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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,*

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

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

Disclosure Statement: R.D. Madder and J.C. Reynolds have nothing they wish to disclose.
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

0733-8651/18/Ó 2017 Elsevier Inc. All rights reserved.
86 Madder & Reynolds

with varying degrees of injury along each of these Seizures are diagnosed clinically in 5% to 20%
domains.3 Understanding the clinical manifesta- of comatose patients after cardiac arrest19,20 and
tions of these domains is useful to recognize signs the true incidence of nonconvulsive electrographic
of injury and guide appropriate therapy. seizures may be higher. Electroencephalographic
seizures are commonly categorized as “malig-
nant” electroencephalographic (EEG) patterns,
Hypoxic Brain Injury
along with status epilepticus (seizures
Brain injury after ischemia is an active process that lasting >5 minutes), generalized periodic dis-
develops over hours to days after resuscitation. charges (generalized discharges <3 Hz not satis-
Multiple cellular and molecular mechanisms fying criteria for seizure), epileptiform discharges
contribute to this brain injury, including release of (spikes or sharp waves not satisfying criteria for
excitatory amino acids and free radicals, energy seizure), and myoclonic status epilepticus
failure, inhibition of protein synthesis, and focal (myoclonic jerks or facial movements synchro-
disturbances of cerebral blood flow.4–6 Specific nized with EEG bursts).21 It is important to distin-
intracellular and extracellular signaling pathways guish a burst-suppression pattern (discontinuous
are activated for several hours after brain EEG background with alternating periods of bursts
ischemia,7,8 which may lead to specific changes and suppression of cerebral activity) from true
in gene transcription. The relative contribution of myoclonic status (body movements synchronized
each of these processes to neuronal injury and to the EEG bursts). Burst suppression in and of
their potential as targets for therapeutic interven- itself is not necessarily malignant; it is associated
tion are unknown. with pharmacologic sedation or mild induced
During the first day after resuscitation from car- hypothermia, 2 common entities in post–cardiac
diac arrest, patients commonly exhibit increased arrest patients.
cerebral vascular resistance and impaired cerebral
autoregulation.9–11 When autoregulation is pre-
Systemic Ischemia–Reperfusion Injury
sent, it is right shifted such that cerebral perfusion
pressure declines when the mean arterial pressure As might be expected, whole-body ischemia and
(MAP) decreases below 80 to 120 mm Hg. When reperfusion activates a variety of inflammatory
blood pressure is maintained, regional perfusion pathways, and the clinical sequelae are similar
remains matched to metabolic activity after car- to the systemic inflammatory response syn-
diac arrest on PET.12,13 Thus, available data indi- drome. Changes in various cytokines, soluble
cate that optimal perfusion of the brain requires a receptors, adhesion molecules, and selectins
higher MAP than normal during the first hours to have been described, suggesting leukocyte acti-
days after cardiac arrest. Conversely, the cerebro- vation and endothelial injury.22 Ultimately, the
vascular bed typically retains sensitivity to the par- commonly observed clinical manifestations
tial pressure of carbon dioxide (PaCO2).14 include vasoplegia, hypercoagulability, microcir-
Hyperventilation and a subsequent decrease in culatory dysfunction, adrenal suppression, and
PaCO2 lead to cerebrovascular constriction and a immunosuppression.
decrease in cerebral blood flow.15 Vasoplegia is very common after resuscitation
More severe anoxic brain injury manifests as ce- from cardiac arrest, and is likely related to endo-
rebral edema. It is unclear whether this results thelial dysfunction. One large cohort study found
from increased vascular permeability leading to that nearly one-half of patients received some
extravasation of fluid (vasogenic edema), changes vasopressor support during the first 24 hours after
in ion flow owing to excitotoxicity (cytotoxic cardiac arrest.23 Cardiac arrest is also associated
edema), or both. Gray matter is more vulnerable with activated coagulation that is not balanced by
to ischemia than white matter owing to its higher fibrinolysis. The hematologic profile is reminiscent
metabolic rate, greater blood flow, and suscepti- of disseminated intravascular coagulation, which
bility to excitotoxicity.16,17 The degree of cerebral may contribute to subsequent end-organ dysfunc-
edema can be quantified by the ratio of attenuation tion through microcirculatory dysfunction. Markers
of gray matter to white matter (GWR) on computed of thrombogenesis are not balanced by fibrinolytic
tomography using the average attenuation in factors for at least 24 hours.24–26 At present, use of
Hounsfield units in a region of interest. Increasing anticoagulation is variable, and there are no pro-
edema results in lower attention of gray matter spective trials evaluating the effect of empiric anti-
and a lower GWR. Interestingly, basal ganglia coagulation after resuscitation. Anticoagulation
GWR and cerebrum GWR can vary independently and even fibrinolytic drugs are safe after cardiopul-
of each other, suggesting regional differences in monary resuscitation.25,27,28 One retrospective se-
propensity for edema.18 ries noted a univariate relationship between
Management of the Post–Cardiac Arrest Patient 87

anticoagulation and 6-month survival that was not Underlying Etiology of Cardiac Arrest
significant in a multivariate model.29 Given the
Overarching the post–cardiac arrest syndrome is
hematologic evidence of active thrombogenesis,
the persistent acute pathology that initially
anticoagulation should be used whenever any
precipitated the cardiac arrest. The most
thrombotic etiology is possible.
common etiologies include acute coronary syn-
Relative adrenal insufficiency is common after
drome, dysrhythmias, pulmonary disease,
cardiac arrest, defined as failure to respond to
asphyxia, hemorrhage, pulmonary embolism,
corticotrophin despite increased plasma cortisol
electrolyte disturbances, sepsis, and poisoning.
levels.30,31 One observational study found that
The management of each of these conditions is
basal cortisol levels after return of spontaneous
beyond the scope of this article, but clinicians
circulation (ROSC) were lower in patients who sub-
should note that the diagnosis and management
sequently died from early refractory shock
of these etiologies can complicate or be compli-
compared with patients who died later from neuro-
cated by the simultaneous pathophysiology of
logic injury.30 Both an ischemia-triggered systemic
other domains of injury. Specific treatment for
inflammatory response and infections are com-
these underlying disturbances must be coordi-
mon after cardiac arrest.32 Thus, the accurate
nated with specific support for post–cardiac
diagnosis of post–cardiac arrest infections is
arrest neurologic and cardiovascular dysfunction
hampered by an associated increase in inflamma-
(Fig. 1).
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-
Minimizing Secondary Brain Injury
rest patients are pneumonia, bloodstream
infections, and catheter-related infections.36,37 Despite detailed knowledge of the mechanisms
Post–cardiac arrest pneumonia is associated involved with brain ischemia, no drug to date has
with the duration of mechanical ventilation and demonstrated clear benefit in human trials
duration of intensive care unit stay, but does not (thiopental, lidoflazine, magnesium, and diaz-
seem to have an impact on mortality or neurologic epam).42–44 One explanation is that multiple mech-
outcome.32,36,37 Despite these observations, the anisms contribute simultaneously to the process
role of prophylactic antibiotics or antipyretics is of ischemic neuronal death. Antagonizing 1
unknown, and selective treatment of identified pathway leading to neuronal death may leave
infections is reasonable. other backup mechanisms unaffected. Thus, less
specific therapies may prove more effective. For
example, 2 prospective randomized clinical trials
Myocardial Dysfunction
found that induction of whole-body mild hypother-
Oxidative stress during ischemia and reperfusion mia (32 C-34 C) for 12 to 24 hours after resuscita-
leads to myocyte injury, which generally peaks 8 tion improved survival and neurologic
to 24 hours after cardiac arrest.38 Hemodynamics recovery.19,45 Whether this type of temperature
are often variable immediately after ROSC as management itself conferred an actual benefit, or
transient surges in endogenous and exogenous just served to prevent deleterious hyperthermia,
catecholamines stabilize. Any regional injury from it is important to note the success of this type of
an acute coronary occlusion may be superim- systemic therapy. Observational data also support
posed on this global injury. Clinically, myocardial coronary revascularization and meticulous avoid-
dysfunction manifests as global myocardial ance of hyperthermia, hypotension, hypocarbia,
stunning and hypokinesis, with decreased stroke hypoxia, and hyperglycemia. Taken together, sys-
volume, decreased cardiac output, and increased tematic brain-oriented intensive care, rather than a
left ventricular end-diastolic pressure.39,40 The single therapeutic drug or intervention, is required
global dysfunction is usually transient and re- to improve the outcome.
covers completely or near completely in 24 to If tolerated by the heart, relative hypertension
48 hours.40 Occasionally, patients will experience (MAP of 80–100 mm Hg) should be considered
more sustained depression of ejection fraction using inotropes and/or pressors to prevent brain
over weeks to months.41 The period of depressed hypoperfusion in the setting of impaired autoregu-
cardiac output is responsive to inotropic medica- lation. Episodes of hypotension after resuscitation
tions, but depending on the severity of injury, can are associated with death and poor neurologic
evolve into frank cardiogenic shock requiring mul- recovery in postarrest patients.46,47 Conversely, a
tiple inotropes and/or mechanical circulatory higher MAP is associated with survival and better
support. 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 However, the incidence of hypoglycemic events
Hg) is associated with higher inpatient mortality was higher in the strict versus moderate control
than normoxia.50,51 These studies speculate that group (18% vs 2% of patients). Given the available
high oxygen concentrations increase oxidative data, treatment of glucose levels of greater than
free radical damage. One multicenter cohort study 180 mg/dL (10 mmol/L) is reasonable.
found a linear, dose-dependent relationship
between levels of oxygen tension and inpatient
Targeted Temperature Management
mortality, but could not identify a single threshold
for harm.52 In the absence of evidence to support Meticulous temperature control is important dur-
a specific PaO2 goal for patients, it is reasonable to ing the first 24 to 48 hours after ischemic brain
titrate FiO2 to the lowest values sufficient to main- injury. Bacteremia and spontaneous fever are
tain normal arterial oxyhemoglobin saturation common in the resuscitated patient, making active
(94%–98%). Both hypocapnia (PaCO2 30 mm prevention of hyperthermia mandatory.35,59 Fever
Hg) and hypercapnia (PaCO2 50 mm Hg) are inde- prevention is beneficial for injured brain after trau-
pendently associated with poor neurologic matic brain injury, stroke, and cardiac arrest.7,60–62
outcome.53 As in traumatic brain injury, hypoventi- Mechanistically, mild hypothermia lowers brain
lation and hyperventilation result in dysfunctional metabolic rate, modifies signaling pathways,
cerebral perfusion, so it is best to ventilate with a reduces intracranial pressure, and reduces vulner-
goal of normocarbia (PaCO2 of 35–45 mm Hg). ability to seizures.8,63–65
Increased serum glucose is common after For more than a decade, mild induced hypother-
cardiac arrest and is associated with poor mia (32 C-34 C) for 12 or 24 hours has been the
outcome,54,55 but hyperglycemia may be simply a cornerstone of post–cardiac arrest intensive
marker of greater illness severity. Both epinephrine care. Two randomized trials published in 2002,
and physiologic stress can elevate serum glucose, found a 24% to 30% relative risk reduction for
and mild hypothermia may reduce insulin sensi- death or poor neurologic outcome66 and signifi-
tivity.56 However, multivariate models that account cant improvement in the odds of survival and
for resuscitation time and medication use still show good neurologic outcome for subjects resusci-
an effect of serum glucose on admission and dur- tated from ventricular fibrillation–related cardiac
ing the first 48 hours of intensive care on long- arrest.19,45 More recently, a large, prospective,
term outcome.29,57 After cardiac arrest, there was randomized trial comparing a targeted tempera-
no difference in outcome when a moderate glucose ture of 33 C with 36 C found that both groups
was targeted (108–144 mg/dL; 6–8 mmol/L) versus had similar mortality and neurologic outcome at
a strict lower range (72–108 mg/dL; 4–6 mmol/L).58 180 days.67–69 The most notable difference
Management of the Post–Cardiac Arrest Patient 89

between the 2002 trials compared with the more After cardiac arrest, temperature management
recent trial is that the earlier studies did not can be achieved by a variety of techniques,
adequately control temperature in the control including surface cooling with ice packs, cooling
arm. Temperatures greater than 37 C occurred in blankets, or endovascular devices.45,60,72 Initial
subjects for both control groups, whereas tight studies using surface cooling alone suggested
control at 36 C was followed in the more recent that it is slow and may require 4 to 6 hours to reach
trial. Additionally, the recent trial used a blinded 34 C.19,61,73 However, neuromuscular blockade
neurologic assessment along with regimented and sedation to prevent shivering greatly acceler-
decisions about prognosis. Although controlling ates surface cooling.74 There are few direct com-
temperature at 36 C is not superior to strict tem- parisons of surface cooling and endovascular
perature control at 33 C, it is not clear which tem- cooling, but endovascular catheters may provide
perature is best for patients who differ from the more stable control of temperature over
study population. Patients in the 33 C versus time.75,76 Local cooling of the head is unlikely to
36 C trial had very high rates of witnessed cardiac produce brain hypothermia when there is
arrest, bystander cardiopulmonary resuscitation, adequate perfusion by warm core blood,70
and initial shockable rhythm; and very brief inter- although the head can be an effective site for
vals from collapse until start of basic life support. removing heat from the body.77
It is possible that unidentified subgroups of Rapid infusion of 30 mL/kg cold (4 C) crystalloid
patients may benefit from a specific target temper- produces a rapid decrease in core temperature in
ature or from titrated use of temperature. post–cardiac arrest patients.71,78–80 Cold fluid
Current recommendations are to keep all coma- boluses must be administered quickly into the
tose post–cardiac arrest patients at a constant central circulation (via central line or under pres-
target temperature between 32 C and 36 C. This sure infusion via peripheral line). The volume
is different from enforced normothermia and reac- required may limit this intervention to select pa-
tive treatment of fever, which is being studied in an tients. Recent clinical trials show no outcome
ongoing clinical trial (NCT02908308). It is erro- benefit when paramedics use cold intravenous
neous to assume that selection of 36 C as a target fluids for undifferentiated cardiac arrest patients
temperature is synonymous with not managing before hospital arrival, and did detect an increase
temperature or fever prevention without active in complications.81–83 Therefore, this intervention
control. Active measures require thermostatically is best used in a hospital critical care setting with
controlled devices, of which there are many. adequate monitoring and resources. The adminis-
Importantly, there is no clinical situation where tration of cold intravenous fluids only produces a
control of temperature in this range is contraindi- transient decrease in core temperature, requiring
cated; even bleeding will not be increased at that a maintenance technique (endovascular or
36 C. At the time of resuscitation, many patients surface cooling device) be in place after the
are already mildly hypothermic, with core temper- infusion.71,80
atures between 35 C and 35.5 C.19,45,70 This Induction of cooling can result in peripheral
spontaneous cooling likely results from mixing of vasoconstriction, with an apparent reduction in
core and peripheral blood compartments during vascular volume, increase in CVP, and diuresis.84
circulatory arrest, and patients typically rewarm Rewarming causes vessels to dilate, CVP to
within a few hours unless specific interventions decrease, and the patient to seem relatively hypo-
are instituted.60,71 A biological basis demon- volemic. Inattention to these fluid shifts was cited
strating that the neurologic benefit of temperature as a pitfall in trials of therapeutic hypothermia for
management is specific to patients with 1 type of traumatic brain injury.84 Hypokalemia, hypophos-
cardiac rhythm has not been identified. phatemia, and hypomagnesemia also occur at
The optimal duration of temperature manage- cooling, followed by hyperkalemia at rewarm-
ment, the maximum delay in achieving target tem- ing.85,86 Frequent monitoring and correction of
peratures, the optimal target temperature, and the electrolytes is warranted.
preferred rate of rewarming are unknown. Labora- Primary angioplasty is safe in patients under-
tory studies suggest that cooling to between 32 C going hypothermia treatment.72,87,88 Mild hypo-
and 35 C for 12 to 24 hours is beneficial, particu- thermia greater than 30 C does not interfere
larly if cooling is achieved within 6 hours after with defibrillation. Cooling from 37 C to 31 C
resuscitation. These studies also suggest that actually has a positive inotropic effect, increasing
rewarming should be performed slowly (<0.25 C/ stroke volume to a greater extent than it
h). A regimen similar to the largest clinical trials decreases heart rate.89 Clinical data report a
(24–28 hours, followed by meticulous fever transient 18% decrease in cardiac index with
suppression for at least 3 days) is reasonable.67 cooling to 33 C.90
90 Madder & Reynolds

Infections may become more common when Box 1

patients are cooled for 24 hours or longer.19,45 Checklist to minimize secondary brain injury
Elevations of pancreatic enzymes have been re- after resuscitation from cardiac arrest
ported in cooled patients, but these changes
resolve with rewarming.19,90 Creatinine clearance  Obtain baseline neurologic examination
and platelet count may decrease during cooling,  Brainstem reflexes
but both parameters normalize with rewarming.90
 Best motor examination
Although mild hypothermia can inhibit platelet
function and coagulation,91 these changes are of  Manage temperature (32 C–36 C)
small magnitude, leading to few bleeding compli-  Intravascular/surface
cations, even in subjects with concurrent trauma
 Meticulously avoid hyperthermia
or administration of heparinoids and glycoprotein
IIb/IIIa inhibitors.61,72 Bleeding after hypothermia  Goal MAP 65 to 80 mm Hg
and cardiac catheterization was reported in 6.2%  Crystalloid before vasopressors
of post–cardiac arrest patients.92 However, mild
 Additional inotropes as needed
hypothermia can inhibit antiplatelet medications
(ticagrelor, prasugrel, and clopidogrel). Early  Normoxia (SaO2 94%–99%)
studies of post–cardiac arrest patients treated  Normocarbia (35–45 mm Hg)
with mild hypothermia and percutaneous coronary  CT head to screen for edema
intervention (PCI) found a high incidence of stent
thrombosis (11%–31%), but it was impossible to  Coronary revascularization
distinguish between the relative contributions of  STEMI
post–cardiac arrest syndrome and iatrogenic  Suspicious non-STEMI
mild hypothermia.93 Subsequent large observa-
tional studies comparing post–cardiac arrest sub-  EEG monitoring
jects with and without mild hypothermia found no  Treat malignant patterns
difference in stent thrombosis (approximately  Neuromuscular blockade if needed
4%).94 Mild hypothermia seems to disproportion-
ately affect platelet inhibition by clopidogrel Abbreviations: CT, computed tomography; EEG, elec-
troencephalography; MAP, mean arterial pressure;
compared with other antiplatelet medications,95
STEMI, ST-segment elevation myocardial infarction.
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).
Neurologic Prognostication
Most patients with circulatory arrest of more than 1
to 2 minutes will be comatose at initial presenta-
The greatest usefulness of the EEG in post–car- tion, but some of these same patients can recover
diac arrest patients is to screen for seizures and and awaken. Signs of neurologic activity immedi-
exclude nonconvulsive seizures as an etiology of ately after ROSC are encouraging, but their
unresponsiveness. Termination of seizures, if absence does not preclude eventual recovery.
possible, allows untainted assessment of the Unfortunately, many cardiac arrest survivors fail
neurologic examination. Prolonged epileptiform to completely awaken and eventually meet criteria
activity is associated with secondary brain injury for a persistent vegetative state or minimally
in other disease states, and it is reasonable to conscious state.99–101 Fewer than 10% of patients
extrapolate this to post–cardiac arrest brain injury. who are hospitalized after cardiac arrest progress
However, there are no direct comparator studies to formal brain death.102
to date of treating seizures in post–cardiac arrest Determining the neurologic prognosis of pa-
patients. Neither is there evidence to support the tients resuscitated from cardiac arrest has been
prophylactic use of antiepileptic drugs.44,97,98 the subject of multiple reviews and guideline state-
There are reports of patients surviving with good ments before and after the setting of modern
neurologic function after being treated for post– intensive care.103–107 With advances in post–car-
cardiac arrest seizures or status epilepticus,21 diac arrest management, good survival has been
but there is no evidence that one specific drug or reported after some situations previously believed
combination of drugs is superior. Fig. 2 contains to have universally poor outcome (eg, seizures,
one approach to treating post–cardiac arrest status myoclonus, and absence of cortical
epileptiform activity. 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 support are not blinded to the results of the prog-
the 3 days recommended in historical publica- nostic tool under investigation. Such self-fulfilling
tions.103,104 Therefore, longer periods of support prophecies are problematic confounders in clinical
and observation are appropriate for many patients. research, leading to an overestimation of test per-
Furthermore, a multimodal approach including formance for the given prognostic tool under
clinical examination, imaging, and neurophysio- study. In post–cardiac arrest patients, a useful
logic studies is useful. In a practical approach, measure to assess prognostic tools is the false-
clinicians can make an initial estimate of the prob- positive rate (FPR), that is, the percentage where
ability of recovery based on clinical examination. a test predicted poor outcome, but the patient
As more information becomes available from clin- actually had a good outcome. However, there
ical progression, imaging studies, and neurophys- are unavoidable mathematical constraints on the
iological studies, this estimate can be revised up confidence intervals around the estimated false
or down to advise families and proxy decision positive rate. Even if one observes no survivors
makers (Fig. 3). At least daily reevaluation is in a cohort with a certain test result, the sample
required to decide if ongoing therapy is consistent size of that subgroup dictates the upper bound
with the patient’s goals in light of the best estimate of the binomial confidence interval (CI) around
of the probability of various outcomes. the 0% point estimate.
It is important to understand that neurologic By 72 hours, persistent absence of pupillary light
prognostication is prone to cognitive pitfalls and reflex and corneal response are highly predictive
fallacies. The findings of many post–cardiac arrest of permanent coma,105,106 but the motor examina-
prognostication studies are tainted by frequent tion is much less reliable. Motor response less
withdrawal of life-sustaining therapies for than flexion at 3 days had FPR 14% (95% CI,
perceived (accurately or not) poor neurologic 3%-44%) or 8% (95% CI, 2%-25%).21,109 The
prognosis. This creates a self-fulfilling prophecy presence of myoclonus is not reliable for predict-
if providers deciding whether or not to withdraw 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 Preliminary imaging of the brain, usually a non-
myoclonus). Status myoclonus on admission is contrast computed tomography scan, is important
associated with death or vegetative state with to exclude intracranial causes of collapse and
0% FPR (95% CI, 0%–14%). Status myoclonus injury incurred at the time of collapse. The exclu-
at 24 hours after cardiac arrest has a more precise sion of intracranial hemorrhage is prudent in the
0% FPR (95% CI, 0%–3%).105,106 Similar patterns comatose patient before anticoagulation or fibri-
of findings are true among patients treated with nolysis.113,114 The GWR on the initial brain
therapeutic hypothermia, although longer periods computed tomography is associated with survival
of observation may be required to clear potential and functional outcome.18,115 Whether treatment
confounding by sedation. Physiologic response of cerebral edema is worthwhile or futile has not
to targeted temperature management provides yet been studied. MRI visualizes more subtle
another avenue for insight into the potential for changes after cardiac arrest. Increased cortical
neurologic recovery. The presence of shivering, signals of diffusion-weighted images or fluid-
the amount of patient heat generation (derived attenuated inversion recovery sequences are
from the inverse average water temperature of associated with a poor neurologic outcome.116
cooling devices), and the presence of bradycardia For patients who remain comatose for several
(<60 beats/min) during the induction and mainte- days and in whom clinical or electrophysiologic
nance of temperature management are each asso- testing is indeterminate, MRI can provide addi-
ciated with a favorable neurologic outcome.110–112 tional information about the extent of brain injury.
Management of the Post–Cardiac Arrest Patient 93

Expectations and enthusiasm for long-term sup- higher than the traditional 65 mm Hg are likely
port may be reduced if extensive cortical lesions needed to optimize cerebral perfusion. Unless pre-
are present, whereas persistence may be justified cluded by severe myocardial stunning and frank
if anatomic extent of injury seems to be limited. An cardiogenic shock, a MAP of 80 mm Hg or
important caveat with the interpretation of all brain greater120 is desirable. Volume replacement
imaging after global ischemia is the differing clin- should occur with isotonic fluids (hypotonic fluids
ical impact of lesions in different brain regions. can exacerbate cerebral edema) and a bedside
The anatomic complexity of the brain precludes assessment of volume status. Although a central
any simple quantitative relationship between the venous pressure of 8 to 12 mm Hg has historically
number or size of lesions and outcome. been used to denote adequate volume replace-
EEG patterns after resuscitation change over ment, recent literature calls this measure into
time.20,117 Certain malignant EEG patterns have question.121 Other metrics include pulse pressure
a strong association with poor outcome. Specif- variability, sonographic assessment of inferior
ically, generalized suppression (<20 mV), burst- vena cava filling, and end-expiratory occlusion
suppression pattern associated with generalized test. There is no evidence demonstrating the supe-
epileptic activity, or diffuse periodic complexes riority of any 1 vasopressor after cardiac arrest.
on a flat background during the first week after Commonly used vasopressors include dopamine
resuscitation are associated with a poor neuro- (5–20 mg/kg/min), norepinephrine (0.01–1 mg/kg/
logic outcome.118 The presence of these malig- min), and epinephrine (0.01–1 mg/kg/min). Dopa-
nant EEG patterns provides information that is mine is associated with tachydysrhythmias and
additive with clinical evaluation.119 A detailed greater mortality in patients with cardiogenic
primer on EEG analysis is beyond the scope of shock.122 Epinephrine has more positive inotropy
this article, but the quantitative and qualitative than norepinephrine, but can prolong lactic
evolution of EEG over time provides prognostic acidosis. Thus, we recommend norepinephrine
information that is additive with clinical evalua- as a first-line vasopressor for post–cardiac arrest
tion.119 Electrophysiologic response to stimuli patients. Additional inotropic support may be
also can be used to assess whether cortical re- necessary in cases of ongoing shock despite
gions are intact. The absence of short-latency normalized hemoglobin and MAP (as assessed
(N20) cortical response to somatosensory evoked by severe global hypokinesis, low SvO2, low urine
potentials is very specific for poor neurologic output, and/or failure to clear serum lactate).
outcome (FPR, 0%; 95% CI, 0%–2% among Commonly used inotropes include dobutamine
patients treated with therapeutic hypother- (2–15 mg/kg/min) or milrinone (loading dose of 50
mia).104,106,118 Like an EEG, somatosensory mg/kg/min over 10 minutes, then 0.375–0.75 mg/
evoked potential responses vary with the elapsed kg/min). Both medications can precipitate hypo-
time since resuscitation.117 tension from vasodilation, and dobutamine may
induce tachydysrhythmias.
Most post–cardiac arrest patients require some Emergency Revascularization Strategies
type of pharmacologic circulatory support, many All cardiac arrest patients with ROSC should have
require coronary revascularization, and some an electrocardiogram (ECG) performed to assess
require mechanical circulatory support. It is impor- for ST-segment elevation myocardial infarction
tant to recognize that cardiogenic shock is a (STEMI). Large registries of cardiac arrest patients
self-perpetuating downward spiral and that treat- demonstrate that 26% to 31% of all postarrest pa-
ment goals center around restoring adequate tients have ECG findings consistent with
end-organ perfusion and unloading the ventricles. STEMI.123,124 Immediate coronary angiography
Ultimately, therapy should match the degree of and PCI in cardiac arrest patients with ROSC
shock with a clear plan for the escalation of sup- and STEMI is supported by a class I recommenda-
port. Further details are provided in the section tion from the American College of Cardiology and
of this text on cardiogenic shock. American Heart Association.125 This recommen-
dation is supported by the high positive predictive
Medical Management
value of ST-segment elevation on the post-ROSC
Titrated resuscitation to specific targets is a ECG for a severe underlying coronary artery
reasonable approach to the medical management lesion.123 Conversely, the post-ROSC ECG has a
of post–cardiac arrest hemodynamics. Supporting poor negative predictive value for identifying
evidence is primarily observational in nature. As significant underlying coronary artery lesions trig-
discussed elsewhere in this article, MAP goals gering the cardiac arrest. Hence, the absence of
94 Madder & Reynolds

ST-segment elevation is insufficient to rule out an the identification of such patients, but a recent
underlying culprit coronary lesion. Large registries American College of Cardiology expert panel pro-
demonstrate that 29% to 33% of postarrest pa- posed one algorithm to aid in this decision making
tients without ST-segment elevation on the post- (Fig. 4).133
ROSC ECG who underwent coronary angiography
had a culprit lesion identified that was thought to Mechanical Circulatory Support
be responsible for the cardiac arrest.124,126
Although observational studies overwhelmingly Among patients with persistent shock despite
demonstrate an association between coronary medical management, mechanical circulatory
angiography, improved survival, and improved support should be strongly considered. Historical-
neurologic outcome in post–cardiac arrest ly, the intraaortic balloon pump was frequently
patients with or without ST-segment elevation,127 used for hemodynamic support in cardiac arrest
selection bias is inherent in observational studies patients.134 However, a multicenter randomized
of postarrest coronary angiography. There are controlled trial evaluating the efficacy of the intra-
currently 4 randomized trials of post–cardiac aortic balloon pump in patients with STEMI and
arrest coronary angiography underway that should cardiogenic shock failed to demonstrate a reduc-
provide more definitive evidence on this topic.128 tion in 1-year mortality.135 This lack of efficacy is
In the meantime, the persistent association be- perhaps not surprising, considering that balloon
tween immediate angiography and improved out- counterpulsation does not have a major impact
comes combined with the high prevalence of an on cardiac output.136 In contrast, temporary de-
acute obstructive lesion support the practice of vices that augment left ventricle-to-aorta blood
strongly considering an early invasive strategy for flow via an axial pump can be rapidly placed
post–cardiac arrest patients without ST-segment percutaneously and provide superior hemody-
elevation and without an obvious extracardiac namic support to the intraaortic balloon pump.137
etiology. These devices, already in clinical use, can provide
In contrast, most patients are comatose after up to 3.5 L/min of blood flow when placed percu-
cardiac arrest,124 predisposing them to risk of taneously, and up to 5 L/min of blood flow when
death from neurologic injury regardless of coro- placed surgically.138 Extracorporeal circulatory
nary intervention. Fortunately, nearly one-half of support using a venous-to-arterial circuit is an
those comatose at the time of early revasculariza- additional means of providing hemodynamic sup-
tion eventually survive to hospital discharge and port. This option may be preferred in patients with
the majority has favorable neurologic recovery.129 ongoing cardiopulmonary resuscitation, right heart
Postprocedural mortality data in post–cardiac ar- failure, or those who cannot be adequately
rest patients do not currently distinguish between oxygenated. Ultimately, the means of mechanical
different causes of death. Given the lower survival support selected depends on the patients’ hemo-
rate in post–cardiac arrest patients compared with dynamics, the expected hemodynamic impact of
traditional PCI patients, appropriate early revascu- the device, the ease and rapidity of insertion, un-
larization in post–cardiac arrest patients has the derlying comorbidities or contraindications, and
unintended consequence of increasing total post- the ultimate goals of support.
procedural mortality. Performance reporting at
PCI centers is tied to awards, reimbursement, REGIONALIZATION OF CARE
recognition, public reporting of hospital perfor-
mance, and physician decision making.130,131 To It is the opinion of these authors that multidisci-
mitigate the temptation to reduce personal and/ plinary care of the post–cardiac arrest patient
or institutional PCI mortality by avoiding early should occur at a regionalized cardiac arrest cen-
revascularization in the post–cardiac arrest pa- ter. This is not a new model for patients requiring
tient, a recent American Heart Association Scienti- time-sensitive interventions. Trauma, STEMI, and
fic Statement recommends tracking post–cardiac acute stroke all take advantage of established,
arrest cases separately from other PCI cases.132 regionalized systems of care that coordinate pre-
Some post–cardiac arrest patients will have hospital providers with receiving centers.
overwhelming injury severity or a terminal combi- Community-based hospital providers treat post–
nation of comorbid conditions. In such cases, cardiac arrest patients infrequently, given the low
emergency revascularization may not be appro- rates of resuscitation in individual communities,
priate owing to the high likelihood of futility, and whereas regionalized cardiac arrest centers in-
it is appropriate to consult with the interventionalist crease referral volumes, and thereby provider
before activating STEMI protocols. There are no experience.139 For complex diagnoses or proced-
official guidelines or consensus statements on 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

correlation between greater provider experience 2. Daya MR, Schmicker RH, Zive DM, et al. Out-of-
and a better patient outcome.140 hospital cardiac arrest survival improving over
There is accumulating observational evidence in time: results from the Resuscitation Outcomes Con-
both regional and large, population-based cohorts sortium (ROC). Resuscitation 2015;91:108–15.
for improved outcomes when cardiac arrest pa- 3. Rittenberger JC, Tisherman SA, Holm MB, et al. An
tients are treated at regionalized centers.141–143 early, novel illness severity score to predict
Even with longer transport intervals, patients trans- outcome after cardiac arrest. Resuscitation 2011;
ported to high-volume centers were more likely to 82(11):1399–404.
survive to hospital discharge, compared with low- 4. Neumar RW. Molecular mechanisms of ischemic
volume centers. Prehospital transport time does neuronal injury. Ann Emerg Med 2000;36:483–506.
not seem to impact patient outcome after cardiac 5. White BC, Grossman LI, O’Neil BJ, et al. Global
arrest.144,145 Taken together, available data sug- brain ischemia and reperfusion. Ann Emerg Med
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hypotensive or hypoxic event during transfer.146 thermia differentially increases extracellular
signal-regulated kinase and stress-activated pro-
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