ORIGINAL ARTICLE

Postresuscitation Encephalopathy
Current Views, Management, and Prognostication
Boby Varkey Maramattom, MD, DM, and Eelco F.M. Wijdicks, MD
Background: Cardiac arrest has a high mortality rate. Postresusci-
tation encephalopathy is commonly associated with signicant mor-
bidity.
Review Summary: Among those patients who achieve a return to
spontaneous circulation, more than half die during the subsequent
hospital course. Few survivors recover without signicant neuro-
logic disability. Clinical examination is often used for predicting
subsequent neurologic outcome in these patients. The role of ancil-
lary investigations and the judicious combination of these parame-
ters with the ndings on clinical examination to achieve accurate
prognostication is discussed in this review. Only a few parameters
have a strong predictive value in coma after cardiac arrest. These
include pupillary light reexes and motor responses at 3 days, absent
somatosensory evoked potential, and possibly diffuse magnetic
resonance imaging changes.
Conclusion: The authors discuss the physiology, pathology, and
consequences of cardiac arrest to the central nervous system, and the
use of various parameters in prognostication. Induced hypothermia
is a new therapeutic development.
Key Words: cardiopulmonary resuscitation, cardiac arrest, coma
(The Neurologist 2005;11: 234243)
C
ardiac arrest leads to a sudden loss of cardiac output and
circulation. This is potentially reversible, with a success-
ful restoration of spontaneous circulation (ROSC) and oxy-
gen delivery. In contrast, sudden cardiac death (SCD) refers
to death occurring within 1 hour from a primary cardiac cause
and involves at least 2 to 5 minutes of absent pulses.
1
In the
United States in 1998 alone, there were around 450,000
deaths attributed to SCD.
2
Additionally 375,000 to 750,000
patients undergo attempted resuscitation each year. When the
heart stops, the lack of blood ow injures the brain. With 40%
of these patients attaining ROSC in the United States, almost
100,000 to 200,000 cases present to intensive care units
(ICUs) annually with brain injury after cardiac arrest.
The nancial implications of this condition are stagger-
ing. In 1999 alone, hospital costs averaged $160,000 to
$180,000
3
per patient discharged alive after cardiac arrest,
and the mean hospital stay was 12 days.
4
The emotional
burden of this devastating condition on the immediate family
is incalculable. As advance directives become prevalent,
family members increasingly prefer withdrawing medical
support if the chances of a meaningful recovery are remote.
Neurologists have to be able to predict reasonably the out-
come of a particular patient. Important questions that arise
during this period include the likelihood of severe disability
or dependence and the ability to return to baseline function-
ing. Currently neurologists and neurointensivists have a
largely consulting role in the management of these patients.
However, with the promise of new therapies such as hypo-
thermia, neurointensivists should probably be closely in-
volved in management to improve outcomes in these patients.
This review summarizes current knowledge about the patho-
physiology and consequences of cardiac arrest, and tools of
the trade used in the prognostication and management of this
devastating condition.
Strictly speaking, the term hypoxic-ischemic encepha-
lopathy is not entirely correct in this setting because it implies
a common pathophysiologic mechanism for hypoxia and
ischemia (discussed later). The term postresuscitation en-
cephalopathy (PRE) is preferred in the setting of brain injury
after cardiac arrest and is used throughout this article.
PHYSIOLOGY OF CARDIAC ARREST
AND RESUSCITATION
Cardiac arrhythmias account for around 50% of cases
of cardiac arrest. The remainder is associated with acute
respiratory failure or hypotension.
5
In witnessed arrests, the
most common arrhythmia is ventricular tachycardia (VT) or
ventricular brillation (VF) in a third of patients (33%).
Respiratory causes (27%), asystole or bradyarrhythmias
(18%), and electromechanical dissociation (18%) make up
the remainder.
6
As rescuer arrival time lengthens, the
From the Division of Critical Care Neurology and Neurology, Mayo Clinic
College of Medicine, Rochester, Minnesota.
Reprints: Eelco F.M. Wijdicks, MD, Mayo Clinic College of Medicine, 200
First Street SW, Rochester, MN 55905. E-mail: wijde@mayo.edu.
Copyright 2005 by Lippincott Williams & Wilkins
ISSN: 1074-7931/05/1104-0234
DOI: 10.1097/01.nrl.0000159985.07242.22
The Neurologist Volume 11, Number 4, July 2005 234
proportion of asystole increases as other arrhythmias convert
into asystole. The type of arrhythmia at rescuer arrival does
impact survival rates. The best prognosis is seen with ven-
tricular tachycardia (survival to discharge, 34%) and the
worst prognosis with asystole (610%) or bradyarrhythmias.
5
In a large cohort, pulselessness for more than 10 minutes was
incompatible with survival.
7
In general, the shockable
rhythms (VT and VF) have a better outcome than the
nonshockable rhythms (asystole and bradyarrhythmias).
Even with shockable rhythms, the time difference between
collapse and debrillation should not probably exceed 5 to 6
minutes.
8
Unfortunately, even in the best of circumstances,
the combined time between onset of cardiac arrest, and
rescuer arrival and debrillation is on the order of 7 to 10
minutes, by which time irreversible brain injury has often
set in.
The American Heart Association divides cardiopulmo-
nary resuscitation (CPR) into 2 phases: basic life support
(BLS) and advanced cardiac life support (ACLS).
9,10
BLS
consists of airway maintenance, breathing, and circulatory
support. ACLS consists of drug administration and debril-
lation. Closed chest compression is a major component of
BLS. During BLS, compression of the chest wall maintains
cardiac output via 2 mechanisms. Chest compression actively
forces blood out from the heart by compressing it between the
sternum and the spine (cardiac pump theory). A primary
increase in the intrathoracic pressure could also drive blood
passively from the heart into the great vessels (thoracic pump
theory). Backow is often minimal because venous valves are
intact. Both theories are likely valid; recent echocardio-
graphic studies show valvular closure and forward ow
analogous to the normal cardiac physiology with closed chest
massage.
11
Standard CPR generates 1.3 L/minute forward ow and
25-mmHg systemic perfusion ow.
12
Nevertheless, this is
able to maintain only 30% of prearrest cerebral blood ow
(CBF) and not even enough coronary ow to maintain the
demands of a brillating heart.
13
This has spurred efforts to
nd more effective ways of establishing adequate vital organ
perfusion pressure. Simultaneous interposed abdominal com-
pression, when alternate chest and abdominal compression
are carried out (chest compressed/abdomen relaxed, chest
relaxed/abdomen compressed), improves forward ow to
some extent (2.4 L/minute).
12
Open chest compression car-
diac massage and active compression-decompression CPR
(ACD CPR) devices have also been used.
ACD CPR uses a hand-held suction device that is
applied to the mid sternum and it actively decompresses and
compresses the chest. Although short-term survival im-
proved, there was no signicant difference when compared
with standard CPR in any of the studies.
1417
Life-stick CPR
is a new 2-handled device that alternately compresses and
decompresses the chest and abdomen through adhesive pads
and improves forward ow (3.1 L/minute), although clinical
benets are yet to be seen.
12
(Fig. 1)
With successful CPR, patients either achieve ROSC or
develop a low-output cardiac state requiring inotropic sup-
port. Among the survivors, nearly 70% will succumb during
FIGURE 1. This drawing illustrates
the different methods of resuscita-
tion (see text for details).
The Neurologist Volume 11, Number 4, July 2005 Postresuscitation Encephalopathy
2005 Lippincott Williams & Wilkins 235
the subsequent hospital course. Although cardiac electro-
physiologic instability is common after resuscitation, recur-
rent arrhythmias such as recalcitrant complex ventricular
ectopics are only responsible for 10% of subsequent deaths.
The majority of subsequent deaths in hospital are due to PRE
(38%) or continued low cardiac output states (31%).
18
Fur-
thermore, distant organ damage and systemic complications
can develop and worsen the outcome (Table 1).
19,20
Some
patients develop a postresuscitation syndrome as a result of
whole-body ischemia and reperfusion injury. This resembles
the sepsis response and manifests with a systemic inamma-
tory response (increase in cytokine levels), myocardial dys-
function, coagulopathy, and adrenal dysfunction, and contrib-
utes to vasoparalysis and electrophysiologic instability during
the postresuscitative period.
21
CENTRAL NERVOUS SYSTEM
PATHOPHYSIOLOGY
Within 20 seconds of cardiac arrest, the neuronal oxy-
gen stores are depleted and the patient becomes unconscious.
The central nervous system (CNS) is able to tolerate only
very brief periods of circulatory arrest, and glucose and ATP
stores are depleted in 5 minutes. This is the critical period
during which vulnerable tissue can be salvaged. During the
immediate postresuscitation period, global CBF and cerebral
metabolic rate of oxygen (CMRo
2
) transiently increase (tran-
sient hyperemia) for 15 to 30 minutes. Subsequently CBF
decreases along with decreased CMRo
2
(delayed hypoperfu-
sion phase). The CBF is decreased to 50% of baseline values
between 90 minutes and 12 hours after arrest. This decrease
is heterogenous and patchy. During this phase the cerebral
autoregulation curve is often shifted to the right,
22
which has
important implications for blood pressure management.
The underlying mechanism of cerebral necrosis is
ischemia. Pure hypoxia alone does not result in cerebral
necrosis
23
even with extreme hypoxia (PaO
2
20 mmHg).
24
Pure hypoxia results in a marked increase in CBF
25
that
washes out metabolic waste products. Consequently, neuro-
nal damage is ameliorated even though oxygen delivery is
compromised. In this situation, GABA-ergic deciency and
synaptic dysfunction are often readily reversible.
26
Conse-
quently, respiratory arrest alone has a better prognosis than
when associated with cardiac arrest.
In ischemia there is a massive outpouring of excitotoxic
glutamate. This activates NMDA and AMPA receptors,
opens calcium and sodium channels, and initiates cata-
strophic enzymatic processes, leading to neuronal death.
Unfortunately, although tissue perfusion is restored, neuronal
damage continues. Vulnerable neuronal populations (such as
hippocampal CA1 neurons) briey recover from the ischemic
process before delayed neuronal death sets in.
27
The neuritic
processes (axons and dendrites) of these cells seem particu-
larly susceptible to subcellular organelle disruption. Even
though the cell body is relatively resistant to ischemia and
demonstrates regenerative changes after restoration of CBF,
cell death eventually ensues via a die-back phenomenon. An
exciting new discovery is the role of unfolded protein re-
sponses (UPR) in the endoplasmic reticulum. These pathways
are abnormally activated during ischemia and increase apo-
ptosis in vulnerable neurons.
28
Two patterns of neuronal death are seen. Neuronal necro-
sis and reactive astrocytes are seen in vulnerable areas. In
addition, multifocal microinfarcts or conuent pan-cellular ne-
crosis are seen in laminar and border zone arterial areas second-
ary to postresuscitation microcirculatory disturbances.
29
Preferential areas of involvement in the CNS include
the frontoparietal cortex, hippocampus, basal ganglia, cere-
bellum, and spinal cord. Laminar necrosis of the cortex (with
involvement of layers 3, 4, and 5) is often noted. The CA1
TABLE 1. Systemic Complications After Successful
Restoration of Spontaneous Circulation
Acute tubular necrosis
Traumatic liver damage (due to CPR)
Shock liver
Ischemic colon and sepsis
Pneumothorax
Bone marrow embolus
Rib fractures
Ventilator-associated pneumonia
Sepsis
Postresuscitation syndrome
Adapted with permission from Wijdicks EF. Neurologic Complications
of Critical Illness. 2nd ed.
20
The central nervous system (CNS) is able to
tolerate only very brief periods of circulatory
arrest, and glucose and ATP stores are depleted
in 5 minutes.
The underlying mechanism of cerebral necrosis
is ischemia.
Maramattom and Wijdicks The Neurologist Volume 11, Number 4, July 2005
2005 Lippincott Williams & Wilkins 236
area of the hippocampus (Sommers sector) is particularly
affected by ischemia. Damage to the hippocampus can even
increase with time and produce crippling amnesia.
30
With
increasing ischemia the mid brain and deep gray matter are
also involved. Ischemic myelopathy is found at autopsy in
approximately 46% of patients; however, it is often unrecog-
nized during life. Involvement predominates at the lumbar or
lumbosacral spinal cord whereas other areas are involved less
frequently.
31
Mild degrees of ischemia involve the lumbosa-
cral spinal cord (69%), intermediate degrees affect the lum-
bosacral and cervical spinal cord in a patchy manner (9%),
and severe ischemia results in holo-cord necrosis (17%).
Large neurons in the anterior and paramedian groups of the
anterior horns and Clarkes column of the low thoracic and
lumbar levels are preferentially involved. With severe cases,
the gray matter is completely infarcted. The location of
lesions in the CNS reects the selective vulnerability of
tissues to global ischemia, high metabolic demand, and the
presence of receptors for excitatory neurotransmitters in sus-
ceptible areas. In contrast, other areas of more resistant
neurons can withstand the same injury.
CLINICAL FEATURES
Patients who are resuscitated from cardiac arrest dis-
play a wide variety of manifestations of PRE. A few patients
awaken or have purposeful motor movements almost imme-
diately after CPR. These patients progress from an amnesic,
confused state to gradual alertness within a few hours. This
group has the best prognosis. Others are comatose, and many
patients are found to be spontaneously hypothermic. In gen-
eral, the outcome of PRE worsens with the duration of coma.
If the duration of coma exceeds 6 hours, the proportion
of patients who will regain independence during the rst
postarrest year drops to 10%. Within 3 days most comatose
patients who are destined to awaken will do so,
32,33
and
earlier awakening is associated with lesser impairment.
The initial degree of motor responsiveness is a good
indicator of outcome. A motor response consisting of local-
ization or better at the initial assessment has a good progno-
sis. The lack of motor response to pain at initial assessment
suggests a poor recovery; less than 22% of patients recover to
independence. However, one must rule out a man-in-the-
barrel syndrome before categorizing the upper limb motor
response.
34
This syndrome appears with bilateral border zone
infarctions in the prerolandic areas at the ACA-MCA water-
shed region, which subserves proximal upper limb motor
function. The syndrome presents with severe bilateral prox-
imal upper limb weakness with preservation of lower limb
and distal upper limb power.
After ROSC, brainstem reexes such as pupillary,
oculocephalic, and corneal responses are often abnormal.
Pupillary dilatation starts within 1 to 2 minutes of cardiac
arrest. However, if dynamic pupillary changes are seen
during CPR (such as progressive decreases in pupil size or
the presence of light reactivity) a better prognosis is
implied than if the pupils are xed and dilated throughout
the procedure.
35
In survivors, the pupillary reexes return
quickly by 6 hours.
36
Administration of atropine during
resuscitation can produce dilated pupils, which persist for
several days, and this drug effect must be considered.
Sustained upgaze is seen almost immediately after arrest in
patients who have sustained severe ischemia. Pathologic
studies show diffuse cerebral and cerebellar damage in
these patients with sparing of the mid brain.
37
These
patients have a poor prognosis. Occasionally patients show
jerky upward movements of the eyeballs along with myo-
clonic facial jerking. Sustained downgaze has also been
reported, appearing a few days after arrest. Patients with
this sign often develop a persistent vegetative state (PVS)
but have a better outcome than those with sustained up-
gaze.
38
Other eye movements such as ping-pong gaze or
periodic lateral gaze are associated with a poor prognosis,
although some reports question their prognostic value.
39
Generalized tonic-clonic seizures are uncommon and
may be related to lidocaine administration during CPR. A
more portentous development is the appearance of myoclonic
status epilepticus (MSE). Intermittent or continuous, synchro-
nous or asynchronous jerky movements affect the face, trunk,
and limbs. The prognosis is uniformly poor and MSE is
considered to be an agonal phenomenon.
40
The Lance-Adams
syndrome, which occurs after hypoxia-induced cardiac arrest,
is seen in awake patients, has a better outcome and may
respond favorably to sodium valproate,
41
baclofen,
42
or leve-
tiracetam.
43
Rarer types of seizures seen in these patients
include area-specic stimulus-provoked seizures such as
hemiclonic seizures provoked by stimulation of the trigemi-
nal areas.
44
Within 3 days most comatose patients who are
destined to awaken will do so.
The lack of motor response to pain at initial
assessment suggests a poor recovery; less than
22% of patients recover to independence.
The Neurologist Volume 11, Number 4, July 2005 Postresuscitation Encephalopathy
2005 Lippincott Williams & Wilkins 237
Researchers have tried to identify variables that help in
prognostication in PRE. A seminal paper by Levy et al
32
presented rules to differentiate patients who had almost no
chance of regaining independence from those who had the
best chance, based on clinical examination at specied inter-
vals (Table 2). However, these rules still had a poor speci-
city. Other authors used predictive models based on 4
parametersmotor response, pupillary light reaction, spon-
taneous eye movements, and the blood glucose level on
admissionfrom which a composite score from 0 to 9 points
was generated.
33
These scores had a high error rate in
identifying poor-prognosis patients. A more recent meta-
analysis of predictive studies suggested only 4 variables had
a high specicity: absent pupillary light reactions on day 3,
absent motor response to pain on day 3, bilaterally absent
median somatosensory evoked potentials (SSEPs) within
week 1, and burst suppression or isoelectric EEGs within
week 1.
45
Evaluation for outcome prediction may thus be best
undertaken at 72 hours after the onset of coma. However, the
sensitivity of these predictors is still very low. Absent pupil
reactions are seen in less than 20% of patients, and absent
motor responses or SSEPs are seen in only about a third of
these patients. Obviously, more robust predictors of outcome
need to be developed.
Prognosis is also inuenced by other factors such as
age, comorbidities, and circumstances of cardiac arrest. El-
derly patients (75 years) with organ failure and unwitnessed
or out-of-hospital arrest have the worst prognosis (2%
chance of ROSC). Better outcomes are seen with younger
patients and witnessed or in-hospital cardiac arrest. In wit-
nessed arrests, the availability of automated external debril-
lators and increased prevalence of bystander CPR have
improved survival rates. Indeed, in earlier studies, it was seen
that bystander CPR improved survival rates by prolonging the
duration of shockable rhythms until emergency medical
services (EMS) arrived for debrillation.
46
There is also a
TABLE 2. Levys Rules for Prognostication of Patients After Cardiac Arrest
Time of Examination Poor Prognosis Good Prognosis
Initial exam No pupillary light reex Pupillary light reex present
Motor response exor or extensor
Roving or orienting conjugate eye movements
1 day Motor response no better than exor Withdrawal motor response or better
Disconjugate or nonorienting eye movements Spontaneous eye opening
3 days Motor response not better than exor Normal spontaneous eye movements
Withdrawal motor response or better
1 week Not obeying commands Obeying commands
Disconjugate or nonorienting eye movements
No spontaneous eye opening at 3 days
2 weeks Abnormal oculocephalic reexes Normal oculocephalic reexes
No spontaneous eye opening at 3 days
Not obeying commands at 3 days
TABLE 3. Poor Prognostic Factors in Postresuscitation
Encephalopathy
Asystole or bradycardia at rescuer arrival (nonshockable
rhythm)
ICU setting, critical illness, multiorgan dysfunction syndrome
Out-of-hospital or unwitnessed arrest
Sustained upward and downward gaze
Absent pupil light response by day 3
Absent motor response to pain by day 3
Myoclonic status epilepticus
Bilaterally absent median somatosensory evoked potential within
week 1
Burst suppression with epileptiform activity within week 1
Diffuse cortical MRI abnormalities
A more recent meta-analysis of predictive
studies suggested only 4 variables had a high
specificity: absent pupillary light reactions on
day 3, absent motor response to pain on day
3, bilaterally absent median SSEPs within
week 1, and burst suppression or isoelectric
EEGs within week 1.
Maramattom and Wijdicks The Neurologist Volume 11, Number 4, July 2005
2005 Lippincott Williams & Wilkins 238
large difference in survival between those patients who arrest
in-hospital or out-of-hospital. Of patients who arrest in-
hospital, 44% attain ROSC
5
and 15 to 17% survive to
discharge. Out-of-hospital arrests have a poorer survival rate
of 2 to 5% at 1 month.
47,48
Two thirds of all survivors suffer
varying degrees of neurologic impairment, and a third are
able to return to work.
6,49
Poor prognosis is also seen with ICU patients who often
have a critical illness, chronic underlying medical disease, or
multiorgan dysfunction syndrome in whom the survival to
discharge approaches zero.
50
Table 3 details all poor prog-
nostic features collected from the previously mentioned lit-
erature.
Once the recovery phase begins, it follows characteris-
tic patterns during the rst postresuscitation year. In the
initial phase, cranial nerve reactivity, miosis, and spontane-
ous respiration return. Patients then develop motor respon-
siveness with decerebrate posturing followed by decorticate
posturing. The EEG shows only intermittent electrocortical
activity at this time. Subsequently the EEG shows continuous
cortical activity along with stereotypic motor reactivity and
spontaneous eye opening. After awakening, recovery with
variable degrees of disability is seen.
51
The spectrum of
recovery ranges from severely affected patients with demen-
tia and total dependency to those with minimal involvement
and return to normal functioning.
LABORATORY INVESTIGATIONS
Drugs, sepsis, and metabolic abnormalities could
hamper the interpretation of the EEG and make it less
useful than evoked potentials. Immediately following re-
suscitation, the EEG may show electrographic silence, and
distinct patterns tend to evolve only after 24 hours. Thus
the EEG is most useful after 24 hours. Certain patterns are
associated with a poor prognosis, including the generalized
suppression and the burst suppression patterns.
52,53
Gen-
eralized suppression patterns may even evolve after 2 to 3
days and are associated with a grave prognosis. Burst
suppression patterns may be compatible with an outcome
equivalent with a PVS. Drug-induced changes (propofol,
midazolam) can mimic all these patterns and should be
excluded as inuences on the EEG. Generalized epilepti-
form discharges can be seen in a periodic or pseudoperi-
odic pattern, associated with myoclonic jerks or eye
blinks.
54
These discharges are usually associated with a
fatal outcome. -, -/-, or -pattern coma may be tran-
siently seen and by itself is not associated with a poor
outcome. They tend to evolve over 5 days into a more
denitive pattern, and subsequent EEG reactivity is a
better predictor of outcome.
55
Evoked potentials are less susceptible to sedative drugs,
metabolic changes, or artifactual interference. Median N20
SSEPs are conventionally used in the prediction of recovery
after cardiac arrest. Absence of potentials has more value
than their presence. If the N20 potential is absent in the
presence of preserved lower potentials (Erbs point, neck),
there is a specicity of 100% for mortality, provided con-
founding focal lesions affecting the cortical potential have
been ruled out. If the N20 potential is present, there is no
prognostic value in PRE. SSEP has the disadvantage of low
sensitivity (5567%). Due to variations in SSEP with time in
different studies,
56,57
this modality is more accurate if used
24 hours or more after the event.
Computed tomographic (CT) scans are normal imme-
diately after resuscitation. Changes are seen after a few days.
Diffuse cerebral swelling with effacement of basal cisterns
and sulci or diffuse hemispheric hypodensities from edema
are seen. Basal ganglia, cerebellar, and watershed area in-
farcts can be seen. These areas are particularly involved due
to their large metabolic demand and consequent need for a
high blood supply.
58
A reversal sign is sometimes seen
when the gray matter becomes hypodense with a diffuse
relative white matter hyperdensity.
59
Elevated intracranial
pressure (ICP) leading to partial obstruction of cerebral ve-
nous drainage and consequent distension of the deep medul-
lary veins may underlie this phenomenon. This sign is a
marker of poor prognosis.
60
Magnetic resonance imaging (MRI) could play a role in
the prediction of outcome. In the rst week following cardiac
arrest, the presence of widespread diffusion or FLAIR abnor-
malities in the cortex, thalamus, and cerebellum could por-
tend poor outcome. Other areas that are typically involved in
PRE are the striatum and hippocampus. Cortical abnormali-
ties are thought to be more important than changes in other
locations. Diffuse abnormalities suggest devastating PRE in
contrast to restricted abnormalities.
61,62
Reperfusion can also
cause microhemorrhages in the basal ganglia, which can be
detected by MRI.
63
Conventional MRI can be normal; how-
ever, diffusion-weighted MRI (DW MRI) will likely show
some changes (Fig. 2). DW MRI also helps to date the injury
by showing gray matter changes in the acute and early
subacute stages, and white matter changes in the late subacute
stage. In the chronic stage, DW MRI is normal.
64
The
In the first week following cardiac arrest, the
presence of widespread diffusion or FLAIR
abnormalities in the cortex, thalamus, and
cerebellum portends irreversibility could portend
poor outcome.
The Neurologist Volume 11, Number 4, July 2005 Postresuscitation Encephalopathy
2005 Lippincott Williams & Wilkins 239
disadvantages of MRI lie in the logistic difculties of trans-
porting patients on multimodality support, ventilators, and
inotropic agents to the MRI scanner. The need for close
monitoring for recurrent arrhythmias or hemodynamic sup-
port may also preclude MRI. Nevertheless, the costs of
unnecessary medical support may be offset by the important
information afforded by this modality.
Positron emission tomographic (PET) scans provide
additional information. Globally decreased CBF and oxygen
extraction is seen with devastating PRE.
65
Patients destined
to remain in a prolonged coma demonstrate progressive
reductions in CMRo
2
over the rst week following resusci-
tation.
66
However, as yet PET cannot differentiate good-
outcome from poor-outcome patients or add to prognostic
information derived from other variables.
67
Moreover, cur-
rently it is a cumbersome technique.
TREATMENT
Evidence-based guidelines have not been developed for
the management of the postresuscitation phase. The primary
goals of treatment at this stage are hemodynamic stability,
maintenance of adequate oxygenation, and prevention of
secondary brain damage. The patient is typically intu-
bated and ventilated in the eld. PaO
2
goals are 100 to
150 mmHg, and PCO
2
goals are 40 to 45 mmHg. Rat models
demonstrate a reduction in volume of necrotic tissue if PaO
2
levels are maintained at more than 200 mmHg.
23
This has
been achieved at normobaric levels and may be applicable in
humans, although randomized, controlled trials are needed to
settle this issue.
Midazolam and fentanyl are used to decrease the stress
associated with invasive procedures and to facilitate ventila-
tion. Neuromuscular blockers are helpful in preventing shiv-
ering. Head position is optimally maintained at 30. Twisting
of the neck can increase jugular venous pressure and theo-
retically may increase ICP. Ideally, the head should be
maintained straight without turning it from side to side.
The blood pressure temporarily increases in some pa-
tients, partly due to the effect of epinephrine administered
during resuscitative measures. In other patients, a sepsislike
state (the postresuscitation syndrome) develops, requiring
intravenous (IV) uids and pressors to maintain the blood
pressure.
21
Because the cerebral autoregulation curve is
shifted to the right and microcirculatory disturbances are
present, it is advantageous to maintain normotension or
induced hypertension to increase tissue perfusion. Mean ar-
terial pressure (MAP) is raised with crystalloid infusions
analogous to the management of subarachnoid hemorrhage.
Vasopressors such as epinephrine, norepinephrine, dopamine,
dobutamine, or vasopressin can be used if these measures fail.
It must be stated that although induced hypertension with
epinephrine has not demonstrated improved outcomes after
cardiac arrest, MAPs are typically maintained at more than 60
mmHg to ensure adequate CBF.
68
Blood sugar management is also controversial. Hyper-
glycemia has been associated with decreased regional CBF
69
and worse outcome.
70
However, it is undetermined whether
hyperglycemia is an epiphenomenon or a primary factor.
Currently, administration of small amounts of glucose solu-
tions during the postresuscitation phase does not seem to
worsen outcome even when 5% dextrose is used.
71
In the
long term, physicians should probably avoid the use of
dextrose-containing solutions to attenuate cerebral swelling
as well as to prevent chronic hyperglycemia and hyperinsu-
linemia.
Myoclonic jerks prove troublesome in some patients.
MSE can interfere with mechanical ventilation and be a
source of distress for family members. The jerks do not
respond to conventional antiepileptics such as phenytoin or
barbiturates. In these circumstances, propofol or neuromus-
cular-blocking agents can prove very useful.
72
Lamotrigine
has the potential to be useful in MSE, especially as it has
shown promise in rat models by decreasing hippocampal cell
FIGURE 2. DW MRI shows restricted diffusion in the thalamus
bilaterally and in the frontal cortices. Corresponding FLAIR
images are normal.
Hypothermia is postulated to improve outcome
by reducing CMR, ICP, glutamate release, and
production of reactive oxygen species.
Maramattom and Wijdicks The Neurologist Volume 11, Number 4, July 2005
2005 Lippincott Williams & Wilkins 240
loss after cardiac arrest (via inhibition of glutamate release).
73
Again, human trials are lacking for this indication.
Although ICP elevations are expected in these patients,
this is not often the case. In one study of 7 patients who
underwent ICP monitoring, 6 had an ICP of less than
20 mmHg, and the only patient with raised ICP had concur-
rent seizures.
74
ICP is often normal in these patients because
lesions are small and patchy. Currently, there is no good
evidence to suggest that ICP monitoring is helpful in the
management of patients with PRE. The use of jugular venous
oxygen saturation or other invasive modalities has likewise
not been demonstrated to improve outcome.
New and exciting developments have taken place in
resuscitation physiology with the introduction of induced
hypothermia. Two controlled trials have demonstrated a mod-
est improvement in outcome with this therapy.
75,76
Hypother-
mia is postulated to improve outcome by reducing CMR, ICP,
glutamate release, and production of reactive oxygen spe-
cies.
77
Various techniques have been used to reduce core
temperatures, including cooled helmets, ice packs, rapid in-
fusion of cold IV uids (30 mL/kg ice-cold crystalloids),
external cooling devices, and water-cooled mattresses. Addi-
tional measures include gastric lavage hourly with ice-cold
saline, axillary ice packs, and air-cooled blankets. Hypother-
mia has been used only in comatose or stuporous patients
because it is extremely uncomfortable for awake patients.
Nevertheless even comatose patients required neuromuscu-
lar-blocking agents to control compensatory shivering. In
these 2 trials, hypothermia was initiated within 2 to 3 hours
after cardiac arrest, and core temperatures were reduced to 32
to 34C (measured by bladder probes). The optimum duration
of induced hypothermia is currently unclear, although these
trials used durations of 12 to 24 hours with gradual rewarm-
ing thereafter. In the 2 trials, hypothermia has been achieved
over a 2- to 8-hour period, although it is likely that faster
cooling rates could result in better outcomes. Potentially
these can be achieved by rapid IV infusion of cold saline via
a central venous catheter (with a reduction of 23C within
30 minutes).
78
Limitations of these studies include poor documenta-
tion of neurologic ndings after resuscitation and inadequate
outcome determination. Additionally, we do not yet know
how soon after resuscitation hypothermia needs to be induced
or the duration of treatment necessary. Other practical limi-
tations of hypothermia include complications such as pneu-
monia, sepsis, coagulopathy, electrolyte shifts, and cardiac
arrhythmias. Fortunately, brief hypothermia (1224 hours)
seems to produce few complications and is relatively safe.
Most patients with PRE are encountered in the cardiac ICUs,
where the neurologist plays a consulting role. Cardiologists
are unlikely to initiate induction of hypothermia, and are
concerned about electrophysiologic instability and medical
complications. Hence, unless neurologists take an active part
in the management of these patients, this aspect of therapy is
likely to be neglected. A word of caution is necessary.
Although the results of the trials look promising, large,
randomized, controlled trials are needed before this mode of
therapy becomes the standard of care. For the interested
reader, comprehensive reviews of hypothermia are available
that provide more information on this subject.
79,80
Elevated body temperature has been shown to worsen
outcome in these patients,
81,82
and acetaminophen is used if
body temperature exceeds 38C. If induced hypothermia is
not achievable, at least normothermia should be maintained
for neuronal integrity.
Another new development has been the use of throm-
bolytics after cardiac arrest. A pilot placebo-controlled, ran-
domized trial using tenecteplase showed a modest benet in
ROSC (36% difference compared with placebo), although
survival to discharge was not affected.
83
However, patients in
the treatment arm were younger (P 0.04) and more likely
to have VF as the rhythm at rescuer arrival (44%). It is
possible that the benet seen with this drug is likely due to the
inuence of age and shockable rhythms. Again, a larger
randomized study is necessary to shed more light on the
effectiveness of this therapy.
CONCLUSION
As the patient arrives in the ER, the physician should
obtain information regarding circumstances, location, dura-
tion of CPR, and type of arrhythmia encountered at arrest. At
admission, ndings suggestive of a poor outcome are sus-
tained upgaze and MSE. Serial clinical examination is man-
datory, although neurologic ndings have the strongest pre-
dictive value after 3 days. Investigations including SSEP,
EEG, and neuroimaging provide corroborative information.
An SSEP is ideally obtained after 24 hours. Although an EEG
is often obtained urgently, a repeat EEG after 4 to 5 days will
more likely display patterns with a higher predictive value.
Neuroimaging should be delayed for a few days because
radiologic changes evolve slowly. MRI is more sensitive than
CT. It should be realized that, ultimately, clinical ndings are
still the best predictors of neurologic outcome.
With the increasing use of antiarrhythmic agents and
-blockers, increasing numbers of patients are presenting to
ERs with cardiac arrest due to asystole rather than VF or VT.
This is balanced by an increase in public awareness, by-
stander CPR, automated external debrillators, faster EMS
response times, and the advent of therapies such as induced
hypothermia. Hence, it is likely that the numbers of patients
with PRE will increase over time.
To reduce neurologic morbidity and disability among
survivors, aggressive intervention is necessary to ameliorate
primary and secondary neuronal injury. There is promise for
neuroprotective agents
84
and therapies such as hypothermia
and thrombolysis during this critical juncture, and these
The Neurologist Volume 11, Number 4, July 2005 Postresuscitation Encephalopathy
2005 Lippincott Williams & Wilkins 241
modalities represent a vast area of potential research. Fur-
thermore, the elucidation of subcellular mechanisms of brain
injury is likely to provide the key to the management of PRE.
REFERENCES
1. Wijdicks EF, Diringer MN. Electrocardiographic activity after terminal
cardiac arrest in neurocatastrophes. Neurology. 2004;62:673674.
2. Zheng ZJ, Croft JB, Giles WH, et al. Sudden cardiac death in the United
States, 1989 to 1998. Circulation. 2001;104:21582163.
3. Thel MC, OConnor CM. Cardiopulmonary resuscitation: historical
perspective to recent investigations. Am Heart J. 1999;137:3948.
4. Gray WA, Capone RJ, Most AS. Unsuccessful emergency medical
resuscitationare continued efforts in the emergency department justi-
ed? N Engl J Med. 1991;325:13931398.
5. Peberdy MA, Kaye W, Ornato JP, et al. Cardiopulmonary resuscitation
of adults in the hospital: a report of 14720 cardiac arrests from the
National Registry of Cardiopulmonary Resuscitation. Resuscitation.
2003;58:297308.
6. Bedell SE, Delbanco TL, Cook EF, et al. Survival after cardiopulmonary
resuscitation in the hospital. N Engl J Med. 1983;309:569576.
7. van Walraven C, Forster AJ, Stiell IG. Derivation of a clinical decision
rule for the discontinuation of in-hospital cardiac arrest resuscitations.
Arch Intern Med. 1999;159:129134.
8. Holmberg M, Holmberg S, Herlitz J. Factors modifying the effect of
bystander cardiopulmonary resuscitation on survival in out-of-hospital
cardiac arrest patients in Sweden. Eur Heart J. 2001;22:511519.
9. Emergency Cardiac Care Committee and Subcommittees. American
Heart Association guidelines for cardiopulmonary resuscitation and
emergency cardiac care.Emergency Cardiac Care Committee and Sub-
committees, American Heart Association. Part III. Adult advanced
cardiac life support. JAMA. 1992;268:21992241.
10. Emergency Cardiac Care Committee and Subcommittees. American
Heart Association guidelines for cardiopulmonary resuscitation and
emergency cardiac care. Emergency Cardiac Care Committee and Sub-
committees, American Heart Association. Part II. Adult basic life sup-
port. JAMA. 1992;268:21842198.
11. Higano ST, Oh JK, Ewy GA, et al. The mechanism of blood ow during
closed chest cardiac massage in humans: transesophageal echocardio-
graphic observations. Mayo Clin Proc. 1990;65:14321440.
12. Babbs CF. CPR techniques that combine chest and abdominal compres-
sion and decompression: hemodynamic insights from a spreadsheet
model. Circulation. 1999;100:21462152.
13. Niemann JT. Differences in cerebral and myocardial perfusion during
closed-chest resuscitation. Ann Emerg Med. 1984;13:849853.
14. Cohen TJ, Goldner BG, Maccaro PC, et al. A comparison of active
compression-decompression cardiopulmonary resuscitation with stan-
dard cardiopulmonary resuscitation for cardiac arrests occurring in the
hospital. N Engl J Med. 1993;329:19181921.
15. Lurie KG, Shultz JJ, Callaham ML, et al. Evaluation of active compres-
sion-decompression CPR in victims of out-of-hospital cardiac arrest.
JAMA. 1994;271:14051411.
16. Wolcke BB, Mauer DK, Schoefmann MF, et al. Comparison of standard
cardiopulmonary resuscitation versus the combination of active com-
pression-decompression cardiopulmonary resuscitation and an inspira-
tory impedance threshold device for out-of-hospital cardiac arrest.
Circulation. 2003;108:22012205.
17. Lafuente-Lafuente C, Melero-Bascones M. Active chest compression-
decompression for cardiopulmonary resuscitation. Cochrane Database
Syst Rev. 2004;CD002751.
18. Myerburg RJ, Conde CA, Sung RJ, et al. Clinical, electrophysiologic
and hemodynamic prole of patients resuscitated from prehospital car-
diac arrest. Am J Med. 1980;68:568576.
19. Birgens HS, Henriksen J, Matzen P, et al. The shock liver. Clinical and
biochemical ndings in patients with centrilobular liver necrosis follow-
ing cardiogenic shock. Acta Med Scand. 1978;204:417421.
20. Wijdicks EF. Neurologic Complications of Critical Illness. 2nd ed.
New York: Oxford University Press; 2002.
21. Adrie C, Laurent I, Monchi M, et al. Postresuscitation disease after
cardiac arrest: a sepsis-like syndrome? Curr Opin Crit Care. 2004;10:
208212.
22. Sundgreen C, Larsen FS, Herzog TM, et al. Autoregulation of cerebral
blood ow in patients resuscitated from cardiac arrest. Stroke. 2001;32:
128132.
23. Miyamoto O, Auer RN. Hypoxia, hyperoxia, ischemia, and brain necro-
sis. Neurology. 2000;54:362371.
24. Sadove MS, Yon MK, Hollinger PH, et al. Severe prolonged cerebral
hypoxic episode with complete recovery. JAMA. 1961;175:11021104.
25. Kogure K, Scheinberg P, Fujishima M, et al. Effects of hypoxia on
cerebral autoregulation. Am J Physiol. 1970;219:13931396.
26. Sloper JJ, Johnson P, Powell TP. Selective degeneration of interneurons
in the motor cortex of infant monkeys following controlled hypoxia: a
possible cause of epilepsy. Brain Res. 1980;198:204209.
27. Petito CK, Feldmann E, Pulsinelli WA, et al. Delayed hippocampal
damage in humans following cardiorespiratory arrest. Neurology. 1987;
37:12811286.
28. Kumar R, Krause GS, Yoshida H, et al. Dysfunction of the unfolded
protein response during global brain ischemia and reperfusion. J Cereb
Blood Flow Metab. 2003;23:462471.
29. Taraszewska A, Zelman IB, Ogonowska W, et al. The pattern of
irreversible brain changes after cardiac arrest in humans. Folia Neuro-
pathol. 2002;40:133141.
30. Cummings JL, Tomiyasu U, Read S, et al. Amnesia with hippocampal
lesions after cardiopulmonary arrest. Neurology. 1984;34:679681.
31. Duggal N, Lach B. Selective vulnerability of the lumbosacral spinal cord
after cardiac arrest and hypotension. Stroke. 2002;33:116121.
32. Levy DE, Caronna JJ, Singer BH, et al. Predicting outcome from
hypoxic-ischemic coma. JAMA. 1985;253:14201426.
33. Longstreth WT Jr, Inui TS, Cobb LA, et al. Neurologic recovery after
out-of-hospital cardiac arrest. Ann Intern Med. 1983;98:588592.
34. Elting JW, Haaxma R, Sulter G, et al. Predicting outcome from coma:
man-in-the-barrel syndrome as potential pitfall. Clin Neurol Neurosurg.
2000;102:2325.
35. Zhao D, Weil MH, Tang W, et al. Pupil diameter and light reaction
during cardiac arrest and resuscitation. Crit Care Med. 2001;29:825
898.
36. Snyder BD, Gumnit RJ, Leppik IE, et al. Neurologic prognosis after
cardiopulmonary arrest: IV. Brainstem reexes. Neurology. 1981;31:
10921097.
37. Keane JR. Sustained upgaze in coma. Ann Neurol. 1981;9:409412.
38. Johkura K, Komiyama A, Kuroriwa Y. Sustained downgaze in coma
after cardiac arrest. J Neurol Neurosurg Psychiatry. 2001;71:278279.
39. Diesing TS, Wijdicks EF. Ping-pong gaze in coma may not indicate
persistent hemispheric damage. Neurology. 2004;63:15371538.
40. Wijdicks EF, Parisi JE, Sharbrough FW. Prognostic value of myoclonus
status in comatose survivors of cardiac arrest. Ann Neurol. 1994;35:
239243.
41. Rollinson RD, Gilligan BS. Postanoxic action myoclonus (Lance-Adams
syndrome) responding to valproate. Arch Neurol. 1979;36:4445.
42. Coletti A, Mandelli A, Minoli G, et al. Post-anoxic action myoclonus
(Lance-Adams syndrome) treated with levodopa and GABA-ergic drugs.
J Neurol. 1980;223:6770.
43. Krauss GL, Bergin A, Kramer RE, et al. Suppression of post-hypoxic
and post-encephalitic myoclonus with levetiracetam. Neurology. 2001;
56:411412.
44. Gatzonis SD, Zournas C, Michalopoulos A, et al. Area-selective
stimulus-provoked seizures in post-anoxic coma. Seizure. 2002;11:
294297.
45. Zandbergen EG, de Haan RJ, Stoutenbeek CP, et al. Systematic review
of early prediction of poor outcome in anoxic-ischaemic coma. Lancet.
1998;352:18081812.
46. Cummins RO, Eisenberg MS, Hallstrom AP, et al. Survival of out-of-
hospital cardiac arrest with early initiation of cardiopulmonary resusci-
tation. Am J Emerg Med. 1985;3:114119.
47. Murphy DJ, Murray AM, Robinson BE, et al. Outcomes of cardiopul-
monary resuscitation in the elderly. Ann Intern Med. 1989;111:199205.
48. Herlitz J, Eek M, Engdahl J, et al. Factors at resuscitation and outcome
among patients suffering from out of hospital cardiac arrest in relation to
age. Resuscitation. 2003;58:309317.
Maramattom and Wijdicks The Neurologist Volume 11, Number 4, July 2005
2005 Lippincott Williams & Wilkins 242
49. Earnest MP, Yarnell PR, Merrill SL, et al. Long-term survival and
neurologic status after resuscitation from out-of-hospital cardiac arrest.
Neurology. 1980;30:12981302.
50. Myrianthefs P, Kalafati M, Lemonidou C, et al. Efcacy of CPR in a
general, adult ICU. Resuscitation. 2003;57:4348.
51. Jorgensen EO, Holm S. The natural course of neurological recovery
following cardiopulmonary resuscitation. Resuscitation. 1998;36:111
122.
52. Kuroiwa Y, Celesia GG. Clinical signicance of periodic EEG patterns.
Arch Neurol. 1980;37:1520.
53. Young GB. The EEG in coma. J Clin Neurophysiol. 2000;17:473485.
54. Nilsson BY, Olsson Y, Sourander P. Electroencephalographic and his-
topathological changes resembling Jakob-Creutzfeldt disease after tran-
sient cerebral ischemia due to cardiac arrest. Acta Neurol Scand. 1972;
48:416426.
55. Young GB, Blume WT, Campbell VM, et al. Alpha, theta and alpha-
theta coma: a clinical outcome study utilizing serial recordings. Elec-
troencephalogr Clin Neurophysiol. 1994;91:9399.
56. Gendo A, Kramer L, Hafner M, et al. Time-dependency of sensory
evoked potentials in comatose cardiac arrest survivors. Intensive Care
Med. 2001;27:13051311.
57. Nakabayashi M, Kurokawa A, Yamamoto Y. Immediate prediction of
recovery of consciousness after cardiac arrest. Intensive Care Med.
2001;27:12101214.
58. Kjos BO, Brant-Zawadzki M, Young RG. Early CT ndings of global
central nervous system hypoperfusion. AJR Am J Roentgenol. 1983;141:
12271232.
59. Brancatelli G, Lagalla R. Reversal sign after cardiopulmonary arrest.
J Neurol Neurosurg Psychiatry. 2000;68:525.
60. Bird CR, Drayer BP, Gilles FH. Pathophysiology of reverse edema in
global cerebral ischemia. AJNR Am J Neuroradiol. 1989;10:9598.
61. Singhal AB, Topcuoglu MA, Koroshetz WJ. Diffusion MRI in three
types of anoxic encephalopathy. J Neurol Sci. 2002;196:3740.
62. Wijdicks EF, Campeau NG, Miller GM. MR imaging in comatose
survivors of cardiac resuscitation. AJNR Am J Neuroradiol. 2001;22:
15611565.
63. Fujioka M, Okuchi K, Sakaki T, et al. Specic changes in human brain
following reperfusion after cardiac arrest. Stroke. 1994;25:20912095.
64. Arbelaez A, Castillo M, Mukherji SK. Diffusion-weighted MR imaging
of global cerebral anoxia. AJNR Am J Neuroradiol. 1999;20:9991007.
65. De Reuck J, Decoo D, Vienne J, et al. Signicance of white matter
lucencies in posthypoxic-ischemic encephalopathy: comparison of clin-
ical status and of computed and positron emission tomographic ndings.
Eur Neurol. 1992;32:334339.
66. Edgren E, Enblad P, Grenvik A, et al. Cerebral blood ow and metab-
olism after cardiopulmonary resuscitation. A pathophysiologic and prog-
nostic positron emission tomography pilot study. Resuscitation. 2003;
57:161170.
67. Schaafsma A, de Jong BM, Bams JL, et al. Cerebral perfusion and
metabolism in resuscitated patients with severe post-hypoxic encepha-
lopathy. J Neurol Sci. 2003;210:2330.
68. Gueugniaud PY, Mols P, Goldstein P, et al. A comparison of repeated
high doses and repeated standard doses of epinephrine for cardiac arrest
outside the hospital. European Epinephrine Study Group. N Engl J Med.
1998;339:15951601.
69. Duckrow RB, Beard DC, Brennan RW. Regional cerebral blood ow
decreases during chronic and acute hyperglycemia. Stroke. 1987;18:
5258.
70. Mullner M, Sterz F, Binder M, et al. Blood glucose concentration after
cardiopulmonary resuscitation inuences functional neurological recov-
ery in human cardiac arrest survivors. J Cereb Blood Flow Metab.
1997;17:430436.
71. Longstreth WT Jr, Copass MK, Dennis LK, et al. Intravenous glucose
after out-of-hospital cardiopulmonary arrest: a community-based ran-
domized trial. Neurology. 1993;43:25342541.
72. Wijdicks EF. Propofol in myoclonus status epilepticus in comatose
patients following cardiac resuscitation. J Neurol Neurosurg Psychiatry.
2002;73:9495.
73. Crumrine RC, Bergstrand K, Cooper AT, et al. Lamotrigine protects
hippocampal CA1 neurons from ischemic damage after cardiac arrest.
Stroke. 1997;28:22302236. Discussion.Stroke.1997;28:2237.
74. Sakabe T, Tateishi A, Miyauchi Y, et al. Intracranial pressure following
cardiopulmonary resuscitation. Intensive Care Med. 1987;13:256259.
75. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypo-
thermia to improve the neurologic outcome after cardiac arrest. N Engl
J Med. 2002;346:549556.
76. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survi-
vors of out-of-hospital cardiac arrest with induced hypothermia. N Engl
J Med. 2002;346:557563.
77. Winfree CJ, Baker CJ, Connolly ES Jr, et al. Mild hypothermia reduces
penumbral glutamate levels in the rat permanent focal cerebral ischemia
model. Neurosurgery. 1996;38:12161222.
78. Rajek A, Greif R, Sessler DI, et al. Core cooling by central venous
infusion of ice-cold (4 degrees C and 20 degrees C) uid: isolation of
core and peripheral thermal compartments. Anesthesiology. 2000;93:
629637.
79. Wijdicks EF. Induced hypothermia in neurocatastrophies: feeling the
chill. Rev Neurol Dis. 2004;1:1015.
80. Bernard SA, Buist M. Induced hypothermia in critical care medicine: a
review. Crit Care Med. 2003;31:20412051.
81. Takasu A, Saitoh D, Kaneko N, et al. Hyperthermia: is it an ominous
sign after cardiac arrest? Resuscitation. 2001;49:273277.
82. Zeiner A, Holzer M, Sterz F, et al. Hyperthermia after cardiac arrest is
associated with an unfavorable neurologic outcome. Arch Intern Med.
2001;161:20072012.
83. Fatovich DM, Dobb GJ, Clugston RA. A pilot randomised trial of
thrombolysis in cardiac arrest (The TICA trial). Resuscitation. 2004;61:
309313.
84. Damian MS, Ellenberg D, Gildemeister, et al. Coenzyme Q10 combined
with mild hypothermia after cardiac arrest: a preliminary study. Circu-
lation. 2004;110:30113016.
The Neurologist Volume 11, Number 4, July 2005 Postresuscitation Encephalopathy
2005 Lippincott Williams & Wilkins 243