebral
ischemia. At this point ICP rises dramatically with only increases in intracranial volume.
-Second Edition
2011

149


INCRACRANIAL MEASUREMENT;
Uses of ICP monitoring:
1) Managing critically ill neurosurgical patients in the intensive care unit.
2) Head injury patients.
3) Management of patients having liver transplant for fulminant hepatic failure.
4) Large brain tumours / aneurysms- perioperative management of patients.
5) Useful during prolonged non-neurosurgical operative procedures in multiple
trauma victims at high risk for development of intracranial hemorrhage and / or
brain swelling.
6) Early detection and prompt treatment of brain hemorrhage, swelling and
herniation.
Methods of measuring - ICP are classified based on transducer location as below
1. Ventricular catheter
2. sub-arachnoid-subdural screw/ bolt
3. Epidural transducers.
All these are external fluid coupled transducers

-Second Edition
2011

150


VENTRICULAR CATHETER
This is the standard method relatively safe for continuous ICP monitoring but most
invasive method.
This involves measurement of ventricular fluid pressure by means of a catheter inserted
into lateral ventricle through a burr hole & fluid coupled to an external transducer.
Advantage:
Can be used to withdraw small amounts of CSF to decrease intracranial hypertension.
Injection of small amounts of preservative free saline can be done to test intracranial
compliance
Disadvantage:
This technique is not possible or is tough as in Severe brain swelling large mass
lesions due to distortion/compression of ventricular system/subdural space
Passage of catheter through brain tissue leading to creation of pathway for
infection.
Risk of epidural / subdural/ intracranial / ventricular hemorrhage
Possibility of brain tissue damage.
SUBARACHNOID SCREW OR BOLT
This is also a fluid coupled intracranial monitor with an external transducer system.
A threaded hollow screw is inserted through a bur hole just far enough for its
unthreaded tip to protrude about a mm beyond the inner surface of dura. Screw is then
linked to the external transducer through a saline, filled tubing
Disadvantage:
Small leaks & frequent obstruction of tubing or brain substance obstructing the tip of
the bolt.
Cannot be used to lower ICP by CSF drainage or test compliance reliably.
Advantage:
Less invasive compared to ventricular catheters
Does not require brain tissue penetration.

-Second Edition
2011

151


EPID URAL TRANSDUCERS:
There are LADD, GAELTEC,
LADD MONITOR
Principle: It detects the changes is ICP by deflection of a mirror which in turn alters the
return of fibro-optically transmitted light. An external monitor detects the change in
returned light & activates a servo-system which increases the air pressure in
intracranial transducer just enough to return mirror to its original portion.
The counter balance in air pressure generated by monitor is measure of ICP. The
transducer can be placed both epidurally & subdurally
GAELTEC MONITOR:
Uses a device that has a pressure sensitive membrane mounted close to or contacting
the dura.
RECENT ADVANCES
-
USING FIBROPTIC CATHETERS:
Intraparenchymal devices use a fibre optic catheter that is inserted within cortical gray
matter. Allows direct measurement of brain tissue pressure.
ANESTHETIC DRUGS AND ICP:
Net effect of anesthetics on ICP is the result of immediate 1) changes in CBV, 2) delayed
alterations of CSF dynamics that is production and absorption and 3) arterial CO2
tension.
Ketamine potentially increase ICP which decreases intracranial compliance due to (a) It
impedes the absorption of CSF without affecting formation and increase CSF volume (b)
Increase CBF by dilating cerebral vasculature (c) Increase in CBV.
o By increasing CBV, ICP is increased with halothane, isoflurane,
sevoflurane and lidocaine.
o By decreasing CBF, CBV and increasing CSF absorption, barbiturates,
etomidate, propofol, benzodiazepines decreases ICP.
o Because of anticonvulsant property and effective decrease in ICP
(barbiturate) thiopentone is advantageous in neurosurgical patients.
Opioids have minimal effects on ICP unless PaCO2 rises secondary to
respiratory depression.
o Increase in ICP with intracranial tumours following administration of
sufentanil appears to be (A) Precipitous drop in BP (B) Reflex cerebral
vasodilation., which increases intracranial volume and potentially ICP.
Neuromuscular blocking agents: Lack direct effect on brain. Hypertension and
histamine mediated cerebral vasodilatation increase ICP, while systemic hypotension
(from histamine release or ganglionic blockade) lowers CPP.
-Second Edition
2011

152


Succinylcholine can increase ICP, possibly as a result of cerebral activation associated
with enhanced muscle spindle activity but increase is generally minimal if an adequate
dose of thiopentone is given and hyperventilation is initiated at induction.
ELECTROPHYSIOLOGICAL FUNCTIONS
Electrophysiological functions attempts to assess the functional integrity of the CNS.
They are EEG (Electroencephalogram)
Evoked potential
BIS (bispectral analysis)
Proper application of these monitoring modalities is dependent on
1) Monitoring the specific area at risk.
2) Recognizing anesthetic - induced changes.
Interpretation of changes requires connect correlation with
Anesthetic depth - and drugs related changes.
Blood pressure
Body temperature
Respiratory gas tension

-Second Edition
2011

153


Regardless of the technique employed, recordings should be bilateral for comparison of
correlated with the intraoperative course of events.
ELECTRO ENCEPHALOGRAM:
EEG is a recording of electrical potentials generated by the cells in the cerebral cortex
through electrodes placed over the scalp.
16 leads placed at respective positions
Indications: Assessing the adequacy of cerebral perfusion during.
Carotid endarterectomy (CEA)
Controlled hypotension.
Assessing anesthetic depth.
Description:
Activation
EEG changes can be simplistically described as
Depression
EEG activation means shift to predominately high frequency and low voltage activity.

seen light anesthesia and surgical stimulation
EEG depression means shift to predominantly low frequency and high voltage activity.

Biphasic means initial activation at sub anesthetic doses followed by dose dependent
depression.

Benzodiazepine, Barbiturate, Etomidate, Propofol, halothane.
EEG monitoring has been limited by
Requirements of space
Difficulty of interpretation.
Equivocal efficacy
The need to avoid high cone of anesthetic agents.
EEG changes that accompany ischemia, such as high frequency activity can be mimicked
by hypothermia.
Anesthetic agents
Electrolytic disturbances
Marked hypocapnia

-Second Edition
2011

154


BISPECTRAL ANALYSIS (BIS) (Bispectral index scale):
New two channeled processed EEG devices pass the EEG signal through a fast Fourier
transform leading to a traditional power spectrum.
Bispectral index represents a numerical value that has been.
Advantages of BIS:
1. It may reduce patient awareness during anesthesia.
2. It may also reduce resource of utilization because less drug is required to ensure
amnesic, facilitating a faster and perhaps a shorter stay in the recovery room.
Disadvantage of BIS:
Artifacts can be a problem.
Monitor in and of itself, costs several thousand dollars also the electrodes.
Electrodes cannot be reused.
BIS is a dimensionless scale from D (complete cortical EEG suppression) to 100
(awake).
65-85 for sedation.
40-65- for general anesthesia.
-Second Edition
2011

155


the Bispectral index scale (BIS versions 3.0 and higher) is a dimensionless scale
from 0 (complete cortical electroencephalographic suppression) to 100 (awake).
BIS values of 65-85 have been recommended for sedation, whereas values of 40-
65 have been recommended for general anesthesia. At BIS values lower than 40,
cortical suppression becomes discernible in a raw electroencephalogram as a
burst suppression pattern.
<40 cortical suppression becomes descendible in a raw EEG as a burst
suppression pattern.
Calculation of bispectral index.
EVOKED POTENTIAL:
It's a noninvasive monitor assessing the neural function by measuring
electrophysiological responses to sensory or motor pathway stimulation.
-Second Edition
2011

156


Commonly monitored EPs are:
Brain stem auditory evoked responses (BAERs).
Somatosensory evoked response (SEP).
Motor evoked potentials (increasingly).
Visual evoked potentials.
Evoked potentials are represented by a plot of voltage versus time. The resulting
waveforms are analyzed for their post stimulus latency (the time between
stimulations potential detection and peak amplitude.
Indications: Intraoperative monitoring in surgical procedures as
Spiral fusion with instrumentation.
Spine and spinal cord tumour resection.
Brachial plexus repair.
Thoraco-abdominal aortic aneurysm repair.
Epilepsy surgery.
Cerebral tumour resection.
Ischemia in spinal cord or cerebral cortex can be detected by EP's.
Contraindications: Nothing specific
Motor evoked potentials are contraindicated in patients with retained intra cranial
metal, with a skull defect, after seizures and after any major cerebral insult.
EPs limited by availability of monitoring sites, equipment, and trained personnel.
SSSEP test integrity of the dorsal spinal columns and the sensory cortex usually to
identify spinal cord damage.
MEP Adequacy of perfusion of the spinal cord better assessed.
BFEP test the integrity of the 8`
h
cranial nerve and the auditory pathway above the
pons and used in posterior fossa surgery.
VEP used to monitor the optic nerve and upper brain stem during resection of large
pituitary tumours.
Clinical consideration: In general balanced anesthetic technique (nitrous oxide,
neuromuscular blocking agents and opioids) cause minimal changes.
Changes in BAER may provide a measure of depth of anesthesia.
Persistent obliteration of EPs is predictive of post operative neurological deficit.
Advantage of using MEPs as opposed to SEPs for spinal cord monitoring is
a) The MEP monitors the ventral spinal cord.
-Second Edition
2011

157


b) If sensitive and specific enough, can be used to indicate which patients might
develop a post operative motor deficit.
Complications: Skin irritation and pressure ischemia at the sites of electrode
application.

-Second Edition
2011

158



-Second Edition
2011

159


Chapter 14 - NEUROMUSCULAR JUNCTION
PHYSIOLOGY AND ITS ANEASTHETIC IMPLICATIONS
INTRODUCTION:
Neuromuscular blocking drugs provide skeletal muscle relaxation to facilitate tracheal
intubation, control mechanical ventilation, and optimize surgical operating conditions.
These drugs principally interrupt the transmission of nerve impulses at the
neuromuscular junction.
The junction is the most thoroughly studied synapse of any type and is a model for our
understanding of the synaptic transmission.
PHYSIOLOGY OF NEUROMUSCULAR TRANSMISSION
Motor unit: A motor neuron innervating a muscle, divides into many nerve fibres, each
of which supplies one muscle fibre. This motor neuron and the muscle fibres it
innervates constitute a motor unit. The number of muscle fibres per unit varies, from as
few as 5 to 2000 depending on the function of the muscle involved.
The motor neuron that controls skeletal muscle contraction is:
1) Long cells, with their bodies in the ventral horn of the spinal cord, and axons that
extend to the peripheral muscle cells, up to 1 meter away.
2) Typically 10-20 m in diameter and
3) Myelinated

-Second Edition
2011

160


Neuromuscular junction:
Nerve terminal
NMJ Synaptic cleft
Motor end plate
1) The nerve terminal:
o Areas of the nerve lying closest to the muscle cell, situated opposite a specialized
area of the muscle cell called the end plate.
2) The synaptic cleft
o Part of the ECF between the nerve terminal and motor end plate.
o Is 20mm wide
3) The motor end plate:
o Risk in acetylcholine receptors
o Surface of the muscle, at the end plate, is deeply folded, with many ridges and
secondary clefts.
o The ridges have a high concentration of acetylcholine receptors on the crests of
their folds.
- There are 1-10 million receptors at each endplate.
- Density of 10,000-20,000 / m
2
.
-Second Edition
2011

161


Acetylcholine (Synthesis, storage, release):
Synthesized in the presynaptic terminal from substrate choline and acetyl CoA.

Different pools of acetylcholine in the nerve terminal have variable availability
for release.
a) The immediately releasable stores, VP2.
- Responsible for the maintenance of transmitter release under conditions
of low nerve activity.
- 1% of vesicles.
b) The reserve pool, VP1.
-Second Edition
2011

162


- Released in response to nerve impulses.
- 80% of vesicles.
c) The stationary store
- The remainder of the vesicles.
Each vesicle contains approx 12,000 molecules of acetylcholine, which are loaded into
the vesicles by an active transport process in the vesicle membrane involving a Mg
2+

dependent H
+
pump ATPase. Contents of a single vesicle constitute a quantum of
acetylcholine.
Release of acetylcholine may be
a) Spontaneous. (A single quanta release can produce random miniature end plate
potentials of 0.5-1 mv which can be detected by intracellular electrodes in the
absence of an axon potential) or
b) In response to a nerve impulse.
When a nerve impulse invades the nerve terminal, calcium channels in the nerve
terminal membrane are opened up. Calcium enters the nerve terminal and there is
calcium dependant synchronous release of the contents from 50-100 vesicles.
The number of quanta released by each nerve impulse is very sensitive to extracellular
ionized calcium concentrations. Increased calcium concentration results in increased
quanta released.
To enable this, the vesicles must be docked at special release sites (active zones)
in that part of the terminal where the axonal membrane faces the post junctional
acetylcholine receptors. These are vesicles from the immediately releasable stores.
Once the contents have been discharged, they are rapidly refilled from the reserve
stores. The reserve vesicles are anchored to actin fibrils in the cytoskeleton, by vesicular
proteins called synapses.
Some calcium that enters the axoplasm, on the arrival of the of the nerve impulse binds
to calmodulin, which activates protein kinase - 2 which phosphorylate synapsins, which,
in turn dissociates the vesicle from the actin fibrils allowing, it to move forward to the
release site.
Docking of the vesicle and subsequent discharge of acetylcholine by exocytosis, involves
several other proteins. Membrane protein called SNARE's (soluble N-ethylmatrirnide-
sensitive attachment proteins) are involved in fusion, docking, and release of acetyl
choline at the active zone. SNARE includes - synaptic vesicle protein synaptobrevin,
syntaxin and SNAP-25.
-Second Edition
2011

163


Margin of safety:
Acetylcholine release and receptor stimulation in response to a nerve action
potential is far greater than that required to elicit a single muscle fibre contraction.
This large safety margin means that up to 70-80% of the receptors can be
occupied by a muscle relaxant before surgical relaxation develops. Conversely, reversal
can be clinically adequate even though as many as 70% receptors are still blocked.
Acetylcholine receptors:
Structure of acetylcholine receptors varies in different tissues and at different times of
development.
Post junctional receptors:
Present in the post-junctional membrane of the motor end plate and are of nicotinic
type. These receptors exist in pairs.
It consists of a protein made up of 1000 amino-acids.
Made up of 5 protein subunits designated as u- ( , , and c joined to form a
channel that penetrates through and projects on each side of the membrane.
The subunits have different molecular weights and properties.
All receptors contain 2 and 1 , 1 and 1 , subunit.
In the fetus, replaces . The protein subunits are assembled like barrel staves
into cylindrical receptors. Each receptor has a central funnel shaped core, which
is an ion channel 4 nm in diameter at the entrance, narrowing to less than 0.7 nm
within the membrane.
The receptor is 11 nm in length and extends 2 nm into the cytoplasm of the
muscle cell.
-Second Edition
2011

164


-Second Edition
2011

165


The receptor has two gates, an upper voltage dependent and the lower time dependent.
When acetylcholine receptors bind to the pentamer complex, they induce a
conformational change in the proteins of the subunits which opens the channel.
This conformational change and consequent channel opening occurs only if the
acetylcholine molecules are bound to both the binding sites.
For ions to pass through the channel both the gates should be open. Cations flow
though the open channel, sodium and calcium in and potassium out, generating end
plate potential.
Potassium ions leak from the inside of the cell to the outside, but this movement is
minor compared to the movement of sodium from the outside to the inside.

The inside of the cell has a resting membrane potential of - 80 mV with respect to
the outside.
Sodium ions are attracted to the inside of the cell which induces depolarization.
Once a threshold of - 50 mV is reached, voltage gated sodium channels on the
sarcolemma are opened and this allows the flow of sodium ions into the muscle.
Peri-junctional areas of the muscle membrane have a higher density of sodium
channels than other parts of the membrane. This increases the rate of
depolarization forming an action potential that passes around the whole
-Second Edition
2011

166


sarcolemma, and T-tubule system releasing calcium from the sarcoplasmic
reticulum causing muscle contraction.
Only 6-25% of acetylcholine normally released is required to reach the threshold
potential. The activated acetylcholine receptors stay open for 1 ms. These
receptors also act as a switch. which are closed until acetylcholine binds to the 2
et binding sites. The receptor then snaps open and current passes through it.
When acetylcholine leaves, the channel shuts and the current ceases.
In addition to the post functional receptors there are also
Prejunctional receptors:
These are nicotinic receptors that control ion channel specific for sodium which
is essential for synthesis and mobilization of acetylcholine.
They contain protein subunits that are blocked by non depolarizing muscle
relaxants, resulting in fade and exhaustion.
Theyre also blocked by aminoglycosides and polymyxin antibiotics.
Extra Junctional receptor:
These tend to be concentrated around the end plate, where they mix with post
junctional receptors, but may be found anywhere on the muscle membrane. In
them, the adult F- subunit is replaced by the fetal unit.
Theyre not found in normal active muscle, but appear very rapidly after injury
or whenever muscle activity has ended.
They can appear within 18 hrs of injury and an altered response to
neuromuscular blocking drugs can be detected in 24 hrs of the insult.
When a large number of extra junctional receptors are present. resistance to non
depolarizing muscle relaxants develops, yet there is an increased sensitivity to
depolarizing muscle relaxants.
In most extreme cases, increased sensitivity to succinylcholine results in lethal
hyperkalemic response due to depolarization of both post junctional and extra
junctional receptors with an exaggerated efflux of intracellular potassium.
The longer opening time of the ion channel on the extra junctional receptor also results
in larger efflux.
Contractile apparatus:
It is formed by thin actin and thick myosin filaments and tropomyosin, troponin. The
shortening of this apparatus causes the contraction of the muscle.

-Second Edition
2011

167


Role of calcium:
The concentration of calcium and the length of time during which it flows into the nerve
ending, determines the number of quanta released. Calcium current is normally stopped
by the out flow of potassium. Calcium channels are specialized proteins, which are
opened by voltage change accompanying action potentials.
Part of it is captured by proteins in the endoplasmic reticulum are sequestrated.
Remaining part is removed out of the nerve by the Na
+
/Ca
+
antiport system. The
sodium is eventually removed from the cell by ATPase.
Sequence of events during neuromuscular transmission
Action potential through motor nerve fibre

Axonal terminal

Opening of voltage gated Ca
2+
channels

Entry of Ca
2+
ions from ECF

Opening of vesicles and release of acetylcholine
Synaptic cleft

passage of acetylcholine

Post synaptic membrane

Binding of acetylcholine receptor and formation of acetylcholine receptor
complex

Opening of ligand gated sodium channels and entry of Na
+
ions from ECF.

Development of endplate potential

Muscle fibre

Generation of action potential

Excitation contraction coupling

Muscle contraction

-Second Edition
2011

168


Acetyl cholinesterase:
This protein enzyme is secreted from the muscle, but remains attached to it by thin
stalks of collagen, attached to the basement membrane.
Acetylcholine molecules that don't interact with a receptor or are released from the
binding site are destroyed almost immediately by acetylcholinesterase, in < 1 ms, after
its release into the functional cleft.
Physical channel blockade:
Various drugs can block the neuromuscular junction and prevent depolarization.
Blockade can occur in two modes.
Blocked when open
blocked when closed.
Open channel block: In this, the drug molecule enters a channel which has been opened
by acetyl choline. This is use dependent block.
Physical blockade by a molecule of an open channel (ie by cationic drugs only) relies on
the open configuration of the channel and the development of this is proportional to the
frequency of channel opening.
Provided that the molecular size is small enough and concentration is high enough, any
drug may enter and occlude open ion channels.
This mechanism may explain the synergy that occurs with certain drugs such as local
anesthetic, antibiotics and muscle relaxants.
In addition, the difficulty in antagonizing profound neuromuscular blockade may be due
to open channel block by the muscle relaxant itself.
Closed channel block: The drugs occupy the mouth of the channel and prevents ions
from passing through the channel to depolarize the end plate.
Tricyclic drugs and naloxone may cause physical blockade of a closed channel by
impeding interaction of acetylcholine with the receptor.
For drugs interfering with the function of the acetylcholine receptor, without acting, as
an agonist or antagonist. the receptor lipid membrane interface may also be another site
of action.
Eg: Volatile agents, local anesthetic and ketamine.
Characteristics of muscle relaxants:
Peripherally acting muscle relaxants an be
a) Non depolarizing muscle relaxant (Pachycurares)
b) Depolarizing muscle relaxant (Leptocurares)
-Second Edition
2011

169


Under certain circumstances depolarizing muscle relaxant can exert a non
depolarizing effect, termed phase 11 or dual block.
Muscle relaxation can also be produced centrally by deep inhalational
anesthetics or peripherally by nerve blocks.
Sequence of muscle blockade:
For both, depolarizing muscle relaxants and non depolarizing muscle relaxants, the
sequence of muscles to be blocked are.
Muscles of face (fasciculations after succinylcholine are first seen in the eyelids).
Jaw, pharynx, larynx and muscle of respiration.
Clinical blockade of diaphragm (ie 60-70% receptor occupancy) do occur with other
respiratory muscle, but to block it completely it is most resistant and complete blockade
may occur even after peripheral and muscles.
After central muscles, the last to be blocked are those of the trunk and limbs.
Mechanism of neuromuscular blockade:
Cholinergic agonists (depolarizing muscle relaxant) and antagonist (non depolarizing
muscle relaxant) act at the a subunit binding site on the nicotinic receptor.
Neuromuscular blocking drugs have positively charged quaternary ammonium
moieties, that combine with the a subunit in the same way as the quaternary nitrogen
radical of acetylcholine.
All blocking drugs contain one or more quaternary ammonium groups which are
separated by a lipophilic bridging structure of varying length and this may be a major
determinant of potency.
Depolarizing (non competitive) neuromuscular block:
Succinylcholine consists of two molecules of acetylcholine that are linked together
through an acetate methyl group.
SUCCINYLCHOLINE ACETYLCHOLINE
O O
|| ||
COCH2CJ2N
+
(CH3)3 COCH2CH2N
+
(CH3)3
| |
(CH2)2 CH3
COCH2CH2N
+
(CH3)3
||
O
-Second Edition
2011

170


The feature which lends it acetylcholine like activity are:
Two quaternary ammonium group
An intervening 8 carbon chain which makes the molecule long slender and
flexible.
The two quaternary ammonium radicals of succinylcholine interact with 2 subunits of
a receptor and open the ion channel the same way as acetylcholine.
Receptors physiology of depolarizing blockade:
Current understanding of the receptor physiology ascribes depolarizing block to the
sodium ion channel which are present at the trough of the post functional membrane, in
the vicinity of end plate. This channel does not respond to chemicals but opens when
exposed to a transmembrane voltage change.
Structure:
This sodium channel is a cylindrical transmembrane protein. Its two ends act as gates.
Both should be open to allow passage of ions. The voltage dependent gate is closed in
resting state and opens only on application of a depolarizing voltage, remaining open as
long as the voltage persists.
The time dependent gate is normally open at rest, closing a few milliseconds after the
voltage gate opens and remains closed as long as the voltage gate is open. It reopens
after the voltage gate closes. The channel is patent, allowing entry of sodium ions only
when both the gates are open.
Possible configuration of the Na
+
channel:
1. Resting state voltage gate closed
Time gate open
Channel closed
2. Depolarization Voltage gate open
Time gate open
Channel open
3. Within a few Voltage gate open
milliseconds Time gate closed
Channel closed
4. End of Voltage gate closed
depolarization Time gate open
Channel closed
As Succinylcholine isn't metabolized by
acetylcholinesterase in the synaptic cleft,
depolarization of the end plate continues for
-Second Edition
2011

171


longer, than with acetylcholine, inactivating the voltage gated sodium channels in the
muscle membrane, which are immediately adjacent to the motor end plate. This is
because opening of the lower gate in the peri junctional sodium channel is time limited.
Thus 3 zones can be seen.
End plate a zone is created around the end plate through which the impulses
temporarily cannot pass, preventing further action potentials hence it is
persistently depolarized.
Peri junctional areas sodium channels are frozen in closed state.
Rest of muscle relaxed, as sodium channels return to resting state.
Muscle becomes flaccid and repolarization doesnt occur.
Recovery only occurs as the drug diffuses away from the receptor, down a
concentration gradient, as the plasma levels fall.
Desensitization block:
Prolonged exposure of the neuromuscular junction to agonist, leads to receptor
desensitization which represents a safety mechanism that prevents over excitation.
Mechanism:
Mechanism is not fully known, but desensitization is accompanied by phosphorylation
of a tyrosine unit in the receptor protein.
Agonists promote the transition to a desensitized state by binding very tightly to a
desensitized receptor and trap it in the desensitized state.
Desensitization leads to significant misinterpretation of data. The responsiveness to
agonists and antagonists is altered. Desensitization may explain the apparent increased
sensitivity to non-depolarizers after prior administration of succinylcholine.
If many receptors are desensitized, neuromuscular transmission may not occur owing
to insufficient number of normal receptors.
Membrane potential may returns almost to its resting levels despite the continued
presence of the agonist, yet neuromuscular transmission remains blocked.
Prolonged apnoea after succinylcholine:
Low pseudocholinesterase
o Protein synthesized by the liver and present in the plasma.
o Normal serum levels are 80 units / ml.
o Levels are reduced in
Liver disease and consequent hypoproteinemia
Uremia
-Second Edition
2011

172


Nephrosis
Newborns
Alcoholics, Malnutrition
Malignancies, Cytotoxic / Alkylating drugs
Anti cholinesterases which may also inhibit pseudocholinesterase and can
prolong apnea upto 60 min.
Metoclopramide, pancuronium, oral contraceptives
Atypical pseudocholinesterase
Plasma cholinesterase structure is determined genetically by autosomal genes.
Over 95% of the population has normal genes, E1
U
E1
U
.
The presence of variant genes, prolongs the action of succinylcholine.
The commonest of these is the atypical gene E1
a
, present in about 4% of the
population
An individual, heterozygous for the atypical gene (E1
U
E1
a
) may have a slightly
prolonged neuromuscular block (upto 40 mins), following a bolus of
succinylcholine.
An individual, homozygous for the atypical gene (E1
a
E1
a
) may remain paralyzed
for a longer duration (1-4hrs) following a bolus, the prevalence being approx (1
in 2500).
Genotyp
e
Relativ
e
mean
enzym
ic
activit
y
Dibucaine
number
Fluoride
number
Frequenc
y
Suxamethonium
sensitivity
Mean Range Mean range
E1
u
E1
u
100 80 77-83 61 56-56 96% ? 1 in 2,599
moderately sensitive
E1
u
E1
s
50 80 77-83 61 56-68 1 in 190 ? 1 in 1,000
moderately sensitive
E1
u
E1
f
86 74 70-83 52 46-54 1 in 200 ? 1 in 100 moderately
sensitive
E1
U
E1
a
77 62 48-69 50 44-54 1 in 25 ? in 500 moderately
sensitive
E1
a
E1
a
43 21 8-28 19 10-28 1 in 2,000 All very sensitive

-Second Edition
2011

173


Other rarer genes include:
The, E1
s
, silent gene
The, E1
f
, fluoride resistant gene
The activity of plasma cholinesterase can be measured using a
spectrophotometric technique, examining the hydrolysis of benzolycholine.
Phenotype classification is obtained by adding different enzyme inhibitors. (eg:
Dibucaine, sodium fluoride, RO-020683) which cause differential enzyme
inhibition depending upon the enzyme phenotype present.
Dibucaine number:
It's the percentage of inhibition of the enzyme with 10
-5
M of dibucaine.
In patients with normal enzyme activity, the dibucaine number is usually over
75.
Patients heterozygous for the atypical gene have a dibucaine number around 50.
Patients homozygous for the atypical gene have a dibucaine number around 30.
Acquired causes for reduced plasma cholinesterase activity.
a) Reduced enzyme synthesis
Hepatic diseases, carcinomatosis, malnutrition.
b) Administration of drugs which share the same metabolic pathway and therefore
compete with succinylcholine for the enzyme. Esmolol, MAO inhibitors,
methotrexate
c) Anticholinesterase drugs which inhibit both acetylcholinesterases as well as
plasma cholinesterase e.g. edrophonium, neostigmine and euthiopate eye drops.
d) Pregnancy (enzyme activity is reduced by 25%).
e) Plasmapheresis and cardiopulmonary bypass.
Phase II block:
High doses of succinylcholine (>2 mg/kg) generate the dual block, when a short lived
depolarizing block changes into a non depolarizing block, -characterized by fade of train
of four, tetanic fade and post tetanic facilitation.
Mechanism;
The repeated opening of channels causes a post junctional ion channel blockade
allowing a continuous efflux of K
+
and Na
+
, resulting in abnormal electrolyte
balance.
-Second Edition
2011

174


The Ca
2+
ion enters the muscle via the opened channels, causing disruption of
receptors and end plate elements.
Pre-functional receptor inhibition with reduced release of acetyl choline.
Post functional receptor desensitization.
It may be reversed by low doses of anticholinesterase.
Factors influencing the development of phase II block
The duration of exposure of drug.
Type of drug used and its concentration.
Type of muscle (slow / fast).
Interaction with anesthetics and other agents.
Features of depolarizing neuromuscular blockade:
They cause muscle fasciculations (but not in myasthenic humans) and
extraocular muscles exhibit a tonic response.
Sodium channels are blocked and muscle is unresponsive to other mechanical or
electrical stimuli and the repolarization doesn't happen until phase 2 block
develops when the resting membrane potential returns to-SO mv.
Fast dissociation at receptors.
Block is not reversed by anticholinesterase.
In partial paralysis there is depression of muscle twitch, no fade and no post
tetanic facilitation.
They are potentiated by inhalational agents (especially isoflurane), respiratory
alkalosis, hypothermia and magnesium.
They are antagonized by acidosis and non-depolarizing muscle relaxant.
Repeated or continuous use leads to phase II block.
Non depolarizing (competitive) neuromuscular block:
They are mostly hydrophilic mono-or bis quaternary salts with an interonium distance
of 0.7-1.4nm.
They don't cause structural conformation of the receptor but prevent depolarization by
combining reversibly with one or both subunits, preventing access by acetylcholine
and ion channel opening.
This results in a lower end plate potential which does not reach the threshold necessary
to fire off a propagating action potential.

-Second Edition
2011

175


The block depends on
a. Relative concentrations of acetylcholine and the blocking drug and
b. Their relative affinities for the post synaptic nicotinic receptor.
70-80% of the receptors have to be occupied by a nondepolarizing muscle relaxant
before the response to nerve stimulation is affected.
Thus during recovery from a nondepolarizing block, even when the vital capacity is
normal and head lift is sustainable for 5 seconds, 70% of post synaptic receptors may
still be blocked.
The phenomena of fade and post tetanic facilitation are thought to be due to block of the
pre-junctional nicotinic receptors by the nondepolarizing muscle relaxant which
inhibits the positive acetylcholine feedback further inhibiting the acetylcholine
synthesis and mobilization in the presynaptic nerve endings.
Features of nondepolarizing muscle blockade:
No muscle fasciculations
Relatively slow onset (1-5 mins) and slow dissociation at the receptors.
Reversed by anticholinesterase.
Relaxed muscle remains responsive to other mechanical or electrical stimuli.
In partial paralysis there is depression of muscle twitch, `fade' and post tetanic
facilitation', followed by exhaustion.
Effects are reduced by succinylcholine (but not in myasthenic).
They are potentiated by volatile agents acidosis, magnesium and Hypokalemia.
Mild cooling antagonizes their effects but further cooling below 33
C potentiates
them.
Factors influencing neuromuscular blockade
- Physiological
- Pharmacological
Physiological:
Age: The neuromuscular junction reaches mature level at 2yr of age. So the dosage must
be adjusted. The initial loading dosage is not decreased because of larger volume of
distribution, but maintenance dose need to be adjusted.
Geriatrics: There is reduced clearance and increased duration of action of non-
depolarizing relaxants.
Obesity: Elimination is decreased in obese patient. The dosage should be about 20%
more than the lean body mass rather than actual body weight.
-Second Edition
2011

176


Protein binding: Increased protein binding will increase the volume of distribution
reducing the free drug available at neuromuscular junction.
Temperature: There is prolonged effect of all neuromuscular blocking agents following
a drop in the core body temperature or temperature of the muscle.
Acid base balance: Acidosis intensifies neuromuscular blockade, requiring a lower
dose of blocking agent or a higher dose of reversal agent.
Alkalosis requires a higher dose of paralyzing agent or a lower dose of reversal agent.
Blood flow: An actively contracting muscle has greater blood flow and more delivery
of" blocking agent.
Disorders: There is altered response in states like myasthenia Gravis, burns,
myopathies malignancy sepsis prolonged immobilization.
Pharmacological:
1) Drug interaction
2) Organ failure
3) Electrolyte imbalance
Drug interaction:
a) Interaction with inhalational agents:
The anesthetic vapors potentiate neuromuscular blockade when administered in high
concentration.
The cause of potentiation is unknown, but the Greater effect on tetany and TOF
responses than on single twitch responses suggests that prejunctional mechanism are
involved.
b) Intravenous agents:
Slight potentiation of non-depolarizing neuromuscular blocking agent has been seen
with most i.v. induction agents.
c) Local anesthetics:
Lidocaine, procaine, and other LA produce neuromuscular blockade on their own and
potentiate the effect of depolarizing and non-depolarizing neuromuscular blocking
drug.

-Second Edition
2011

177


Neuromuscular blocking drugs:
a)Non-depolarizing - non-depolarizing interaction:
Combination of pancuronium-vecuronium; atracurium- mivacurium have
additive effects.
Combination of rocuronium and cisatracurium are synergistic.
This is because, the drugs acts separately at pre-synaptic and postsynaptic components.
It may be entirely post-synaptic as a result of asymmetric binding of different relaxants
to the u.-subunits of acetylcholinesterase receptor.
b) Non-depolarizing - depolarizing interaction
When d-tubocurarine or other non-depolarizing agents are given before succinylcholine
to prevent fasciculation and muscle pain, the succinylcholine becomes less potent and
has shorter duration of action.
If anticholinesterase has been Oven, the effect of succinylcholine is potentiated because
of inhibition of plasma cholinesterase.
c) Antibiotics
Neomycin and streptomycin are the, most potent of the aminoglycosides in
depressing neuromuscular junction. They augment both depolarizing and non-
depolarizing block.
Aminoglycosides (gentamycin, netilmycin) also potentiate nondepolarizing
neuromuscular blockade.
Clindamycin and lincomycin have pre-junctional and post-junctional effects and
the block cannot be reversed with Ca
2+
or anticholinesterase.
d) Anticonvulsants
Resistance to pancuronium, vecuronium and rocuronium, but not to atracurium or
mivacurium have been demonstrated in patient receiving chronic anticonvulsant
therapy with carbamazepine or phenytoin.
Miscellaneous
Potentiation of depolarizing and non-depolarizing blockade occurs with -agonists and
Ca channel blocker. Abnormal reaction occurs in the presence of diuretics,
corticosteroids, immunosuppressants and psychotropic drugs.

-Second Edition
2011

178


2) Organ failure
Patient with altered hepatic or renal function have an increased risk of prolonged
blockade. Organ failure may cause accumulation of drug by decreased drug clearance
and therefore prolonged neuromuscular blockade.
Vecuronium and pancuronium are accumulated in patient with hepatic failure,
atracurium is preferred.
3) Electrolyte imbalance:
The normal physiology of muscle contraction depends on the regulation of electrolytes.
Abnormal level of Na
+
, K
+
alters the excitability of the motor end plate, while Mg
2+
, Ca
2+

levels effect the quality of contraction.
Increased Ca
2+
level causes increase release of acetylcholine and increase in
muscular contraction.
Increased Mg
2+
level cause decreased release of acetyl choline and decrease in
muscular contraction.
Decreased Ca
2+
or increased Mg
2+
enhances neuromuscular blockade with non-
depolarizing agents.
Increase in Mg
2+
enhances neuromuscular blockade with depolarizing agents.
An acute decrease in extracellular K
+
will result in hyperpolarization. Hence
hypokalemia augments non-depolarizing agent and antagonizes depolarizing
agent.
Hyperkalemia decrease the resting membrane potential causing partial depolarization
of cell membrane and thus facilitates depolarizing agents and resist the non-
depolarizing agents.
Potentiation (+) and resistance (_) of neuromuscular blocking agents by other drugs:
Drug
Effect on
depolarizing
blockade
Effect on
nondepolarizing
blockade
Comments
Antibiotics + + Streptomycin, aminoglycosides,
kanamycin, neomycin, colistin,
polymyxin, tetracycline,
lincomycin, clindamycin
Anticonvulsants ? - Phenytoin, carbamazepine,
primidone, sodium valproate
Antiarrhythmics + + Quinidine, calcium channel
blockers
Cholinesterase inhibitors + - Neostigmine, pyridostigmine
Dantrolene ? + Used in treatment of malignant
hyperthermia (has quaternary
ammonium group)
-Second Edition
2011

179


Inhalational anesthetics + + Volatile anesthetics
Ketamine ? +
Local anesthetics + + High doses only
Lithium carbonate + ? Prolongs onset and duration of
succinylcholine
Magnesium sulfate + + Doses used to treat
preeclampsia and eclampsia of
pregnancy

-Second Edition
2011

180


Diseases with altered responses to muscle relaxants:
Disease Response to depolarizers
Response to non-
depolarizers
Amyotrophic lateral sclerosis Contracture Hypersensitivity
Autoimmune disorders (systemic lupus
erythematosus, polymyositis,
dermatomyositis)
Hypersensitivity Hypersensitivity
Burn injury Hyperkalemia Resistance
Cerebral palsy Slight hypersensitivity Resistance
Familiar periodic paralysis
(hyperkalemic)
Myotonia and
hyperkalemia
Hypersensitivity?
Guillain-barre syndrome Hyperkalemia Hypersensitivity
Hemiplegia Hyperkalemia Resistance on affected side
Muscular denervation (peripheral nerve
injury)
Hyperkalemia and
contracture
Normal response to
resistance
Muscular dystrophy (Duchenne type) Hyperkalemia and
malignant hyperthermia
Hypersensitivity
Myasthenia gravis Resistance and proneness
to phase II block
Hypersensitivity
Myasthenic syndrome Hypersensitivity Hypersensitivity
Myotonia (dystrophica, congenital,
paramyotonia)
Generalized muscular
contractions
Normal or hypersensitivity
Severe chronic infection (tetanus,
botulism)
Hyperkalemia resistance
Antagonism of neuromuscular blockade:
Acetylcholine has an esteric site and an anionic site in close proximity.
The positively charged quaternary amine of acetylcholine binds to the anionic site and
the acetyl ester combines with the esteric site of acetylcholinesterase and acetylcholine
is hydrolyzed. Anticholinesterase competitively occupy these sites and prevent
acetylcholine access.
a) Increase the number of acetyl choline molecules in the functional cleft, thereby
increasing the probability that acetyl choline will occupy the reorganization site.
b) Increase the length of time acetyl choline is in the cleft. Normally the non-
depolarizers attach to the receptor for about 1 millisecond which is more than the life of
acetyl choline. So increasing the length of time acetylcholine is in the cleft, increases
chances of it binding to the receptor.
Anticholinesterase have a quaternary amine group that is attracted to the anionic site
and a carbamyl ester that binds covalently to the serene amino acid of the
acetylcholinesterase esteric site.
-Second Edition
2011

181


The quaternary amine group conveys enhanced potency and stability and poor
gastrointestinal absorption and transfer of the drug across lipid barriers.
Anti cholinesterase also have some direct agonistic cholinergic action.
Subsequent to the increased cholinergic, (muscarinic and nicotinic) activity, they
decrease the heart rate and blood pressure (vasomotor tone).
Excess acetylcholine causes bronchoconstriction, increased gastrointestinal tone /
motility and increased bronchial and gastrointestinal secretions with hyperhidrosis and
lacrimation. These can be prevented by the concomitant use of antimuscarinic drugs as
atropine and glycopyrrolate.
Anticholinesterase can cause depolarizing blockade when administered in excess or in
the absence of nondepolarizing muscle relaxant.
With their usage, the clearance of the relaxants is not accelerated but the dose response
CL11
-
VC for neuromuscular blockade shifts to the right. The pharmacodynamic
recovery is therefore accelerated and this is superimposed upon the mechanisms
responsible for relaxant clearance.
Termination of neuromuscular blockade is either by:
1) Diffusion of the blocking agent away from the neuromuscular junction and
endogenous metabolism and elimination of the muscle relaxant (spontaneous reversal)
or
2) In case of nondepolarizing muscle relaxant, the effects can be overcome in part by
inhibiting the metabolism of acetylcholine (pharmacological reversal).
Neostigmine forms covalent bonds with acetylcholinesterase hence the longer duration
of action is explained by the stability of the bond.
The choice and dose of cholinesterase inhibitor determine the choice and dose of
anti cholinergic.
Cholinesterase
inhibitor
Usual dose of
cholinesterase
inhibitor
Recommended
anticholinergic
Usual dose of
anticholinergic per mg of
cholinesterase inhibitor
Neostigmine 0.04 0.08 mg/kg Glycopyrrolate 0.2 mg
Pyridostigmine 0.1-0.4 mg/kg Glycopyrrolate 0.05 mg
Edrophonium 0.5-1 mg/kg Atropine 0.014mg
Physostigmine 0.01-0.03 mg/kg Usually not
necessary
NA

-Second Edition
2011

182


In addition to the above the following drugs are used:
1) Potassium channel-blocking drug - best known is 4-aminopyridine. Action is pre-
functional. It prevents the efflux of K+ from the nerve ending, so prolonging the
depolarizing time of the nerve. So more acetyl choline is released and for a longer
time. These drugs are not used routinely because of a variety of undesirable
effects, most serious being seizures.
2) Cyclodextrins
This is a approach in which the neuromuscular block is reversed by direct binding of
relaxant by chemical means. The most promising of these is the -cyclodextrin
derivative ORG-2969. It is specific for rocuronium. It has very fast action usually 2-3
minutes.
NEUROMUSCULAR MONITORING
Introduction:
Peripheral nerve stimulators are extensively used for monitoring neuro-muscular
blockade after administration of muscle relaxant in the operation theatre as well as in
ICU.
Neuromuscular monitoring permits administration of NMBs such that optimal surgical
relaxation is achieved and yet the block reverses spontaneously or reversed reliably and
quickly with antagonists.
Residual neuromuscular block is a major risk factor for may critical events in the
immediate postoperative period. Wide spread use of perioperative NMJ monitoring was
found to be helpful in reducing these complications.
Neuromuscular function is monitored by evaluating the muscle evoked response to
supramaximal stimulation of peripheral motor nerve.
Nerve stimulators should be used in at least the following situations.
Whenever a long acting muscle relaxants is used.
When the pharmacokinetics of a muscle relaxant is abnormal severe liver,
kidney disease, severe illness, extremes of age.
During pharmacodynamics change as in neuromuscular disease like
myasthenia gravis, burns, prolonged immobilization, myopathies.
When one wishes to avoid drug induced reversal for neuromuscular blockade
as in severe heart disease or bronchial asthma.
When it is important that post-operative muscle power be maximal - severe
pulmonary disease; marked obesity.
-Second Edition
2011

183


Lengthy surgery
When neuromuscular blockade is produced by continuous infusion of
neuromuscular blocking drug.
Two types of stimulation can be used
A) Electrical stimulation - commonly used
B) Magnetic stimulation - not commonly used.
Principle of peripheral nerve stimulation:
Strength of contraction a number of activated muscle fibres intensity of the
stimulus.
Following blockade response of a muscle decreases in parallel with the number
of fibres blocked.
Equipment required
a) Nerve stimulator
Essential features
Square-wave impulse, < 0._5 msec, > 0.1 msec duration.
Constant current variable voltage
Battery powered.
Multiple patterns of stimulation (single twitch, train-of-four, double-burst, post-
tetanic count).

c) Response detection / Recording devices
Stimulus strength:
Depends on
a) Duration (pulse width) ->0.1 ms < 0.5 ms (0.2 ms)
b) current intensity (in mA)

-Second Edition
2011

184


Supra maximal current:
20-25% above the intensity required for maximal response or
Approximately 2.75 times the intensity that produces the first detectable
response.
Patterns of nerve stimulation:

Single twitch stimulation:
A single supramaximal electrical stimulation is applied at frequency of 1Hz to 0.1 Hz.
The frequency of 0.1 is generally used and during induction of anesthesia 1Hz is used
occasionally. The rate of delivery should not be more than 0.15Hz because evoked
response will gradually decrease and settle at lower level.
-Second Edition
2011

185


Disadvantages
Requires a prerelaxant control value for comparison.
Employment of a recording device is usually essential.
Single twitch depression occurs only after 75% - 80% receptor blockade.
Train of four (TOF stimulation)
In this four supramaximal stimuli are given every 0.5 second i.e. 2 Hz, repeated 10 20
sec interval. The amplitude of contraction is noted. The TOF ratio = T1: T4
Fade forms the basis of evaluation
Following results can be obtained
a). In normal muscle TOF ratio = 1
b). During partial non depolarizing block - < 1 and is inversely proportional to
degree of block.
c). During partial depolarizing block 1 because no fade occurs.
A ratio of <1 during succinylcholine administration signifies phase II block.
Advantages of TOF:
a). Degree of block can be obtained directly even in absence of preoperative value.
b). It is less painful.
c). Does not affect degree of neuromuscular blockade.
Tetanic stimulation:
In this a 50Hz stimulation is given for 5 seconds and response is noted. Two patterns
are noted.
a). No fade occurs During a normal neuromuscular transmission
During a pure depolarizing block
b). Fade occurs - During a non-depolarizing block
During phase II block of succinylcholine
Use: In evaluation of residual neuromuscular blockade.
Disadvantages:
a). Very painful cannot be used in unanesthetized patient.
b). In late phase of neuromuscular recovery, titanic stimulation may produce a
lasting antagonism of neuromuscular blockade which is not the representative of
the other muscle group.

-Second Edition
2011

186


Post titanic count stimulation
During very intense neuromuscular blockade (during intubation) where no response to
single twitch or TOF occurs. Quantification can be done by applying a titanic
stimulation (50Hz for 5 sec) and observing the post titanic response to single twitch
stimulation given at 1Hz after 3 sec of ending titanic stimuli. The first response to post
titanic twitch stimuli occurs before 1
st
response to TOF reappears.
For a given neuromuscular blocking drug, the time until return of 1
st
response to TOF
stimuli is related to the number of post titanic twitch response present at a given time
(post titanic count)
Uses:
To evaluate the degree of neuromuscular blockade when there is no reaction to
single twitch or TOF nerve stimulation.
Whenever sudden movements are to be eliminated (ophthalmic surgery)
To prevent bucking / coughing in response to tracheo bronchial stimulation.
Double burst stimulation
It consists of 2 short bursts (lasting 0.2 m sec0 of 50 Hz titanic stimulation separated by
750 m sec. Most commonly used in DBS 3.3. i.e. 3 impulses in each of the 2 tetanic
bursts.
Following responses can be seen
a). In normal non paralyzed muscle response is 2 short muscle contraction of
equal strength.
b). In partly paralyzed muscle 2
nd
response in weaker than 1
st
i.e. the response
fades.
DBS was developed with specific aim of allowing manual (tactile) detection of small
amounts of residual blockade under clinical conditions and during recovery
immediately after surgery.
-Second Edition
2011

187


Site of Nerve stimulation
Any superficially located peripheral motor nerve may be stimulated, ulnar nerve being
the most popular. Various sites are

-Second Edition
2011

188


Importance
The risk of overdosing is decreased if response of a relatively sensitive muscle is
used as a guide to administration of muscle relaxants during surgery.
During recovery when adductor pollicis has recovered sufficiently, it can be
assumed that no residual neuromuscular blockade exists in diaphragm.
Recording of evoked responses
Following methods can be used for recording
Mechanomyography (MMG) measurement of evoked mechanical response of
the muscle
Electromyography (EMG) measurement of evoked electrical response of
muscle.
Acceleromyography (AMG) measurement of acceleration of muscle response.
Piezoelectric neuromuscular monitors (PzEMG) measurement of evoked
electrical response in a piezoelectric film sensor attached to the muscle.
Phonomyography (PMG)
Evaluation of recorded evoked responses
Nerve stimulation in clinical anesthesia is usually synonymous with TOF nerve
stimulation.
1). Non-depolarizing neuromuscular blockade: Three phases of block are seen
after injection of a dose sufficient for smooth tracheal intubation.
a). Intense neuromuscular block: Occurs within 3-6 mins. Also called as period of
no response because no response to TOF or single twitch stimulation occurs.
b). Moderate or surgical block: It begins when the first response to TOF
stimulation appears. It is characterized by a gradual return of four responses to
TOF stimulation. A good correlation exists between the degree of neuromuscular
blockade and the number of responses to TOF stimulation.

-Second Edition
2011

189


Number of responses detected Degree of neuromuscular blockade
1 95%
2 90%
3 80%
4 75%
Presence of one or two responses in TOF pattern normally indicates sufficient
relaxation for most surgical procedures.
c). Recovery
Criteria for recovery from block:
A). Subjective:
Ability to open eyes widely
Sustained tongue protrusion
Head lift sustained for 5 seconds
Sustained hand grip
Adequate cough capacity
B). Objective
Inspiratory force 20 25 cm H2O
Adequate tidal volume (5 ml / kg)
Vital capacity (15 20ml / kg)
C). Evoked Response
Return of single twitch
Return of the 4
th
response in the TOF / TOF recovery to ratio > 0.7
Absence of titanic fade
2). Depolarizing neuromuscular blockade (Phase I and II blocks)
Patients with normal plasma cholinesterase activity who are given a moderate dose of
succinylcholine undergo a typical depolarizing neuromuscular block (phase I block),
characterized by
The response to TOF does not fade
The response to titanic stimulation does not fade
No post titanic facilitation of transmission

-Second Edition
2011

190


Phase I block Phase II block
Titanic stimulation No fade Fade
Post titanic potentiation None Marked
Train of four No fade Marked fade
TOF ratio > 1 <0.4
Recovery Rapid Prolonged
Dose mg / kg 1 1.5 > 2
Potentiated by Anticholinesterase Non-depolarizers
Use of a peripheral nerve stimulator during induction of anesthesia
Nerve stimulates should attached before induction but to be turned on only after patient
becomes unconscious. When the response to TOF stimulation disappears, trachea is
intubated.
Use of peripheral nerve stimulator during surgery:
When using a non-depolarizing neuromuscular drug fro tracheal intubation, a longer
lasting period of intense blockade usually follows. The time until return of response to
TOF stimulation may be evaluated by using post titanic count.
A twitch depression of about 90% is sufficient for most surgical procedures. To ensure
paralysis of diaphragm, neuromuscular blockade of peripheral muscle must be so
intense that PTC stimulation is zero in the thumb.
Use during reversal of neuromuscular blockade:
Antagonism of a non-depolarizing neuromuscular blockade should not be initiated
before at least two response to TOF stimulation can be felt.
Limitations of neuromuscular monitoring
Following limitations are usually there
1). Neuromuscular response may appear normal despite the blocking agent
occupying the receptors. A T4: T1 ratio is 1 even when 40 50% of the receptors
are occupied.
2). Because of wide individual variability is evoked responses some patient may
exhibit weakness at TOF ratio as high as 0.8 0.9
3). The established cut-off values for adequate recovery do not guarantee adequate
ventilatory function or airway protection.
4). Increased skin impedance resulting from hypothermia limits the correct
interpretation of evoked responses.

-Second Edition
2011

191


CONCLUSION
As neuromuscular blocking agents from an integral component in an anesthesiologists
arsenal, its not only our skill in utilizing this weaponry, but our knowledge about the
normal functioning of the NMJ integrated with the methods of monitoring, with the
optimum usage of our wits at the most critical moments that makes us what we are.

-Second Edition
2011

192



-Second Edition
2011

193


Chapter 15 - SUPRATENTORIAL TUMOUR AND ANESTHESIA
Cerebral hemodynamic
Intracranial content:
Brian 80%
Cerebral blood volume 12%
CSF 8%
At any time cranium contains 75 100ml of CSF, 75 100ml of blood. Brain weighs
about 1.4 1.5 kg in adult, 2% of total body weight. As each f these three components is
relatively incompressible, the combined volume at any time must be constant the
Munro Kellie doctrine
Cerebral blood flow
The brain receives approximately 12 15% of cardiac output, yet makes only 2% of the
body weight. This disproportionately large blood flow is due to high metabolic rates of
the brain. At rest, the brain consumes oxygen at an average rate approximately 3-5ml
per 100 gm of brain tissue per min.

Total blood flow is 750 ml / min. (45 50 ml / 100 gm / min)
Gray matter 70 ml / 100gm / min
White matter 20 ml / 100 gm / min
O2 consumption 50 ml / min (3 3.5 ml /100gm / min)
Factors influencing CBF
PaCO2
PaO2
Anesthetics
Temperature
Blood Viscosity
PaCO2
CBF varies directly with PaCO2
-Second Edition
2011

194


CBF changes 1- 2 ml / 100gm / min for each 1 mm Hg change in PaCO2 around normal
PaCO2 values.
Increasing CO2 level causes vasodilatation and increased blood flow. Increasing the CO2.
Tension from 40 80mm Hg doubles the flow, reducing the CO2 from 40 20mm Hg,
halves the flow. These changes are transient and blood flow returns to normal in 6 8
hr, even if the altered CO2 levels are maintained.
PaO2
Hypoxia is a potent stimulus for arteriolar dilatation. CBF increases rapidly below
60mm Hg, roughly doubles at 30mmHg.

Temperature:
CMR and CBF decreases with decrease in Temperature
CBF decrease 6 7% per CO
Hyperthermia has got opposite influence on CBF.
-Second Edition
2011

195


Anesthesia agents
Most of volatile agents and intravenous drugs have got effect on CBF
Agent CBF CMRO2 Vasodilatation
Halothane
Enflurane
Isoflurane
Desflurane
Sevoflurane
N2O

Yes
Yes
Yes
Yes
Yes
--
Thiopentone
Etomidate
Propofol
Midazolam
Ketamine
Fentanyl

/O

/O
No
No
No
No
Yes
No
Viscosity:
Blood viscosity can influence CBF. Hematocrit is single most determinant of blood
Viscosity. In healthy subjects, the variation of Hematocrit within normal range (33
45%) probably results in only trivial alteration in CBF.
Hematocrit Viscosity CBF (In Anemia)
Hematocrit viscosity CBF (in Polycythemia)
Intracranial pressure
Normal ICP is 10 15 mm Hg in healthy, non obese adult, in supine position, up to 25
mm Hg in obese patient. In fully upright position, ICP normally drops to 3 to 5 mm Hg.
Measured by an intraventricular catheter, subdural / extradural transducer. An
approximate value for ICP can be obtained from CT scan.
Cerebral perfusion pressure
CPP is the difference between mean arterial pressure and intracranial pressure (ICP)
Intra cranial pressure volume relationship: The cranium has got a fixed volume i.e.
brain, CSF, blood. If any of the components located in cranial vault increase in
volume, the ICP will increase. The plateau phase occurring at low volume reveals
that the intracranial space is not completely closed one and that there is some
compensatory latitudes.

-Second Edition
2011

196


Compensation is accomplished principally by the
1. Translocation of CSF to spinal CSF space
2. Venous blood to extracranial veins
3. Increased in CSF absorption
4. Decreased CSF production

Intracranial hypertension
ICP more than 15mm Hg
Symptom and signs
Headache
Vomiting
Papilledema
Drowsiness
Bradycardia
Hypertension
Effects of increased ICP
Ischemia of brain
CPP = MAP ICP. If ICP to a greater extent than MAP, CPP is reduced resulting
in ischemia of brain.

-Second Edition
2011

197


Herniation of brain tissue: (Brain herniation syndrome)
1. Cingulate gyrus under falx cerebri
2. The uncinate gyrus though tentorium cerebri. Results in compression of 3
rd

cranial nerve, mid brain and posterior cerebellar artery.
Earliest sign is ipsilateral papillary dilation followed by stupor, coma,
decerebrate posturing and respiratory arrest.
3. The cerebellar tonsils though the foramen magnum
Results in apnea, circulatory collapse, death
4. Any area beneath the defect in the skull.
Factors that increase the ICP
Cough, Sneeze straining increases ICP by 60mm Hg, decreasing the venous
return.
Any venous obstruction like turning head, ETT ties, collars around neck.
Cerebral edema
Head down position
Arterial dilatation e.g. high PaCO2, Nitroprusside, CCB, N2O.
Hypertension (CPP = MAP ICP)
Hypoxia PaO2 less than 60mm hg
Volatile agent arterial dilatation more than 1 MAC but less than 0.5 MAC there
is decreased cerebral metabolism.
Halothane >> Enflurane > Isoflurane > Desflurane > Sevoflurane
Hyperthermia
Anesthetic drugs Ketamine
Increased intra thoracic pressure Bronchospasm, Pneumothorax, Tube kinking.
Seizure

-Second Edition
2011

198


Intracranial tumours
WHO classification
1. Neuro epithelial tumors
Gliomas
Astrocytoma
Oligodendromas
Ependymoma
Choroids plexus tumour
Pineal tumor
Neuronal Tumour
Gangliomas
Gangliocytoma
Neuroblastoma
Medulloblastoma
2. Nerve sheath tumour
Acoustic neuroma
3. Meningial tumour
4. Pituitary tumour
5. Germ cell tumour
Germinoma
Teratoma
6. Lymphoma
7. Metastatic tumour
Etiology
Exposure to ionizing radiation is the only well documented environmental risk
factor for the development of Gliomas.
A number of hereditary syndromes are associated with an increased risk of brain
tumour.

-Second Edition
2011

199


Syndrome Gene Neoplasm
Von Recklinghausens disease NS1 Neuroma, Schwannoma, meningioma
Tuberous sclerosis TSC1
TSC2
Astrocytoma
Von Hippel Lindau VHL Hemangioblastoma
Clinical features
a. Increased intracranial pressure
Head ache initially head ache is worst in the morning and progressive
Nausea
Vomiting
Disturbance in vision Papilledema
Altered consciousness
b. Focal neurological signs
Motor Posterior frontal lobe
Sensory Anterior parietal lobe
Language Aphasia dominant lobe
Apraxia Non dominant lobe
Visual symptom Optic pathway
Temporal lobe Focal seizure with aura and visual field defects
Frontal lobe Altered cognition and personality
Hydrocephalus Ventricular system
Brain stem and cerebellar Pontine angle cranial nerve palsy
Cerebellar vermis Ataxia
c. Organic mental changes
d. Seizures late onset epilepsy (more than 30 years)
Anesthetic consideration
Problems faced by anesthetist during neurosurgery:

Difficulties in maintaining ICP
Maintenance of airway
Control of venous pressure by absence of straining or cough at any stage
of the operation
Length of surgery
Positioning
-Second Edition
2011

200


Air embolism in head up position
Fits
Post op care of airway and respiration
Preoperative assessment
Aim:
1. Estimate ICP
2. The degree of impairment of intracranial compliance.
3. To assess the homeostatic reserve for ICP and cerebral blood
perfusion before brain ischemia and neurological impairment
occurs.
4. A discussion with surgeon position and expected complication
History
H/O Seizure
H/O increased ICP
Decreased level of consciousness
Focal neurological deficits
H/o Drug intake
1. Antiepileptic drug Phenytoin, Carbamazepine increases the dose of NMJ
blocker.
2. Anti cancer therapy Adriamycin may be associated with cardiomyopathy
3. Steroid
4. Diuretics electrolyte abnormality
Physical evaluation:
General physical examination
Head to examination Pallor, Cyanosis, Clubbing, Lymphadenopathy and Weight
CNS Examination
Mental status
Papilledema
Bp hypertension
Pupil size
Heart rate
Speech deficit
-Second Edition
2011

201


Glasgow coma scale
Focal signs
Cranial nerve evaluation
Evaluation of hydration status
CARDIVASCULAR AND RESPIRATORY SYSTEMS EXAMINATION
These are important because brain perfusion and oxygenation ultimately depend on
them.
Technical Examination (CT/MRI)
Helps in assessing size and location of tumour.
Intracranial mass effect mid line shift, decreased size of ventricle, herniation
Hydrocephalus, edema
Investigations
1. Serum Electrolyte
Na
+
- (136 145 mEq/L)
K
+
- (3.5 5.0 mEq/L)
Electrolyte abnormality is seen in excessive vomiting, diuretic therapy
2. Osmolality (285 295 mosm/L)
3. Hematocrit (35 45%)
4. Serum glucose (80 120 mg/dl)
Preoperative preparation
Pre-medication
Sedation carries the risk of hypercapnia, hypoxia, partial upper airway
obstruction ; all of which has got detrimental effect on ICP. However avoiding
stress is also desirable. Thus analgesia Fentanyl 25 100 gm; Sufenatnyl 5
20 gm, sedation midazolam 0.5 2 mg should be provided.
Steroid should be continued on the morning of operation 4 mg Dexamethasone.
Effectively cerebral edema. However require to start 2- 3 days before surgery.
For long term steroid treatment with probable Pituitary axis suppression, stress
coverage should be provided. (Methyl prednisone 100mg)
H2 blocker: Ranitidine 1 mg / kg
Gastric Prokinetic drugs Metoclopramide 0.2 mg / kg. H2 blocker and Gastric
prokinetic drugs should be considered to counteract the decreased gastric
emptying time and increased acid secretion associated with ICP and steroid
therapy, in CN (IX, X) palsy absent Gag reflex.
-Second Edition
2011

202


Continue anticonvulsant drugs. Consideration should be given to starting anti
convulsant agents if not already initiated.
Glycopyrrolate 0.01 mg / kg useful as antisialagogue.
Vascular access
Two large bore peripheral intravenous lines are usually placed. Local anesthetic cream
should be applied before placing cannula to avoid hypertensive response to pain.
Urinary catheter has to be placed for
Osmotic diuresis
Long duration of surgery
Monitoring urine output
To avoid distension of bladder
Ryles tube for aspiration of gastric content
Monitoring
Clinical monitoring
Anesthetist himself acts as a good monitor
1. Colour of the skin and blood oxygenation
2. Temperature of the skin body temperature
3. Pulse character and rate cardiac performance and arterial pressure
4. Degree of filling jugular vein circulating volume
5. Urine flow > 0.5 ml / kg / hr circulatory status, fluid volume
6. Perspiration, lacrimation, - depth of anesthesia
7. Muscle tone and movement relaxation
8. Surgeons comment tightness ICP
Non invasive
End tidal CO2
Arterial CO2 (PaCO2) plays central role in controlling CBF, central blood volume,
and ICP.
Continuous FETCO2 analysis is useful in detecting venous air embolism.
Failure of central circulatory perfusion during elective hypotension.
-Second Edition
2011

203


Oximetry
Hypoxia results in hyperemia and edema resulting in brain swelling
3. Bp monitor
4. ECG
5. EEG
Helps in assessing depth of anesthesia
Detects brain ischemia
Assessment of pharmacological interventions, such as
barbiturate induced burst suppression, assessment of coma,
or brain death.
Diagnosis and management of intractable epilepsy.
EEG frequency ranges
Delta rhythm (0 3Hz) Deep sleep, deep anesthesia, brain tumour
Theta rhythm (4 7 Hz) Sleep and anesthesia in adults, hyperventilation
Alpha rhythms (8 13 Hz) Resting, awake with eyes closed
Beta rhythm (> 13 Hz) Light anesthesia
Precordial Doppler
Detects venous air embolism
Invasive
Beat to beat monitoring of BP
Intra cranial pressure monitoring: with the help of continuous ICP monitoring, it is
possible to optimize CPP. Techniques used to monitor ICP include ventricular
catheters, subdural subarachnoid bolts or catheters, various epidural
transducers, and intraparenchymal fiberoptic devices.
Serum electrolyte: Helps in diuretic induced Hyponatremia, Hypokalemia
Blood glucose and osmolality: Hyperglycemia worsen the neuronal damage
Temperature: Esophageal lead = 35
o
C neuro protective.
CVP: When possible, CVP catheter should be inserted for the measurement of cardiac
preload and intra operative fluid management. CVP should be inserted through
antecubital vein instead of jugular or subclavian veins. This avoids ICP from
both the head down position and cerebral venous outflow.

-Second Edition
2011

204


Induction and intubation sequence
Adequate axolysis and premedication
Adequate fluid loading (5 7 ml / kg of NaCl 0.9%)
Monitors
i.v. cannula
Fentanyl 1 2 gm/ kg
Pre-oxygenation and voluntary hyperventilation
Propofol 1.25 2.5 mg / kg or Thiopentone 3 -6 mg / kg
Non depolarizing muscle relaxant Vecuronium 0.08 0.1 mg / kg
Lignocaine 1.5 mg / kg, 90 sec prior to intubation
Intubation
LA and IV Fentanyl 1 2 gm / kg before head pin / skin incision.
Position, Adequate head up position.
Analgesia
Narcotic analgesics
Little effect on CBF and CO2 reactivity is preserved
Fentanyl 1-2 gm / kg
Induction of anesthesia
Intravenous barbiturate
Thiopentone 3 7 mg / kg
Cerebral metabolism and blood flow are reduced. A major problem with barbiturate is
that they can substantially reduce MAP, which if not controlled, can reduce CPP.
Barbiturates are also effective in reducing elevated ICP and controlling epileptic form
activity.
Methohexitone is an exception with regard to epileptic form activity; it can activate
some seizure foci in patients with temporal lobe epilepsy.
Propofol
Dose 1.25 2.25 mg / kg
Reduces CMR and CBF
Ketamine
Raises CBF Should be avoided
-Second Edition
2011

205


Etomidate
It has similar effects as Thiopentone, reduce CMR and CBF.
Thiopentone, Propofol, Etomidate are the inducing agents in neuro-anesthesia.
Muscle Relaxants
Modern non depolarizing muscle relaxants have minimal effects on intra
cerebral Hemodynamics.
Vecuronium (0.1 0.2 mg / kg) has no effect on the brain, but Phenytoin therapy
may increase requirement.
Avoid using a atracurium because of release of histamine and the Laudanosine
level which the seizure threshold.
Reserve the use of succinylcholine for difficult intubation as it causes transient in
CMR, CBF and ICP.
Other drugs that can be used are Pancuronium, Rocuronium.
Positioning
Goal
a). To facilitate the surgeons technical approach while balancing risk factor
b). To prevent cerebral venous stasis or venous obstruction.
Different positions are
Supine
Prone
Sitting
Semi lateral
Lateral
Supine position
Indication: This position is used with the head in neutral or rotated for frontal,
temporal, or parietal access.
a). Most commonly used position with 10
o
30
o
head up position so that cerebral
venous drainage is free.
b). Frequently the head is turned to one or other side and it is important to ensure
that the degree of neck rotation is not excessive usually by raising the shoulder
support.
c). Eyes should be closed and covered especially for frontal operations.
-Second Edition
2011

206


-Second Edition
2011

207


Prone position
Indication
This position is used for occipital lobe, posterior fossa procedures.
1. The airway must be carefully secured, the difficulties of re-intubation should be
considered.
2. Positive pressure ventilation is required and great care should be taken to
ensure that no undue increase in CVP results.
3. Compression of the abdomen by faulty position will result in CVP this can be
avoided by placing pillows under chest and hip so that the abdomen is hanging
freely down without compression. The pillows are given at legs with slight
flexion at knee and foot in order to facilitate venous return.
4. Eyes needs to be closed and covered, attention should be given to retinal
ischemia and blindness caused by occlusion of the central retinal vessel as a
result of orbital compression, it must be intermittently confirmed (every 15
min).
5. The arms padded, either by the patients side or on arm board. Direct pressure
necroses of the forehead, maxillae, and chin can result.

-Second Edition
2011

208


Sitting position
Indication supracerebellar infratentorial approach to the pineal area.
Advantages
Improves surgical exposure, avoids problems of cerebral retraction that occur
with occipital, transtentorial or transcallosal approach.
Avoids the large venous structures lying over the pineal region.
Reduces the airway pressures during mechanical ventilation.
As an anaesthetized patient is placed in sitting position blood tends pool in
lower extremity venous return CO. If hypotension is found on moving the
patient, the patient should be returned to the supine position and the cause of
hypotension should be identified and treated.
Manure help in decreasing hypotension
Wrapping the legs in firm bandage
Flexion in things and knees
Complication with sitting position is venous air embolism
-Second Edition
2011

209


-Second Edition
2011

210


Semi lateral position
This is achieved by lateral tilting of the table 10 20 degrees.

-Second Edition
2011

211


Lateral position
Indication: Posterior parietal and occipital lobes

Maintenance
Most commonly administered maintenance anesthetic for patients with Supratentorial
tumours are N2O Opioid and N2O volatile anesthetics
a). Nitrous oxide: Commonly used in neurosurgery. N2O 50 70% in oxygen, is
typically administered to decrease the total dose of intravenous agents or
required concentration of volatile agents. Nitrous oxide diffuses into air filled
spaces e.g. air embolism and perhaps the subarachnoid space after dural closure.
Should be turned off if air embolism occurs.
Inhalational agents
1. Isoflurane
Only mild cerebral vasodilator with little impairment of autoregulation
No increase in CBF below 1-1.5 MAC (1.15-1.7%)
May increase ICP in susceptible patients, but this can be controlled before
lowering.
The PaCO2
Sevoflurane
Similar to Isoflurane.
There is no increase in CBF below about 1 MAC

-Second Edition
2011

212


Halothane
Most potent vasodilator of the volatile agent, but decreases metabolism to a
moderate degree.
CBF is tripled and autoregulation abolished at 1 MAC (0.75%)
The associated ICP is prevented by prior reduction of PaCO2 at about 25mm Hg
by hyperventilation.
Enflurane
Cerebral vasodilation (less than halothane, more than Isoflurane)
CBF is doubled at 1 MAC (1.68%)
Tends to cause EEG discharges and sometimes convulsion over about 1.5 MAC
(2.5%)
Isoflurane and sevoflurane are the volatile anesthetics of choice.
Narcotic analgesics
Fentanyl 1-2 gm/kg/hr
Maintenance of ICP
Treatment of ICP > 20mm Hg
ICP falls to atmospheric pressure when the skull is open, as at craniotomy
This leads to
Herniation of brain tissue
Difficulty to retract the tissue by surgeon.
Avoid the factor ICP such as
Inadequate muscle relaxation
Poor cerebral venous drainage
Jugular venous obstruction
Neck rotation
mean intrathoracic pressure
PEEP
Inadequate head up position.
Hypercapnia
Hypoxia
Over transfusion
Hypertension

-Second Edition
2011

213


Treatment
Hyper ventilation
In adults the frequent recommendation is to maintain the PaCO2 near 30-35 mm Hg.
For every 1 mm Hg PaCO2 change there is 1-2 ml/100gm/min change in CBF. Avoid
PaCO2 less than 20mm Hg as it causes ischemia.
Hyper osmolar diuretics
Mannitol 20% solution osmolality of 1098 Mosm/kg 25% solution with
osmolality of 1372 Mosm/kg.
Dose 0.25 to 1gm/kg IV given over 20-30 min initially, with maintenance
doses given to keep serum osmolality near 305-310 mosm/kg.
Mechanism of action Mannitol increases the osmolality of 10 mosm of blood
reduces the edema brain volume
Mannitol is effective when the blood brain barrier is intact. When BBB is
disrupted
Mannitol may enter the brain and the osmolality. It could pull water into brain,
as the plasma concentration of agent declines and causes rebound in ICP.
Onset 10-15 min, the ICP effect is prompt, removes about 90ml of brain water at
peak effect and lasts for 2-3 hr.
Complications
1. Hyponatremia
2. Acute Hypervolemia
3. Hypokalemia
Loop diuretics
Furosemide 0.5 - 1mg/kg
Mechanism of action
Diuresis mediated brain dehydration
CSF formation.
Improved cellular H2O transport.
Slow in onset and less effective compared to Mannitol. (30-45 min)
Useful in LVF

-Second Edition
2011

214


Complication
Hypokalemia, hypochloremic metabolic alkalosis
Skeletal muscle weakness
Potentiation of neuromuscular blocker
Hypotension
Combined diuretic therapy
Mannitol induced in blood volume can be attenuated by furosemide, before the
administration of Mannitol.
However, with administration of combined diuretics vigorous intravascular fluid
and electrolyte replacement are considered.
A urine loss of 2-3 lover 2 hr is common with combined diuretic therapy
Corticosteroid
Dexamethasone 8 mg iv stat followed by 4mg 6 hrly postulated mechanism of action -
brain edema by
Brain dehydration
Blood brain barrier repair
Prevention of lysosomal activity
Enhanced cerebral electrolyte transport
Improved brain metabolism
Promotion of water and electrolyte excretion
Inhibition of Phospholipase A2 activity.
Complications
Hyperglycemia
Glucosuria
GI bleed
Electrolyte disturbance
Incidence of infection
Deliberate hypotension.
Blocker may be more appropriate for hyperdynamic states than
Vasodilators, due to their effects upon CBV. Esmolol (1mg/kg IV) may be ideal
choice.

-Second Edition
2011

215


Metabolic suppression.
Hypothermia
MAO The protection afford by the hypothermia is attributed to reduction in calcium
entry, in glutamate release, in glycine and dopamine release, recovery of ubiquitin
synthesis, inhibition of protein kinase c, and in free radical triggered lipid
peroxidation.
Complication
Increased tendency of bleeding by cold induced defect in platelet function and
impairs the enzyme of coagulation cascade.
Drug metabolism is markedly duration of action of Vecuronium is doubled by 2
0 c core temperature.
Barbiturates
Thiopentone -10-12 mg/kg given over 30 min followed by 5mg/kg each hour for three
doses. The maintenance dose 1-2 mg/kg/hr adjusted so that ether the serum level is
therapeutic range of 30-50 g/ml or EEG has burst suppression pattern.
CSF drainage
Normally 10-20 ml of CSF is effective in ICP. Drainage of CSF done from lateral
Ventricle during intra op. drainage can also be done from lumbar puncture through LP
Catheter placed pre op. the latter is effective only if there is no caudal block to CSF.
Because of risk of causing acute brain herniation, lumbar CSF drainage should be used
cautiously and only when dura is opened.
-Second Edition
2011

216


-Second Edition
2011

217


Fluid therapy
Maintain the normovolemia, normotension.
Avoidance of reduction of serum osmolality.
Avoid hyperglycemia which worsens the cerebral ischemic damage by promoting
neuronal lactate production and hyposmolality (target Osmolality 290-320
Mosm/kg which can increase brain edema.
Glucose containing/hypo osmolar (RL 254 Mosm/kg) should be avoided.
Suitable choice of infusion liquid during intracranial surgery include 0.9% NaCl,
6% starch solution (304 mOsm/kg)
Reversal and extubation
Emergency from anesthesia should be smooth as possible, avoiding straining or
bucking on the ETT. Bucking can cause arterial hypertension and ICP during
termination of anesthesia, which can cause post operative hemorrhage and
cerebral edema.
To avoid bucking during emergency, muscle relaxants are not reversed until the
head dressing applied.
Iv lignocaine 1.5mg/kg can be administered 90 sec before suctioning and
extubation to minimize cough, straining, and hypertension.
Esmolol 1mg/kg iv can be given.
Reversal done with neostigmine 0.05mg/kg iv with glycopyrrolate 0.02mg/kg iv.

Transfer to recovery room: After resection of supratentorial tumour, most patient who
have recovered sufficiently from anesthesia are positioned in a semi-recumbent
position with head elevation 30
0
to maximize cerebral venous drainage and are then
transported to recovery.
Supplemental oxygen, direct arterial blood pressure monitoring and if possible pulse
oximetry should continued during transport.
Post operative care
Pain
Carefully titrated doses of Morphine 1 mg IV

-Second Edition
2011

218


Management of nausea and vomiting
Nausea vomiting the BP and ICP treated with Ondansetron 4 mg iv Refractory
nausea vomiting should prompt consideration of the development of ICP secondary to
brain edema/hematoma.
Hypovolemia
After craniotomy, patient may be relatively Hypovolemia secondary to intraoperative
use of diuretics/acute blood loss. As a first line guide to the adequacy of blood volume,
urine output should be maintained at > 0.5ml/kg/hr through infusion of isotonic
solution. Electrolyte should be assessed early in the post op period.
Seizure:
Seizure may be precipitate serious complication including secondary intracranial
bleeding, hypoxia, and aspiration. If seizure occurs despite of preop administration of
anticonvulsant, control should be obtained with small dose of Benzodiazepine
(diazepam 10 mg IV) while ensuring an adequate airway. If seizure continues, there is a
need of evaluation (e.g., CT)
Hypothermia:
Hypothermia can be corrected with warming lights, application a circulating warm air,
warm infused solution.

-Second Edition
2011

219



-Second Edition
2011

220


Chapter 16 - BRAIN PROTECTION
Brain injury may be exogenous (an injurious agent that originates outside the
brain, e.g., trauma) or endogenous (originates from pathology inside the brain eg,
cerebral aneurysm, cerebral tumor).
o Protection of neuronal tissue in the brain is of ultimate importance and
the main goal of the neuro anesthesiologist. Therefore, the purpose of this
review is to concentration on the pathophysiology of brain ischemia and
recent advance in brain protection, and to evaluate the theoretical and
practical techniques that anesthesiologists employ to procedures for
trauma, ischemia, space- occupying lesion, and aneurysms.
o Dramatic advances in our understanding of the nervous system over the
past century and particularly the past several years have lead to
tremendous changes in the way we think about the brain. These new
neurobiological concepts have caused significant changes in neuro
anesthesiological practices.
Modern brain- injury research, with emphasis on brain protection, began in the
late 1960 s.
12
. Brain injury can produce neurologic sequelae via direct (ie,
immediate mechanical disruption of neural circuits in tissue) and indirect (ie,
delayed, or secondary) mechanisms, which develop injury over anywhere from
several hours to several weeks. These secondary cellular changes may include
alterations in neurotransmitter release and reuptake, changes in presynaptic or
postsynaptic binding, synthesis of inflammatory mediators, or alterations of
endogenous neuroprotective or trophic factors. Investigators have attempted to
influence the pathologic neurochemical ischemic cascade by using potentially
neuroprotective pharmacological agents. To avoid cerebral ischemia, the brain
must be kept well perfused. Usually, the brain tolerates wide swings in blood
pressure because of autoregulation mechanisms that maintain blood flow.
The ischemic cascade is unleashed by impaired cerebral perfusion. Cerebral
perfusion and auto-regulation is impaired by mechanisms such as hypotension
or hypertension, intracranial anatomical imbalance, cerebral trauma, hypoxemia,
or regional increase in tissue pressure from localized cerebral edema or surgical
manipulations. These events can create a mismatch between O2 demand and O2
supply. The oxygen deficit results in a decrease of ATP production by oxidative
phosphorylation. Instead, an insufficient amount of ATP is produced by
anaerobic metabolism. Decrease ATP production causes failure of the sodium-
potassium ATPase pump at the level of the cell membrane.
In addition, there is decreased function of hydrogen-calcium ATPase in the
endoplasmic reticulum and failure of the sodium-calcium ATPase pump in the
-Second Edition
2011

221


mitochondria, resulting in an increase in intracellular calcium, which in turn
triggers a proteolytic cascade and cell disintegration. Increases in extracellular
potassium, can also be seen. These ionic displacements result in ionic imbalance
at the cell membrane and presynaptic release of excitatory neurotransmitters
(eg, aspartate, glutamate).
The flood of glutamate that pours into the synaptic cleft over stimulates the
following 3 main types of receptors: -amino-3hydroxyl-5-methyl-4-
isoxazoleproprionate (AMPA) kainate receptors, N-methyl-D-aspartate ( NMDA)
receptors, and metabotropic receptors. AMPA receptors open and allow sodium
influx and potassium efflux. AMPA receptors are important in ischemic cell
death, probably because excessive activation of these receptors leads to
depolarization of the cell membrane and activation of NMDA receptors.
NMDA receptors are activated by all depolarization and glutamate release.
Activation of these receptors allows for the influx of sodium and calcium and the
efflux of potassium. The subsequent rush if ions across the membrane wall,
particularly the passage of calcium ions through NMDA-receptor mediated
channels, creates an unstable ionic balance, which leads to cascading
intracellular events and eventually results in neuronal cell death when it occurs
in the brain.
This flux of calcium ions into the cell precipitates glycolysis. Glycolysis during
hypoxia results in anaerobic metabolism and lactic acidosis. It takes about 20
minutes during anoxia in the grain for the reserve brain glucose to be exhausted.
Lactic acidosis, the inability to wash out CO2 adequately, results in a mixed tissue
acidosis that causes structural damage to the neuronal cell. Without
reoxygenation, brain cells progress from an initially reversible damaged to the
neuronal cell. Without reoxygenation, brain cells progress from an initially
reversible damaged state to an irreversible structurally damaged state that
ultimately results in necrosis of all neurons.
Lactate also causes increased iron release from the proteins in the cell. Ferrous
ion is a catalyst for generating hydroxyl radicals. These hydroxyl radicals, in
conjunction with other oxygen radicals such as superoxide and nitric oxide, also
contribute to cell death. Increased free radicals can cause oxidation of proteins
and lipids in membranes at the mitochondrial and cellular levels, which result in
cell-membrane disruption. This may then lead to cell lysis. Proteins are severely
damaged and aggregate in neurons after focal ischemia, which contributes to
neuronal death.
In light of the above mechanisms, the end result of cerebral ischemia is an
irreversible necrosis secondary to energy and membrane failure. The area of the
-Second Edition
2011

222


brain between infracted tissue and normal brain tissue has a relatively decreased
blood flow, perturbed physiological processes, and an energy imbalance. This
zone of peri-infracted tissue is called the ischemic penumbra. In the absence of
appropriate and timely therapeutic intervention, the penumbra will progress to
infarction and programmed cell death (apoptosis).
NEUROPROTECTIVE AGENTS
There are several in vivo and in vitro approaches to the study of neurotoxicity and
neuro protection. In this section, we review potentially neuroprotective agents based on
their known primary mechanism of action.
NMDA and AMPA/ Kainate-Receptor Antagonists:
NMDA and AMPA/Kainite-receptor antagonists have been investigated
extensively in animal models of brain ischemia. However, despite the remarkable
promise demonstrated in vitro and in animal studies, none of these antagonists
demonstrated clear efficacy in human phase III trials. Trials with cerestat (CNS 1102),
selfotel, ZK-200775, eliprodil, and lubeyusole did not demonstrate significant benefits
for the treated group.
Calcium-Channel Blockers:
Calcium-channel blockers theoretically could play an important role in
neuroprotective treatment. The mechanism would be the interruption of calcium flow
into the cell, which would prevent the ischemic cascade and improve post-ischemic
hypoperfusion. Five main calcium-channel receptors have been described to date. But
what are the important channels with respect to the central nervous system?
Because of their clinical availability, long-lasting L-type channel antagonists
(nimodipine and nicardipine) have been studied the most regarding neuroprotective
effects. It has been hypothesized that nimodipine could influence subarachnoid
hemorrhage because of its vasodilatory effect. MK-801:
MK-801 is an experimental drug with NMDA- receptor antagonist action. It is an
NMDA-receptor blocker (it block calcium channel of the NMDA receptor). By entering
the ion channel and binding to the phencyclidine receptor site, MK-801 can block
calcium entry into the cell. However, it also has the potential for adverse effects. Other
compounds, such as dextrorphan and ketamine, are similar to MK-801 in their ability to
block NMDA receptors. Short-term acute antagonist therapy with these agents will
probably be manageable, but chronic therapy can have adverse effects on normal CNS
processes such as learning and memory.

-Second Edition
2011

223


Free Radicals and Lipid Antioxidants
Free radicals and lipid antioxidants are believed to have neuroprotective
properties. They have been effective in reducing neurologic damage in some animal
models. Endogenous enzymes such as glutathione peroxidase, superoxide dismutase
(SOD), and catalase have been shown to provide protection against free-radical damage
in models of brain injury. Polyethylene glycol-SOD and tirilazad are also target reactive
oxygen species. Although there is evidence that these compounds are neuroprotective
in animal models of brain injury, recent human studies have failed to demonstrate any
significant benefit in the treated groups. Despite the difficulty of proving the benefit of
these models, research to discover the ideal antioxidant is ongoing.
Nitric Oxide: Nitric oxide (NO) by itself can be toxic or neuroprotective, depending on
its redox state. The NO radical is toxic, whereas the NO+ nitrosonium is neuroprotective.
Administration of NO in rabbits and rats caused the beneficial effect of early restoration
of cerebral circulation after cerebral ischemia. There are several forms of Nitric oxide
synthesis (NOS) including neuronal and endothelial. Several studies have demonstrated
that activations of neuronal NOS exacerbate ischemic necrosis. On the other hand,
endothelial NOS is neuroprotective. As yet, we do not know how to selectively activate
one type of NOS over the other.
Caspases:
Caspases (cystein aspartate-specific proteases) are also essential for the process
of apoptosis. To date, at least a dozen caspases have been described. Caspase 3
(mammalian cystein protease) activity contributes to delayed neuronal death after
transient ischemia. Selective and nonselective caspase inhibitors attenuate infarction
size in several models of injury.
Intraventricular injections of caspase inhibitors have demonstrated decreased
caspase-3 activity and infarction volumes in a mouse model of transient global ischemia.
These antiapoptotic caspase inhibitors can be successfully used in combination with
other drugs. Synergistic effects of dextrorphan and cycloheximide (the antiapoptotic
drug that blocks mRNA production) reduce infarction volumes after transient focal
ischemia by more than 80%. Co-administration of MK-801 with zVAD fmk (caspase
inhibitor) causes a reduction in infarction size.
Calpains:
During the process of the biochemical cascade leading to cell death, a rise in
intracellular calcium also activates calpains, which are cytosolic neutral cysteine
-Second Edition
2011

224


protease that degrade into small molecular fragments. The resulting compounds cause
irreversible proteolysis of critical cytoskeletal and membrane-associated proteins.
Several selective and membrane-permeable calpain inhibitors have been developed,
and some of them have demonstrated a reduction in infarction volume in animal
ischemic models. There are some advantages to calpain inhibit calpain damage is
extended. Also, the side effects are not as severe because calpain is not involved in
critical neuron communication. Once again, human clinical trials are lacking.
Inflammatory Agents:
An inflammatory cascade in the ischemic zone frequently accompanies cerebral
ischemia and reperfusion. Migration of leukocytes into the ischemic zone may begin
within 6 hours of reperfusion. Calcium-induced elevation of the level of cytokines is
very important in experimental brain injury models. It was demonstrated that the level
of cyclooxygenase-2 (COX-2, the enzyme that is involved in synthesis of inflammatory
prostanoids) is increased in traumatic brain injuries, and that selective COX-2 inhibitors
may play in important role in the treatment of these injuries. It is important that COX-2
inhibitors do not affect platelet aggregation and thromboxane, and so they do not cause
increased bleeding. Unfortunately, although oral formulations of these COX-2 specific
inhibitors are readily available in clinical practice, an intravenous formulation is still not
available, and ketorolac is not specific enough.
In the future, neurotrophic and growth factors will play a very important role in
brain protection. Multiple different growth factors have been described. They support
neuronal survival and speed up the recovery from brain injury. Their neuroprotective
effects have been demonstrated in phase I and phase II trials. Nerve growth factor,
nuclear immediate early response genes, free-radical scavengers, adenosine and other
endogenous defenses work to lessen the damage. The neuroprotective agents and
anesthetic techniques widely used in the operating room to protect the brain. They are
the following:
1. Hypothermia
2. Barbiturates, propofol, etomidate
3. Inhalation anesthetics
4. Magnesium
5. Lidocaine
6. Hypocarbia
7. Hemodilution; colloid versus crystalloid solutions
8. Glucose solutions versus normal saline

-Second Edition
2011

225


Hypothermia:
The use of hypothermia date back to the 1940s, when it was used in an attempt
to slow down the progress of metastatic carcinoma. Moderate hypothermia for repair of
intracranial aneurysms was introduced in the late 1950s. In the 1950s and 1960s,
hypothermia was used for patients with head injury, on cardiopulmonary bypass, and
after resuscitation from cardiac arrest. Mild hypothermia by surface cooling in humans
has been used effectively for brain protection since 1980.
It is well established that when ischemia reduces oxygen supply, hypothermia
reduces oxygen demand. By decreasing whole body and brain metabolic rate (CMRO2)
by hypothermia, oxygen requirements are reduced and the brain protected.
Oxygen consumption is reduced about 7% per degree Celsius decrease in body
temperature. However, a decrease of CMRO2 is not considered to be the only major
mechanism for neuro-protection. Hypothermia also positively affects the ischemic
cascade by reducing glutamate, glycine, and dopamine release, inhibiting protein Kinase
C, and reducing free-radical-triggered lipid peroxidation. It also causes an increase in
cell-membrane stability and restores the blood-brain barrier.
The following appear to be 3 factors that influence the effect of hypothermia in
patients with brain injury: time of onset, duration, and depth of hypothermia. It has
been shown that patients with hypothermia on admission had the lowest percentage of
poor outcome after brain injury.
Patients with Glasgow coma scores of 5 to 7 on admission had faster neurologic
recovery and better outcome if they were treated with moderate hypothermia soon
after injury. Patients with Glasgow coma scores of 3 or 4 did not show improvement
from hypothermia. It has been shown that comatose patients with cardiac arrest
pretreated with mild to moderate hypothermia had improved neurologic outcome and
reduced mortality. In terms of duration of hypothermia, if it is aborted prematurely, cell
death can occur.
The depth of hypothermia is very important. Advanced research in brain
protection enabled the introduction of profound hypothermia with circulatory arrest.
Profound hypothermia with circulatory arrest. Profound hypothermia to 15
0
C was used
for aneurysm repair requiring cardiopulmonary bypass. Today this technique is very
rarely used. However, mild hypothermia (33-34
0
C) has experienced a new wave of the
interest in neurosurgical procedures. Mild hypothermia has been broadly used as a
protective therapy during intracranial aneurysm surgery.
Despite the fact that hypothermia is one of the most effective methods of brain
protection for global and local ischemia, it has numerous adverse effects that need to be
considered. Use of hypothermia can be associated with bleeding dyscrasias, atrial or
-Second Edition
2011

226


ventricular arrhythmias, acidosis, sensory neuropathies, slow emergence, and shivering
if appropriate rewarming is not done.
Currently, mild hypothermia (33-35
0
C) is widely used in operating rooms by
anesthesiologists for brain protection during neurosurgical procedures, most commonly
during cerebral aneurysm clipping. It is accomplished by the infusion of cold
intravenous fluids and by surface cooling of the patient. Unfortunately, the
intraoperative benefit of hypothermia may not carry positive effects into the post-
operative period. Therefore, the long-term benefit of hypothermia for brain protection
remains to be determined.
Barbiturates, Propofol, Etomidate, Volatile Anesthetics, Lidocaine :( for details refer
pharmacological neuro protection)
Magnesium:
Magnesium is one of the agents used for brain protection. It has been proven in
animal studies that magnesium has significant neuroprotective effects in both global
and focal cerebral ischemia and head trauma. It has been shown that intraneuronal and
cerebrospinal fluid magnesium levels were decreased after stroke and brain trauma.
The neuroprotective action of magnesium is likely to be explained by the fact that it is a
NMDA receptor and/or voltage-dependent calcium channel blocker, glutamate
antagonist, and free-radical antioxidant. In addition, magnesium can improve CBF
resulting from cerebrovascular dilation.
However, there are a number of issues that remain to be clarified, including the
route of administration, dose schedule, and appropriate magnesium salt. A variety of
different administration routes have been used. The most common is intravenous
administration of magnesium with an initial bolus followed by continuous infusion. It
has been suggested that serum magnesium levels should be empirically elevated to
twice physiological levels. Magnesium also may be injected intrathecally, which can
prevent spinal cord ischemia.
Unfortunately, multiple studies came to the conclusion that magnesium offers
more neuro-protection when administered preischemically as opposed to post
ischemically. It is remarkable that both MgSO4 and MgCl2 are neuroprotective
preischemically, but only MgSo4 is neuroprotective 8 hours after ischemia.
Magnesium is cheaper and more readily available than other neuroprotective
agents. Magnesium also has a limited and well-established side-effect profile.
The neuroprotective action of magnesium in stroke, head trauma, and cardiac
surgery patients is now being tested in larger studies to confirm earlier findings.

-Second Edition
2011

227


Hypocarbia:
Hyperventilation has always for control of intracranial hypertension in patients
with TBI. Recently, this view has been challenged. Decrease of carbon dioxide content in
the blood causes cerebral vasoconstriction and reduction in cerebral blood volume and
CBF. Reduction of CBF may lead to a worsening of ischemia and affect outcome. On the
other hand, moderate transient hyperventilation can temporarily improve the efficiency
of autoregulatory responses that are disturbed in severe head injury.
This improvement can be achieved by different mechanisms such as improved
cerebral perfusion pressure (CPP), alterations in cerebrospinal fluid pH value, increase
in vascular tone, and increase in adenosine level in the brain. It also has been shown
that hyperventilation can increase extracellular concentrations of brain injury
mediators such as glutamate, lactate, and pyruvate in the ischemic penumbra.
Although moderate hyperventilation improves autoregulation, it is a temporary
response, because after prolonged hyperventilation vascular tone returns to baseline
and improvement in autoregulation may be lost. Despite continuous hyperventilation,
the vessels return to their baseline diameter within 20 hours. Therefore, we should use
hyperventilation in the operating room with extreme caution. Hyperventilation should
be mild to moderate and extend for a limited period of time (less than 4 hours). We
should use it in TBI when necessary, and avoid it in craniotomies for aneurism clipping
because of the possibility of vasospasm.
Hemodilution: Colloids versus Crystalloids Solutions:
Hemodilution is the most important issue related to fluid administration in
patients with cerebral ischemia. Hemodilution reduces blood viscosity, which can
improve cerebral perfusion and CBF. Normovolemic hemodilution in the acute phase of
stroke increases CBF and improves EEG activity. Patients with subarachnoid
hemorrhage can reverse neurological deterioration due to cerebral vasospasm by
hypervolemic hemodilution.
There are 2 issues that can complicate the patients condition after hemodilution;
hypervolemia can produce cardiac failure or myocardial ischemia in the presence of
coexisting cerebrovascular or coronary occlusive disease. On the other hand, reduction
in blood oxygen content may decrease oxygen delivery to the ischemic area of the brain.
Therefore, hemodilution has to be performed carefully. It has been shown that for brain
protection, the optimum hemodilution should be ~ 30%. Hemodilution with colloids is
more beneficial than crystalloid hemodilution in focal cerebral ischemia.
The results of different studies strongly supported the concept that albumin therapy is
beneficial in transient focal ischemia if applied soon after insult. Albumin diminishes the
volume of the brain infarction and swelling, and increases local perfusion to the
-Second Edition
2011

228


infracted zone. Because of blood-brain barrier interruption, albumin can penetrate
cortical parenchyma and protect neurons from ischemic injury.
Other effects of albumin therapy are the following: hemodilution effect, antioxidant
properties, endothelial effect by maintaining normal micro vascular permeability and
inhibition of endothelial cell apoptosis, and anti-edema effect by crossing the damaged
blood- brain barrier and holding the fluid within the ischemic area.
It has been concluded that 20% mannitol also has a neuroprotective effect. In a rat
model of cortical ischemia, it caused a decrease in water in the ischemic area as well as a
decrease in tissue pressure. It is important to note that mannitol has better
neuroprotective effects if administered after rather than before the production of
ischemia.
Glucose Solutions versus Normal Saline
Based on many animal and human studies, it has been concluded that hyperglycemia at
the time of onset of brain ischemia (global and focal) worsens post ischemic neurologic
outcome. It is also a prognostic indicator of poor outcome in subarachnoid hemorrhage
and acute ischemic non lacunar stroke.
The most important mechanism by which glucose enhances cerebral ischemia is an
increase in lactate production (acidosis). But this is not the only mechanism of
worsening cerebral ischemia caused by an elevated blood glucose level. Hyperglycemia
also induces progressive cerebrovascular changes, and causes more severe breakdown
of the blood-brain barrier. It aggravates production of hydroxyl free radicals, which
further increases an already ischemic brain-cell acidosis, and exacerbates DNA
fragmentation induced by ischemia.
On the basis of these factors, it is recommended to monitor blood glucose concentration
closely in patients who are at increase risk for cerebral ischemia. Maintenance of
normoglycemia is recommended. In the operating room, it is important to draw glucose
levels often because of the use of corticosteroid drugs during some neurosurgical
procedures. Crystalloid solutions, containing glucose or Lactate Ringer solution, should
not be used. For patients with diabetes mellitus, infusion of insulin with dextrose should
be considered.

-Second Edition
2011

229


Chapter 17 - PHARMACOLOGICAL NEUROPROTECTION
The term 'Neuro protection' signifies treatments used to protect neural tissue from
cellular events induced by deprivation of oxygen or glucose or both to the brain.
Neurons are particularly susceptible to ischemic injury because they have a higher
demand for energy and limited energy stores. Depletion of intrinsic central nervous
system energy stores occurs within 2 to 4 minutes of anoxia. Important strategies in
neuro protection include maintenance of normoxia & adequate cerebral perfusion
pressure, maintenance of mild hypothermia, timely surgical intervention &other
methods (such as mannitol) to reduce increasing intracranial pressure (ICP), and
several methods of pharmacological neuro protection.
Cellular energy failure threatens cell survival in 3 ways. 1) In the absence of adequate
energy stores, anaerobic glycolysis is stimulated, leading to lactic acidosis. 2) Energy
failure disrupts ion homeostasis. Cellular influx of sodium & chloride with osmotically
obligated water and the influx of calcium occur. 3) Breakdown of cell structure occurs
and is due both to a loss of ATP-and to a rise in calcium concentration.
The concept of an ischemic penumbra, the final lesion following middle cerebral artery
occlusion consists of a central focus which always becomes infarcted unless reperfusion
is quickly established, and a perifocal area which may be prevented from doing so not
only by reperfusion but also by drugs. Pharmacologically the penumbra may be defined
as that part of an infarct, which is potentially salvageable. The finding of separate blood
flow thresholds for cessation of electrical signals & for loss of ion homeostasis led to the
concept of the ischemic penumbra. The perifocal tissues contain electrically in excitable
but essentially viable cells. With time, the infarct grows in size because the perifocal
tissues are recruited in the infarction process. This implies that a 'therapeutic window'
exists during which perifocal tissues may be salvaged by reperfusion or by use of
pharmacological agents that support cells at risk over a critical period.
Cerebral protection may be initiated prior to the occurrence of brain ischemia. Certain
prophylactic, measures can interfere with the cascade of events triggered by the injury.
Such a salutary effect may be achieved by reducing demand for energy (using
barbiturates or hypothermia) or blocking mediators of ischemic injury. In designing the
anesthetic plan for patients at high risk of cerebral ischemia (e.g., carotid
endarterectomy, open-heart procedures), it is useful to consider the relative degree of
protection provided by various agents. Treating patients with neuroprotective agents
after cardiac arrest or a focal ischemic insult may be a consideration in improving
overall neurological outcome. Focal ischemia encompasses stroke, subarachnoid
haemorrhage (SAH) and trauma. With few exceptions, animal studies have shown that
therapeutic efficacy is lost if treatment is delayed more than 1 hour after impact. Sooner
the neuroprotective drug is given, the better. The requirement for informed consent in
-Second Edition
2011

230


the clinical situation (such as road accident) may preclude administration of neuro
protectants within the laboratory-defined therapeutic window of efficacy.
Pharmacological brain protection may be employed to rest the brain while a temporary
regional disruption in nutrient flow is expected to occur. Appropriate monitoring (EEG,
evoked potentials, stump pressure, trans-cranial doppler) is needed to optimize
therapy.
Multimodality neuro monitoring facilitates tailoring neuro protection protocols to
various clinical circumstances. This permits rapid application of the most appropriate
means for correcting an imbalance. Electroencephalography has been used to assess the
electrical activity of the brain. Hypoxia and ischemia are commonly associated with
changes in electrical activity. With EEG monitoring, barbiturate therapy can be titrated
to the point of burst suppression. Transcranial Doppler ultrasonography, which
measures blood flow velocity, is finding usefulness for the identification of both low
flow states and embolic phenomena. Reflectance oximetry, by using a fiberoptic
catheter has allowed for continuous jugular venous oxygen saturation monitoring. This
saturation is a measure of global cerebral oxygenation and the normal value is about 55
to 75%.
Continuous near-infrared spectroscopy (NIRS) monitoring may prove useful in
determining episodes of impaired cerebral oxygenation. NIRS continues to examine the
oxygenation state of capillary hemoglobin even during deep hypothermic circulatory
arrest (DHCA). Neurochemical monitoring is the use of microdialysis for sampling of
chemical substances from the interstitial fluid of the brain. In vivo microdialysis may be
performed intraoperatively and as a bedside monitoring in the intensive care unit.
Application of microdialysis in neurosurgery and neuro intensive care is rapidly
expanding in a number of clinical centers around the world. Many interstitial markers
reliably reflect secondary brain ischemia & infarction. pH is used for monitoring
acidosis. Glutamate has been used as markers for excitotoxity. Increased lactate and
decreased glucose, indicating accelerated glycolysis commonly occurs with cerebral
ischemia or hypoxia.
There are many clinical situations in which brain protection is considered a major goal
of treatment.
I. Perioperative brain protection
1) Cardiopulmonary bypass (CPB)
In cardiopulmonary bypass, there is evidence of marked focal ischemic insult due to
micro gaseous or thrombotic emboli and at least subtle neuropsychological
deterioration in approximately two-thirds of cases. Several studies demonstrated
protective effects- of thiopental in humans during cardiopulmonary bypass.
-Second Edition
2011

231


It is found that reduced neuropsychiatric complications in patients undergoing open-
ventricle cardiac surgery when 30 to 50mgkg
-1
of thiopentone was administered during
bypass. Inotropic & vasoconstrictive agents were required after separation from bypass
& in the intensive care unit (ICU). This study used a bubble oxygenator & no arterial
filter & did not involve hypothermia. Was thiopentone effective because of cerebral
vasoconstriction & a lower cerebral embolic load during normothermic conditions
(37C), an advantage that could be insignificant in hypothermic CPB? This mechanism
might explain the absence of any cerebral protective effect of thiopentone in Zaidan et
al's study" of coronary artery bypass graft patients who were moderately hypothermic
during CPB.
Pascoe et al retrospectively reviewed 236 adult cardiac surgical patients who had
received a mean of 30mgkg
-1
of thiopental before open chamber cardiac surgery.
Inotropic requirements were not increased & no complications were reported.
2) Deep hypothermic circulatory arrest (DHCA)
DHCA is used to facilitate surgery in complex congenital cardiac malformations, aortic
arch replacement and giant intracerebral aneurysms of the posterior circulation. DHCA
is currently standard practice for aortic arch repair. The most important problem with
this technique is the limited time allowable for circulatory arrest before cerebral
ischemic damage arises. The safe period for DHCA is generally considered to be 60
minutes or less. Cerebral ischemic time exceeding 45 minutes was associated with a
high risk of stroke. Complicated surgery frequently requires longer period of circulatory
arrest thus necessitating increased protection against cerebral ischemia. Barbiturates or
etomidate or propofol have been used before DHCA to convey additional cerebral
protection.
When DHCA is to be employed, many anesthesiologists choose to administer
barbiturates because they may offer additional neuro protection beyond that provided
by hypothermia alone. It appears that the cerebral protective properties of barbiturate
anesthesia & hypothermia are additive, increasing the tolerance of the cerebral tissues
to temporary global ischemia. Cooling is an imperfect process & barbiturates may
provide a safety net in the case of focal incomplete cooling. A second and perhaps more
compelling reason for administering barbiturates before DHCA is the probability that
they provide neuro protection against air emboli during the , rewarming period.
If thiopental is administered shortly before the onset of circulatory arrest, blood & brain
tissue levels will be present when bypass flow is restarted because no redistribution or
hepatic metabolism will occur during arrest. Thus, the brain should benefit from
barbiturate neuro protection throughout the rewarming period & potentially into the
early post bypass period, when it is no longer protected by hypothermia.
-Second Edition
2011

232


There are 2 reasons why thiopental should not be administered early in the cooling
phase. 1) At normothermia & hypothermia, barbiturates cause cerebral
vasoconstriction & reduce cerebral blood flow to nearly half of control values. If
barbiturate is administered before the onset of CPB or early during the cooling process,
it may impair effective brain cooling because effective global cooling is dependent on
cerebral blood flow. 2) Barbiturates prevent the increase in high-energy phosphate
stores & intracellular pH in the brain that normally occurs during cooling. This finding
suggests that early thiopental administration may be detrimental because it may impair
the brains ability to prepare for the period of arrest.
If barbiturates are withheld until reaching 18C, cerebral energy state should be
expected to increase normally & barbiturates may then be administered just before
arrest to maximize metabolic suppression. The onset of circulatory arrest should be
delayed by 5 minutes after barbiturate administration to allow effective circulation to
the brain.
Rung et al reported a series of 15 infants who received a thiopental dose of 8mgkg
-1

before DHCA. Free serum thiopental concentrations were 8.9 gml
-1
before arrest, 9.2
gml
-1
at the onset of rewarming, & 3.2 gml
-1
after separation from CPB. All infants
except one separated easily from bypass without inotropic requirements. In general, a
thiopental dose of 10mgkg
-1
is hemodynamically well tolerated in nearly all neonatal
infants when administered before circulatory arrest & does not seem to be associated
with difficulty in weaning. Stone et al reported 24 adult neurosurgical patients
undergoing cerebral artery aneurysm clipping who received a mean of 45mgkg
-1
of
thiopental before CPB & DHCA. All patients separated easily from bypass without
inotropic support.
Burst suppression or isoelectric EEG for cerebral protection:
Doyle PW and Matia BF have shown that in humans, there is a greater reduction in
cerebral blood flow with a completely isoelectric EEG than with 50% burst suppression.
Reduction in EEG activity was associated with a significant reduction in middle cerebral
artery flow velocity (VMCA), but a constant cerebral arteriovenous O2 difference (A-V
DO
2
) suggesting intact flow metabolism coupling. If flow-metabolism coupling is
maintained, the assumption that cerebral metabolism during 50% EEG burst
suppression is equivalent to isoelectric EEG may not be justified. They have concluded
that if suppression of metabolic activity has a part in cerebral protection complete EEG
silence may give more protection than 50% burst suppression.
Hirotani et al studied 50 patients who underwent aortic arch repair under DHCA. EEG
and partial pressures of O2 in the internal jugular vein (PjO2) were monitored. Systemic
cooling was continued until the body temperature reached 2 to 3C below the
temperature at which EEG activity totally disappeared. After the temperature and PjO2
-Second Edition
2011

233


had stabilized, 15 or 30mgkg
-1
thiopental was infused into the venous reservoir of the
CPB circuit. In addition, 20mg nicardipine and 300ml mannitol were also administered
in the venous reservoir. Circulatory arrest was established 5 minutes after the infusion
of thiopental, nicardipine, and mannitol. After thiopental infusion, PjO2 increased
significantly from 430 to 499 mmHg, indicating that thiopental reduces cerebral
O2consumption. The cerebral metabolic rate during circulatory arrest is considered to
correlate with the rate of decrease in PjO2. The rate of decrease in PjO2 during
circulatory arrest was slower with the higher thiopental dose, suggesting that when,
more thiopental was infused before circulatory arrest, the brain consumed less O2
during circulatory arrest, and so the time allowable for circulatory arrest could be
extended. As a result of the use of a pharmacological combination of thiopental,
nicardipine, and mannitol, there was no neurologic complication attributable to
extended circulatory arrest duration although there were 21 patients (42%) in whom
the DHCA time exceeded 45 minutes. 4 patients required DHCA time over 60 minutes &
no neurologic complication was observed in them.
3) Carotid surgery
It is generally agreed that the main cause of ischemic damage during carotid
endarterectomy is the formation and migration of emboli from the plaque. A decrease in
cerebral perfusion during clamping can also lead to brain ischemia. Some surgeons and
anesthesiologists consider it very important to use cerebral protection methods during
cross clamping. They point out that use of pharmacological brain protection may
obviate the need to place shunts. Spetzler et al used barbiturate therapy in more than
400 carotid endarterectomy. Before the planned period of temporary vascular occlusion
during surgery, patients were given thiopental until the point of EEG burst suppression.
This degree of cerebral protection has been adequate with respect to EEG response for
most patients. Approximately 2% of the patients will show a profound asymmetry in
EEG activity, despite burst suppression with depression of ipsilateral hemisphere
following occlusion of the carotid artery. These patients are treated with a temporary
shunt in addition to barbiturate anesthesia. Frawley J et al, who use thiopental for
protection, have not noted large decreases in cardiac output or drops in BP. Those who
do not employ pharmacological cerebral protection methods point out that monitoring
for cerebral ischemia & placing a shunt if it develops obviate the need for pharmacologic
protection. They also point out that thiopental at doses required for cerebral protection
may decrease mean arterial BP and cardiac output, thereby causing decreased effective
cerebral perfusion. Drugs used for cerebral protection may leave the patient sedated for
a number of hours after the procedure. This may inhibit neurological evaluation in the
immediate postoperative period, which is considered important for picking up cerebral
perfusion abnormalities.
-Second Edition
2011

234


Frawley JE reported that in a prospective study of 37 carotid endarterectomy, cerebral
protection prevented intraoperative ischemic stroke, safely replaced intraluminal
shunting as a means of ischemic stroke prevention and has no inherent stroke risk.
These authors have suggested that thiopental protection may be preferable to shunting
(shunting has its inherent risk). Techniques such as awake patient monitoring under
local cervical block anesthesia and stump pressure measurement, which are designed to
indicate the necessity for shunting, become no longer applicable if no shunting need be
applied. High dose thiopental was used for cerebral protection in all patients. The drug
was titrated by hand injection in doses sufficient to produce burst suppression activity
on continuous EEG monitoring, with minimum inter burst intervals of 60 seconds. The
total dose of thiopental required to produce this burst suppression pattern & maintain it
during the carotid occlusion period by incremental bolus doses varied from 1350mg to
4000 mg (average 1800mg). Ischemic EEG changes that appeared with carotid occlusion
were managed by increasing the inter burst interval to as long as 5 minutes by
administration of further bolus doses of thiopental. No further thiopentone was given
after completion of endarterectomy and clamp release. During the period of thiopental
administration, nitrous oxide and isoflurane were discontinued and anesthesia relied on
oxygen and thiopental.
When cerebral protective drugs are employed, they must be given prior to the carotid
cross clamping. If drug treatment is initiated after cross clamping, areas of lowered
cerebral perfusion may not get adequate doses of the drug (for maximum protection)
from collateral flow. Continuous IV infusions are better than intermittent infusions for
cerebral protection. Intermittent boluses of thiopental give protection for
approximately 15 minutes. Cross clamping can last for periods of 15 minutes to 1 hour.
After the bolus is given and the carotid cross clamp is applied, the protective effect will
be decreasing while the ischemic risk is increasing. This implies that a number of
boluses must be given. Repeated boluses of thiopental may produce prolonged
drowsiness after anesthesia. This is undesirable. Another problem with bolus injection
of a cerebral protectant is that the high dose required to achieve the desired effect may
go too far & cause a flat line on the EEG. This is undesirable in this situation because flat-
line effect of the cerebral protectant may mask the onset of ischemic changes on the
EEG. Continuous infusions of IV anesthetics have the benefit of maintaining their
cerebro-protective effect over the duration of the carotid occlusion period. Infusions
also allow the anesthesiologist to titrate the infusion rate carefully to maintain burst
suppression while minimizing the flat-line periods that occur with the bolus technique.
Etomidate may be used for cerebral protection in patients with a significant cardiac
history.
-Second Edition
2011

235


Intraoperative measurement of common carotid stump pressure, monitoring of
somatosensory evoked potentials or homolateral cerebral blood flow have been used to
guide the decision to use a temporary bypass shunt. Pharmacological brain protection
may be employed during carotid endarterectomy if electrophysiologic or clinical
evidence of ischemia does not resolve with conventional therapy such as increasing
circulating volume, increasing BP and shunt insertion. It may also be used if your
surgeon never shunts and EEG is not available for ischemia monitoring.
During carotid surgery, barbiturate-induced burst suppression consistently induces
significant inverse steal to such an extent that very significant increases in stump
pressure (up to 50mmHg) may be seen. Increase of stump pressure of this magnitude
explains a significant part of the 'protective effect seen with barbiturates in carotid
endarterectomy. Volatile agents suppress metabolism and are cerebral vasodilators. In
the same carotid model, stump pressure did not rise when sevoflurane was
administered to the same EEG effect as barbiturates, suggesting that inverse steal does
not occur with sevoflurane.
Barbiturates, mild hypothermia, mild hypocarbia and hypertension are recommended
for protection during regional ischemia as in carotid surgery.
4) Cerebral aneurysm surgery
During cerebral aneurysm surgery, temporary clamping of feeder vessel may become
necessary to control bleeding or for proper placement of the final clip. This is a valuable
technique. However, this practice is complicated by a risk of focal infarction, particularly
in sensitive areas of the brain such as that territory supplied by the middle cerebral
artery MCA. In this situation, pharmacological brain protection may be used to protect
against ischemic sequelae. Barbiturates have been widely used for the protection of
brain during aneurysm surgery.
Samson et al demonstrated that after induction of etomidate burst suppression, patients
routinely tolerated 14 minutes of temporary focal occlusion during clip ligation of
cerebral aneurysms. Charbel et al used an anesthetic protocol of mannitol and
pentobarbital bolus prior to and during temporary ischemia. They determined that the
maximal occlusion time without immediate postoperative neurological deficit was 8
minutes in their patients undergoing temporary occlusion of the middle cerebral artery.
Ogilyy evaluated 126 patients who underwent temporary clip ligation for aneurysms in
multiple locations. These patients were treated under a protocol of hypothermia,
induced hypertension, and intravenous mannitol. Ogilvy et al concluded that, in general
20 minutes was a critical threshold for focal infarction. They had excluded from analysis
those patients with infarction who demonstrated new neurological deficits
postoperatively that resolved within 2 hours. Lavine studied 49 operations in which
MCA aneurysm ligations were performed with the aid of temporary clips. In 38 of these
-Second Edition
2011

236


procedures, intravenous brain protection anesthesia (pentobarbital as primary
anesthetic) as a deliberate bolus prior to occlusion or propofol / etomidate or etomidate
and propofol or pentobarbital and propofol) was used. In the case of propofol and
etomidate, evidence of adequate brain protection was defined as the presence of EEG
burst suppression prior to and during iatrogenic focal ischemia. 11 of the 49 patients
received isoflurane, narcotics, benzodiazepines and no IV brain protection anesthesia
(IVBP). All received IV mannitol (1gkg
-1
) at the time of skin incision. The infarction rate
was 15.8% in the IVBP group versus 45.5% in the group that did not receive IVBP. The
maximal occlusion time without postoperative infarction was 13.6 6 minutes in the
IVBP group.
5) After cerebrovascular surgery
If an ischemic deficit is found which can be surgically corrected (intimal flap, thrombus,
or malpositioned aneurysm clip), pharmacological brain protection may be employed
while preparations are made to re-operate.
II) Subarachnoid haemorrhage
The most conspicuous cause of brain ischemia following subarachnoid haemorrhage
(SAH) is secondary "vasospasm". The use of nimodipine (60 mg every 4 hours for
3weeks) has shown some benefit in the management of vasospasm. A large controlled
British multicentre trial in 554 patients suffering SAH with all grades of severity showed
that with nimodipine as compared to placebo, the risk of cerebral infarction was
reduced by 34% and the incidence of poor outcome by 40%. Since that study,
Nimodipine has been widely accepted as a standard treatment in SAH patients in the
acute stage.
III) Stroke
Gelmers reported a reduction in mortality (8 deaths in the nimodipine group versus 19
deaths in controls) and improvement in neurological outcome in patients randomized
to oral nimodipine 120mgday' within 24 hours of stroke onset. 30 mg nimodipine was
given 4 times per day for 28 days. Those with moderately severe deficits at the
beginning of the study obtained the greatest benefit.
Estanol compared the effects of naloxone in 4 groups of patients: 1) CT proven cerebral
infarction of > 7 days duration; 2) Acute cerebral ischemia of less than 24 hours; 3) CT
proven intracerebral haemorrhage of less than 24 hours duration; and 4) Hyperacute
cerebral ischemia observed during angiography. Naloxone treatment, at a dose of
0.8mg, improved outcome in 7 of 20 patients with acute ischemia and was markedly
effective in each of 3 patients with hyperacute ischemia. In contrast, naloxone had no
effect in chronic cerebral infarction or in intracerebral haemorrhage.
-Second Edition
2011

237


Findings of these investigators suggest that intravenous naloxone treatment may be
used in the evaluation of acute cerebral ischemia to determine the potential reversibility
of such injury.
IV) Brain trauma
Ischemia is the most common type of secondary insult observed in head injuries.
Barbiturate may be used for immediate reduction of ICP. Nimodipine treatment has
been found beneficial in patients with SAH diagnosed on first CT.
High - dose barbiturate therapy is an appropriate intervention for lowering ICP in those
patients refractory to conventional management. Pentobarbital has been used
extensively for high dose barbiturate therapy because of the predictability of metabolic
clearance (serum half life 21 hours), the availability of serum drug levels, and the lack of
active metabolites. Serum drug levels of 25 to 40 mgl
-1
, are associated with barbiturate
induced coma, electrically silent EEG, and a maximal reduction in cerebral metabolic
rate (CMR). Successful loading with large doses of (36 mgkg
-1
) is possible without
cardio-respiratory collapse as long as cardiac output & cerebral perfusion pressure are
supported during the loading process. Vasoconstrictors, inotropes and volume
expansion may be required to support CPP. Once, a therapeutic barbiturate effect has
been achieved, a maintenance infusion of 1 to 3 mgkg
-1
hour
-1
is usually sufficient to
cover clearance of the drug. Continuous EEG monitoring is useful in tracking the depth
of barbiturate therapy.
V) Spinal trauma:
In patients treated within 8 hours of injury with high doses of methylprednisolone (30
mgkg
-1
bolus and 5.4 mgkg
-1
hr
-1
for 23 following hours), a certain degree of increased
recovery of neurological function was seen at 6 weeks and 6 months and confirmed at 1
year follow up. Following these results, the use of high doses of methylprednisolone has
become standard practice in some countries for patients suffering acute spinal cord
trauma.
VI) Induced (Deliberate) hypotension:
Theoretically the best recipe for cerebral protection in this setting involves both
metabolic suppression and cerebral vasodilatation. Total cerebral blood flow at any
given pressure (under equal conditions of electrical silence) is likely to be higher with
sevoflurane than with a barbiturate. Hence it is likely that an agent like sevoflurane may
be better than barbiturates in this setting, since it induces the triad of metabolic
suppression, hypotension, and vasodilation.

-Second Edition
2011

238


VII) After cardiac arrest:
A retrospective study examined the clinical outcome following cardiac arrest in 18
patients who received either the organic calcium channel blocker verapamil or the ionic
calcium channel blocker magnesium and 11 patients who were given neither drug.
Among the treated patients, 39% regained consciousness and 33% were neurologically
normal at 2 and 6 months, whereas only 27% of control patients emerged from coma &
none had a full neurologic recovery.
Mechanism of action of neuro protectant drugs:
Conventionally neuro protection by anesthetics has been considered in terms of their
ability to modify cerebral metabolic rate. Total CMRO2 consists of demand for energy by
cellular "housekeeping" functions (membrane function, mitochondrial function etc.) and
by neuronal electrical activity. Approximately 40% of energy produced is consumed in
the maintenance of neuronal and glial integrity & the remainder is used for
electrophysiological activity. Anesthetics appear only to depress metabolism associated
with neuronal electrical activity. Hypothermia suppresses both components of cerebral
energy utilization. Hypothermia, by depressing the rates of all biochemical reactions,
can reduce the energy requirements associated with maintaining cellular integrity and
may be neuroprotective even in the face of an isoelectric EEG.
However, available literature provides little support for the hypothesis that depression
of cerebral metabolic rate (CMR) is the principal means of anesthetic neuro protection.
First, the different susceptibilities of various brain regions do not reflect the metabolic
activity in these regions. Second, isoflurane, which has EEG and CMR effects of similar
magnitude to those seen with barbiturates, does not provide comparable neuro
protection. An article by Warner et al provides support for the notion that differences in
the degree of CMR suppression provided by various anesthetics may have limited
relevance with respect to the extent to which they protect the brain in the setting of
cerebral ischemia. Their observations also leave open the possibility that the protective
effects of volatile agents are the result of the prevention of a cerebral hyperthermic
response to ischemia. Thirdly, moderate hypothermia is more neuroprotective than
barbiturates at dosages that provide greater depression of CMR. There are many other
anesthetic effects, which may contribute to neuro protection These include reduction of
intracranial pressure (ICP), anti-convulsant action, free- radical scavenging, drug-
induced inverse steal, antagonism at voltage-sensitive calcium or sodium channels or
ligand gated calcium channels, potentiation of GABA menergic transmission or
attenuation of ischemia induce neurotransmitter release.
Drug-induced inverse steal requires reduction cerebral metabolism (usually to the point
of EEG burst suppression) with an agent, which maintains flow metabolism coupling.
-Second Edition
2011

239


This will result in reductions in blood flow in well perfused regions with subsequent
increases in upstream perfusion pressures leading to redistribution of this excess flow
down pressure gradient to more ischemic areas.
Thiopental and drugs that decrease CBF similar to thiopentone have the potential to
decrease the number of emboli delivered to the cerebral circulation. Presumably, for
such a mechanism to provide protection there must also be an accompanying decrease
in cerebral metabolism. Propofol has similar effects to thiopental on cerebral
metabolism and blood flow.
Hypocarbia worsens global ischemia (where redistribution cannot take place) since it
further reduces global cerebral blood flow. Prolonged hyperventilation has been shown
to worsen outcome following severe head injury. On the other hand, it seems likely that
hyperventilation is capable of protecting against major regional ischemia, such as
occurs during carotid endarterectomy by inverse steal.
There is reason to believe that thermoregulation is critical for defining the effects of
drugs on ischemic outcome. Mild reductions of temperature during global ischemia
reduce ischemia-induced elevations in extracellular excitatory amino acid
concentrations and associated neurologic/histologic damage. Further, ischemia induced
translocation of protein kinase C and induction of heat shock protein expression are
inhibited by mild hypothermia.
Anesthetic agents as neuro protectants:
A) Intravenous anesthetic agents
Barbiturates: Of the clinically available anesthetics, barbiturates have the
greatest potential to protect the brain from ischemic injury. Early studies in
cerebro protection suggested that barbiturate associated protection is mediated
via reduced metabolic demand. Greatest efficacy has been observed when EEG
activity remains present during the ischemic period (e.g. focal ischemia). Little
efficacy was observed when the EEG is ablated during ischemia. (e.g. complete
transient global ischemia). In global total ischemia or global total anoxia,
barbiturates only reduce the rate of ATP fall for the first 20 to 30 seconds. This is
because profound ischemia flattens the EEG in 15 to 20 seconds, after which time
the rate of ATP fall will be the same regardless of the presence or absence of
barbiturates. This contrast with hypothermia, which prolongs cell survival and
reduces the rate of ATP fall in proportion to the degree of hypothermia. Deep
barbiturate anesthesia can reduce CMR to the same extent as hypothermia to
30C.
Other potential beneficial effects of barbiturates are reduction of elevated
intracranial hypertension, producing favorable redistribution of blood towards
-Second Edition
2011

240


ischemic tissue by constricting the vessels in the non-ischemic cortex and
suppression of abnormal or seizure-like activity. It has also been suggested that
barbiturates exert neuroprotective effects through anti-oxidant or free radical
scavenging actions. Barbiturates may also reduce ischemia induced
neurotransmitter release. Inhibition of the release of excitatory
neurotransmitters (aspartate, taurine, glutamate and GABA) has been
demonstrated even if barbiturates are administered after the period of ischemia,
suggesting that at least some of the benefit occurs after reperfusion.
In patients with intracranial hypertension, barbiturate therapy would be
expected to reduce CMRO2, which limits cell energy demand at a time when
blood flow may be compromised. In these patients, barbiturates may increase
perfusion pressure through reduction of ICP (cerebral perfusion pressure=mean
arterial pressure-ICP).
Focal versus global ischemia Barbiturates appear to be protective in the setting
of focal and incomplete ischemia, but not complete, global cerebral ischemia.
In a randomized clinical study of 286 comatose cardiac arrest survivors, the
Brain Resuscitation Clinical Trial I Study Group found no significant
improvement with thiopentone loading within 50 minutes following cardiac
arrest. The failure to see a significant effect with post-treatment in global
ischemia is consistent with the abundant literature from animal models.
Barbiturate neuro protection is likely to be most marked in focal ischemia where
there remains a marginally perfused penumbral zone in which oxygen supply is
reduced but synaptic activity is still going on. Cardiac bypass offer a clinical
situation more akin to focal ischemia with the additional opportunity for
prophylactic treatment. Convincing evidence for efficacy of barbiturates has been
reported in patients with focal brain injury following open-heart surgery and
warm cardiopulmonary bypass. Nussmeier et al found reduced neuropsychiatric
complications in patients undergoing open-ventricle cardiac surgery when 30-50
mgkg
1
of thiopentone was administered during bypass. This study used a bubble
oxygenator, did not use arterial line filter and did not involve hypothermia.
16

Mechanism of protection during focal ischemia may be due to decreased
production of free fatty acids during ischemia or inhibition of excite-toxin
mechanisms.
Barbiturates appear to be only effective at brain protection, when ischemia is
incomplete, i.e. there is still some electrical activity. In focal ischemia, synaptic
electrical activities is partially preserved so that barbiturate therapy can reduce
CMRO2 and improve balance between energy demand and supply and therefore
be effective. In global ischemia (especially cardiac arrest), cerebral electrical
-Second Edition
2011

241


synaptic activity is already depressed, so that significant further reduction in
CMRO2 by barbiturates would not be expected, thus accounting for the
ineffectiveness of barbiturates in global ischemia.
Pentobarbital may be used for elective induction of barbiturate coma. It has a
serum half life (elimination) of about 30 hours. It is administered by a loading
dose (3 to 10 mgkg
1
) at 1 mgkg
-1
min
-1
, followed by continuous infusion at 1 to 2
mgkg
-1
hour
-1
. Monitoring of blood level and maintaining it at 25 to 40 gml
-1

range may prevent excessive recovery times from barbiturate coma.
Thiopentone is a rapidly acting barbiturate which is often used if the desired
effect is necessary immediately. In this context, doses of 3 to 5mgkg- IV will
produce transient (<10minutes) burst suppression & blood thiopentone levels of
10 to 30 mcgml
-1
. Following are the various regimens used:
1. High initial dose to produce burst suppression on EEG, which may or may not be
followed by an infusion. This use is applicable to situations of focal ischemia.
Loading dose consists of 25 to 50 mgkg
-1
. This is followed by an infusion 2 to 10
mgkg
-1
hr
-1
to give plasma concentration of 10 to 50 mgL
-1
. Accumulation occurs
and recovery may be prolonged over a period of days before neurological
assessment can be made. Nitrous oxide (N2O) is not used when barbiturates are
used for providing brain protection. This regimen is usually' reserved for high-
risk cases. The potential benefit should outweigh the necessity for postoperative
ventilatory and circulatory support. It is preferable that barbiturates be
administered prior to vessel occlusion so that it can circulate to the area, which is
to become ischemic. There appears to be a narrow therapeutic window post-
insult, during which therapy may also be effective. Treatment upto 2 hours post-
insult may be beneficial, but after this time, it may actually be harmful.
2. Low initial dose followed by infusion. This regimen is used to control ICP. A dose
of 1 to 3 mgkg
-1
IV is followed by an infusion of 0.06 to 0.2mgkg
-1
min
-1
. This
regimen is useful in head injuries to decrease raised ICP. Intermittent low doses
of thiopentone (1 to 3 mgkg
1
) will lower ICP and brain-bulk during intracranial
operations.
3. Small bolus dose for short term protection. A dose of 4 mgkg
-1
over 3 minutes
produces EEG burst suppression for about 6 minutes. This time is much shorter
than the probable period of surgically induced reversible focal ischemia (carotid
surgery or extracranial-intracranial bypass or temporary clamping during
surgery for management of intracranial aneurysm). It is suggested that the drug
may be delivered to the area to become ischemic prior to clamping. When
ischemia is induced after this, the level would remain high in severely ischemic
-Second Edition
2011

242


areas since the drug would not be washed out of the area. Local protective effects
could thus continue longer than the general EEG suppression. N2O is avoided.
Duration of therapy: When used prophylactically, therapy is usually discontinued
when the period of potential or actual insult is over. The duration of therapy when
instituted after an insult is controversial and has varied from bolus doses to infusions
for 24 to 72 hours or more. The long duration has been advocated because post insult
injury may last for this period and cerebral edema peaks at 48 hours after an ischemic
injury.
Timing of barbiturate therapy: Cerebral protection is best initiated prior to the
occurrence of brain ischemia. Barbiturate therapy appears to provide some benefit even
if administered after a focal ischemic insult. Barbiturates have been shown to diminish
infarct size (animal study) when administered after focal ischemia. A beneficial effect
was seen in primates when barbiturates were given upto 120 minutes after middle
cerebral artery occlusion.
Methohexitone is less frequently used because of the possibility of exacerbation of
seizure disorders.

Use In Head Injury: High-dose barbiturate therapy should only be considered for
hemodynamically stable salvageable severe head injury patients with intracranial
hypertension refractory to maximal medical & surgical ICP lowering therapy. One
randomized clinical protocol used a loading dose of 10 mgkg-1 of pentobarbital over 30
minutes, with 5 mgkg-1 every hour for 3 doses, and maintenance dose of 1 mgkg-1hr-1.
Pentobarbital dose should be adjusted to avoid systemic complications it to achieve an
EEG pattern of burst suppression.
Problems during barbiturate therapy:
1. Barbiturate therapy may cause depression of cardiac output and cerebral
perfusion pressure, and even frank cardiovascular collapse in poorly hydrated
patients as well as in those with a reduced cardiac function. It is often necessary
to reverse hypovolemia and provide pharmacologic inotropic support. This may
necessitate invasive cardiovascular monitoring including the use of pulmonary
artery catheter. Use of cerebral protection with barbiturates may be limited in
patients with a reduced cardiac function.
2. The profound respiratory depressant effect of barbiturates makes controlled
mechanical ventilation mandatory.
3. Long-term barbiturate therapy is associated with hypothermia and depression of
immune responses. This introduces the risk of pulmonary infectious
complications.
-Second Edition
2011

243


4. Neurologic evaluation of the patient in barbiturate coma is difficult. The use of
intracranial pressure monitoring devices and electrophysiologic monitoring (e.g.
evoked potentials, which can be monitored even when the EEG is isoelectric),
coupled with early CT scan, MRI or angiography can help identify adverse
developments in a timely fashion.
5. 99% of administered thiopental is metabolized in the liver. Therefore special
attention is required in patients with hepatic dysfunction.
6. Barbiturate coma should not be instituted lightly. A sophisticated intensive care
setting is required to support patients who are going to benefit from this mode of
therapy.
7. Ventilator Associated Pneumonia is very high patients on Barbiturate therapy.
2) Etomidate:
Like barbiturates, etomidate produces EEG burst suppression and reduces CMR for
glucose and oxygen. Clinically, etomidate decreases CBF, CMRO2, and ICP whereas
carbon-dioxide (CO2) reactivity, hemodynamic stability and cerebral perfusion pressure
(CPP) are maintained. It inhibits release of excitatory neurotransmitters. It may be
useful for neuro protection when temporary vessel occlusion is required. It is routinely
used in some centers to increase safety during temporary arterial occlusion employed
for surgery of complex cerebral aneurysms. Dose of 0.4 to 0.5 mgkg
-1
, cause burst
suppression in less than 2 minutes in the majority of patients, with a maximum drop in
BP of 5%. Consciousness is usually regained in 3 to 5 minutes due to redistribution.
Additional doses in increments of 0.l mgkghr
-1
may be given as electrical activity returns.
Batjers group report using etomidate 1 mgkg
-1
as a bolus followed by an infusion of 10
gkg
-1
to maintain burst suppression during temporary arterial occlusion for complex
intracranial aneurysms. This regimen was well tolerated.
Etomidate has a low incidence of hemodynamic instability at doses sufficient to depress
the EEG. In this respect, it has a major advantage over thiopental. However, etomidate
has been associated with significant adrenocortical suppression, even when
administered as a single injection. This effect of the drug has greatly limited its utility in
usual anesthetic care but not its utility in neurosurgical cases in which patients are
routinely administered high doses of steroids. EEG excitation, abnormal movements and
vomiting are other adverse effects that could occur. Etomidate has been associated with
renal failure presumed secondary to the propylene glycol vehicle.
3) Propofol:
The metabolic changes resulting from propofol anesthesia closely resemble the
homogenous depression of CMR caused by barbiturates and etomidate. Propofol
reduces cerebral metabolism with a consensual reduction in EEG activity,
-Second Edition
2011

244


O2consumption and cerebral blood flow. Propofol also reduces voltage-activated sodium
channel conductance at concentrations within the clinical range. Its antioxidant
properties may also be of benefit. High doses may produce hypotension, which reverses
rapidly upon discontinuation (usually within 5-10 minutes). Administration of propofol
to head injured patients with elevated ICP has been associated with a reduction in ICP
but also of CPP. Propofol infusion titrated to produce unresponsiveness (8 mgkg
-1
hr
-1
)
in humans, resulted in 55% depression in CMR for glucose, as measured using positron
emission tomography.
A study by J Gilbert Stone et al demonstrated that an EEG suppressive dose of propofol
does not depress cardiovascular performance or excessively prolong emergence from
anesthesia when administered, in conjunction with DHCA in 13 patients who underwent
cerebral aneurysm surgery requiring CPB and DHCA. Before initiating bypass, each
patient received propofol: first as a 1 mgkg
-1
bolus, and then by 100 mgkg
-1
min
-1
infusion. The dose was increased every few minutes until the EEG displayed a burst
suppression pattern with a 1:5 ratio. Within 20 minutes, at a propofol infusion rate of
between 200 and 300 mgkg
-1
min
-1
, burst suppression with a 1:5 ratio was achieved. The
infusion was continued at that rate until circulatory arrest, even though die EEG became
isoelectric during bypass cooling. When CPB was resumed, the propofol infusion was
begun again at the rate that provided pre bypass normothermic burst suppression and
continued until the end of surgery. There are reports of possible anaphylactic reaction
with angioneurotic edema of the airways. Seizure-like activity has been reported after
anesthesia with propofol
4) Ketamine:
Following ischemia, the pathological mechanism which results in cerebral infarction
involves the release of a number of neurotransmitters a major -one being N-methyl-D-
aspartate (NMDA). Ketamine is a non-competitive antagonist at NMDA receptors and
may therefore offer protection from the adverse effects of cerebral ischemia
B) Inhalational agents:
1) Isoflurane:
Isoflurane offers a similar level of metabolic depression as barbiturates at a
concentration less likely (than barbiturates) to be accompanied by severe
cardiovascular depression or prolonged recovery. Isoflurane can suppress brain
electrical activity to the point of isoelectricity at clinically useful concentrations
(<2MAC). Isoflurane is a potent inhibitor of CMR and CMRO2, in all species studied. In
addition to its GABAergic effects, isoflurane has also been shown to inhibit multiple
voltage-gated calcium currents in hippocampus pyramidal neurons. Isoflurane has been
shown to significantly inhibit glutamate receptor activation and ischemia induced
-Second Edition
2011

245


calcium influx. The majorities of human studies indicate that isoflurane below 1% has
little effect on ICP. Isoflurane at inspired concentrations of 0.6 to 1.1 MAC does not alter
CBF although 1.6 MAC doubles CBF. In a study to compare the relative effects of
isoflurane, enflurane, and halothane in a human model, Michenfelder al retrospectively
reviewed the incidence of ischemic EEG changes and the critical blood flow below which
these changes occurred following carotid occlusion during endarterectomy at the Mayo
clinic Consistent with a neuroprotective role of isoflurane, isoflurane-anaesthetized
patients demonstrated fewer ischemic EEG changes during carotid surgery than
patients anaesthetized with enflurane or halothane. The critical cerebral blood flow
(CBF) below which ischemic EEG changes occurred was 10ml100g
-1
min-
1
during
isoflurane anesthesia versus 15ml100g
-1
min
-1
during enflurane anesthesia. The
ischemic threshold (cerebral blood flow at which ischemic EEG changes occur) was
higher in halothane-anaesthetized patients (18 to 20 ml 100 g
-1
min
-1
, observed in a
previous study) as compared to patients anaesthetized with isoflurane (8 to 10 ml 100g
-
1
min
-1
). These results suggest some beneficial effect of isoflurane during transient
incomplete regional ischemia in humans.
2) Sevoflurane:
In common with isoflurane and barbiturates, sevoflurane produces a dose-dependent
decrease in CMR. Autoregulation appears to be well maintained in patients with
cerebrovascular disease undergoing sevoflurane anesthesia. In animal models,
sevoflurane not only reduced brain damage following focal ischemia but also improved
neurological outcome following incomplete global ischemia.
3) Desflurane:
Although thiopental treatment for brain protection is effective in decreasing ischemic
injury, the doses required for EEG suppression prolong recovery times. Inhalation
anesthetics such as desflurane can also produce EEG silence but allow a more rapid
recovery at the end of surgery. Desflurane treatment for cerebral protection
significantly increases brain tissue oxygenation and pH above control levels. Desflurane
attenuates hypoxic changes during brain artery occlusion. It also attenuates ischemic
lactic acidosis and decreases in pH during brain artery occlusion.
William E Hoffman measured brain tissue gases & pH during thiopental or desflurane
treatment that was administered for brain protection during temporary brain artery
occlusion in patients scheduled for cerebral aneurysm clipping or extracerebral-to-
intracerebral artery bypass. A neuro trend probe inserted into a tissue region
determined to be at risk for ischemia during brain artery occlusion was used to measure
brain tissue O2 pressure (PO2), carbon dioxide pressure (PCO2) and pH. Before brain
artery occlusion, one group of patients received thiopental, 1.5mgkg
-1
IV bolus, and then
-Second Edition
2011

246


1 mgkg
-1
min
-1
to produce burst suppression EEG. The other group received desflurane
(end-tidal concentration of 9%) to produce the same burst suppression pattern. Both
groups received phenylephrine infusion to maintain mean arterial BP greater than 90
mmHg during the period of burst suppression on EEG. Thiopental produced no change
in tissue gases or pH, but temporary artery clipping in thiopental-treated patients
decreased PO2 30%. Significant increases in tissue PO2 and pH and decreases in PCO2
were observed during desflurane treatment for brain protection. During brain artery
occlusion, tissue PCO2 and pH returned to baseline levels and tissue oxygenation
remained elevated in the desflurane group. The enhanced tissue oxygenation and CO2
clearance that is observed with desflurane may be caused by the cerebral vasodilating
effect of desflurane compared with thiopental.
4) Nitrous oxide:
Some forms of cerebral protection may be adversely affected by the presence of nitrous
oxide (N2O). In general, barbiturates have limited efficacy as cerebral protectants in
animal studies that employed nitrous oxide as part of the anesthetic management.
However, barbiturates were efficacious in those studies that did not employ nitrous
oxide as part of the anesthetic management.
Nitrous oxide decreases isoflurane efficacy as a neuro protectant when used during
incomplete cerebral ischemia in rat.
Non-anesthetic agents as neuro protectants:
1) Glucocorticosteroids:
Their efficiency in reducing vasogenic peritumoral edema is well documented. The
Second National Acute Spinal Cord Injury Study (NASCIS II) demonstrated that high
dose methylprednisolone (30 mgkg
-1
bolus followed by 5.4mgkg
-1
for 23 hours) was of
benefit in spinal cord -injury if treatment was instituted within 8 hours of injury. At
these doses, methylprednisolone inhibits lipid peroxidation of neuronal, glial, and
vascular membranes caused by O2 free radicals. Lipid peroxidation is a process
implicated in the pathophysiology of secondary central nervous system (CNS) injury.
Lower doses had proven ineffective in the NASCIS I study. It has been demonstrated that
similar high doses of methylprednisolone were of benefit in humans with severe head
injury. The major mechanism for the neuroprotective effect of Corticosteroids is
probably inhibition of lipid peroxidation. This effect is extremely dose-dependent,
which can account for methylprednisolone effect at high doses (30mgkg
-1
) but not low
dose. Methylprednisolone possible efficacy in subarachnoid haemorrhage induced
vasospasm has also been ascribed to inhibition of lipid peroxidation. The anti edema
effect of methylprednisolone may at least in part be a result of other actions that are not
-Second Edition
2011

247


so dependent on high dose administration. Gastrointestinal bleeding and infection are
two complications attributed to corticosteroids use. Glucocorticosteroids such as
dexamethasone and methylprednisolone cause or exacerbate hyperglycemia.
Hyperglycemia has been shown to increase brain injury in ischemia. When
corticosteroids are used it is essential to maintain precise control of blood glucose levels.
The use of glucocorticoids is not recommended for improving outcome or reducing ICP
in patients with severe head injury.
2) Tirilazad mesylate (TM):
Tirilazad mesylate (TM) is a 21-aminosteroid (lazaroid) that was developed specifically
to maximize the inhibition of lipid peroxidation by glucocorticoids such as
methylprednisolone, but eliminate the unwanted glucocorticoids effects. The lazaroid
are potent antioxidants, 100 times more potent than the corticosteroids, & therefore
may be efficacious in the clinical management of acute CNS injury. In animal
experiments, TM has been of benefit in both focal and global ischemia with reperfusion.
Its mechanism of action appears to be cell membrane preservation by inhibition of lipid
peroxidation. Brain levels of the antioxidants vitamin E and, to a lesser extent, vitamin C
are preserved in ischemia-reperfusion, when TM is used. Post ischemic recovery of
extracellular calcium is more rapid with TM use, as is the recovery of intracellular pH
and somatosensory evoked potentials.
In subarachnoid haemorrhage, a large phase II trial showed an improvement in
outcome with 6mgkg
-1
day
-1
(given in divided doses 6 hourly) lirilazad administered for
10 days. The effect was most marked in men in whom mortality was reduced from 20%
to 6%. Multicentre studies of high dose (15mgkg
-1
day
-1
) tirilazad in women have indeed
shown a significant reduction in the incidence of vasospasm associated with aneurysmal
subarachnoid haemorrhage and the mortality in patients who were neurological grade
IV or V on admission.
There is also increasing interest in using tirilazad in combination with thrombolytic
agents in the management of ischemic strokes.
3) Superoxide dismutase:
Superoxide dismutase (SOD) is a specific scavenger of superoxide anion. Superoxide
anion is capable of producing significant biological injury. It is generated on reperfusion
of post ischemic tissues. Because, Superoxide dismutase (SOD) has a biological half-life
of only 5 minutes, it has been conjugated with polyethylene glycol (PEG-SOD) for use in
humans, in a trial of PEG-SOD in patients with severe head injury, treatment was a
single bolus IV administration, with a mean time from injury to treatment of
approximately 4 hours. The % of time the ICP was above 20mmHg and the amount of
mannitol required to control ICP were less in the moderate-dose PEG-SOD (5000 Ukg-1)
-Second Edition
2011

248


and high-dose PEG-SOD (10000 Ukg
1
) treated patients than in controls. Furthermore,
outcome at 6 months was better in the high-dose PEG-SOD treated patients (i.e., fewer
vegetative or dead).
4) Nimodipine:
This drug antagonizes the entry of calcium into cells, which in turn ameliorates the
lactic acidosis, which occurs during ischemia. Nimodipine probably increases CBF,
particularly in regions of moderate ischemia. Nimodipine may be particularly effective
at neuro protection during hyperventilation, which is a common intervention during
brain surgery. Alkalosis is particularly detrimental to neuronal survival during ischemia.
The protection provided by nimodipine during brain retraction ischemia is not
surprising, in light of its amelioration of hyperventilation alkalosis.
Nimodipine is particularly effective in focal cerebral ischemia, and thus would be
expected to offer protection for intraoperative focal ischemia such as temporary vessel
occlusion and brain retraction.
In light of nimodipine safety as well as its efficacy when given prior to injury, it appears
reasonable to consider nimodipine for intraoperative use, particularly where focal
ischemia can be anticipated (e.g., brain retraction or temporary vessel occlusion).
Nimodipine has a beneficial effect on neurological outcome in patients recovering from
aneurysmal subarachnoid haemorrhage and has become a standard prophylactic
therapy in such patients. In these patients, use of nimodipine result in a lower incidence
of delayed ischemic deficits or death. This effect is thought to be mediated by
nimodipine effect on small vessel cerebral vasospasm. Treatment with Nimodipine
decreases BP, decreases systemic vascular resistance & increases cardiac output.
Nimodipine produced equivocal preservation of memory function 6 months
postoperatively in a small controlled cardiac surgical trial. However, a large placebo-
controlled trial" of nimodipine in patients undergoing cardiac valve replacement was
terminated early because of both an unexpected disparity in death rates between
groups and a lack of evidence of a beneficial effect of nimodipine. The lack of a
neuroprotective effect was disappointing and may be attributable to the fact that
nimodipine is a cerebral vasodilator, conferring a physiologic effect of increased
embolic load and obliterating any protective effect at the cellular and biochemical level.
Neurological outcome was found to be better in patients treated with nimodipine within
24 hours of the onset of ischemic stroke.
5) Nicardipine:
This drug is a calcium antagonist. Cerebral ischemia causes a rapid shift of calcium from
the extracellular spaces into cells. Nicardipine directly reduces calcium entry into
ischemic cells. Nicardipine has been administered into venous reservoir before DHCA.
-Second Edition
2011

249


6) Lidocaine:
Neuropsychologic deficits remain vexing complications after both coronary artery and
valve operations. Studying patients undergoing aortic or mitral valve operation, Mitchell
and colleagues found that a relatively simple and low-risk intervention, prophylactic
infusion of lidocaine, substantially improved neuropsychologic outcome at 10 days, 10
weeks, and 6 months compared to a placebo control. Lidocaine infusion was begun at
induction of anesthesia and continued for 48 hours. The infusion protocol was designed
to deliver a 1 mgkg-
1
bolus over 5 minutes, followed by 240 mg over the first hour,
120mg over the second hour, and then 60 mghour
-1
. Blood specimens for lidocaine
assay taken at 8 and 24 hours after starting the infusion were used to adjust the infusion
rate. The target plasma concentration of 6 to 12 mol litre
-1
was selected on the basis of
successful in-vivo & in-vitro trials of lidocaine in brain injury.
Possible mechanisms for cerebral protection by lidocaine include deceleration of
ischemic transmembrane ion shifts; reduction in CMR; modulation of leukocyte activity;
and reduction of ischemic excitotoxin release.
7) Furosemide:
It is a sulfonamide that inhibits distal tubular reabsorption. It has been shown to
decrease ICP effectively without the transient ICP increase that can be seen with
mannitol. An additional action of furosemide, which may be of benefit, is its reduction of
cerebrospinal fluid formation. The dose of furosemide may be upto 1 mgkg
-1
, depending
on the degree of diuresis required.
8) Mannitol:
Mannitol is widely used in neurosurgical operations involving patients with cerebral
edema and/or mass effect. Some of mannitols potentially beneficial effects include
osmotic diuresis, increased blood viscosity & free radical scavenging.
Mannitol is used for control of raised intracranial pressure (ICP) after brain injury. It
may be given even before computed tomographic scanning, e.g., in patients who develop
a fixed, dilated pupil or neurologic deterioration. This agent may also be used when high
ICP is demonstrated in the intensive care unit. It should be given as a bolus intravenous
infusion, over 10 to 30 minutes, in doses ranging from 0.25 to 1g kg
-1
body weight. It is
more effective and safer when administered in bolus infusion doses than as a
continuous infusion.
In patients receiving mannitol, hypovolemia should be avoided, serum Osmolarity
should be kept below 320 mOsm and serum sodium should be kept below 150mEqL
-1
.
Mannitol has been added to the venous reservoir before DHCA is employed. Mannitol is
well known to reduce cerebral edema after ischemia. Mannitol can also scavenge free
radicals & thus reduce tissue damage caused by superoxide radicals.
-Second Edition
2011

250


19) Papaverine:
It is a smooth muscle relaxant and may work by blocking calcium channels. It is used for
topical application on arteries to reverse vasoconstriction resulting from manipulation
(mechanical vasospasm). It has also been given as intra-arterial injection. However,
there is one case report of transient severe brain stem depression during intraarterial
papaverine infusion for cerebral vasospasm. Usual concentration used is 30mg in9cc
saline. It is applied on to vessels with gelfoam or cotton pledget soaked in this mixture &
left in contact with vessels for 2 minutes. The solution can directly be applied to the
vessels with a syringe and left in contact with them.
Local application of controlled-release papaverine drug pellets have been safely used in
preventing vasospasm. During cerebral aneurysm surgery, drug pellets were placed in
cisterns over arterial segments.
10) Insulin:
Elevated intracellular glucose concentration at the time of a cerebral ischemic insult
may result in increased cellular lactic acidosis, and this worsens ischemic injury.
11) Tromethamine:
Tromethamine (THAM), a weak base which crosses the plasma membrane and acts
directly on intracellular acidosis has been used with success in models of experimental
head injury. THAM has been used in head injuries in man with favorable effects on brain
edema and intracranial pressure.
12) Perfluorocarbons:
Use of Perfluorocarbons is a novel approach to decreasing cerebral emboli associated
with cardiac surgery. These compounds have high gas affinity and so may decrease
cerebral gaseous micro-emboli. They may improve flow characteristics in areas of
decreased perfusion.
13) Other drugs:
Levy and others have reported a trend toward decreased incidence of stroke in patients
receiving high-dose aprotinin. The mechanism of action it unknown; however it is
tempting to speculate that the anti-inflammatory properties of aprotinin may be
responsible.
A trial designed to determine the myocardial effects of acadesine, an adenosine-
regulating agent, demonstrated lower incidence of stroke in patients receiving the drug.
Again, the possible mechanism of action is unknown, but may involve decreased
excitatory transmitter release or reduced granulocyte accumulation.

-Second Edition
2011

251


Chemical brain retractor concept:
This concept includes the use of a total IV anesthesia technique, mild hypocapnia and
mannitol with strict monitoring and maintenance of the global cerebral homeostasis.
This contributes to decrease brain volume and ICP. It allows the best possible access to
the operation site, while avoiding excessive pressures under the surgical brain
retractors. Prevention of ischemic cerebral insults during neurosurgical procedures
includes maintenance of cerebral perfusion pressure and use of: 1) specific
pharmacological agents, 2) chemical brain retractor concept, 3) hemodilution and 4)
hypothermia.

-Second Edition
2011

252



-Second Edition
2011

253


Chapter 18 - RECENT ADVANCES IN NEUROPROTECTION
Abstract:
Neuro protection meant enhancing the tolerance of neuronal cells against
ischemia.
Neuro protection is afforded by affecting one or more biochemical and metabolic
consequences of ischemia and protecting at least part of the compromised brain tissue
from evolving into infarction.
The brain is an obligate aerobe with very little oxygen stores. The brains high
metabolic requirement (3-5mlO2/gm/mg) are usually adequately met by an oxygen
delivery of one and half to two times the requirement.
When O2 delivery fails to meet the metabolic requirement, a complex cascade of
biochemical events takes place, that results in ischemia as a mismatch between energy
supply and demand resulting in an excess of some substances i.e. calcium, excitatory
amino acids, hydrogen ions and a deficiency of other substances i.e. ATP, neurotrophic
factor.
As the initial event is a supply demand imbalance, many therapeutic
approaches attempt to redness this imbalance.
Techniques to improve oxygen supply:
Can be achieved by improving cerebral blood flow which includes hypertension
with and without hypervolemia.
Unresolved issues include the timing of hypertension (during ischemia or during
reperfusion), the extent and the duration of hypertension.
These techniques are not without risk, especially in the elderly and patients with
cardiac compromise.
The use of vasopressors for hypertensive therapy may result in myocardial
ischemia and hypervolemia which is associated with pulmonary edema.
Other techniques include the use of oxygen carrying compounds such as stroma-
free hemoglobin and perfluorochemical (i.e. flurol).
Technique to reduce oxygen demand:
The major techniques of suppressing metabolism during ischemia are the use of
anesthetic agents.
(Studies have showed) that barbiturate does not have a role in the treatment of
global complete ischemia following cardiac arrest, but the use of barbiturates in
incomplete ischemia (both global and focal) has role.
-Second Edition
2011

254


If barbiturates are to be given, they should be administered before the event in a
dose adequate to produce burst suppression / isoelectricity, and continued throughout
the period of risk. But, the major problems are delayed recovery and cardiovascular
depression which may necessitate the use of vasopressors.
Propofol has not consistently demonstrated a benefit although some have shown
improved outcome or bi-modes outcome.
Clinical reports of myocardial failure in severe head injury patients following prolonged
sedation with propofol have been seen.
Maximum dose of 5mg/kg/hr is the safe limit of propofol for sedation in patients with
severe head injuries.
Lidocaine: infusion begun at induction of anesthesia and continued for 48 hours with a
target plasma concentration between 6 and 12 Hmol/L increased scores in 6 of 11
neuropsychological tests and sensory inventory after cardiac valve surgery under
cardiopulmonary bypass.
B) Isoflurane: has cerebral protection because it has metabolic affects that are similar
to barbiturates.
3) Techniques to alter the cascade:
Release of intracellular calcium and excitatory amino acids following ischemia
play havoc and expedite the neuronal disintegration at a faster pace. Increase in
intracellular calcium plays a pivotal role in the ischemia cascade.
A) Calcium channel blockers. Nimodipine following cardiac arrest and global
ischemia have been found to be of very little help.
Excitatory amino acids are endogenous neurotransmitter and amino acids such as
glutamate and aspartate have been shown in vitro and in vivo to be potentially
neurotoxic.
The mechanisms underlying neurotoxicity are thought to have at least two components
acute neuronal order in patients with severe head injury with subarachnoid
haemorrhage.
Gavertinel: an antagonist of the glycine site of the N-methyl-D-aspartate (NMDA)
receptor as neuroprotective therapy for acute ischemic stroke.
Remacemide: Is not a powerful neuro protector.
Its mechanism of action is glutamate antagonism through NMDA channel
blockade.
-Second Edition
2011

255


C) Magnesium: Magnesium blocks both ligand and voltage dependent Ca++ entry.
Magnesium is also powerfully protective in vitro suggests that it may critically reduce
calcium influx, in distinct from primarily improving CBF subsequent to cerebrovascular
dilation.
D) Mild hypothermia:
It has been appreciated for decades that profound systemic hypothermia lowers
metabolic rate and is useful for organ protection during cardiovascular and
neurosurgical procedures.
Minor degree (1-3
0
C) of reduction in case temperature may have profound
influence on the outcome of cerebral ischemia.
Mild hypothermia has been found to control intracranial hypertension, improve
neurologic outcome following severe head injury and also decreases excitatory amino
acids in the CSF.
Mild hypothermia and cardiac arrest: increase in number of good outcome has also
been seen in patients with out of hospital cardiac arrest who were exposed to mild
hypothermia (330C) for 12 hours.
Mild hypothermia in SAH and massive cerebral infarction:
Intraoperative use of mild hypothermia during intracranial aneurysms has
shown encouraging result.
Hemicraniectomy:
(Schwab and colleagues reported a 60% reduction in mortality).
Cerebral preconditioning:
Using retina as a model for the CNS, Barbe and his colleagues found that
subjecting rats to heat shock (15 min at 41
0
C) protected neurons from high
intensity light damage if the rats were allowed to recover for 18 hours
subsequent to heat exposure.
This phenomenon was soon replicated in a model of cerebral ischemia and the
induction of endogenous proteins of repair is now well documented and
understood.
A rich environment may stimulate mechanisms that enhance brain plasticity and
better functional recovery.

-Second Edition
2011

256


E) Neurotrophic factors:
Development of neuronal and glial cells and their maintenance are under control
neurotrophic factors (NTFs). An exogenous
F) Gene therapy:
DNA transfer may be achieved using retrovirus, herpes simplex virus, adenovirus
and adeno associated virus vectors or liposomes. After cerebral ischemia these vectors
are used to up regulate genes that increase survival and inhibit those that promote
death in the injured cells. In contrast, in brain turrocys gene therapy aims to kill the
target cells.
Anti-apoptotic baculovirus protein p35 has been used recently to achieve better
neurologic recovery following cardiac arrest.
G) Combination therapies:
The rationale for combination therapy is based in the increasing knowledge of
the pathophysiologic mechanisms of ischemic brain damage.
Given the complex mechanisms involved in the ischemic cascade, it seems
unlikely that any single neuroprotective agent is able to cover the whole cascade.
Each agent affects only one of the several mechanisms in the ischemic cascade
whereas, a combination therapy effects several points in the cascade.

-Second Edition
2011

257


Chapter 19 - GLASGOW COMA SCALE
Glasgow coma scale evaluates neurological state of individual after head injury and
also severity of injury and outcome.
Glasgow coma score < 8 poor prognosis, require intubation, controlled ventilation and
further neurosurgical management.
Function Adults Infants and children Score
Eye
opening
Spontaneous
To command
To pain
None
Spontaneous
To speech
To pain
None
4
3
2
1
Verbal
response
Oriented
Confused
Inappropriate words
Incomprehensive sounds
None
Coos and babbles
Irritable cries
Cries to pain
Moves to pain
None
5
4
3
2
1
Motor
response
Obeys commands

Localize pain
Withdrawn to pain
Abnormal flexion
Abnormal extension
None
Obeys commands
spontaneous
Withdrawn to touch
Withdrawn to pain
Abnormal flexion
Abnormal extension
None
6

5
4
3
2
1
Total score 15

GCS 8 : Deep coma, severe head trauma, poor outcome
GCS 9-12 : Not in coma, moderate injury
GCS > 12 : Mild injury
According to GCS, head injured patients may be divide into 3 group to aid in
deciding what best to do for them.
-Second Edition
2011

258


Group I GCS = 15

Group II GCS 8-14: Impaired consciousness and or with some neurological signs

Fully arrest and oriented on
arrival
No H/o loss of
consciousness
Minimal rest from
hematoma
Allowed to go home with
specific instructions
Loss of consciousness
amnesia
Skull x-ray
No II Fracture
Minimal risk
Observation at
home with specific
instructions
Risk of
hematoma
CT scan
Fracture +
hematoma
Fracture +
without
hematoma
Refer to
neurosurgical
Observation in
hospital
Urgent CT scan
Hematoma
Monitor in hospital
No hematoma
Refer neurosurgical
-Second Edition
2011

259


Group III GCS 3-7:
Those with coma deteriorating consciousness

Refer directly to neurosurgical without CT scan

-Second Edition
2011

260


Chapter 20 - SPINAL SHOCK
Spinal cord injuries cause spinal shock.
Most spinal cord injuries often traumatic and result in partial or complete
transection.
Due to fracture and dislocation of vertebral column.
Clinical manifestations depend on the level of transection.
Injuries above C3-C5 - Diaphragmatic innervation involved
- Require ventilatory support
o Injuries above T1 quadriplegia
o Injuries above L4 paraplegia
Most common transection are C5C6 and T12-L1
Acute spinal cord transection or acute high spinal cord injury can cause spinal shock
with
a. Loss of sensation
b. Flacid paralysis below level of injury
c. Loss of spinal reflexes
d. Lasts 1 to 3 weeks
e. Loss of sympathetic tone in capacitance and resistance vessels below the level of
lesion resulting in hypotension, bradycardia, areflexia and GI atony.
f. Infarct venous distension in the leg is a sign of spinal cord injury.
g. Abnormalities ECG VPB and ST-T changes suggest MI.
h. Autonomic hyperreflexia is associated with lesions above T5. Unusual with
lesions below T10 due to interruption of normal descending inhibitory impulses
in the cord.
i. Cutaneous or visceral stimulation below the level of injury can induce intense
autonomic reflexes. Sympathetic stimulation HTN and vasoconstriction below
transection and a baro receptor mediated reflex bradycardia and vasodilatation
above transection.
During this period the major cause of morbidity and mortality is alveolar
hypoventilation and inability to protect the airway and to clear bronchial secretions.
Aspiration of gastric contents as well as pneumonia and pulmonary embolism are
constant threats during spinal shock.

-Second Edition
2011

261


Management:
Early care of acute injuries:
1. Prevent further spinal cord damage during patient movement, airway
manipulation and positioning.
2. Head stabilized in neutral position using in-line stabilization with the help of an
assistant or should remain in traction during intubation.
3. Awake fiber optic intubation after topical anesthesia may be safest.
4. Patients with high transection often have impaired airway reflexes and are
predisposed to hypoxia by a FRC.
5. Hypotension requires aggressive fluid therapy
6. Short term high dose corticosteroid therapy with methyl prednisolone 30mg/kg
over 1
st
hr followed by 5.4mg /kg / hr for 23 hrs improves neurologic outcome.
7. Hypotension and bradycardia are often present prior to IV fluids and ketamine
prevent hypotension induction
8. Monitoring: Direct arterial pressure
CVP
Pulmonary artery pressure monitoring
I. Succinylcholine is safe in first 48 hrs following injury.
II. Vasopressor may be needed.
III. Muscle relaxants given depending on site of operation and level of spinal
transection. Pancuronium sympathomimetic effects.

-Second Edition
2011

262


Chapter 21 - ELECTROENCEPHALOGRAM
Definition:
Refers to study, observation and recording of brain waves or electrical potentials of
brain, which are measurable expression of electrical activity of brain.
If potential is measured in terms of voltage referred to near point as on scalp or
brain, this is bipolar reading. If reference point is fixed point remote from brain unipolar
recording is obtained.
Standard EEG: A standardized placement system (10-20) has been developed. This
system is symmetric array of scalp electrodes. This setup permits
electroencephalographer to select pair of electrodes with discrete anatomic location
from which to record.
Standard electroencephalogram show set of 8-12 wave lines each being graph of
electrical signals from one region of head and designated as channel.
EEG signal:
It contains 3 basic parameters
1. Amplitude
2. Frequency
3. Time
Amplitude: Electrical height of wave ranging 0-200 v (microvolts).
Frequency: Number of times / seconds the wave crosses zero voltage time. This
depends on degree of activity of cerebral cortex.
Alpha waves (8-13 Hz): In normal adult person when awake and in quiet resting states.
Beta waves (> 13 Hz): High frequency waves recorded from person who is over
excited and with specific mental activity.
Theta waves (4-8 Hz).
Delta waves (0-4 Hz): They occur in very deep sleep, in infancy and serious organic
brain diseases.
Normal EEG:
Symmetric, patterns are predictable with absence of spike waveforms. Usual base
frequency in awake patient is alpha range (8-13 Hz).This range is usually used as
reference signal during anesthesia.
-Second Edition
2011

263


Activated EEG: When events that lead the brain to produce higher frequencies occurs,
EEG described as activated EEG.
Depressed EEG: When lower frequency are recorded on EEG.
Abnormal EEG:
Asymmetry of patterns of amplitude and frequency that are not predictable or
expected to occur in usual recorded.
E.g. Anatomic / metabolic disturbance in brain epilepsy, cerebral infarction.
Processed EEG: Converting raw EEG data which many clinicians found difficult in
interpreting into easily understandable digital signal.
Uses of EEG:
1. Monitoring functional integrity of neural structures that may be at risk.
2. Identification of specific structures.
3. Monitoring effects of anesthetic agents and other drugs that affect nervous
system.
4. Diagnosis and monitoring of various pathophysiological condition that can alter
neurological function in critically ill patients
5. Diagnosis of hypercarbia / anoxia.
ANESTHESIA AND EEG
Ketamine: Rhythmic theta activity (4-8 Hz), also associated with increased epileptiform
activity.
Opioids: Dose related in frequency if further dose, of opiates are not given, high
frequency waves eventually return (suggesting the patient is more awake and
attentive). Epileptiform activity occurs with large doses of opioids especially after
induction with fentanyl.
N2O: When used in combination with other agents, it increases depth of anesthesia both
clinically and with respect to EEG pattern.
Isoflurane: Slowing of EEG activity that increases with increasing depth of anesthesia, it
produces periods of EEG suppression which become longer with increasing doses until
electrical silence is produced at 2-2.5 MAC.
-Second Edition
2011

264


Halothane: Produces similar effects like isoflurane, but greater degree of EEG
suppression seen with isoflurane are not seen with halothane until dosage associated
with profound CVS depression are used (3-4 MAC).
Sevoflurane (Enflurane): Similar effect as isoflurane except that epileptiform activity
on EEG is considerably more prominent.
Surgery and EEG:
To monitor adequacy of cerebral blood flow during carotid endarterectomy.
As many anesthetic drugs do affect EEG and many of EEG changes may mimic EEG
changes associated with inadequate cerebral blood flow some guidelines about
anesthetic management during EEG monitoring for cerebral ischemia might be helpful.
1. No change in anesthetic technique should be made during critical periods of
monitoring.
2. E.g. Induced hypotension, carotid clamping, aneurysm clipping
3. Avoid major changes in anesthetic gas level or boluses of opioids barbiturates /
benzodiazepines near times of increased ischemic risk.
4. If drugs must be given that cause EEG slowing, it is sometimes possible to
monitor SSEP and may remain relatively unaffected.
EEG during cardiovascular surgery:
Mainly done to detect earliest ischemic changes due to cerebral hypoperfusion.
E.g. Aneurysm clipping
Carotid endarterectomy
EEG during surgery for epileptic foci
EEG during carotid endarterectomy:
Mainly to acquire data to use as basis for therapeutic intervention. Eg. placement
of shunt.
To see changes in EEG, when shunt become kinked or displaced or when cerebral
emboli occur during dissection to of plaque.
During hypotension or even after repair should a patient suffer intra cerebral
Hemorrhage.
Main aim of brain monitoring in carotid procedures is to aid in identifying
patient who needs a shunt. This is done by temporary occlusion of carotid artery
and noting ischemic changes on EEG.

-Second Edition
2011

265


Pathophysiological effects on EEG:
Hypoxia:
Slowing of EEG during hypoxia is nonspecific global effect. Fast frequencies are lost and
low frequencies dominate. Eventually EEG is abolished as cerebral metabolic activity is
severely reduced depending upon severity of hypoxic event.
Hypotension:
Normal EEG pattern is preserved with CBF 45-60 ml/100g/min, isoelectric EEG with
loss of evoked potentials is seen with CBF of 15-20 ml/100g/min.
Significant levels of hypotension seem to be needed to cause earliest of CNS signs
as measured by discrimination test such as flicker fusion test. This test examines flicker
rate at which observer perceives light to be continuous.
Clear signs of confusion and inability to concentrate or respond properly to
simple commands must represent very low level of cerebral perfusion.
EEG changes associated with even this level of hypotension are not dramatic
although they are clear by comparison with previous active reading.
Also changes due to acute onset hypotension as caused by sudden arrhythmia
are easier to read than when compared to chronic hypotension.
Hypothermia:
At temperature between 15-18
0
C, it causes global EEG suppression indicating very low
level of brain activity.
Hypocarbia:
Hyperventilation is known to activate excitable seizure foci.
Hypercarbia:
Hypotension with accumulation of CO2 has effects similar to increasing end tidal tension
of volatile anesthetics.
Advantages of EEG:
Non invasive
High accuracy
Disadvantages of EEG:
Needs trained personal
Technical difficulties
Affected by some anesthetic drugs which cause EEG slowing
-Second Edition
2011

266


Normal alpha and sleep rhythm:

I. Normal variation in amplitude of alpha rhythm as encountered in different
normal persons and taken on frontooccipital electrodes prior to anesthesia
appearance during eye blinks is shown at B.
II. Bottom tracing shows recording from normal person asleep without anesthesia.
Note mixture of fast and slow waves, pattern being different from any
encountered during anesthesia although sleep rhythms maybe encountered
during recovery from anesthesia.

- During early sleep can recollect
- Active / awake
, - coma
-Second Edition
2011

267


Chapter 22 - CEREBRAL EDEMA
Increase in brain-water content
Causes:
Vasogenic edema
Most common
Disruption of BBB allows entry of plasma- like fluid into the brain.
in B.P. enhance this type of edema
Common causes: Mechanical trauma
Inflammatory lesions
Brain tumors
HTN
Infarction
Cytotoxic edema
Cerebral edema following metabolic insults
Hypoxemia or ischemia
Failure of brain cells to actively extrude Na
+
progressive cell swelling
Interstitial cerebral edema
Result of obstructive hydrocephalus entry of CSF into brain interstitium
Water intoxication
Intracellular movement of water secondary to acute decrease in serum osmolality
Treatment: Ideally directed at underlying cause
Metabolic disturbances corrected.
Operative interventions undertaken where indicated
Vasogenic edema-due to tumors respond to steroids (dexamethasone) appears
to promote repair to BBB
Fluid Restriction:
Osmotic Agents: Mannitol
0.25 0.5 g/kg effective in rapidly decrease ICP.
1
0
related to its effect on serum osmolality a serum osmolality of 300-315
mosm/L is desirable.
Weak vasodilating properties transiently decrease B.P.
-Second Edition
2011

268


Transient increase in intravascular volume can cause pulmonary edema in
patient with borderline cardiac and Renal function
Should not generally used in patients with Intracranial aneurysms AVM or
intracranial hemorrhage until cranium is opened
Rapid osmotic diuresis in elderly patients subdural Hematoma due to
rupture of fragile bridging veins entering sagittal Sinus.
Rebound edema.
Loop Diuretics: (Furosemide)
Less effective requiring 30 min to act
Advantage of directly decreasing CSF formation
Combined with Mannitol Monitor Serum K concentration.
Lowers ICP by removing intracellular water from normal brain tissue.
Moderate Hyperventilation: (PaCo2 25-30 mmHg) is helpful in decreasing CBF
normalizing ICP
May aggravate Ischemia in patients with focal Ischemia
Fluid Restriction, osmotic agents and Loop diuretics are usually effective in
temporarily decrease brain edema and lowering ICP until more definitive
measures can be undertaken.

-Second Edition
2011

269


Chapter 23 BRAIN DEATH

This branch of medicine spirited the hopes is many people and its development
was life saving, and for others it was delaying diagnosis of death.
This helped in:
1. Organ transplantation became really.
2. Many of them benefited from new organs.
3. Organ could be taken from heart beating cadavers.
Definition of death:
1959, French medical literature:
Definition: Total unresponsiveness, absent brain stem reflexes and apnoea. COMA
DEPASSE (brain damage beyond coma)
1976, Medical Royal College.
a) Deeply comatosed patient-Other causes as depressant drugs, 1
0
hypothermia,
metabolic and endocrine causes must be ruled out.
b) Patient on ventilator when spontaneous respiration inadequate or ceased.
c) In the diagnosing of irreversible brain damage there should not be any doubt.
Confirmatory Test: All brain stem reflexes should be absent such as --No pupil reflex
to light, corneal, vestibular, ocular, gag reflex absent.
No respiratory movement, PaCo2 -50mmHg.
Other tests such as:
Repeating the tests.
Integrity of spinal reflexes (It will be present even after brain death)
Body temperature should not be less than 35
0
C.
Subjective diagnosis of the doctor concerned, specialist opinion when first
diagnosis is in doubt such as neuro-physician or neurosurgeon.
Legal perspective (1977):
Brain death occurs when, in the opinion of a licensed physician based on ordinary or
respected standard of medial practice, there has been total and irreversible cessation of
spontaneous brain function and further attempts at resuscitation or continued
supportive maintenance would not be successful in restoring such functions.
1994, India:
Brain death is equivalent to death but criteria and determination defer to medical
profession.
-Second Edition
2011

270


A person will be considered medically and legally dead of in the opinion of a physician
there is absence of spontaneous brain functions, respiration and cardiac function and
attempt at sensitization are considered hopeless.
Clinical evaluation of brain death:
Declaration of brain death is made when there is loss of brain stem and cortical
functions which is irreversible.
A) Brain stem function documented by
a) Pupillary and corneal reflex
b) Oculocephalic and vestibular reflex
While assessing physician should consider the other aspects of blunting this reflex.
B) Loss of medullary function elicited by apnoea test interpretation: Period of apnoea
should be long to allow PaCO2 = 50-60 mm of Hg. Oxygenation may be maintained.
C) Loss of cortical function by loss of responsiveness and receptiveness, also with iso-
electric EEG.
D) Establishing irreversibility (Matter of clinical judgment)
a. First clinical diagnosis
b. Appropriate period of observation
c. No improvement in neurological function for 12-24 hrs
d. Exclusion of reversible causes of COMA
Confirmatory test may be done especially if the period between examination is less than
12hrs and in children under 5 yrs of age.
In general brain death is a clinical diagnosis; it is left to physician and reasonable
standard of medial practice.
Most organ recipients rely on the gift of an organ from the brain dead donor.
Tragically significant organ loss occur due to poor understanding of the
pathophysiology of brain death and improper management of the problems associated
with brain death.
Donor problems such as
a. Hypotension, hypothermia
b. Central diabetes insipidus
c. Electrolyte abnormality
d. Pulmonary abnormalities and Coagulopathies should be promptly intervened
and rectified on time.

-Second Edition
2011

271


Criteria for Diagnosis of Brain Death
In 1981, the President's Commission for the Study of Ethical Problems in Medicine and
Biomedical and Behavioral Research (USA) developed standards for the determination
of brain death which with some modifications are accepted worldwide.
Some steps are important to be followed:
Unresponsiveness
The patient is completely unresponsive to external visual, auditory, and tactile stimuli
and is incapable of communication in any manner.
Absence of cerebral and brain stem function
o Pupillary responses are absent, and eye movements cannot be elicited by the
vestibulo-ocular reflex or by irrigating the ears with cold water.
o The corneal and gag reflex are absent, and there is no facial or tongue movement.
o The limbs are flaccid, and there is no movement, although primitive withdrawal
movements in response to local painful stimuli, mediated at a spinal cord level,
can occur.
Apnea Test:
o An apnea test should be performed to ascertain that no respirations occur
at a PCO2 level of at least 60 mmHg. The patient oxygenation should be
maintained with giving 100% oxygen by a cannula inserted into
endotracheal tube as the PCO2 rises. The inability to develop respiration
is consistent with medullary failure.
Nature of coma must be know
o Known structural disease or irreversible systemic metabolic cause that can
explain the clinical picture.
Some causes must be ruled out
o Body temperature must be above 32 C to rule out hypothermia
o No chance of drug intoxication or neuromuscular blockade
o Patient is not in shock
Persistence of brain dysfunction
o Six hours with a confirmatory isoelectric EEG or electrocerebral silence,
performed according to the technical standards of the American
Electroencephalographic Society
o Twelve hours without a confirmatory EEG
-Second Edition
2011

272


o Twenty-four hours for anoxic brain injury without a confirmatory iso-electric
EEG
Confirmatory tests (are not necessary to diagnose brain death)
o EEG with no physiologic brain activity
o No cerebral circulation present on angiographic examination( is the principal
legal sign in many European countries)
o Brain stem-evoked responses with absent function in vital brain stem structures

-Second Edition
2011

273


Chapter 24 - ANESTHESIA FOR NEUROMUSCULAR DISORDERS
INTRODUCTION
Neuromuscular disorders consist of conditions affecting any major component of the
motor unit:
Neuromuscular junction
Muscle
Motor neuron
Peripheral nerve
CLASSIFICATION OF NEUROMUSCULAR DISORDERS (NMD):
I. Disease of neuromuscular junction:
Myasthenia gravis
Myasthenic syndrome - Eaton Lambert syndrome
Familial periodic paralysis
o Hypokalemic
o Normokalemic
o Hyperkalemic
II. Disease of the muscle:
i) Muscular dystrophies:
a. Duchene's Muscular Dystrophy (DMD)
b. Becker's Muscular Dystrophy (BMD)
c. Emery-Dreifuss Dystrophy
d. Congenital Muscular Dystrophy
ii) Myotonia:
a. Myotonic Muscular Dystrophy
b. Myotonia Congenital
c. Paramyotonia Congenital
I. Disease involving NMJ:
Myasthenia gravis (MG):
MG is an autoimmune disorder involving NMJ
Characterized by weakness and fatigability of skeletal muscles on exertion and
improvement in muscle power at rest.
-Second Edition
2011

274


Weakness and fatigability characteristically involves muscles of eyelids -
producing ptosis - it may be localized to few groups of muscles or it may be
generalized.
Depending on the group of muscles involved and severity
they are classified as follows: Adult Myasthenia:
Group I: Ocular myasthenia (15-20%)
Group IIa: Mild generalized disease (30%)
Group IIb: Moderately severe generalized without respiratory failure (20%)
Group III: Acute fulminate disease (11%) (Bulbar involvement with respiratory
failure},
Group IV: Late severe disease (Respiratory failure and Burnt out disease)
Pediatric myasthenia
Neonatal transient
Neonatal persistent
Juvenile myasthenia
It can also be classified as:
Type I: Is limited to involvement of the extraocular muscles. About 10% of
patients show signs and symptoms confined to the extraocular muscles and are
considered to have ocular MG.
Type IIA: Is a slowly progressive mild form of skeletal muscle weakness that
spares the muscles of respiration. Responses to anticholinesterase drugs and
occasionally corticosteroids are good in these patients.
Type IIB: Is a more severe, rapidly progressive form of skeletal muscle weakness
than that which occurs with type IIA. Poor responses to drug therapy. Muscle of
respiration may be involved.
Type III: Is characterized by an acute onset and rapid deterioration of skeletal
muscle strength (within 6 months) and is associated with high mortality.
Type IV: Is a severe form of skeletal muscle weakness that results from
Progression of Type II or I.
Clinical features:
MG is characterized by weakness and fatigability of voluntary muscles, which improve
at rest.
Patients generally; presents with ocular manifestations initially, some may have
breathing and swallowing problems with the involvement of bulbar musculature
dysphagia, dysarthria, difficult in eliminating oral secretion.
-Second Edition
2011

275


Peripheral muscles involvement may result in weakness, clumsiness and
difficulty in walking and during other activity especially towards the end of the
day.
MG is at high risk for pulmonary aspiration.
Pathophysiology:
MG is an autoimmune disorder with auto antibodies being demonstrated to the
skeletal muscle acetylcholine (Ach) receptor.
Decrease in number of Ach receptors results in decrease deficiency of
transmission of nerve impulse to the muscle.
In severe cases it may result in destruction of large number of receptor, which
may result in no response to anticholinesterase (Burnt out disease).
In MG the number of activated postsynaptic receptors may be insufficient to
trigger an action potential with repeated stimulation, the decline in release of
Ach correlates with characteristic fatigability.

Mechanism proposed includes:
1. Accelerated degradation of Ach on the post synaptic membrane.
2. Immuno pharmacologic blockade in which the antibody hinders interaction
between Ach and Ach R.
3. Modulation or accelerated internalization with intracellular degradation of AchR
and AchR antibody complex.
-Second Edition
2011

276


4. Reduced synthesis of AchR this may be due to AchR antibody.
5. It has also hypothesized that thymic factor is essential for the development of MG.
80% of patients with MG have pathological changes in their thymus gland and
thymectomy affects the clinical course of the disease.
Thymectomy may influence cell-mediated immunity and peripheral T-cell counts.
Thymectomy may serve to remove the source of (1) AchR antigen (2) AchR
antibody production (3) sensitized killer.
Diagnosis:
Diagnosis of MG is suspected from history and confirmed by (1) Pharmacological (b)
Electrophysiological and (c) immunological testing
Pharmacological Testing:
1) Tensilon testing (Edrophonium):
This drug is short acting anticholinesterase. Its administration improves the
mechanical and electrical decrement with repetitive muscle stimulation in 95%
of MG patient.
2-10mg of Edrophonium is administered intravenously a positive response
generally develops within30-60 seconds and lasts for approximately 1to 5mm.
2) Neostigmine Test: Neostigmine has longer latency and duration. Neostigmine used
in dose of 1.5mg IV improvement is seen within 10-30min and lasts up to 4 hours.
3) Regional curare test:
MG patients are sensitive to neuromuscular blocking effects of curare. This
heightened sensitivity is used to confirm the diagnosis when routine EMG results are
equivocal. A tourniquet is applied to isolate the upper limb. EMG studies are performed
before and after the administration of 0.2mg of curare. A positive test shows a dramatic
sensitivity to curare.
Electrophysiological testing:
Supramaximal repetitive stimulation of the nerve leads to decrement in evoked muscle
action potential.
Jolly test: It consists of repetitive stimulation of a peripheral nerve. In normal patients
safety margin is large enough so that repetitive stimulation can be tolerated to a rate of
40 to 50/sec. In MG patient's abnormal diminution begins at stimulation rates of 2-3 per
second.

-Second Edition
2011

277


Single fibre electromyography:
1. This is a more sensitive test. A single fibre needle electrode is placed between 2
muscle fibres innervated by the same motor unit. The variation in latency
between the 2 action potentials is referred as jitters or blocking of one of the
action potentials is severe.
2. In patients with purely ocular symptoms, the frontalis and levator palpebrae
superioris muscle should be examined. This requires expensive complex
machinery.
3. Stapedial reflex decay: Preliminary results indicate high sensitivity with ocular
MG than generalized MG
c. Immunological testing:
A high titer of anti-acetylcholine receptor antibodies is considered diagnostic. These
may be present in high titers even in subclinical MG (pre-myasthenic state).
Drug
Dosage (Mg)
Oral IV IM Efficacy
Pyridostigmine 60 2.0 2-4 1 (tid/qid regimen)
Neostigmine 15 0.5 0.7 1 (2-3 hourly)

2) Corticosteroids: They are the drug of choice for severely ill patients.
Mechanism: Corticosteroids work by decreasing antibody synthesis and inhibiting
CD4 cell and T-Cell proliferation, prednisone leads to marked improvement in
remission. In about 80% of cases improvement begins between 12 hour to 30 days.
Usual dose of prednisone is 1 mg/kg alternate day or OD tapered over 2 weeks after
symptom resolve.
3) Antimetabolites: Antimetabolites that have been used are azathioprine.
Cyclophosphamide and cyclosporine. They are used when response to steroids is not
adequate. Azathioprine is converted to metabolite mercaptopurine and inhibits T-cell
activity. Azathioprine is found to reduce serum anti Ach-R antibody titers. The dose is
50mg/d PO may be weekly increased to 3mg/kg/PO.
4) Immunoglobulins: They are useful in myasthenic crisis. They neutralize circulating
myelin antibodies. They are thought to interfere with anti-Ach R antibodies.
Improvement is noticeable in 3-21 days and lasts as long as 3 months. Adult dose is 0.4
gm/kg/day/IV over 5 days.
5) Plasmapheresis: (Plasma exchange) it may be used alone or along with steroids for
preparing the patients for thymectomy, a dramatic decrease in the level of antibodies is
seen following the first few treatment
-Second Edition
2011

278


Improvement usually begin between 1
st
and 4
th
exchange
Course of Plasmapheresis usually lasts for 1-2 weeks
Exchange volumes ranges from 1 to 4 liters
Replacement fluids commonly used are saline, albumin plasma protein fractions.
Improvement may last for 4 day to 12 weeks
6) Surgical treatment: Thymectomy in some centers is considered as primary mode of
therapy in MG patients.
Various surgical approaches are (1) Transcervical thymectomy (2) Median sternotomy
and thymectomy 3) Median sternotomy plus cervical incision.
Differential Diagnosis:
Congenital myasthenic syndromes
Drug-induced myasthenia gravis penicillamine
Nondepolarizing muscle relaxants
Aminoglycosides
Procainamide
Eaton - Lambert syndrome
Hyperthyroidism
Graves' disease
Botulism
Progressive external ophthalmoplegia
Intracranial mass compressing cranial nerve

-Second Edition
2011

279


-Second Edition
2011

280


Formula to predict need for post op mechanical ventilation:
1 = 3.192 2.874 FVC + 0.117 (% of predicts value of FVC) + 2.491MEF -
0.17 (% of the predicted value of MEF) 0.95 FEF + 0.087 (% of predictor value of FEF)
+ 0.623
A numerical value of (1) more than 0 means patient would not require postoperative
ventilatory support whereas less than 0 means patient would need postop ventilation.
Medical Treatment:
The medical management of MG includes:
1. Anticholinesterase
2. Immune therapy and
3. Thymectomy
Anticholinesterase: By preventing hydrolysis of acetylcholine, improves
neuromuscular transmission and muscle weakness. Long acting drug like
pyridostigmine, which are given orally 30 to 120mg every 3 to 6 hours.
Immunotherapy: is directed towards prevention of destruction of acetylcholine
receptors.
Corticosteroids usually improve the condition particularly after thymectomy.
Prednisolone 10 to 40mg / day
Azathioprine 2.5 to 3.5 mg / kg
Patient with severe disease and with respiratory failure can be benefited by
Plasmapheresis, which presumably reduces the antibody levels and improvement in
respiratory function and fasten the weaning from the ventilator.
Thymectomy is beneficial in large number of patients; improvement is usually
seen in20 to 30% of patients.
Anesthetic management:
MG patients commonly come for thymectomy
Patient requiring thymectomy are often with severe disease and may present
with respiratory failure.
The stress of surgical procedures in these patients under remission, may
precipitate an acute attack, and require intensive care for respiratory failure.
Before going to the anesthetic management we need to know the drugs to be
avoided in MG:
1. Antibiotics: Polymyxin, Neomycin, Kanamycin, Streptomycin, Gentamicin,
Tetracycline, Erythromycin, Colistin and Linomycin.
2. Cardiovascular drugs: Beta Blockers, Quinidine
3. CNS Drugs: Diphenylhydantoin, Chlorpromazine, Lithium
-Second Edition
2011

281


4. Anti-Rheumatic Drugs: d-Penicillamine, Chloroquine. .
5. Others: Magnesium, Procaine
Risk factors predicting the need for mechanical ventilation in MG
Described by Laventhal et al
Preoperative factors Points
Duration of MG > 6 months 12
H/o Co-existing respiratory disease 10
Pyridostigmine >750 mg day 8
Vital capacity < 2.91 4
Total score 10-readily extubate.
11 to12-Borderline
13 to 34-Needs ventilation
Preoperative evaluation:
PFTS:
Nonspecific bed side test
Specific
Non-specific (bed side test)
Breath holding > 30 normal ; < 15 sec VC
Sniders match blowing 6 inch / 15 cm.
Debonos whistle test
Auscultation over trachea
Specific tests:
Test for ventilation
Test for distribution of ventilation
Test for diffusion
Test for perfusion
Other test like
o CC and volumes
o Airway resistance
o Lung compliance
o Flow volume loops

-Second Edition
2011

282


Steroids:
Perioperative / preop steroids to be given to avoid Addisonian crisis
It suppress ACTH from pituitary adrenocortical atrophy
5-7 days course may produce depression of adrenal cortex
Prednisone and prednisolone are intermediate acting.
Anesthetic considerations:
Perioperative hypotension
CVS problem
Addisonian crisis
Systemic Effects:
glucose tolerance
Infection, delayed healing
GIT bleed and perforation
Electrolyte imbalance ]
Preoperative evaluation of MG patient includes
1. Review of severity of myasthenia-specific attention to be paid to
Voluntary muscle strength
Respiratory muscle strength-assessed by pulmonary function tests (PFT). These
include bedside clinical methods like single breath count or breath holding time
or measuring negative inspiratory pressure, forced vital capacity (FVC), etc.
These tests help in deciding the time of extubation after thymectomy. Studies
have shown that low PFT values were associated with increased need for
postoperative ventilation.
Bulbar involvement compromises patient's ability to protect .and maintain
patent airway postoperatively and increases the incidence of postoperative
pulmonary aspiration.
1. Review of treatment regimen. Patients on long-term high steroids develop
myopathy that can increase the duration of postoperative ventilation.
2. Presence of thymoma-look for airway or vascular obstruction by tumor
Preoperative Preparation:
Regarding the use of anticholinesterase on the morning of surgery.
Some prefer to avoid the morning dose to decrease the need for muscle relaxants.
So that patient is weak on arrival at operating room.
-Second Edition
2011

283


Some choose to continue its use on the morning of surgery for psychological
support of the patient.
In patients who are having bulbar involvement or respiratory muscle weakness,
the morning dose is routinely given.
The steroid dependent patient will require Perioperative coverage
Anxiolytic sedative and opioids premedication are rarely given to patients who
have diminished respiratory reserve.
If the patient is having primarily ocular symptoms, a small dose of
benzodiazepine can be given.
A preoperative visit by the anesthesiologist explaining the details of
intraoperative management and postoperative respiratory maneuvers is
mandatory. Breathing exercises and incentive spirometry may be indicated and
advised during the preoperative period
Intraoperative Management:
MG patient is typically sensitive to non-depolarizing neuromuscular blockers.
Long acting muscle relaxants such as d-tubocurarine, pancuronium.
Pipecuronium and doxacurium are best avoided.
Short acting or intermediate acting non-depolarizing muscle relaxants can be
used in titrated doses preferably with a peripheral nerve stimulator.
In the study by Naguib, it was demonstrated that, with titrated doses and
adequate neuromuscular monitoring, intermediate and short acting
nondepolarizing muscle relaxants could be used safely and patients were
extubated in the OR.
Patients with MG show resistance to depolarizing agents but their administration
can lead to prolonged blockade for example anticholinesterase drug such as
pyridostigmine not only inhibits true cholinesterase but also impair plasma
cholinesterase activity, introducing possibility of prolonged response to
succinylcholine.
Inhalational anesthetics induced muscle relaxation is more profound in MG and
deep level anesthesia, with these agents can lead to delayed recovery.
Intravenous anesthetics like barbiturates and propofol can be used without
untoward effect.
Propofol has the theoretical advantage of shorter duration of action without
effect on neuromuscular transmission.

-Second Edition
2011

284


Propofol:
Induction: 1 to 2.5 mg / kg I.V
Maintenance of GA: 50 to 150 mic g/kg / min
Sedation: 25 to 75 micro / kg / min
Infusion: 2mg / kg / hr (2 gm/ ml)
Atracurium: 0.4 to 0.5 mg/kg intubation ED 95 -0.2
Vecuronium: 0.08 to 0.1 mg/kg intubation ED 95- 0.05]
Opioid analgesics in therapeutic concentration do not appear to depress
neuromuscular transmission. However, central respiratory depression may be
problem. Short action opioids are preferred.
Regional or local anesthesia technique should be performed by reduced doses of
amide local anesthetics.
Intraoperative monitors:
Nerve stimulator: Should be used to monitor muscle strength whether or not they
are going to receive muscle relaxants intraoperatively, this is because inhalation
anesthetics have been shown to cause twitch suppression in the absence of muscle
relaxants. Patients with Mg are extremely sensitive to the neuromuscular depressing
properties of the volatile anesthetics.
Pulse oximeter
Blood pressure (NIBP)
Electrocardiogram
Esophageal temperature
End tidal capnometry
Central venous catheter for fluid management.
Premedication: T. Diazepam 5mg orally
Analgesic: Inj Fentanyl 1 to 2 micrograms/kg- in titrated dose
Induction: Inj. propofol 1to 2 mg/kg IV along with Sevoflurane 6-7 %
Intubation: As MG patients are more sensitive to neuromuscular depressant effects of
anesthesia; hence intubation of trachea, maintenance of relaxation can be achieved with
inhalation anesthetic.
Muscle relaxants: If at all has to be used then Atracurium 5mg or Vecuronium 1mg is
preferred with neuromuscular functioning monitoring.
Invariably patient may require postoperative ventilation for a period of 24 to 48
hours to allow spontaneous recovery. Extubation should be considered if ET-tube is not
longer tolerated.

-Second Edition
2011

285


Reversal of muscle relaxants:
One major concern is the use of muscle relaxants intraoperative and its reversal
post operatively.
Some prefer to avoid muscle relaxants altogether and use potent inhaled agents
both for facilitating tracheal incubation and providing relaxation for surgery.
These agents allow neuromuscular transmission to recover.
Titrated small doses of intermediate acting relaxants like Atracurium (10-25% of
ED 95) to facilitate tracheal incubation and surgical relaxation using a peripheral
nerve stimulator.
If in doubt regarding requirement of neostigmine for reversal of NM blocked,
edrophonium 2 to 8mg may be given to test for improvement in muscle power.
Weaning and Extubation:
Weaning methods:
The term weaning suggests gradual reduction of a patients dependence on
ventilator.
Once the patient has recovered from the residual action of anesthetics, and
demonstrate adequate muscle power with head lift and adequate respiratory
effort, they can be extubated
Some prefer to give a short period of pressure support ventilation or
T-piece trial and monitor the ABG before extubation.
The differential diagnosis includes myasthenic crisis, residual effects of
anesthetic drugs, non-anesthetic drugs interfering with neuromuscular
transmission and cholinergic crisis.
Strategies to reduce postoperative pulmonary complications:
Lung expansion maneuvers
Pain control
Aspiration precaution
Role of tracheostomy
The difficult to extubate patient
Cholinergic crisis/ myasthenic crisis
Lung expansion maneuvers:
Deep breathing exercises, incentive spirometry, chest physiotherapy, and
CPAP/BIPAP are the commonly used lung expansion maneuvers used
postoperatively to reduce pulmonary complication
-Second Edition
2011

286


CPAP or PAP should be instituted early in patients showing reduced arterial
oxygen saturation (because of atelectasis or respiratory impairment) after
extubation
Patent should be continuously monitored for respiratory depression
All the patient should be encouraged to cough and get good pulmonary toilet to
prevent infection and aggressive chest physiotherapy.
Pain control:
Adequate postoperative pain control facilitates tracheal extubation, early
ambulation and deeper breathing.
This can be achieved by epidural analgesia or non- narcotic drug. Thoracic
epidural analgesia with local anesthetics like bupivacaine combined with
fentanyl is superior to parenteral narcotics.
Patients should be carefully monitored for signs of depressed mental status and
hypercarbia as severe hypercarbia often co-exists with normal oximetry.
Use of thoracic epidural catheter with bupivacaine 0.25% for pain relief is of
immense use in these patient
Aspiration precautions:
Aspiration often is a major concern in the immediate postoperative period
especially in patients with bulbar symptoms preoperatively.
Evaluation of laryngeal cough reflex can help predict risk of aspiration
pneumonia with oral feeding.
Other precaution include the use of prokinetic, antiemetics and gastric acid
secretion blockers.
The difficult to extubate patient
Difficulty to wean and extubate can be anticipated in some myasthenic patients
undergoing thymectomy.
The three common indicators are change s in the patients respiratory pattern or
rate, changes in PCO2 and inability of a patient to protect the airway.
A patient who is difficult to extubate/ re-intubated usually is the result of
worsening of myasthenic status (myasthenic/ cholinergic ) or to a new problem
that occurred during surgery or immediate postoperative period
Immunoglobulin therapy (IVIG) or Plasmapheresis may be helpful to promote
remission if respiratory muscle weakness has increased. After extubation BiPAP
may help avoid re-intubation.

-Second Edition
2011

287


Cholinergic/ Myasthenic crisis:
In the post operative period, patient can go in for a cholinergic or myasthenic
crisis increasing the duration of postoperative ventilation.
Cholinergic crisis results from an excess of acetylcholine at the nicotinic and
muscarinic receptors.
Excess anticholinesterase drugs lead to this.
Involuntary twitching, fasciculations, and weakness develop as a result of
nicotinic over stimulation.
The weakness results from an inability to coordinate muscle contraction and
relaxation.
To differentiate this from myasthenic crisis, Tensilon test may be done. Over medication
of MG can lead to cholinergic crisis. In the absence of muscarinic symptoms, simply
allowing the patient to recover, while maintaining mechanical ventilation is the safest
approach.
Treatment of myasthenic crisis:
- Timely intubation + mechanical ventilation
- Withdrawal of anticholinergic drugs.
- Immuno-adsorption and immunoglobulin as useful alternatives
- Steroids therapy prior weaning

Immuno-adsorption: Is a technique that removes antibodies and immune complexes by
running blood over a tryptophan column.
Anticholinesterase in immediate postoperative period:
The common practice of withholding anticholinesterase drugs for 48 hours after
thymectomy is of questionable value as it prolongs duration of mechanical
ventilation and thereby, increases pulmonary morbidity.
Monitor the patient for weakness, hypoxemia and cholinergic side effects.
Pyridostigmine can be administered parenterally also at equivalent doses (30mg
orally is equivalent to 1mg IV or IM).
Pregnant patient with MG problem coming for emergency LSCS:
In pregnancy MG patient behave unpredictably
They show severe weakness in the immediate postoperative period, returning to
normal pre-pregnant state within 24 to 48 hours.
Regional technique is usually preferred.
Epidural technique may particularly be useful for postoperative analgesia, than
the anesthetic technique itself.
-Second Edition
2011

288


20% of neonates born to MG mother may show myasthenic feature, immediately
after birth and may require resuscitation, ventilation and/or anticholinesterase
therapy
Myasthenic syndromes:
Eaton Lambert Syndrome (ELS):
ELS is rare disorder, which affects neuromuscular transmission.
It resembles MG, In that there is decreased neuromuscular transmission
Pathophysiology:
Most of the cases are associated with small cell (oat cell) carcinoma of bronchus,
though it has been associated with other tumour like carcinoma of prostate,
breast, stomach and rectum.
A defect in presynaptic acetylcholine release has identified as the cause of the
weakness.
The quanta of acetylcholine released per nerve impulse is reduced due to down
regulation of voltage gated calcium channels.
Auto-antibodies have been identified against these calcium channels and the IgG
antibodies.
ELS show progressive increase in muscle response to single twitch stimuli.
Clinical features:
ELS is characterized by muscle weakness and hyporeflexia mainly affecting
proximal limb muscles with improvement in muscle power with exercise.
The ocular and bulbar muscles are generally not affected
Associated with autonomic dysfunction such as dry mouth, impaired lacrimation,
impaired sweating, urinary retention, constipation and orthostatic hypotension.
ECG may show decrease interval variation normally associated with respiration.
Patient with ELS usually may require anesthesia for biopsy or surgical excision of
tumors
These patients are very sensitive to both depolarizing and non-depolarizing muscle
relaxants.
Hence sevoflurane may be the drug of choice for induction and intubation.
If muscle relaxants are required Atracurium 5mg may be used, keeping
postoperative ventilation in mind.
NM blocked must be monitored with nerve stimulator
Residual paralysis at the end of the surgery may be reversed with 3,4 di-
aminopyridine and / or Neostigmine or pyridostigmine.
Local and regional blocks can be performed in most cases.
-Second Edition
2011

289


Comparison of Myasthenia Gravis and myasthenia Syndrome:
Clinical
Features
Myasthenia Gravis EatonLambert
Syndrome
Sex Females more than males Males more than females
Presenting
symptoms
Extraocular, bulbar and
facial muscle weakness
Proximal limp weakness (legs
more than arms)
Other symptoms Fatigue with activity
myalgia uncommon
reflexes normal
Activity increases
Strength myalgia
Common reflexes
Reduced or absent
Electromyography Initial action potential with
normal amplitude
decremental response to
repetitive stimulation (< 10
Hz)
Initial action potential with
abnormally small amplitude
decremental response to low
frequency (< 3 Hz) and
incremental response to high
frequency (20 50 Hz)
Response to
neuromuscular
blockers
Sensitive to non
depolarizers resistance to
depolarizers
Sensitive to both depolarizers
and non depolarizers
Response to
anticholinesterase
Good response Poor response
Associated
pathologies
Thymoma (25%) and
thymic hyperplasia (75%)
Small cell to carcinoma,
carcinoma prostate, breast,
return and stomach
Familial Periodic paralysis (FPP):
FPP is a group of diseases producing intermittent episode of muscle weakness
associated with changes in K
+
levels
There is a defect in the sodium channels of the muscle membrane, with decrease
in resting membrane potential and inability to conduct an action potential.
There are three types
- Hypokalemic periodic paralysis.
- Hyperkalemic periodic paralysis.
- Normokalemic periodic paralysis.

-Second Edition
2011

290


Difference between Hypokalemic FPP and Hyperkalemic FFP
Features Hypokalemic FPP Hyperkalemic FPP
Inheritance Autosomal dominant Autosomal dominant
Sex Males Males and females
Age group Starts in adolescents age Early in life, as age increases
attacks became less common
but more severe
Precipitating Large glucose meals
strenuous exercise, Glucose
insulin influence Stress,
menstruation, pregnancy
Anesthesia, hypothermia
metabolic Alkalosis
Exercise, K
+
infusion metabolic
acidosis hypothermia

Serum K
+
concentration
< 3.0 m E q /L >5.5 mEq/L
Mechanism Excessive high sodium
permeability in resting state,
resulting in decrease in
resting in membrane
potential

There is defect in alpha
subunits of Na
+
channels
resulting in high permeability
resulting in and
hyperpolarization inability to
conduct action potential, which
is responsible for weakness
Muscle involved Upper and lower extremities
with proximal to distal
spread neck muscle can be
involved.
Upper and lower limbs trunk
muscle facial muscles
ECG

K
+
- 3mnmol/l
Low wave
High U wave
K
+
2.5 mmol
Inverted T waves
High U waves
Low ST segment
PR interval is prolonged
Treatment iv K
+

0.2Eq/kg/hr
K
+
-7 mmol
High T waves
K
+
-9mmol
Intraventicular block
Atrial standstill
Treatment
- Calcium gluconate
- 10-20 ml of 10% iv
- Sodium bicarbonate
- 50 100 Eq/kg/hr
- Glucose and insulin infusion
-Second Edition
2011

291


9.Treatment Potassium supplementation
Acetazolamide by causing
metabolic acidosis
Potassium spacing diuretics
like amiloride and
triamterene
Insulin and dextrose infusion
High carbohydrate diet help to
prevent attack
Thiazide diuretics helps in
excretion of potassium
Anesthetic
management Aim:
To prevent
Hypokalemia, potassium
supplement, pre operatively
K
+
and glucose levels to be
monitored intraoperative
along with Na
+

Pulse oximetry, ECG
temperature, nerve
stimulator, BP
Regional anesthesia can be
used safely
To prevent hypokalemia
K
+
free dextrose solution should
be administered
K
+
glucose, Na
+
to be
continuously monitored
Succinylcholine is
contraindicated as it cases
hyperkalemia
Ketamine should be also
avoided as hyperactivity may
release K
+
and cause an attack
Regional anesthesia can be
used safely
Duchenes Muscular Dystrophy (DMD):
It is also called pseudo hypertrophic muscular dystrophy 3 per 10,000 birth
It is x- linked recessive disorder almost always affecting males.
It is characterized by absence or abnormal sarcolemmal protein dystrophin
which is responsible for binding the actin to sarcolemma and extracellular
matrix.
It presents in early childhood ( 3-5 year ) with weakness, prominent in hip
girdle muscle
Child uses hands to climb up from the floor (Gowers maneuver), waddling gait
and frequent falling.
There is pseudo hypertrophy of calf muscles (fat replacing the muscles).
By 7-8 years there is contractures of the Tendo-Achilles and other muscles.
Gradually the disease spread to muscles of the upper limb, thoracic and
abdominal muscles resulting in kyphoscoliosis, resulting respiratory difficulty.
Death usually occurs by 15 to 25 years due to congestive heart failure and or
pneumonia.
The muscle injury results in increased serum enzymes like creatinine kinase,
SGOT, and SGPT.
-Second Edition
2011

292


Cardiopulmonary dysfunction:
Degeneration of cardiac muscle invariably accompanies muscular dystrophy.
Characteristic changes on the electrocardiogram include tall R waves in V1 deep
Q waves in the limb leads, short PR intervals & sinus tachycardia.
Mitral regurgitation may be due to papillary muscle dysfunction and to
decreased myocardial contractility.
Chronic weakness of inspiratory respiratory muscles and a decreased ability to
cough can result in loss of pulmonary reserve and accumulation of secretions,
which predispose to recurrent pneumonia.
Respiratory insufficiency often remains covert because impaired skeletal muscle
function.
Anesthetic Management:
Children with pseudohypertrophic muscular dystrophy often require anesthesia
for skeletal biopsy or correction of progressive orthopedic deformities.
Preparation for anesthesia in patients afflicted with pseudohypertrophic
muscular dystrophy must take into consideration the implications of increased
permeability of skeletal muscle membranes and decreased cardiopulmonary
reserve.
Succinylcholine is contraindicated because of the risks of rhabdomyolysis:
hyperkalemia and cardiac arrest.
Succinylcholine induced hyperkalemia during acute rhabdomyolysis is more
likely to result in cardiac arrest and unsuccessful resuscitation.
Potassium efflux resulting from up regulation of acetylcholine receptors.
A malignant Hyperthermia like episode (rhabdomyolysis and cardiac arrest) has
been reported in a patient with Becker muscular dystrophy undergoing surgery
with anesthesia provided with isoflurane and skeletal muscle paralysis produced
by Rocuronium.
Dantrolene should be available, as there is an increased incidence of malignant
hyperthermia in these patients.
Usually patients present for release of contractures and correction of
kyphoscoliosis
May also require anesthesia for skeletal muscle biopsy or correction of
progressive orthopedic deformities.
Patient are usually at risk pulmonary aspiration because of hypomotility of GI
tract and delay gastric emptying, 8-12 hour fasting.
Monitors: Capnography NIBP temperature, pulse oximeter, CVP and Nerve
stimulator.
-Second Edition
2011

293


Succinylcholine is contraindicated because of the risks of malignant
hyperthermia, rhabdomyolysis, hyperkalemia and cardiac arrest.
Cardiomyopathies found 50 to 70% of patient ECHO shows MVP, posteriorbasal
and lateral wall hypokinesia (due to contractures of these walls).
Halothane should be avoided because it may increase incidence of MG.
Regional or local anesthetic is the best
Dose of Dantrolene:
2.5mg/kg every 5min
Until episode is terminated

Max. 10mg/kg

1mg/kg I.V every 6 hr for 24-48hr to prevent relapse
Postoperative care:
Patient with DMD should be monitored for MH like symptoms. Risk of pulmonary
aspiration prolonged mechanical ventilation
Becker Muscular Dystrophy (BMD):
Becker Muscular Dystrophy (BMD) is an X-linked disorder occurring in 1 in
80,000 males. In DMD, the protein dystrophin is virtually absent, where as in BMD, the
dystrophin is abnormal. The disease present in adult age group (late onset), with more
mild features than DMD. Many patients have only myalgia and muscle cramps, exercise
intolerance and myoglobinuria. There is increase in CPK and other enzymes. Dilated
cardiomyopathy may be present. The anesthetic management is similar to DMD
patients. However, these patients have better outcome than DMD patients.
Emery Dreifuss Dystrophy:
This is also an X-linked disorder with involvement of proximal muscles (biceps and
triceps) in upper limb and distal muscles in lower limb. The disease progresses more
slowly and may cause contractures of elbow and neck making positioning and
intubation difficult. This disease is characterized by severe involvement of cardiac
muscles than the skeletal muscles. Cardiomyopathy due to fibrosis of entire ventricle,
atrial arrhythmias and sudden death has been reported. Prophylactic pacemaker early
in the disease in indicated.

MYOTONIAS:
-Second Edition
2011

294


Myotonic disorders are characterized by delayed relaxation after voluntary contraction
muscles and sustained contraction following direct stimulation (myotonia).
MYOTONIA DYSTOTOPHICA:
Myotonia Dystrophica (MD) is one of the common myotonic disorder inherited
autosomal dominant disease. It occurs typically in adults between 20-40 yrs.
The myotonic feature consists of persistent contraction after voluntary act (such
as inability to release after hand shake).
As the agonist muscles go into spasm as the patient tries to relax, the antagonist
contraction of the muscles go into spasm, referred to as after spasm.
Repeated contraction of the muscles reduces the muscles spasm warm up
phenomenon.
Muscular wasting and weakness involving forearm, facial, sternomastoid and
bulbar muscles are common. Ptosis and foot drop may also occur.
Local infiltration of procaine was shows to reduce the muscles spasm.
Therefore procainamide and phenytoin, which suppress spontaneous discharges,
have been used to control myotonic features.
Myotonic Dystrophica is a multisystemic disease. The cardiac abnormalities are
present. Conduction problem such as varying degree of A-V Block with prolonged
PR interval with extremely low heart rate with Stokes- Adams syndrome.
Atrial flutter has been observed & ST elevation is also frequently seen.
Tachyarrhythmias like paroxysmal ventricular tachycardia, which may lead to
sudden death.
Wall motion abnormalities have also been observed with ECHO. Patients have
associated coronary diseases, which cause coronary insufficiency.
Myotonic involvement of diaphragm and the chest muscles lead to moderate to
severe respiratory difficulty.
Respiratory function tests shows features of Restrictive Pulmonary Disease.
There is decreased vital capacity parallel with the severity of disease. Reduction
in maximal breathing capacity and expiratory reserve volume is commonly
observed.
This restrictive picture is due to myotonic contraction of diaphragm and
intercostals muscles, which has been shown to move abnormally under
fluoroscopically resulting in fatigue.
Central nervous system involvement consists of hypersomnolence and
obstructive sleep apnea.
-Second Edition
2011

295


Patients have personality changes like lethargy and apathy and mental
retardation, in whom decreased cerebral blood flow has been reported, point to
primary CNS manifestation probably due to cerebral atrophy.
Many patients have difficulty in swallowing and show greater risk of aspiration
pneumonitis.
Presenile cataract and insulin resistance diabetes has been reported.
Treatment:
Treatment for muscular weakness. Manage myotonia without the need for drugs.
However, in severe cases phenytoin or procainamide has been used to control
myotonia.
Thiopentone produce severe apnoea, and hence contraindicated view has been
existing for long time, careful analysis has shown that apnoea can be caused by
any central nervous depressant like opiates, benzodiazepines etc and not
necessarily thiopentone alone.
Respiratory arrest has reported with diazepam sedation following spinal
anesthesia, and with propofol.
Since many of combination of these drugs are used under anesthesia, severe
respiratory depression is very common, electively ventilated postoperatively,
often for 3 to 4 days, till adequate spontaneous ventilation is restored.
Muscle relaxants use, pose challenge to the anesthesiologists. Depolarizing
muscle relaxants has been shown to induce generalized myotonia in some
patients.
Myotonia involving muscle of respiration and larynx may make ventilation
difficult or impossible.
The duration of myotonia may last more than the succinylcholine action.
Succinylmonocholine may is also reported to cause myotonia. Hence
succinylcholine should be avoided in patients with Myotonia
The non-depolarizing muscle relaxants may or may not produce adequate
muscle transmission and do not modify myotonic response.
The recovery from muscle relaxants however has been unpredictable although
safe reversal of residual block has been reported; anticholinesterase
(neostigmine) has been reported to cause generalized myotonic contractures or
inadequate reversal.
Short acting muscle relaxants like atracurium and vecuronium have been use
without much problems.
-Second Edition
2011

296


Myotonic response to direct muscle stimulation by electrocautery may not be
prevented despite adequate block by muscle relaxants.
Myotonic response can be modified by local infiltration of local anesthetics,
phenytoin or procainamide, which stabilize muscle membranes.
Because of problems of all the above drugs, it is preferable to use nerve block,
particularly if muscle relaxation is not needed.
Intravenous regional anesthesia with local anesthetic produce good operating
conditions with muscle relaxation and without myotonic responses.
When general anesthesia is necessary, it is preferable to use potent inhalational
anesthetic agents.
They however should be used carefully in presence of cardiac failure.
Intubation should be achieved with short acting Nondepolarizing muscle
relaxants. Controlled ventilation is mandatory should be continued till
neuromuscular block recovers spontaneously. Post- operative hypothermia and
shivering should be avoided, as itself may induce myotonia and respiratory
difficulty.
MD in Pregnancy:
MD may be associated with ovarian atrophy. However, many patients may
conceive and require caesarian section.
Most patients have normal first stage of labour. The straining associated with
second stage may induce myotonia and produce respiratory distress and hence
should be avoided.
These patients should have elective caesarian section. Regional anesthesia rather
than general anesthesia is preferred in such cases.
Uterine atony has been reported in most patients, which require oxytocic agents,
and often require massive blood transfusion.
Children born to mothers with MD tend to have myotonic symptoms. They tend
to have respiratory difficulty due to poor respiratory reserve and also feeding
difficulties.
They may have hypoplastic diaphragm. These infants have characteristic tent
shaped upper lip with lower jaw tending to hang open, and often with talipes and
mental retardation.
Most premature infants require long-term ventilation, and the perinatal
mortality is high. Those who survive invariably develop MD later in life
The patients with myotonic dystrophica have multisystem involvement with
severe cardiac and respiratory failure. They should be managed by avoiding CNS
depressants and depolarizing muscle relaxants
-Second Edition
2011

297


Non depolarizing muscle relaxants can be used but recovery should be
spontaneous. Postoperative ventilation should be continued or instituted
without hesitation.

-Second Edition
2011

298



-Second Edition
2011

299


Chapter 25 - TRAUMA SCALES
Trauma scales are used as a useful prognostic tool and also to predict the outcome and
direct patients to appropriate facilities. Various trauma scales have been developed on
the brain of the vital parameters obtained during the primary survey.
I Trauma Score:
Systolic B.P
>90 4
70-90 3
59-69 2
<50 1
0 0
R/R
10-24 4
25-35 3
>35 2
10 1
0 0
R/R
Normal 1
Shallow 0
or
retractions
None 0
Capillary Refill
Normal 1
Delayed 1

GCS 14 15 5
11 13 4
8 10 3
5 - 7 2
3 4 1
Trauma Score (A+B+C+D+GCS) = 12 15 Mild trauma
9 11 Moderate trauma
Below 9 Severe trauma
II Revised Trauma Score
GCS Systolic B.P Respiratory Rate Coded Value
13-15 >89 10-29 4
9-12 76-89 >29 3
6-8 50-75 6-9 2
4-5 1-49 1-5 1
3 0 0 0
RTS 0.9368 GCS + 0.7326 SBP + 0.2908 RR

-Second Edition
2011

300


CRAMS Scale:
Circulation
Normal Capillary refill and BP > 100mmHg
Delayed capillary refill or BP 85-99 mm Hg
No capillary refill or BP <85 mmHg

2
1
0
Respiration
Normal
Abnormal (Shallow)
Absent

2
1
0
Abdomen
Abdomen and thorax non-tender
Abdomen and thorax tender
Abdomen rigid or flail chest

2
1
0
Motor
Normal
Responds only to pain
No response

2
1
0
Speech
Normal
Confused
No intelligible

2
1
0
Score 8 indicates major trauma
Score 9 indicates minor trauma
Pediatric Trauma Score:
Weight (In pounds)
>20 +2
10-20 +1
<10 -1
Airway
Normal +2
Maintained +1
Unmentioned -1
Systolic B.P
>90 +2
50-90 +1
<50 -1
CNS Function
Awake +2
Obtunded +1
Coma -1
Open Wound
None +2
Minor +1
Major -1
Skeletal Trauma
None +2
Closed +1
Open or Multiple -1

-Second Edition
2011

301


Secondary Survey:
The purpose of the secondary survey is to identify all problems in a systematic way
leading to the examination which will evolve into an orderly diagnostic plan.
Head Examination: May reveal depressed skull fractures needing elevation and
laceration needing suturing. Basilar skull fractures should be suspected if there are
blood and CSF in the auditory canal.
Neck Examination: Should be performed once more for pain, crepitus, distended
neck veins and tracheal deviation.
Chest Examination: For fractures of the clavicles and ribs.
Abdomen: Examined for distension, changes in girth and evidence of peritoneal
irritation.
Pelvic fractures with long bone fractures: Must be identified to allow for
stabilization to reduce occult bleeding.
Treatment of Full stomach in the Traumatized patient
a. Nasogastric decompression (not in open eye or penetrating neck injuries with
hematoma formation.
b. Preinduction antacids -Not in suspected penetrating injury of the GI tract
c. Nothing by mouth -Interval from meal to accident more important than interval
from meal to induction of anesthesia.
d. Regional Anesthesia
e. Awake endotracheal intubation -Not in open eye or penetration wounds of the
neck with hematoma formation.
f. Anti fasciculation -small dose of Non-depolarizing relaxant prior to scoline using
the priming participle.
g. Rapid sequence intubation
h. Crico esophageal compression

-Second Edition
2011

302


Chapter 26 - HYPOXIC BRAIN DAMAGE DURING ANESTHESIA
INCIDENCE:
Cardiac arrest being the major cause of hypoxic brain death, the incidence of cardiac
arrest gives an approximate idea about the magnitude of the problem. Different studies
have indicated different rates of cardiac arrest. Death and brain damage accounted for
32% and 12% of claims in closed claims analysis. The majority of cases involve healthy
adults undergoing non-emergency surgery under general anesthesia.
CAUSES OF HYPOXIC BRAIN INJURY:
Hypoxic brain injury results from a variety of accidents that occur during anesthesia.
The majority of them are related to cardiovascular catastrophes, adverse respiratory
events or dangerous equipment failure. Some of these common causes are described
below.
Cardiac Arrest:
Cardiac arrest is a common cause of hypoxic brain damage. The primary causes to
which the cardiac arrests are related to are: 1.Drug administration 2.Vagal stimulation
3.Hypoventilation 4.Bleeding 5. Anaphylaxis and 6.Direct cardiac stimulation.
Mechanisms of Intraoperative Cardiac Arrest
Causes:
Anesthetic overdose, hypovolemia, difficult tracheal intubation
Inadequate ventilation, overdose of inhalational agent, hemodynamic instability
Histamine release, postoperative respiratory depression
Blood loss, preoperative anemia, succinylcholine, accidental administration of
potassium, airway problems, inadequate ventilation
Drug overdose, hypovolemia, hypoxemia, myocardial ischemia, anaphylactic
stock, protamine, hypokalemia
Ventilatory problem, succinylcholine, post-induction hypotension, hypovolemia
Inadequate fluid management, respiratory insufficiency, cardiac complications,
technical error, inadequate supervision
Adverse Respiratory Events:
Three mechanisms accounted for three fourths of the respiratory events in the closed
claims analysis: 1. Inadequate ventilation (38%), (2) Oesophageal intubation (18%),
and (3) Difficult intubation (17%).
-Second Edition
2011

303


Inadequate ventilation:
The major proportion of these are due to Disconnections, Complete failure to ventilate,
Leaks associated with failure of the absorber valves, Misconnections.
Oesophageal intubation:
Capnography was very sensitive to identify this complication.
Difficult intubation:
Obesity, limited neck mobility and mouth opening and inadequate assistance accounted
for two thirds of all contributing factors.
Other less frequent respiratory causes:
Airway trauma, pneumothorax, airway obstruction, aspiration and bronchospasm are
less frequent events leading to adverse outcomes. Death and brain damage occurred in
47% of these patients. Airway injury occurred to larynx, pharynx or oesophagus.
Pneumothorax resulted from needle punctures for regional block or central venous
catheter placement. Aspiration occurred before intubation in those who were intubated
or in patients who were managed by mask.
Equipment Related Problems: Misuse of equipment was 3 times more common than
equipment failure. Equipment misuse is defined as error in preparation, maintenance or
deployment of the equipment.
CONTEXT-SPECIFIC ISSUES
Pediatric Anesthesia:
An analysis of the closed claims in pediatric subgroup of patients revealed that there
were some prominent differences between adults and children:
Respiratory events were more frequent in children (43% Vs 30%)
Mortality rate was greater in pediatric claims (50% Vs 35%).
Anesthetic care was considered less than appropriate in a greater percentage of
pediatric patients (54% Vs. 44%) and were considered preventable with monitoring in
a greater percentage of pediatric patients (45% Vs. 30%).
Regional Anesthesia:
The risk of cardiac arrest and neurological damage associated with regional anesthesia
is less well appreciated than that associated with general anesthesia. The higher
incidence of cardiac arrest during spinal anesthesia (6.4 1.2 per 10,000 patients)
compared with all other regional anesthetics (1.0 0.4 per 10,000 patients) was
statistically significant (P < 0.05). The study concluded that the incidence of cardiac
-Second Edition
2011

304


arrest related to regional anesthesia is very low, but it is more frequent after spinal
anesthesia than after other regional procedures.
Cardiac arrests resulted from 3 primary mechanisms:
1) Hypovolemia, (2) Sedation, (3) High spinal anesthesia.
Cardiac arrest during subarachnoid anesthesia is an uncommon but well reported
phenomenon. Bradycardia with resultant hypotension is thought to occur by two
mechanisms. The first involves block of the cardio-acceleratory sympathetic fibres,
which may occur with a sensory block as low asT10; it has been shown that the sensory-
sympathetic differential may be up to six segments. This allows unopposed
parasympathetic input with a negative chromotropic effect. The other mechanism is a
manifestation of decreased venous return, which may trigger reflexes mediated by caval
and atrial receptors and the pacemaker stretch reflex. Acute reductions in venous
return have also been reported to activate the Bezold-Jarisch reflex with resultant
bradycardia.
Two mechanisms accounted for all these cardiac arrests under spinal anesthesia: (1)
Excessive sedation that produced a comfortable sleep-like state without any
spontaneous verbalization, (2) Inability to understand the effect of high sympathetic
blockade on effectiveness of cardiopulmonary resuscitation. Early administration of an
alpha-agonist or efforts to increase central venous pressure would have been more
effective in preventing the adverse outcome. It was hypothesized that the adverse
outcome was a result of poor coronary perfusion during cardiac massage in the
presence of sympathetic blockade. Based on this, a recommendation was made to
administer epinephrine early in response to severe bradycardia or hypotension in
patients undergoing spinal anesthesia.
Obstetric Anesthesia
Aspiration and convulsions are the major causes in obstetric patients.
Cardiac Anesthesia:
Death and brain damage were the complications that accounted for the majority of
claims during cardiac anesthesia. Equipment malfunction was more frequently
responsible for adverse events in cardiac than non-cardiac patients. On the contrary,
respiratory mechanisms of injury were significantly lower in cardiac anesthesia (9% in
cardiac Vs 32% in others types of anesthesia).
PATHOGENESIS OF ERRORS CAUSING ADVERSE EVENTS:
Anesthesiologist is a part of a complex dynamic system comprising of the patient,
colleagues, and equipment. This environment is, in turn, influenced by a number of
-Second Edition
2011

305


personal, administrative, political and cultural factors. Errors are bound to occur in such
a complex environment. By and large, these errors take predictable forms and have
identifiable mechanisms. Identifying these mechanisms helps to evolve strategies to
prevent them.
Normally, the anesthesiologists specific goals and intentions lead to a sequence of
acceptable actions that result in acceptable outcomes. These outcomes are constantly
perceived and compared with the intended goals and intentions by the anesthesiologist.
But under the influence of latent shaping factors, errors take place, which may lead to
unintended incidents or in their most serious form lead to accidents that would
culminate in cardiac arrest and brain damage. Fatigue and stress might increase their
occurrence.
Errors may be classified into active and latent errors.
Active Errors: These errors are usually immediate precursors to an incident or
accident. There are three taxonomic forms of active errors:
a. Contextual errors: The error is completely context-dependent.
b. These errors are totally context-free, phenomenological, these are in turn
categorized as omissions, repetitions, substitutions and insertions.
c. Psychological: This form of analysis makes inferences about the underlying
internal mechanism giving rise to the error, psychological classification of
divides errors into 5 categories:
1. Knowledge-based errors: These errors result from wrong intentions due to
inexperience and unfamiliarity.
2. Rule-based errors: Failure to apply the correct rule or applying an inappropriate
rule results in this form of error.
3. Skill-based errors: These errors result from dissociation between automatic and
conscious control of actions. In general terms, most of these are called as slips.
Technical errors: These errors are said to have occurred when after a right
intention and action, the expected outcome does not occur or an unforeseen
outcome occurs.
Latent Errors: These errors are the shaping factors for incidents. They are not
only a function of the knowledge, but also influenced by physical and cultural
environment and by rules.
Contributing Factors for "Latent" Errors
1. Task requirements
2. Physiological status
3. Design of equipment
4. Workspace layout and conditions
-Second Edition
2011

306


5. Product design
6. Training of personnel
7. Workplace policies and procedures
8. Assistance/supervision
9. Social/cultural factors
10. Multi-personal factors
11. Chance
Prevention and Management of Errors:
The major steps in prevention and management of errors, and the consequential
incidents and accidents are:
1. Finding out what is going on from various sources of information: e.g. Mortality
and morbidity committee reports, "closed claims" studies, anecdotes,
observational studies and incident monitoring studies.
2. Collecting information.
3. Categorizing problems, contributing factors and errors.
4. Developing preventive strategies.
5. Putting strategies into place.
6. Assessing if the strategies are working.

-Second Edition
2011

307


Chapter 27 - ANESTHETIC MANAGEMENT OF INTRACRANIAL
HYPERTENSION
PATHOPHYSIOLOGY OF INTRACRANIAL HYPERTENSION
The adult brain is enclosed within a rigid cranial vault, the content of which can be
divided into three main compartments: the cerebral tissue, which also includes the
extra- and intracellular fluid and accounts for 90% of the contents, arterial and venous
blood, and cerebrospinal fluid (CSF), which together make up the remaining 10%. The
Monroe-Kellie hypothesis, as modified by Cushing at the beginning of the. previous
century, States that, if the cranium is intact, the sum of the volume occupied by the brain
tissue, the CSF and blood compartment is constant Hence, any increase of the volume of
one of the components must be compensated by a decrease of volume of one or both of
the other components (compensatory mechanism) for the intracranial pressure (TCP)
to remain constant
Consequently, IH can develop when one of the three intracranial compartment
increases in volume or when an expansive lesions develops in presence of exhausted
compensatory mechanisms. Expansive lesions, with or without perilesional edema, are
the primary cause of IH in the perioperative period. Non-communicating hydrocephalus
and increase of blood volume by vasodilation or venous obstruction are less common
causes.
The relationship existing between intracranial volume variations and ICP is not linear
(Fig 1). Initially, a slow increase of the intracranial volume will not cause the ICP to rise
due to the translocation of CSF to the medullar compartment, an eventual increase of
CSF reabsorption, and a reduction of the venous fraction of intracranial blood volume.
In this case, the intracranial compliance is normal (portion 1 of the curve, Fig 1). Once
the compensatory mechanisms are exhausted, even a small increase of volume will lead
to a tremendous rise of ICP and intracranial compliance is decreased (portion 2 and 3 of
the curve, Fig 1). The normal ICP is between 10 and 15 mm Hg. A value in excess of 18 to
20 mm Hg is abnormal and should be treated. Cerebral perfusion pressure (CPP) is
defined as the difference between the mean arterial pressure (MAP) and the ICP, if the
ICP is known and higher than the central venous pressure. The cerebral arterial
circulation is normally auto-regulated to maintain a constant cerebral blood flow (CBF)
for CPPs between 50 and 150 mm Hg (Fig 2). Outside of these limits, or when
autoregulation is impaired, the CBF varies linearly with changes of MAP. Below a CPP of
50 mm Hg, the vasodilating capacity of cerebral vessels is exhausted, the CBF drops, and
there is a risk of cerebral ischemia. Above 150 mm Hg of CPP, the diameter of the vessel
is reduced to its minimum and the increase of CBF can lead to the formation of edema.
When autoregulation is normal, the CBF returns to its baseline value within 5 seconds of
-Second Edition
2011

308


an abrupt change of MAP. Autoregulation may be globally or regionally impaired by
traumatic brain injury, subarachnoid hemorrhage, by the use of some anesthetic agents,
in the presence of a brain tumor or an arteriovenous malformation, and by hypoxia and
marked hypercapnia. The autoregulation curve is shifted toward the right in the chron-
ically hypertensive patient (Fig 2). It is assumed that the autoregulation curve quickly
returns to its normal position once an effective anti-hypertensive treatment is begun,
although this has not been convincingly demonstrated in humans.

-Second Edition
2011

309


There is still debate regarding an ideal CPP for traumatic brain injury patients. Despite
this controversy, it is generally recommended in the perioperative period to maintain a
CPP above the estimated lower limit of autoregulation in patients with IH or a
decreased intracranial compliance.
SECONDARY BRAIN INJURY
Complications related to IH range from mild cerebral ischemia to rapidly fatal trans-
tentorial herniation. In the Traumatology literature, these complications are classified
as "secondary brain injuries" or avoidable damages. Secondary brain injuries can be
caused by IH itself and by factors aggravating it, such as hypercarbia. Hypoxemia,
hyperglycemia, hyperthermia, and arterial hypotension are important contributing
factors. In the perioperative period, in addition to these factors, brain herniation
through the craniotomy bone flap, cerebral ischemia secondary to brain retraction, and
suboptimal surgical conditions are all complications contributing to secondary brain
injuries.
INTRACRANIAL HYPERTENSION IN THE PERIOPERATIVE PERIOD
The position of the patient is an important factor in the treatment of IH in the
perioperative period. Even a 10-degree head up tilt can effectively decrease ICP with no
effect on CPP. The head should be placed in neutral position when the surgery allows for
it to facilitate jugular venous outflow. Coughing and bucking must be prevented because
they can lead to increases in ICP. Pain, agitation, and convulsions must be treated,
ideally with short acting drugs to allow for a neurological exam, if necessary. ICP
treatment modalities are meant to prevent the increases of volume or aimed at
decreasing the volume of one or some of the intracranial space components.
Induction of Anesthesia
Induction of anesthesia in a patient with IH is ideally performed with intravenous
agents such as thiopental, propofol, or etomidate. All these drugs decrease cerebral
metabolism in the same proportion causing an indirect vasoconstriction, a reduction of
the cerebral blood volume, and a decrease of ICP. To a variable extent, they are also
likely to cause a decrease of CPP. Thiopental and etomidate decrease ICP more than the
MAP; the CPP is therefore maintained or increased. Propofol may have a more
pronounced effect on MAP than ICP; the CPP is therefore maintained or decreased. Eto-
midate possesses a profile of hemodynamic stability and it can be used for the
hypotensive patient when a satisfactory reanimation cannot take place before the
induction of anesthesia. A reduced dosage of thiopental or propofol is also appropriate
in this case. The anesthesiologist should not base the choice of an anesthetic induction
agent on its alleged cytoprotective properties. The best neuroprotective measure during
-Second Edition
2011

310


induction of anesthesia remains the maintenance of adequate oxygenation and CPP. A
synthetic opioid devoid of histamine-liberation (fentanyl and its derivative) and/or
lidocaine(1.5 mg/kg) are also used for a better hemodynamic control during tracheal
intubation. The goal is to maintain an adequate CPP, and a significant drop of MAP
should therefore be avoided. There are no data favoring a particular opioid in patients
with IH, provided that the CPP is maintained within the range of autoregulation. The
chosen opioid should be administered immediately before or after the induction agent
to avoid hypoventilation before the anesthesiologist gains control on ventilation. When
the patient with IH presents with a full stomach, a rapid sequence induction should be
performed. IH in itself is not an indication for a rapid sequence induction. It is not
helpful to ask a patient with IH to voluntarily hyperventilate before a rapid sequence
induction. In addition to being stressful for the patient, this does not result in a lower
post-tracheal intubation PaCO2 than a standard rapid sequence induction. A
nondepolarizing muscle relaxant with rapid onset, such as rocuronium, or
succinylcholine preceded by a defasiculating dose of nondepolarizing muscle relaxant
are good choices to facilitate tracheal intubation in patients with IH. It is important to
carefully monitor the degree of neuromuscular block, to make sure the patient is
completely curarized before instrumenting the airway.
Mannitol, Furosemide, Hypertonic Saline
Osmotic agents such as mannitol and hypertonic saline cause a water shift from cerebral
tissue, across the blood brain barrier (BBB), and into the intravascular space. Osmotic
pressure is the principal force regulating the movement of fluids through an intact BBB;
its preservation is essential in the prevention of peritumoral edema formation. In
comparison, oncotic pressure plays only a minor role.
Mannitol
20% mannitol (0.5 to 1.0 g/kg), administered at the time of cutaneous incision (30 to 45
minutes prior to dura opening) is the most often used osmotic agent (1280 mosm/kg).
Mannitol dehydrates the cerebral tissue and eventually decreases the cerebral blood
volume and the production of CSF. The efficacy of mannitol is dependent on an intact
BBB, and it could therefore be less effective in case of extensive brain damage. The
action of mannitol is biphasic with an initial and brief rise of ICP, because of the increase
of cerebral blood volume, followed by a prolonged and marked drop in ICP (about 4
hours). This initial increase of ICP bears no clinical significance during general anes-
thesia and is more important when baseline ICP is normal. Mannitol possesses
antioxidant properties and at clinical doses it decreases the size of cerebral infarct in a
rodent model of focal cerebral ischemia up to 7 days after reperfusion. No proof of its
brain protective properties exists in humans, but additional doses of mannitol are
-Second Edition
2011

311


sometimes given prior to temporary arterial occlusion in neurovascular procedures in
the hope that it will confer some neuro protection.
Furosemide
Mannitol is frequently combined with small doses of furosemide (0.1 to 0.2 mg/kg) for a
synergistic and long duration effect on ICP. The use of furosemide alone does not
systematically reduce the ICP, and its mechanism of action is not fully understood.
Furosemide does not increase plasmatic osmolarity and hence does not decrease brain
water content. Only high doses of furosemide can decrease CSF production. In combina-
tion with mannitol, furosemide potentialize the increase in plasmatic osmolarity and
inhibits active mechanisms of cellular ionic regulation, preventing the cerebral cell from
restoring its intracellular volume. The use of furosemide as a sole agent can be
considered for a patient with severe congestive heart failure prohibiting the use of
mannitol. In this case, initiation of a significant diuresis with furosemide could also
precede the use of mannitol.
Hypertonic saline
Hypertonic saline, although not as frequently used as mannitol in the perioperative
period, produces similar surgical conditions. Only a few human studies have reported
the use of hypertonic saline for the treatment of cerebral edema and IH. The mechanism
of action of hypertonic saline is similar to that of mannitol and is based on the same
premise, notably an intact BBB. The safety of hypertonic saline has not been correctly
evaluated in human, but besides hypernatremia and its potential consequences, few
side effects have been reported.
In the perioperative period, 3% hypertonic saline is administered at a dose of 250 to
500 cc 45 minutes before dura opening. The resultant ICP reduction is of shorter
duration than that obtained by mannitol (about 2 hours). For the same indication, 2.5
ml/kg of 7.5% hypertonic saline can also be used. The natriuresis and secondary
increase of diuresis induced by hypertonic saline is less important than with mannitol.
Hypertonic saline could therefore be a better choice than mannitol in patients with
precarious volemic status, although no prospective study has assessed hypertonic saline
in this clinical context. Furosemide could theoretically potentiate the effect of
hypertonic saline. The fear of hypernatremia, the safety profile of mannitol together
with its potential antioxidant and brain protective effect, make hypertonic saline an
agent of second choice for the treatment of IH in the perioperative period. Anecdotally,
30 to 60 ml of 23.4% saline decreased the ICP in patients resistant to the usual
treatment of IH including mannitol.

-Second Edition
2011

312


Volume Repletion
Hypo-osmolar intravenous solution (5% dextrose, lactated Ringer) should not be used
during the perioperative period in neurosurgical patients. It has been shown on several
occasions in different animal models that these solutions increase ICP and cerebral
water content in both intact and injured brain. The use of colloid offers no advantages
over the use of normal saline solution (0.9%).Normovolemia should be maintained. A
substantial dehydration, in addition to compromising the integrity of other organ
systems, does not result in a larger reduction of brain water content than the judicious
use of hyper-osmolar solutions.
Anesthesia Maintenance
Although, several anesthetic techniques give satisfactory results for intracranial
surgery, the patient with IH deserves special attention.
The normal CBF is between 50 and 55 ml/100g of cerebral tissue/min (ml/100gr/min)
in human. There is a close relationship between brain metabolism and the CBF. An
increase in brain metabolism will yield an increase of CBF through vasodilation, and
conversely a decrease of metabolism will cause an arteriolar vasoconstriction and hence
a decrease of CBF. This vasomotor activity of cerebral vessels is considered to be
indirect because it is mediated by changes in cerebral metabolism and not by the result
of a direct effect on the vessels themselves. This metabolic coupling can be disrupted by
traumatic brain injury and the use of volatile anesthetics.
Volatile anesthetics exert a mixed effect on the cerebral circulation. They reduce brain
metabolism and then have an indirect vasoconstrictive effect (preservation of metabolic
coupling). Concomitantly, volatile anesthetics are potent direct vasodilators and can
therefore increase the CBF. The net effect on the cerebral vasculature depends both on
the agent and dosage used. Sevoflurane is the least vasodilating agent, followed by
isoflurane, and lastly desflurane, the more potent cerebral vasodilator. Sevoflurane has
a net cerebral vasoconstrictive effect and also preserves autoregulation up to a
concentration of 2 MAC. Isoflurane has a minimal effect on CBF up to 1 MAC, but
autoregulation is abolished at a concentration of 1.5 MAC. Desflurane disrupts
autoregulation at low concentration (0.5 MAC) and abolishes it completely at 1.5 MAC.
Despite this theoretical disadvantage, desflurane does not cause variations of ICP in
patients undergoing removal of supratentorial brain tumors without midline shift. How-
ever, caution should be exercised when using a potent vasodilating agent in patients
with symptoms and/or signs of a severe increase in ICP.
In conformation with their respective solubility, the return to the baseline neurological
exam after an extended duration anesthesia for a craniotomy is faster with, sevoflurane
when compared with isoflurane. However, it is important to note that the choice of a
particular anesthetic agent is not the only factor that has an influence on the rapidity of
-Second Edition
2011

313


emergence in patients with an intracranial pathology. It has already been shown that
patients with a voluminous brain tumor (diameter of more than 30 mm with more than
3 mm of midline shift) have a prolonged emergence when compared with patients with
a smaller lesion or patients undergoing a laminectomy.
Nitrous oxide (N2O) increases brain metabolism and should not be used in patients with
IH. With the growing availability of low solubility agents, such as sevoflurane and
desflurane, its use should decline.
There is a threshold under which the CBF is not sufficient to meet cerebral metabolic
needs. This threshold is called the critical CBF (CBF crit), under which the brain becomes
ischemic in a majority of patients. In awake patients, this threshold is around 25
ml/l100gr/min. CBF crit, is lowered extensively by the use of some volatile anesthetic
agents. Thus, CBF crit with isoflurane is 10 ml/100gr/min, and 11.5 ml/100gr/min with
sevoflurane, while it remains at 20 ml/100gr/min with halothane. Based on these
studies, isoflurane and sevoflurane appear to possess an advantage if the clinician
anticipates a drop of CBF.
Propofol is also a good choice for the anesthetic maintenance of patients with IH.
Propofol is an indirect cerebral vasoconstrictor without direct vasoconstrictive or
vasodilating properties, and in the clinical setting its effect on ICP and brain relaxation
is equivalent or superior to that of isoflurane.
Cerebral blood vessels are very sensitive to PaCO
2
variations. The relationship between
the CBF and PaCO2 is directly proportional and linear for PaCO2 between 20 and 80 mm
Hg. The CBF varies by 4% for each 1 mm Hg of PaCO2 variation. CO2 reactivity is not
influenced by volatile anesthetics at the usual neuro anesthetic dosage, and propofol
slightly decreases it. In the perioperative period, it is recommended to maintain a PaCO2
between 30 and 35 mm Hg in patients with IH. Hyper ventilation lowers CBF with no
reduction in brain metabolism. This situation could be harmful for certain areas of the
brain where substrate delivery is already compromised. Hyperventilation, as an
adjuvant technique for the treatment of IH, should be used as a last resort in the
perioperative period when other methods have failed to control the ICP.
THERAPEUTICAL APPROACH TO INTRAOPERATIVE TIGHT BRAIN
The most common cause of intraoperative tight brain is the presence of a brain tumor
or some other space-occupying lesion (hematoma). When the bone flap is removed, the
dura will appear very tense, a sign of eminent brain herniation once it is opened. A tight
brain usually indicates an increased ICP. This can make the surgeon's work very difficult
and limit the surgical exposure. For the patients, there are direct repercussions: a longer
duration of surgery, the need to put more pressure on brain retractors giving rise to the
risk of secondary brain ischemia. Hydrocephalus is frequently associated with high-
grade subarachnoid hemorrhage, and CSF drainage, at the lumbar or ventricular level, is
-Second Edition
2011

314


a very efficient therapeutically modality, A brain that suddenly becomes tense should
quickly alert the anesthesiologist to a cerebral or intratumoral hemorrhage. An ill-timed
reversal of neuromuscular blockade could also result in brain protrusion through the
craniotomy flap. Patients under anticonvulsant medications recover quickly from
neuromuscular blockade and they should be closely monitored.
Several maneuvers can be undertaken by the anesthesiologist to decrease cerebral
tightness. It should be recognized that, in some cases, the resection of the tumor will be
the only efficient way of creating intracranial space. Logically, sequential modifications
of different anesthetic parameters could allow the clinician to determine the etiology of
IH or its contributive factors. However, it is usually preferable, and above all faster, to
make several changes simultaneously.
Notably, the patient's position, level of neuromuscular blockade, peripheral oxygen
saturation, and level of end-tidal CO2 must be quickly assessed. FiO2 should be increased
to 1.0 during the critical period. The MAP should be controlled, especially if an impaired
autoregulation is suspected. In such cases, any increases of MAP could lead to an
increase of CBF and a tense and hyperemic brain. It is important, however, to keep the
MAP above 60 to 70 mm Hg to ensure an adequate CPP.
Nitrous oxide, if used, should be stopped and fresh gas flow increased to quickly purge
the anesthetic circuit. Volatile anesthetic concentration should be decreased, especially
if 1 MAC or more was used. Alternatively, the clinician can completely stop the
administration of volatile anesthetic and give thiopental or propofol boluses followed by
an infusion. Of note, if only a small concentration (0.3 to 0.5 MAC) of isoflurane or
sevoflurane was used, such a procedure will generally not be very useful. An additional
dose of mannitol (0.5 to 1.0 mg/kg) can also be administered. This additional dose,
although effective, will take 20 to 30 minutes before improving the situation. If the
patient's fluid balance is positive, furosemide (0.1 to 0.2 mg/kg) can be added to manni-
tol. Finally, it is also possible to increase the patient's minute ventilation to obtain a
PaCO2 between 25 and 30 mm Hg. This should significantly decrease CBF in only a few
minutes. Steroids are not useful in the acute phase of IH and are moreover only effective
to treat vasogenic peritumoral edema.
Anesthesia Emergence
One of the main goals during anesthesia emergence for the neurosurgical patient is a
rapid awakening to enable neurological testing immediately after the end of the surgery
while insuring stable hemodynamics and an adequate control of the airway. For
unknown reasons, neurosurgical patients are frequently hypertensive in the
postoperative period. A formal link between postoperative arterial hypertension and
the formation of an intracranial hematoma has never been established. However, since
an intracranial hemorrhage is a serious complication, it is recommended to control
-Second Edition
2011

315


arterial blood pressure during this period. Labetalol (0.5 to 1.0 mg/kg) is an excellent
choice, with minimal intracranial effect. Nitroprusside and nitroglycerine are potent
vasodilators and they should be avoided in patients with IH. Postoperative nausea and
vomiting should be prevented. The reported prevalence is greater than 50% in certain
series, especially for posterior fossa craniotomy.

-Second Edition
2011

316


Chapter 28 - ICP MONITORING
Type of Waves
3 types of spontaneous pressure fluctuation designated as A, B and C wave and 4 stages.
A-wave also called plateau waves, represents severe pathological elevation of ICP
caused by changes is regional CBV. During this ICP rises above 40 mmHg.
B-wave has amplitude about 20mmHg and occurs at a rate of 1-2 per min. They are less
dramatic importance than a waves, but acts as warning signs of decreased intracranial
compliance and enhanced risk of intracranial hypertension. B-wave more often occurs
synchronous with Cheyne-stroke breathing.
Percussion (n) wave seen with arterial pulse
Breathing: associated with breathing
Three waves:
1. n percussion wave
2. Tidal wave and
3. Diacrotic wave
4 stages of raised ICP:
Stage 1: In this stage spatial compensation occurs with very little increase in ICP.
EEG, CBF and cerebral O2 are normal.
Stage 2: Exponential increase occur in ICP, ICP increases by more than 15mmHg.
Abnormal ICP waves are triggered by hypoxia / hypercapnia.
Stage 3: ICP approaches the level of BP, vasomotor reflexes are less effective,
EEG is slowed. BP changes produce identical changes is ICP.
Stage 4: Decompensation becomes irreversible, hypotension and death ensure.
Extradural hemorrhage:
In any head-injury patient who fails to improve or continuous to deteriorate.
C/F:
Head injury is almost invariable.
Skull fracture present in over 90%
Headache and vomiting may occur
Impaired level of consciousness
Seizures
Contralateral hemi paresis and extensor plantar may be elicited
Sign of midline shift
-Second Edition
2011

317


Causes: common
Head injury = tearing of meningeal artery (commonly middle meningeal)
Rare:
1. Head injury dural sinus tear
2. Intracranial infection (sinuses, middle ear orbit)
3. Anti-coagulates / blood dyscrasias
Management:
Medical
Surgical
Medical:
1. Stabilize the patient
Airway
Breathing
Circulation
Assume C-spine injury till excluded
2. Treat seizures if present
3. Urgent CT-scan: hematoma with >5mm mid line. If the hemorrhage is too small
repeat scan after few hr.
4. Closely monitor neurological scale (GCS)

Subdural haemorrhage:
It is the result head injury
Types:
Acute
Chronic
Both result of tearing of bridging vein between the cortical surface and venous
sinuses. (dura)
Acute hemorrhage into the subdural space follows head injury and can be
impossible to distinguish on clinical grounds from extradural.
Chronic hematoma is also preceded in most cases by head injury, patients are
unable to recollect.

-Second Edition
2011

318


C/F:
1. Skull fracture
2. Headache
3. Seizure
4. Sign and midline shift
5. Impaired and fluctuating levels of consciousness (impaired memory)
6. Focal neurological defects (hemi paresis, dysphasia, )
Common predisposing factors:
- Head injury old or young
- Old age cortical atrophy stretches bridge veins Long standing alcohol abuse
- Anticoagulant use
Assessment of severity:
- Bilateral spasticity or extensor plantar
- Extensor response to painful stimuli
- Coma
Management:
- Medical
- Surgical

-Second Edition
2011

319


Chapter 29 - ICP AND ANESTHESIA
Intra cranial pressure is the pressure within the cranium and reflects the CSF
pressure. The source of this pressure is the secretary pressure of the choroids plexus. It
has to be sufficient to overcome the flow resistance of the microtubules of the arachnoid
villi. It is closely related to the venous pressure and oscillates with the arterial pulse and
with respiration. Falls with inspiration and rises with expiration.
Normal intra ventricular ICP = 5-15 mmHg
ICP greater than 20 mmHg is an indication for intracranial hypertensive therapy.
Factory which increase ICP:
Physiological
Coughing
Sneezing
Straining
Pathological
Pressure from outside bony tumour or craniostenosis
Presence of a space occupying lesion neoplasm, abscess, hematoma
Hydrocephalus
Venous obstruction
Arterial dilatation secondary to hypercarbia
Cerebral edema Inflammation
-neoplasm
-Trauma
-hypoxia
-venous obstruction
Head-down position
Factors which decrease ICP
Haemorrhage
Hypovolemia
Following removal of an intra cranial space occupying lesion.
Head up position Raising the head 20 cm above horizontal reduces ICP by 20
cm H2o.

-Second Edition
2011

320


Importance:
Cerebral perfusion pressure CPP= Mean arterial pressure (MAP) intracranial pressure
(ICP). Any rise in ICP causes a reduction in the CPP. So careful monitoring and prompt
treatment of intracranial hypertension is the most important factor in the reduction of
mortality following head trauma.
Control of ICP prevents pressure gradients between various compartments of
intracranial cavity and prevents shifts of brain structures. (Brain herniation)

Lundbergs classic work demonstrated that there are 3 waves in ICP tracing
A waves (Plateau waves)
B waves
C waves
A waves or plateau waves are recurring increases in intracranial pressure to values of
50-100 mmHg lasting 5-20 min which usually arise with severe decomposition of ICP
control mechanism. Seen only when base line ICP is more than 20 mmHg. At 60 mmHg
headache, restlessness incontinence, non purposive movements etc appear. At 80 mm
Hg loss of consciousness, deceleration, respiratory arrest etc. occur.

-Second Edition
2011

321


B waves occur at a rate of 1 or 2 per min, are of small amplitude and may be precursors
of plateau waves. Warns against impending intracranial hypertension and impairment
of intracranial compliance. They were initially thought to be related to Cheyne - Stokes
respiration, but can occur in patients on controlled ventilation. They are particularly
prominent during REM sleep, an may occur I normal people

C waves occur more frequently (6/min) and are of less amplitude and if little clinical
significance except that they only occur in the presence of brain pathology and imply an
unstable control of cerebral blood flow.
There are waves which do not fall into any of the categories (Fig. 4) and it may be that
the recognized groups are not distinct entities but merely points in a spectrum.

-Second Edition
2011

322


Advantage:
High fidelity recording
Compliance studies possible
Ventricular pressure response more than 4 mmHg per ml is always associated with a
mass lesion.
Permits emergency tapping of CSF for acute rise in ICP
Cheap and simple
Recalibration can be possible at any time.
Disadvantages:
High infection rate
Intracerebral hemorrhage
Difficult to insert when ventricles are small or collapsed.
May not be suitable in head injury
Zeroed with change in position of the head.
Fluid Filled Surface Monitoring Devices:
Balloon devices Fluid-filled balloons are placed subdurally or epidurally and connected
to external fluid filled system.
Disadvantages:
1. Small balloons are too sensitive to changes in internal volume
2. Large balloons are difficult to introduce
3. Rupture of balloon exposes brain to the contents of the balloon.
Hallow screw Devices
Here a hollow screw is placed through a twist drill hole and this utilizes the arachnoid
as the sensitizing membrane. It is then connected to a fluid filled system.
Advantages:
high fidelity traces
cheap, simple
recalibration possible
Avoids cerebral trauma.
Disadvantages:
high infection rate
can get occluded by edematous cerebrum

-Second Edition
2011

323


Intracranial Pressure/Volume Curve:
The intracranial pressure volume curve shows that as intracranial volume
increases there is very little change in pressure during the phase of compensation. With
further increase in volume pressure begin to rise forming a knee. Still further increase
in volume causes marked rise in pressure during the phase of decomposition.
Indications for ICP Monitoring:
1. Head injury when Glasgow Coma Scale is less than 8.
2. Hepatic encephalopathy
3. Reyes syndrome
4. Anoxic encephalopathy
5. Large intra cranial space-occupying lesion.
6. Intra operatively in cases where the ICP is deemed very
high and likely to increase further.
Uses of ICP Monitoring:
Diagnostic
1. Early detection of cerebral edema or other causes of raised ICP.
2. Confirms that neurological deterioration is due to rising ICP and prevents
inappropriate therapy.
3. Suggests the need for repeat CT scan in a patient with heat injury.
Prognostic: in patients with head injury
Techniques of ICP Monitoring:
Intraventricular Catheter
The Catheter is placed inside the ventricles through twist drill hole and its
exteriorized through the skin connected to a fluid coupled system kept on
patients
1. Can underestimate ICP monitoring
2. Produces artifact on CT scan
3. Fluid drainage not possible
Cup catheter: This is a hollow ribbon-shaped device with a cup on the flat surface of the
ribbon at its end. The cup utilizes the arachnoid as its sensing membrane.

-Second Edition
2011

324


Advantages:
It can be brought out through a scalp incision remote from the area of opening in
the skull. So chance of infection is reduced.
Can be inserted through a craniotomy
Non Fluid Coupled Devices for Surface Monitoring of ICP:
Mechanical (ICP pressure switch)
A small balloon containing electrical contacts fastened to its inner walls is introduced
into the subdural or intradural space. When the balloon is fastened because of raised
ICP the electrical contacts remain in contact, thereby completing a servo circuit. Servo
circuit powers an infusion which pressurizes the inside of the balloon upto a point
which separates the electrodes and breaks the circuit. The applied pressure at this stage
represents the ICP.
Optical (Ladd ICP monitor)
It utilizes a fiberoptic system. Distortion of a tiny mirror inside a balloon system by the
raised ICP is transmitted through a fine fiberoptic cable; this signal switches on an
infusion pump which applies adequate intraluminal pressure to the balloon to restore
the position of the mirror.
Electronic devices:
Convert ICP into an electric signal which is transmitted through cables to the monitor. A
device which detects changes in capacitance is commonly utilized.
Fully Implantable Devices:
Good for long term monitoring. Pressure signal is converted into electrical signal
which is detected transcutaneous by external sensing antennae.
Disadvantages:
1. Infection
2. Loss of accuracy
Epidural Sensory:
Advantages:
Low risk of infection
Can be used in children
No CT artifacts

-Second Edition
2011

325


Disadvantages:
1. Difficult to calibrate
2. Expensive
3. Compliance studies not possible
4. Fiberoptic epidural devices have a high latency and transmit waveforms poorly.
Properties of an ideal transducer:
1. Recording must be from the intracranial space
2. Minimum risk of infection
3. Insertion of the device should produce no brain damage
4. Procedure for insertion and removal must be simple
5. If transducer is to be implantable it must be small.
6. It must be drift-free with time and temperature and capable of being calibrated
in situ.
7. It should allow freedom of patient movement
8. It should have adequate sensitivity.
9. It should be impervious to the environment.
10. It should have extended use.
11. It should not be too expensive.
Limitations:
1. None of the methods are universally useful.
2. Errors can occur as a result of technical fault.
3. Monitoring of ICP alone does not ensure a good outcome as other factors like
regional blow flow distribution and changes in cellular level also influence the
outcome.

-Second Edition
2011

326


Chapter 30 - NEUROGENIC PULMONARY EDEMA
Current clinical and experimental data leave little doubt that the injured brain is highly
vulnerable to secondary ischemic insults. Many insults, such as hypoxemia and
hypotension, occur after patients have entered the medical care system. Consequently,
prevention, early diagnosis, and effective treatment of hypoxemia and hypotension in
patients with acute severe brain injury should help to limit personal, social, and
economic costs.
Severe brain injury disrupts multiple respiratory functions, depending on the site and
extent of the neurological injury (Table 1). Importantly, each of these respiratory
complications as well as other medical sequelae can contribute significantly to short-
and long-term morbidity, disability, and mortality related to severe brain injury.
Familiarity with important respiratory complications is an integral part of the
management of critically ill patients with brain injury.
The development of pulmonary edema in the setting of an acute neurologic event is
termed neurogenic pulmonary edema (NPE) and was first described in 1908 by
Shanahan in patients with epilepsy who died of postictal respiratory distress. Acute NPE
is an uncommon, perhaps inconsistently recognized, clinical entity that can occur after
virtually any form of insult to the central nervous system (CNS). Most commonly, NPE
follows subarachnoid hemorrhage (SAH), but the syndrome is also associated with
other acute neurologic insults such as traumatic brain injury, seizures, stroke,
intracranial hemorrhage, infection, induction of anesthesia, and electroconvulsive
therapy.
CLINICAL SYNDROME
The clinical presentation of NPE is often abrupt and dramatic but resembles other forms
of acute pulmonary edema. Often, the acuteness of onset of respiratory failure is the
primary aspect that suggests the diagnosis. Colice described 2 patterns of evolution of
NPE. In the early or classic form, which occurs most commonly, pulmonary edema
develops within minutes to a few hours after an acute CNS insult. The delayed form of
NPE develops more slowly, progressing over 12 hours to several days after the
precipitating event.
Most patients present with symptoms of respiratory failure soon after the acute
neurologic event (Table 2). The most common presenting signs of NPE are dyspnea,
tachypnea, tachycardia, and cyanosis. One of the hallmark characteristics, though
evident in only about one third of patients, is the development of pink, frothy sputum,
accompanied by crackles, rales, and fever. Chest radiography demonstrates diffuse
bilateral alveolar and interstitial pulmonary infiltrates ("whiteout"). The diagnosis is
supported by marked hypoxemic respiratory failure and pulmonary edema with low
-Second Edition
2011

327


pulmonary arterial occlusion pressure (PAOP). PAOP may be increased shortly after
onset, but is usually normal after several hours, thereby leading many clinicians to
consider NPE a form of non cardiogenic pulmonary edema. Other causes of acute
respiratory failure that must be excluded include congestive heart failure, fluid
overload, foreign body aspiration, gastric aspiration, and barotrauma.
In the delayed form of NPE, the clinical presentation typically includes gradual
development over several days of hypoxemia, chest radiographic abnormalities, and
dyspnea. Distinguishing the delayed form of NPE from other etiologies in patients with
acute neurologic insults can be challenging. In intubated critically ill patients, atelectasis
or pneumonia can produce similar hypoxemia, chest radio-graphic abnormalities, and
dyspnea. In addition, the characteristic pattern of pulmonary edema may be less evident
in portable chest radiographs.

Respiratory Complications of Severe Brain Injury
Impaired chest wall mechanics and diaphragm function
Abnormal breathing patterns
- Cheyne-Stokes respiration
- Central neurogenic hyperventilation
- Apneustic breathing
- Ataxic breathing
- Hypoventilation or apnea
Pulmonary embolism
Dysphagia, aspiration, and pneumonia
Neurogenic pulmonary edema

Although NPE should be suspected in any patient in whom symptoms of respiratory
failure follow an acute neurologic event, the diagnosis of NPE remains one of exclusion.
Therefore, the incidence of NPE is difficult to establish; given its nonspecific
presentation, it is likely that the diagnosis is missed, especially in the later onset form,
but also that it is applied incorrectly to patients with other reasons for respiratory
compromise. The physician faced with the difficult task of caring for a patient with a
combination of acute neurologic disease and respiratory complications must balance
several competing priorities.
-Second Edition
2011

328


Common sign &symptoms of neurogenic pulmonary Edema
Hypoxemia
Dyspnea
Tachypnea
Pink frothy sputum
Pulmonary crackles, rales
Angina
Tachycardia
Lung findingsbilateral, diffuse interstitial / alveolar
Infiltrates ("whiteout")
Normal to high pulmonary artery wedge pressure
ECGsigns of cardiac ischemia
Cardiovascular instability
Normal to high CK-MB, troponin
Leukocytosis
PATHOGENESIS OF NPE:
NPE is characterized by an increase in extra-vascular lung water in patients who have
sustained a sudden change in neurologic condition. The mechanism by which NPE
occurs is not clear. Possible pathophysiological mechanisms of NPE include alterations
in capillary permeability, elevations in pulmonary venous hydrostatic pressure, or left
ventricular dysfunction.

Permeability Abnormalities
In both animal and human studies of NPE, the demonstration of elevated interstitial or
alveolar fluid protein concentrations suggests that increased capillary permeability
Acute brain injury
NPE
Cardiorespiratory
syndrome
-Second Edition
2011

329


contributes to pulmonary edema. Increased permeability may be caused either by
hydrostatic over distension of the pulmonary capillaries or by direct neural influences
on capillary permeability. Theodore and Robin advanced the "blast theory," which
proposes that a neurally induced, transient rise in pulmonary intra-vascular pressure,
caused by a massive sympathetic surge, may damage the endothelium, causing protein-
rich plasma to escape into the interstitial and alveolar spaces. The high protein content
in the edema fluid supports the -blast theory. Investigators have speculated that this
"stress failure" of the pulmonary capillaries resembles alveolar hemorrhage
seen in galloping racehorses.
In support of this theory, high intravascular pressures have been shown to damage
pulmonary capillaries, and such high pressures can develop in animals during
experimental NPE. In humans, elevated PAOP has been observed in a few cases.
However, pulmonary edema can develop with normal PAOP, suggesting the possibility
of a neural-mediated, pressure-independent influence on capillary permeability. It is
important to note that the typical sequence of NPE would be one in which acute
pulmonary edema unexpectedly occurs, after which both treatment and invasive
monitoring are initiated. Consequently, the acute increase in PAOP or pulmonary
arterial pressure could be resolved before hemo-dynamic data are obtained. Neurally
and humoral mediated increases in sympathetic tone after CNS injury that lead to
pulmonary venoconstriction with pulmonary capillary hypertension may cause
endothelial damage and increased pulmonary capillary permeability. Consistent with
this theory, NPE induced experimentally by infusion of epinephrine can be attenuated
by a-adrenergic blocking agents.
Hydrostatic Pulmonary Edema
Hydrostatically induced pulmonary edema can occur without endothelial damage. One
possible sequence leading to NPE is acutely increased sympathetic tone that abruptly
increases left ventricular after load and causes intense venoconstriction, thereby
elevating left ventricular filling pressures and inducing pulmonary capillary
hypertension. This is consistent with the finding that cardiac filling pressures are
normal in some patients with NPE and elevated in others.
Active pulmonary venoconstriction can increase pulmonary capillary pressure and
produce hydrostatic edema. In isolated lung models, induced intracranial hypertension
resulted in venoconstriction and elevated resistance to pulmonary blood flow, perhaps
due to increased circulating catecholamines, predominantly epinephrine. Pulmonary
venoconstriction could result in increased capillary hydrostatic pressure that is
reflected in increased pulmonary systolic and diastolic pressure but not in increased
PAOP. During balloon occlusion, no flow would enter the occluded vascular segment and
-Second Edition
2011

330


normal left atrial pressure would be measured. Such a mechanism could explain both
the observed variance in pulmonary edema protein concentration in the presence of
normal PAOP in patients with NPE. Once again, it is important to note that pulmonary
arterial catheterization after an acute episode of NPE could be too late to document
increased PAOP.
It is likely that a combination of factors in differing proportions produces NPE and that
explains the differing clinical presentations. The role that adrenergic tone might play in
the cardiac response of NPE is also potentially important. In experimental animal
models, extreme sympathetic nervous system over activity can generate acute
hemodynamic derangements, acute left ventricular failure, and pulmonary edema. -
Adrenergic antagonists have been shown to prevent NPE.
Other Possible Mechanisms
Various forms of noncardiac pulmonary edema have been explained on the basis of
hypoxic pulmonary vasoconstriction leading to pulmonary hypertension, arterial wall
rupture, and leakage of protein-rich fluid into the interstitium and alveoli. An
alternative theory is that damaged arterial walls attract fibrin and platelets, which form
thrombi and micro emboli, producing pulmonary capillary hypertension, capillary
rupture, and edema formation. Activated intravascular clotting or fibrinolysis may have
an important role in NPE, as well as in other forms of noncardiac pulmonary edema.
The clinical and pathologic features of NPE are quite similar to those of other forms of
acute respiratory distress syndrome. Moss et al postulate that acute respiratory distress
syndrome in many clinical situations has a common cerebral cause - the initiating
trauma interferes with hypo-thalamic cellular metabolism, which leads to automatically
mediated increased pulmonary venular resistance. This condition results in increased
capillary pressures and vascular congestion, interstitial and intra alveolar edema and
hemorrhage, and right-to-left shunting. The transudate of plasma and resulting hyaline
membrane formation inactivate surfactant and predispose to atelectasis. This is an
attractive unifying theory to explain posttraumatic pulmonary insufficiency and acute
respiratory distress syndrome, as well as the varied forms of noncardiac pulmonary
edema such as NPE.
MEDIATORS OF NPE
Although brain injury results in NPE in scattered clinical cases and in a variety of
experimental models, the mechanisms through which CNS injury produces NPE are
unclear. Experimental studies provide evidence for direct sympathetic mechanisms as
well as circulating mediators.
-Second Edition
2011

331


The high-pressure component of NPE is probably mediated both by circulating
vasoactive agents and by direct stimulation of sympathetic nerves leading to pulmonary
vessels. The pulmonary vasculature is richly innervated by sympathetic nerves, and
stimulation of the stellate ganglion causes pulmonary venous and arterial spasm.
Studies with isolated lung lobes have shown that a vasoactive agent, released into the
venous circulation after CNS injury, is an important mediator of pulmonary
hypertension. This agent is probably a catecholamine, because a-adrenergic blockers
inhibited its effect. Catecholamines increase dramatically within seconds of a variety of
brain injuries. After SAH, the concentrations of epinephrine, norepinephrine, and
dopamine increase almost immediately to 1,200,145, and 35 times the normal limits,
respectively. Furthermore, epinephrine can remain increased in the circulation for at
least 10 days. This could explain why NPE can occur as much as 14 days after a CNS
insult.
After CNS insults, a-adrenergic blockers also prevent systemic hypertension, suggesting
that increased circulating catecholamines are responsible for systemic as well as
pulmonary and vascular constriction. A pulmonary vascular membrane permeability
defect in NPE might be mediated by the increase in circulating catecholamines, release
of non-catecholamine mediators after the massive a-adrenergic discharge, direct a-
adrenergic effects on endothelial cells, or some alteration in -adrenergic tone. -
Adrenergic blockers prevent changes in lymph protein clearance after intracranial
hypertension and stellate ganglion stimulation, suggesting a catecholamine-mediated
change in pulmonary endothelial permeability.
The role of -adrenergic tone in altering pulmonary endothelial permeability is unclear.
-Adrenergic agonists prevented experimental histamine-induced permeability
abnormalities, but -adrenergic antagonists seem to influence pulmonary
transendothelial protein flux by changing vascular surface area.
CNS Involvement
The specific neurologic loci or pathways that generate NPE remain conjectural and
controversial, with somewhat contradictory animal data and limited human data. Based
primarily on animal data, multiple "edemagenic" sites that have been postulated as the
origin of the pathophysiologic process include the hypothalamus and several loci in the
medulla oblongata. The posterior medulla, which forms the inferior aspect of the floor
of the fourth ventricle, includes adrenergic areas 1 and 5 and the nucleus of the solitary
tract. Nerve fibers pass from area 5 to the intermediolateral cell column of the
thoracolumbar spinal cord (the site of sympathetic outflow) and from area 1 to the
hypothalamus. In experimental animals, stimulation of these areas generated NPE.
-Second Edition
2011

332


Clinical evidence suggesting specific anatomic sites has necessarily been anecdotal.
Because NPE is extremely rare in patients with cervical spinal cord lesions, the CNS
regions responsible for NPE are assumed to be supraspinal. Brain-imaging techniques
provide evidence that derangements of the medulla (which contains the vasomotor
center) contribute to NPE.
By causing sympathetic activation, posterior hypothalamic lesions also can precipitate
NPE in humans. In a series of 106 patients dying from SAH, 65 had hypothalamic lesions
that had histological evidence of ischemia, micro hemorrhages, massive hemorrhage, or
a combination of ischemia and hemorrhage. The hypothalamus probably is part of an
integrated response, also involving portions of the medulla, that initiates NPE. Several
studies have shown that the hypothalamus, along with the nucleus tractus solitarius and
ventrolateral medulla, plays an important role in regulating cardiovascular responses
by the autonomic nervous system.
CLINICAL MANAGEMENT OF NPE
There are no specific treatments for NPE, other than immediate management of such
precipitating causes as intracranial hypertension or evacuation of intracranial space-
occupying lesions. Maintenance of intentional hypocarbia, diuretics, and mannitol may
also be helpful in controlling ICP, at least temporarily. Management of respiratory com-
promise is largely supportive and does not differ substantially from supportive care of
acute respiratory failure caused by other factors. Respiratory support consists of
various combinations of supplemental oxygen therapy, mechanical ventilation, judicious
fluid management and, possibly, sodium nitroprusside, which may be useful for its
ability to directly dilate peripheral and pulmonary vessels . Care should be taken with
the administration of sodium nitroprusside because of its potential for increasing ICP.

-Second Edition
2011

333


Management of Patients with Neurogenic Pulmonary Edema
Methods to control intracranial hypertension
- Position to improve cerebral venous return (neutral, head-up position)
- Avoiding drugs that increase ICP
- Diuretics: osmotic (mannitol, hypertonic saline); tubular (furosemide)
- Adequate ventilation: PaO2> 100 mm Hg, PaCO2 35 mm Hg,
hyperventilation on demand Optimize hemodynamics (MAP, CVP, PAOP,
HR), maintain CPP
- Temperature control: avoid hyperthermia CSF drainage
Improvement of oxygenation
- Oxygen supply: via nasal mask (6 L/min); if necessary, intubation
(ventilation, PEEP <4-8 cm H2O)
Decreases pre- and after load
- Vasodilators (nitroglycerine, sodium nitroprusside, blockers of a-
adrenoreceptors)
- Diuretics: tubular (furosemide)
Inotropic treatment
- -adrenergic drugs: Dobutamine
Mechanical ventilation with PEEP rapidly improves both oxygenation and radiographic
evidence of NPE. PEEP is titrated to attain an acceptable balance between systemic
hemodynamics, arterial oxygenation, and FiO2. An assisted mode of ventilation, such as
intermittent mandatory ventilation or pressure control ventilation, with PEEP is often
sufficient to resolve NPE, and weaning can be achieved fairly rapidly in many patients.
The use of PEEP to improve oxygenation may increase ICP in some patients with brain
injury by increasing cerebral venous pressure. PEEP may further decrease cerebral
perfusion pressure by decreasing cardiac output and ABP, Excessive reduction of
cerebral perfusion pressure could aggravate neurologic injury. If PEEP is required for
management of hypoxemia, ICP should be monitored concomitantly. PEEP therapy may
need to be reduced or combined with head elevation if PEEP is associated with
increasing ICP or neurological deterioration.
-Second Edition
2011

334


In patients with considerable hemodynamic instability, assessment of cardiac function
with pulmonary arterial catheterization, transesophageal echocardiography, or
esophageal Doppler may help to guide therapy. Inotropic support may be necessary.
Although massive release of catecholamines in association with acute neurologic
injuries may contribute to ventricular injury and NPE, the much smaller circulating
levels associated with inotropic infusion may improve systemic hemodynamics and
increase systemic oxygen delivery. For example, dobutamine improves cardiac
contractility and decreases after load, thereby maintaining cardiac output and
potentially improving cerebral perfusion while reducing sympathetic tone.
Theoretically, pharmacologic blockade of the sympathetic surge associated with some
acute brain injuries should limit the occurrence and severity of NPE. Prophylactic -
blockade with Phenoxybenzamine prevented death and pulmonary edema in rabbits
infused with high doses of epinephrine. There are few data from clinical trials, but
prophylactic combined a- and -blockade with phentolamine and propranolol may
reduce pulmonary and myocardial injury from catecholamines after SAH. However,
clinical application of this information in patients with NPE is difficult. In many patients,
the acute sympathetic surge will have passed by the time NPE is recognized, and
sympathetic blockade would no longer be expected to be helpful. In other patients,
systemic hypertension may be a response to intracranial hypertension, in which case
the reduction in ABP without a reduction in ICP could lead to severe brain ischemia. In a
subset of patients in whom severe systemic hypertension persists after control of intra-
cranial hypertension, reduction of ABP is indicated but may, not have any direct effect
on the course of NPE.

-Second Edition
2011

335



-Second Edition
2011

336


Chapter 31 - Head Injury Pathophysiology & Anesthetic
Management
INTRODUCTION:
Traumatic neurologic injury is a major public health problem in both technically
advanced countries and developing countries in urban and rural areas, and in patients
of all ages and socio-economic backgrounds.
Head injury is the leading cause of death or permanent disability in adolescents, young
adults and people >75 years of age. Males are affected more. Most common causes of
head injury - motor vehicle crashes, violence and falls.
The anesthesiologist is closely involved in all areas of care of the patient with traumatic
neurologic injury from initial resuscitation, through neuro diagnostic testing, surgical
intervention and post anesthetic and intensive care.
HEAD INJURY
Definition and statistics:
Brain injury is a dynamic process not only does the patient's pathologic picture,
continue to evolve over the first few hours and days after trauma often with devastating
secondary injury but the physiologic and clinical aspects of the recovery process can
continue for years. The many poorly understood variables involved include, changes in
nutrition, intracranial dynamics, cardiopulmonary status.
MUNRO KELLIE DOCTRINE
To protect the brain, nature has encapsulated it in a rigid closed container. However due
to this very reason, increase in size of any of the contents of the cranium, viz., The brain,
Cerebrospinal fluid or Blood, can only be at the expense of one of the other two
contents. This is the Munroe-Kellie Doctrine. Acute TBI rapidly leads to brain swelling,
hematoma or obstructive hydrocephalus.
The normal contents of the cranium are:
1. Brain neural tissue and interstitial fluid 1400g (80%)
2. Blood 75ml (912%)
3. CSF 75ml (+75ml spinal cord) (8%)
4. ICP 7-18 cmH2O
-Second Edition
2011

337


Normal ICP is defined as the pressure inside the lateral ventricles /lumbar
subarachnoid space in supine position. The normal value is 10-15 mmHg in adults and
around 2-4 mmHg in neonates and infants.
Cerebral perfusion pressure CPP = MAP - ICP.
Intracranial hypertension: Sustained pressure within the subarachnoid space >20
mmhg.
The brain is further compartmentalized by rigid dural membranes into two lateral
hemispheres in the supra tentorial compartments and the infra-tentorial
compartment. Increase in pressure in any 1 compartment can lead to herniation of
brain into the other compartment.

CEREBRAL AUTOREGULATION
The Cerebral Blood flow (CBF) is maintained consistent over a wide range of cerebral
perfusion pressure (CPP) from 50-150mm hg. Above and below this range it becomes
pressure Passive, i.e., It increases ad decreases passively with arterial pressure. Hence
increase CBF leads to increased cerebral blood volume resulting in increased ICP and
decreased cerebral perfusion pressure (Fig).

-Second Edition
2011

338


Hence it is essential to maintain MAP within Auto-regulatory range.
Severe TBI leads to disruption of cerebral autoregulation
Flow-Metabolism coupling
CBF is directly related to cerebral metabolism. Any increase in metabolism (e.g., hyper
pyrexia) causes increase CBF leading to raised ICP.
Vascular response to C02 & 02.
CBF shows a linear response to PaCO2 from 20-80 mmHg. Hence any
hypercapnia leads to increased CBF volume causing increased ICP and decreased
cerebral perfusion:
CBF is independent of Pa)2 till a pa)2 of 50 mmHg. Below this the CBF increase
steeply with further fall of Pa)2 hence any hypoxia leads to increased CBF
volume and worse outcome. (Fig).

MECHANISM OF BRAIN INJURY
The CSF and the skull both protect the brain.
Rapid acceleration / deceleration and focal forces can all injure the brain.
A coup injury results from trauma at the site of impact.
A countercoup injury is remote from the site of the impact.
Trauma imparted to the cranium can thus either take the form of translational
acceleration or deceleration forces, rotational forces, direct, focal, sharp penetrating or
blunt forces. These can involve scalp skull, brain, independently or in any combination.
Abrupt deceleration: Abrupt deceleration of a moving head is characterized by a
relatively minor injury at the site of impact (coup injury) and extensive contusion of
brain, remote and usually opposite to the point of impact (countercoup) injury.
Contusion occurs along the undersurface of the frontal lobes, the tips of the temporal
lobes, beneath the falx and in the brain stem.
-Second Edition
2011

339


Abrupt acceleration: Of an unsupported head occurs, when it is struck by a moving
object. The skull accelerates against brain causing an extensive coup injury of the brain.
The remainder of brain remain unchanged. When a moving object strikes a well
supported head, there is little movement of the skull and brain. Most of the forces is
absorbed by the skull, which will fracture. Damage to the underlying brain results from
direct perforation or laceration by skull fragments. So most cerebral contusions occur
without skull fracture and why patients with spectacular fractures are often awake with
only minor neurological dysfunction.
PATHOPHYSIOLOGY:
PRIMARY INJURY:
Primary brain damage is defined as the damage to neurons (especially axonal damage)
astrocytes, and cerebral vessels resulting from brief application of shearing forces, with
consequent tissue deformation, at the time of injury. Following trauma primary results
from the effect of biomechanical forces applied to skull and brain at the time of insert
and is manifested within milliseconds.

Primary brain damage is believed to be irreversible and therefore, not amenable to
therapy prevention strategies for vehicles, drive safety, and the environment, are thus
very important.

-Second Edition
2011

340


SECONDARY INJURY
Secondary brain damage may be defined as delayed damage to cerebral tissue, as a
result of 1) harmful ionic shifts, 2) hypoxia; 3) ischemia, 4) cerebral edema, S) elevated
intra cranial pressure (ICP), 6) infection, 7) seizures and 8) other less clearly
understood mechanisms.
MAIN PATHOLOGICAL MANIFESTATIONS
Brain swelling - post traumatic enlargement of the brain mass by 1) brain edema or 2)
vascular engorgement.
1) Brain edema - increased extra or intracellular water content is termed brain
edema caused by different pathophysiological mechanisms.
i) Cytotoxic edema - intracellular water content is markedly increased due to
energy depletion, due to failure of Na+, K+ ATPase and stimulation of the
neurons - due to massive glutamate release after head injury.
ii) Vasogenic edema - cause is transient impairment of the blood brain barrier.
iii) Osmotic edema - of decreased blood osmotic pressure leads to inflow of water
into extracellular space. Inadequate secretion of ADH is another possible cause
but rare.
iv) Hydrostatic edema - due to increase in hydrostatic pressure free water may
diffuse, into the brain tissue. Cause is impaired autoregulation mechanisms and
high blood pressure.
v) Interstitial edema - disturbances in the drainage of CSF result perventricular water
accumulation.
Vascular engorgement: Cerebrovascular dilation due to vasomotor paralysis or post-
ischemic reperfusion.

-Second Edition
2011

341


CLASSIFICATION OF HEAD INJURY:
There are several classification of head injuries
Head injury classification:
Based on
1. Severity -Mild (GCS 13-15)
-Moderate (GCS 9-12)
-Severe (GCS 8 or less)

2. Pathology -Skull fractures
-Intracranial lesion

3. Mechanism - Non missile injuries (closed head injuries)
- Missile injuries (Penetrating injuries)

4. CT findings - Diffuse injury I (DAI)
-Diffuse injury II
-Diffuse injury III
-Diffuse injury IV
SEVERITY OF INJURY:
Neurological examination in emergency room after cardiopulmonary resuscitation is
used to determine the severity of injury.
This is based on Glasgow Coma scale. GCS defines impairment in terms of eye opening,
speech and motor function.

-Second Edition
2011

342


Glasgow coma scale:
Eye opening:
1. Spontaneously -4
2. To verbal command -3
3. To painful stimuli - 2
4. None -1
Best motor response:
1. Obeys verbal commands -6
2. Localizes to pain -5
3. Withdraws -4
4. Abnormal flexion (decorticate) -3
5. Abnormal extension (Decerebrate) - 2
6. No response -1
Best verbal response:
1. Oriented, conversing - 5
2. Disoriented, conversing -4
3. In appropriate words -3
4. Incomprehensible sounds -2
5. No verbal response -1
The GCS described by Teasdale and Jennett is used to quantitate the neurological
examination.
Patient who open their eyes spontaneously, obey commands, and are oriented score the
maximum of 15 points. And those who have neurological functions score 3 points.
Patients with a post resuscitations GCS score of 8 or less have suffered a severe head
injury, and patients with a GCS score of 9-12 and 13-15 have moderate and mild injury
respectively.
Coma strictly as the inability to obey commands, utter words, or open the eyes. No
single GCS score within the range of 3-15 forms on absolute cut of points for coma by
this strict definition, a GCS of 8 or less as generally be considered synonymous with
coma.

-Second Edition
2011

343


The mortality rate with a GCS score of
GCS 6-7 : 24%
GCS 4-5 : 49%
GCS 3 : 83%
GCS 9-15 : 12%
GCS gives information about the level of consciousness, where as papillary response to
light and oculocephalic or vestibular reflexes give complementary information about
brainstem function. For patients with severe lead injury (less than 8), abnormalities of
these reflexes have additional predictive power.
Modified of Glasgow Coma Scale for Children
Response Score Age
Eye response
Spontaneous
To Speech
To pain
None

4
3
2
1

Best motor response in upper limbs (Score highest appropriate for age)
Obeys commands
Localizes to pain
Normal flexion to pain
Spastic flexion to pain
Extension to pain
None
6
5
4
3
2
1
> 2 years
6 months 2 years
> 6 Months
< 6 Months
Best verbal response (Score highest appropriate for age)
Oriented to place
words
Vocal sounds
Cries
None
5
4
3
2
1
> 5 years
> 12 years
< 6 months
< 6 months
Based on pathology of injury:
Head injury can be 1. Skull fractures and
2. Intra cranial lesions.
SKULL FRACTURES:
May or may not be associated with underlying brain injury the cranial vault is fractured
three times as often as skull base (62% compared with 20%). Skull fractures associated
with CSF, rhinorrhea and otorrhea are definite signs of a dural tear and predispose
acutely head injured patient to the development of post traumatic meningitis. CSF
rhinorrhea is usually associated with transverse fractures of the petrous bone and
usually stops within a week. Meningitis is more common in otorrhea than rhinorrhea.
-Second Edition
2011

344


Intra-cranial lesions:
Intra cranial lesions classified as a) focal, b) diffuse the two may co-exist.
Focal - Subdural hematoma
- Epidural hematoma
- Intracerebral hematoma
- Subarachnoid hematoma

Diffuse - I, II, III
THE SUBDURAL HEMATOMA:
1. The hematoma is between the dura and the brain.
2. Usually resulting from a torn bridging vein between the cortex and the draining
sinuses.
3. Appears on a CT scan as a high density homogenous crescent shaped mass
paralleling the calvarium.
4. Subacute 3-15 days,
5. Chronic > 2 weeks
EPIDURAL HEMATOMAS:
1. Collections of blood between the skull and dura are less common.
2. Although patients with subdural hematomas are usually immediately comatose,
only 1/3 of patients with an epidural hematoma are unconscious from the time
of injury, 1/3 have a lucid interval, 1/3 are never unconscious.
3. An epidural hematoma is almost always associated with a skull fracture.
4. The blood comes from torn dural vessel, usually arterial, from the fractured skull
bones or occasionally, from torn venous sinuses.
5. CT scan an epidural hematoma is characterized by a biconvex uniformly
hyperdense lesion.
INTRA-CEREBRAL HEMATOMA
From a spontaneous haemorrhage differentiating by the presence of associated
contusion, fracture, or air fluid in the sinus helps in identifying the hematoma as
traumatic. In contrast to spontaneous hemorrhage, traumatic intra cerebral hematomas
are irregular and poorly marginated. A zone of surrounding hypodensity denotes
contusion or edema.
-Second Edition
2011

345


DIFFUSE BRAIN INJURIES(DBI)have no mass lesion requiring surgery, traumatic loss of
consciousness of less than 6 hours is considered a concussion and is usually associated
with amnesia for the events related to the injury. The three levels of severity for DBI are
1. Mild DBI, coma of 6-24 hours duration
2. Moderate DBI, coma of more than 24 hours without decerebrate posturing.
3. Severe DBI, coma of more than 24 hours. With decerebrate posturing or flaccidity.
Severe DAI has a 50% mortality.
Based on mechanism of injury:
Head injuries can be divided into two general categories based on the mode of injury.
a) Non missile or closed head injuries are usually associated with moto-vehicle
accidents, falls, and assaults.
b) Missile or penetrating injuries are most commonly due to gunshot wounds.
This differentiation is important because of surgical management and outcome of
missile injuries are somewhat different form non-missile injuries.
Based on CT scan:
Diffuse injury I No visible intracranial pathology seen on CT scan
Diffuse injury II - Cisterns are present
- Midline shift: 0-5 mm
- No high/mixed density lesion > 25cc
- May include bone fragments or foreign bodies.

Diffuse injury III
(Swelling)
- Cisterns are compressed or absent
- Midline shift: 0-5 mm
- No high/mixed density lesion > 25cc
- May include bone fragments or foreign bodies
Diffuse injury IV (Shift) - Midline shift:> 5mm
- No high / mixed density lesion > 25cc
Evacuated mass lesion Any lesion surgically evacuated.
Non evacuated mass lesion High/mixed density lesion > 25cc that is not surgically
evacuated.
CHANGES IN CNS
a. Cerebral metabolism:
Cerebral metabolic rate of oxygen (CMR02) is depressed following head trauma. A liner
correlation has been reported between Glasgow Coma Score (GCS) and CMR02. 1) In
patients with severe head injury CTOR02 is generally less than 1.5 ml/ 100g/min as
-Second Edition
2011

346


against a normal value of 3.0 ml/ 100g/min. Head trauma may also affect the cerebral
blood flow metabolism coupling to a variable extent. Orbits et al showed that a low flow
state representing a normal CBF-CMR relation occurs in 45% of head injured patients.
Absolute or relative hyperthermia representing impaired CBF-CMR relation is seen in
55% of head injured patients 2) The patients with hyperemia are likely to have
intracranial hypertension with its perioperative implications.
b) Cerebral blood flow
Both ischemic and hyperemic ranges of CBF have been documented following head
injury.
CBF changes following head trauma have been divided into 4 phases
Early ischemic phase: The first phase lasting upto 12 hour is characterized by
very low blood flow,
Phase II hyperemia phase: following which blood flow increases rapidly to
reach a hyperaemic level within 24 hours. The hyperaemic phase lasts upto to
about 72 hours and is followed by a
Phase III delayed ischemic phase: stage of progressively decreasing CBF
lasting for about 15-20 days. This delayed ischemic phase is followed by a,
Phase IV recovery of CBF: The degree of hypoperfusion during the early or
delayed ischemic phases is an important determinant of ,the mortality.
Therefore, there is a need to maintain stable hemodynamic status in patients
undergoing surgery during the acute phase.
Autoregulation:
A variable degree of impairment of autoregulatory control of CBF follows head trauma.
The time course of autoregulatory impairment after traumatic brain injury is not clearly
understood. However, the lower limit of autoregulation - normally believed to be 50-60
mmHg mean arterial pressure (MAP) - is understood to be elevated following severe
head injury. Therefore, a higher cerebral perfusion pressure (CPP) has to be maintained
to protect the brain from ischemic insults resulting from systemic hypotension.
Cerebral vascular response to carbon dioxide
The linear relationship between PaC02 and CBF within physiological ranges of PaC02 is
preserved till late in the course of head trauma. Therefore, hyperventilation is effective
in decreasing ICP in most of the patients. Loss of response to C02 heralds poor
prognosis.
-Second Edition
2011

347


Raised intracranial pressure
Raised ICP and the consequent reduction in the CPP is one of the major mechanisms of
cerebral ischemia after traumatic brain injury. Mass lesions such as hematomas,
cerebral hyperemia,, and brain edema are responsible for raised ICP. Apart from
reducing CPP, high ICP may also cause Brian herniations that lead to neurological
deterioration.
Generally patients who follow commands (GCS 9-15) have a very low risk of intracranial
hypertension. About 3% of patients with mild head injury (GCS 13-15) and 10-20% of
patients with moderate injury (GCS 9-12) deteriorate into coma (3). In contrast with
mild and moderate injuries, severe head injuries (GCS <8) have a high incidence of
intracranial hypertension.
Abnormalities of coagulation
The incidence of clotting abnormalities in TBI is reported to vary between 15 and 100%,
Some studies have established a direct association between the severity of coagulopathy
and the likelihood of adverse outcome, a relationship that was not dependent on the
severity of injury alone. Data from traumatic coma data bank in the United States also
found coagulopathy to be a significant independent predictor of an unfavorable
outcome. The effect of coagulopathy was second only to that of shock.
MULTISYSTEM SEQUELAE OF SEVERE HEAD INJURY:
Cardiopulmonary
Abnormal breathing patterns
Airway obstruction
Hypoxemia
Shock
Adult respiratory distress syndrome
Neurogenic pulmonary edema - marked pulmonary vascular congestion intra-
alveolar haemorrhage a protein rich edema fluid, (cause is massive sympathetic
discharge from injured brain).
Fat embolism
Electrocardiographic changes - peaked P waves, prolonged QT, depressed ST,
Inverted / Flattened T, Prominent U waves, SVT, AF, Block VT.
Diaphragmatic paralysis
Hematologic
Trauma and coagulation
Disseminated intravascular coagulation
-Second Edition
2011

348


Endocrinology
Anterior pituitary insufficiency
Posterior pituitary dysfunction
Diabetes insipidus - Polyuria, polydipsia, hypernatremia, serum ECF
hyperosmolality and dilute urine. Treatment was water replacement exogenous
vasopressin.
Syndrome of inappropriate antidiuretic hormone secretion - hyponatremia -
Treatment - water restriction, hypertonic saline.
Metabolic
Metabolic response to head injury
Cerebrospinal fluid metabolic changes
Non-ketotic hyperosmolar hyperglycemic coma - because of use of steroids,
prolonged mannitol tube feeding, phenytoin - diagnosis hyperglycemia, glucose
urea absence of ketones. Plasma osmolality >330 mosm, dehydration and CNS
dysfunction. Treatment - Replace Na+ and water deficiency (0.45% normal
saline), small dose of insulin.
Gastrointestinal
Ulceration
Gastroparesis
Swallowing disorders
Skeletal
Maxillofacial injuries,
PREHOSPITAL MANAGEMENT OF HEAD INJURY:
Goals of preclinical management
Stabilization of vital functions
Evaluation of consciousness and injury pattern
Stabilization of the vertebral column
Adequate pain treatment
Gathering of useful information about the injury mechanism.
Transport of the patient to an adequate medical center, close monitoring of vital and
neurologic functions.
The most important goals of pre-hospital management are to maintain the airway and
to support blood pressure to preserve cerebral perfusion pressure (CPP). Prehospital
hypoxia and hypotension are common in severely head-injured patient.

-Second Edition
2011

349


EMERGENCY ROOM MANAGEMENT OF HEAD INJURY
Goals of clinical management
Stabilization of vital functions
Comprehensive monitoring vital functions
Precise diagnosis
Acute surgical treatment of major mass lesions and hematomas
Adequate pain treatment
Transfer to a specialized ICU.
Mild Head Injury
Patient with no history of loss of consciousness, no vomiting or amnesia, a normal
neurologic examination, and minimal, if any, subgaleal swelling can be released into the
care of relatives who are given a special instruction sheet (x-rays studies are
unnecessary).
Patients with at least one of the following features should undergo a CT scan: transient
loss of consciousness, posttraumatic amnesia, a single episode of vomiting, or significant
subgaleal swelling. If the CT scan is normal, only a short period of observation is
necessary.
Patients with at least one of the following symptoms: impaired consciousness, repeated
episodes of vomiting, neurologic deficits, otorrhagia, otorrhea, rhinorrhea, signs of basal
skull fracture, seizures, penetrating or perforating wounds, or lack of cooperation for
varying reasons; patients who have undergone previous intracranial operations or have
been affected by coagulopathy or submitted to anticoagulant therapy; and epileptic or
alcoholic patients should receive a CT scan immediately and, if necessary, again before
discharge. Comatose patients should undergo a CT scan immediately after resuscitation
and before any surgical intervention.

Moderate Head Injury
Patients with a GCS score of 9 to 12 should have an emergent CT scan and be admitted
for observation even though their initial CT scan is normal. The goals of monitoring are
the same as for severe head injuries, except the neurologic status is monitored by serial
neurologic examinations. ICP monitoring is reserved for those patients
,
who clinically
deteriorate or, possibly, for patients who, because of treatment of systemic injuries,
cannot be observed with serial neurologic examinations.

-Second Edition
2011

350


Severe Head Injury
Resuscitation
The first goal of resuscitation of a severely head-injured patient is cardiopulmonary
stabilization. All patients are intubated to protect their airway from aspiration and to
callow controlled ventilation.
Hypotension should be rapidly treated with volume replacement n adults, hypotension
is rarely caused by head injury alone, and another injury site should be sought. Blood
loss from another injury, an associated spinal cord injury, cardiac contusion or
tamponade, and tension pneumothorax are other causes of hypotension to be
considered.
Standard resuscitation fluids include. Crystalloids, colloids, and blood products
Crystalloids should not include glucose to minimize hyperglycemia.
ICP should be assumed to be elevated in patients with severe head injury before
definitive treatment.
ICP controlled temporarily with controlled ventilation (Pao2 > 100 mm Hg; Pac02, 30 to
35 mm Hg) to prevent hypoxia and hypercapnia and with sedation and paralysis until
definitive treatment of surgical lesions and an ICP monitor can be placed. Mannitol (1 g/
kg IV) is given if the patient has signs of herniation or is neurologically deteriorating.
Diagnostic Evaluation
History: Even though obtaining a detailed history is often not possible in patients with
severe head injuries, the approximate time and mechanism of injury at the scene of the
accident may be obtained from the paramedics. The time of intubation and the patient's
vital signs and neurologic deficits at the scene of accident and during transportation,
especially the presence of apnea and hypotension, will help in subsequent evaluations.
In addition, progressive deterioration of the level of sensorium before the patient
reaches the hospital suggests an expanding intracranial mass lesion, and the I patient
who was unconscious from the time of injury is more likely to have diffuse axonal
injury.
Neurologic Examination: The neurologic examination should include, in addition to
vital signs, the GCS score to assess functional capacity of the cerebral cortex, the
papillary examination and the corneal-reflex to assess brainstem function, and the
oculocephalic and oculovestibular reflex to assess eye movement.
-Second Edition
2011

351


Radiological Examination: Before, the advent of CT scanning, the common radiologic
procedures in the management of head-injured patients included skull x-ray films,
cerebral angiography, ventriculography, and radionuclide brain scanning.
MEDICAL MANAGEMENT OF HEAD INJURY:
Treatment of intracranial hypertension:
General measures. In all patients with severe head injury, simple measure should be
taken to minimize systemic factors that can cause or aggravate intracranial
hypertension. Commonly recommended practices include elevating the head of the bed
15 to 30 degrees, sedation, controlled ventilation, seizure prophylaxis, and treatment of
systemic hypertension and fever when present.
Specific measures
For patients with sustained ICP greater than 20 mm Hg, despite the general measures
described previously, specific measures are added in a stepwise fashion until the ICP is
controlled.
Pharmacologic paralysis:
A reasonable regimen is morphine and lorazepam for sedation and cisatracurium or
vecuronium as a muscle relaxant, with the dose titrated by twitch response to
stimulation.
Hyperventilation:
Induced hyperventilation constricts cerebral blood vessels, reducing global CBF and
cerebral blood volume.
British Trauma Foundation 2001 guidelines recommend avoiding prophylactic
hyperventilation (PaC02 <35 mmHg) during 1
st
24 hours after TBI. The ideal goal is to
maintain permissive hypocapnia (PaC02 -35 mmHg).
The vascular response to C02 is a robust phenomenon and is unlikely to be lost even in
severe TBI, a short period of hyperventilation is a useful weapon in the hands of the
anesthesiologist to reduce ICP and buy time in patients who are potentially coning until
other definitive measures can be instituted.
CSF drainage
Although removal of l mL of CSF normally does not change ICP by more than 1 to 2mm
Hg, in patients with an elevated ICP, drainage of 1 to 2 ml of CSF through the
ventriculostomy catheter can temporarily lower ICP. This modality can be an important
adjunct therapy for lowering ICP.
-Second Edition
2011

352


Osmotherapy:
The osmotic diuretic mannitol is given as an intravenous infusion of 0.25 to 1g/kg and
will maximally reduce the ICP within 10 minutes of administration. The reduction in
ICP usually persists for 3 to 4 hours. Serum osmolarity appears to be optimal when
raised to 300 to 320 mosm and should be kept below 320 mosm to avoid side effects of
therapy, such as hypovolemia, hyperosmolarity, and renal failure.
Loop diuretics, such as furosemide, decrease the CSF production and increase serum
osmolarity by increasing the free-water clearance by the kidney.
Barbiturate coma:
Barbiturate coma is another treatment modality that has been used to lower ICP in head
injured patients.
Barbiturate coma is usually reserved for patients with intracranial hypertension
resistant to other modalities.
Large doses required to produce electrical silence
12 mg/kg first hour
6 mg/kg next 6 hours
3 mg / kg > 7 hours
ANESTHETIC MANAGEMENT:
The important considerations during anesthesia in a head injured patient with raised
ICP are:
1. Effect of anesthetic and adjuvant agents on ICP
2. Effects of tracheal intubation on ICP
3. Considerations related to the actual technique of anesthesia
4. Effect of intraoperative fluid management on ICP.
Practical Anesthesia
Induction: Every severely injured patient should already be intubated by the time he or
she is brought into the operating room. The neck should be secured with the help of an
assistant by gentle in line traction during the intubation process.

-Second Edition
2011

353


Mannitol 1 gm / Kg
Dexona 8 mg Stat
Pre-oxygenation 100% O2 5 min
Vecuronium 0.5 mg (0.01 mg / hg precurarization)
Lignocaine 1.5 mg / kg IV
Esmolol infusion Thiopentone 5 mg / kg
Cricoid Pressure Scoline 2mg / kg
Hyperventilation Additional thiopentone 2 mg / kg
Intubation - Armoured tube
- Neutral position

To minimize the risk of aspiration rapid sequence induction should be performed. After
a precurarization dose of a non depolarizing muscle relaxant (e.g. 0.01 mg / kg
-1

vecuronium) and breathing 100% oxygen for 4 minutes an induction dose of etomidate
(0.3 mg / kg
-1
) or thiopental (3-5mg/kg
-1
) is administered, followed by succinylcholine
(1.5mg / kg
-1
). Next cricoid cartilage is pressed slightly towards esophagus by an
assistant. After 60 seconds the trachea is intubated, immediately after inflating the cuff
and confirmation of the correct tube location, the pressure on the cricoid cartilage can
be released.
Rocuronium (0.6 1.0 mg / kg
-1
) may be used as an alternative to succinylcholine,
primary the vecuronium is not then necessary. Good intubation conditions are usually
achieved 60 90s after administration of rocuronium. In order to prevent ICP increases
during intubation, either smaller dose of an opioid (e.g. 1-4 g / kg
-1
of fentanyl) or
lidocaine 1.5 mg / kg
-1
may be administered intravenously.
Maintenance: Although so for there is no anesthesia regime that has proved superior
over the other in regards to the maintenance of anesthesia in head injured patients.
Propofol 3-10 mg / kg-1 is used to maintain sedation. Isoflurane or sevoflurane
combined with moderate doses of opioids can be used. N2O should be voided because
of influence on CBV, ICP, and CBF. In patients with cardiovascular concerns,
benzodiazepines preferred because of negligible effect on cardiac ionotrophy.
Sufficient analgesia should be provided by opioids (fentanyl, sufenatnyl, Remifentanyl)
which may be administered continuously or intermittently.

-Second Edition
2011

354


Dosage of opioids during neurosurgery after traumatic brain injury
Fentanyl Intermittently
Continuously
0.5 2.5 g / kg
-1

2-10 g / kg
-1
h
-1

Sufentanil Intermittently
Continuously
0.1 0.5 g lg
-1

0.3 1.0 g / kg
-1
h
-1

Remifentanyl Continuously 0.1 0.5 g / kg
-1
min
-1

(very variable, depending on propofol dosage and surgical stimulation)
Muscle relaxation can be achieved by intermittent or continuous administration of non-
depolarizing relaxants. Adequate relaxation prevents, coughing, and therefore sudden
increase in ICP, as well as sudden and potentially deleterious movement of the patient.
However relaxation must be accompanied by appropriate sedation and analgesia.
Dosage of muscle relaxant during neurosurgery after traumatic brain injury
Atracurium Intermittently
Continuously
100 200 g / kg
-1

6 - 8 g / kg
-1
h
-1

Mivacurium Intermittently
Continuously
100 150 g lg
-1

4 8 g / kg
-1
h
-1

Rocuronium Intermittently
Continuously
75 150 g / kg
-1
min
-1
8 11 g / kg
-1
min
-1

Vecuronium Intermittently
Continuously
30 50 g/kg
-1

1-2 g / kg
-1
min
-1

USES OF OTHER ADJUVANTS:
Role of Hyperoxia
Evidence suggesting that cerebral ischemia is responsible for poor outcome in head
injury led to the hypothesis that measures that increase cerebral oxygen delivery might
avert the ischemic injury. One of the measures in this direction is mechanical
ventilation with high FiU2 during the early stages when the CBF is at its lowest. Some
recent studies have demonstrated that a significant increase in brain tissue oxygen
tension and decrease in brain tissue lactate levels can be achieved with hyperoxic (FIO2
0.6) mechanical ventilation in severely head injured patients. Hyperoxia has also been
shown to prevent cerebral oxygen desaturation caused by hyperventilation. Therefore,
it seems to be logical to ventilate the patients with a high FiO2 early during their course,
especially if hyperventilation is instituted.
Temperature regulation
Hyperthermia is associated with an increase in CMRO2. Therefore normothermia
should be maintained. Symptomatically, hyperthermia may be controlled by
paracetamol, cold saline infusion and cooling blankets. While there is no convincing
evidence to show that mild hypothermia (32-35
o
C) improves the neurological outcome,
-Second Edition
2011

355


rapid rewarming of patients brought in a hypothermic state has been shown to worsen
he outcome.
Anti-seizure prophylaxis:
The incidence of early post traumatic seizure ranges form 4- 92%. The risk factors for
enhanced post traumatic seizures are: GCS < 10, cortical contusion, depressed skull
fractures, subdural hematoma, epidural hematoma, intracerebral hematoma,
penetrating injury, seizures within 24 h. There are definite benefits of preventing these
seizures; in acute phase, seizures may be associated with significant changes in CBF,
CMRO2 ICP and cerebral oxygenation. The brain trauma foundation advocates that anti
consultants may be used to prevent early post traumatic seizures in patients at high
risk. Phenytoin and carbamazepine have been found to be effective for this purpose.

-Second Edition
2011

356


MONITORING DURING SURGERY
Standard monitoring
Arterial blood pressure (invasive and non invasive)
Central venous pressure
Intracranial pressure
Cerebral perfusion pressure (MAP ICP)
Heart rate and rhythm (ECG)
Core body temperature
Fluid balance (Foley catheter)
End tidal CO2
Repeated blood gas analysis
Laboratory analysis: hemoglobin, hematocrit, serum electrolytes, glucose,
coagulation status
Optional monitoring
Electrophysiologic examination
Jugular venous oxygen saturation
NEUROMONITORING
The major fluid shifts and haemorrhage associated with surgery may increase brain
edema and intracranial pressure. It is not possible to detect neurological deterioration
in a patient under anesthesia. This necessitates some form of Neuro monitoring in the
intraoperative period.
ICP monitoring:
In patients prone for intracranial hypertension, rapid changes in the ICP during non
neurological surgery may be detected only by direct ICP monitoring. Recommendation
of the Brain trauma foundation suggest that ICP monitoring may benefit the following
groups of head trauma victims.
1. Patients with severe head injury (GCS 3- 8 after cardiopulmonary resuscitation)
with an abnormal admission CT scan. An abnormal CT scan of the head is one that
reveals hematomas, contusions, edema, or compressed basal cisterns.
10mmHg (0-13 cmH2O), levels over 15mmHg (20cm H20) being abnormal. Lundberg
suggested that mean levels above.
20mmHg are moderately elevated and sustained levels above 40mmHg are severely
increased.

-Second Edition
2011

357


The ICP wave has a pulsatile quality at two
different frequencies one synchronous with
the arterial pulse while the other is slower, in
time with breathing. The vascular waves are
caused by arterial pulsations in the large vessels
within the brain, producing an oscillation in the
volume of the ventricular system. The shape of
the CSF pressure wave is similar to that of
systemic blood pressure and it has three fairly consistent components he percussion
wave (P1) tidal wave (P2) and dicrotic wave (P3). The dicrotic notch between 2 and P3
corresponds to the dicrotic notch of the arterial pulsation. The respiratory wave s
synchronous with alterations in central venous pressure, reflecting intrathoracic
pressure.
Pulse amplitude: As ICP increases above the resting level, the amplitude of the cardiac
pulse component increases while that of the respiratory component may decrease, due
to loss of compliance. This ICP pulse amplitude increases linearly with increasing ICP.
This widening of the pulse pressure may even precede the actual increase in mean ICP.
Pressure waves: Lundberg identified three different types of ICP variations
characterized as follows.

Lundberg identified three different types of ICP variations. A, B and C waves.
Plateau waves (A waves) are clinically very important because they indicate
dangerously reduced intracranial compliance. They rise steeply from near normal or
slightly raised ICP to 50mmHg or more and persist for 5-20 minutes before falling
precipitously, even to below the original level. The most frequent type of pressure
wave, although of less adverse clinical significance than the plateau wave, is the B
wave. These are rhythmic oscillations, sharply peaked and occurring once every 1-2
minutes, in which mean ICP rises in a crescendo manner from a variable baseline to a
-Second Edition
2011

358


level 20 30mmHg higher, and then falls abruptly with no intervening period of
sustained intracranial hypertension. C waves seem to be of little clinical significance.
Interpretation of ICP measurement
Trends in ICP are more important than isolated readings. Response to small changes in
intracranial volume can give an indication of intracranial compliance. Changes in pulse
amplitude pressure and pressure waves can allow prediction of clinical deterioration.
Noninvasive ICP monitoring: There are different monitors are being developed based
on Ultrasonic and MRI technology.
2. Patients with severe head injury with a normal CT scan if two or more of the
following features are noted at admission: age over 40 years, unilateral or bilateral
motor posturing, systolic blood pressure < 90mmHg.
ICP monitoring is not routinely indicated in patients with mild or moderate head injury.
Sties of invasive ICP measurement:
Extradural transducer
Subdural subdural bolt
Intraparenchymal Spiegelberg air pouch balloon catheter
Intraventricular catheter / ventriculostomy
Subarachnoid screw
Non invasive techniques of ICP monitoring:
Transcranial Doppler
Palpation of fontanelle
Tissue resonance analysis
Tympanic displacement analysis
CT Scan
Interpretation ICP
ICP recordings have two components: baseline pressure and variations of pressure, i.e.
pressure waves.
Baseline pressure: The normal mean ICP is 0-10 mmHg levels over 15mm Hg (20 cm
H2O) being abnormal.

-Second Edition
2011

359


Jugular venous oximetry:
Continuous monitoring of jugular venous oxygen saturation along with arterial oxygen
saturation gives information relating to demand versus supply of oxygen to the brain.
Detection of the common causes of decrease in SjVO2 (hypoxia, hypovolemia,
hypotension, anemia, intracranial hypertension) helps to optimize cerebral oxygen
delivery. It must, however be remembered that SjVO2 is only a global estimate of the
adequacy of CBF and focal events cannot be detected by this technique.
In head injured patients, TCD has been used to monitor CBF. While it is an attractive
non invasive technology, caution is required in extrapolating the flow velocity
information on actual blood flow changes.
Brain tissue oxygen tension monitoring
Direct monitoring the brain tissue oxygen tension 9PbtO2) with fiberoptic probes
incorporating miniature electrodes is currently under investigation. This device
provides regional oxygen tension. One study reported that poor outcome in traumatic
brain injury is related to the duration of time period for which the PbtO2 was less than
15 mm of hg or the occurrence of even a single episode of PbtO2 less than 6 mmHg. A
good correlation between SjVO2 and PbtO2 is seen only in normal brain and not in the
brain areas with pathology.
Intraoperative administration of diuretics
Osmotic diuretics are generally indicated intraoperatively to decrease brain water
content and ICP in patients with cerebral contusion and subdural hematoma. Mannitol,
the most commonly used osmotic diuretic, does not cross the intact blood brain barrier
and decreases extracellular brain water content both in normal and abnormal areas of
the brain. In addition, it also decreases the viscosity of blood and induces a reflex
vasoconstriction. Low doses of mannitol (0.25 0.5 g / kg) have been shown to be as
effective as high doses (1.0 1.5 g / kg). Serum osmolality must be kept below 320
mosm / kg to avoid renal dysfunction associated with severe hyperosmolality.
Euvolemic should be maintained during mannitol administration. Intermittent boluses
have been found to be more effective than continuous administration.
Massive intra operative brain swelling or tight brain
Protocol for emergency management of acute intracranial hypertension, causing
herniation of brain through craniotomy wound, is shown in table.

-Second Edition
2011

360


Table: Emergency therapy for herniation
Decrease PaCO2 to 25 30 mmHg.
Ensure PaO2> 100mmHg
Discontinue volatile agent
Discontinue nitrous oxide
Elevate the head of the bed to 30
o
(if tolerated hemodynamically)
Maintain MAP > 80mmhg.
Ensure profound muscle relaxation
Administer sedatives, narcotics, hypnotics (thiopentone or propofol infusion, if
tolerated)
Administer diuretics
Mannitol 1.0 1.5 g / kg
Furosemide 0.5 1.5 mg / kg
Intraoperative fluid management
Adequate volume resuscitation is necessary to maintain normal CBF in the acute phase
of TBI. Vigorous fluid resuscitation should not be withheld for the fear of increasing
brain edema. While choosing solutions for volume resuscitation, it must be
remembered that even minor changes in plasma osmolality have a profound effect on
brain edema. Therefore, all transfused fluids should be isotonic or hypertonic. A
decrease in colloid oncotic pressure due to large volume crystalloid transfusion may
also have an effect on brain edema. Therefore, it may be advisable to use a judicious
combination of colloids and crystalloids in patients who are grossly hypovolemic. Large
volumes of Ringers lactate also should be avoided as Ringers lactate is mildly
hypotonic. Glucose containing fluid should be strictly avoided during resuscitations
hyperglycemia has been proven to worsen ischemic neurological injury. Intraoperative
glucose estimation is essential to rapidly correct any hyperglycemia.
RECOVERY
Up on completion, of the surgery, patients who were unconscious preoperatively for a
long time may not be awakened or extubated. Rapid emergence and extubation are
possible only if the patient was conscious preoperatively or had rapidly deteriorated in
the immediate preoperative period (e.g. Due to an expanding extradural clot). Those
patients who are not awakened, should receive additional doses of muscle relaxants and
narcotics for facilitation of ventilation in the postoperative period.

-Second Edition
2011

361


Outcome form severe head injury
The functional status of patients with severe head injury often continues to improve for
months after the injury. Assessments before 6 months may significantly underestimate
functional recovery.
Assessing outcome
Glasgow Outcome Scale
In 1975, Jennett and Bond described a 5 point scale called the Glasgow outcome scale
(GOS) for quantitating neurologic recovery after head injury. A good recovery means
that the patient has returned to the pre-injury level of function. A moderate disability
describes a patient who has some neurologic impairment but is able to care for himself
or herself. A severely disabled patient has some evidence of higher mental function but
depends on others. A vegetative patient has no evidence of higher mental function. The
fifth outcome category is death. A modification of the GOS, called the Edinburgh
expanded Glasgow outcome scale (EEGOS), has been developed to allow comparison of
behavioral, cognitive, and physical function.
FUTURE TRENDS IN THE MANAGEMENT OF HEAD INJURIES
With a clear understanding of the pathophysiology of head trauma, a number of
potentially useful therapies are under trial. Some such therapies are listed below:
1. Mild hypothermia (30 34
o
C) which has been shown to offer protection against
cerebral ischemia and decrease intracranial hypertension not amenable for the
traditional methods.
2. Calcium channel blockers for their potential to counteract the calcium mediated
cell necrotizing cascades.
3. Tirilazad, a 21-aminosteroid that has no glucocorticoid activity, but has a
potential to prevent lipid peroxidation at cellular level.
4. Polyethylene glycol conjugated superoxide dismutase used as a free radical
scavenger.
5. MK-801 for its potential to suppress the activity of n-methyl d-aspartate (NMDA)
receptors through which excitatory amino-acids act.
6. Magnesium therapy: The intracellular concentration of magnesium has been
shown to be low during ischemia. In addition to counteracting the ill effects of
high intracellular calcium, magnesium may also competitively block the action of
excitatory amino acids on NMDA receptors.

-Second Edition
2011

362


CONCLUSION
Anesthetic management of a head injured patient requires an understanding the
intracranial and extracranial effects of brain trauma and an understanding of the effects
of the various perioperative interventions on the cerebral pathophysiology.

-Second Edition
2011

363



-Second Edition
2011

364


Chapter 32 - Head Injury Pathophysiology &
Anesthetic Management
Head injury is one of the leading causes of death all over the world. In USA overall head,
Injury-associated mortality has been estimated to be 16.9 to 30 per 100000 residents.
Trauma deaths have a typical trimodal distribution: Immediate deaths are due to brain
and heart injuries; one to two hours later deaths occur due to hemorrhage and visceral
injuries and late deaths are a result of sepsis, multiorgan failure and head injury.
The Characteristics of neurotrauma patients are:
1. The peak incidence occurs at summer weekend nights.
2. They present with a disease constellation of unconsciousness, raised intracranial
pressure (ICP), hypoxia and hypocarbia.
3. The patient's history may not be known:
4. The head-injured patient may be under the influence of alcohol or drugs
5. The victim may present with full stomach
6. These patients require lengthy surgical procedures
7. They may require advanced intraoperative management like one lung ventilation
8. The resuscitation and critical care should be performed in the operation theatre
9. Head injured patients may also have polytrauma.
Pathophysiology of Head Injury
Head injury is classifier) as primary and secondary according to the pathophysiology.
Primary damage occurs now of impact or injury. Secondary damage is due to vascular
and biochemical events which lead to hypoxia and ischemia. Broadly, the factors
responsible for secondary injury are hypotension, hypertension, hyperglycemia,
hyperemia, hypercapnia and coagulopathy.
According to the Glasgow Coma Score (CCS), head injury is classified as mild when th
GCS is 13-15, moderate when the GCS is 9-12 and severe if the GCS is 8 or less.
Anesthetic Management
Upon arrival in the operation theatre preoperative evaluation must be carried out,
which should include brief and rapid assessment of the Patient's airway, cervical spine,
breathing, circulatory status, associated injuries, GCS, pre existing illnesses, allergies
and medications. Past medical, surgical and anesthetic history and history of drug abuse
should be noted. Appropriate laboratory data, which include hematocrit, coagulation
profile, electrolytes, glucose, blood urea nitrogen and creatinine, must be obtained.
Adequate intravenous access must be established to administer fluids and blood.
-Second Edition
2011

365


The primary anesthetic objectives are to continue the initial resuscitation, maintain vital
organ function and avoid hypotension by maintaining systolic blood pressure greater
than 100 mmHg. Hypoxemia should be prevented by maintaining a Pa02 greater than
70 mmHg and increases in ICP should be avoided. The objectives also include
prevention of failure of other organ systems, correction of coagulation abnormalities,
fluid and electrolyte disturbances and prevention of the occurrence of seizures.
The main goal of anesthetic management is to avoid secondary brain damage, which
may be caused by inadequate CBF secondary to arterial hypotension elevated ICP,
excessive hyperventilation and hyperemia.
The physiological considerations involved in the anesthetic management of a patient
with head injury may be discussed under the following heads:
1. Intracranial contents
2. Intracranial compliance/ elastance
3. Cerebral blood volume and cerebral blood flow
4. Flow metabolism coupling
Intracranial contents
The adult skull is a rigid box containing 80% brain, 5% blood and 15% Cerebrospinal
fluid (CSF). According to Munro-kellie doctrine an increase in volume o? any component
can increase ICP and reduce cerebral perfusion pressure (CPP) (CPP = MAP - ICP)
leading to a decrease in cerebral blood flow (CBF) if autoregulation is not intact or if the
CPP is lower than the lower limit of autoregulation
lntracranial compliance/ elastance
The increase in ICP with the expansion of intracranial components is dependent on the
compliance or more accurately, the elastance of the system. Elastance is measured
clinically by volume pressure response (VPR) i.e., change in ICP in response to an
addition of 1-2 ml of saline to the ventriculostomy catheter. Another way is to quantify
the elastance is to measure the pressure volume index (PVI). PVI is the volume of saline
injected or withdrawn that would result in a 10-fold change in the ICP.
Volume of saline
PVI = ----------------------------------
Log (final ICP)/initial (ICP)
The normal value for PVI is 25 ml, a value of 18m1 indicates a significant decrease in the
compliance and the compliance is critical if the PVI is 13ml
-Second Edition
2011

366


CBF and CBV
In head injury, increase in the cerebral blood volume results in raised ICP. Reduction of
CBV forms the basis of various therapies to decrease the intracranial pressure. Normal
brain can tolerate a 50% reduction in CBF; however injured brain requires adequate
perfusion Major factors that influence CBF are C02 reactivity, autoregulation, and
cerebral vascular response to hypoxemia and cerebral metabolism. C02 reactivity and
autoregulation play an important role in determining the adequacy of cerebral blood
flow. Autoregulation may be impaired in head injury but C02 reactivity is the last to
disappear, which indicates vasomotor paralysis a grave sign Hyperventilation is thus a
very effective mechanism of controlling CBV" and ICP. CBF changes by 3-4% and CBV by
1% for each mmHg change in the PaC02. CPP is the driving force it maintaining
adequate CBF. In a normal person, CPP in the range of 50-150 mmHg does not affect the
CBF. To prevent ischemia in head injured patients; their CPP should be maintained
above 70 mmHg.
Flow-Metabolism Coupling
Cerebral metabolic rate of oxygen (CMR02) is the product of CBF and arteriovenous 02
differences (A-VD02) which, normally is 6-7 vole at a PaC02 of 40 mmHg. The use of
jugular venous catheters to measure A-VD02 provides an estimate of CBF. A high A-
VD02 means low CBF and vice versa. Normal CMR02 is 3.2 ml/100gm/min. Oxygen
extraction is high if CBF is critically low. Inadequate analgesia/anesthesia in head
injured patients leads to cerebral stimulation with increase in flow/metabolism ratio,
vasodilation and increase in ICP.
Effects of Anesthetic Agents on Cerebral Physiology
The choice of anesthetic agents depends on its effect on CBF, CMR02, ICP,
autoregulation and C02 reactivity (Table 1).
Intravenous Anesthetics
Barbiturates, propofol and etomidate produce cerebral vasoconstriction and reduction
in CBF, secondary to reduction in CMR02. Once the electroencephalogram (EEG)
becomes isoelectric, there is no additional benefit in giving extra doses of barbiturates.
Ali the three agents cause isoelectric EEG. Etomidate is a less potent cardiac depressant
compared to the other two agents but it suppresses the adrenal cortex. All the above
three agents can be used for induction. Benzodiazepines cause minimal reduction in the
cerebral metabolism and flow. Barbiturates offer cerebral protection by the following
mechanisms reduction of CMRO2 and ICP, reduction of post perfusion hyperemia, free
radical scavenging, reduction of catecholamine induced hypermetabolism, control of
seizure activity, blockade of noxious stimuli, immobilization and hypothermia.
-Second Edition
2011

367


Volatile Anesthetics
The volatile agents commonly used are halothane, enflurane, isoflurane, desflurane and
sevoflurane. All volatile anesthetics impair autoregulation in a dose-related manner and
autoregulation is preserved at 0.5 MAC but abolished at 1.5 MAC. So low doses are safe,
but when there is brain swelling, they may have to be discontinued. All volatile
anesthetic agents are vasodilators and increase CBF in a dose related manner, which can
result in uncoupling of flow-metabolism relationship. Halothane and enflurane increase
CSF formation and decrease its absorption, whereas isoflurane has a negligible effect on
CSF dynamics. Halothane has less effect on CMR02 and is a potent vasodilator.
Isoflurane has a metabolic depressant effect on brain and has the lowest cerebral
vasodilatory potential among the volatile agents. The effect of enflurane is intermediate
between halothane and isoflurane; but it can cause seizures. Desflurane and sevoflurane
are similar to isoflurane except that they have lower blood/gas solubility and have a
quicker onset and offset of action.
Nitrous oxide (N20)
N2O is a potent cerebro vasodilator and it increases the ICP. I: has no effect on
autoregulation and CO2 reactivity. Cerebral vasodilation is minimal when used with
intravenous anesthetic agents such as thiopentone, propofol and benzodiazepines and
with the introduction of desflurane and sevoflurane N20 can be avoided in head injuries
especially with brain swelling.
Narcotics
Morphine has no effect on cerebral circulation or metabolism. Histamine release with
morphine can cause hypotension. Fentanyl, sufentanil and alfentanil have complex
effects on cerebral vasculature and metabolism. All three have systemic hypotension
but fentanyl has the least effect and is the preferred narcotic. Remifentanyl is another
promising short acting narcotic in neuro anesthesia.
Ketamine
Ketamine increases CBF and CMRC2. It is a noncompetitive N-methyl d-aspartate
receptor antagonist. It is not used in neuro anesthesia as it increases ICP though it has
the potential for cerebral protection

-Second Edition
2011

368


Muscle relaxants
Succinylcholine increases ICP directly, by stimulating gamma motor neurons, which
results in cerebral stimulation and raised CBF and indirectly, by producing
fasciculations, which increase intra-abdominal and intrathoracic pressure. This can be
reduced by thiopentone or giving subparalysing dose of nondepolarizing relaxants.
Nondepolarizing relaxants like pancuronium, vecuronium and rocuronium have no
effect on CBF, CMR02 and ICP. Rocuronium is an alternative to suxamethonium in a
dose of 0.6 mg/Kg for rapid sequence intubation.
Vasoactive agents
Alpha agonists like dopamine, ephedrine and phenylephrine, beta-blockers and
ganglion blockers have no effect on CBF, CBV and ICP. Directly acting vasodilators like
hydralazine, nitroglycerine and nitroprusside cause raised ICP. Hence, they are used in
conjunction with ICP monitoring. Beta-blockers, ACE inhibitors and centrally acting
drugs such as clonidine are the drugs of choice to decrease systolic blood pressure in a
patient with raised ICP.
Anesthetic, Techniques
The principles of anesthetic management are a paten; clear airway, smooth induction
controlled ventilation to prevent hypoxia and hypercarbia, prevention of a raise In the
ICP, appropriate fluid balance and a slack brain
General anesthesia
The preoperative considerations in head insured patients are they may present as an
emergency with or without ETT. ICP may be raised, aspiration might have occurred and
the patient may present the problems of full stomach. Patient may be dehydrated,
hypotensive, hypoxic, hypercapnic and restless.
Narcotic premeditation is generally avoided as it causes respiratory depression and
papillary changes. Preoxygenation should be carried out with 100% oxygen for 5
minutes to prevent hypoxic. Anesthesia may be Induced with thiopentone 4-6 mg/kg
depending on blood pressure of the patient Induction with propofol may cause
hypotensive and excitatory movements. Midazolam and etomidate provide good
circulatory stability.
Succinylcholine in a dose of 1-2mg/kg is used commonly to facilitate rapid sequence
intubation. Nondepolarizing relaxants used are vecuronium 10.1 mg/kg,
which offers cardiac stability, atracurium 0.5mg/kg in-patients with renal problems
and pancuronium 0.1 mg/kg for long duration surgery. Stress response to
intubation is attenuated by intravenous lignocaine 2 mg/kg or fentanyl 10-15
micrograms/kg or repeated smaller doses of thiopentone and by spraying the vocal
cords with 4% lignocaine 3-4 ml.
-Second Edition
2011

369


Shorter acting narcotic like fentanyl 1-2 micrograms/kg is preferable for surgeries of
ort duration and morphine 0.1 mg/kg or pethidine 1-1.5mg/kg if the duration of
surgery is long.
Reinforced endotracheal tubes are preferred because they are non kinkable and can be
used in prone and lateral positions. Orotracheal intubation is preferred to nasotracheal
intubation in head injury because of the possibility of basal skull fractures.
Cerebral venous pressure can be reduced by positioning the head slightly above the
heart level and avoiding extreme neck flexion that may result in venous obstruction and
increased ICP. Local injection of lignocaine 2% at the site of pins during positioning will
prevent the hemodynamic response.
Anesthesia is maintained by using oxygen and nitrous oxide in a ratio of 40:60. N2O is
discontinued if there is brain swelling and substituted with higher doses of narcotics.
Propofol is used as an infusion. Isoflurane is the preferred volatile anesthetic in lower
doses Halothane may be used in doses of 0.5 MAC. Volatile agents have to be
discontinued if there is brain swelling. Ventilation is adjusted to maintain a PaCC2 of 30-
35mmHg.This reduces the brain edema by cerebral vasoconstriction. The effect of PEEP
is unpredictable and. A PEEP of 10 cm H2O does not seem to increase the ICP
appreciably, particularly in patients with poor lung compliance. ICP monitoring is
desirable if PEEP is used.
Mannitol 0.5-1 gm/kg is started at the time of first burr hole and is infused over a period
of 15-20 minutes taking care not to cause fluid overload. Urine output is measured to
know the response. Serum osmolality should be checked if mannitol is used repeatedly.
Mannitol acts by creating osmotic gradient and drawing water into the intravascular
compartment. It causes diuresis and free radical scavenging and decreases CSF
formation. It also decreases the blood viscosity. Furosemide 0.5-1.0 mg/kg augments he
response of mannitol. Steroids are less effective in head injury though methyl
prednisolone is beneficial in acute spinal cord injury.
Mild to moderate hypothermia is beneficial to the injured brain but coagulation
disturbances can occur. Profound hypothermia requires cardiopulmonary bypass.
Perioperative fluid balance
Volume replacement and not volume expansion is the ultimate goal. Over hydration
should be avoided as it causes cerebral edema. Hypotonic solutions should be solution
used widely in the operation theater. Hypertonic 3% or 7.5% saline is helpful in
hypotension and hyponatremia but studies that are more clinical are required before its
routine clinical use. Colloids are used in cases of severe hypotension. Blood loss should
be replaced adequately.
-Second Edition
2011

370


Monitoring
Noninvasive monitoring includes electrocardiogram, noninvasive blood pressure, end
tidal carbon dioxide, pulse oximetry, temperature, urine output, inspired oxygen
concentration. Doppler sonography. Invasive monitoring includes invasive blood
pressure, arterial blood gases, central venous pressure. jugular venous oximetry and
intracranial pressure. Other important investigations required are hematocrit, serum
electrolytes, serum osmolality and neuromuscular monitoring.
Emergence
The plane of anesthesia is gradually lightened at the end of surgery. A small dose of
volatile anesthetic is continued until extubation to prevent coughing. Lignocaine 1.0-
1.5mglkg will also help if given 2-3 minutes before extubation. As a rule, extubation is
carried out after a full neurological examination. Neostigmine 0,04mg/kg and atropine
0.02mg/kg is given if extubation is desired, alternatively, patient is electively ventilated
in the ICU depending on the requirements of each individual patient. Postoperatively,
supplemental oxygen (FiO2-0.3) is administered by mask or nasal prongs. Blood and IV
fluids are replaced as required and intensive monitoring continued.
The indications for postoperative ventilation are:
1. Drowsy patients
2. Airway obstruction
3. Massive brain swelling
4. Preoperative chest problems
5. Obesity
6. Massive transfusions
7. Excessive intraoperative brain retraction
Intraoperative Complications
The main intraoperative complications are:
1. Bleeding
2. Severe brain swelling
3. Sudden hypotension
Arterial bleeding is secondary to bone fragments. Venous bleeding is the most common
source and is difficult to control due to raised ICP, venous obstruction, hypothermia and
coagulation disturbances. The cause has to be corrected to prevent further bleeding.
-Second Edition
2011

371


Brain swelling is due to an increase in the CBV. Prolonged hyperaemia of the brain leads
to vasogenic edema and increased ICP. Increased brain density and compressed
ventricles are seen on a computerized tomographic scan. Arteriovenous oxygen content
differences across the brain (A-JD02 = Systemic arterial oxygen content- Jugular venous
bulb oxygen content) less than 7.5 indicates CBF Is probably adequate. Brain swelling
may be treated through a reduction of CBV by avoiding hypoxia and hypercarbia,
optimal hyperventilation (PaC02 of 32-35mrnHg) to cause cerebra! Vasoconstriction,
promotion of venous drainage by a 30 degree head up position, and the administration
of cerebral vasoconstrictors like barbiturates in resistant cases.
Brain edema is defined as increased water content of the extravascular spaces_
Computerized tomographic scan shows lower white matter density than the normal
brain. AJD02 is greater than 10 indicating reduced CBF and increased oxygen extraction.
Therapy should increase CBF by maintenance of normocarbia and administration of
mannitol and diuretics.
Sudden hypotension may result from an acute decompression of an intracranial
hematoma. Intracranial hematomas raise the ICP and invoke Cushings response, which
normally should cause systemic hypertension and bradycardia. But most often, in head
injury, the patient may exhibit tachycardia/hypertension when he is normovolemic and
tachycardia/normotension when hypovolemic. Actute withdrawal of Cushings
response due to sudden decompression of the mass lesion might precipitate
hypotension. So a good venous access should be available and adequate fluid
resuscitation should be carried out before decompression of hematoma.
Continuous jugular venous oximetry may be useful during anesthesia. Jugular venous
oximetry measures oxygenation of the blood in the jugular bulb, which is the main
draining vein of the brain. The normal value for jugular venous oxygen saturation
(SjVO2) is 60-80%; hyperemia is indicated by values > 90% and values < 50-54%
indicate low flow.

-Second Edition
2011

372


Table 1. Cerebral effects of anesthetic drugs
Agent ICP CMRo2 CBF
Thiopentone
Propofol
Etomidate

Halothane
Isoflurane

Desflurane
Sevoflurane
Nitrous oxide
Fentanyl

Sufentanil
Ketamine
Benzodiazepines
Lidocaine

Decrease; Increase; Increase/Decrease or no effect

HEAD INJURY & ITS EFFECTS
Head injury causes abnormalities of systemic homeostasis and organ dysfunction. This
is because the brain affects the function of various organs through autonomic and
hormonal influences. So alteration in brain function due to trauma has profound effects
on systemic organ functions. These responses can occur immediately after head injury
or may evolve over hours to days. Immediate responses are mainly because of the
dysfunction of brainstem centers for cardiorespiratory functions due to direct trauma.
Ventilatory dysfunction like apnea, hypoventilation or hypoxemia can occur.
Cardiovascular dysfunction may be in the form of hypotension, bradycardia,
hypertension or cardiac arrhythmias. These cardiorespiratory complications may
worsen the primary brain injury, thus influencing the clinical outcome.
In traumatic coma data bank (TCDB) cohort study (1) hypoxemia (Pa02<60 mm Hg)
which occurred in 11 % of patients was associated with 33% mortality and hypotension
(single episode of SBP <90 mm Hg) which occurred in 18% of patients was associated
with 60% mortality, compared to 27% mortality when neither of them occurred.
Hypoxemia and hypotension occurred together in 8% of patients and was associated
with 75% mortality. Other systemic complications, which may occur following head
injury, include coagulation abnormalities, water and electrolyte abnormalities and
metabolic abnormalities.

-Second Edition
2011

373


Respiratory complications
The respiratory dysfunction is common after head injury. The most dramatic of them is
neurogenic pulmonary edema. Others include hypoxemia, hyper or hypocarbia,
abnormal respiratory patterns, pulmonary embolism, aspiration and pneumonia.
Neurogenic pulmonary edema
Neurogenic pulmonary edema (NPE) is pulmonary edema arising after a central
nervous system insult that is non cardiogenic and not related to damaged alveolar
epithelium or capillary endothelium (2) It is difficult to differentiate from the more
common forms of pulmonary edema such as those following aspiration or sepsis or
right ventricular dysfunction. Its true incidence is therefore unknown. It occurs much
less commonly in patients who survive (3) than those who die of severe isolated head
injury(4).
Clinically NPE can be divided into early and late forms. Early forms occur more
commonly after epilepsy and late forms after head injury. Early forms present within 2-
12 hrs and late forms present from 12 hrs to several days after the CNS event. The usual
clinical findings are dyspnea and tachypnea, tachycardia, rales, fever, hypoxemia,
decreased pulmonary compliance and he ARDS like pattern of "fluffy" infiltrates on
chest x-rays. The infiltrate may be asymmetrical (2). NPE is usually self limited if the
patient survives and will resolve in a matter of hours to days.
NPE is also found in many other pathologic CNS conditions. The common anatomic site
of damage with NPE is brain stem with a resultant massive sympathetic discharge. The
areas most likely associated with NPE include A, and AS areas in the medulla, the
nucleus tractus solitarius, the area postrema, the vagal nuclei and the hypothalamus (5).
There are many mechanisms that cause NPE after brain injury (5). A major role is
ascribed to a massive transient neural discharge with concomitant increase in
sympathetic activity. This leads to massive increases in systemic arterial, pulmonary
arterial, pulmonary venous and superior venacaval pressures accompanied by a
dramatic increase in total peripheral resistance. As a result of increase in total
peripheral resistance, blood shifts from the peripheral to the pulmonary vascular bed as
documented by pressure and volume changes (increased size of left atrium, pulmonary
venous engorgement). This transient phenomenon called "Blast effect" damages the
pulmonary endothelium, causing a persistent permeability defect. This mechanism, may
be involved include direct sympathetic control of the number and size of pulmonary
endothelial pores, constriction of the pulmonary lymphatics resulting from the
sympathetic discharge, lung micro-embolization from activation of the clotting cascade
that is possibly caused by damaged pulmonary vasculature during sympathetic
discharge or by release of brain tissue thromboplastin into the systemic circulation, or
the direct effect of increased sympathetic activity on lung vasculature that result in
-Second Edition
2011

374


pulmonary hypoperfusion and consequent hypoxemia (5) Humans with severe head
injury uniformly exhibit increase in lung water. Perhaps increased lung water is the
earliest evidence of the pulmonary effects of head trauma, which in its extreme form
manifests as NPE.
The treatment of NPE consists of lowering the intracranial pressure (ICP) and
supporting the ventilation of the patient. Lowering the ICP Is the primary mechanism
for reversing the underlying stimulus for generation and maintenance of NPE. This is
accomplished by head end elevation by 15-30
, use of osmotic diuretics and sedation

with opioids, or surgery. Ventilatory support involves maintenance of normal
oxygenation and normocapnia. Supplemental oxygen administration, intubation,
mechanical ventilation and PEEP accomplish this. PEEP must be used cautiously as
necessary. It is unclear if a level of PEEP<20cm H20 in mechanically ventilation. Head
injury patients affect ICP deleteriously. However monitoring of ICP generally
recommended if the level of PEEP exceeds 10cmsHz0.
Hypoxemia
Early hypoxemia usually associated with hyperventilation and hypocarbia occurs in
over 50% of severely head-insured patients even in the absence of NPE. In survivors
1rypoxennia mild and transient. But in non-survivors it is progressive, and is often
associated with increase shunt fraction and late severe hypercarbia. The mechanism of
this early hypoxemia include neurally induced ventilation perfusion mismatch,
pulmonary micro-embolism causing increase dead space ventilation, depletion of lung
surfactant after massive sympathetic stimulation and the abnormal breathing patterns
frequently seen following head trauma (5). Head-injured patients also have associated
chest trauma, which may cause hypoxia.
Respiratory pattern
Abnormal respiratory patterns are seen in approximately 60% of head injured patients.
Cheyne-stokes respiration, tachypnea and irregular breathing occur with nearly equal
frequency. Tachypnea (>25 breaths per minute) and hyperventilation (PaC02<30 mm
Hg) are associated with poor prognosis. Even in the absence of airway obstruction, 30-
50% of head injured patients demonstrate hypoxemia and spontaneous
hyperventilation. They also have bronchoconstriction with abolished compensatory
hypoxic pulmonary vasoconstriction resulting in hyperperfusion of hypoventilated
alveoli. Brain injured patients may have low cerebrospinal fluid (CSF) pH and
bicarbonate levels, and high lactic acid levels, that correlate with severity of injury;
hyperventilation tends to return CSF pH to normal (6). Supplementary oxygen corrects
hypoxemia without terminating the hyperventilation.

-Second Edition
2011

375


Pneumonia
Pneumonia occurs in 35-70% of head injured patients with a 50% mortality. According
to TCDB cohort pneumonia is an independent predictor of outcome in head injured
patients. The factors influencing incidence of pneumonia in these patients are
depressed airway reflexes. Intubation, full stomach, sedation and paralysis to facilitate
ventilation causing mucociliary dysfunction and inadequate chest physiotherapy and
postural drainage because of head-end elevation and raised ICP. These factors makes
the head injured patients more prone for aspiration, atelectasis, inspiration of
secretions and nosocomial infection. The risk of pneumonia increases with duration of
mechanical ventilation, reintubation, history of COPD, use of PEEP, presence of ICP
monitor, use of barbiturates in treating ICP use of corticosteroids and use of H2 blockers
for neutralization of gastric pH.
Clinically pneumonia may be divided into early and late phases. Early pneumonia
occurring within 48-120 hours appears to be related to aspiration of oropharyngeal
secretions c
,
e to depression of protective reflexes. It is commonly caused by gram-
positive organisms. It is usually caused by gram negative organisms.
Diagnosis of pneumonia in the intubated ICU patient is difficult. The diagnosis depends
on clinical signs like fever, leukocytosis, and diminution of breath sounds, copious
purulent secretions, and new or progressive infiltrates on chest x-ray and identification
of pathogenic organisms with the above clinical background. The treatment includes
antibiotics based on sensitivity of the organisms, postural drainage, and chest
physiotherapy. The use of rotating table appears to lessen chances of pneumonia.
Other pulmonary complications include aspiration, ARDS, pulmonary embolus, fat
embolism. Diaphragmatic paralysis causing poor coughing ability and difficulty in
weaning occurs infrequently after head injury. It is possibly due to hyperextension of
the neck resulting in stretching, edema, or hemorrhage in the nerve without complete
avulsion. Recovery occurs in 16 months.
Cardiovascular complications
An initial hyperdynamic cardiovascular response occurs following head injury leading
to elevation in blood pressure, heart rate and cardiac output. This response appears to
be sympathetically mediated and directly proportional to the degree of catecholamine
released. Because of this response three clinical symptom complexes can occur 1.
Neurogenic hypertension, 2. Myocardial ischemia, 3. Cardiac dysrhythmias.
Neurogenic hypertension after head injury is related to raised ICP and brain stern
compression causing medullary ischemia. It is usually accompanied by vagally mediated
bradycardia. In upto 25% of cases hypertensive response is not associated with raised
ICP where it is due to other causes. In neurogenic hypotension, blood pressure is quite
labile with varying cardiac output and systemic vascular resistance. Treatment of
-Second Edition
2011

376


neurogenic hypertension is controversial. It is difficult to determine ideal blood
pressure in a given patient with brain injury. Current guideline is to maintain a cerebral
perfusion pressure of 80-100 mm Hg. Blood pressure control is required only when
systolic arterial pressure approaches 200 mm Ha. For transient hypertension, sedation
or analgesia is sufficient, but for persistent hypertension in the setting of raised ICP -
blocking drugs are preferable.
Myocardial injury in the absence coronary artery disease may occur in upto 50% of
head injury patients. The lesions produced were similar to those after myocardial
infarction or catecholamine infusions. Myofibrillar degeneration and subendocardial
hemorrhages were found at autopsy. In patients with myocardial injury, cardiac iso-
enzymes (ck-MB) may be elevated and ECG changes consistent with infarction may
occur. Inhibition of catecholamine release (5) and adrenergic receptor blockade (2) has
been shown to prevent or ameliorate myocardial injury. Hemodynamically insignificant
myocardial ischemia should be followed with serial ECGs and cardiac enzymes.
Hemodynamically significant ischemia should be treated by correction of tachycardia
with blockers and normalization of after load with sedation or analgesia and if
necessary vasodilators.
A wide variety of dysrhythmias are described after head injury. The incidence is
unknown but their occurrences are probably related to changes in both sympathetic
and vagal tone. A variety of electrocardiographic changes are described in head injured
patients. Their occurrence in order of frequency is QT prolongation (>440 msec)-60%,
tachycardia (>100/min)-45,%, ST depression -20%, QRS prolongation -15%, large U
waves -15%, ST elevation -15%, ventricular extrasystoles -10%, heart block -8%,
peaked T waves -8%, PT interval prolongation -5% and bradycardia 2%(7). The cardiac
arrhythmias described in head injured patients are sinus bradycardia, supraventricular
tachycardia, atrial fibrillation, AV block, ventricular ectopics, ventricular flutter,
ventricular fibrillation (2). Hemodynamically insignificant, benign and transient
arrhythmias need no treatment. But those, which persist longer and hemodynamically
significant, need standard therapy; tacky-arrhythmias with -blockade and brady-
arrhythmias with atropine, -agonists or rarely a pacemaker.
Neurogenic shock is rare after head injury. A fatal degree of cerebral compression
usually develops before there is a vasomotor collapse. In a study of 721 head-injured
patients, 49 had shock attributable to the head injuries and 46 among them died (6).
Hematological complications
Deep venous thrombosis
The incidence of deep venous thrombosis (DVT) in head injured patients 40% (2)
symptomatic DVTs occur in 17% of patients and only 10% have findings on clinical
examination. The incidence of DVT is correlated with surgery, immobility, motor deficit,
-Second Edition
2011

377


lower extremity trauma, and gram-negative sepsis. The diagnosis of DVT on clinical
grounds is unreliable. Contrast venography is the gold standard for diagnosis of DVt.
Other investigations like 125 scanning, venous Doppler ultrasonography and impedance
plethysmography can be used. In head injured patients DVT occurs commonly in lower
extremity and pelvic vessels. Thrombus in thigh vessels may result in pulmonary
embolism (PE) (generally sub clinical) in approximately 50% of cases and that in calf
vessels, may embolize in 30% of cases. In 1% of cases PE in fatal in head injured.
The treatment of choice in patients without contraindications is heparinization followed
by treatment with coumarin for 3-12 months. Heparin is given in a bolus dose of 5000-
10000 U followed by 800-1000 IU/hr infusion. Coumarin is started 48-72 hours later
and adjusted to 1.5 to 2.0 times control. Heparin is discontinued once PT is in the
desired range. Head injured patients may have relative or absolute contraindication for
anticoagulation including intracranial hemorrhage, craniotomy, or multiple trauma.
The question how soon after craniotomy of head trauma anticoagulation can be started
is undetermined. A threshold of 5 days after incompliance craniotomy in general
neurosurgical population is suggested (2) but in head injured patients are threshold is
unclear. An alternative to anticoagulation in these patients is insertion of infer or
venacaval fitter.
The best and the simplest method of prophylaxis for DVT is a head injured patient is the
use of intermittent external pneumatic compression devices on the lower leg (5). Other
methods are graded compression devices, rotating beds, graduated compression
devices, low molecular weight heparin and mini dose heparin.
Coagulopathy
Brain tissue is a potent stimulator of DIC. In head injured patients abnormalities in tests
or coagulopathy are common. The presumed inciting mechanism in massive release of
thromboplastin into the circulation by injured brain. The common coagulation tests of
prothrombine time, activated partial thromboplastin time, and thrombin clotting time
are said to be cures because they may not show abnormal results until considerable
depletion of clotting factors despite this, abnormal test results are extremely common in
head injured patients. Jugular vein samples even in patients with normal clotting
function in peripheral blood may indicate a localized coagulopathy (5). Indeed some
degree of fibrinogen degradation products level appears in vast majority of head injury
patients, including patients with GCS scores of 13 or above with norms CT scans.
Platelet aggregation is impaired both in vivo and in vitro in these patients (6)
Hypercoagulability is correlated with high catecholamine levels. The severity of
coagulopathy reflects the severity of head injury as well as survivability. A manor
abnormality in a mildly injures patient may be a precursor of a poor outcome.
-Second Edition
2011

378


Table 1: Laboratory evaluation of DIC
Coagulation Tests
Evidence of coagulopathy Abnormal values in APTT, PT, Platelet count,
plasma Fibrinogen level
Highly suggestive of DIC Abnormal values in thrombin time, Fibrin split
products
Confirmatory of DIC Abnormal values in plasma protamine test, Ethanol
gelation
Test, Double-D-Dimer degradation product, Fibrin
peptide A level.
Impact of Ischemia due to intravascular thrombi is not fully understood, but may be
even more significant.
It is not clear whether treating DIC will alter the outcome, because coagulopathy is a
reflection of the severity of the injury. However, because it is clear that DIC parallels
outcome it is appropriate to take an aggressive approach. Treatment consists of
replacement of depleted clotting factors, generally with fresh frozen plasma. If
fibrinogen is excessively low, cryoprecipitate can be used platelet concentrates and red
cells may be used as necessary. Heparin therapy may produce dramatic effects but may
predispose the patient to intracranial hematomas and is therefore not recommended.
Antifibrinolytic agents and lytic enzymes are also not recommended.
Endocrinologic complications
anterior pituitary insufficiency
Following head injury deficiency of many anterior pituitary hormones may occur. The
commonest abnormality is growth hormone deficiency followed in order of frequency
by ACTH, F5'H and LH They are usually associated with transient or permanent diabetes
insipid-is, Anterior lobe necrosis caused by shearing of small postal vessels in pituitary
stalk at the time of impact is believed to be the cause of anterior pituitary insufficiency.
It may manifest as secondary amenorrhea, galactorrhea, and regression of secondary
sexual characters, poor recovery, post traumatic psychosis, persistent general malaise,
precocious or delayed puberty or hypogonadism. Appropriate replacement therapy is
indicated when specific deficiencies are proved through endocrinologic testing.
Posterior pituitary dysfunction
Diabetes insipidus
Diabetes insipidus (DI) due to deficiency of antidiuretic hormone (ADH) is a relatively
common, phenomenon after head injury. It is characterized by polydypsia, polyuria,
hypernatremia, high serum osmolarity (320-330 mosm/1), dilute urine, and urine to
serum osmolarity ratio of less than one implying a negative water balance. In severe
cases, urine output may exceed 1L/hr leading to dehydration, hypotension and life
-Second Edition
2011

379


threatening electrolyte imbalances, Post traumatic DI is transient in 50-60% of cases;
polyuria developing in 12-24 hours and normal regulation returning in 3-5 days In 30-
40% of cases it is permanent. In 5-10% a triple response or DI with inter-phase is seen.
Following injury to the infundibular stalk 'there is a decrease in ADH reserve. 2-5 days
later excessive ADH is released from degenerating cell bodies. The result is a period of
high urine output, followed by a period of water retention and hyponatremia, followed
by permanent DI. The diagnosis is by dehydration test, plasma ADH assay, and
simultaneous measurement of urine and plasma osmolarity.
Therapy is by correction of free water deficit, which can be calculated by the formula.
Free water = Body weight x 0.6 ((serum sodium/940)-1).
In awake patients oral fluids can be given. Intravenous replacement is done with use of
5% dextrose or hypotonic saline. Neutralization of glucose with insulin may be done
considering the large volumes of fluids needed. Hypernatremia of more than 6-12 hrs
duration has to be corrected slowly over 48 hrs to avoid rebound brain edema. If urine
output exceeds 250m!/hr for two consecutive hours or 6-7 L/day aqueous vasopressin
in a dose of 2.5iU s/c can be used Alternatively desmopressin 10-20 g bid. intranasally
or 0.5-4ug 3/C or IM bid can be used. Drugs that enhance the release of ADH or enhance
its renal effect (chlorpropamide, dofibrate) can be used in less severe cases.
Syndrome of inappropriate ADH secretion (SIADH)
SIADH occurs in 4.6% of ail head injured patients (6). It begins 3-15 days after trauma
and lasts no more than 10-15 days. Inappropriate ADH secretion results from over
production or release of ADH in response to irritation of hypothalamo-pituitary axis;
limbic structures may facilitate or fall to inhibit ADH release. It is characterized by
hyponatremia, hypo-osmolar serum, inappropriately concentrated urine and urinary
sodium excretion >25mcq/L. the symptoms of hyponatremia depends on the speed
with which is develops. Early signs include anorexia, nausea, vomiting, lethargy and
irritability. At concentration less than 110meq/L stupor, extrapyramidal signs,
convulsions and coma may supervene.
SIADH is treated by fluid restriction to <700m1/day hyponatremia may need to De
corrected with 3%or 5% saline to values at least 120-125megiL. The rise in serum
sodium should not exceed 2meq/lit. More rapid correction may cause neurological
deterioration. Diuretics may be used if rapid control of hyponatremia and fluid overload
is warranted. Drugs like demeclocycline, phenytoin are tried, but their role remains to
be established.
Cerebral Salt Wasting Syndrome (CSWS)
In CSWS hyponatremia is associated with dehydration. The kidneys are unable to
conserve sodium. An unidentified natriuretic factor released from brain has been
-Second Edition
2011

380


proposed to be the cause of this condition. Treatment requires replacement of both
water and sodium.
Metabolic changes
Water and electrolyte balance
Apart from sodium and water disturbances caused by DI, SIADHH and CSWS, the head
injury patients are prove for disturbances of potassium, calcium and magnesium. Early
correction of these disturbances is importance in the maintenance of homeostasis.
Glucose metabolism,
Glucose intolerance is common after head injury. High catecholamine levels decrease
insulin levels. ACTH, cortisol and GH levels are elevated. All these along with
exogenously administered steroids cause hyperglycemia. Hyperglycemia is correlated
with poor outcome. With the potential for hyperglycemia in the background, mannitol
therapy, hyperosmolar tube feedings, phenytoin therapy and fluid restriction
predisposes these patients to nonketotic hyperosmolar hyperglycemic coma (NHHC)(6).
NHHC is characterized by hyperglycemia (4002700mgldL), glycosuria, absence of
ketosis, plasma osmolarity >330mgm/L, dehydration, CWS dysfunction. Hypovolemia
and hypertonicity are immediate threats to life. Therapy consists of correction of water
deficit with hypotonic fluids and correction of hyperglycemia by insulin.
Gastrointestinal changes
Gastric ulcers can occur within 24 hrs and can occur in over 75% of head injured
patients (8). The mechanism includes mucosal barrier disruption, increased mucosal
permeability. Excessive gastric acid secretion and defects in mucosal microcirculation.
Sucralfate 1G Cid, a cytoprotective agent that maintains mucosal barrier integrity
without altering pH is the treatment of choice.
Gastroparesis leading to intolerance of enteral feedings is common following head
injury. It can last upto 2 weeks. Metoclopramide improves gastric emptying. Delayed
triggering of swallowing reflex occurs commonly after head injury. Other swallowing
disorders such as dysfunction of oromotor function, pharyngeal peristalsis, and airway
protection mechanisms may also occur.
Liver enzymes are elevated following head injury, This may be because of splanchnic
hypoperfusion that occurs due to sympathetic stimulation and catecholamine storm
that follows head injury. The other mechanisms involved are stress response following
trauma, systemic hypotension, blood transfusions, or drugs used in the ICU (antibiotics,
anticonvulsants).

-Second Edition
2011

381


Renal changes
Renal hypoperfusion can occur because of sympathetic stimulation and catecholamine
storm following head injury. This may manifest as decrease in urine output, or elevated
BUN and creatinine. The other causes include systemic hypotension, septicemia, or use
of aminoglycoside antibiotics.
To summarize head injury cannot be considered as an isolated single system injury.
Head injured patients frequently sustain other organ trauma. Equally important are the
systemic effects of trauma particularly its effect on hypothalamic-pituitary axis, which
influences such diverse pan systemic functions as blood coagulation, pulmonary venous
tone, gastric acid secretion, renal water conservation, and glucose metabolism.
(Management of most head injuries.)

-Second Edition
2011

382



-Second Edition
2011

383


Chapter 33 RECENT ADVANCES RELEVANT TO
NEUROANESTHESIA CARE OF TRAUMA PATIENT
By G.S.Umamaheshwar RAO
Neuroanesthetic care of trauma victims has greatly improved over the last 10-15 years.
This improvement has been possible due to advances in the fields of pharmacology and
monitoring technology and evolution of some basic concepts related to cerebral
protection during ischemia. The following is a discussion on some of the advances,
which possibly could have a significant impact on the perioperative management and
intensive care of the patients with head trauma in future.
Advances in Pharmacology
An ideal pharmacologic agent used in a patient with cerebral in Jury should not increase
intracranial pressure (ICP) or cerebral blood flow (CBF). The drug should not cause
uncoupling of CBF and CtV1R02. It should not adversely affect the vascular response to
carbon dioxide or autoregulation. A potent cerebral metabolic suppressant effect is
preferred as it offers brain protection. Rapid induction and rapid recovery are desirable,
Some of the intravenous and inhalational agents and muscle relaxants introduced in the
last decade possess many of these desirable properties.
Propofol
Propofol offers a number of pharmacological advantages for total intravenous
anesthesia (TIVA) in neurosurgical patients. In addition, its pharmacological properties
also make it an ideal agent for sedation in neuro ICU. Propofol decreases cerebral blood
flow (CBF) and cerebral metabolism (CMROZ) and increases cerebrovascular resistance
(CVR). Cerebral autoregulation and vascular response to carbon dioxide remain
unaltered. Its effects on neuronal activity are similar to those of thiopentone. Therefore,
it was proposed that, like thiopentone, it could offer cerebral protection. During
complete global ischemia in cats, In doses sufficient to produce isoelectric EEG, the
cerebral blood flow was much better in propofol-treated animals than those treated
with thiopentone or no drug at all (1). In yet another study in dogs, comparing propofol,
thiopentone and fentanyl, aerobic metabolism could be sustained with only propofol
(pretreatment in doses that produce burst suppression (2). The protection offered by
propofol seems to be a result of a decrease in CIv1R02, maintenance or redistribution of
CBF and prevention of large increases in blood glucose that generally accompanies and
worsens cerebral ischemia (3).
Propofol may be used for induction and maintenance of anesthesia in neurosurgical
patients with head trauma. Doses in the range of 6-12 mg/kg/h provide surgical
anesthesia while sedation can be achieved with 2-3 mg/kg/h. Propofol may also be used
-Second Edition
2011

384


for neuroimaging procedures such as CT scanning and cerebral angiography. Propofol
has been used for sedation in head injured patients requiring mechanical ventilation
(4). Incremental doses may be used to prevent rises in ICP during stimulating
procedures such as physiotherapy.
Sevoflurane
Low solubility of this inhalational anesthetic agent makes it possible to adjust the
concentration precisely. Induction and recovery are very rapid, which is very essential
in neurosurgical patients. It is less prone than isoflurane and desflurane to increase heat
rate at high concentration (5). Cerebral blood flow is preserved or slightly decreased.
Cerebral oxygen consumption is reduced to 50% at 1 MAC. Autoregulation and vascular
response to C02 are preserved. Dose-dependent decrease in cerebrovascular resistance
and increase in ICP have been noted, but such changes have not been observed under
hypocapnia. It causes a dose cognitive and psychomotor function is faster than with
isoflurane. With all the above favorable properties. sevoflurane may be a valuable
addition while managing a patient with intracranial pathology.
Desflurane
Desflurane causes a dose-related decrease in cerebral metabolism in 0.5-2,0 MAC
concentration. Cerebral autoregulation is impaired at concentrations higher than 1
MAC. Cerebrovascular response to C02 is maintained well with 0.5-1.5 MAC of
desflurane (6). In hyperventilated neurosurgical patients, CBF under 1 MAC desflurane
was similar to that under 1 MAC of isoflurane (7). In patients with supratentorial mass
lesions, 1 MAC desflurane and not isoflurane increases intracranial pressure (8).
Thus, while its low solubility favors rapid induction and recovery and cerebral blood
flow effects do no, seem to be significantly different from those of isoflurane, caution
may have to be exercised with regard to its unfavorable effects on intracranial pressure
and autoregulation.
Rocuronium
Rocuronium is a new muscle relaxant introduced into clinical practice recently. The
advantage with this agent is its rapid onset of action that makes it a suitable agent for
rapid sequence induction and intubation in head injured patients with full stomach (9).
In a dose of 0.6 mg/kg (2 x ED90) intubating conditions provided by rocuronium
are similar to those of succinylcholine (10). It is expected that it would be a substitute
for succinylcholine in future. The drug seems to have selectivity for laryngeal muscles,
which explains its rapid action. It offers good hemodynamic stability. Unlike atracurium,
it does not produce any active metabolites. There is no histamine release even at doses
as high as 4-5 ED50. The drug can be used either in intermittent boluses or as a
continuous infusion with a predictable reversibility, which facilitates neurological
-Second Edition
2011

385


examination at the end of the surgery. The neuromuscular block is potentiated by
inhalational anesthetics (isoflurane > halothane).
Advances in Monitoring
Despite significant advances in intensive care, monitoring cerebral hemodynamics and
cerebral oxygenation still remains far from satisfactory. Some of the recent advances in
this direction are:
1. Jugular Venous Oxygen Saturation Monitoring
2. Transcranial Doppler Ultrasonography
3. Laser Doppler Flowmetry
4. Near-infrared spectroscopy
Jugular Venous Oximetry
Cerebral arteriovenous oxygen difference is a reflection of the ratio of the cerebral
metabolism to cerebral blood flow (A-VDO2 = CMRO2 1 CBF). Continuous monitoring of
jugular venous oxygen saturation along with arterial oxygen saturation provides
information relating to demand versus supply of oxygen to the brain. Jugular venous
oximetry offers at least 3 indices that can be helpful in assessing the adequacy of CBF: 1)
jugular venous oxygen saturation (SjVO2), 2) cerebral A-V oxygen difference (A-VDO2)
and 3) cerebral oxygen extraction (CEO2). Normal and abnormal values for these 3
indices are given in table 1.
A low SjVO2, a high SjVO2, or a high CEO2 indicates increased extraction of oxygen, which
could be an early sign of cerebral ischemia. For example, an SjVO2<50%, when using
hyperventilation to decrease ICP, indicates occurrence of cerebral ischemia.
In head injured patients, CBF changes could be reliably estimated based on the
calculation of cerebral A-V oxygen difference (11). Head injured patients have been
shown to have cerebral venous oxygen desaturation as a function of intracranial
hypertension, systemic hypotension, hypocapnia and hypoxia (12). SjVO2 monitoring
could be very helpful to decide the optimal level of PaCO2 and cerebral perfusion
pressure in a given patient.

-Second Edition
2011

386


Table 1. Cerebral Effects of Anesthetic Drugs
Agent ICP CMR02 CBF
Thiopentone
Propofol
Etomidate

Halothane
Isoflurane

Desflurane
Sevoflurane
Nitrous Oxide
Fentanyl

Sufentanil
Ketamine
Benzodiazepines
Lidocaine

Decrease; Increase; Increase/Decrease or no effect

1. SjVO2 Normal: 60-80%
Hyperaemia:> 90%
Ischemia:< 50%

2. AVDO2 Normal: 5.0-7.5 vol%
Hyperaemia:< 5% vol%
Ischemia:> 7.5% vol%

3. CEO2 = SaO2 SjVO2 Normal: 24-40 vol%
Hyperaemia:< 24%
Ischemia:> 40%
SjVO2 monitoring gives only a global estimate of the adequacy of CBF and focal events
can not be detected by this technique. Continuous SjVO2 monitoring is possible with the
help of oximetry catheters. Table 2 shows the algorithm for the management of
cerebral ischemia based on the information from SjVO2 monitoring.

-Second Edition
2011

387


SjVO2< 50%

Verify SaO2 SaO2 < 90% (Correct Hypoxia)

SaO2 > 90%

Verify PaCO2PaCO2 < 25 mmHg ( PaCO2 to > 25 mmHg)

PaCO2 > 25mm Hg

Verify Hct Hct < 30% ( Hct to 30%)

Hct > 30% ( ICP, CMR, CPP)
Transcranial Doppler examination with a 2 MHz probe is a noninvasive technique for
measuring the systolic, diastolic and mean cerebral blood flow velocities. Middle
cerebral artery is commonly chosen for examination, as it can be easily insonated and
75-80% of ipsilateral carotid blood flow flows through it. In head injured patients, TCD
is useful: i) as a noninvasive monitor of CBF, ii) to diagnose post-traumatic vasospasm
and iii) for indirect estimation of ICP or CPP. Provided the vascular diameter remains
constant, a change in the flow velocity should be proportional to the change in the flow.
Pulsatality and resistance indices, which are calculated from peak systolic, end-diastolic
and mean velocities, are useful as indices of cerebral vascular resistance.
An increase in MCA velocity may indicate cerebral hyperaemia or cerebral vasospasm.
The distinction between the two can be made by calculating hemispheric index (MCA
flow velocity/ipsilateral ICA flow velocity). With the advent of TCD, post-traumatic
vasospasm has been demonstrated in 20-40% of patients with traumatic brain injury. It
has also been shown that posttraumatic vasospasm follows the same time course as
vasospasm of subarachnoid haemorrhage (13) (starts between 48-72 hour, peaks at 4-5
days, subsides by 7-10 days).
Changes in the morphology of flow velocity waveform with increasing ICP may be used
for semiquantitative prediction of ICP. With an increase in ICP, the diastolic velocity
decreases and the pulsatality index increases. When the ICP is higher than the diastolic
but lower than the systolic blood pressure, a biphasic pattern occurs, followed later, by
a total disappearance of the wave form when the intracranial circulatory arrest occurs
(14). A good correlation has been shown to exist between the pulasatality index and
ICP.
-Second Edition
2011

388


Laser Doppler Flowmetry (LDF)
Laser Doppler flowmetry is helpful to measure the CBF of the cortex and subcortex after
craniotomy. LDF measures the movement of red blood cells within the microcirculation
using the Doppler shift of a laser light source. LDF signal has been correlated well with
the changes in CBF (15). LDF has been used as a continuous CBF measurement
technique in the perioperative period and neurocritical care. In patients undergoing
craniotomy for resection of arteriovenous malformations (16) and tumours (17), LDF
reflected the changes in CBF during manipulations of blood pressure and CO2. LDF may
also be helpful to assess vascular response to CO2 and autoregulation (18). This
knowledge might guide intraoperative manipulations of CO2 and blood pressure to suit
the requirements of individual patients so that both cerebral ischemia and cerebral
hyperaemia can be carefully avoided.
Near Infrared spectroscopy
Near infrared spectroscopy based on the principle of absorption of light by colored
compounds is emerging as a non invasive monitor of regional cerebral oxygenation
and cerebral hemodynamics. The depth of penetration of the tissues by the infrared
light is upto 8 cm in contrast with 1 cm for visible light. In the near infrared region of
the spectrum, there are only three compounds namely oxyhaemoglobin,
deoxyhemoglobin and cytochrome aa3 which absorb the light. The ability of the tissues
to absorb near infrared spectrum provides information on the concentration of these
substances in a given region from which it is possible to derive the regional cerebral
oxygenation as well as cerebral hemodynamics. Experience with this system, at present,
is limited.
Cerebral Protection
After nearly two decades of their usage, the role of barbiturates as cerebral protective
agents remains controversial, clinical evidence is divided with regard to their ability
affect the final outcome.
Recent evidence shows the potential of mild hypothermia in protecting the injured
brain.
Mild Hypothermia
Experimental evidence over years has documented the benefits of hypothermia in
neuronal preservation. Animal studies have suggested that mild (33
o
C) rather than
moderate (29
o
C) hypothermia is more optimal to treat cerebral ischemia (19).
According to one estimate 34% of the neurosurgeons advocate 24 hours of hypothermia
in the ICU following head injury (20). A survey conducted in 1993 94 indicates that
more than 40% of neuro anesthesiologists are already using mild to moderate
hypothermia intraoperatively and 26% of them, in every patient (21). The protection
-Second Edition
2011

389


offered by intra ischemic mild hypothermia has been attributed to (i) reduction of
calcium entry, (ii) reduction of glutamate release, (iii) reduction of glycine and
dopamine release, (iv) inhibition of protein kinase C and (v) reduction of free radical
triggered lipid peroxidation. The threshold for the protective effect seems to be 36
o
C
(22). It has been shown that one degree of hypothermia (to 36
o
C) maintains ATP at
normoxic levels during a hypoxic insult that depletes ATP by 50% at normothermia
(37
o
C). A 3
o
C hypothermia more than doubles the preservation of phosphocreatine
(23). Marion et al (24), randomly assigned 40 consecutive patients to normothermic
(37 38
o
C) and hypothermic (32
o
-33
o
C brain temperature maintained for 24 hour)
groups. Hypothermia significantly decreased the ICP (40%) and CBF (265) during the
cooling period and neither parameter showed a rebound on rewarming at the end of 24
hours. At the end of 3 months, there was a trend for better outcome in hypothermic
group (12 out of 20 in hypothermic groups Vs 8 out of 20 in normothermic group). The
incidence of systemic complications was similar between the two groups. The same
group, in yet another recent publication, report findings suggesting an improved
outcome with mild hypothermia at the end of 12 months in a sub group of patients with
a Glasgow Coma Score (GCS) between 5 and 7 (table 3) (25).
3 months 6 months 12 months
All patients 0.3 (0.1 0.8) 0.4 (0.2 1.0) 0.4 (0.2 0.9)
Patients with GCS 5-7 0.2 (0.1 0.7) 0.2 (0.1 0.7) 0.2 (0.1 0.8)
Who are the patients who are likely to benefit from therapy with mild hypothermia ? A
recent study suggests that mild hypothermia is effective in preventing ICP elevations
only in patients without diffuse brain swelling in whom ICP remains higher than
20mmHg but less than 40 mmHg (26). Cooling blankets, cold saline gastric lavage and
peritoneal dialysis are some of the techniques used to achieve mild hypothermia in a
critical setting.
Hypertonic Solutions for Fluid Resuscitation
Hypertonic crystalloid solutions (3% or 7.5% NaCI) increase plasma osmotic pressure
and remove water from brain interstitial compartment. In a human prospective
randomized controlled study, resuscitation of hypotensive polytrauma patients with
hypertonic saline (7.5%) hemorrhagic or endotoxic shock, systemic perfusion was well
maintained without an increase in ICP by using 3 or 7% saline (28). Resuscitation with
small volumes of hyperosmotic, hyperoncotic solutions expands extracellular fluid
volume, increases central venous pressure and cardiac output without a significant rise
in ICP and only a transient increase in CBF. Therefore, hypertonic solutions may have a
role in resuscitation in a combined setting of hemorrhagic shock and head injury.
Its effect on ICP and brain edema seems to be more pronounced in patients with head
trauma and postoperative edema rather than in patients with intracranial haemorrhage
-Second Edition
2011

390


and infarction (29). Apart from its effects on ICP, hypertonic saline improves
myocardial contractility, precapillary dilation and reactive vasoconstriction. It has a
plasma expansive factor of 3.8. NaCI 7.5% in combination with Dextran 70.6% is under
clinical investigation at present. The addition of dextran prolongs the systemic effect
without affecting the brain. The current opinion seems to be that the usage of
hypertonic saline should be restricted only to initial resuscitation of traumatized
patients.

Central Nervous System

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Central Nervous System

Uploaded by

Copyright:

Available Formats

2011

Dr. Mohammed Azam Danish

, use of osmotic diuretics and sedation

You might also like