Resuscitation (2006) 69, 1522

REVIEW

Post resuscitation care

What are the therapeutic alternatives and
what do we know?
J. Herlitz a,, M. Castren b, H. Friberg c, J. Nolan d, M. Skrifvars b,
K. Sunde e, P.-A. Steen e

a Division of Cardiology, Sahlgrenska University Hospital, Goteborg, Sweden

b Department of Anaesthesiology and Intensive Care Medicine, Helsinki University Hospital, Helsinki,
Finland
c Anaesthesia and Intensive Care Lund University Hospital, Lund, Sweden
d Anaesthesia and Intensive Care Medicine, Royal United Hospital, Bath, UK
e Department of Anesthesiology, Ulleval University Hospital, Oslo, Norway

Received 1 April 2005; accepted 11 August 2005

KEYWORDS Summary A large proportion of deaths in the Western World are caused by
Cardiac arrest; ischaemic heart disease. Among these patients a majority die outside hospital due
Treatment; to sudden cardiac death.
Post resuscitation The prognosis among these patients is in general, poor. However, a signicant
proportion are admitted to a hospital ward alive. The proportion of patients who
survive the hospital phase of an out of hospital cardiac arrest varies considerably.
Several treatment strategies are applicable during the post resuscitation care
phase, but the level of evidence is weak for most of them. Four treatments are
recommended for selected patients based on relatively good clinical evidence:
therapeutic hypothermia, beta-blockers, coronary artery bypass grafting, and an
implantable cardioverter debrillator. The patients cerebral function might inu-
ence implementation of the latter two alternatives. There is some evidence for
revascularisation treatment in patients with suspected myocardial infarction. On
pathophysiological grounds, an early coronary angiogram is a reasonable alternative.
Further randomised clinical trials of other post resuscitation therapies are essential.
2005 Elsevier Ireland Ltd. All rights reserved.

A Spanish translated version of the summary of this article appears as Appendix in the online version at

10.1016/j.resuscitation.2005.08.006.
Corresponding author. Tel.: +46 31 3421000; fax: +46 31 827375.

E-mail address: johan.herlitz@hjl.gu.se (J. Herlitz).

0300-9572/$ see front matter 2005 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.resuscitation.2005.08.006
16 J. Herlitz et al.

Contents

Background ....................................................................................................... 16
Predictors for outcome ........................................................................................... 16
Therapeutic possibilities (Table 1) ................................................................................ 17
Optimizing physiology/general intensive care treatment ......................................................... 17
Body temperature............................................................................................ 17
Indication for hypothermia ............................................................................ 17
Blood pressure ............................................................................................... 17
Indication for optimizing blood pressure ............................................................... 18
Blood glucose ................................................................................................ 18
Indication for optimizing blood glucose ................................................................ 18
Acidbase status............................................................................................. 18
Indication for optimizing acidbase status............................................................. 18
Serum potassium............................................................................................. 18
Indication for optimizing serum potassium ............................................................. 18
Serum magnesium............................................................................................ 18
Indication for optimizing serum magnesium............................................................ 18
Revascularization ................................................................................................. 18
Thrombolysis................................................................................................. 19
Indication for thrombolysis ............................................................................ 19
Percutaneous transluminal coronary intervention ............................................................ 19
Indication for PCI ...................................................................................... 19
Coronary artery bypass grafting (CABG) ...................................................................... 19
Indication for CABG.................................................................................... 19
Anti-arrhythmic therapy .......................................................................................... 19
Implantable cardioverter debrillator (ICD) .................................................................. 19
Indication for ICD ...................................................................................... 20
Beta-blockers ................................................................................................ 20
Indication for beta-blockers ........................................................................... 20
Amiodarone .................................................................................................. 20
Indication for amiodarone ............................................................................. 20
Anticonvulsant therapy ........................................................................................... 20
Indication for anticonvulsants ................................................................................ 20
Conclusion........................................................................................................ 20
References ....................................................................................................... 20

Background charged from hospital alive.25 The cerebral func-

A large proportion of deaths in the Western World
are caused by ischemic heart disease. Among these
patients a majority die outside hospital due to sud-
den cardiac death.1
The prognosis among these patients is, in gen-
eral, poor.1 However, a signicant proportion are
admitted to a hospital ward alive: 2035% in Scan-
dinavian studies.24 This means that about 125
patients per million inhabitants require post resus-
citation care each year. If survivors from in hospital
cardiac arrest are included, the number of patients
requiring post resuscitation care is double this g-
ure.
The proportion of patients who survive the hospi-
tal phase of an out-of-hospital cardiac arrest varies
considerably.35 From large patients series it has
been shown that between 30 and 60% can be dis-
tion of these patients is also highly variable.4
Predictors for outcome
Survival with complete neurological recovery
depends on several interventions during the chain
of survival and includes both pre- and post admis-
sion factors. Preadmission factors cannot be inu-
enced by the post resuscitation care. They include
increasing age, a previous history of diabetes or
heart failure and various factors related to the
resuscitation event: initial rhythm, whether the
arrest was witnessed or not, bystander CPR, time
of rst debrillation attempt for patients in ven-
tricular brillation,2 and the duration of arrest,
i.e. the severity of the ischaemic insult to the
brain.6
Post resuscitation care
The patients status on admission to hospital
is a very important determinant of outcome; fac-
tors to consider include: level of consciousness2,7,8
presence of cardiogenic shock79 and presence
of sinus rhythm.2 Prehospital post resuscitation
care therefore is important and may inuence
outcome signicantly, but only a few studies
exist.10
Post admission factors and the nal out-
come are inuenced signicantly by the quality
of post resuscitation care, which differs among
hospitals.3,4 Treatment of both the global ischaemic
brain damage and the dysfunctional heart dur-
ing the reperfusion phase is the main challenge.
The post-resuscitation phase is associated with a
sepsis-like syndrome, with high levels of circulat-
ing cytokines, adhesion molecules, plasma endo-
toxin and unregulated leukocyte production of
cytokines.11
Several post admission factors have been high-
lighted recently.4,12 Langhelle et al. reported
four factors that were associated with an
adverse outcome: elevation of serum glucose
(>10.7 mmol/l), pyrexia (>37.8 C), acidosis (base
access 3.5 mmol/l), and seizures.4 Skrifvars
et al. identied the following to be associ-
ated with an adverse outcome: elevation of
serum glucose >6.8 mmol/l, absence of treat-
ment with beta-blockers, and serum potassium
>4.2 mmol/l.12
With the exception of temperature control,
which is an established post-resuscitation therapy,
a cause and effect relationship was not investigated
and should be the focus of further interventional
studies.
Therapeutic possibilities (Table 1)
The therapeutic strategies that can be adopted in
the post-resuscitation period can be divided into
four main categories:
1. optimizing physiology/general intensive care
treatment;
2. revascularization;
3. anti-arrhythmic therapy;
4. anticonvulsant therapy.
The four categories include 13 topics. The
levels of evidence are dened as: (A) data
derived from multiple randomized clinical tri-
als; (B) data derived from a single randomized
clinical trial or non-randomized studies; and (C)
expert consensus or data derived from small
studies.
17
Table 1 Therapeutic possibilities
1. Optimising physiology
Body temperature
Blood pressure
Blood glucose
Acid-base status
Electrolytes (potassium)
2. Revascularisation
Thrombolysis
PTCA
CABG
3. Antiarrhythmic therapy
ICD
Betablockers
Amiodarone
4. Anticonvulsant therapy
Optimizing physiology/general intensive
care treatment
Body temperature
The role of therapeutic hypothermia in post resus-
citation care has been investigated extensively
during the last decade. Two randomized trials of
moderate size published in 2002 strongly support
the use of therapeutic hypothermia in comatose
patients admitted to hospital after witnessed out of
hospital ventricular brillation cardiac arrest.13,14
A recent published meta-analysis and systematic
review gives further evaluation evidence.15
In the larger of these two trials from 2002,
273 patients were randomized to be treated with
either therapeutic hypothermia (3234 for 24 h)
or normothermia. Fifty-ve percent of the patients
in the hypothermia group were discharged alive
with a good neurological outcome versus 39%
in the group who were treated conventionally
(p = 0.009).13 Therapeutic hypothermia may also be
benecial for other primary rhythms.16 If therapeu-
tic hypothermia is contraindicated, hyperthermia,
which is common during the rst 24 hours after car-
diac arrest, must be avoided.4,17
Indication for hypothermia
Patients remaining comatose after return of sponta-
neous circulation following a witnessed ventricular
brillation cardiac arrest should receive therapeu-
tic hypothermia management (level of evidence A).
Blood pressure
There are few randomized trials evaluating the
role of blood pressure on the outcome after out
18
of hospital cardiac arrest. One randomized study
demonstrated no difference in the neurological
recovery of patients randomised to a mean arterial
blood pressure of >100 mmHg versus 100 mmHg
5 min after return of spontaneous circulation. How-
ever, good functional recovery was associated with
a higher blood pressure during the rst 2 h after
return of spontaneous circulation.18 In a similar
study of patients with out-of-hospital ventricular
brillation, Herlitz et al. reported higher mor-
tality if the systolic blood pressure was below
120 mmHg on hospital admission.19 On the other
hand, a recent study of survivors of out-of-hospital
cardiac arrest monitored using pulmonary artery
catheters showed that hypotension and myocar-
dial dysfunction is common during the rst 24 h
but not predictive of survival or neurological
recovery.9 Despite a signicant improvement in
cardiac index at 24 h, continued vasodilatation
delayed the discontinuation of vasoactive drugs,
and the myocardial dysfunction was reversible only
in the survivors.9 Myocardial dysfunction, a result
of global myocardial stunning, is well described in
several studies2021 and may be improved by dobu-
tamine at 5 g/kg/min.2223
Indication for optimizing blood pressure
Based on the available data, severe hypotension
and hypertension should be avoided (level of evi-
dence C).
Blood glucose
An infusion of glucose and insulin improves cere-
bral outcome after asphyxial cardiac arrest in rats24
and in an intervention study with glucose infu-
sion before complete cerebral ischaemia in mon-
keys, lower blood glucose levels were associated
with better outcome.25 Intensive insulin therapy
improves outcome among surgical patients in the
intensive care unit.26 A recent trial of insulin ther-
apy in critically ill patients indicated that con-
trol of glucose levels, with a target level of less
than 8.0 mmol/l, rather than the dose of exoge-
nous insulin therapy accounts for the improved
survival.27
In the DIGAMI I study,28 the infusion of glucose
and insulin followed by long-term insulin improved
long-term outcome among diabetic patients with
acute myocardial infarction; however, this has
not been conrmed in the more recent DIGAMI
2 study.29 The latter study did, however, demon-
strate that elevation of blood glucose is an inde-
pendent predictor for an adverse outcome among
diabetic patients with a threatened myocardial
infarction.29
J. Herlitz et al.
Indication for optimizing blood glucose
Hypo- and hyperglycaemia should be avoided. The
threshold blood glucose value that should trigger
insulin therapy is unknown but is likely to be in the
range 6.18.0 mmol/l (level of evidence C).
Acidbase status
There is no randomized trial evaluating the possible
benet of treating acidbase disturbances; how-
ever, acidosis per se is an adverse prognostic factor
in the post resuscitation phase.4,7
Indication for optimizing acidbase status
Undetermined; although avoidance of severe aci-
dosis is reasonable (level of evidence C)
Serum potassium
There is no randomized trial evaluating the value
of changing serum potassium in post resuscitation
care; however, hyperkalaemia is an adverse prog-
nostic factor among these patients.7,12 Whether or
not this is an epiphenomenon of acidosis or renal
insufciency is uncertain.
Indication for optimizing serum potassium
Based on previous experiences it is reasonable to
recommend avoidance of hyperkalaemia and avoid-
ance of hypokalaemia (level of evidence C).
Serum magnesium
Hypomagnesaemia is associated with adverse out-
come in critically ill patients30,31 and may have
a role in mitigating neurological injury; however,
there is no randomization trial evaluating magne-
sium in post-resuscitation care.
Indication for optimizing serum magnesium
Avoid hypomagnesaemia (level of evidence C).
Revascularization
A post mortem study of 82 cardiac arrest victims
in Finland, indicated that coronary artery disease
was the cause of the arrest in 78%32 ; furthermore,
coronary thrombi are found frequently in patients
after sudden cardiac death.33 Acute changes in
coronary plaque morphology are found in 4086%
cardiac arrest survivors, and in 1564% in autopsy
studies.34
Immediate coronary angiography among sur-
vivors of out of hospital cardiac arrest showed a
Post resuscitation care
coronary occlusion in 48% of cases; not all patients
had an ECG-pattern indicating such a nding.35
Thrombolysis
There are limited data on the impact of throm-
bolysis on survival during the post resuscitation
period. An observational study of relatively few
patients (n = 69) showed a survival benet for
thrombolysis36 : the mortality was 13 of 33 (39%)
among those receiving thrombolysis versus 24 of
36 (67%) in those who did not. The difference was
in deaths attributed to cardiac, rather than neu-
rological causes.36 Similar ndings are reported
from Finland,10 Sweden,19 Great Britain37 and
Germany.38 Although bleeding has been reported
in a few cases,37,38 thrombolysis seems to cause
few side-effects, even when given in the prehos-
pital setting.10
Indication for thrombolysis
In-hospital thrombolysis is recommended for
patients with ST-elevation who have not received
pre-hospital thrombolysis if there are no facilities
for immediate percutaneous transluminal coronary
intervention (PCI) (level of evidence C).
Percutaneous transluminal coronary
intervention
Sixty of 84 (71%) out of hospital cardiac arrest
survivors undergoing immediate coronary angiog-
raphy had signicant coronary artery disease.35
PCI was attempted in 37 patients and success-
ful in 28 patients; the overall survival rate was
38%. Successful PCI was an independent predictor
for an increased survival.35 Similarly, Bendz et al.
reported almost 70% survival in 40 cardiac arrest
patients arriving at the hospital after primary suc-
cessful cardiopulmonary resuscitation,39 showing
the practical approach and perhaps benet for this
intervention on these patients.
Indication for PCI
PCI is indicated when cardiac arrest is thought to
be caused by myocardial ischaemia/infarction and
a culprit lesion is found at coronary angiography
(level of evidence C).
Coronary artery bypass grafting (CABG)
There is no randomized trial evaluating the impact
of CABG on survival in the post resuscitation phase.
In an observational study with 5 year follow up
of immediate survivors of out of hospital cardiac
19
arrest, 26% of 85 patients undergoing CABG had car-
diac arrest or died versus 62% among 180 who were
on medication without surgery.
When adjusting for differences at baseline, CABG
was associated with a signicant reduction in the
risk of a new cardiac arrest, but not death.40
Randomized clinical trials4143 and meta-
analysis44 have shown that among patients with
angina pectoris and a left main stenosis or three
vessel coronary artery disease, CABG will improve
survival.
Indication for CABG
Coronary artery bypass grafting is indicated in the
post resuscitation phase for patients with left main
stenosis or triple vessel coronary artery disease if
the cardiac arrest was thought to be caused by
ischaemic heart disease (level of evidence A or C
depending on interpretation).
Anti-arrhythmic therapy
Implantable cardioverter debrillator (ICD)
Previous experiences indicate that among patients
with acute myocardial infarction and depressed sys-
tolic myocardial function (ejection fraction less
than 35%) treatment with an ICD, compared with
antiarrhythmic therapy, will improve prognosis dur-
ing long term follow up.45 Some of these patients
had sustained a cardiac arrest before randomisa-
tion; however, three secondary prevention ICD tri-
als have evaluated the impact of this device on
survival among patients having suffered from a pre-
vious cardiac arrest. The rst of these, the anti-
arrhythmic versus implantable debrillator (AVID)
study included patients with prior ventricular b-
rillation as well as patients with haemodynamically
unstable ventricular tachycardia.46 One thousand
and sixteen patients were randomised to receive
either an ICD or drug therapy: either amiodarone
or sotalol. Over a mean follow up of 18 months,
death rates were 15.8 3.2% for the ICD versus
24.0 3.7% for drug therapy (p < 0.02). The prolon-
gation of life was modest just over 3 months.
The Cardiac Arrest Study Hamburg (CASH) trial
enrolled patients with prior ventricular brillation
and recruited patients into three arms: ICD (n = 99);
amiodarone (n = 92); and metoprolol (n = 97).47
Over a mean follow up period of 57 months therapy,
an ICD was associated with a 23% (non-signicant)
reduction in all cause mortality rates compared to
treatment with amiodarone/metoprolol.
The Canadian Implantable Debrillator Study
(CIDS) enrolled patients with prior ventricular
20
brillation as well as patients with haemodynami-
cally unstable ventricular tachycardia and patients
with reduced left ventricular function, syncope and
inducible ventricular tachycardia.48 Six hundred
and fty-nine patients were assigned randomly to
treatment with an ICD or with amiodarone. At 5
years a non-signicant reduction in the risk of death
was observed with the ICD (8.3% per year) com-
pared with 10.2% per year in the amiodarone group
(a relative risk reduction of 20%).
A meta-analysis of the three trials showed a sig-
nicant reduction in death from any cause with an
ICD with a summary hazard ratio of 0.72 (95% con-
dence interval 0.600.87; p = 0.0006).49 The ICD
extended survival by a mean of 4.4 months during
a follow up period of 6 years. Patients with a left
ventricular ejection fraction 35% derived signif-
icantly more benet from ICD therapy than those
with better left ventricular function.
Indication for ICD
The balance of evidence favours ICD-therapy over
anti-arrhythmic medical therapy (level of evidence
A or B).
Beta-blockers
Beta-blockers reduced total mortality (particularly
sudden death) among patients with myocardial
infarction50 and/or heart failure5153 and are asso-
ciated with improved survival in cardiac arrest
registries.12,54,55
Indication for beta-blockers
The indications for beta-blockers are (1) Known or
recent myocardial infarction and/or heart failure
(level of evidence A or C); (2) cardiac arrest of pre-
sumed cardiac aetiology (level of evidence B).
Amiodarone
The two largest trials evaluating patients at risk
of sudden death both showed that amiodarone
reduced arrhythmic deaths but not the total
deaths.5657 Meta-analysis from all 13 randomised
controlled trials of amiodarone (89% after myocar-
dial infarction) showed a signicant reduction
in total mortality and a signicant reduction in
arrhythmic death.58,59
Indication for amiodarone
Recurring ventricular arrhythmias despite beta-
blockade or if beta-blockade is not tolerated (level
of evidence C).
The balance of evidence favours ICD-
therapy over anti-arrhythmic medical therapy
J. Herlitz et al.
in patients with a history of severe ventricular
arrhythmias.
Anticonvulsant therapy
Seizures occur after cardiac arrest in up to
3040% of cases6061 and are associated with
a worse outcome.4,6061 Early prevention and
treatment of seizures is advocated although the
scientic evidence for this strategy is weak;
the link between seizures and outcome may be
causative or simply an epiphenomenon. Anticon-
vulsants such as thiopental and especially pheny-
toin are neuroprotective,6264 but a clinical trial of
thiopental after cardiac arrest showed no benet.65
Further clinical studies are required.
Indication for anticonvulsants
The indication for anticonvulsants is undetermined,
although treatment of seizures is reasonable (level
of evidence C).
Conclusion
Several treatment strategies are applicable dur-
ing the post resuscitation care phase, but the
level of evidence is weak for most of them.
Four treatments are recommended for selected
patients based on relatively good clinical evidence:
therapeutic hypothermia, beta-blockers, coronary
artery bypass grafting, and an implantable car-
dioverter debrillator. The patients cerebral func-
tion might inuence implementation of the lat-
ter two alternatives. There is some weak evidence
for revascularisation treatment in patients with
suspected myocardial infarction. On pathophysio-
logical grounds, an early coronary angiogram is a
reasonable alternative. Further randomised clini-
cal trials of other post resuscitation therapies are
essential.
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