Multidisciplinary

Management of the
P o s t – C a rd i a c A r res t P a t i e n t
Ryan D. Madder, MDa, Joshua C. Reynolds, MD, MSb,*

KEYWORDS
 Cardiac arrest  Post cardiac arrest  Post–cardiac arrest syndrome
 Targeted temperature management  Neurologic prognostication  Cardiogenic shock
 Emergency revascularization  Mechanical circulatory support

KEY POINTS
 Post–cardiac arrest patients present with varying degrees of injury within 4 domains: hypoxic brain
injury, whole-body ischemia–reperfusion injury, myocardial dysfunction, and the underlying etiology
of cardiac arrest.
 Systematic, brain-oriented intensive care is likely more important than a single therapeutic interven-
tion to minimize secondary brain injury and maximize neurologic recovery.
 Neurologic prognostication is best conducted to include serial clinical examinations, imaging, and
neurophysiologic studies. Short of brain death, neurologic recovery continues over a period of at
least 3 days.
 Most post–cardiac arrest patients require pharmacologic circulatory support, many require
coronary revascularization, and some require mechanical circulatory support.
 The association between early revascularization and improved outcomes, the high prevalence of
acute obstructive lesions, and the poor negative predictive value of the postarrest ECG support
the consideration of early coronary angiography in post–cardiac arrest patients.

OVERVIEW AND GOALS OF CARE
The management of the post–cardiac arrest
patient is complex, and addresses multiple key is-
sues simultaneously: diagnosing and treating the
etiology, minimizing hypoxic brain injury, address-
ing sequelae of global ischemia–reperfusion injury,
and managing cardiovascular dysfunction. The
goal of clinical practice is to restore patients to
full consciousness and function, which also neces-
sitates robust, multimodal neurologic prognostica-
tion. Regional efforts to improve resuscitation
practices at multiple levels, including post–cardiac
arrest care, have yielded significant improvements
in meaningful survival.1,2 Thus, an organized and
evidence-based approach to post–cardiac arrest
intensive care management and post–intensive
care recovery is warranted.
PATHOPHYSIOLOGY
The core pathophysiology of the post–cardiac
arrest syndrome centers around 4 components:
hypoxic brain injury, systemic ischemia–reperfu-
sion injury, myocardial dysfunction, and the under-
lying etiology of cardiac arrest. Patients present
cardiology.theclinics.com

Disclosure Statement: R.D. Madder and J.C. Reynolds have nothing they wish to disclose.
a
Frederik Meijer Heart and Vascular Institute, Spectrum Health, 100 Michigan Street Northeast, Grand Rapids,
MI 49503, USA; b Department of Emergency Medicine, Michigan State University College of Human Medicine,
15 Michigan Street Northeast, Suite 735, Grand Rapids, MI 49503, USA
* Corresponding author.
E-mail address: reyno406@msu.edu

Cardiol Clin 36 (2018) 85–101

https://doi.org/10.1016/j.ccl.2017.08.005
0733-8651/18/Ó 2017 Elsevier Inc. All rights reserved.
86 Madder & Reynolds
with varying degrees of injury along each of these
domains.3 Understanding the clinical manifesta-
tions of these domains is useful to recognize signs
of injury and guide appropriate therapy.
Hypoxic Brain Injury
Brain injury after ischemia is an active process that
develops over hours to days after resuscitation.
Multiple cellular and molecular mechanisms
contribute to this brain injury, including release of
excitatory amino acids and free radicals, energy
failure, inhibition of protein synthesis, and focal
disturbances of cerebral blood flow.4–6 Specific
intracellular and extracellular signaling pathways
are activated for several hours after brain
ischemia,7,8 which may lead to specific changes
in gene transcription. The relative contribution of
each of these processes to neuronal injury and
their potential as targets for therapeutic interven-
tion are unknown.
During the first day after resuscitation from car-
diac arrest, patients commonly exhibit increased
cerebral vascular resistance and impaired cerebral
autoregulation.9–11 When autoregulation is pre-
sent, it is right shifted such that cerebral perfusion
pressure declines when the mean arterial pressure
(MAP) decreases below 80 to 120 mm Hg. When
blood pressure is maintained, regional perfusion
remains matched to metabolic activity after car-
diac arrest on PET.12,13 Thus, available data indi-
cate that optimal perfusion of the brain requires a
higher MAP than normal during the first hours to
days after cardiac arrest. Conversely, the cerebro-
vascular bed typically retains sensitivity to the par-
tial pressure of carbon dioxide (PaCO2).14
Hyperventilation and a subsequent decrease in
PaCO2 lead to cerebrovascular constriction and a
decrease in cerebral blood flow.15
More severe anoxic brain injury manifests as ce-
rebral edema. It is unclear whether this results
from increased vascular permeability leading to
extravasation of fluid (vasogenic edema), changes
in ion flow owing to excitotoxicity (cytotoxic
edema), or both. Gray matter is more vulnerable
to ischemia than white matter owing to its higher
metabolic rate, greater blood flow, and suscepti-
bility to excitotoxicity.16,17 The degree of cerebral
edema can be quantified by the ratio of attenuation
of gray matter to white matter (GWR) on computed
tomography using the average attenuation in
Hounsfield units in a region of interest. Increasing
edema results in lower attention of gray matter
and a lower GWR. Interestingly, basal ganglia
GWR and cerebrum GWR can vary independently
of each other, suggesting regional differences in
propensity for edema.18
Seizures are diagnosed clinically in 5% to 20%
of comatose patients after cardiac arrest19,20 and
the true incidence of nonconvulsive electrographic
seizures may be higher. Electroencephalographic
seizures are commonly categorized as “malig-
nant” electroencephalographic (EEG) patterns,
along with status epilepticus (seizures
lasting >5 minutes), generalized periodic dis-
charges (generalized discharges <3 Hz not satis-
fying criteria for seizure), epileptiform discharges
(spikes or sharp waves not satisfying criteria for
seizure), and myoclonic status epilepticus
(myoclonic jerks or facial movements synchro-
nized with EEG bursts).21 It is important to distin-
guish a burst-suppression pattern (discontinuous
EEG background with alternating periods of bursts
and suppression of cerebral activity) from true
myoclonic status (body movements synchronized
to the EEG bursts). Burst suppression in and of
itself is not necessarily malignant; it is associated
with pharmacologic sedation or mild induced
hypothermia, 2 common entities in post–cardiac
arrest patients.
Systemic Ischemia–Reperfusion Injury
As might be expected, whole-body ischemia and
reperfusion activates a variety of inflammatory
pathways, and the clinical sequelae are similar
to the systemic inflammatory response syn-
drome. Changes in various cytokines, soluble
receptors, adhesion molecules, and selectins
have been described, suggesting leukocyte acti-
vation and endothelial injury.22 Ultimately, the
commonly observed clinical manifestations
include vasoplegia, hypercoagulability, microcir-
culatory dysfunction, adrenal suppression, and
immunosuppression.
Vasoplegia is very common after resuscitation
from cardiac arrest, and is likely related to endo-
thelial dysfunction. One large cohort study found
that nearly one-half of patients received some
vasopressor support during the first 24 hours after
cardiac arrest.23 Cardiac arrest is also associated
with activated coagulation that is not balanced by
fibrinolysis. The hematologic profile is reminiscent
of disseminated intravascular coagulation, which
may contribute to subsequent end-organ dysfunc-
tion through microcirculatory dysfunction. Markers
of thrombogenesis are not balanced by fibrinolytic
factors for at least 24 hours.24–26 At present, use of
anticoagulation is variable, and there are no pro-
spective trials evaluating the effect of empiric anti-
coagulation after resuscitation. Anticoagulation
and even fibrinolytic drugs are safe after cardiopul-
monary resuscitation.25,27,28 One retrospective se-
ries noted a univariate relationship between
 Management of the Post–Cardiac Arrest Patient
anticoagulation and 6-month survival that was not
significant in a multivariate model.29 Given the
hematologic evidence of active thrombogenesis,
anticoagulation should be used whenever any
thrombotic etiology is possible.
Relative adrenal insufficiency is common after
cardiac arrest, defined as failure to respond to
corticotrophin despite increased plasma cortisol
levels.30,31 One observational study found that
basal cortisol levels after return of spontaneous
circulation (ROSC) were lower in patients who sub-
sequently died from early refractory shock
compared with patients who died later from neuro-
logic injury.30 Both an ischemia-triggered systemic
inflammatory response and infections are com-
mon after cardiac arrest.32 Thus, the accurate
diagnosis of post–cardiac arrest infections is
hampered by an associated increase in inflamma-
tory markers and body temperature.33,34 Transient
bacteremia occurs in 39% of patients during the
first 12 hours after resuscitation.35 The most com-
mon infectious complications in post–cardiac ar-
rest patients are pneumonia, bloodstream
infections, and catheter-related infections.36,37
Post–cardiac arrest pneumonia is associated
with the duration of mechanical ventilation and
duration of intensive care unit stay, but does not
seem to have an impact on mortality or neurologic
outcome.32,36,37 Despite these observations, the
role of prophylactic antibiotics or antipyretics is
unknown, and selective treatment of identified
infections is reasonable.
Myocardial Dysfunction
Oxidative stress during ischemia and reperfusion
leads to myocyte injury, which generally peaks 8
to 24 hours after cardiac arrest.38 Hemodynamics
are often variable immediately after ROSC as
transient surges in endogenous and exogenous
catecholamines stabilize. Any regional injury from
an acute coronary occlusion may be superim-
posed on this global injury. Clinically, myocardial
dysfunction manifests as global myocardial
stunning and hypokinesis, with decreased stroke
volume, decreased cardiac output, and increased
left ventricular end-diastolic pressure.39,40 The
global dysfunction is usually transient and re-
covers completely or near completely in 24 to
48 hours.40 Occasionally, patients will experience
more sustained depression of ejection fraction
over weeks to months.41 The period of depressed
cardiac output is responsive to inotropic medica-
tions, but depending on the severity of injury, can
evolve into frank cardiogenic shock requiring mul-
tiple inotropes and/or mechanical circulatory
support.
87
Underlying Etiology of Cardiac Arrest
Overarching the post–cardiac arrest syndrome is
the persistent acute pathology that initially
precipitated the cardiac arrest. The most
common etiologies include acute coronary syn-
drome, dysrhythmias, pulmonary disease,
asphyxia, hemorrhage, pulmonary embolism,
electrolyte disturbances, sepsis, and poisoning.
The management of each of these conditions is
beyond the scope of this article, but clinicians
should note that the diagnosis and management
of these etiologies can complicate or be compli-
cated by the simultaneous pathophysiology of
other domains of injury. Specific treatment for
these underlying disturbances must be coordi-
nated with specific support for post–cardiac
arrest neurologic and cardiovascular dysfunction
(Fig. 1).
NEUROLOGIC SUPPORT
Minimizing Secondary Brain Injury
Despite detailed knowledge of the mechanisms
involved with brain ischemia, no drug to date has
demonstrated clear benefit in human trials
(thiopental, lidoflazine, magnesium, and diaz-
epam).42–44 One explanation is that multiple mech-
anisms contribute simultaneously to the process
of ischemic neuronal death. Antagonizing 1
pathway leading to neuronal death may leave
other backup mechanisms unaffected. Thus, less
specific therapies may prove more effective. For
example, 2 prospective randomized clinical trials
found that induction of whole-body mild hypother-
mia (32 C-34 C) for 12 to 24 hours after resuscita-
tion improved survival and neurologic
recovery.19,45 Whether this type of temperature
management itself conferred an actual benefit, or
just served to prevent deleterious hyperthermia,
it is important to note the success of this type of
systemic therapy. Observational data also support
coronary revascularization and meticulous avoid-
ance of hyperthermia, hypotension, hypocarbia,
hypoxia, and hyperglycemia. Taken together, sys-
tematic brain-oriented intensive care, rather than a
single therapeutic drug or intervention, is required
to improve the outcome.
If tolerated by the heart, relative hypertension
(MAP of 80–100 mm Hg) should be considered
using inotropes and/or pressors to prevent brain
hypoperfusion in the setting of impaired autoregu-
lation. Episodes of hypotension after resuscitation
are associated with death and poor neurologic
recovery in postarrest patients.46,47 Conversely, a
higher MAP is associated with survival and better
neurologic recovery.48,49
88 Madder & Reynolds
Fig. 1. Four components of the post–cardiac arrest syndrome and their typical clinical manifestations. ACS, acute
coronary syndrome; EEG, electroencephalography.
Post–cardiac arrest hyperoxia (PaO2 300 mm
Hg) is associated with higher inpatient mortality
than normoxia.50,51 These studies speculate that
high oxygen concentrations increase oxidative
free radical damage. One multicenter cohort study
found a linear, dose-dependent relationship
between levels of oxygen tension and inpatient
mortality, but could not identify a single threshold
for harm.52 In the absence of evidence to support
a specific PaO2 goal for patients, it is reasonable to
titrate FiO2 to the lowest values sufficient to main-
tain normal arterial oxyhemoglobin saturation
(94%–98%). Both hypocapnia (PaCO2 30 mm
Hg) and hypercapnia (PaCO2 50 mm Hg) are inde-
pendently associated with poor neurologic
outcome.53 As in traumatic brain injury, hypoventi-
lation and hyperventilation result in dysfunctional
cerebral perfusion, so it is best to ventilate with a
goal of normocarbia (PaCO2 of 35–45 mm Hg).
Increased serum glucose is common after
cardiac arrest and is associated with poor
outcome,54,55 but hyperglycemia may be simply a
marker of greater illness severity. Both epinephrine
and physiologic stress can elevate serum glucose,
and mild hypothermia may reduce insulin sensi-
tivity.56 However, multivariate models that account
for resuscitation time and medication use still show
an effect of serum glucose on admission and dur-
ing the first 48 hours of intensive care on long-
term outcome.29,57 After cardiac arrest, there was
no difference in outcome when a moderate glucose
was targeted (108–144 mg/dL; 6–8 mmol/L) versus
a strict lower range (72–108 mg/dL; 4–6 mmol/L).58
However, the incidence of hypoglycemic events
was higher in the strict versus moderate control
group (18% vs 2% of patients). Given the available
data, treatment of glucose levels of greater than
180 mg/dL (10 mmol/L) is reasonable.
Targeted Temperature Management
Meticulous temperature control is important dur-
ing the first 24 to 48 hours after ischemic brain
injury. Bacteremia and spontaneous fever are
common in the resuscitated patient, making active
prevention of hyperthermia mandatory.35,59 Fever
prevention is beneficial for injured brain after trau-
matic brain injury, stroke, and cardiac arrest.7,60–62
Mechanistically, mild hypothermia lowers brain
metabolic rate, modifies signaling pathways,
reduces intracranial pressure, and reduces vulner-
ability to seizures.8,63–65
For more than a decade, mild induced hypother-
mia (32 C-34 C) for 12 or 24 hours has been the
cornerstone of post–cardiac arrest intensive
care. Two randomized trials published in 2002,
found a 24% to 30% relative risk reduction for
death or poor neurologic outcome66 and signifi-
cant improvement in the odds of survival and
good neurologic outcome for subjects resusci-
tated from ventricular fibrillation–related cardiac
arrest.19,45 More recently, a large, prospective,
randomized trial comparing a targeted tempera-
ture of 33 C with 36 C found that both groups
had similar mortality and neurologic outcome at
180 days.67–69 The most notable difference
 Management of the Post–Cardiac Arrest Patient
between the 2002 trials compared with the more
recent trial is that the earlier studies did not
adequately control temperature in the control
arm. Temperatures greater than 37 C occurred in
subjects for both control groups, whereas tight
control at 36 C was followed in the more recent
trial. Additionally, the recent trial used a blinded
neurologic assessment along with regimented
decisions about prognosis. Although controlling
temperature at 36 C is not superior to strict tem-
perature control at 33 C, it is not clear which tem-
perature is best for patients who differ from the
study population. Patients in the 33 C versus
36 C trial had very high rates of witnessed cardiac
arrest, bystander cardiopulmonary resuscitation,
and initial shockable rhythm; and very brief inter-
vals from collapse until start of basic life support.
It is possible that unidentified subgroups of
patients may benefit from a specific target temper-
ature or from titrated use of temperature.
Current recommendations are to keep all coma-
tose post–cardiac arrest patients at a constant
target temperature between 32 C and 36 C. This
is different from enforced normothermia and reac-
tive treatment of fever, which is being studied in an
ongoing clinical trial (NCT02908308). It is erro-
neous to assume that selection of 36 C as a target
temperature is synonymous with not managing
temperature or fever prevention without active
control. Active measures require thermostatically
controlled devices, of which there are many.
Importantly, there is no clinical situation where
control of temperature in this range is contraindi-
cated; even bleeding will not be increased at
36 C. At the time of resuscitation, many patients
are already mildly hypothermic, with core temper-
atures between 35 C and 35.5 C.19,45,70 This
spontaneous cooling likely results from mixing of
core and peripheral blood compartments during
circulatory arrest, and patients typically rewarm
within a few hours unless specific interventions
are instituted.60,71 A biological basis demon-
strating that the neurologic benefit of temperature
management is specific to patients with 1 type of
cardiac rhythm has not been identified.
The optimal duration of temperature manage-
ment, the maximum delay in achieving target tem-
peratures, the optimal target temperature, and the
preferred rate of rewarming are unknown. Labora-
tory studies suggest that cooling to between 32 C
and 35 C for 12 to 24 hours is beneficial, particu-
larly if cooling is achieved within 6 hours after
resuscitation. These studies also suggest that
rewarming should be performed slowly (<0.25 C/
h). A regimen similar to the largest clinical trials
(24–28 hours, followed by meticulous fever
suppression for at least 3 days) is reasonable.67
89
After cardiac arrest, temperature management
can be achieved by a variety of techniques,
including surface cooling with ice packs, cooling
blankets, or endovascular devices.45,60,72 Initial
studies using surface cooling alone suggested
that it is slow and may require 4 to 6 hours to reach
34 C.19,61,73 However, neuromuscular blockade
and sedation to prevent shivering greatly acceler-
ates surface cooling.74 There are few direct com-
parisons of surface cooling and endovascular
cooling, but endovascular catheters may provide
more stable control of temperature over
time.75,76 Local cooling of the head is unlikely to
produce brain hypothermia when there is
adequate perfusion by warm core blood,70
although the head can be an effective site for
removing heat from the body.77
Rapid infusion of 30 mL/kg cold (4 C) crystalloid
produces a rapid decrease in core temperature in
post–cardiac arrest patients.71,78–80 Cold fluid
boluses must be administered quickly into the
central circulation (via central line or under pres-
sure infusion via peripheral line). The volume
required may limit this intervention to select pa-
tients. Recent clinical trials show no outcome
benefit when paramedics use cold intravenous
fluids for undifferentiated cardiac arrest patients
before hospital arrival, and did detect an increase
in complications.81–83 Therefore, this intervention
is best used in a hospital critical care setting with
adequate monitoring and resources. The adminis-
tration of cold intravenous fluids only produces a
transient decrease in core temperature, requiring
that a maintenance technique (endovascular or
surface cooling device) be in place after the
infusion.71,80
Induction of cooling can result in peripheral
vasoconstriction, with an apparent reduction in
vascular volume, increase in CVP, and diuresis.84
Rewarming causes vessels to dilate, CVP to
decrease, and the patient to seem relatively hypo-
volemic. Inattention to these fluid shifts was cited
as a pitfall in trials of therapeutic hypothermia for
traumatic brain injury.84 Hypokalemia, hypophos-
phatemia, and hypomagnesemia also occur at
cooling, followed by hyperkalemia at rewarm-
ing.85,86 Frequent monitoring and correction of
electrolytes is warranted.
Primary angioplasty is safe in patients under-
going hypothermia treatment.72,87,88 Mild hypo-
thermia greater than 30 C does not interfere
with defibrillation. Cooling from 37 C to 31 C
actually has a positive inotropic effect, increasing
stroke volume to a greater extent than it
decreases heart rate.89 Clinical data report a
transient 18% decrease in cardiac index with
cooling to 33 C.90
90 Madder & Reynolds
Infections may become more common when
patients are cooled for 24 hours or longer.19,45
Elevations of pancreatic enzymes have been re-
ported in cooled patients, but these changes
resolve with rewarming.19,90 Creatinine clearance
and platelet count may decrease during cooling,
but both parameters normalize with rewarming.90
Although mild hypothermia can inhibit platelet
function and coagulation,91 these changes are of
small magnitude, leading to few bleeding compli-
cations, even in subjects with concurrent trauma
or administration of heparinoids and glycoprotein
IIb/IIIa inhibitors.61,72 Bleeding after hypothermia
and cardiac catheterization was reported in 6.2%
of post–cardiac arrest patients.92 However, mild
hypothermia can inhibit antiplatelet medications
(ticagrelor, prasugrel, and clopidogrel). Early
studies of post–cardiac arrest patients treated
with mild hypothermia and percutaneous coronary
intervention (PCI) found a high incidence of stent
thrombosis (11%–31%), but it was impossible to
distinguish between the relative contributions of
post–cardiac arrest syndrome and iatrogenic
mild hypothermia.93 Subsequent large observa-
tional studies comparing post–cardiac arrest sub-
jects with and without mild hypothermia found no
difference in stent thrombosis (approximately
4%).94 Mild hypothermia seems to disproportion-
ately affect platelet inhibition by clopidogrel
compared with other antiplatelet medications,95
and more stent thrombosis has been observed in
post–cardiac arrest patients under mild hypother-
mia treated with clopidogrel compared with tica-
grelor96 (Box 1).
Seizures
The greatest usefulness of the EEG in post–car-
diac arrest patients is to screen for seizures and
exclude nonconvulsive seizures as an etiology of
unresponsiveness. Termination of seizures, if
possible, allows untainted assessment of the
neurologic examination. Prolonged epileptiform
activity is associated with secondary brain injury
in other disease states, and it is reasonable to
extrapolate this to post–cardiac arrest brain injury.
However, there are no direct comparator studies
to date of treating seizures in post–cardiac arrest
patients. Neither is there evidence to support the
prophylactic use of antiepileptic drugs.44,97,98
There are reports of patients surviving with good
neurologic function after being treated for post–
cardiac arrest seizures or status epilepticus,21
but there is no evidence that one specific drug or
combination of drugs is superior. Fig. 2 contains
one approach to treating post–cardiac arrest
epileptiform activity.
Box 1
Checklist to minimize secondary brain injury
after resuscitation from cardiac arrest
 Obtain baseline neurologic examination
 Brainstem reflexes
 Best motor examination
 Manage temperature (32 C–36 C)
 Intravascular/surface
 Meticulously avoid hyperthermia
 Goal MAP 65 to 80 mm Hg
 Crystalloid before vasopressors
 Additional inotropes as needed
 Normoxia (SaO2 94%–99%)
 Normocarbia (35–45 mm Hg)
 CT head to screen for edema
 Coronary revascularization
 STEMI
 Suspicious non-STEMI
 EEG monitoring
 Treat malignant patterns
 Neuromuscular blockade if needed
Abbreviations: CT, computed tomography; EEG, elec-
troencephalography; MAP, mean arterial pressure;
STEMI, ST-segment elevation myocardial infarction.
Neurologic Prognostication
Most patients with circulatory arrest of more than 1
to 2 minutes will be comatose at initial presenta-
tion, but some of these same patients can recover
and awaken. Signs of neurologic activity immedi-
ately after ROSC are encouraging, but their
absence does not preclude eventual recovery.
Unfortunately, many cardiac arrest survivors fail
to completely awaken and eventually meet criteria
for a persistent vegetative state or minimally
conscious state.99–101 Fewer than 10% of patients
who are hospitalized after cardiac arrest progress
to formal brain death.102
Determining the neurologic prognosis of pa-
tients resuscitated from cardiac arrest has been
the subject of multiple reviews and guideline state-
ments before and after the setting of modern
intensive care.103–107 With advances in post–car-
diac arrest management, good survival has been
reported after some situations previously believed
to have universally poor outcome (eg, seizures,
status myoclonus, and absence of cortical
responses on evoked potentials).21,108 Neurologic
 Management of the Post–Cardiac Arrest Patient 91

Fig. 2. Sample institutional algorithm to treat epileptiform activity. AED, automated external defibrillator; EEG,
electroencephalograph. (From Callaway CW, Reynolds JC. Chapter 50. Cardiopulmonary cerebral resuscitation.
Textbook of critical care. 7th edition. Philadelphia: Elsevier; 2017; with permission.)

recovery continues over a longer time period than
the 3 days recommended in historical publica-
tions.103,104 Therefore, longer periods of support
and observation are appropriate for many patients.
Furthermore, a multimodal approach including
clinical examination, imaging, and neurophysio-
logic studies is useful. In a practical approach,
clinicians can make an initial estimate of the prob-
ability of recovery based on clinical examination.
As more information becomes available from clin-
ical progression, imaging studies, and neurophys-
iological studies, this estimate can be revised up
or down to advise families and proxy decision
makers (Fig. 3). At least daily reevaluation is
required to decide if ongoing therapy is consistent
with the patient’s goals in light of the best estimate
of the probability of various outcomes.
It is important to understand that neurologic
prognostication is prone to cognitive pitfalls and
fallacies. The findings of many post–cardiac arrest
prognostication studies are tainted by frequent
withdrawal of life-sustaining therapies for
perceived (accurately or not) poor neurologic
prognosis. This creates a self-fulfilling prophecy
if providers deciding whether or not to withdraw
support are not blinded to the results of the prog-
nostic tool under investigation. Such self-fulfilling
prophecies are problematic confounders in clinical
research, leading to an overestimation of test per-
formance for the given prognostic tool under
study. In post–cardiac arrest patients, a useful
measure to assess prognostic tools is the false-
positive rate (FPR), that is, the percentage where
a test predicted poor outcome, but the patient
actually had a good outcome. However, there
are unavoidable mathematical constraints on the
confidence intervals around the estimated false
positive rate. Even if one observes no survivors
in a cohort with a certain test result, the sample
size of that subgroup dictates the upper bound
of the binomial confidence interval (CI) around
the 0% point estimate.
By 72 hours, persistent absence of pupillary light
reflex and corneal response are highly predictive
of permanent coma,105,106 but the motor examina-
tion is much less reliable. Motor response less
than flexion at 3 days had FPR 14% (95% CI,
3%-44%) or 8% (95% CI, 2%-25%).21,109 The
presence of myoclonus is not reliable for predict-
ing poor outcome and must be distinguished
92 Madder & Reynolds

Fig. 3. Simplified neurologic prognostication algorithm adopted by the European Resuscitation Council. a At 24
hours or longer after return of spontaneous circulation (ROSC) in patients not treated with targeted tempera-
ture. b See text for details. CI, confidence interval; CT, computed tomography; FPR, false-positive rate; NSE,
neuron-specific enolase; SSEP, somatosensory evoked potential. (Data from Nolan JP, Soar J, Cariou A, et al. Eu-
ropean Resuscitation Council and European Society of Intensive Care Medicine Guidelines for Post-resuscitation
Care 2015: section 5 of the European Resuscitation Council Guidelines for Resuscitation 2015. Resuscitation
2015;95:212; with permission.)

from status myoclonus (persistent, repetitive
myoclonus). Status myoclonus on admission is
associated with death or vegetative state with
0% FPR (95% CI, 0%–14%). Status myoclonus
at 24 hours after cardiac arrest has a more precise
0% FPR (95% CI, 0%–3%).105,106 Similar patterns
of findings are true among patients treated with
therapeutic hypothermia, although longer periods
of observation may be required to clear potential
confounding by sedation. Physiologic response
to targeted temperature management provides
another avenue for insight into the potential for
neurologic recovery. The presence of shivering,
the amount of patient heat generation (derived
from the inverse average water temperature of
cooling devices), and the presence of bradycardia
(<60 beats/min) during the induction and mainte-
nance of temperature management are each asso-
ciated with a favorable neurologic outcome.110–112
Preliminary imaging of the brain, usually a non-
contrast computed tomography scan, is important
to exclude intracranial causes of collapse and
injury incurred at the time of collapse. The exclu-
sion of intracranial hemorrhage is prudent in the
comatose patient before anticoagulation or fibri-
nolysis.113,114 The GWR on the initial brain
computed tomography is associated with survival
and functional outcome.18,115 Whether treatment
of cerebral edema is worthwhile or futile has not
yet been studied. MRI visualizes more subtle
changes after cardiac arrest. Increased cortical
signals of diffusion-weighted images or fluid-
attenuated inversion recovery sequences are
associated with a poor neurologic outcome.116
For patients who remain comatose for several
days and in whom clinical or electrophysiologic
testing is indeterminate, MRI can provide addi-
tional information about the extent of brain injury.
 Management of the Post–Cardiac Arrest Patient
Expectations and enthusiasm for long-term sup-
port may be reduced if extensive cortical lesions
are present, whereas persistence may be justified
if anatomic extent of injury seems to be limited. An
important caveat with the interpretation of all brain
imaging after global ischemia is the differing clin-
ical impact of lesions in different brain regions.
The anatomic complexity of the brain precludes
any simple quantitative relationship between the
number or size of lesions and outcome.
EEG patterns after resuscitation change over
time.20,117 Certain malignant EEG patterns have
a strong association with poor outcome. Specif-
ically, generalized suppression (<20 mV), burst-
suppression pattern associated with generalized
epileptic activity, or diffuse periodic complexes
on a flat background during the first week after
resuscitation are associated with a poor neuro-
logic outcome.118 The presence of these malig-
nant EEG patterns provides information that is
additive with clinical evaluation.119 A detailed
primer on EEG analysis is beyond the scope of
this article, but the quantitative and qualitative
evolution of EEG over time provides prognostic
information that is additive with clinical evalua-
tion.119 Electrophysiologic response to stimuli
also can be used to assess whether cortical re-
gions are intact. The absence of short-latency
(N20) cortical response to somatosensory evoked
potentials is very specific for poor neurologic
outcome (FPR, 0%; 95% CI, 0%–2% among
patients treated with therapeutic hypother-
mia).104,106,118 Like an EEG, somatosensory
evoked potential responses vary with the elapsed
time since resuscitation.117
CARDIOVASCULAR SUPPORT
Most post–cardiac arrest patients require some
type of pharmacologic circulatory support, many
require coronary revascularization, and some
require mechanical circulatory support. It is impor-
tant to recognize that cardiogenic shock is a
self-perpetuating downward spiral and that treat-
ment goals center around restoring adequate
end-organ perfusion and unloading the ventricles.
Ultimately, therapy should match the degree of
shock with a clear plan for the escalation of sup-
port. Further details are provided in the section
of this text on cardiogenic shock.
Medical Management
Titrated resuscitation to specific targets is a
reasonable approach to the medical management
of post–cardiac arrest hemodynamics. Supporting
evidence is primarily observational in nature. As
discussed elsewhere in this article, MAP goals
93
higher than the traditional 65 mm Hg are likely
needed to optimize cerebral perfusion. Unless pre-
cluded by severe myocardial stunning and frank
cardiogenic shock, a MAP of 80 mm Hg or
greater120 is desirable. Volume replacement
should occur with isotonic fluids (hypotonic fluids
can exacerbate cerebral edema) and a bedside
assessment of volume status. Although a central
venous pressure of 8 to 12 mm Hg has historically
been used to denote adequate volume replace-
ment, recent literature calls this measure into
question.121 Other metrics include pulse pressure
variability, sonographic assessment of inferior
vena cava filling, and end-expiratory occlusion
test. There is no evidence demonstrating the supe-
riority of any 1 vasopressor after cardiac arrest.
Commonly used vasopressors include dopamine
(5–20 mg/kg/min), norepinephrine (0.01–1 mg/kg/
min), and epinephrine (0.01–1 mg/kg/min). Dopa-
mine is associated with tachydysrhythmias and
greater mortality in patients with cardiogenic
shock.122 Epinephrine has more positive inotropy
than norepinephrine, but can prolong lactic
acidosis. Thus, we recommend norepinephrine
as a first-line vasopressor for post–cardiac arrest
patients. Additional inotropic support may be
necessary in cases of ongoing shock despite
normalized hemoglobin and MAP (as assessed
by severe global hypokinesis, low SvO2, low urine
output, and/or failure to clear serum lactate).
Commonly used inotropes include dobutamine
(2–15 mg/kg/min) or milrinone (loading dose of 50
mg/kg/min over 10 minutes, then 0.375–0.75 mg/
kg/min). Both medications can precipitate hypo-
tension from vasodilation, and dobutamine may
induce tachydysrhythmias.
Emergency Revascularization Strategies
All cardiac arrest patients with ROSC should have
an electrocardiogram (ECG) performed to assess
for ST-segment elevation myocardial infarction
(STEMI). Large registries of cardiac arrest patients
demonstrate that 26% to 31% of all postarrest pa-
tients have ECG findings consistent with
STEMI.123,124 Immediate coronary angiography
and PCI in cardiac arrest patients with ROSC
and STEMI is supported by a class I recommenda-
tion from the American College of Cardiology and
American Heart Association.125 This recommen-
dation is supported by the high positive predictive
value of ST-segment elevation on the post-ROSC
ECG for a severe underlying coronary artery
lesion.123 Conversely, the post-ROSC ECG has a
poor negative predictive value for identifying
significant underlying coronary artery lesions trig-
gering the cardiac arrest. Hence, the absence of
94 Madder & Reynolds
ST-segment elevation is insufficient to rule out an
underlying culprit coronary lesion. Large registries
demonstrate that 29% to 33% of postarrest pa-
tients without ST-segment elevation on the post-
ROSC ECG who underwent coronary angiography
had a culprit lesion identified that was thought to
be responsible for the cardiac arrest.124,126
Although observational studies overwhelmingly
demonstrate an association between coronary
angiography, improved survival, and improved
neurologic outcome in post–cardiac arrest
patients with or without ST-segment elevation,127
selection bias is inherent in observational studies
of postarrest coronary angiography. There are
currently 4 randomized trials of post–cardiac
arrest coronary angiography underway that should
provide more definitive evidence on this topic.128
In the meantime, the persistent association be-
tween immediate angiography and improved out-
comes combined with the high prevalence of an
acute obstructive lesion support the practice of
strongly considering an early invasive strategy for
post–cardiac arrest patients without ST-segment
elevation and without an obvious extracardiac
etiology.
In contrast, most patients are comatose after
cardiac arrest,124 predisposing them to risk of
death from neurologic injury regardless of coro-
nary intervention. Fortunately, nearly one-half of
those comatose at the time of early revasculariza-
tion eventually survive to hospital discharge and
the majority has favorable neurologic recovery.129
Postprocedural mortality data in post–cardiac ar-
rest patients do not currently distinguish between
different causes of death. Given the lower survival
rate in post–cardiac arrest patients compared with
traditional PCI patients, appropriate early revascu-
larization in post–cardiac arrest patients has the
unintended consequence of increasing total post-
procedural mortality. Performance reporting at
PCI centers is tied to awards, reimbursement,
recognition, public reporting of hospital perfor-
mance, and physician decision making.130,131 To
mitigate the temptation to reduce personal and/
or institutional PCI mortality by avoiding early
revascularization in the post–cardiac arrest pa-
tient, a recent American Heart Association Scienti-
fic Statement recommends tracking post–cardiac
arrest cases separately from other PCI cases.132
Some post–cardiac arrest patients will have
overwhelming injury severity or a terminal combi-
nation of comorbid conditions. In such cases,
emergency revascularization may not be appro-
priate owing to the high likelihood of futility, and
it is appropriate to consult with the interventionalist
before activating STEMI protocols. There are no
official guidelines or consensus statements on
the identification of such patients, but a recent
American College of Cardiology expert panel pro-
posed one algorithm to aid in this decision making
(Fig. 4).133
Mechanical Circulatory Support
Among patients with persistent shock despite
medical management, mechanical circulatory
support should be strongly considered. Historical-
ly, the intraaortic balloon pump was frequently
used for hemodynamic support in cardiac arrest
patients.134 However, a multicenter randomized
controlled trial evaluating the efficacy of the intra-
aortic balloon pump in patients with STEMI and
cardiogenic shock failed to demonstrate a reduc-
tion in 1-year mortality.135 This lack of efficacy is
perhaps not surprising, considering that balloon
counterpulsation does not have a major impact
on cardiac output.136 In contrast, temporary de-
vices that augment left ventricle-to-aorta blood
flow via an axial pump can be rapidly placed
percutaneously and provide superior hemody-
namic support to the intraaortic balloon pump.137
These devices, already in clinical use, can provide
up to 3.5 L/min of blood flow when placed percu-
taneously, and up to 5 L/min of blood flow when
placed surgically.138 Extracorporeal circulatory
support using a venous-to-arterial circuit is an
additional means of providing hemodynamic sup-
port. This option may be preferred in patients with
ongoing cardiopulmonary resuscitation, right heart
failure, or those who cannot be adequately
oxygenated. Ultimately, the means of mechanical
support selected depends on the patients’ hemo-
dynamics, the expected hemodynamic impact of
the device, the ease and rapidity of insertion, un-
derlying comorbidities or contraindications, and
the ultimate goals of support.
REGIONALIZATION OF CARE
It is the opinion of these authors that multidisci-
plinary care of the post–cardiac arrest patient
should occur at a regionalized cardiac arrest cen-
ter. This is not a new model for patients requiring
time-sensitive interventions. Trauma, STEMI, and
acute stroke all take advantage of established,
regionalized systems of care that coordinate pre-
hospital providers with receiving centers.
Community-based hospital providers treat post–
cardiac arrest patients infrequently, given the low
rates of resuscitation in individual communities,
whereas regionalized cardiac arrest centers in-
crease referral volumes, and thereby provider
experience.139 For complex diagnoses or proced-
ures, there is a well-documented positive
 Management of the Post–Cardiac Arrest Patient 95

Fig. 4. Proposed framework to guide decision making for emergency revascularization in post–cardiac arrest pa-
tients. CPR, cardiopulmonary resuscitation; VF, ventricular fibrillation. (From Rab T, Kern KB, Tamis-Holland JE,
et al, Interventional Council, American College of Cardiology. Cardiac arrest: a treatment algorithm for emer-
gency invasive cardiac procedures in the resuscitated comatose patient. J Am Coll Cardiol 2015;66(1):64; with
permission.)

correlation between greater provider experience
and a better patient outcome.140
There is accumulating observational evidence in
both regional and large, population-based cohorts
for improved outcomes when cardiac arrest pa-
tients are treated at regionalized centers.141–143
Even with longer transport intervals, patients trans-
ported to high-volume centers were more likely to
survive to hospital discharge, compared with low-
volume centers. Prehospital transport time does
not seem to impact patient outcome after cardiac
arrest.144,145 Taken together, available data sug-
gest that a modest increase in transport interval
owing to bypassing a closer community hospital is
reasonable. For those patients transferred from a
community hospital to a regional cardiac arrest cen-
ter, the survival benefit seems to offset the risk of a
hypotensive or hypoxic event during transfer.146
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