Monitor 21

Volume 21 No.
4
July/August 2014
ICM Index Numbers:
21/039 - 21/051
EDITORIAL
CONTENTS
Editorial
Cardiovascular
Haematology
Infection Control
Neurology
Nutrition
Organization
Outcome
Respiratory
Sedation
Sepsis
61
62
64
66
66
67
68
70
74
76
77
EDITORIAL BOARD
M.N. Smithies, Cardiff, UK

Editor
J. Cohen, Brisbane, Australia.
Associate Editor
P.J.D. Andrews, Edinburgh, UK
D.B. Chalfin, New York, U.S.A.
D.J. Cook, Hamilton, Canada
G.J. Dobb, Perth, Australia
B. Du, Beijing, PR China
R. Freebairn, Hastings, New Zealand
C.D. Gomersall, Hong Kong
A.F. Grootendorst, Rotterdam,
The Netherlands
I. R. Jenkins, Fremantle, Australia
F. N. Kapadia, Mumbai, India
H. Kern, Berlin, Germany
J. Lipman, Brisbane, Australia
M. Malbrain, Antwerp, Belgium
P.E. Marik, Norfolk, USA
D.J.J. Muckart, Congella, South Africa
M. Ostermann, London, UK
M.M. Parker, New York, USA.
R. Raper, Sydney, Australia
J. Soar, Bristol, UK.
J. Villar, Las Palmas de Gran Canaria,
Spain
S.T. Webb, Cambridge,UK
J. Wendon, London, UK
Information Specialist: Mala K. Mann,
Support Unit for Research Evidence,
Cardiff University, Cardiff, Wales, UK
PUBLISHER
Lynda A. Wirth
INTENSIVE CARE MONITOR Ltd.,
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WHATS IN A NAME?
There has been some recent controversy surrounding brain death1. Interestingly, this has not
related to organ donation with which the term has become inextricably linked but rather to nonacceptance of brain death as death. Of course, brain death has been imbued with controversy for
years. Controversies2 over the years have related to the concept itself the idea that irreversible loss
of brain function is a sufficient condition for the certification of death, and to the philosophical
underpinning of the concept3 that was consequently re-formulated in a rather unsatisfactory
manner4. And there have been challenges to the practical instantiation of the philosophical concept challenges to the way in which irreversible loss of brain function is established and even some
questioning of the certainty of the outcome.
Perhaps part of the ongoing controversy relates to the terminology. This has become more apparent
with the re-emergence of cadaveric organ donation where the certification of death has not relied on
the neurological (brain function) criterion. This was originally called non-heart-beating donation
(NHBD) and then Donation after Cardiac Death (DCD). This latter term was never accurate and was
altered to Donation after Circulatory Death to better reflect the statutory definition of death as
irreversible cessation of circulation. Perhaps this change was also stimulated by a burgeoning
interest in expanding cardiac transplantation to include this source of organs. The semantic difficulty
of transplanting the heart from a donor whose death was defined by cardiac death is obvious.
The problem with all of these terms brain death, cardiac death and circulatory death- is that
they are inaccurate and potentially misleading. In most if not all jurisdictions, none of these exist as
statutory entities. No patient can be certified or declared or even diagnosed as brain dead.
Moreover, this term, at least, has lost a good deal of its cache as a result of its widespread
inaccurate and even comical use. And the qualification of death leaves open the interpretation that
there is another, more complete or unqualified form of death, perhaps real death.
Amongst the semantic difficulties has been the problem of finding terms that are more accurate and
which are not too excessively clumsy for regular usage. Over the last few years in the American
literature predominantly but also in European journals5-7, some new and more accurate terminology
has emerged. This has predominantly resulted in a replacement of the inaccurate DCD but has
wider implications. The new term is Donation after Circulatory Determination of Death abbreviated
as DCDD. Somewhat less pervasive has been the companion term Donation after Neurological
Determination of Death (DNDD). At last with these we have a nomenclature that is accurate and not
misleading. In this paradigm, it is death that is certified or declared or diagnosed and this accords
with statutory definitions of death. Consistent with statutes, the variation is limited to the criterion
used to determine that death has occurred. So the patient is simply dead, not brain dead or
cardiac dead or circulatory dead or even really dead.
This change in terminology will have no impact on the other controversies that surround practice in
this area. Concerns over the lack of a sound scientific construct underpinning the neurological
determination of death8 persist as will concerns that current practice necessarily relies on legal
fictions9. Nevertheless, the consistent use of accurate terminology might in some measure at least
contribute to a broader and more widespread acceptance of these sometimes troublesome
concepts. And it is difficult to see any downside.
Raymond Raper, AM
Head of the ICU,
Royal North Shore Hospital
Sydney, Australia.
References:
1. Magnus DC, Wilfond BS, Caplan AL. Accepting brain death. N Engl J Med 2014;370:891-894.
2. Bernat JL. Controversies in defining and determining death in critical care. Nature Rev Neurol 2013;9:164-173.
3. Shewmon DA. Chronic Brain Death: Meta-analysis and conceptual consequences. Neurology 1998;51:1538-1545.
4. The Presidents Council on Bioethics (2008) Controversies in the determination of death. A White Paper of the Presidents
Council on Bioethics. Washington, DC. Available at: https://bioethicsarchive.georgetown.edu/pcbe/reports/death/.
5. Halpern SD, Hasz RD, Abt PL. Incidence and distribution of transplantable organs from donors after circulatory determination of
death in U.S. intensive care units. Ann Am Thoracic Soc 2013;10:73-80.
6. Sourdon J. Dornbierer M. Huber S et al. Cardiac transplantation with hearts from donors after circulatory declaration of death:
haemodynamic and biochemical parameters at procurement predict recovery following cardioplegic storage in a rat model. Eur
J Cardiothorac Surg 2013;44:87-96.
7. Gries CJ, White DB, Truog RD et al. An official American Thoracic Society/International Society for Heart and Lung
Transplantation/Society of Critical Care Medicine/Association of Organ and Procurement Organizations/United Network of
Organ Sharing Statement: ethical and policy considerations in organ donation after circulatory determination of death.
American Thoracic Society Health Policy Committee. Am J Respir Crit Care Med 2013; 188:103-109.
8. Truog RD. Brain Death is a useful fiction. Crit Care Med. 2012;40:193-194.
9. Shah SK, Truog RD, Miller FG. Death and legal fictions. J Med Ethics 2011;37:719-722.
C A R D I O V A S C U L A R
Cardiac complications
associated with goal-directed
therapy in high-risk surgical
patients: a meta-analysis.
ICM Index Number: 21/039
Top quality research
Authors: Arulkumaran N, Corredor C, Hamilton MA et al.
Reference: Br J Anaesth 2014;112:648-659.
The Board of Management and Trustees of the British Journal
of Anaesthesia.
ICM ABSTRACT
Objective
To determine whether goal-directed therapy (GDT) designed
to augment the oxygen delivery index is associated with
an increased risk of cardiac complications in high-risk,
non-cardiac surgical patients in the ICU.
analysis showed that fluid plus inotrope therapy was

associated with a significant reduction in cardiovascular
events (OR 0.55, 95% CI: 0.34 to 0.89; p=0.01) whereas
fluids alone were not (OR 0.57, 95% CI: 0.31 to 1.04;
p=0.07). Supranormal oxygen delivery goal was also
associated with a reduction in cardiovascular complications
(OR 0.50, 95% CI: 0.31 to 0.79; p=0.002). In addition, GDT
using minimally invasive cardiac output monitors, targeting
either normal or supranormal physiological goals, was
associated with a significant reduction in cardiovascular
events (OR 0.47, 95% CI: 0.31 to 0.73; p=0.0008), whereas
GDT using the pulmonary artery catheter was not
associated with benefit or harm (OR 0.70, 95% CI: 0.38 to
1.29; p=0.25). Fifteen studies (n=1393) reported arrhythmia
rates. Overall, GDT was associated with a significant
reduction in arrhythmias vs. controls (OR 0.54, 95% CI:
0.35 to 0.85; p=0.007). Specifically, there were reductions
in perioperative arrhythmias in the GDT group vs. controls in
patients treated with fluids plus inotropes (OR 0.58, 95% CI:
0.35 to 0.96; p=0.03), with a supranormal oxygen delivery
goal (OR 0.55, 95% CI: 0.32 to 0.94; p=0.03), or with
minimally invasive cardiac output monitoring devices
(OR 0.45, 95% CI: 0.24 to 0.83; p=0.01). GDT was not
associated with significant changes in rates of acute
pulmonary oedema or myocardial ischaemia.
Discussion
Introduction
Patients with limited cardiopulmonary reserve are at risk of
mortality and morbidity after major surgery. Augmentation
of oxygen delivery with intravenous fluids and inotropes can
reduce postoperative mortality and morbidity in high-risk
patients. This type of perioperative GDT uses flow-based
haemodynamic monitoring and therapeutic interventions to
augment the patients global oxygen delivery to achieve a
predetermined haemodynamic endpoint. However, the
riskbenefit balance of GDT in high-risk surgical patients
is debated and there are concerns regarding cardiac
comp lications as s ociated w ith fluid challenges
and inotropes.
Study design
Meta-analysis.
Patients and methods

A systematic search of Medline, Embase, and CENTRAL
databases for randomized controlled trials (RCTs) of GDT
in high-risk adult surgical patients was carried out. Studies
including cardiac surgery, trauma, and paediatric surgery
were excluded. For a study to be included in the metaanalysis GDT must have been started pre-emptively in the
perioperative period (24 hours before, intraoperative,
or immediately after surgery) and applied using a clear
protocol. Rates of all cardiac complications, arrhythmias,
myocardial ischaemia, and acute pulmonary oedema
were recorded. Meta-analyses were performed using
RevMan software.
Evidence Level: I
Results
Of 12,398 studies initially identified, 307 were relevant
to perioperative GDT; 22 RCTs reported cardiovascular
complications and were suitable for meta-analysis. Data
from 2129 patients were included, 1104 in the GDT arm
and 1025 in the control treatment arm. GDT was associated
with a reduction in total cardiovascular complications
(OR 0.54, 95% CI: 0.38 to 0.76; p=0.0005). Subgroup
In the treatment of high-risk surgical patients, administration

of fluid challenges and inotropes guided by haemodynamic
monitoring is not associated with an increased rate of
cardiovascular events. Perioperative GDT was associated
with a reduction in the total number of cardiovascular
events, particularly arrhythmias. The greatest reductions in
morbidity were in patients treated to achieve supranormal
oxygen delivery targets, treated with fluids plus inotropes,
a n d m a n a g e d u s i n g m i n i m a l l y i n v a s i v e c a rd i a c
output monitors.
ICM COMMENT
A recent Cochrane review on perioperative goal
directed therapy concluded that the balance of
current evidence does not support widespread
implementation of this approach1. The findings
of the Cochrane analysis contrast with those
of Arulkumaran et al. who demonstrated that
perioperative GDT significantly reduced the risk of
postoperative cardiovascular complications. The
contrasting findings of these two meta-analyses
is explained by the fact that the Cochrane review
included patients undergoing cardiac surgery
whereas these were excluded by Arulkumaran et al.
Due to the nature of the surgery, GDT is less likely
to benefit cardiac surgery patients. In addition,
Arulkumaran et al. excluded the study by Sandham
et al. as this study did not have an explicit protocol
for haemodynamic optimization2. Current evidence
demonstrates that perioperative GDT reduces both
infectious and non-infectious complications in low,
moderate and high-risk surgical patients, while
this approach also reduces mortality in high-risk
patients3. The concept of GDT is supported by the
observation that patients develop an oxygen
debt in the postoperative period, the degree
of the oxygen debt being related to the risk of
postoperative complications4. Current evidence
would suggest that haemodynamic optimization
should begin intraoperatively and continue into
the postoperative period for at least 6 hours.
These are abstracts of original papers. Readers are recommended to obtain and read the original published article.
62

Haemodyn ami c opti mi z ati on may best be
performed with non-invasive or minimally invasive
cardiac output monitors using a combination of
fluids and vasoactive agents. Fluids should be
given until the patient is no longer fluid responsive
and vasoactive agents to ensure a mean arterial
pressure (MAP) > 65 mmHg and a cardiac index
of > 2.5 L/min/m2.
References:
1. Grocott MP, Dushianthan A, Hamilton MA et al. Perioperative increase in
global blood flow to explicit defined goals and outcomes after surgery:
A Cochrane Systematic Review. Br J Anaesth 2013; 111:538-548.
2. Sandham JD, Hull RD, Brant RF et al. A randomized, controlled trial of the
use of pulmonary-artery catheters in high-risk surgical patients. N Engl J
Med 2003; 348:5-14. (See also Intensive Care Monitor 2003;10:22).
3. Cecconi M, Corredor C, Arulkumaran N et al. Clinical review: goaldirected therapy-what is the evidence in surgical patients? The effect on
different risk groups. Crit Care 2013; 17:209.
4. Shoemaker WC, Appel PL, Kram HB. Tissue oxygen debt as a determinant
of lethal and nonlethal postoperative organ failure. Crit Care Med 1988;
16:1117-1120.
The bottom line is that perioperative GDT

improves patient outcomes and should be
considered in all high-risk surgical patients.
As GDT reduces the risk of complications
in low- to moderate risk patients this
intervention should also be considered
in these patients. PEM
Effect of prehospital induction

of mild hypothermia on survival
and neurological status among
adults with cardiac arrest: a
randomized clinical trial.
Authors: Kim D, Nichol G, Maynard C et al.
Reference: JAMA 2014: 311; 4552.
Trial registration number: NCT00391469
American Medical Association.
ICM ABSTRACT
Objective
To investigate whether prehospital cooling improves survival
and neurological outcomes after resuscitation in cardiac
arrest patients with or without ventricular fibrillation (VF).
Introduction
Hypothermia has been shown to aid brain recovery
following resuscitation from VF and is now recommended
for patients who remain in coma after resuscitation.
However, the optimal timing of induction of hypothermia is
unclear. Although it has been theorized that early cooling
would be beneficial, this was not shown in clinical studies
of prehospital hypothermia to date.
Study design
Randomized, controlled clinical trial.
Adults with prehospital cardiac arrest and resuscitated

by paramedics without return of consciousness were
randomized to standard care with or without prehospital
cooling. Randomization was stratified according to the
first recorded rhythm (VF or no VF). Patients with traumatic
cardiac arrest were excluded. Hypothermia was induced
by infusing up to 2 litres of 4C normal saline as soon as
possible following return of spontaneous circulation, with a
goal temperature of under 34C. Once admitted to hospital,
standard treatments were used, which included cooling
protocols for those patients resuscitated from VF, and at
one hospital, cooling was also indicated for patients without
VF. The primary outcomes were survival and neurological
status at hospital discharge. The number of days to
awakening (or death if the patient never regained
consciousness) was calculated. Neurological status on
discharge for survivors was categorized as full recovery,
mild to moderate impairment, severely impaired or
comatose. Data on patient demographics, clinical variables
and treatments received before and during the hospital stay
were also collected.
Evidence Level: II
Results
Over a 5-year period, 1,359 patients (583 with VF and
776 without VF) were randomized. Patients randomized to
prehospital cooling had their core temperature lowered by
a mean of 1.20C (95%CI, 1.33C to 1.07C) in patients
with VF and by 1.30C (95% CI, 1.40C to 1.20C) in
patients without VF by hospital arrival. Within the
intervention group, the target cooling temperature of less
than 34C was achieved by 26% of patients with VF
(95% CI, 2131%) and 29% (95% CI, 2534%) of patients
without VF. Patients randomized to prehospital cooling who
also received hospital cooling achieved a goal temperature
in a mean of 4.2 hours (95% CI, 3.84.6 hours) compared
with 5.5 hours (95% CI, 5.06.0 hours) in patients who only
received hospital cooling (p < 0.001). Survival to hospital
discharge was similar in the intervention and control groups,
both for patients with VF (62.7% [95% CI, 57.068.0%]
vs. 64.3% [95% CI, 58.669.5%], respectively; p = 0.69)
and patients without VF (19.2% [95% CI, 15.623.4%]
vs. 16.3% [95% CI, 12.920.4%], respectively; p = 0.30).
Similarly, there were no differences in neurological
outcomes. For example, the number of patients achieving
a neurological status of full recovery or mild impairment at
discharge was not significantly different between
intervention and control groups for patients with VF
(57.5% [95% CI, 51.863.1%] vs. 61.9% [95% CI,
56.267.2%], respectively; p = 0.69) nor for those without
VF (14.4% [95% CI, 11.318.2%] vs. 13.4% [95% CI,
10.417.2%], respectively; p = 0.30). However, prehospital
cooling was associated with more adverse events: re-arrest
en route to hospital was more common in the intervention
group than the control group (26% [95% CI, 2229%] vs.
21% [95% CI, 1824%], respectively; p = 0.008), and the
intervention group tended to need more diuretics, have
lower oxygenation and show early pulmonary oedema on
first chest x-ray.
Discussion
This large trial of prehospital hypothermia following
resuscitation from cardiac arrest, found no improvement in
outcomes compared with standard treatment in patients
with or without VF. Although the patients had a reduced
core temperature by hospital arrival and reduced the time to
63
reach a temperature of 34C for patients who received

hospital cooling, early hypothermia did not appear to be
of benefit but was associated with more adverse events.
The authors discuss possible reasons for these findings
including insufficient prehospital cooling or that the harms
from cooling outweighed the benefits.
ICM COMMENT
Post-resuscitation care should be currently getting
attention in your own institution. There is now
mounting high-quality evidence available to guide
clinical practice in order to provide the best care we
can for this group of patients. Two landmark papers
were recently published online simultaneously, the
study by Kim et al. commented on here and the
Targeted Temperature Management (TTM) study
by Nielsen et al.1.
Induced hypothermia is currently recommended for
comatose patient resuscitated after out-of-hospital
VF arrest 2. What remains unclear is the timing,
duration and method of cooling. Recently the
International Liaison Committee on Resuscitation
(ILCOR) have provided an update following the
results of the TTM study stating that some
clinicians may make a local decision to use a target
temperature of 36C pending further guidance3.
Although prehospital cooling may have theoretical
advantages, the study by Kim et al. along with a
previous study by Bernard et al.4 confirm that
p re h o s p i t a l i n d u c t i o n o f h y p o t h e r m i a b y
intravenous (IV) infusion of cold fluid is not
beneficial. Patients in the intervention group
received up to 2 litres of 0.9% saline at 4C
administered through a peripheral intravenous
cannula of at least 18 gauge, using a pressure
bag inflated to 300 mmHg. Not only were there
no differences in survival or neurological outcome
between the two groups but prehospital
administration of cold IV fluid more frequently
resulted in re-arrest and pulmonary oedema. This
was a well conducted trial set in a high performing
prehospital care system which took 5 years to
complete. More than half the patients eligible for
inclusion were enrolled into the trial. In-hospital
care for all patients consisted of hypothermia with
a target temperature of 34C for up to 24 hours as
well as early coronary angiography and withdrawal
of life support if appropriate.
The authors speculate on the potential reasons
for the lack of benefit demonstrated by early
hypothermia. Perhaps the intervention was not
applied early enough? Ongoing studies are
investigating initiation of hypothermia during
cardiopulmonary resuscitation using cold IV fluid5
and nasopharyngeal cooling6. Perhaps the method
used to apply hypothermia was harmful? Animal
models suggest that IV volume loading during
cardiopulmonary resuscitation increases right atrial
pressure, increases left ventricular end-diastolic
pressure and reduces coronary perfusion pressure
after return of spontaneous circulation 7. A no
volume method of cooling using surface or
intravascular devices may prove to be beneficial.
2. Peberdy MA,Callaway CW,Neumar RW et al. American Heart Association.

Part 9: post-cardiac arrest care: 2010 American Heart Association
guidelines for cardiopulmonary resuscitation and emergency
cardiovascular care. Circulation 2010;122(suppl 3):S768-S786.
3. http://www.ilcor.org/data/TTM-ILCOR-update-Dec-2013.pdf
4. Bernard SA, Smith K, Cameron P et al. Rapid Infusion of Cold Hartmanns
(RICH) Investigators. Induction of therapeutic hypothermia by paramedics
after resuscitation from out-of-hospital ventricular fibrillation cardiac
arrest: a randomized controlled trial. Circulation 2010;122:737-742.
5. Deasy C, Bernard S, Cameron P et al. Design of the RINSE trial: the rapid
infusion of cold normal saline by paramedics during CPR. BMC Emerg
Med 2011;11:17.
6. Nordberg P, Taccone FS, Castren M et al. Design of the PRINCESS trial:
Pre-hospital Resuscitation Intra-Nasal Cooling Effectiveness Survival
Study (PRINCESS). BMC Emerg Med 2013;13:21.
7. Yannopoulos D,Zviman M,Castro V et al. Intra-cardiopulmonary
resuscitation hypothermia with and without volume loading in an
ischemic model of cardiac arrest. Circulation 2009;120:1426-1435.
8. Bernard S. Inducing hypothermia after out of hospital cardiac arrest.
BMJ 2014;348:2735.
The bottom line is that we now know that

prehospital administration of cold IV fluid to
induce hypothermia is not beneficial and may
be harmful. Although the timing and method
of hypothermia can be questioned, in the
light of recent evidence I tend to concur with
Bernard who has commented that a target
temperature goal of 36C is simpler, cheaper,
and easier to manage 8.STW
ICM RECOMMENDED REVIEW PAPERS
Bjrk M. Surgery for ruptured abdominal aortic aneurysm.
BMJ 2014;348:g95. 13 references.
Hollenberg SM. Hemodynamic monitoring. Chest
2013;143:1480-1488. 60 references.
H A E M A T O L O G Y
A no-prophylaxis platelettransfusion strategy for

hematologic cancers.
Hot topic
Authors: Stanworth SJ, Estcourt LJ, Powter G et al. for the TOPPS
Investigators.
Reference: N Engl J Med 2013; 368: 17711780.
Trial registration number: ISRCTN08758735.
Massachusetts Medical Society.
ICM ABSTRACT
Objective
References:
1. Nielsen N, Wetterslev J, Cronberg T et al. Targeted temperature
management at 33 degrees C versus 36 degrees C after cardiac arrest.
N Engl J Med 2013;369:2197-206. (See also Intensive Care Monitor
2014;21:22).
To determine, in patients with haematological cancers,

whether a policy of not giving platelet transfusions as
prophylaxis against clinical bleeding was as safe and
effective as giving prophylactic platelet transfusions.
64
Introduction
Severe thrombocytopaenia often develops in patients with
a haematological cancer, either as a consequence of the
disease or its treatment. Prophylactic platelet transfusions
are usually administered to increase platelet counts and
reduce the risk of bleeding. However, previous studies have
questioned whether prophylactic platelet transfusions are
sufficiently effective at preventing bleeding in these patients
and suggested that therapeutic only transfusion might be
more appropriate.
haematological cancers: the proportion of patients who had

bleeding events of WHO grade 2, 3, or 4 was reduced by
7% overall in the group that received prophylactic platelet
transfusions. However, despite prophylaxis, the rate of
bleeding events of WHO grade 2, 3, or 4 remained high.
The authors suggest that the possibility of a no-prophylaxis
policy for platelet use in patients undergoing autologous
stem-cell transplantation should be an area for further
investigation.
ICM COMMENT
Study design
Randomized, parallel-group, open-label, non-inferiority trial.

The study was carried out at 14 centres in the UK and
Australia. Patients had a haematological cancer, were 16
years old, receiving chemotherapy or undergoing stem-cell
transplantation and had, or were expected to have,
thrombocytopaenia (platelet count <50109/litre) for at least
5 days. Patients received either prophylactic platelet
transfusions or no prophylaxis. In both trial groups
therapeutic use of platelet transfusions were permitted.
The primary end point was bleeding of World Health
Organization (WHO) grade 2 (moderate), 3 (severe), or
4 (debilitating or life-threatening) occurring up to 30 days
after randomization. Secondary outcomes included the
numb er of d ays w ith b leed ing events , time from
randomization to first bleeding, numbers of platelet and
red cell transfusions, number of days with a platelet count
<20109/litre, time until recovery from thrombocytopaenia,
and duration of hospital stay. A prespecified subgroup
analysis assessed bleeding rates in patients undergoing
autologous stem-cell transplantation.
Evidence Level: II
Results
Between 2006 and 2011, 600 patients underwent
randomization: 301 to no-prophylaxis, 299 to prophylaxis.
Baseline characteristics were well matched between
groups. Bleeding of WHO grade 2, 3, or 4 occurred in 151
of 300 patients (50%) in the no-prophylaxis group vs. 128 of
298 (43%) in the prophylaxis group (adjusted difference in
proportions, 8.4 percentage points; 90% CI, 1.7 to 15.2;
p=0.06). In other words, a no-prophylaxis strategy for
platelet transfusions was not non-inferior to a prophylaxis
strategy. A post-hoc superiority analysis showed that noprophylaxis was inferior to prophylaxis (p=0.04). Compared
with patients in the prophylaxis group, those in the noprophylaxis group had more days with bleeding episodes
(rate ratio, 1.52; 95% CI, 1.14 to 2.03; p=0.004), a shorter
time to the first bleeding episode (hazard ratio, 1.30; 95%
CI, 1.04 to 1.64; p=0.02) and a greater number of days with
a platelet count <20109/litre (p<0.001) and <10109/litre
(p<0.001). Overall platelet use was markedly reduced in
the no-prophylaxis group. The proportion of patients with
serious adverse events was not different between groups.
In a predefined subgroup analysis, the autologous stem-cell
transplantation group had no significant difference in
bleeding rates within the prophylaxis and no-prophylaxis
groups. However, the effect of platelet prophylaxis was seen
to be greater in patients being treated with chemotherapy
or allogeneic haematopoietic stem-cell transplantation
i.e. significantly reduced bleeding events.
Discussion
This study indicates that prophylactic platelet transfusion
is beneficial in reducing bleeding in patients with
Thrombocytopaenia is a common clinical

manifestation of both haematological malignancies
and their chemotherapeutic treatments with or
without autologous bone marrow transplantation.
Intuitively, the risk of spontaneous bleeding
increases with decreasing platelet count below a
certain threshold. Therefore, it is common practice
i n man y h aematol ogy cen tres, an d i n ICUs
admitting patients with haematological malignancy,
to administer platelet transfusions prophylactically
below a certain platelet count- in many centres
when the platelet count is <10 x 109/litre.
However, there is scant evidence for this practice,
in fact quite the reverse. Two large studies, one of
prophylactic platelet transfusion threshold and the
other of platelet dose showed no increase in
bleeding with a lower threshold or a smaller dose of
platelets transfused 1,2 .This reasonably large
randomized trial of prophylactic versus noprophylactic platelet transfusion did demonstrate a
small increase in the significant bleeding when no
protocol-based prophylactic platelet transfusions
were administered. However there was no
difference in the reported serious adverse events
(WHO grade 3 and 4 bleeding) for 30 days after
randomization. Interestingly, the authors were silent
on 30-day mortality within the two arms, but one
assumes that death would have been counted as a
serious adverse event. Whilst the conclusion of the
authors that bleeding events of WHO grades 2, 3
and 4 was reduced by 7% (from 50% to 43%), the
p value for non-inferiority was only 0.06; a noninferiority margin of 10% was an a priori cut off.
A predefined subgroup analysis of patients
undergoing autologous bone marrow
transplantation demonstrated that there was no
difference in bleeding incidence between the noprophylaxis and platelet prophylaxis group.
Confusingly, this was in contradistinction to a
recent study, which demonstrated the opposite
in this cohort3.
Those receiving platelet prophylaxis had a longer
median time to first bleeding episode (19.5 vs.
17.2 days; p=0.02); this difference (2.3 days) appears
small, but is more impressive when graphically
displayed as the hazard plot shown in the paper.
References:
1. Rebulla P, Finazzi G, Marangoni F et al. The threshold for prophylactic
platelet transfusions in adults with acute myeloid leukemia. N Engl J Med
1997;337:1870-1875.
2. Slichter SJ, Kaufman RM, Assmann SF et al. Dose of prophylactic platelet
transfusions and prevention of haemorrhage. N Engl J Med 2010;
362:600-612.
3. Wandt H, Schaefer-Eckart K, Wendelin K et al. Therapeutic platelet
transfusion versus routine prophylactic transfusion in patients with
haematological malignancies: an open-label, multicentre, randomised
study. Lancet 2012; 380:1309-1316.
65
The bottom line is that haematological

patients who received prophylactic platelet
transfusion when their platelet count was
< 10 x 109/litre versus those who didnt had
a small absolute reduction in risk of bleeding
(43% vs. 50%) in this randomized, controlled
trial. There was also an increase to time to
first bleed in those receiving prophylaxis.
This effect appeared limited to those
receiving chemotherapy and was not seen
in those undergoing autologous stem-cell
transplantation. Given the different outcomes
in other, recent trials further studies are
probably warranted. IRJ
I N F E C T I O N
C O N T R O L
ICM RECOMMENDED REVIEW PAPER

Zhanel GG, Chung P, Adam H. Ceftolozane/tazobactam: A
novel cephalosporin/[beta]-lactamase inhibitor combination
with activity against multidrug-resistant Gram-negative
bacilli. Drugs 2014;74:31-51. 79 references.
N E U R O L O G Y
Noninvasive regional cerebral

oxygen saturation for neurological prognostication of
patients with out-of-hospital
cardiac arrest: A prospective
multicenter observational study.
a near-infrared spectrometer were applied to the forehead

and rSO2 measured within 3 minutes of hospital arrival. The
primary endpoint was neurological outcomes, categorized
by Cerebral Performance Category (CPC) at 90 days after
cardiac arrest. A receiver operating curve (ROC) analysis
was conducted to evaluate the prognostic accuracy of
good neurological outcome, and the optimal cutoff point
was determined by estimating the Zero-One index.
Evidence Level: IV
Results
From 1017 cases of OHCA, 672 patients were enrolled,
including 52 comatose patients with detectable pulse (8%)
at hospital arrival. The mean (SD) rSO2 at hospital arrival
was 2114%. There were 38 patients who survived to
hospital discharge: 29 patients with good neurological
outcome at 90 days (CPC 12) and 9 patients with poor
neurological outcome (CPC 34). The patients with good
neurological outcome had significantly higher rSO2 on arrival
at hospital compared with those who subsequently died or
who had a poor neurological outcome at 90 days (mean
[SD] 55.620.8% vs. 19.7 11.0%; p<0.001). ROC
analysis indicated an optimal rSO2 cutoff point of >42% for
predicting good neurological outcome, with sensitivity 0.79
(95% CI, 0.600.92), specificity 0.95 (95% CI, 0.930.96),
positive predictive value 0.41 (95% CI; 0.280.55), negative
predictive value 0.99 (95% CI, 0.981.00), and area under
the curve 0.90 (95% CI, 0.880.92). For the subgroup of
patients with detectable pulse on arrival at hospital, ROC
analysis found the optimal cutoff point for predicting good
neurological outcome was rSO2 >62%, whereas, in patients
with persistent cardiac arrest at hospital arrival, the optimal
cutoff point was rSO 2 >21%. When patients were
categorized according to their rSO2, only 0.7% of patients
rSO2 with a value 15% and 1.8% of those with an rSO2
value of 1642% had a good neurological outcome,
compared with 41% of those with an rSO2 value >42%.
Discussion
Authors: Ito N, Nishiyama K, Callaway CW et al.
Reference: Resuscitation 2014;85:778-784.
The Authors.
ICM ABSTRACT
This study was able to demonstrate that the rSO2 on hospital

arrival can predict good neurological outcome at 90 days
after OHCA, with high specificity and positive predictive
value. The optimal value of rSO 2 for good neurological
outcome was 42% or above, regardless of the presence or
absence of a detectable pulse on arrival. Whether rSO2 can
also provide a real-time measure of cerebral perfusion during
resuscitation is worthy of future investigation.
Objective
ICM COMMENT
To investigate whether regional brain oxygen saturation (rSO2)

on hospital arrival can predict neurological outcomes at
90 days in patients with out-of-hospital cardiac arrest (OHCA).
In this paper, Ito et al. assess the utility of a device that

is reported to measure regional cortical oxygen tension.
Cerebral oximetry estimates the oxygenation of
regional tissue by transcutaneous measurement of
the cerebral cortex, an area of the brain that is
particularly susceptible to changes in the demand
and supply of oxygen, and which has a very limited
oxygen reserve. Measurement is based on the
ability of light to penetrate the skull and to
determine haemoglobin oxygenation according to
the amount of light absorbed by haemoglobin, and
called near-infrared spectroscopy (NIRS).
Measurement of oxygenation within an organ of
interest has inherent advantages over measurement
of oxygen supply (SpO 2 ) and venous saturation
(i.e. ScvO 2 ) alone. Such devices have been
available for more than 30 years. The normal
range is considered 60-80%.
Introduction
As the brain is the organ most vulnerable to ischaemia, the
ability to monitor cerebral perfusion during resuscitation
might help in predicting neurological outcomes after cardiac
arrest, particularly in the case of OHCA where global cerebral
ischaemia often results in poor neurological outcomes.
Study design
Prospective, multicentre, cohort study.

Patients who had suffered an OHCA and who were
unresponsive during and after resuscitation at hospital
arrival were eligible for the study. Two disposable probes of
66
Data from the Society of Thoracic Surgeons (STS)

National Database strongly suggest that the intraoperative use of cerebral oximetry in cardiac
surgery patients frequently (23%) served as an early
warning of an intraoperative event that could lead
to potential adverse clinical outcomes in both adult
and paediatric patients. The STS has the worlds
largest database of cardiothoracic cases, with more
than 500 participating centres contributing
procedural data for in excess of 3.77 million.
Monitoring and management of rSO 2 has been
tested in a randomized controlled trial (RCT),
leading to a reduction in morbidity and length of
stay in ICU1 after cardiac surgery.
The authors have acknowledged a number of
shortcomings of this observational study, including the
very short duration of rSO2 measurement, described
as >1 minute, the lack of pre-hospital measurements
and a large cohort of poor outcome patients making
modeling difficult. The spread of CPC outcomes is
skewed, with many CPC 5 but very few 3, 2 or 1.
The contemporary data from rSO 2 monitoring
is more convincing than historic data 2 and the
previously asked question, did the Invos NIRS
measure brain or scalp tissue oxygenation? seems
less relevant. Even if brain penetration is limited,
does that matter after cardiac arrest as it is a
condition of global hypoperfusion? Cerebral
measurement is supported to a limited extent by
data showing a greater sensitivity for rSO2 >42%
than lactate or base excess but not by much!
References:
1. Murkin JM, Adams SJ, Novick RJ et al. Monitoring brain oxygen
saturation during coronary bypass surgery: a randomized, prospective
study. Anesth Analg. 2007;104:51-58.
2. McKeating EG, Monjardino JR, Signorini DF, Souter MJ, Andrews PJ.
A comparison of the Invos 3100 and the Critikon 2020 near-infrared
spectrophotometers as monitors of cerebral oxygenation. Anaesthesia
1997;52:136-140.
The bottom line is that this is something for

the future, but a portable device is needed.
PJDA
N U T R I T I O N
Early parenteral nutrition in

critically ill patients with shortterm relative contraindications
to early enteral nutrition: a
randomized controlled trial.
Authors: Doig GS, Simpson F, Sweetman EA et al.
Reference: JAMA 2013;309:21302138.
Trial registration number: ACTRN012605000704695
ICM ABSTRACT
Objective
To examine the impact on outcomes of early parenteral
nutrition for critically ill adults ineligible for early enteral

nutrition due to a short-term relative contraindication.
Introduction
The benefit of parenteral nutrition when enteral nutrition fails
to provide sufficient calories for critically ill patients is well
established. However, in the case of a patient who has
short-term contraindications to enteral nutrition, the
question remains as to whether it is best to wait until enteral
nutrition can be instigated or to provide parenteral nutrition
in the interim. Previous, small studies, have suggested that
survival improves but at the cost of an increased risk of
infection with early parenteral nutrition in these patients.
Study design
Randomized, controlled, trial.

Adult ICU patients expected to remain in the ICU for more
than 2 days, with a central venous line in place, and who
were ineligible for enteral nutrition because of short-term
contraindications were randomized to receive standard
care or early parenteral nutrition. The protocol for the
parenteral nutrition group specified that caloric (up to
35 kcal/kg/day) and macro- and micronutrient targets be
achieved by day 3 of the study. On day 3 patients were
assessed for eligibility for oral or enteral nutrition. The
primary outcome was mortality at day 60. Other outcomes
included quality of life and physical functioning measures,
body composition changes (based on Subjective Global
Assessment), days of clinically significant organ failure,
infection rates, lengths of stay and the number of days
on mechanical ventilation, renal replacement therapy and
antibiotic therapy. An algorithm was used to identify baseline
characteristics to create a covariate-adjusted logistic
regression model to control for factors that would influence
mortality. A covariate-adjusted average risk difference
and appropriate 95% CI were calculated for the whole
population and for different subgroups based on body mass
index (BMI), age and the presence of insulin-treated
diabetes.
Evidence Level: II
Results
There were 1372 patients enrolled, in 31 participating ICUs.
Of 682 patients receiving standard care, patients remained
unfed for a mean of 2.8 days after randomization; 29.2%
initially started enteral nutrition, 27.3% were started on
parenteral nutrition, and 40.8% remained unfed throughout
their ICU stay. The standard care group received 2.9 days
of parenteral nutrition (95% CI, 2.73.1) and 4.0 days of
enteral nutrition (95% CI, 3.64.6) while in the ICU. In the
intervention group, parenteral nutrition was started a mean
of 44 minutes after enrolment (95% CI, 3655). Patients
received a mean of 6.0 days of parenteral nutrition (95% CI,
5.66.4) and 3.1 days of enteral nutrition (95% CI, 2.83.5)
while in the ICU. Mortality at 60 days was similar between
the two groups (22.8% for standard care vs. 21.5% for early
parenteral nutrition; risk difference, 1.26%; 95%CI, 6.6%
to 4.1%; p=0.60). There was a statistically significant
improvement in quality of life (RAND-36 General Health
Status) in the early parenteral nutrition group but the
difference between groups was not clinically meaningful
(45.5 vs. 49.8; mean difference, 4.3; 95% CI, 0.957.58;
p=0.01). Early parenteral nutrition patients required fewer
days of invasive ventilation (7.73 vs. 7.26 days per
10 patientICU days, risk difference, 0.47; 95% CI, 0.82
67
to 0.11; p=0.01) and experienced less muscle wasting and

fat loss. There were no significant differences between the
groups in rates of infection, nor in the length of stay in the
ICU or hospital. Subgroup analyses gave similar results to
the whole population analysis.
Discussion
This study failed to show any survival benefit in starting
parenteral nutrition early in patients unable to receive enteral
nutrition due to short-term relative contraindications. While
early parenteral nutrition appeared to prevent loss of muscle
and fat, this did not translate to improved recovery overall.
However, the authors speculate that this may have
contributed to the shorter duration of mechanical ventilation
in the intervention group.
ICM COMMENT
This is another well designed, large - for a nutrition
study - clinical trial of early parenteral nutrition in
ICU patients. As the authors point out though, it
differs from the EPaNIC trial 1 in the patient
population included. As indicated by the title, these
were patients with contraindications to early enteral
nutrition, so just the group that the protagonists of
early nutritional support would suggest should
benefit from early parenteral nutrition. Those in the
standard treatment arm were treated as determined
by the treating physician and it is worth noting that
27% of these received parenteral nutrition, 29%
enteral nutrition and 3% both after a mean of only
about 2 days after ICU admission. Only 41% did not
receive nutritional support during a mean ICU stay
of 3.7 days.
However, whichever way you look at it, the patients
given early parenteral nutrition had minimal if any
benefit in terms of any patient-centred outcome
and even when the differences between groups
were statistically significant they were of marginal
or no clinical significance.
The study appears to have been well conducted
to reflect real-world standards of care. Although
participants were not blinded as to the study
intervention arm, the objective nature of many of
the study end points, including the primary end
point, makes bias unlikely. If there was any bias
from the investigators, it would have likely been
towards early parenteral nutrition rather than the
reported outcome.
It remai n s to be seen i f advocates of earl y
parenteral nutritional support will change their
practice they can point to the lack of harm from
early parenteral nutrition in this study but it does
come at a financial cost that is difficult to justify.
While few patients were included with a BMI
<18.5 (a total of 46, 20 allocated to standard care),
even in this subgroup there was no difference in the
primary end-point.
Reference:
1. Casaer MP, Hermans G, Wilmer A, Van den Berghe G. Impact of early
parenteral nutrition completing enteral nutrition in adult critically ill
patients (EPaNIC trial): a study protocol and statistical analysis plan
for a randomized controlled trial. Trials 2011;12:21.
The bottom line is that this is another study

suggesting there is no hurry to provide early
parenteral nutrition to critically ill patients.
GJD
O R G A N I Z A T I O N
Psychiatric diagnoses and

psychoactive medication use
among nonsurgical critically ill
patients receiving mechanical
ventilation.
Authors: Wunsch H, Christiansen CF, Johansen MB et al.
Reference: JAMA 2014;311:11331142.
ICM ABSTRACT
Objective
To examine the burden of psychiatrist-diagnosed psychiatric
illness and all psychoactive medication prescriptions before
nonsurgical critical illness, and to determine whether critical
illness itself can cause psychiatric illness in patients with no
prior history.
Introduction
Results from a number of small studies show a possible link
between the ICU treatment of critical illness and psychiatric
illness. However, the burden of psychiatric illness prior to
critical illness, and the risk of psychiatric illness following
critical illness are unclear.
Study design
Population-based cohort study.

Data were from Danish national medical databases.
A cohort was created including all adults (15 years) with
a first-time nonsurgical admission to a Danish ICU and
requiring mechanical ventilation between 1 January 2006
and 31 December 2008. Two matched comparison cohorts
were also created: (1) patients admitted to the same
hospital during the same period (one for every ventilated
patient) and (2) individuals from the general population (five
for every ventilated patient). The main outcome measures
were any psychiatric diagnoses by psychiatrists and any
redeemed prescriptions for a psychoactive medication.
Secondary outcomes included specific psychiatric disease
categories and medication types. Prevalence ratios (PRs)
were calculated for any psychiatric illness in patients
receiving mechanical ventilation and were compared with
PRs for the hospital and general population cohorts, both
1 and 5 years before the index admission. The incidence of
new psychiatric illness in the first year after admission was
also determined and hazard ratios (HRs) calculated.
Evidence Level: IV
Results
Between 2006 and 2008, 24,179 nonsurgical patients
admitted to a Danish ICU received mechanical ventilation.
During the preceding year, 2.9% of patients receiving
mechanical ventilation had one or more psychiatric
diagnoses. This prevalence was higher than for the hospital
cohort: 2.3% (adjusted PR, 1.50; 95% CI, 1.34 to 1.69;
p<0.001) or the general population cohort: 0.8% (adjusted
PR, 3.69; 95% CI, 3.35 to 4.07; p<0.001). In the preceding
68
5 years, 6.2% of mechanically ventilated patients had one or

more psychiatric diagnoses vs. 5.4% for the hospital cohort
(adjusted PR, 1.31; 95% CI, 1.22 to 1.42; p<0.001) or 2.4%
for the general population cohort (adjusted PR, 2.57; 95%
CI, 2.41 to 2.73; p<0.001). For the mechanically ventilated
patients, 5-year preadmission psychoactive prescription
rates were 48.7% vs. 48.8% for the hospital cohort
(adjusted PR, 0.97; 95% CI, 0.95 to 0.99; p<0.001) or
33.2% in the general population cohort (adjusted PR, 1.40;
95% CI, 1.38 to 1.42; p<0.001). Among the 9912 critical
illness survivors with no psychiatric history, the absolute risk
of new psychiatric diagnoses was low (0.5%), but higher
than the hospital cohort (0.2%) over the first 3 months
(adjusted HR, 3.42; 95% CI, 1.96 to 5.99; p<0.001), or the
general population (0.02%; adjusted HR, 21.77; 95% CI,
9.23 to 51.36; p<0.001). The risk of new psychoactive
medication prescriptions was also increased in the first
3 months: 12.7% vs. 5.0% for the hospital cohort (adjusted
HR, 2.45; 95% CI, 2.19 to 2.74; p<0.001) and 0.7% for the
general population (adjusted HR, 21.09; 95% CI, 17.92 to
24.82; p<0.001). These differences had largely resolved by
9 to 12 months after discharge.
Discussion
Prior psychiatric illness is more common in critically ill
patients who receive mechanical ventilation in the ICU than
in most hospitalized patients or the general population, so
psychiatric disease may predispose patients to critical
illness. In addition, among survivors of critical illness, there
appears to be an increased, but transient, risk of new
psychiatric diagnoses and treatment. This has implications
for discharge planning, as patients treated for critical illness
may require higher than normal levels of psychiatric
assessment and families and caregivers may need
information on possible psychiatric needs.
ICM COMMENT
Survivors of critical illness frequently have severe
and long-lasting cognitive impairments and
psychiatric disorders, which adversely affect
functional outcomes including quality of life,
independent living and return to work. In this recent
study by Wunsch, the incidence of new psychiatric
disorders and prescription of psychoactive
medications is increased in the year following
discharge in survivors of critical illness. Recognition
of the impaired cognitive functions has significant
interest, and if the choice between two treatment
strategies influences not just the mortality outcome
but the quality of life and mental health experienced
after discharge, we need to be better informed
about our acute clinical choices.
The study also shows a higher incidence of
psychiatric disorders in the critically ill population
than in either general hospital patients, or the
general population, and a higher use of
preadmission psychoactive prescription medication
than the general population. This is probably not
surprising to anyone involved in intensive care
delivery. Even ignoring the increased incidence of
suicidal overdose and drug interaction-related
admissions, patients with psychiatric disorders
s u ff e r f ro m m o re i l l n e s s e s a n d a re m o re
p re d i s p o s e d t o h o s p i t a l i z a t i o n f o r m e d i c a l
conditions than those without psychiatric
diagnoses 1,2,3 . Euripides wrote two and a half
centuries ago that, Those whom God wishes to
destroy, he first makes mad. It seems now that,
even in those whom intensive care saves from

destruction, the madness persists. In addition,
the mental health issues may not only be confined
to the patient, as family and friends suffer sleep
disorders and other stresses4.
While intensive care physicians may be impotent
at preventing the preexistent psychiatric disease,
increased awareness that ICU stay is associated
with increased new mental health needs in
survivors may help longer term management.
At present we remain relatively ignorant about
the effects of our multiple treatment regimens and
strategies as catalysts for longer term mental health
issues. An analysis of a subset of survivors from the
Fluid and Catheter Treatment Trial (FACTT)
demonstrated that enrolment in a conservative fluid
management strategy was associated with both
cognitive and psychiatric impairment5. If this occurs
with conservative fluid management and mild
hypoxaemia, what then are the longer term
psychiatric effects of steroids, lighter or no
sedation, hypothermia, hyperthermia, or a wide
variety of vasoactive agents and antibiotics, either
alone or in combination?
ICU psychiatric burden is an important issue, and
is worthy of further study. With increasing interest in
improving patient-centered outcomes and with the
development of post-ICU follow up clinics, the
re c o g n i t i o n , a s s e s s m e n t a n d p re v e n t a t i v e
management of these conditions may improve.
References:
1. Fitch K, Iwasaki K, Villa KF. Resource utilization and cost in a commercially
insured population with schizophrenia. Am Health Drug Benefits
2014;7:18-26.
2. Minassian A, Vilke GM, Wilson MP. Frequent emergency department visits
are more prevalent in psychiatric, alcohol abuse, and dual diagnosis
conditions than in chronic viral illnesses such as hepatitis and human
immunodeficiency virus. J Emerg Med 2013;45:520-525.
3. Leucht, S, Burkard T, Henderson J, Maj M, Sartorius N. Physical illness
and schizophrenia: a review of the literature. Acta Psychiatrica Scand
2007;116:317-333.
4. Verceles, AC, Corwin DS, Afshar M et al. Half of the family members of
critically ill patients experience excessive daytime sleepiness. Intensive
Care Med 2014. Article in Press.
5. http://www.scopus.com/inward/record.url?eid=2-s2.0-84901728946
&partnerID=40&md5=0bc0eb1fffb52ce1a72affc6fb1063e7
6. Mikkelsen ME, Christie JD, Lanken PN et al. The adult respiratory distress
syndrome cognitive outcomes study: long-term neuro-psychological
function in survivors of acute lung injury. Am J Respir Crit Care Med
2012;185: 1307-1315. (See also Intensive Care Monitor 2012;19:91).
The bottom line is that the incidence of

psychiatric illnesses, both those preexisting,
and those arising after intensive care
admission, are higher in the critically ill and
contribute to a significant burden on
healthcare. The predisposing catalysts
(including our current therapies) require
further careful scrutiny. RF
ICM RECOMMENDED REVIEW PAPERS
Brindley PG. Improving teamwork in anaesthesia and critical
care: many lessons still to learn. Br J Anaesth 2014;
112:399-401. 13 references.
69
Lamas D. Chronic critical illness. N Engl J Med

2014;370:175-177. 7 references.
Wang Y, Eldridge N, Metersky ML et al. National trends in
patient safety in four common conditions, 2005-2011.
N Engl J Med 2014;370:341-351. 39 references.
O U T C O M E
An exploration of social and

economic outcome and
associated health-related
quality of life after critical
illness in general intensive
care unit survivors: a 12-month
follow-up study.
Authors: Griffiths J, Hatch RA, Bishop J et al.
Reference: Crit Care 2013; 17: R100. doi:10.1186/cc12745
This article is published under the Creative Commons Attribution License.
0.69 (IQR, 0.520.80) at 6 months and 0.69 (IQR,

0.520.81) at 12 months. The majority reported no change
in accommodation or relationship status between preadmission and 12 months following discharge from an ICU.
Employment status was adversely affected in 33% of cases
at 6 months and 28% at 12 months, with nearly a
50% reduction in the number of patients who reported
employment as their sole source of income at 12 months
(19% to 11%). Further, overall family income was affected,
with 32% reporting a drop in income at 12 months.
A quarter of ICU survivors reported still requiring assistance
with activities of daily living at 6 months and this had
changed little at 12 months (22%), with care being mainly
provided by family members (around 80% of cases), who
in turn suffered a negative impact on employment. The
amount of care needed was high with 26% requiring more
than 50 hours a week. Mobility problems were common
with 64% of patients suffering such disability at 6 months
compared with 32% before ICU admission. Continuing
morbidity was also common with 73% reporting moderate
or severe pain at 12 months and 44% remained significantly
anxious or depressed. Over 90% of respondents had used
healthcare services within 6 months of discharge from the
ICU, with 79% having visited their primary care physicians
and 44% having used community nursing services.
Discussion
ICM ABSTRACT
Objective
To examine the effects of critical illness on family
circumstances, social and economic stability, care
requirements and access to health service at 1 year
after discharge from ICU.
This study is the first in Europe to examine the socioeconomic burden following critical illness. Survivors
of critical illness in the UK face a negative impact on
employment and most have a prolonged need for
assistance with activities of daily living after discharge from
hospital. This has a corresponding negative impact on
family income; the majority of the care required is provided
by family members. This effect was apparent by 6 months
and had not greatly improved by 12 months.
Introduction
Survivors of an admission to intensive care have been
shown to have a subsequently higher risk of death, reduced
cognitive function and physical as well as psychological
impairment. However, little is known about the social and
economic impact on patients and their families.
Study design
Prospective, multi-centre, questionnaire-based study.

Patients who had spent 48 hours or more in one of
22 participating ICUs were recruited to the study and asked
to complete a questionnaire at 6 and 12 months after ICU
discharge. The questionnaire comprised three health
outcome instruments: the EuroQoL 5-dimension descriptive
system (EQ-5D, the associated visual analogue scale
(EQ-VAS) and the short form health survey 36 version
2 (SF-36v2), combined with a series of questions aimed
at collecting information on family circumstances,
socioeconomic stability and care requirements. The patients
also completed the EQ-5D regarding their health before ICU
admission. Information about the patients ICU stay was
extracted from the appropriate databases.
Evidence Level: IV
Results
There were 293 patients who completed both 6- and
12-month questionnaires. The median scores for overall
quality of life using the EQ-5D decreased from
0.79 (interquartile range [IQR], 0.671.0) pre-admission to
ICM COMMENT
Critical illness, and for that matter any significant
medical ailment, is not an isolated episode limited
to a particular patient at one identifiable point in
time. Instead, its impact extends well beyond the
point of discharge and further impacts a patients
next of kin and loved ones for periods probably far
beyond their hospitalization. From a purely medical
standpoint, we know that discharge from an acute
care setting does not necessarily equate with
recovery, as any patient for example with critical
illness polyneuropathy - will attest. However, what
medical providers, healthcare decision makers, and
policy and public health professionals frequently
neglect is the social and financial toll that critical
illness extracts and its profound and prolonged
reach , l argel y becau se of th e absen ce of
quantitative data to assess the scope of this issue.
Griffiths and colleagues performed a novel and
fascinating study to address this very issue and in
fact have provided evidence of the far and wide
socioeconomic impact of critical illness in the UK.
In brief, the authors surveyed approximately 300
ICU survivors and their families over the course of
a year following their care and provide good
exploratory evidence that illustrates some of the
burdens that patients and their families face after
discharge. While this survey corroborates, in part,
the findings from others regarding the persistent
decrement in a patients health status for many
months following ICU care, it goes beyond healthrelated issues and provides thought-provoking
70
evidence with regard to decreased quality of life,

income, earning potential, and financial well-being
that many patients and their families face. For
example, 33% of patients reported a negative
impact upon employment at 6 months and 28%
at 12 months.
Clearly, the findings from this study need to be
placed into context, from the standpoint of
limitations associated with survey data including,
but not limited to, recall bias and the absence of
corroborative, empirically derived evidence to
comprehensively quantify cost, quality of life
measures, and related metrics.
The bottom line is that despite the

exploratory nature of this work, the authors
clearly demonstrate that the impact of
critical illness lingers long after the initial
event and affects not just health status but
socioeconomic well-being of the patient,
their next of kin, and for that matter society
in general. DBC
Associations between palliative

chemotherapy and adult
cancer patients end of life
care and place of death:
prospective cohort study.
Authors: Wright AA, Zhang B, Keating NL, Weeks JC, Prigerson HG.
Reference: BMJ 2014;348:g1219 doi: 10.1136/bmj.g1219
British Medical Association.
ICM ABSTRACT
Objective
To investigate whether the end-of-life care given to cancer
patients who had received palliative chemotherapy months
before death is different from those who did not have
chemotherapy.
analysis. All patients receiving chemotherapy at enrolment,

as any part of their treatment (outside a clinical trial), were
included in the chemotherapy group. After each patients
death, a chart review and postmortem interview with their
caregivers were conducted to establish the medical care
received at the end of life, the patients place of death, and
whether the patient died in his or her preferred place of
death. Logistic regression and propensity score analyses
were used to examine associations between chemotherapy
and outcomes. The primary outcomes were intensive
medical care (cardiopulmonary resuscitation, mechanical
ventilation, or both) in the last week of life and patients
place of death. Secondary outcomes included survival time
from study enrolment, late hospice referrals (1 week before
death), and dying in the preferred place of death.
Evidence Level: III

Results
Palliative chemotherapy was being received by 16 (56%)
of 386 terminally ill cancer patients at study enrolment, a
median of 4 months before death. Patients receiving
palliative chemotherapy were more likely to be younger,
married, insured, better educated, with better performance
status, overall quality of life, physical functioning, and
psychological wellbeing compared with patients who were
not receiving chemotherapy. They were also more likely to
express a preference to receive life extending care over
comfort care. They were less likely to have acknowledged
that their illness was terminal, to have discussed end-of-life
issues with their doctor, or to have completed a do not
resuscitate order. After propensity score weighted
adjustment, use of chemotherapy at enrolment was
associated with significantly higher rates of cardiopulmonary
resuscitation, mechanical ventilation, or both in the last
week of life (14% vs. 2%; adjusted risk difference, 10.5%;
95% CI, 5.015.5%) and late hospice referrals
(54% vs.37%; adjusted risk difference, 13.6%; 95% CI,
3.623.6%) but no difference in survival (hazard ratio 1.11;
95% CI, 0.901.38). Patients receiving palliative
chemotherapy were more likely to die in an intensive care
unit (11% vs. 2%; adjusted risk difference, 6.1%; 95% CI,
1.111.1%), less likely to die at home (47% vs. 66%;
adjusted risk difference, 10.8%; 95% CI, 1.0% to
20.6%), and less likely to die in their preferred place,
(65% vs. 80%; adjusted risk difference, 9.4%; 95% CI,
0.8% to 18.1%) compared with those who were not.
Discussion
Introduction
Palliative chemotherapy is given to up to half of patients
with incurable cancers despite a lack of evidence for its
effectiveness in palliating symptoms. The authors
hypothesized that receiving such chemotherapy is
associated with a greater use of intensive medical care in
the last days of life and hence would be more likely to result
in patients dying in hospital rather than where they would
have preferred.
Study design
Secondary analysis of prospectively collected observational
data.

Data obtained from patients enrolled in the Coping with
Cancer study of terminally ill cancer patients were analyzed.
Adult patients with metastatic cancers refractory to at least
one chemotherapy regimen, who were terminally ill at study
enrolment and who subsequently died were included in the
This analysis found that the use of chemotherapy in

terminally ill cancer patients in the last months of life was
associated with an increased use of intensive interventions
in the last week of life and an increased risk of dying in an
ICU. Over half of the patients in this study were willing to
undergo chemotherapy even if it extended their lives by as
little as a week but the survival time for patients who had
palliative chemotherapy was not significantly different.
Patients who did not have palliative chemotherapy were
more likely to receive hospice care and, presumably,
experienced a better quality of life in their last days.
End-of-life discussions are particularly important for patients
receiving palliative chemotherapy, who should be informed
about the likely outcomes and should discuss their preferred
site of death with their oncology providers.
ICM COMMENT
Palliative care improves quality of life for patients
dying from metastatic malignancy 1. Palliative
71
chemotherapy is administered without curative

intent and might enhance or degrade the quality of
life in the terminal phases of malignancy. This report
looks at many aspects of the last days and the
deaths of a large series of patients with metastatic
malignancy, and tries to specifically address the
effects of palliative chemotherapy..
The stated conclusion for this study is that less use
of chemotherapy in this group of patients may
improve the quality of end-of-life care by reducing
intensive care admission and promoting earlier
hospice care. As detailed in the printed abstract,
however, there were some differences between the
two groups although most of these did not stand up
to propensity analysis. Nevertheless, it may well be
that there are differences in clinical characteristics
or patient, family and physician attitudes that might
increase the likelihood of undertaking both palliative
chemotherapy and more aggressive end-of-life
management. No such variables were identified but,
of course, unknown confounders cannot be
considered and are entirely plausible in this context.
Several interesting features emerge from this paper.
Firstly, the number of patients receiving palliative
c h e m o t h e r a p y i s r a t h e r l a r g e . S e c o n d l y, a
considerable majority of patients in both groups
reported a preference for chemotherapy that offered
a benefit of prolonged survival of as little as one
week. This is a very low benchmark for assessment
of acceptable benefit from potentially toxic therapy.
The second is the importance of end-of-life
discussions. These certainly need to include the
possibility that palliative chemotherapy may not
p ro l o n g s u r v i v a l a n d , a s s u g g e s t e d i n t h e
accompanying editorial2, may be part of a culture
that increases the risk of a small number of patients
being exposed to potentially burdensome intensive
interventions at the end of life.
Given the severity of illness of the study cohort at
enrolment, it is difficult to believe that ICU would
really offer much benefit. It is perhaps worth pointing
out, however, that even in the palliative chemotherapy group, only a small minority of these patients
was admitted to ICU and not all of those admitted to
ICU died there. More than one in three was evidently
discharged to the ward at least. So perhaps the oneweek survival benefit that was considered sufficient
to justify chemotherapy was applied to ICU
admission decision-making. Certainly, if patient
interests are kept paramount, it is unlikely that ICU
admissions among this group of patients could be
completely averted.
References:
1. Higginson IJ and Evans CJ. What is the evidence that palliative care
teams improve outcomes for cancer patients and their families?
The Cancer Journal 2010;16:423-435.
2. Rabow MW. Chemotherapy near the end of life. A difficult decision with
potentially unexpected implications. BMJ 2014;348:g1529.
The bottom line is that palliative chemotherapy administration is associated with

more aggressive end-of-life management
and this should be considered in discussions
with patients with end-stage malignancy.
While this association may well not be
causal, it is, nevertheless, highly relevant to
the management of this group of patients. RR
Risk of cardiovascular events in

survivors of severe sepsis.
Authors: Yende S, Linde-Zwirble W, Mayr F, Weissfeld LA, Reis S,
Angus DC.
Reference: Am J Respir Crit Care Med 2014; 189: 10651074.
The American Thoracic Society.
ICM ABSTRACT
Objective
To investigate the long-term risk of cardiovascular events
among survivors of severe sepsis and to determine the
factors contributing to this risk.
Introduction
Patients who survive severe sepsis are known to have a
higher risk of mortality in the long-term than the general
population. This increased risk is not explained by factors
prior to the infection, thus the course of the disease and its
treatment appears to confer an increased risk of death,
perhaps by worsening co-morbid conditions or by creation
of new chronic disease states. This study aimed to
determine whether severe sepsis increases the subsequent
risk of cardiovascular events.
Study design
Retrospective, unmatched and matched cohort analysis.

Patients with severe sepsis and control subjects were
selected from a 5% random sample of fee-for-service
Medicare beneficiaries aged over 65 years from 20022006.
Firstly, the risk of cardiovascular events among patients with
severe sepsis admitted to the ICU who survived
hospitalization, were compared with that of all Medicare
beneficiaries (unmatched population control subjects).
Secondly, the same group was propensity-score matched
with four control groups: ICU patients without severe sepsis,
patients hospitalized with infection, patients hospitalized
without infection, and the general population. The cases
were matched to control subjects based on age, sex,
admission for medical or surgical reasons, cardiovascular
disease before the index hospitalization, and propensity to
be hospitalized with severe sepsis. The propensity score
included age, sex, and detailed measures of different
chronic diseases. The primary outcome was the 1-year
incidence rate of hospitalization for cardiovascular events
that broadly included myocardial infarction, stroke, transient
ischaemic attack (TIA) and coronary artery revascularization.
Evidence Level: III

Results
The Medicare 5% dataset included 1,638,566 eligible
subjects. The matched analyses included 4179 patients
with severe sepsis matched to 16,716 control subjects. In
the unmatched analyses, 4179 patients with severe sepsis
were compared with 819,283 unmatched population control
subjects. The mean age of the subjects was 77 years and
44% were men. All subjects had a high burden of chronic
diseases, particularly cardiovascular disease, diabetes,
chronic lung disease and cancer. Cardiovascular events
were common among patients discharged alive after severe
sepsis hospitalization (29.5%; 498.2 events/1000 person-
72
years), most commonly stroke. In the unmatched controls,

the rate of cardiovascular events was 13-fold lower
(36 events/1000 person-years; p < 0.0001), whereas the
matched-population control subjects had a 1.9-fold lower
risk (257.6 events/1000 person-years; p < 0.0001).
Imp or tantly, comp ared w ith the matched control
hospitalized patients and those hospitalized with infection,
the survivors of severe sepsis had only a 1.1-fold higher risk
(p = 0.002 and 0.001), while compared with matched ICU
controls there was no significant difference in the rate of
cardiovascular events.
Discussion
This analysis was able to show that although survivors of
severe sepsis have a high risk of cardiovascular events, this
is mainly due to poor health status prior to hospitalization,
and is also seen in a broader population of acutely ill
patients. The authors point out that their study focused on
older subjects and further studies of younger patients as
well as studies on potential strategies to improve long-term
outcomes in ICU patients are needed.
ICM COMMENT
In the early years of critical care, it was assumed
that the acute and severe, but reversible, illness
did not cause residual morbidity. Over the last
two decades it has become apparent that sepsis
with multi-organ failure and multimodal organ
s u p p o r t d o e s i n d e e d c a r r y l o n g e r- t e r m
consequences. Survivors of ARDS show
irreversible damage on CT scanning and
pulmonary function testing. Critical illness
polyneuropathy and myopathy decrease
functional recovery for months, and occasionally
for years. More recently, there has been a clear
documentation of long-term renal loss in those
with acute kidney injury, and, even more
distressing, significant cognitive loss in survivors
of critical illness. Now Yende and colleagues
have looked at the risk of cardiovascular events
in survivors of severe sepsis from a large
M e d i c a re d a t a b a s e . T h e y u s e t h e t e r m
cardiovascular to include all cardiovascular
events including myocardial infarction, stroke,
transient ischemic attack (TIA), and coronary
artery revascularization. The incidence of these
cardiovascular events was high at 29.5%. Even
those without prior documented coronary artery
disease (CAD) had an event rate of 25.9%. They
noted that survivors of sepsis had a 13 fold
higher risk of cardiovascular events compared
to unmatched controls and a 1.9 fold higher risk
compared to matched-population control
subjects. However, they did note that matched
ICU controls had a similar risk. Their interpretation was that vascular events were common
in survivors of severe sepsis, but this was better
explained by pre-existing risk, than by the severe
sepsis per se.
The relationship between cardiovascular disease
and CAD in critical illness is complex. Many
patients have underlying CAD, and the
haemodynamic stress, along with inflammation
and hyper-coagulability, can precipitate an acute
coronary syndrome (ACS). Others will have a fall
of myocardial contractility despite normal
coronary arteries. In addition, many critically ill
patients have new onset ECG, biomarker and
echocardiography changes in the absence of

underlying CAD. The usual diagnostic criteria
become less specific for diagnosis of a new ACS
during a critical illness. It is unclear if anti-platelet
medications are beneficial and if angiography
and angioplasty have any role in these settings.
Could the choice of non-cardiac therapeutic
options during the critical illness influence
subsequent CAD events? The NICE-SUGAR
study had an interesting observation1 the group
with intensive control of glucose had a similar
28-day mortality but a higher 90-day mortality
and more deaths from cardiovascular causes.
This could suggest that treatment strategies in
ICU can have adverse cardiovascular
consequences by currently unknown
mechanisms. In March-April 2014 Intensive Care
Monitor covered the role of statins during critical
illness2. Introducing them during a critical illness
was not beneficial, but we do not have enough
data to know if they are protective, in patients
already on them prior to the critical illness.
If there is a real increase in coronary artery
related events following a critical illness, it could
be due to several factors. Chronic inflammation
is believed to be atherogenic and also believed
to make plaques unstable. Kidney injury, poor
physical activity or discontinuation of previous
prophylactic medications could increase the risk
of CAD. It could also simply be due to the
emotional stress caused by a life-threatening
illness with functional, occupational and financial
consequences. Regardless of the mechanism, it
would be prudent to manage survivors of severe
sepsis above the age of 65 as having an
increased risk of cardiovascular or cerebrovascular events. Appropriate prophylactic
measures should be an integral part of the
recovery and rehabilitation programme.
References:
1. The NICE-SUGAR Study Investigators. Intensive versus conventional
glucose control in critically ill patients. N Engl J Med 2009;360:12831297. (See also Intensive Care Monitor 2009;16:44).
2. Papazian L, Antoine Roch A, Charles PE et al. Effect of statin therapy on
mortality in patients with ventilator-associated pneumonia: a randomized
clinical trial. JAMA 2013;310:1692-1700. (See also Intensive Care
Monitor 2014;21:37).
The bottom line is that survivors of sepsis

should be viewed as patients with a high
risk of developing cardiovascular and
cerebrovascular events, and managed
accordingly. FNK
73
R E S P I R A T O R Y
The effect of intravenous

interferon-beta-1a (FP-1201)
on lung CD73 expression
and on a c u t e r e s p i r a t o r y
distress syndrome mortality:
an open-label study.
Authors: Bellingan G, Maksimow M, Howell DC et al.
Reference: Lancet Respir Med 2014; 2: 98107.
Trial registration number: NCT00789685
Elsevier Ltd.
ICM ABSTRACT
Objective
To determine whether interferon-beta-1a (IFNb-1a) can
reduce vascular leakage and mortality in patients with
acute respiratory distress syndrome (ARDS).
Introduction
ARDS is characteried by the development of increased
pulmonary capillary permeability, causing plasma exudation
into the alveolar space with subsequent hypoxaemia. IFNb1a upregulates CD73 expression, an enzyme carried on
vascular endothelium, epithelial cells and a leukocyte
subset. CD73 mediates anti-inflammatory effects including
prevention of vascular leakage and inhibition of leukocyte
recruitment. Animal studies have suggested that
upregulation of CD73 by IFNb-1a may improve outcome
in ARDS.
Study design
Open-label, dose-escalation, phase I/II study.

Cultured human lung tissue samples were first used to
determine whether IFNb-1a upregulates CD73 in vitro.
Samples were incubated for 1 and 4 days with IFNb-1a
before staining for CD73 expression. Adult patients
with ARDS were then enrolled into an open-label,
dose-escalation study of IFNb-1a. Patients received
a daily intravenous dose of IFNb-1a for 6 days. The doseescalation phase tested four dose levels: 0.44 g, 4.4 g,
10 g and 22 g. The optimal tolerated dose was set at 10 g
and the remaining patients received this dose. Patients were
followed up for 28 days. All cause mortality at 28 days and
6 months was calculated and compared with a control
group of patients who had received no IFNb-1a. Safety and
tolerability were assessed. Serum concentrations of CD73
activity, and pro-inflammatory cytokines were measured.
Evidence Level: III

Results
IFNb-1a (1000 IU/ml) increased the number of CD73-positive
blood and lymphatic vessels in lung tissue samples in vitro
by four-fold on day 1 and by 14.3 times by day 4 (p < 0.05).
The dose-escalation phase involved 3 patients receiving
0.44 g, 3 receiving 4.4 g, 5 receiving 22 g and a total of
26 receiving the optimal tolerated dose of 10 g. There
were 59 patients in the control group. The 28-day all cause

mortality was 8% in the treatment group compared with
32% in the control group, giving an odds ratio of 0.19
(95% CI, 0.030.72; p = 0.01). IFNb-1a was well tolerated
at doses of 0.44 g, 4.4 g, and 10 g, but two of five
patients receiving the 22 g dose experienced fever, rigors
and tachycardia after receiving two doses, which resolved
on stopping treatment. Thus, the optimal dose was set at
10 g. No systemic adverse events were seen in the
patients receiving 10 g. Serum CD73 activity rose steadily
in response to treatment, from 265.0 nmol/ml/hour on
day 1 to 732.5 nmol/ml/hour on day 9, a 2.8-fold increase
(95% CI, 2.13.64; p < 0.0001). In the 10 g/day group,
interleukin-8 reduced by 46.5% (95% CI, 58.7% to
30.9%; p < 00001) and interleukin-6 by 84.4% (95% CI,
90.1% to 75.4%; p<00001). Administration of IFNb-1a
was associated with an improvement in PaO2/FiO2 ratio
from 18.5 kPa at screening to 38.2 kPa on day
27 (p<00001).
Discussion
This small, phase I/II study of IFNb-1a in ARDS suggests
that doses up to 10 g/day are well tolerated and are
associated with increased expression of CD73. The
improvements in clinical characteristics and outcome seen
in this trial suggest that further study is warranted. The
authors also suggest that consideration should be given to
the use of CD73 as a marker of disease severity in ARDS.
ICM COMMENT
The damage observed in ARDS reflects the
primary injurious stimuli and the secondary
complex interactions of inflammatory mediators
on alveolar epithelial and capillary endothelial
cells. Endothelial cell injury is an important
component of sepsis and acute lung injury.
Increased microvascular permeability leads to
oedema formation without actual rupture of the
lung. Because the pulmonary endothelial barrier
is damaged during ARDS and sepsis, lung
cytokines released into the circulation can initiate
or propagate a systemic inflammatory response
and play an active role in the development of
multiple system organ dysfunctions.
Searching for biomarkers for ARDS and sepsis
has been an ongoing journey in critical care
research, and many biomarkers proposed by
experimental studies have not been validated
in clinical practice. The lack of convincing
biomarkers further promotes investigations along
this line. Villar et al.1 have recently reported that
CD31, also termed platelet-endothelial cell
adhesion molecule-1, is decreased during
sepsis-induced lung injury and can be modulated
during mechanical ventilation. Since CD31 is
required for restoring endothelial continuity,
targeting the integrity of this cell adhesion
molecule may open new therapeutic approaches
for sepsis and ARDS.
CD73 is an enzyme that in humans is encoded by
the NT5E gene 2 . CD73 commonly serves to
convert AMP to adenosine, an anti-inflammatory
molecule that helps maintain endothelial barrier
function by preventing vascular leakage.
Upregulation of CD73 expression by IFNb has
been shown to decrease vascular permeability3.
In this paper, Bellingan et al. studied the effects
of an optimal dose of IFNb-1a on circulating
74
levels of CD73 and 28-day mortality in a phase

1/2 study enrolling a selected population
of 37 ARDS patients. A cohort of 59 ARDS
patients who did not receive the treatment
served as controls. They reported that treatment
with IFNb-1a was associated with an increased
activity of circulating CD73 by almost 3-fold,
a significant decrease in systemic levels of proinflammatory cytokines, and a 24% absolute
reduction in mortality (32% vs. 8%). These results
are spectacular, but several comments of caution
should be considered before sounding the siren.
First, some of the authors are employees of the
pharmaceutical company that sponsored and
participated in the study design, data analysis
and interpretation of data. Second, this was not
a randomized controlled trial, and therefore, we
cannot exclude a selection bias. We do not have
sufficient information about the precise method
for patient allocation. From 150 eligible patients
admitted into 8 ICUs, only 37 were non-randomly
assigned to receive the drug. From the 113
remaining patients, only 59 served as controls,
and all of them were selected from two ICUs only.
Third, there was no stratification of patients
based on the degree of lung severity. All we know
is that the mean PaO 2 /FiO 2 of patients under
treatment with CD73 was about 140 mmHg at
study entry, rising to above 200mmHg at 4 days
after screening; such numbers are compatible
with mild ARDS, a condition that has very low
mortality. Fourth, there is no information at all
on how mechanical ventilation was applied,
therapeutic goals, the use of adjunctive
therapies, range of tidal volumes, levels of FiO2
and applied PEEP, plateau pressures, ventilator
free-days, and number of organ dysfunctions in
all and each group. Fifth, as a result of all these
limitations, we do not know whether the results
are a direct consequence of differences in lung
severity, mechanical ventilation strategies or drug
administration. And finally, the beneficial effects
of administration of IFNb -1a may be due to the
broad effects at sites other than the lungs.
References:
1. Villar J, Muros M, Cabrera-Benitez N et al. Soluble platelet-endothelial
cell adhesion molecule-1, a biomarker of ventilator-induced lung injury.
Crit Care 2014; 18:R41.
2. Misumi Y, Ogata S, Ohkubo K et al. Primary structure of human placental
5-nucleotidase and identification of the glycolipid anchor in the mature
form. Eur J Biochem 1990; 191:563-569.
3. Kiss J, Yegutkin GG, Koskinen K et al. IFN-beta protects from vascular
leakage via up-regulation of CD73. Eur J Immunol 2007; 37:3334-3338.
The bottom line is that although the results

of this report suggest that CD73 could be the
first effective pharmacotherapy against early
ARDS, conclusive proof of efficacy can only
be seen in a randomized controlled trial.
Such a study is already planned. JV
Effect of pressure support vs

unassisted breathing through
a tracheostomy collar on
weaning duration in patients
requiring prolonged mechanical
ventilation. A randomized trial.
Authors: Jubran A, Grant BJB, Duffner LA et al.
Reference: JAMA 2013; 309: 671677.
Trial registration number: Clinicaltrials.gov number, NCT01541462.
ICM ABSTRACT
Objective
To compare weaning duration with pressure support or
unassisted breathing through a tracheostomy collar in
patients transferred to a long-term acute care hospital
(LTACH) for weaning from prolonged ventilation.
Introduction
In the USA, patients requiring prolonged mechanical
ventilation (>21 days) are commonly weaned at LTACHs.
Studies of ICU patients have shown that the duration of
ventilation is influenced by the weaning method used, with
the two most common weaning methods being pressure
support and spontaneous breathing trials. However, the
relative efficacy of these two methods has not been studied
in patients receiving care in LTACHs.
Study design
Randomized study.

Between 2000 and 2010, the study enrolled patients with
a tracheotomy who were transferred to a single LTACH
(90 beds, of which 56 were devoted to ventilator
weaning) for weaning from prolonged ventilation.
Of 500 patients who underwent a screening procedure
consisting of unassisted breathing for 5 days, 316 did
not tolerate the procedure and were randomly assigned
to receive weaning with pressure support (155 patients)
or a tracheostomy collar (161 patients). Patients in the
tracheostomy collar group were rested on assist-control
ventilation at night. The primary outcome was weaning
duration, measured from the first day of randomization to
the day the patient was successfully weaned. Weaning
was considered successful when a patient breathed
without ventilator assistance for at least 5 days. Weaning
was considered a failure when a patient was not
successfully weaned by 45 days after randomization.
Secondary outcomes included survival at 6 and 12
months after enrolment.
Evidence Level: II
Results
Of 316 patients randomized, four were withdrawn and
not included in analysis. Of 152 patients in the pressuresupport group, 68 (44.7%) were weaned successfully;
22 (14.5%) died. Of 160 patients in the tracheostomy
collar group, 85 (53.1%) were weaned successfully;
16 (10.0%) died. The median weaning time was shorter
75
with a tracheostomy collar (15 days; interquartile range

(IQR), 825 days) than with pressure support (19 days;
IQR, 1231 days; p=0.004). The hazard ratio (HR) for
successful weaning rate was higher with a tracheostomy
collar than with pressure support (HR, 1.43; 95% CI,
1.03 to 1.98; p=0.033) after adjusting for baseline clinical
covariates. Weaning was faster with a tracheostomy
collar than with pressure support among patients who
did not tolerate the screening procedure between 12 and
120 hours (9 days (IQR, 719 days) vs. 20 days (IQR,
1031 days); p=0.008), whereas weaning time was
similar with the two methods in patients who did not
tolerate the screening procedure between 0 and
12 hours (16 days (IQR, 930 days) vs. 19 days (IQR,
1231 days); p=0.058). Mortality was similar in the
pressure support and tracheostomy collar groups at
6 months (55.9% vs. 51.2%; 4.7% difference; 95% CI,
6.4% to 15.7%) and at 12 months (66.4% vs. 60.0%;
6.4% difference, 95% CI, 4.2% to 17.1%).
Discussion
This study showed that among patients requiring
prolonged mechanical ventilation and treated at a single
long-term care facility, the median weaning time was
s h o r t e r w i t h u n a s s i s t e d b re a t h i n g t h ro u g h a
tracheostomy collar than with pressure support, though
the weaning mode had no effect on survival at 6 months
or 12 months. The authors note that 160 of the 500
patients enrolled (32%) were successfully weaned during
the screening procedure, which suggests that many
patients transferred to the long-term acute care facility
could have been weaned in the ICU, if physicians
had been more aggressive in pursuit of
ventilator disconnection.
ICM COMMENT
P ro l o n g e d m e c h a n i c a l v e n t i l a t i o n u s e s
substantial and disproportionate resources in
critical care. For this reason in the United States
these long term ICU patients are generally
transferred to alternative step down facilities LTACHs.
Following the publication of Brochard's influential
paper1 in 1994, the use of pressure support for
weaning patients from mechanical ventilation
became widespread practice. A more recent
Cochrane review 2 considers, however, that
evidence from those studies comparing pressure
support to T-tube ventilation were of generally
low quality and that outcomes were imprecise;
except in the use of pressure support for simple
weaning. Another key publication by Esteban et
al.3 (who considered their work complementary
to Brochard's) might be interpreted as showing
that physicians can better assess the ability of
the patient to wean by use of regular spontaneous breathing trials. Pressure support may
give ICU physicians too pessimistic a view of a
patient's capabilities.
Jubran et al. give an interesting new perspective
to previous work undertaken in more critically ill
patient populations within the ICU. They confirm
that for those sicker patients, with little capacity
to endure spontaneous breathing trials, the
primary determinants for weaning remain patientrelated factors. However, for patients closer to
liberation from mechanical ventilation, the
method of weaning appears more important. It
would appear, as suggested by Esteban, that

spontaneous breathing trials (or tracheostomy
collar trials as they are referred to here) may be
quicker and more efficient than pressure support
weaning in the more chronic patients.
Further evidence that we are unduly pessimistic
with regards to weaning patients from prolonged
mechanical ventilation, is provided here. Jubran
and colleagues show that on step down from ICU
to LTACH, 32% of patients passed an initial
screen of a successful 5-day tracheostomy collar
trial, and were liberated from the ventilator before
they could be randomized into this trial!
References:
1. Brochard L, Rauss A, Benito S et al. Comparison of three methods of
gradual withdrawal from ventilatory support during weaning from
mechanical ventilation. Am J Respir Crit Care Med 1994;150:896-903.
2. Ladeira MT, Vital FMR, Andriolo RB, Andriolo BNG, Atallah N, Peccin MS.
Pressure support versus T-tube for weaning from mechanical ventilation
in adults. Cochrane Database of Systematic Reviews 2014, Issue 5. Art.
No.: CD006056. DOI: 10.1002/14651858.CD006056.pub2.
3. Esteban A, Frutos F, Tobin MJ et al.. Spanish Lung Failure Collaborative
Group. A comparison of four methods of weaning patients from
mechanical ventilation. N Engl J Med 1995;332:345- 350.
The bottom line is that we are not good at

assessing the ability of patients to liberate
themselves from mechanical ventilation
during pressure support weaning. Rather, we
should observe patients capabilities during
spontaneous breathing trials of tracheostomy collar. This 10-year long study
suggests that we will wean quicker and more
effectively if we do. MNS

Arabi YM, Arifi AA, Balkhy HH et al. Clinical course and
outcomes of critically ill patients with Middle East respiratory
syndrome coronavirus infection. Ann Intern Med
2014;160:389-397. 36 references.
S E D A T I O N

Reade MC, Finfer S. Sedation and delirium in the intensive
care unit. N Engl J Med 2014;370:444-454. 56 references.
76
S E P S I S
Reappraisal of routine oral care

with chlorhexidine gluconate
for patients receiving mechanical ventilation systematic
review and meta-analysis.
Top quality research
Authors: Klompas M, Speck K, Howell MD, Greene LR, Berenholtz SM.
Reference: JAMA Intern Med 2014; 174:751-76.
ICM ABSTRACT
respect to the rate of VAP in double-blind studies of

noncardiac surgery patients (RR, 0.88; 95% CI,
0.661.16). The cardiac surgery studies did not report
VAP rates but rather the rate of upper and lower
respiratory tract infections or of nosocomial pneumonia.
Meta-analysis of these studies found a lower rate of
lower respiratory tract infections or nosocomial
pneumonia with chlorhexidine use compared with
placebo (RR, 0.56; 95% CI, 0.410.77). There was no
significant difference in mortality between chlorhexidine
and placebo in either cardiac surgery studies (RR, 0.88;
95% CI, 0.253.14) or noncardiac surgery studies (RR,
1.13; 95% CI, 0.991.29). There appeared to be a
stepwise increase in the RR for mortality with increasing
chlorhexidine concentration although statistical
significance was not reached. There were no significant
differences in mean duration of mechanical ventilation or
intensive care length of stay. Data on hospital length of
stay and antibiotic prescribing were limited.
Discussion
Objective
To estimate the effect of using chlorhexidine for daily oral
care in patients receiving mechanical ventilation on the rate
of ventilator-associated pneumonia (VAP), mortality, use
of antibiotics and durations of stay and of mechanical
ventilation.
Introduction
Although most hospitals use chlorhexidine in routine oral
care of mechanically ventilated patients, its impact on VAP,
mortality and other patient-centred outcomes has not been
adequately investigated. There is some evidence that VAP is
reduced but this is not certain and the impact, if any, on
mortality, length of stay, duration of mechanical ventilation
and use of antibiotics has not been established.
Study design
Meta-analysis.

A literature search, of the PubMed, Embase, Cumulative
Index to Nursing and Allied Health Literature (CINAHL)
and Web of Science databases, was conducted for
randomized clinical trials comparing chlorhexidine with
placebo in adults receiving mechanical ventilation. Eligible
trials were independently identified, evaluated for risk of
bias, and extracted by two investigators. Differences
were resolved by consensus. Studies were stratified
according to whether or not patients had had cardiac
surgery and according to study blinding. The main
outcomes were VAP, mortality, length of stay, duration of
mechanical ventilation and use of antibiotics. All trials that
provided data on one or more of these outcomes were
included. Eligible studies were pooled using MantelHaenszel random-effects meta-analysis. Relative risks
(RR) and weighted mean differences were calculated for
dichotomous and continuous outcomes, respectively.
Evidence Level: I
Results
171 studies were identified, of which 16 studies involving
3630 patients met the inclusion criteria. Of these, three
studies involved cardiac surgery patients and 13 noncardiac surgery patients. There was no significant
difference between chlorhexidine and placebo with
Routine oral care with chlorhexidine does not appear to

affect patient-centred outcomes in either cardiac surgery
or non-cardiac surgery patients, despite a reduction in
the rate of nosocomial pneumonia in cardiac surgery
patients. The authors note that the duration of
mechanical ventilation in cardiac surgery patients was
considerably shorter than in non-cardiac surgery
patients, which may have influenced the findings. They
express concern over the mortality findings and call for
re-evaluation of policies encouraging routine oral care
with chlorhexidine for noncardiac surgery patients as
well as further investigations in large randomized,
controlled trials.
ICM COMMENT
VAP is a common and potentially life-threatening
problem. Unfortunately, almost every aspect of
analyzing this condition is flawed due to
ambiguity in diagnosing it and in evaluating its
impact on outcome. Inconsistent and variable
diagnostic criteria further muddy the data in
terms of strategies to prevent, treat and improve
outcome. Probably the most robust scientific
data comes from Rouby et al.1 who performed
both, pre mortem bronchoalveolar lavage and
immediate post mortem whole lung histology and
culture in patients dying on a ventilator in the
ICU. In that series, 60/83 (72%) had a VAP at the
time of death. Based on the method of
diagnosing and reporting, VAP rates have been
quoted to vary from 5-35% in ventilated patients.
Various studies quote a crude mortality varying
from 30-70% and an attributable mortality of
33-50%. Given these adverse figures, multiple
strategies have been proposed to prevent VAP.
Some target exogenous infections and others
endogenous flora.
A relatively well-accepted strategy is the use of
chlorhexidine for oral care as this is presumed to
be safe and could plausibly prevent pathogens
colonizing the upper airway. Klompas et al.
performed a meta-analysis of studies evaluating
the usefulness of this specific VAP prevention
strategy. In 13 studies (1762 patients) analyzing
non-cardiac surgery patients, the use of
chlorhexidine did not lower the VAP rate
77
compared to placebo. Three studies (1868

patients) in cardiac surgical patients evaluated
all upper & lower chest infections, not VAP
specifically, and found a decreased rate of these
infections compared to placebo. In both groups
mortality, duration of mechanical ventilation, and
ICU stay were not improved. The authors
separated cardiovascular surgical patients from
other intensive care patients. This is useful, as
the potentially beneficial result in one group may
not apply to the whole ICU population. In the
cardiovascular group, the duration of ventilation
is very limited and the diagnosis of chest
infection is necessarily less specific than that of
VAP. In this cardiovascular surgical group, the
observed reduction in infections was largely
influenced by a single study using low specificity
diagnostic criteria. The other feature of interest is
the observation of a trend to increased mortality
in the treatment group with some correlation to
the dose used. This is a new observation and
should prompt a safety review.
So once again we are faced with a potentially
useful treatment failing to meet the test of
improving clinical outcomes. This highlights
the need to constantly review practices and
recommendations based on data from small
studies. In fact in this situation we are not even
able to demonstrate that it prevents VAP, let
alone improve, clinical outcomes. Should we be
disappointed? I do not think so. As we change
our focus from physiological plausibility to
clinical outcomes, we shall have to review most
of our practices. Of course, poorly designed or
executed studies may make us prematurely give
up on effective treatments. There is probably
little to gain by repeatedly analyzing these or
other small studies. A large RCT focusing on
patient outcomes is the only way to demonstrate
the safety and efficacy. In the absence of this,
I feel we can say that chlorhexidine for oral care
in preventing VAP need not be considered as a
standard of care and guidelines recommending
its routine use need to review the strength of
their recommendation.
Reference:
1. Rouby JJ, De Lassale ME, Poete P et al. Nosocomial bronchopneumonia
in the critically ill. Histologic and bacteriologic aspects. Am Rev Respir Dis
1992;146:1059-1066.
The bottom line is that oral care with

chlorhexidine in ventilated patients does not
improve patient outcomes and need not be
used routinely. FNK
Health care use and serious

infection prevalence
associated with penicillin
allergy in hospitalized
patients: a cohort study.
Hot topic
Authors: Macy E, Contreras R.
Reference: J Allergy Clin Immunol 2014;33:790796.
American Academy of Allergy, Asthma & Immunology.
ICM ABSTRACT
Objective
To investigate the prevalence of serious infection, antibiotic
use and length of hospital stay among patients with a
history of an adverse reaction to penicillin compared with
those without.
Introduction
Many patients who have had an adverse reaction to
penicillin have been inaccurately diagnosed with penicillin
allergy. The authors report that less than 2% of patients
with a history of penicillin allergy have a positive penicillin
allergy test result. Unnecessary use of alternate antibiotics
to treat penicillin-sensitive infections may increase the rate
of antibiotic resistance. This study examined how a previous
diagnosis of penicillin allergy affects hospitalized patients.
Study design
Retrospective, matched cohort study.

Patients who had been admitted with an active history of
penicillin allergy in their medical records were categorized,
according to their discharge diagnosis, into one of nine
groups (cancer, cardiovascular, nervous system, abdominal
organ system, urology-gynaecological, obstetric,
orthopaedic-trauma, pulmonary and other). These groupings
were used to select two category-matched, sex-matched,
age-matched, and date of admissionmatched control
subjects for each case. Data on total hospital days, new drug
allergy reports, oral antibiotics used and course duration,
positive clinical isolates of Clostridium difficile, multi-drug
resistant Staphylococcus aureus (MRSA) or vancomycinresistant Enterococcus (VRE) were extracted for cases and
controls. Estimation of hospital costs were made.
Evidence Level: III

Results
Two suitable control cases were found for each of 51,582
subjects with penicillin allergy. Cases with penicillin
allergy averaged 0.59 (9.9%; 95% CI, 0.470.71) more
total hospital days during 20.110.5 months of follow-up
compared with control subjects. The difference in length of
hospital stay between cases and controls was greater for
women (0.68 days) compared with men (0.35 days), which
was further increased in cases aged over 50 years
(0.80 days for women vs. 0.26 for men). Cases were treated
with significantly more fluoroquinolones (25.3% of cases vs.
14.3% of controls) as well as clindamycin and vancomycin
78
(p<0.0001) for each antibiotic compared with control

subjects. The prevalence of severe infection was higher for
cases than controls: the odds ratio for C. difficile prevalence
in cases compared with controls was 1.234 (95% CI,
1.1561.317), for MRSA 1.141 (95% CI, 1.0711.317) and
for VRE 1.301 (95% CI, 1.1251.504). Comparing the cost
of testing for penicillin allergy compared with the cost of the
longer hospital stay revealed a potential saving of
$64,626,630.48 over a 3-year period.
Discussion
This study found that a history of penicillin allergy can
result in a significantly longer hospital stay as well as
significantly higher exposure to antibiotics associated with
C. difficile and VRE and an increased risk of infection with
hospital-acquired C. difficile, MRSA and VRE. Allergy testing
all patients with a history of penicillin allergy soon after
admission could, therefore, have multiple benefits, including
a cost saving. The authors point out that even if only 95% of
the subjects with a history of penicillin allergy had negative
penicillin allergy test responses and if only 50% of the
additional hospital days were avoided in that group, it could
still bring cost savings of about four times as much as the
cost of the penicillin allergy testing.
ICM COMMENT
Obtaining an accurate and clinically relevant medical
history is the one of the most essential and important
skills that medical students learn in medical school.
For most components of the medical history obtained
(such as past medical history, chief complaints, and
present medical history), information provided by the
patient/family can be verified by chronic drug use,
laboratory tests, signs and symptoms, and so on. In
contrast, allergy history probably remains the leastverified component of medical history.
Penicillin allergy, the most common drug-class
allergy noted in the medical records, is self-reported
by 30 million patients, or approximately 10% of the
population in the United States1. True penicillin allergy
can range from mild, non-life-threatening rashes (type
4 reaction) to severe, life-threatening reactions (hives,
shortness of breath, throat tightening, anaphylaxis, all
type 1, IgE-mediated reactions). However, less than
2% of patients with a history of penicillin allergy
have a positive penicillin allergy test result2.
Interestingly, this erroneous information has seldom
been verified, with less than 0.1% of those patients
with penicillin allergy undergoing penicillin allergy
testing in the United States annually 3. What is the
potential impact of self-reported penicillin allergy on
clinical outcome, and health care resource use?
The results of this retrospective study by Macy and
Contreras were not surprising. Cases were more likely
t o re c e i v e t h i rd - g e n e r a t i o n c e p h a l o s p o r i n s ,
fluoroquinolones, vancomycin and clindamycin. In
addition, cases were more likely to develop infectious
complications with antibiotic-resistant bacteria (such
as VRE, C. difficile and MRSA), which might explain
the observed longer hospital stay.
Apart from the above benefits in clinical outcome,
the economic impact of this study might be also
enormous1. Among the 36,156,245 annual admissions
to US hospitals4, let us assume that 10% will selfreport penicillin allergy, with 95% or more having
negative skin test responses 1 . This means that
3,434,843 patients who claim to be allergic to
penicillin are actually not. If clinicians consider
performing a penicillin skin test, which is safe even in
critically ill patients5, in at least 10% of these patients

(i.e. 343,484 cases), this will result in a total reduction
of 202,656 hospital days (0.59 days per patient),
corresponding to an annual net saving of
$294,191,792 (average cost per inpatient day $1,6256,
while this paper shows that a penicillin allergy test
costs $131.37). And this does not even take into
account the reduced antibiotic cost by virtue of
removing the penicillin allergy label, as well as the
significantly increased cost of treating the abovementioned infectious complications.
Despite the fact that these calculations are based on
theoretical assumptions, they clearly remind us of the
importance of basic clinical skills (such as obtaining
and verifying an allergy history). These can make
a significant impact not only on patient-centred
outcome, but also healthcare policy, especially in
the era of financial austerity.
References:
1. Solensky R. Penicillin allergy as a public health measure. J Allergy Clin
Immunol 2014;133:797-798.
2. Macy E, Ngor E. Safely diagnosing clinically significant penicillin allergy
using only penicilloyl-poly-lysine, penicillin, and oral amoxicillin. J Allergy
Clin Immunol: In Practice 2013;1:258-263.
3. Joint Task Force on Practice Parameters; American Academy of Allergy,
Asthma and Immunology; American College of Allergy, Asthma, and
Immunology; Joint Council of Allergy, Asthma and Immunology. Drug
allergy: an updated practice parameter. Ann Allergy Asthma Immunol
2010;105:259-273.
4. Fast facts on US hospitals. Available at http://www.aha.org/
research/rc/stat-studies/fast-facts.shtml. Accessed: July 14, 2014
5. Arroliga ME, Wagner W, Bobek MB et al. A pilot study of penicillin skin
testing in patients with a history of penicillin allergy admitted to a medical
ICU. Chest 2000; 118; 1106-1108.
6. Average cost per inpatient day across 50 states in 2010. Available at
http://www.beckershospitalreview.com/lists/average-cost-per-inpatientday-across-50-states-in-2010.html.
The bottom line is that a penicillin allergy

history at hospital admission, although often
inaccurate, is more likely to be associated
with more exposure to antibiotics previously
related to C. difficile and VRE, and increased
hospital use. BD
NEW MEMBER OF THE EDITORIAL
BOARD
We are delighted to welcome Dr. Jasmeet Soar,
Consultant in Intensive Care Medicine at Southmead
Hospital, Bristol, U.K and an Editor of Resuscitation.
Dr. Soar will be commenting on cardiac arrest,
resuscitation, and patient safety papers.
INDEXES
The 2013 Index is available on the website together
with all previous indexes.
For your copy please go to
www.intensive-care-monitor.com
Evidence Type
Systematic Review
RCT
Other experimental
Non-experimental
Expert Opinion
Evidence Level
I score 5
II score 4
III score 3
IV score 2
V score 1
79
SELF-ASSESSMENT QUESTIONS
JOURNALS FEATURED IN THIS ISSUE
The following questions are based on topics in this issue of

Intensive Care Monitor and are not only for self-assessment
but can also be used in your Journal Club. The answers are
True (T) or False (F).
The papers featured in this issue were from the journals

listed below. Further information may be obtained directly
from the publishers of the journals concerned at the
following addresses:-
Correct answers will be available on the Intensive Care

Monitor website www.intensive-care-monitor.com from
October 1st 2014 and will also be published in the next
issue of Intensive Care Monitor.
AMERICAN JOURNAL OF RESPIRATORY & CRITICAL

CARE MEDICINE
American Lung Association,
1740 Broadway,
New York,
NY 10019-4374 USA.
1. Enteral nutrition:
a. In a patient with major burns enteral nutrition should be
started within 6 hours of ICU admission.
b. Enteral feeding should be stopped if 4 hourly gastric
aspirates are 100-150 ml.
c. Jejunal feeding reduces the risk of pulmonary aspiration.
d. A paper reviewed in this issue of the Monitor
demonstrates that patients that are unable to receive
enteral nutrition in the short term benefit from early
parenteral nutrition.
2. Management of severe sepsis:
a. Fluid resuscitation to a CVP of 8-10 mmHg is supported
by good quality evidence.
b. The available evidence suggests that resuscitation to a
higher target than 65 mmHg improves outcome.
c. The available evidence suggests that early goal directed
therapy improves outcome.
d. A paper reviewed in this issue of the Monitor indicates
that there is a high risk of cardiovascular events in
survivors of severe sepsis.
3. Goal directed therapy in high risk surgical patients:
a. The high-risk group of patients are those that have been
identified by large scale epidemiological studies.
b. The high risk group of patients are clearly defined.
c. Goal directed therapy is targeted to a specific mean
arterial pressure and central venous pressure.
d. A paper reviewed in this issue of the Monitor suggests
that goal directed therapy reduces mortality in high risk
surgical patients.
4. Non-invasive regional cerebral oxygen saturation
and cardiac arrest:
a. Non-invasive regional cerebral saturation is based
on absorption of near infrared light.
b. Non-invasive regional cerebral saturation monitoring
is based on subtraction of absorption of light by
extracranial haemoglobin.
c. Clinical features cannot be used to accurately
prognosticate 24 hours after cardiac arrest.
d. A paper reviewed in this issue of the Monitor
demonstrates that noninvasive regional cerebral
saturation can be used to predict good neurological
outcome in survivors of out of hospital cardiac arrest.
BRITISH MEDICAL JOURNAL

BMJ Publishing Group,
BMA House, Tavistock Square,
London WC1H 9JR UK.
BRITISH JOURNAL OF ANAESTHESIA
Oxford University Press,
Great Clarendon Street,
Oxford OX2 6DP UK.
CRITICAL CARE
BioMed Central Ltd
Science Navigation Group
Middlesex House
34-42 Cleveland Street
London W1T 4LB UK.
JOURNAL OF ALLERGY & CLINICAL IMMUNOLOGY
Elsevier Science Inc.,
6277 Sea Harbor Drive,
Orlando,
FL 32887-4800 USA.
JOURNAL OF THE AMERICAN MEDICAL
ASSOCIATION
American Medical Association,
515 N. State Street,
Chicago,
IL 60610 USA.
JOURNAL OF THE AMERICAN MEDICAL
ASSOCIATION INTERNAL MEDICINE
American Medical Association,
515 N. State Street, Chicago,
IL 60610 USA.
NEW ENGLAND JOURNAL OF MEDICINE
Massachusetts Medical Society,
1440 Main Street, Waltham,
MA 02154 USA.
RESUSCITATION
Elsevier Ireland Ltd.,Elsevier House,
Brookvale Plaza, East Park,
Shannon, Co. Clare,
IRELAND.
Answers to questions featured in Intensive Care

Monitor Vol. 21 No. 3 May/June 2014
THE LANCET RESPIRATORY MEDICINE

The Lancet Ltd.,
84 Theobalds Road,
London WC1X 8RR UK.
1. Pulmonary embolism: TFTF

2. Acute kidney injury: FTFT
3. Randomized controlled trials: TTTF
4. Mean arterial pressure: TFFF
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Volume 21 No.

M.N. Smithies, Cardiff, UK

analysis showed that fluid plus inotrope therapy was

Patients and methods

In the treatment of high-risk surgical patients, administration

Patients and methods

The bottom line is that perioperative GDT

Effect of prehospital induction

Adults with prehospital cardiac arrest and resuscitated

reach a temperature of 34C for patients who received

2. Peberdy MA,Callaway CW,Neumar RW et al. American Heart Association.

The bottom line is that we now know that

A no-prophylaxis platelettransfusion strategy for

To determine, in patients with haematological cancers,

haematological cancers: the proportion of patients who had

Patients and methods

Thrombocytopaenia is a common clinical

The bottom line is that haematological

ICM RECOMMENDED REVIEW PAPER

Noninvasive regional cerebral

a near-infrared spectrometer were applied to the forehead

This study was able to demonstrate that the rSO2 on hospital

To investigate whether regional brain oxygen saturation (rSO2)

In this paper, Ito et al. assess the utility of a device that

Patients and methods

Data from the Society of Thoracic Surgeons (STS)

The bottom line is that this is something for

Early parenteral nutrition in

nutrition for critically ill adults ineligible for early enteral

Patients and methods

to 0.11; p=0.01) and experienced less muscle wasting and

The bottom line is that this is another study

Psychiatric diagnoses and

Patients and methods

5 years, 6.2% of mechanically ventilated patients had one or

even in those whom intensive care saves from

The bottom line is that the incidence of

Lamas D. Chronic critical illness. N Engl J Med

An exploration of social and

0.69 (IQR, 0.520.80) at 6 months and 0.69 (IQR,

Patients and methods

evidence with regard to decreased quality of life,

The bottom line is that despite the

Associations between palliative

analysis. All patients receiving chemotherapy at enrolment,

Evidence Level: III

Patients and methods

This analysis found that the use of chemotherapy in

chemotherapy is administered without curative

The bottom line is that palliative chemotherapy administration is associated with

Risk of cardiovascular events in

Patients and methods

Evidence Level: III

years), most commonly stroke. In the unmatched controls,

echocardiography changes in the absence of

The bottom line is that survivors of sepsis

The effect of intravenous

Patients and methods

Evidence Level: III

were 59 patients in the control group. The 28-day all cause

levels of CD73 and 28-day mortality in a phase

The bottom line is that although the results

Effect of pressure support vs

Patients and methods