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Post-cardiac arrest management in adults

Authors: Jon C Rittenberger, MD, MS, Clifton W Callaway, MD, PhD

Section Editor: Ron M Walls, MD, FRCPC, FAAEM
Deputy Editor: Jonathan Grayzel, MD, FAAEM

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Sep 2017. | This topic last updated: Sep 06, 2017.

INTRODUCTION — Cardiac arrest results in over 500,000 deaths per year in North America alone [1].
However, advances in cardiopulmonary resuscitation and post-cardiac arrest care have improved
outcomes in select cohorts of patients [2-6]. Among these advances are the use of therapeutic
hypothermia (TH) and targeted temperature management (TTM), along with other interventions to
improve the care of patients following cardiac arrest.

The critical interventions in post-cardiac arrest management will be reviewed here. Basic and
advanced life support for adult victims of cardiac arrest and long-term care for survivors of cardiac
arrest are discussed separately. (See "Basic life support (BLS) in adults" and "Advanced cardiac life
support (ACLS) in adults" and "Overview of sudden cardiac arrest and sudden cardiac death".)

MAJOR PROBLEMS AND GOALS OF CARE — Management of the post-cardiac arrest patient is
complex and must address multiple major problems simultaneously. Issues to be addressed include:

● Determining and treating the cause of cardiac arrest

● Minimizing brain injury
● Managing cardiovascular dysfunction
● Managing problems that may arise from global ischemia and reperfusion injury

Immediately following resuscitation from cardiac arrest, the patient can develop a number of problems
due to medical comorbidities and the sequelae of ischemic injury sustained during the arrest. The
most immediate threat to survival during the first minutes to hours is cardiovascular collapse.
Interventions to optimize blood pressure and maintain end-organ perfusion (eg, boluses of IV fluid,
vasopressors, and inotropes) can help prevent secondary injury from hypotension. Additional short-
term goals during the first six hours of care include optimizing oxygenation and ventilation and
correcting electrolyte abnormalities. Determination of the etiology of cardiac arrest and the initiation of
relevant treatments are performed concurrently with resuscitation efforts in order to prevent recurrent
arrest and optimize outcome. Evidence supports the use of therapeutic hypothermia (TH) or targeted
temperature management (TTM) to minimize brain injury and target body temperatures should be
achieved within the first few hours following resuscitation.
DETERMINING THE CAUSE AND EXTENT OF INJURY AFTER CARDIAC ARREST — In most
cases of sudden cardiac arrest (SCA), the etiology determines therapy. A focused history and physical
examination are performed and diagnostic studies obtained in order to identify possible causes for the
arrest and ongoing or imminent threats to life. Cardiovascular disease is the most common cause of
SCA, but a broad differential diagnosis should be considered. Common etiologies for SCA are
described in the attached tables and discussed in detail separately (table 1 and table 2). (See
"Overview of sudden cardiac arrest and sudden cardiac death", section on 'Etiology' and
"Pathophysiology and etiology of sudden cardiac arrest", section on 'Etiology of SCD'.)

Cardiac arrest sustained during trauma has different causes than nontraumatic arrest (assuming
cardiac arrest did not precede and thereby cause the trauma) and is managed differently. Issues
related to trauma management are reviewed separately. (See "Initial management of trauma in adults"
and "Initial evaluation and management of shock in adult trauma".)

History — Most patients are comatose after resuscitation from SCA and cannot provide a history of
present illness or preexisting conditions. Therefore, clinicians should speak with anyone who can
provide insight into the history (eg, family, friends, witnesses, emergency medical services personnel)
to help determine the etiology of SCA as rapidly as possible after the return of spontaneous circulation
(ROSC).

Physical examination — Examination begins with an assessment of the airway, breathing, and
circulation (ABC's). Airway patency and security are evaluated first. A dislodged endotracheal tube or
tracheostomy tube will rapidly lead to recurrent cardiac arrest. (See 'Initial interventions' below.)

Once the airway is secure, ventilation is assessed. Listen for abnormal lung sounds (eg, asymmetry,
wheezing, crackles), which suggest a pulmonary or cardiac problem, or possibly a malpositioned
endotracheal tube.

Next, circulation and end-organ perfusion are evaluated. Pulse rate and character (eg, full, thready),
blood pressure, and skin appearance (eg, pink, mottled, cool) provide clues to the adequacy of
perfusion. A loud or harsh cardiac murmur or rub suggests a cardiac etiology. Tachycardia is expected
immediately after ROSC; bradycardia suggests an abnormal cardiac response, hypoxia, or severe
metabolic disturbance (eg, electrolyte abnormality).

A rigid abdomen suggests a surgical emergency or may be due to an air-filled stomach. Significant
quantities of blood in the rectum or nasogastric tube suggest a hemorrhagic cause (eg,
gastrointestinal bleeding). Extremity signs of deep venous thrombosis (eg, unilateral leg edema), IV
drug abuse, or a source of sepsis may suggest a diagnosis.

Baseline neurologic examination — A baseline neurologic examination should be performed to help

determine the possible cause, likely clinical course, and need for neurologic interventions (eg,
therapeutic hypothermia [TH] or targeted temperature management [TTM]). The initial examination
provides a baseline estimate of prognosis that can be modified based on additional information and
observation [7]. Temporary avoidance or cessation of neuromuscular blockade and sedation is
necessary for a valid examination. The examination may be delayed if long-acting drugs have been
administered. Train-of-four testing can be used to determine the degree of neuromuscular blockade.
Train-of-four testing and the neurologic examination in the patient with depressed mental status are
described separately. (See "Use of neuromuscular blocking medications in critically ill patients",
section on 'Administration' and "Stupor and coma in adults", section on 'Neurologic examination'.)

Asymmetric neurologic findings are not expected following ROSC and suggest a structural intracranial
lesion. Brainstem responses, including the pupillary, corneal, oculocephalic, gag, and cough response
to stimulation, correlate with survival and should be assessed [7]. The Glasgow Coma Score or Full
Outline of UnResponsiveness (FOUR) Score should be determined, with particular attention paid to
the motor score, which correlates closely with neurologic outcome. Patients who cannot perform
purposeful movements or follow basic commands generally need specialized neurocritical care
treatment including TH or TTM. (See "Stupor and coma in adults", section on 'Prognosis'.)

Diagnostic tests — Diagnostic tests, including an electrocardiogram, imaging studies, and laboratory
tests, are usually required to determine the etiology of cardiac arrest, to confirm endotracheal tube
positioning and assess for chest trauma from CPR, and to ascertain the involvement of specific organ
systems and gauge the severity of injury.

Electrocardiogram — Acute myocardial infarction, cardiomyopathy, and primary arrhythmia are

the most common causes for cardiac arrest. Following ROSC, a 12-lead electrocardiogram (ECG)
should be rapidly obtained and evaluated for signs of ST-elevation myocardial infarction (STEMI)
(including a new left bundle branch block) that requires emergency reperfusion therapy. Abnormalities
of conduction intervals, electrical axis, and T-waves may provide clues to the etiology. As an example,
a prolonged QTc interval may reflect a primary arrhythmia, accidental hypothermia, or an electrolyte
abnormality. Evidence of right heart strain (eg, right axis deviation) may be present in the setting of
pulmonary embolus.

Among patients with out-of-hospital cardiac arrest (OHCA), significant coronary artery disease is often
present in the absence of an acute STEMI [8,9]. The incidence of coronary artery lesions is highest
among patients whose presenting arrhythmia is ventricular fibrillation (VF) or pulseless ventricular
tachycardia (VT) [8,10]. Thus, emergency cardiac catheterization may be needed in patients without a
STEMI but who have a concerning story (antecedent chest pain or shortness of breath and cardiac
risk factors) or whose presenting arrhythmia was VF or pulseless VT. (See 'Coronary
revascularization' below.)

When the diagnosis of acute coronary syndrome (ACS) is uncertain based on ECG findings, bedside
echocardiography may demonstrate focal wall motion abnormalities, suggesting acute myocardial
infarction. Global but not focal hypokinesis is expected following cardiac arrest. (See 'Imaging studies'
below.)

Ongoing cardiogenic shock may be the sole manifestation of ACS in some patients with ROSC. Such
patients may benefit from reperfusion established via cardiac catheterization or from placement of an
intra-aortic balloon pump.

Imaging studies — Obtain chest radiography to evaluate for pulmonary pathology and to confirm
proper positioning of the endotracheal tube and central venous catheter. Pulmonary edema and
evidence of aspiration are common findings after cardiopulmonary resuscitation, but may be unrelated
to the cause of arrest. Pneumothorax or mediastinal abnormalities suggestive of aortic dissection
represent ongoing threats to patient survival and require immediate intervention. Enlarged aorta or
concerning mediastinal findings on chest radiograph should prompt CT scan imaging. (See "Clinical
features and diagnosis of acute aortic dissection".)

Bedside emergency ultrasound can help to identify causes of arrest that represent ongoing threats to
life, including pericardial tamponade, pneumothorax, catastrophic pulmonary embolism (PE), and
intraperitoneal bleeding [11-15]. Ultrasound can be used to assess right ventricular size and function
(which may be abnormal with PE), determine inferior vena cava diameter (which may be abnormal
with hypovolemia), and assess global cardiac function. (See "Evaluation of the survivor of sudden
cardiac arrest", section on 'Echocardiography'.)

Unenhanced computerized tomography (CT) of the brain can detect early cerebral edema or
intracranial hemorrhage in the comatose post-cardiac arrest patient [16-18]. Approximately 4 percent
of patients in one series exhibited intracranial hemorrhage that was considered to be the cause of
their arrest [16], altering both expected prognosis and precluding the use of anticoagulation. (See
"Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis".)

CT of the chest is useful in cases of suspected pulmonary embolism (PE). However, CT may be
delayed if there is concern for acute renal injury. In this setting, if the clinician strongly suspects that a
massive PE accounts for the patient's arrest, other imaging studies (eg, transthoracic or
transesophageal echocardiography, ultrasonography of the lower extremities) can be performed while
treatment with empiric anticoagulation is started. The high incidence of abnormalities on chest
radiograph limits the utility of V/Q scanning in this population [19]. (See "Overview of acute pulmonary
embolism in adults".)

In patients with a markedly elevated lactate (>15 mmol/L), traumatic mechanism, or clinical findings of
peritonitis, CT imaging of the abdomen and pelvis is useful for determining an intra-abdominal cause
of arrest.

Laboratory testing — Laboratory testing may provide insight into the cause of arrest, but is also
necessary to evaluate the extent and progression of arrest-related injury to organ systems. In
particular, electrolyte and acid-base disturbances require close monitoring during resuscitation and on-
going management.

Following ROSC, we suggest the following approach to laboratory testing:

● Arterial blood gas measurements are obtained every six hours during therapeutic hypothermia
(TH) or targeted temperature management (TTM) and rewarming to assess acid-base status and
are used to guide ventilator management. Arterial vascular access is obtained routinely in
comatose post-cardiac arrest patients given the need for frequent arterial blood gas
measurements and the common use of vasopressor and inotropic drugs [20]. (See "Arterial blood
gases" and "Simple and mixed acid-base disorders".)

● Basic serum electrolyte concentrations, including sodium, potassium, chloride, and bicarbonate,
are obtained every six hours during TH and rewarming to detect abnormalities. Rapid fluctuations
in serum potassium may occur as a result of ischemia, acidosis, and catecholamine
administration. Both high and low potassium can cause arrhythmias and must be treated
immediately. Note that hypokalemia is often accompanied by hypomagnesaemia, which should
also be corrected. (See "Treatment and prevention of hyperkalemia in adults" and "Clinical
 manifestations and treatment of hypokalemia in adults".)

● Blood counts are measured to detect anemia and other hematologic abnormalities. Profound
anemia suggests blood loss as a factor contributing to cardiac arrest. Leukocytosis of 10,000 to
20,000 is common and may represent acute demargination of white blood cells and inflammation.
Markedly elevated leukocytosis should prompt investigation of a cause other than cardiac arrest.

● Serum troponin is measured every 8 to 12 hours for 24 hours to detect myocardial injury. If initial
measurements are elevated, testing continues until there is clear evidence they are decreasing.
Cardiac arrest, CPR, and defibrillation often cause mild increases in the serum troponin (troponin
I 0 to 5 ng/mL), but rising or higher levels suggest acute coronary artery occlusion. Using
biomarkers to diagnose myocardial infarction in patients with renal injury is discussed separately.
(See "Serum cardiac biomarkers in patients with renal failure".)

● Serum lactate concentration is measured every six hours during TH and rewarming. Initial lactate
concentrations and the rate of lactate clearance correlate with survival [21]. Lactic acidosis, with
serum lactate concentrations up to approximately 15 mmol/L, is common after cardiac arrest, but
higher levels suggest ongoing intra-abdominal or muscle compartment ischemia. Lactate should
clear over time after adequate perfusion is restored.

● Specific toxicology studies may be obtained in patients with a history of drug ingestion, signs of a
toxicologic syndrome (eg, sympathomimetic poisoning), or clinical suspicion of poisoning. As
examples, myocardial infarction or arrhythmia may be caused by acute cocaine or
methamphetamine intoxication, cardiopulmonary collapse may be precipitated by massive
antidepressant overdose, and sedative overdose may contribute to and prolong coma
independent of any brain injury sustained during a cardiac arrest. The presence of long-acting
opioids (eg, methadone) may prompt use of a reversal agent (naloxone) before neurologic
testing. Evaluation and management of the unresponsive and critically-ill poisoned patient is
discussed separately. (See "Initial management of the critically ill adult with an unknown
overdose".)

Ischemia can impair kidney and liver function, which may affect drug dosing and decisions to use
intravenous contrast. Thus, we recommend initial measurements of renal and hepatic function. Most
patients require central venous access, arterial access, and potentially other invasive procedures.
Therefore, we recommend assessment of PT, aPTT, and INR along with initial laboratory testing.

RESPIRATORY CONSIDERATIONS

Initial interventions — The clinician must first ensure a patent and functioning airway. An obstructed
airway can rapidly lead to recurrent cardiac arrest. If a temporizing rescue airway device (eg, laryngeal
mask, laryngeal tube) was used during resuscitation, this is replaced with a definitive airway at the
earliest opportunity. Stomach decompression with a gastric tube is indicated.

The details of airway management are discussed separately. (See "Advanced emergency airway
management in adults" and "Basic airway management in adults" and "Rapid sequence intubation for
adults outside the operating room".)

Mechanical ventilation — We suggest the following guidelines for mechanical ventilation in the post-
cardiac arrest patient:

● Target a carbon dioxide tension (PaCO2) approximately 40 mmHg (or end-tidal CO2 of
approximately 35 mmHg).

In observational studies, PaCO2 in a normal range (35 to 45 mmHg) when measured at 37°C is
associated with better outcomes than higher or lower PaCO2 [22]. Avoiding lower PaCO2
prevents hypocapnia-induced cerebral vasoconstriction. Because of the temperature correction
when induced hypothermia is used, the actual PaCO2 in a patient may be slightly lower than the
PaCO2 measured in the laboratory at 37°C, making 40 mmHg a safer target at all temperatures
than 35 mmHg.

● Maintain oxygen saturation (SpO2) >94 percent. Avoid prolonged hyperoxia (PaO2 >300 mmHg),
which has been associated with worse outcomes.

Management of mechanical ventilation in the post-cardiac arrest patient must balance the need to
reverse hypoxia and acidosis with the potential deleterious effects of hyperventilation and hyperoxia.
Specifically, routine hyperventilation should not be used to compensate for metabolic acidosis. The
modes and management of mechanical ventilation are reviewed separately. (See "Overview of
mechanical ventilation" and "Mechanical ventilation of adults in the emergency department".)

Cerebrovascular responses to PaCO2 persist after cardiac arrest [23,24], and hyperventilation causes
cerebral vasoconstriction [25,26]. Therefore, ventilation should be titrated to keep the PaCO2 no lower
than 40 to 45 mmHg [4,27]. It is unknown if higher PaCO2 levels contribute to vasodilation, hyperemia,
or cerebral edema. Hyperventilation can also decrease preload, resulting in reduced cardiac output
and coronary perfusion pressure [28]. In a systematic review of nine observational studies,
normocarbia (PaCO2 35 to 45 mmHg) was associated with higher survival and better functional status
at hospital discharge compared to hypocarbia or hypercarbia [22].

Hypoxia must be avoided in the post-cardiac arrest patient, but hyperoxia (PaO2 >300 mmHg) may
also be harmful. We suggest titrating the fraction of inspired oxygen (FiO2) to the lowest value
necessary to maintain oxygen saturation (SpO2) >94 percent, or the PaO2 to around 100 mmHg. If the
patient’s core temperature is maintained at 33°C, the PaO2 reported by the laboratory may be higher
than the patient’s actual PaO2. Thus, in this clinical setting, maintaining a PaO2 of 100 to120 mmHg is
reasonable.

Although studies of supplemental oxygen in the setting of cardiac arrest are limited, our approach is
supported by several retrospective studies. According to a systematic review of 14 observational
studies, hyperoxia (defined as a PaO2 >300 mmHg) was associated with increased in-patient mortality
among patients with a ROSC following cardiac arrest (odds ratio [OR] 1.4; 95% CI 1.02-1.93),
although not with a poor neurologic outcome (OR 1.62; 95% CI 0.87-3.02) [29]. In one cohort of 6326
post-cardiac arrest patients, the odds ratio for death among patients with hyperoxia (defined as PaO2
>300 mmHg on the first arterial blood gas) was 1.8 (95% CI 1.5-2.2) compared to patients without
hyperoxia [30].

However, not all studies support the importance of avoiding hyperoxia and the optimal oxygen level in
the post-arrest patient remains an area of debate. A retrospective cohort study of 12,108 post-cardiac
arrest patients evaluated the worst arterial blood gas obtained during the first 24 hours following
resuscitation and found no difference in mortality between the hyperoxia (PaO2 >300 mmHg) and
normoxia (PaO2 <300 and >60 mmHg) groups [31]. In addition, a randomized trial of 28 patients with
out-of-hospital cardiac arrest found no difference in survival to hospital discharge among patients
randomly assigned to a goal FiO2 of 30 percent or 100 percent during the first hour of treatment [32].

Ensuring adequate oxygen delivery — Extrapolating from research on sepsis, some researchers
advocate maintaining a central venous oxygen saturation (ScvO2) of ≥70 percent in post-cardiac
arrest patients, but whether this goal is optimal remains unknown [33]. Given that the post-arrest
syndrome can be similar to that of sepsis, our practice is to maintain ScvO2 of ≥70 percent and a
hematocrit of 30 percent in patients with a presumed cardiac etiology for their arrest. This approach is
similar to that of early-goal-directed therapy for sepsis. (See "Evaluation and management of
suspected sepsis and septic shock in adults", section on 'Immediate evaluation and management'.)

We do not advocate transfusion to a normal hematocrit given the prothrombotic state seen in post-
arrest patients. Failure of the serum lactate to clear over time suggests inadequate perfusion, and
prompts us to reevaluate all aspects of oxygen delivery: cardiac output, intravascular volume,
hemoglobin concentration, and blood pressure.

Interpreting blood gas values during therapeutic hypothermia (TH) — When TH is used, arterial
blood gas values can be interpreted with or without correction for the patient's temperature. When a
patient's core temperature is 33°C, the patient's actual PaCO2 may be 6 to 7 mmHg lower than the
value reported by the blood gas machine [34]. However, there is no evidence to determine whether it
is better to use corrected (pH-stat) or uncorrected (alpha-stat) values to adjust ventilation. It is prudent
to target slightly higher PaCO2 values in order to avoid accidental hyperventilation and the resulting
cerebral vasoconstriction.

Note that the metabolic rate of the patient, and thus minute ventilation requirements, decrease as
body temperature falls. A blood gas should be obtained after any major change in patient temperature
(eg, when a patient treated with hypothermia reaches 33°C). (See 'Targeted temperature management
(TTM) and therapeutic hypothermia (TH)' below.)

The interpretation of arterial blood gas results is reviewed separately. (See "Simple and mixed acid-
base disorders" and "Oxygenation and mechanisms of hypoxemia" and "Oxygen delivery and
consumption".)

HEMODYNAMIC CONSIDERATIONS

Maintaining end-organ perfusion — An adequate blood pressure must be maintained in the post-
cardiac arrest patient. Episodes of hypotension can cause secondary injury, in addition to any initial
insult incurred during the arrest by the brain and other organs. Mean arterial blood pressure (MAP)
should be above 65 mmHg to reverse the acute shock state, and preferably 80 to 100 mmHg to
optimize cerebral perfusion.

When determining blood pressure goals, clinicians must balance the metabolic needs of an ischemic
brain with the potential for overstressing a decompensated heart. Cerebral autoregulation is often
impaired after cardiac arrest [35,36], and brain perfusion declines when the MAP falls below 80 to 100
mmHg. However, if the MAP is adequate, regional cerebral perfusion matches metabolic activity,
according to positron emission tomography (PET) studies in post-cardiac arrest patients [37,38]. Thus,
maintaining an adequate MAP helps to avoid further brain injury. Maintaining central venous pressures
between 8 to 12 mmHg and adequate urine output (>0.5 mL/kg per hour) are additional perfusion
goals [33,39].

Volume replacement, with isotonic saline or lactated ringers, is used to maintain a goal central venous
pressure (CVP) of 8 to 12 mmHg. Lactated ringers may avoid hyperchloremic metabolic acidosis in
patients requiring large volume infusions during initial resuscitation. (See "Intraoperative fluid
management", section on 'Fluid therapy'.)

Hypotonic fluids, which can exacerbate cerebral edema, should be avoided. Rapid infusion (infusion at
maximal rate using a pressure bag) of 20 to 30 mL/kg of isotonic saline or other crystalloid at 4°C is
commonly used to induce hypothermia. In patients with known systolic dysfunction, a smaller volume
of isotonic saline may be used. Once an adequate CVP has been established, patients whose MAP
remains below 80 mmHg generally need treatment with an inotropic agent or vasopressor. Prior to
CVP monitoring, it is reasonable to start vasoactive drugs in patients with hypotension that does not
resolve after a rapid infusion of 2 L of isotonic crystalloid.

Inotropic and vasopressor support can mitigate the myocardial dysfunction that is common during the
first 24 to 48 hours after cardiac arrest [20,40]. There is no evidence demonstrating the superiority of
any one vasopressor in the post-cardiac arrest patient. Commonly employed vasopressors include
dopamine (5 to 20 mcg/kg per minute), norepinephrine (0.01 to 1 mcg/kg per minute; 0.5 to 70
mcg/minute), and epinephrine (0.01 to 1 mcg/kg per minute; 0.5 to 70 mcg/minute).

A large cohort study evaluating vasopressor support during the first 24 hours after cardiac arrest,
measured by the cumulative vasopressor index, reported that 47 percent of patients receive some
vasopressor support [41]. In this study, the median dose was <0.05 mcg/kg per minute. Twenty-five
percent of subjects receiving vasopressors required doses of norepinephrine between 0.05 and 0.1
mcg/kg per minute. In 10 percent of subjects, a dose of norepinephrine over 0.1 mcg/kg per minute
was required. Dosing up to 0.15 mcg/kg per minute is relatively common.

Studies in septic patients report no difference in mortality between patients treated with dopamine or
norepinephrine, but the risk of cardiac arrhythmia may be higher in patients treated with dopamine.
Given these data, we use norepinephrine as the first line vasopressor in the undifferentiated post-
arrest patient. (See "Use of vasopressors and inotropes".)

In cases of cardiogenic shock (eg, global hypokinesis on echocardiogram or persistently low SvO2
despite normalized hemoglobin and MAP), inotropic support using dobutamine (2 to 15 mcg/kg per
minute) or milrinone (loading dose: 50 mcg/kg over 10 minutes, then 0.375 to 0.75 mcg/kg per minute)
may be helpful. Either agent may cause hypotension from vasodilation; dobutamine may cause
tachyarrhythmias.

Inotropic and vasopressor agents require titration over the first 12 to 24 hours following cardiac arrest.
Thus, an arterial line for continuous blood pressure monitoring is necessary in the majority of patients.
In patients with ongoing cardiovascular shock despite inotropic and vasopressor support, an intra-
aortic balloon pump may be advised.

Preventing arrhythmia — Antiarrhythmic drugs should be reserved for patients with recurrent or
ongoing unstable arrhythmias. No data support the routine or prophylactic use of antiarrhythmic drugs
after the return of spontaneous circulation following cardiac arrest, even if such medications were
employed during the resuscitation. Determining and correcting the underlying cause of the arrhythmia
(eg, electrolyte disturbance, acute myocardial ischemia, toxin ingestion) is the best intervention. (See
'Determining the cause and extent of injury after cardiac arrest' above.)

Coronary revascularization — Emergency coronary catheterization or medical reperfusion therapy is

indicated for post-cardiac arrest patients with findings on the electrocardiogram (ECG) of ST segment
elevation myocardial infarction (STEMI) or new left bundle branch block (LBBB). (see "Evaluation of
the survivor of sudden cardiac arrest", section on 'Coronary angiography'). The contraindications to
thrombolytic therapy are reviewed separately. (See "Fibrinolysis for acute ST elevation myocardial
infarction: Initiation of therapy", section on 'Contraindications'.)

While patients with ST segment elevation are much more likely to be treated with emergency coronary
angiography, some facilities perform coronary catheterization for all patients with return of
spontaneous circulation following out-of-hospital cardiac arrest from ventricular fibrillation (VF) or
pulseless ventricular tachycardia (VT), regardless of ECG findings, because of the high incidence of
acute coronary artery occlusion in this group [8,42-44]. In one series of 435 patients, over 70 percent
with VF or pulseless VT had significant lesions at catheterization [9].

Some researchers advocate even more liberal criteria for performing coronary catheterization
regardless of the presenting cardiac rhythm. According to a meta-analysis of 11 heterogeneous,
retrospective studies involving several thousand patients, over 30 percent of post-arrest patients with
no ST elevation are found to have acute coronary artery occlusions regardless of their presenting
rhythm [44]. We believe that an early invasive approach is reasonable; however, it may not be feasible
in all institutions and further randomized trials are needed to compare early intervention with more
conservative management in patients without explicit indications for coronary catheterization.

Adjusting for other factors, several studies have reported that cardiac arrest patients treated with
coronary catheterization were twice as likely to be discharged to home or to acute rehabilitation as
patients not so treated [8,9,44]. Even without coronary revascularization, medical treatments for acute
coronary syndrome (ACS) (eg, antiplatelet and anticoagulation therapy) may be beneficial. (See
"Prognosis and treatment of cardiogenic shock complicating acute myocardial infarction".)

Regardless of ECG findings, emergency coronary catheterization may be needed for patients with
ongoing hemodynamic instability, which may be due to cardiogenic shock or associated with rising
troponin levels, or evidence of focal wall-motion abnormalities on echocardiogram. Thus, we
recommend coronary artery catheterization in the post-arrest patient, with precise timing determined
by the initial ECG, trajectory of cardiac biomarker levels, presence of shock, and competing needs of
ongoing resuscitation procedures. Life-saving cardiovascular procedures should never be delayed
because of coma, which may take days to resolve. Immediate discussion of these issues with an
interventional cardiologist is appropriate for all patients who do not have an obvious non-
cardiovascular etiology of arrest. (See "Evaluation of the survivor of sudden cardiac arrest", section on
'Coronary angiography'.)

TH can be started during catheterization using surface cooling (ice packs), cold IV fluid administration,
or intravascular cooling methods. Case series report good outcomes in patients with cardiovascular
shock treated with TH [45,46].
TARGETED TEMPERATURE MANAGEMENT (TTM) AND THERAPEUTIC HYPOTHERMIA (TH)

Rationale, general approach, and definitions — Neurologic injury is the most common cause of
death in patients with out-of-hospital cardiac arrest and contributes to the mortality of in-patients with
cardiac arrest [47]. A meta-analysis of 11 studies that reported achieved temperature (including three
randomized trials and 1381 patients total) found lower mortality (odds ratio [OR] 0.51, 95% CI 0.41-
0.64) and improved rate of good neurologic outcome (OR 2.48, 95% CI 1.91-3.22) in cardiac arrest
patients treated with temperature management compared to those not receiving such treatment [48].
When combined with standard post-cardiac arrest care, lowering core body temperature to the range
of 32 to 34°C during the first hours after cardiac arrest improves neurologic outcome compared to not
controlling body temperature [49]. A large randomized trial reports similar improvements in outcome
whether the temperature is maintained at 33°C or 36°C [50]. (See 'Evidence of benefit' below.)

Hyperthermia must be avoided following cardiac arrest. Failure to control a patient's core temperature
is associated with the development of fever and worse neurologic outcome [2,3,51,52]. According to
an observational study of 151 patients, the risk of death increases for each degree over 37°C during
the first 48 hours after cardiac arrest (OR 2.26; 95% CI 1.24-4.12) [51]. Earlier onset of fever is
associated with worse outcomes, while delayed fever onset has not shown the same deleterious
effects [52]. An observational study that included 179 patients who developed fever following
rewarming reported worse neurologic outcomes in patients with a higher maximum temperature during
pyrexia (OR 0.30; 95% CI 0.10-0.84) [53].

Overall, these data suggest that active control of the post-cardiac arrest patient's core temperature,
with a target between 32 and 36°C, followed by active avoidance of fever, is the optimal strategy to
promote patient survival. In this section, our suggested approach and the evidence for temperature
management, including TH, following cardiac arrest is reviewed. In this discussion, TH refers to a core
body temperature maintained in the range of 32 to 34°C; temperature control refers to a core
temperature maintained no higher than 36°C.

Indications and contraindications — Patients not following commands or showing purposeful

movements following resuscitation from cardiac arrest should have their temperature managed. The
only absolute contraindication for temperature management is an advanced directive that proscribes
aggressive care or a medical scenario for which such care is not appropriate. TH should not be used
in patients with active noncompressible bleeding, but TTM (core temperature maintained ≤36°C) in
this population is reasonable. Either TH or TTM may be used in pregnant or hemodynamically
unstable patients, and those receiving coronary catheterization or thrombolytics [8,19,45,46,54,55].
However, TH is associated with an increased risk of bleeding in the last two populations [8,19]. Fever
prevention is recommended in all cardiac arrest patients without an advanced directive proscribing the
necessary interventions [51,52].

Timing and duration of treatment — In post-cardiac arrest patients, we recommend that active
control of the patient's core temperature be achieved as soon as possible, with control maintained for
at least 48 hours. Clinical data strongly support avoiding fever for at least 48 hours following cardiac
arrest [2,3,50-52]. Regardless of the strategy selected, a cooling device with a feedback mechanism is
necessary to actively control patient temperature. Active control should be undertaken and maintained
even if the patient is already mildly hypothermic at presentation. The approach described here is
consistent with that of the International Liaison Committee on Resuscitation (ILCOR) [56].
It is likely that subgroups of patients respond differently to different durations of temperature
management. In a trial of 355 out-of-hospital cardiac arrest patients randomized to either 48 or 24
hours of TH at 33°C, the rate of good functional outcome at six months (defined as a CPC of 1 or 2)
was 4.9 percent (95% CI -5 to 14.8) higher in the 48 hour treatment group (69 versus 64 percent;
relative risk [RR] 1.08; 95% CI 0.93-1.25) [57]. However, the rate of any adverse event was higher in
the 48 hour treatment group (RR 1.06; 95% CI 1.01-1.12), as was ICU length of stay (151 versus 117
hours). The major limitation of this trial was its small sample size [58]. There are limited data about
longer treatment in animal studies, and neonatal hypoxic-ischemic encephalopathy has been treated
with 72 hours of hypothermia. Some case series using hypothermia durations up to 72 hours have
been reported for severe post-arrest brain injury [59].

Clinical trials have assessed the timing of induction of TH or TTM after the return of spontaneous
circulation (ROSC). Intra-arrest hypothermia may be a future intervention as animal studies have
shown that TH is most beneficial when temperature is lowered prior to or within moments of the ROSC
[60,61]. In randomized trials, prehospital induction of TH using intravenous cold fluids did not improve
outcomes, and resulted in increased diuretic administration and pulmonary edema during the first 24
hours after resuscitation [62-65]. Based on these data, there is no indication for prehospital initiation of
hypothermia using cold intravenous fluids.

Goal temperature — We suggest using 36°C for 24 hours in uncomplicated patients who have
moderate coma (some motor response), no malignant EEG patterns, and no evidence of cerebral
edema on CT scan. We suggest using 33°C for at least 24 hours when coma is deep (loss of motor
response or brainstem reflexes), malignant EEG patterns (eg, epileptiform) appear, or early CT scan
changes suggesting the development of cerebral edema are detected.

Clinical trials in adult patients have used regimens of TH with goal temperatures of 32 to 34°C for 12
or 24 hours, followed by gradual rewarming (0.25°C/hour) [49], or regimens of 36°C for 24 hours,
followed by gradual rewarming (0.25°C/hour) [50]. While data do not support the superiority of either
regimen, lower temperatures may reduce cerebral edema, seizure activity, and metabolic demand,
and may be of benefit in patients with these complications.

A retrospective study reported that changing from an established protocol using a 33°C goal
temperature to a protocol using 36°C resulted in less time at the targeted temperature (87 percent in
33°C cohort versus 50 percent in 36°C cohort), and more frequent fevers (0 percent in 33°C cohort
versus 19 percent in 36°C cohort) [66]. The 36°C cohort was less likely to receive neuromuscular
blockade or sedative medications, which may have contributed to the study results.

Cerebral edema is a frequently lethal complication following cardiac arrest that is detectable on CT
scan in up to 22 to 50 percent of patients [16,67]. Induced hypothermia (33 to 34°C) reduces ICP or
prevents herniation in patients with intracranial hypertension after SAH [68], traumatic brain injury [69],
cerebral edema from hepatic encephalopathy [70], and ischemic stroke [71]. Therefore, the use of
lower temperatures for TH is reasonable when cerebral edema or intracranial hypertension is a
concern following cardiac arrest. Lowering body temperature has long been recognized as a treatment
option to reduce seizure frequency, and induced hypothermia is one method to treat refractory
seizures [72]. When induced hypothermia (33 to 34°C for 72 hours) is used to treat neonatal hypoxic-
ischemic encephalopathy (HIE), the frequency of seizures is reduced [73]. However, seizures may be
more common in the neonatal HIE population than among adults following cardiac arrest [74].
Therefore, we suggest that induced hypothermia be used when epileptiform activity is present in adult
post-cardiac arrest patients.

Methods to maintain temperature and implement therapeutic hypothermia (TH) — Clinicians

should use intravascular or surface methods to control temperature that are readily available and
familiar. Many patients are already mildly hypothermic (35 to 35.5°C) after the return of spontaneous
circulation (ROSC) from the mixing of cooler peripheral blood with core blood [2,3,75]. Therefore,
minimally invasive techniques can often achieve desired temperatures quickly.

Intravenous infusion of 30 mL/kg of cold (4°C [39°F]) isotonic saline, using a pressure bag to increase
the rate of administration, reduces the core temperature by >2°C per hour [62,76,77]. One liter of cold
saline infused via pressure bag over approximately 15 minutes can drop the core temperature by
approximately 1°C. The rate of temperature reduction using this method is comparable or faster than
that achieved with endovascular catheters, but may result in pulmonary edema and increased diuretic
use [63,78]. Patients with a history of heart failure or severely compromised renal function, or signs of
acute pulmonary edema, should not receive rapid fluid infusions to induce TH. Surface cooling
measures or an intravenous cooling device should be used instead. Surface cooling methods,
including ice packs, cooling blankets, and cooling vests can reduce the core body temperature by 0.5
to 1°C per hour. In patients who cannot tolerate rapid fluid administration, cool water baths or cool
water and fans can be used as an adjunct method to induce hypothermia, as is done to treat patients
with heat exhaustion.

We induce TH by infusing 1 to 2 L of cold saline using a pressure bag, while simultaneously

implementing surface cooling using cooling blankets above and below the patient, and ice packs
applied to the axillae, groin, and neck (adjacent to major blood vessels).

When inducing TH, shivering is common and may be too fine to see. Therefore, sedation (and
potentially neuromuscular blockade) is required to facilitate cooling. (See 'Sedation and suppression of
shivering' below.)

There is no evidence demonstrating the superiority of any cooling method and in clinical practice a
combination of intravascular and surface cooling is commonly employed [4,5,33]. The lone
observational study comparing intravascular and surface cooling methods found that neither the time
needed to reach the goal temperature nor neurologic outcome was significantly different in the two
groups [79].

Both surface and intravascular cooling devices are effective at maintaining a goal temperature for 12
to 24 hours. However, the effect of mild temperature fluctuations and excessive hypothermia on
patient outcomes is unknown, and thermostatically controlled devices provide the most precise
minute-to-minute temperature regulation [80]. Such devices are also used to maintain temperature
and avoid fever [50].

Sedation and suppression of shivering — Shivering raises body temperature and must be
suppressed in patients being treated with TH or temperature management [76,81-83]. Failure to
suppress shivering is a common reason for delays in achieving goal temperatures when cooling
patients. Therefore, we suggest titrating sedation to shivering suppression, rather than using standard
sedation scales. High doses of sedatives are frequently necessary to accomplish this.
A continuous infusion of propofol and fentanyl, with or without intermittent treatment with
benzodiazepines (eg, midazolam), is one effective approach to sedation [84]. We start with a propofol
infusion at 30 mcg/kg per minute and titrate as needed to a maximum dose of 50 mcg/kg per minute. If
this is ineffective, we add fentanyl in boluses of 0.1 mcg/kg or as a continuous infusion starting at 0.5
mcg/kg per hour.

In hypotensive patients, a continuous infusion of midazolam (2 to 10 mg/hour) is an effective

alternative to propofol, but accumulation of this drug may interfere with subsequent neurologic
evaluation [85]. Studies in healthy volunteers have demonstrated a decrease in metabolism and
excretion of midazolam during the induction of TH [86]. Consequently, patients receiving infusions of
midazolam may require days to clear the drug. No studies have evaluated the effect of midazolam on
neurologic prognostication after cardiac arrest.

Intermittent treatment with meperidine can suppress shivering, but the proconvulsant effects of its
primary metabolite normeperidine makes this drug unappealing, particularly in post-cardiac arrest
patients. Moreover, meperidine is not recommended in patients with renal dysfunction, which is
common in the post-cardiac arrest population. Dexmedetomidine has been shown to suppress the
shivering threshold in healthy individuals, but its use is limited by the side effects of hypotension and
bradycardia [87].

Neuromuscular blockade is highly effective at suppressing shivering, but can mask seizures, which
develop in 3 to 44 percent of post-cardiac arrest patients [2,4,88-91]. Continuous
electroencephalogram monitoring is needed for the safe use of neuromuscular blockade. (See
'Seizures and myoclonic jerks' below.)

Temperature monitoring and rewarming — Core body temperature should be monitored

continuously during TH and TTM. The gold standard for core temperature measurement is central
venous temperature, but several surrogates are available. In order of preference, surrogate monitoring
methods include esophageal, bladder, or rectal probes [92]. Core temperature is a close
approximation of brain temperature [93].

Esophageal temperature measurement is the most accurate surrogate method used to follow core
temperature during the induction of TH [92,94]. Bladder temperature may be erroneous if urine output
falls below 0.5 mL/kg per hour. Rectal measurements may lag behind acute changes in core
temperature by up to 1.5°C [92]. Many rectal temperature probes can also be placed in the
esophagus, yielding a more accurate measurement. Axillary and tympanic measurements are
inadequate and misleading during TH and should never be used.

During rewarming, the temperature should be raised gradually, with the rate of increase not exceeding
0.5°C per hour. We, along with many other clinicians, advocate a rate of 0.2 to 0.25°C per hour [5,83].
Rapid rewarming can cause electrolyte abnormalities (eg, hyperkalemia), cerebral edema, seizures,
and other problems. In animal studies of traumatic brain injury, rapid rewarming (>0.5°C/hour)
eliminated the benefits of TH [95,96].

Rapid rewarming can occur if the patient's temperature is not closely monitored. The original trials of
TH used surface cooling and passive rewarming, but automated devices using surface or
intravascular methods are now available to control temperatures during the induction, maintenance,
and rewarming phases of TH [97,98]. If such devices are not available, manual rewarming can be
employed.

Manual rewarming is performed most often when cooling blankets and/or ice packs have been used to
cool the patient. One approach to gradual rewarming when a cooling blanket is in place is to increase
the set point for the patient's temperature by 0.5°C every three hours until a normal temperature is
reached. As an example, if the patient's temperature is 33°C, during the first hour the temperature is
set for 33.5°C. After three hours of rewarming, the temperature is set for 34°C. In the case of ice
packs, a few can be removed each hour and the rate of rewarming can be used to determine when
additional ice should be removed if the patient is rewarming appropriately, or added if the patient is
rewarming too quickly.

The rate of rewarming can also be increased by raising the room temperature, applying a convective
heating device, using heating lamps, or warming the inspired air via the ventilator heating circuit on
the humidifier. While there are no data to determine the optimal timing for adding each of these
rewarming interventions, it is reasonable to add them one at a time to avoid the adverse effects from
overly rapid rewarming.

Potential adverse effects of therapeutic hypothermia (TH) — The most significant side effects of
TH are impaired coagulation and increased risk of infection. In addition, TH can adversely affect
several other physiologic processes.

TH induces a mild coagulopathy. With temperatures below 35°C, clotting enzymes operate more
slowly and platelets function less effectively [99-101]. As a result, some bleeding is seen in up to 20
percent of patients treated with TH, although transfusion is rarely required [19,102]. Data demonstrate
the incidence of bleeding is not significantly greater among post-cardiac arrest patients treated with
TH compared to those who remain normothermic [2,3,50,103].

The development of significant bleeding alters the balance of risk and benefit for TH. In the event of
significant bleeding (eg, significant decrease in hemoglobin, hemodynamic instability, intracranial
hemorrhage, noncompressible site), TH should be stopped and the patient rewarmed to a core
temperature of 36°C.

TH impairs leukocyte function. The incidence of significant infections is likely to increase if

hypothermia is maintained longer than 24 hours. While an increase in infection rates was noted in
several cohorts treated with 24 hours of TH [2,19,104], these infections were not associated with
increased mortality. In a large randomized trial, no significant difference in infection rates, including
pneumonia, was found in patients whose temperature was maintained at 33°C compared to patients
maintained at 36°C [50].

Hypothermia slows cardiac conduction and can provoke arrhythmias, including bradycardia and QT
interval prolongation [105]. A heart rate in the 40s is common at 33°C, but does not require
intervention if the blood pressure is acceptable. If intervention is needed for ventricular fibrillation or
pulseless ventricular tachycardia, animal studies report similar or improved first-shock success with
defibrillation in specimens with mild hypothermia compared to those with normothermia [106,107].
Retrospective and prospective observational data suggest that treatment with TH is not associated
with an increased need for vasopressor support [41,108].
Hyperglycemia due to insulin resistance has been noted during TH [105,109]. Large doses of insulin
may be needed in severely hyperglycemic patients. (See 'Glycemic control' below.)

Hypothermia leads to a "cold diuresis," which in turn can cause hypovolemia, hypokalemia,
hypomagnesaemia, and hypophosphatemia [110]. In addition, temperature fluctuations during the
induction of TH and rewarming cause potassium to move between the extracellular and intracellular
compartments [110-112]. Therefore, careful monitoring of volume status and measurement of basic
electrolytes approximately every three to four hours during temperature manipulation is prudent.
Hypokalemia is more frequently encountered in patients maintained at 33°C [50].

TH slows the metabolism and excretion of many drugs and thus the duration of effect may be
prolonged [113-115].

Evidence of benefit — The overall benefit of therapeutic hypothermia (TH) in patients who are
successfully resuscitated following cardiac arrest was summarized in a systematic review and meta-
analysis of six randomized trials including 1413 patients [116]. According to this review, patients
treated with TH were more likely to survive than patients whose temperature was not managed with
TH (relative risk [RR] 1.41; 95% CI 1.09-1.82), however, no difference in outcome was found based on
the target temperature. In a previous systematic review, pooled data from the three trials reporting
such results showed that patients treated with TH (n = 195) had better cerebral performance (RR 1.55;
95% CI 1.22-1.96) and were more likely to survive to hospital discharge (RR 1.35; 95% CI 1.10-1.65)
than those not treated with TH (n = 188) [49].

Conclusions about the absence of any difference in outcome based on the target temperature for TH
are based primarily on the findings of a large, well-performed, multinational randomized trial of 939
unconscious survivors of out-of-hospital cardiac arrest that reported no difference in mortality or
neurologic function between patients treated with TH to a target temperature of 33°C (n = 473)
compared to patients with a target temperature of 36°C (n = 466) [50]. In this trial, 54 percent of
patients in the 33°C target group either died or demonstrated poor neurologic function compared to 52
percent in the 36°C target group (RR 1.02; 95% CI 0.88-1.16). When using an alternative scale for
neurologic assessment (modified Rankin), the rate was 52 percent in each group (RR 1.01; 95% CI
0.89-1.14). Results did not vary significantly when patients were analyzed by several important
subgroups, including initial cardiac rhythm, time to return of spontaneous circulation, or patient age
[50,117]. A follow-up study of survivors performed at six months reported no significant difference in
cognitive function between the two treatment groups [118].

Evidence of benefit according to patients' presenting cardiac rhythm is described below.

Evidence in ventricular fibrillation and pulseless ventricular tachycardia — Mild TH, given
according to the parameters described above, decreases mortality and improves neurologic outcome
in patients with out-of-hospital cardiac arrest who present with ventricular fibrillation or pulseless
ventricular tachycardia [2,3]. Targeted temperature management (core temperature goal of 36°C) has
shown identical results [50]. Benefit has been demonstrated in three randomized trials:

● In one trial, subjects were randomly assigned to normothermia or treatment with TH for 24 hours
using a goal temperature of 32 to 34°C [2]. At six months, 56 of the 137 patients (41 percent)
treated with TH had died compared to 76 of the 138 normothermic patients (55 percent) (RR
 0.74; 95% CI, 0.58-0.95). In addition, 75 (55 percent) of the patients treated with TH had a good
neurologic outcome compared to 54 (39 percent) of the normothermic patients (RR 1.40; 95% CI
1.08-1.81).

● In another trial, 77 subjects were randomly assigned to either normothermia or treatment with TH
for 12 hours with a goal temperature of 32°C [3]. The rate of good neurologic outcome, defined as
discharge to home or an acute rehabilitation facility, was 49 percent in the TH group and 26
percent in the normothermia group. After adjusting for differences in age and time from collapse
to the return of spontaneous circulation, the authors reported the odds ratio for a good outcome
with TH, compared to normothermia, to be 5.25 (95% CI 1.47-18.76).

● A trial of 939 subjects randomized to temperature management using a goal of 33°C or 36°C for
24 hours demonstrated no difference in survival or good neurologic outcome between groups
[50]. In this trial, 54 percent of patients in the 33°C target group either died or demonstrated poor
neurologic function compared to 52 percent in the 36°C target group (RR 1.02; 95% CI 0.88-
1.16). When using an alternative scale for neurologic assessment (modified Rankin), the rate was
52 percent in each group (RR 1.01; 95% CI 0.89-1.14).

Evidence in non-shockable rhythms and in-hospital cardiac arrest — Therapeutic

hypothermia (TH) or temperature management is of potential benefit for minimizing brain injury in all
post-cardiac arrest patients, regardless of their arrhythmia or the location of their arrest. The 2015
Guidelines for Advanced Cardiac Life Support recommend TH or TTM for all unresponsive adult post-
cardiac arrest patients [27]. (See "Advanced cardiac life support (ACLS) in adults".)

Nonetheless, evidentiary support for TH in the treatment of patients with arrhythmias other than
ventricular fibrillation or pulseless ventricular tachycardia is primarily limited to non-randomized
studies using historical or concurrent controls (ie, observational studies with an inherent risk of bias).
One subgroup analysis of 186 patients with a non-shockable rhythm reported no difference in mortality
(HR 1.08; 95% CI 0.79, 1.48) between those treated with temperature management using a target of
33°C versus a target of 36°C [50].

Reports supporting the use of TH and TTM include one multicenter study of subjects with return of
spontaneous circulation following cardiac arrest that reported fewer deaths among the 124 patients
with non-shockable arrhythmias treated with TH compared to historical controls not treated with TH
[119]. Other studies have reported similar results [120-122]. However, several studies have not found
significant improvement in survival or neurologic outcome among those treated with TH whose
presenting arrhythmia was not ventricular fibrillation or pulseless ventricular tachycardia [5,123-128]. A
systematic review of ten nonrandomized studies reported significantly lower in-hospital mortality
among patients treated with TH (RR 0.84; 95% CI 0.78-0.92), but differences in neurologic outcome at
hospital discharge did not reach statistical significance (RR 0.95; 95% CI 0.90-1.01) [129].

Core temperature lability is associated with increased mortality after in-hospital cardiac arrest [130],
and hospitals in many countries use TH as part of the treatment for in-hospital cardiac arrest [5,19]. In
a retrospective review comparing outcomes for 1524 patients receiving TH and 3714 matched patients
who did not receive TH after in-hospital cardiac arrest, those treated with TH were less likely to
survive (27.4 versus 29.2 percent; RR 0.88 [95% CI 0.80-0.97]) or have a good neurologic outcome
(17 versus 20.5 percent; RR 0.79 [95% CI 0.69-0.90]) [131]. However, this study used a dataset that
did not record coma severity, making it unclear if some patients without coma were included in the no-
TH group. According to observational data, patients with cardiogenic shock requiring support with an
intra-aortic balloon pump also benefit from TH [45].

GENERAL CRITICAL CARE

Basic interventions — Routine interventions associated with excellent critical care should be part of
the management of post-cardiac arrest patients [132]. These include:

● Raising the head of the bed to 30 degrees, which helps to prevent aspiration and lowers
intracranial pressure (see "Evaluation and management of elevated intracranial pressure in
adults", section on 'Position')

● Stress ulcer prophylaxis (see "Stress ulcer prophylaxis in the intensive care unit")

● Deep venous thrombosis prophylaxis (see "Prevention of venous thromboembolic disease in

acutely ill hospitalized medical adults")

● Early physical and occupational therapy

Enteral feeding can resume once TH is completed, because bowel motility is usually suppressed
during hypothermia. (See "Nutrition support in critically ill patients: An overview".)

Antibiotic therapy and prophylaxis — Pneumonia is common and signs of disease prompt antibiotic
treatment in the majority of cardiac arrest survivors. Pending prospective trials showing evidence of
benefit, we do not suggest routine prophylactic therapy. Treatment of pneumonia in critically ill patients
is discussed separately. (See "Treatment of hospital-acquired and ventilator-associated pneumonia in
adults".)

Studies of prophylactic treatment of cardiac arrest patients with antibiotics are limited. Retrospective
data suggest an association between prophylactic antibiotic therapy and reduced incidence of
pneumonia among survivors [133]. In a single-center clinical trial, random assignment of 60 out-of-
hospital cardiac arrest patients without obvious evidence of tracheobronchial aspiration to prophylactic
antibiotics versus clinically-driven antibiotics reduced the number of positive cultures from broncho-
alveolar lavage on hospital day 3 [134]. However, there was no clinically or statistically significant
difference in survival or functional recovery between groups. Of note, 22 percent of patients were
excluded because of obvious tracheobronchial aspiration at the time of ICU admission, 13 percent of
patients without obvious aspiration had positive cultures on broncho-alveolar lavage, and subsequent
development of signs of infection during the ICU stay resulted in no difference in the proportion of
patients receiving antibiotics by hospital day 6 (>80 percent).

Glycemic control — Maintain serum glucose between 140 and 180 mg/dL (7.8 and 10 mmol/L)
during the period following cardiac arrest, and strive to avoid hypoglycemic episodes. Hyperglycemia
is associated with worse outcomes in post-cardiac arrest patients [135,136]. (See "Glycemic control
and intensive insulin therapy in critical illness".)

There is no additional benefit from tight control of the serum glucose (70 to 108 mg/dL; 3.9 to 6
mmol/L) compared to more liberal management (108 to 144 mg/dL; 6 to 8.1 mmol/L) following cardiac
arrest [137]. Multiple studies highlight the increased risk of hypoglycemia when lower target ranges
are used [137,138].

Seizures and myoclonic jerks — Seizure activity and myoclonic jerks are common after cardiac
arrest and often a marker of more severe brain injury. Electroencephalogram (EEG) monitoring may
be required to guide appropriate therapy and also provides prognostic information.

Monitoring — Many seizures in patients with hypoxic ischemic brain injury are nonconvulsive and
therefore require continuous EEG monitoring to detect. Whether continuous EEG monitoring should
be performed routinely following cardiac arrest is unclear, in part because of uncertainty as to whether
aggressive treatment of epileptiform activity improves neurologic outcomes. (See "Nonconvulsive
status epilepticus", section on 'How aggressively should one treat?'.)

While our practice is to perform continuous EEG monitoring in all comatose post-cardiac arrest
patients, this may not be feasible in all centers. Overall, available data suggest that EEG monitoring
should be prioritized in patients who are most likely to survive with good neurologic function (eg, those
whose initial brain CT shows no cerebral edema and for whom a structured neurologic examination
reveals a functioning brainstem), because detection and treatment of seizures in this setting may be
most likely to improve outcomes. The findings of a small cohort study suggest that intermittent and
continuous EEG monitoring demonstrate comparable effectiveness for detecting epileptiform patterns
in the post arrest patient [139]. Thus, clinical suspicion of nonconvulsive status epilepticus or daily
intermittent EEG monitoring may be a reasonable monitoring plan.

Interpretation of EEG patterns in comatose patients after hypoxic brain injury can be difficult, and
direct discussion with a consulting epileptologist at serial time points is often required to integrate
clinical and electrographic data. (See "Nonconvulsive status epilepticus", section on
'Electroencephalography'.)

In addition to seizure detection, continuous EEG monitoring provides prognostic information.

Definitions vary by study, but EEG patterns that are generally considered malignant in post-cardiac
arrest patients include: non-convulsive status epilepticus, convulsive status epilepticus, myoclonic
status epilepticus, and periodic epileptiform discharges [140-142]. In a series of 939 patients who
received EEG monitoring after rewarming or when clinically indicated, 29 percent experienced
seizures [140]. Those with seizures were less likely to survive. In another large cohort study, patients
with an intact brainstem examination after cardiac arrest experienced an increase in mortality from 36
to 87 percent when malignant EEG patterns were encountered [143]. Malignant epileptiform patterns
are less common in patients with early, diffuse cerebral edema: these patients usually have
suppression-burst or complete suppression as their primary EEG pattern, and have a poor prognosis
[144].

Prophylaxis and treatment — There is no high-quality evidence that clearly demonstrates benefit
from seizure prophylaxis in the post-cardiac arrest patient. Pending further research, we do not
routinely give such prophylaxis.

We do recommend aggressive treatment when epileptiform discharges progress to outright seizures

(either convulsive or nonconvulsive), based on reports of patients who survive following post-cardiac
arrest status epilepticus. Treatment of seizures in this setting is challenging because many are
refractory to single agent therapy, and the presence of epileptiform seizures may be a sign of severe
brain injury. The literature is limited to single-center case series of nonstandardized treatments with a
variety of agents, including valproic acid, phenytoin, midazolam, and propofol. In one series status
epilepticus was successfully treated in 3 of 3 subjects, but all had poor neurologic outcome [145]. In
another series, 3 of 5 subjects who survived after treatment for status epilepticus had poor neurologic
outcome [141]. As there are no trials specifically comparing treatments for seizures after cardiac
arrest, clinicians can use the same drugs and approaches for post-cardiac arrest seizures as are used
for status epilepticus, which is described separately. (See "Convulsive status epilepticus in adults:
Treatment and prognosis", section on 'Initial treatment' and "Nonconvulsive status epilepticus", section
on 'Treatment'.)

It is unclear whether treatment of epileptiform discharges that are not progressing into clear seizures
is beneficial. Repetitive spike or sharp waves (typically generalized epileptiform discharges) can occur
in up to 45 percent of patients [146]. In one series, 9 of 20 (45 percent) patients with epileptiform
discharges had good outcomes [141]. In another case series, among 46 of 139 patients with
convulsive or nonconvulsive epileptiform discharges, 14 of 17 (82 percent) had a poor outcome with
anticonvulsant drug treatment and 23 of 29 (79 percent) had a poor outcome without anticonvulsant
drug treatment [145]. Because the benefit from anticonvulsant drugs is uncertain, we do not
recommend treating epileptiform discharges unless they are increasing in frequency or showing signs
of progressing to seizures. (See "Nonconvulsive status epilepticus", section on 'EEG patterns of
definite NCSE'.)

Myoclonic jerks and other movements are common after cardiac arrest and can be isolated (non-
epileptic) or epileptic. EEG is generally required to distinguish the etiology (see 'Monitoring' above).
No specific significance has been attributed to isolated myoclonic jerks in patients following cardiac
arrest. Conversely, status myoclonus, defined as repetitive myoclonic jerks lasting more than 30
minutes, is an ominous sign. In 88 percent of cases, status myoclonus is associated with malignant
burst patterns on EEG with suppression of background between bursts [147]. Case series report poor
outcome after this malignant status myoclonus pattern, regardless of treatment. In 12 percent of
cases, status myoclonus is associated with epileptiform discharges with continuous EEG background.
Up to 50 percent of patients with this pattern recover to consciousness, though some continue to have
myoclonus after hospital discharge (Lance-Adam’s syndrome) [147].

Myoclonic jerks can be suppressed with sedatives, such as propofol or midazolam, which may
facilitate mechanical ventilation or other critical care. However, we do not recommend any specific
treatment of malignant status myoclonus. Various anticonvulsant drugs may reduce Lance-Adams
variant myoclonus, and trials of levetiracetam, valproic acid, clonazepam, or others are reasonable for
individual patients.

PROGNOSIS

Assessment of brain injury — Initial illness severity is strongly associated with survival and good
neurologic outcome following cardiac arrest [7]. Many post-cardiac arrest patients sustain
nonsurvivable neurologic injury. Serial neurologic examinations and ancillary diagnostic tests can
identify those patients with no chance of a good neurologic recovery. The neurologic assessment of
post-cardiac arrest patients, including clinical evaluation and ancillary testing, is discussed in detail
separately. (See "Hypoxic-ischemic brain injury: Evaluation and prognosis".)
Illness severity scores — Illness severity scores integrate information from multiple organ systems
to predict patient outcome. They may provide insight into the prognosis of the post-cardiac arrest
patient. (See "Predictive scoring systems in the intensive care unit".)

Several scores have been developed specifically for post-cardiac arrest patients and include event-
related data that often are not reliably recorded [148-151]. Moreover, data about the cardiac arrest
event may not predict the clinical course after the first day of hospitalization [152].

SPECIALIZED CENTERS FOR POST-RESUSCITATION CARE — Regionalized centers for post-

cardiac arrest patients have been proposed [153]. Post-cardiac arrest care requires significant
resources and coordination among multiple specialities. Sites that care for more than 50 post-cardiac
arrest patients per year have better outcomes than facilities with fewer patients [154]. Other hospital
characteristics, such as cardiac catheterization facilities, are associated with more favorable outcomes
[155]. Evidence from retrospective reviews suggests that referral to cardiac arrest centers is
associated with improved outcomes over both the short and long term [156,157]. Since most hospitals
see between 10 and 15 post-cardiac arrest patients per year and some do not have continuous
access to cardiac catheterization or electroencephalogram monitoring, it seems reasonable to transfer
post-cardiac arrest patients to suitable tertiary care centers whenever feasible.

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The
Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at
the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have
about a given condition. These articles are best for patients who want a general overview and who
prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and
are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-
mail these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on "patient info" and the keyword(s) of interest.)

● Basics topic (see "Patient education: Sudden cardiac arrest (The Basics)")

SUMMARY AND RECOMMENDATIONS

● Management of the post-cardiac arrest patient is complex and involves simultaneous

performance of both diagnostic and therapeutic interventions, including the following:

• Determining and treating the cause of cardiac arrest

• Minimizing brain injury

• Managing cardiovascular dysfunction

• Managing problems that may arise from global ischemia and reperfusion injury

● A focused history and physical examination are performed and diagnostic studies obtained in
order to identify possible causes for the arrest and ongoing or imminent threats to life. Acute
myocardial infarction, cardiomyopathy, and primary arrhythmia are the most common causes of
 sudden cardiac arrest (SCA), but a broad differential diagnosis should be considered. Common
etiologies for SCA are described in the attached tables (table 1 and table 2).

● The airway is evaluated first. An obstructed airway will rapidly lead to recurrent cardiac arrest.
Initial interventions include ensuring a patent and functioning airway and providing appropriate
ventilation. Goals for mechanical ventilation include maintaining a PaCO2 no lower than 40 to 45
mmHg and an oxygen saturation >94 percent. The target PaCO2 values are slightly higher in
patients treated with therapeutic hypothermia (TH). (See 'Respiratory considerations' above.)

● A baseline neurologic examination should be performed to help determine the possible cause,
likely clinical course, and need for neurologic interventions. Temporary avoidance or cessation of
neuromuscular blockade and sedation is necessary for a valid examination. Asymmetric
neurologic findings are not expected following return of spontaneous circulation (ROSC) and
suggest a structural intracranial lesion. (See 'History' above and 'Physical examination' above and
'Baseline neurologic examination' above.)

● Diagnostic tests, including an electrocardiogram (ECG), imaging studies, and laboratory tests, are
generally required to determine the etiology of cardiac arrest, to confirm endotracheal tube
positioning and assess for chest trauma from CPR, and to ascertain the involvement of specific
organ systems and gauge the severity of injury. Following the ROSC, a 12-lead ECG should be
rapidly obtained and evaluated for signs of ST-elevation myocardial infarction (STEMI) (including
a new left bundle branch block) that requires emergency reperfusion therapy. Commonly
performed testing is described in the text. (See 'Electrocardiogram' above and 'Imaging studies'
above and 'Laboratory testing' above.)

● Adequate blood pressure must be maintained to avoid exacerbating or causing ischemic brain
injury. IV fluids, inotropes, and vasopressors may be needed. Antiarrhythmic drugs should be
reserved for patients with recurrent or ongoing unstable arrhythmias. (See 'Maintaining end-organ
perfusion' above and 'Preventing arrhythmia' above.)

● Emergency coronary catheterization or medical reperfusion therapy is indicated for patients with
ECG findings of STEMI. Regardless of ECG findings, emergency coronary catheterization may
be needed for patients with ongoing hemodynamic instability or evidence of focal wall-motion
abnormalities on echocardiogram. In general, we also suggest that coronary artery
catheterization be performed in the post-arrest patient who does not have an obvious non-
cardiovascular etiology of arrest, with precise timing determined by the initial ECG, trajectory of
cardiac biomarker levels, presence of shock, and competing needs of ongoing resuscitation
procedures. Life-saving cardiovascular procedures should never be delayed because of coma.
Immediate consultation with an interventional cardiologist is appropriate for all such patients. (See
'Coronary revascularization' above.)

● Neurologic injury is the most common cause of death in patients with out-of-hospital cardiac
arrest. Preventing hyperthermia during the first few hours after cardiac arrest reduces the risk of
neurologic injury. Therefore, in patients who experience a ROSC following cardiac arrest, we
recommend instituting active measures to prevent hyperthermia (Grade 1B). In patients with
deep coma, evidence of cerebral edema, or malignant EEG patterns, we suggest maintaining the
patient's temperature at 33°C for 24 hours, followed by gradual rewarming (0.25°C/hour) (Grade
 2C). For facilities that are not experienced with TH, and for the management of uncomplicated
patients without malignant EEG patterns, evidence of cerebral edema, or deep coma, we suggest
maintaining the patient's temperature no higher than 36°C for 24 hours, followed by gradual
rewarming (0.25°C/hour) (Grade 2C). Methods for implementing and managing temperature
control are described in the text. (See 'Targeted temperature management (TTM) and therapeutic
hypothermia (TH)' above.)

● TH may be associated with complications, including an increased risk of infection if treatment

extends beyond 24 hours. TH induces a mild coagulopathy and should be stopped in the event of
significant bleeding. Hypothermia leads to a "cold diuresis," which in turn can cause hypovolemia,
hypokalemia, hypomagnesemia, and hypophosphatemia. Close monitoring of volume status and
serum electrolyte concentrations is necessary during TH.

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REFERENCES

1. Writing Group Members, Mozaffarian D, Benjamin EJ, et al. Heart Disease and Stroke Statistics-
2016 Update: A Report From the American Heart Association. Circulation 2016; 133:e38.
2. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the
neurologic outcome after cardiac arrest. N Engl J Med 2002; 346:549.
3. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital
cardiac arrest with induced hypothermia. N Engl J Med 2002; 346:557.
4. Sunde K, Pytte M, Jacobsen D, et al. Implementation of a standardised treatment protocol for
post resuscitation care after out-of-hospital cardiac arrest. Resuscitation 2007; 73:29.
5. Rittenberger JC, Guyette FX, Tisherman SA, et al. Outcomes of a hospital-wide plan to improve
care of comatose survivors of cardiac arrest. Resuscitation 2008; 79:198.
6. Tagami T, Hirata K, Takeshige T, et al. Implementation of the fifth link of the chain of survival
concept for out-of-hospital cardiac arrest. Circulation 2012; 126:589.
7. Rittenberger JC, Tisherman SA, Holm MB, et al. An early, novel illness severity score to predict
outcome after cardiac arrest. Resuscitation 2011; 82:1399.
8. Reynolds JC, Callaway CW, El Khoudary SR, et al. Coronary angiography predicts improved
outcome following cardiac arrest: propensity-adjusted analysis. J Intensive Care Med 2009;
24:179.
9. Dumas F, Cariou A, Manzo-Silberman S, et al. Immediate percutaneous coronary intervention is
associated with better survival after out-of-hospital cardiac arrest: insights from the PROCAT
(Parisian Region Out of hospital Cardiac ArresT) registry. Circ Cardiovasc Interv 2010; 3:200.
10. Spaulding CM, Joly LM, Rosenberg A, et al. Immediate coronary angiography in survivors of out-
of-hospital cardiac arrest. N Engl J Med 1997; 336:1629.
11. Moore CL, Copel JA. Point-of-care ultrasonography. N Engl J Med 2011; 364:749.
12. Rose JS, Bair AE, Mandavia D, Kinser DJ. The UHP ultrasound protocol: a novel ultrasound
approach to the empiric evaluation of the undifferentiated hypotensive patient. Am J Emerg Med
2001; 19:299.
13. Jones AE, Tayal VS, Sullivan DM, Kline JA. Randomized, controlled trial of immediate versus
delayed goal-directed ultrasound to identify the cause of nontraumatic hypotension in
emergency department patients. Crit Care Med 2004; 32:1703.
14. Scalea TM, Rodriguez A, Chiu WC, et al. Focused Assessment with Sonography for Trauma
(FAST): results from an international consensus conference. J Trauma 1999; 46:466.
15. Kirkpatrick AW, Sirois M, Laupland KB, et al. Hand-held thoracic sonography for detecting post-
traumatic pneumothoraces: the Extended Focused Assessment with Sonography for Trauma
(EFAST). J Trauma 2004; 57:288.
16. Metter RB, Rittenberger JC, Guyette FX, Callaway CW. Association between a quantitative CT
scan measure of brain edema and outcome after cardiac arrest. Resuscitation 2011; 82:1180.
17. Torbey MT, Selim M, Knorr J, et al. Quantitative analysis of the loss of distinction between gray
and white matter in comatose patients after cardiac arrest. Stroke 2000; 31:2163.
18. Yanagawa Y, Un-no Y, Sakamoto T, Okada Y. Cerebral density on CT immediately after a
successful resuscitation of cardiopulmonary arrest correlates with outcome. Resuscitation 2005;
64:97.
19. Nielsen N, Hovdenes J, Nilsson F, et al. Outcome, timing and adverse events in therapeutic
hypothermia after out-of-hospital cardiac arrest. Acta Anaesthesiol Scand 2009; 53:926.
20. Laurent I, Monchi M, Chiche JD, et al. Reversible myocardial dysfunction in survivors of out-of-
hospital cardiac arrest. J Am Coll Cardiol 2002; 40:2110.
21. Donnino MW, Miller J, Goyal N, et al. Effective lactate clearance is associated with improved
outcome in post-cardiac arrest patients. Resuscitation 2007; 75:229.
22. McKenzie N, Williams TA, Tohira H, et al. A systematic review and meta-analysis of the
association between arterial carbon dioxide tension and outcomes after cardiac arrest.
Resuscitation 2017; 111:116.
23. Kågström E, Smith ML, Siesjö BK. Cerebral circulatory responses to hypercapnia and hypoxia in
the recovery period following complete and incomplete cerebral ischemia in the rat. Acta Physiol
Scand 1983; 118:281.
24. Bisschops LL, Hoedemaekers CW, Simons KS, van der Hoeven JG. Preserved metabolic
coupling and cerebrovascular reactivity during mild hypothermia after cardiac arrest. Crit Care
Med 2010; 38:1542.
25. Buunk G, van der Hoeven JG, Frölich M, Meinders AE. Cerebral vasoconstriction in comatose
patients resuscitated from a cardiac arrest? Intensive Care Med 1996; 22:1191.
26. Buunk G, van der Hoeven JG, Meinders AE. Cerebrovascular reactivity in comatose patients
resuscitated from a cardiac arrest. Stroke 1997; 28:1569.
27. Callaway CW, Soar J, Aibiki M, et al. Part 4: Advanced Life Support: 2015 International
Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science
With Treatment Recommendations. Circulation 2015; 132:S84.
28. Aufderheide TP, Lurie KG. Death by hyperventilation: a common and life-threatening problem
during cardiopulmonary resuscitation. Crit Care Med 2004; 32:S345.
29. Wang CH, Chang WT, Huang CH, et al. The effect of hyperoxia on survival following adult
cardiac arrest: a systematic review and meta-analysis of observational studies. Resuscitation
2014; 85:1142.
30. Kilgannon JH, Jones AE, Shapiro NI, et al. Association between arterial hyperoxia following
resuscitation from cardiac arrest and in-hospital mortality. JAMA 2010; 303:2165.
31. Bellomo R, Bailey M, Eastwood GM, et al. Arterial hyperoxia and in-hospital mortality after
resuscitation from cardiac arrest. Crit Care 2011; 15:R90.
32. Kuisma M, Boyd J, Voipio V, et al. Comparison of 30 and the 100% inspired oxygen
concentrations during early post-resuscitation period: a randomised controlled pilot study.
Resuscitation 2006; 69:199.
33. Gaieski DF, Band RA, Abella BS, et al. Early goal-directed hemodynamic optimization combined
with therapeutic hypothermia in comatose survivors of out-of-hospital cardiac arrest.
Resuscitation 2009; 80:418.
34. Sitzwohl C, Kettner SC, Reinprecht A, et al. The arterial to end-tidal carbon dioxide gradient
increases with uncorrected but not with temperature-corrected PaCO2 determination during mild
to moderate hypothermia. Anesth Analg 1998; 86:1131.
35. Nishizawa H, Kudoh I. Cerebral autoregulation is impaired in patients resuscitated after cardiac
arrest. Acta Anaesthesiol Scand 1996; 40:1149.
36. Sundgreen C, Larsen FS, Herzog TM, et al. Autoregulation of cerebral blood flow in patients
resuscitated from cardiac arrest. Stroke 2001; 32:128.
37. Rudolf J, Ghaemi M, Ghaemi M, et al. Cerebral glucose metabolism in acute and persistent
vegetative state. J Neurosurg Anesthesiol 1999; 11:17.
38. Schaafsma A, de Jong BM, Bams JL, et al. Cerebral perfusion and metabolism in resuscitated
patients with severe post-hypoxic encephalopathy. J Neurol Sci 2003; 210:23.
39. Donnino MW, Rittenberger JC, Gaieski D, et al. The development and implementation of cardiac
arrest centers. Resuscitation 2011; 82:974.
40. Ruiz-Bailén M, Aguayo de Hoyos E, Ruiz-Navarro S, et al. Reversible myocardial dysfunction
after cardiopulmonary resuscitation. Resuscitation 2005; 66:175.
41. Huynh N, Kloke J, Gu C, et al. The effect of hypothermia "dose" on vasopressor requirements
and outcome after cardiac arrest. Resuscitation 2013; 84:189.
42. Camuglia AC, Randhawa VK, Lavi S, Walters DL. Cardiac catheterization is associated with
superior outcomes for survivors of out of hospital cardiac arrest: review and meta-analysis.
Resuscitation 2014; 85:1533.
43. Redfors B, Råmunddal T, Angerås O, et al. Angiographic findings and survival in patients
undergoing coronary angiography due to sudden cardiac arrest in western Sweden.
Resuscitation 2015; 90:13.
44. Millin MG, Comer AC, Nable JV, et al. Patients without ST elevation after return of spontaneous
circulation may benefit from emergent percutaneous intervention: A systematic review and meta-
analysis. Resuscitation 2016; 108:54.
45. Hovdenes J, Laake JH, Aaberge L, et al. Therapeutic hypothermia after out-of-hospital cardiac
arrest: experiences with patients treated with percutaneous coronary intervention and
cardiogenic shock. Acta Anaesthesiol Scand 2007; 51:137.
46. Skulec R, Kovarnik T, Dostalova G, et al. Induction of mild hypothermia in cardiac arrest
survivors presenting with cardiogenic shock syndrome. Acta Anaesthesiol Scand 2008; 52:188.
47. Laver S, Farrow C, Turner D, Nolan J. Mode of death after admission to an intensive care unit
 following cardiac arrest. Intensive Care Med 2004; 30:2126.
48. Schenone AL, Cohen A, Patarroyo G, et al. Therapeutic hypothermia after cardiac arrest: A
systematic review/meta-analysis exploring the impact of expanded criteria and targeted
temperature. Resuscitation 2016; 108:102.
49. Arrich J, Holzer M, Havel C, et al. Hypothermia for neuroprotection in adults after
cardiopulmonary resuscitation. Cochrane Database Syst Rev 2016; 2:CD004128.
50. Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33°C versus
36°C after cardiac arrest. N Engl J Med 2013; 369:2197.
51. Zeiner A, Holzer M, Sterz F, et al. Hyperthermia after cardiac arrest is associated with an
unfavorable neurologic outcome. Arch Intern Med 2001; 161:2007.
52. Gebhardt K, Guyette FX, Doshi AA, et al. Prevalence and effect of fever on outcome following
resuscitation from cardiac arrest. Resuscitation 2013; 84:1062.
53. Grossestreuer AV, Gaieski DF, Donnino MW, et al. Magnitude of temperature elevation is
associated with neurologic and survival outcomes in resuscitated cardiac arrest patients with
postrewarming pyrexia. J Crit Care 2017; 38:78.
54. Rittenberger JC, Kelly E, Jang D, et al. Successful outcome utilizing hypothermia after cardiac
arrest in pregnancy: a case report. Crit Care Med 2008; 36:1354.
55. Chauhan A, Musunuru H, Donnino M, et al. The use of therapeutic hypothermia after cardiac
arrest in a pregnant patient. Ann Emerg Med 2012; 60:786.
56. Donnino MW, Andersen LW, Berg KM, et al. Temperature Management After Cardiac Arrest: An
Advisory Statement by the Advanced Life Support Task Force of the International Liaison
Committee on Resuscitation and the American Heart Association Emergency Cardiovascular
Care Committee and the Council on Cardiopulmonary, Critical Care, Perioperative and
Resuscitation. Circulation 2015; 132:2448.
57. Kirkegaard H, Søreide E, de Haas I, et al. Targeted Temperature Management for 48 vs 24
Hours and Neurologic Outcome After Out-of-Hospital Cardiac Arrest: A Randomized Clinical
Trial. JAMA 2017; 318:341.
58. Callaway CW. Targeted Temperature Management After Cardiac Arrest: Finding the Right Dose
for Critical Care Interventions. JAMA 2017; 318:334.
59. Nagao K, Kikushima K, Watanabe K, et al. Early induction of hypothermia during cardiac arrest
improves neurological outcomes in patients with out-of-hospital cardiac arrest who undergo
emergency cardiopulmonary bypass and percutaneous coronary intervention. Circ J 2010;
74:77.
60. Kuboyama K, Safar P, Radovsky A, et al. Delay in cooling negates the beneficial effect of mild
resuscitative cerebral hypothermia after cardiac arrest in dogs: a prospective, randomized study.
Crit Care Med 1993; 21:1348.
61. Zhao D, Abella BS, Beiser DG, et al. Intra-arrest cooling with delayed reperfusion yields higher
survival than earlier normothermic resuscitation in a mouse model of cardiac arrest.
Resuscitation 2008; 77:242.
62. Bernard SA, Smith K, Cameron P, et al. Induction of therapeutic hypothermia by paramedics
after resuscitation from out-of-hospital ventricular fibrillation cardiac arrest: a randomized
controlled trial. Circulation 2010; 122:737.
63. Kim F, Nichol G, Maynard C, et al. Effect of prehospital induction of mild hypothermia on survival
and neurological status among adults with cardiac arrest: a randomized clinical trial. JAMA 2014;
311:45.
64. Bucher J, Koyfman A. Does Initiation of Therapeutic Hypothermia in the Out-of-Hospital
Environment Improve Neurologic Outcomes? Ann Emerg Med 2015; 66:379.
65. Bernard SA, Smith K, Finn J, et al. Induction of Therapeutic Hypothermia During Out-of-Hospital
Cardiac Arrest Using a Rapid Infusion of Cold Saline: The RINSE Trial (Rapid Infusion of Cold
Normal Saline). Circulation 2016; 134:797.
66. Bray JE, Stub D, Bloom JE, et al. Changing target temperature from 33°C to 36°C in the ICU
management of out-of-hospital cardiac arrest: A before and after study. Resuscitation 2017;
113:39.
67. Cristia C, Ho ML, Levy S, et al. The association between a quantitative computed tomography
(CT) measurement of cerebral edema and outcomes in post-cardiac arrest-a validation study.
Resuscitation 2014; 85:1348.
68. Seule MA, Muroi C, Mink S, et al. Therapeutic hypothermia in patients with aneurysmal
subarachnoid hemorrhage, refractory intracranial hypertension, or cerebral vasospasm.
Neurosurgery 2009; 64:86.
69. Sadaka F, Veremakis C. Therapeutic hypothermia for the management of intracranial
hypertension in severe traumatic brain injury: a systematic review. Brain Inj 2012; 26:899.
70. Stravitz RT, Larsen FS. Therapeutic hypothermia for acute liver failure. Crit Care Med 2009;
37:S258.
71. Schwab S, Schwarz S, Spranger M, et al. Moderate hypothermia in the treatment of patients
with severe middle cerebral artery infarction. Stroke 1998; 29:2461.
72. Corry JJ, Dhar R, Murphy T, Diringer MN. Hypothermia for refractory status epilepticus. Neurocrit
Care 2008; 9:189.
73. Low E, Boylan GB, Mathieson SR, et al. Cooling and seizure burden in term neonates: an
observational study. Arch Dis Child Fetal Neonatal Ed 2012; 97:F267.
74. Azzopardi D, Strohm B, Edwards AD, et al. Treatment of asphyxiated newborns with moderate
hypothermia in routine clinical practice: how cooling is managed in the UK outside a clinical trial.
Arch Dis Child Fetal Neonatal Ed 2009; 94:F260.
75. Callaway CW, Tadler SC, Katz LM, et al. Feasibility of external cranial cooling during out-of-
hospital cardiac arrest. Resuscitation 2002; 52:159.
76. Kim F, Olsufka M, Longstreth WT Jr, et al. Pilot randomized clinical trial of prehospital induction
of mild hypothermia in out-of-hospital cardiac arrest patients with a rapid infusion of 4 degrees C
normal saline. Circulation 2007; 115:3064.
77. Kliegel A, Losert H, Sterz F, et al. Cold simple intravenous infusions preceding special
endovascular cooling for faster induction of mild hypothermia after cardiac arrest--a feasibility
study. Resuscitation 2005; 64:347.
78. Al-Senani FM, Graffagnino C, Grotta JC, et al. A prospective, multicenter pilot study to evaluate
the feasibility and safety of using the CoolGard System and Icy catheter following cardiac arrest.
Resuscitation 2004; 62:143.
79. Tømte Ø, Drægni T, Mangschau A, et al. A comparison of intravascular and surface cooling
 techniques in comatose cardiac arrest survivors. Crit Care Med 2011; 39:443.
80. Merchant RM, Abella BS, Peberdy MA, et al. Therapeutic hypothermia after cardiac arrest:
unintentional overcooling is common using ice packs and conventional cooling blankets. Crit
Care Med 2006; 34:S490.
81. Moore TM, Callaway CW, Hostler D. Core temperature cooling in healthy volunteers after rapid
intravenous infusion of cold and room temperature saline solution. Ann Emerg Med 2008;
51:153.
82. Hostler D, Northington WE, Callaway CW. High-dose diazepam facilitates core cooling during
cold saline infusion in healthy volunteers. Appl Physiol Nutr Metab 2009; 34:582.
83. Badjatia N, Strongilis E, Gordon E, et al. Metabolic impact of shivering during therapeutic
temperature modulation: the Bedside Shivering Assessment Scale. Stroke 2008; 39:3242.
84. Rittenberger JC, Polderman K. Post-Arrest Management. Emergency Neurological Life Support
Course. http://protocols.enlscourse.org (Accessed on April 01, 2011).
85. Chamorro C, Borrallo JM, Romera MA, et al. Anesthesia and analgesia protocol during
therapeutic hypothermia after cardiac arrest: a systematic review. Anesth Analg 2010; 110:1328.
86. Hostler D, Zhou J, Tortorici MA, et al. Mild hypothermia alters midazolam pharmacokinetics in
normal healthy volunteers. Drug Metab Dispos 2010; 38:781.
87. Callaway CW, Elmer J, Guyette FX, et al. Dexmedetomidine Reduces Shivering during Mild
Hypothermia in Waking Subjects. PLoS One 2015; 10:e0129709.
88. Abend NS, Topjian A, Ichord R, et al. Electroencephalographic monitoring during hypothermia
after pediatric cardiac arrest. Neurology 2009; 72:1931.
89. Rundgren M, Rosén I, Friberg H. Amplitude-integrated EEG (aEEG) predicts outcome after
cardiac arrest and induced hypothermia. Intensive Care Med 2006; 32:836.
90. Krumholz A, Stern BJ, Weiss HD. Outcome from coma after cardiopulmonary resuscitation:
relation to seizures and myoclonus. Neurology 1988; 38:401.
91. Nielsen N, Sunde K, Hovdenes J, et al. Adverse events and their relation to mortality in out-of-
hospital cardiac arrest patients treated with therapeutic hypothermia. Crit Care Med 2011; 39:57.
92. Robinson J, Charlton J, Seal R, et al. Oesophageal, rectal, axillary, tympanic and pulmonary
artery temperatures during cardiac surgery. Can J Anaesth 1998; 45:317.
93. Coppler PJ, Marill KA, Okonkwo DO, et al. Concordance of Brain and Core Temperature in
Comatose Patients After Cardiac Arrest. Ther Hypothermia Temp Manag 2016; 6:194.
94. Erickson RS, Kirklin SK. Comparison of ear-based, bladder, oral, and axillary methods for core
temperature measurement. Crit Care Med 1993; 21:1528.
95. Suehiro E, Singleton RH, Stone JR, Povlishock JT. The immunophilin ligand FK506 attenuates
the axonal damage associated with rapid rewarming following posttraumatic hypothermia. Exp
Neurol 2001; 172:199.
96. Suehiro E, Ueda Y, Wei EP, et al. Posttraumatic hypothermia followed by slow rewarming
protects the cerebral microcirculation. J Neurotrauma 2003; 20:381.
97. Heard KJ, Peberdy MA, Sayre MR, et al. A randomized controlled trial comparing the Arctic Sun
to standard cooling for induction of hypothermia after cardiac arrest. Resuscitation 2010; 81:9.
98. Pichon N, Amiel JB, François B, et al. Efficacy of and tolerance to mild induced hypothermia
 after out-of-hospital cardiac arrest using an endovascular cooling system. Crit Care 2007;
11:R71.
99. Michelson AD, MacGregor H, Barnard MR, et al. Reversible inhibition of human platelet
activation by hypothermia in vivo and in vitro. Thromb Haemost 1994; 71:633.
100. Reed RL 2nd, Bracey AW Jr, Hudson JD, et al. Hypothermia and blood coagulation: dissociation
between enzyme activity and clotting factor levels. Circ Shock 1990; 32:141.
101. Valeri CR, Feingold H, Cassidy G, et al. Hypothermia-induced reversible platelet dysfunction.
Ann Surg 1987; 205:175.
102. Jarrah S, Dziodzio J, Lord C, et al. Surface cooling after cardiac arrest: effectiveness, skin
safety, and adverse events in routine clinical practice. Neurocrit Care 2011; 14:382.
103. Stockmann H, Krannich A, Schroeder T, Storm C. Therapeutic temperature management after
cardiac arrest and the risk of bleeding: systematic review and meta-analysis. Resuscitation
2014; 85:1494.
104. Perbet S, Mongardon N, Dumas F, et al. Early-onset pneumonia after cardiac arrest:
characteristics, risk factors and influence on prognosis. Am J Respir Crit Care Med 2011;
184:1048.
105. Polderman KH, Herold I. Therapeutic hypothermia and controlled normothermia in the intensive
care unit: practical considerations, side effects, and cooling methods. Crit Care Med 2009;
37:1101.
106. Rhee BJ, Zhang Y, Boddicker KA, et al. Effect of hypothermia on transthoracic defibrillation in a
swine model. Resuscitation 2005; 65:79.
107. Boddicker KA, Zhang Y, Zimmerman MB, et al. Hypothermia improves defibrillation success and
resuscitation outcomes from ventricular fibrillation. Circulation 2005; 111:3195.
108. Roberts BW, Kilgannon JH, Chansky ME, et al. Therapeutic hypothermia and vasopressor
dependency after cardiac arrest. Resuscitation 2013; 84:331.
109. Cueni-Villoz N, Devigili A, Delodder F, et al. Increased blood glucose variability during
therapeutic hypothermia and outcome after cardiac arrest. Crit Care Med 2011; 39:2225.
110. Polderman KH, Peerdeman SM, Girbes AR. Hypophosphatemia and hypomagnesemia induced
by cooling in patients with severe head injury. J Neurosurg 2001; 94:697.
111. Clifton GL, Miller ER, Choi SC, Levin HS. Fluid thresholds and outcome from severe brain injury.
Crit Care Med 2002; 30:739.
112. Aibiki M, Kawaguchi S, Maekawa N. Reversible hypophosphatemia during moderate
hypothermia therapy for brain-injured patients. Crit Care Med 2001; 29:1726.
113. van den Broek MP, Groenendaal F, Egberts AC, Rademaker CM. Effects of hypothermia on
pharmacokinetics and pharmacodynamics: a systematic review of preclinical and clinical studies.
Clin Pharmacokinet 2010; 49:277.
114. Tortorici MA, Kochanek PM, Poloyac SM. Effects of hypothermia on drug disposition,
metabolism, and response: A focus of hypothermia-mediated alterations on the cytochrome
P450 enzyme system. Crit Care Med 2007; 35:2196.
115. Zhou J, Poloyac SM. The effect of therapeutic hypothermia on drug metabolism and response:
cellular mechanisms to organ function. Expert Opin Drug Metab Toxicol 2011; 7:803.
116. Vargas M, Servillo G, Sutherasan Y, et al. Effects of in-hospital low targeted temperature after
 out of hospital cardiac arrest: A systematic review with meta-analysis of randomized clinical
trials. Resuscitation 2015; 91:8.
117. Winther-Jensen M, Pellis T, Kuiper M, et al. Mortality and neurological outcome in the elderly
after target temperature management for out-of-hospital cardiac arrest. Resuscitation 2015;
91:92.
118. Cronberg T, Lilja G, Horn J, et al. Neurologic Function and Health-Related Quality of Life in
Patients Following Targeted Temperature Management at 33°C vs 36°C After Out-of-Hospital
Cardiac Arrest: A Randomized Clinical Trial. JAMA Neurol 2015; 72:634.
119. Arrich J, European Resuscitation Council Hypothermia After Cardiac Arrest Registry Study
Group. Clinical application of mild therapeutic hypothermia after cardiac arrest. Crit Care Med
2007; 35:1041.
120. Bernard SA, Jones BM, Horne MK. Clinical trial of induced hypothermia in comatose survivors of
out-of-hospital cardiac arrest. Ann Emerg Med 1997; 30:146.
121. Busch M, Soreide E, Lossius HM, et al. Rapid implementation of therapeutic hypothermia in
comatose out-of-hospital cardiac arrest survivors. Acta Anaesthesiol Scand 2006; 50:1277.
122. Storm C, Steffen I, Schefold JC, et al. Mild therapeutic hypothermia shortens intensive care unit
stay of survivors after out-of-hospital cardiac arrest compared to historical controls. Crit Care
2008; 12:R78.
123. Oddo M, Schaller MD, Feihl F, et al. From evidence to clinical practice: effective implementation
of therapeutic hypothermia to improve patient outcome after cardiac arrest. Crit Care Med 2006;
34:1865.
124. Whitfield AM, Coote S, Ernest D. Induced hypothermia after out-of-hospital cardiac arrest: one
hospital's experience. Crit Care Resusc 2009; 11:97.
125. Don CW, Longstreth WT Jr, Maynard C, et al. Active surface cooling protocol to induce mild
therapeutic hypothermia after out-of-hospital cardiac arrest: a retrospective before-and-after
comparison in a single hospital. Crit Care Med 2009; 37:3062.
126. Dumas F, Grimaldi D, Zuber B, et al. Is hypothermia after cardiac arrest effective in both
shockable and nonshockable patients?: insights from a large registry. Circulation 2011; 123:877.
127. Storm C, Nee J, Roser M, et al. Mild hypothermia treatment in patients resuscitated from non-
shockable cardiac arrest. Emerg Med J 2012; 29:100.
128. Vaahersalo J, Hiltunen P, Tiainen M, et al. Therapeutic hypothermia after out-of-hospital cardiac
arrest in Finnish intensive care units: the FINNRESUSCI study. Intensive Care Med 2013;
39:826.
129. Kim YM, Yim HW, Jeong SH, et al. Does therapeutic hypothermia benefit adult cardiac arrest
patients presenting with non-shockable initial rhythms?: A systematic review and meta-analysis
of randomized and non-randomized studies. Resuscitation 2012; 83:188.
130. Suffoletto B, Peberdy MA, van der Hoek T, Callaway C. Body temperature changes are
associated with outcomes following in-hospital cardiac arrest and return of spontaneous
circulation. Resuscitation 2009; 80:1365.
131. Chan PS, Berg RA, Tang Y, et al. Association Between Therapeutic Hypothermia and Survival
After In-Hospital Cardiac Arrest. JAMA 2016; 316:1375.
132. Bjork RJ, Snyder BD, Campion BC, Loewenson RB. Medical complications of cardiopulmonary
 arrest. Arch Intern Med 1982; 142:500.
133. Gagnon DJ, Nielsen N, Fraser GL, et al. Prophylactic antibiotics are associated with a lower
incidence of pneumonia in cardiac arrest survivors treated with targeted temperature
management. Resuscitation 2015; 92:154.
134. Ribaric SF, Turel M, Knafelj R, et al. Prophylactic versus clinically-driven antibiotics in comatose
survivors of out-of-hospital cardiac arrest-A randomized pilot study. Resuscitation 2017; 111:103.
135. Longstreth WT Jr, Diehr P, Cobb LA, et al. Neurologic outcome and blood glucose levels during
out-of-hospital cardiopulmonary resuscitation. Neurology 1986; 36:1186.
136. Skrifvars MB, Pettilä V, Rosenberg PH, Castrén M. A multiple logistic regression analysis of in-
hospital factors related to survival at six months in patients resuscitated from out-of-hospital
ventricular fibrillation. Resuscitation 2003; 59:319.
137. Oksanen T, Skrifvars MB, Varpula T, et al. Strict versus moderate glucose control after
resuscitation from ventricular fibrillation. Intensive Care Med 2007; 33:2093.
138. NICE-SUGAR Study Investigators, Finfer S, Chittock DR, et al. Intensive versus conventional
glucose control in critically ill patients. N Engl J Med 2009; 360:1283.
139. Alvarez V, Sierra-Marcos A, Oddo M, Rossetti AO. Yield of intermittent versus continuous EEG
in comatose survivors of cardiac arrest treated with hypothermia. Crit Care 2013; 17:R190.
140. Lybeck A, Friberg H, Aneman A, et al. Prognostic significance of clinical seizures after cardiac
arrest and target temperature management. Resuscitation 2017; 114:146.
141. Amorim E, Rittenberger JC, Baldwin ME, et al. Malignant EEG patterns in cardiac arrest patients
treated with targeted temperature management who survive to hospital discharge. Resuscitation
2015; 90:127.
142. Rittenberger JC, Popescu A, Brenner RP, et al. Frequency and timing of nonconvulsive status
epilepticus in comatose post-cardiac arrest subjects treated with hypothermia. Neurocrit Care
2012; 16:114.
143. Youn CS, Callaway CW, Rittenberger JC, Post Cardiac Arrest Service. Combination of initial
neurologic examination and continuous EEG to predict survival after cardiac arrest.
Resuscitation 2015; 94:73.
144. Youn CS, Callaway CW, Rittenberger JC, Post Cardiac Arrest Service. Combination of initial
neurologic examination, quantitative brain imaging and electroencephalography to predict
outcome after cardiac arrest. Resuscitation 2017; 110:120.
145. Hofmeijer J, Tjepkema-Cloostermans MC, Blans MJ, et al. Unstandardized treatment of
electroencephalographic status epilepticus does not improve outcome of comatose patients after
cardiac arrest. Front Neurol 2014; 5:39.
146. Amorim E, Rittenberger JC, Zheng JJ, et al. Continuous EEG monitoring enhances multimodal
outcome prediction in hypoxic-ischemic brain injury. Resuscitation 2016; 109:121.
147. Elmer J, Rittenberger JC, Faro J, et al. Clinically distinct electroencephalographic phenotypes of
early myoclonus after cardiac arrest. Ann Neurol 2016; 80:175.
148. Adrie C, Cariou A, Mourvillier B, et al. Predicting survival with good neurological recovery at
hospital admission after successful resuscitation of out-of-hospital cardiac arrest: the OHCA
score. Eur Heart J 2006; 27:2840.
149. Haukoos JS, Lewis RJ, Stratton SJ, Niemann JT. Is the ACLS score a valid prediction rule for
 survival after cardiac arrest? Acad Emerg Med 2003; 10:621.
150. Oksanen T, Tiainen M, Skrifvars MB, et al. Predictive power of serum NSE and OHCA score
regarding 6-month neurologic outcome after out-of-hospital ventricular fibrillation and therapeutic
hypothermia. Resuscitation 2009; 80:165.
151. Rittenberger JC, Martin JR, Kelly LJ, et al. Inter-rater reliability for witnessed collapse and
presence of bystander CPR. Resuscitation 2006; 70:410.
152. Wang HE, Min A, Hostler D, et al. Differential effects of out-of-hospital interventions on short-
and long-term survival after cardiopulmonary arrest. Resuscitation 2005; 67:69.
153. Nichol G, Aufderheide TP, Eigel B, et al. Regional systems of care for out-of-hospital cardiac
arrest: A policy statement from the American Heart Association. Circulation 2010; 121:709.
154. Carr BG, Kahn JM, Merchant RM, et al. Inter-hospital variability in post-cardiac arrest mortality.
Resuscitation 2009; 80:30.
155. Callaway CW, Schmicker R, Kampmeyer M, et al. Receiving hospital characteristics associated
with survival after out-of-hospital cardiac arrest. Resuscitation 2010; 81:524.
156. Schober A, Sterz F, Laggner AN, et al. Admission of out-of-hospital cardiac arrest victims to a
high volume cardiac arrest center is linked to improved outcome. Resuscitation 2016; 106:42.
157. Elmer J, Rittenberger JC, Coppler PJ, et al. Long-term survival benefit from treatment at a
specialty center after cardiac arrest. Resuscitation 2016; 108:48.

Topic 13838 Version 33.0

GRAPHICS

Common etiologies of cardiac arrest in adults

Cardiac
Acute coronary syndrome (most common)

Arrhythmia: Secondary to electrolyte disorder, acidosis, other process; abnormal conduction

syndromes (eg, prolonged QT, Brugada)

Pericardial tamponade

Respiratory
Airway obstruction: Mucus plug, foreign body, tracheostomy decannulation

Asthma/COPD exacerbation

Pneumonia

Pulmonary embolus

Tension pneumothorax

Hemmorhage and hypovolemia

Trauma

Gastrointestinal bleeding

Abdominal aortic aneursym rupture

Intracranial hemorrhage

Profound gastrointestinal fluid loss

Drugs and poisons

Opioids

Beta blockers

Calcium-channel blockers

Benzodiazepines

Tricyclic antidepressants

Digoxin

Electrolyte disturbances
Potassium

Magnesium

Sepsis

Graphic 70060 Version 3.0

Treatable conditions associated with cardiac arrest

Condition Common associated clinical settings

Acidosis Diabetes, diarrhea, drug overdose, renal dysfunction, sepsis, shock

Anemia Gastrointestinal bleeding, nutritional deficiencies, recent trauma

Cardiac Post-cardiac surgery, malignancy, post-myocardial infarction, pericarditis, trauma

tamponade

Hyperkalemia Drug overdose, renal dysfunction, hemolysis, excessive potassium intake,

rhabdomyolysis, major soft tissue injury, tumor lysis syndrome

Hypokalemia* Alcohol abuse, diabetes mellitus, diuretics, drug overdose, profound gastrointestinal
losses

Hypothermia Alcohol intoxication, significant burns, drowning, drug overdose, elder patient,
endocrine disease, environmental exposure, spinal cord disease, trauma

Hypovolemia Significant burns, diabetes, gastrointestinal losses, hemorrhage, malignancy, sepsis,

trauma

Hypoxia Upper airway obstruction, hypoventilation (CNS dysfunction, neuromuscular disease),

pulmonary disease

Myocardial Cardiac arrest

infarction

Poisoning History of alcohol or drug abuse, altered mental status, classic toxidrome (eg,
sympathomimetic), occupational exposure, psychiatric disease

Pulmonary Immobilized patient, recent surgical procedure (eg, orthopedic), peripartum, risk
embolism factors for thromboembolic disease, recent trauma, presentation consistent with
acute pulmonary embolism

Tension Central venous catheter, mechanical ventilation, pulmonary disease (eg, asthma,
pneumothorax chronic obstructive pulmonary disease), thoracentesis, thoracic trauma

* Hypomagnesemia should be assumed in the setting of hypokalemia, and both should be treated.

Adapted from: Eisenberg MS, Mengert TJ. Cardiac resuscitation. N Engl J Med 2001; 344:1304.

Graphic 52416 Version 7.0

Contributor Disclosures
Jon C Rittenberger, MD, MS Grant/Research/Clinical Trial Support: Laerdal Medical [early EEG in
cardiac arrest patients]; American Heart Association [cardiac arrest (amantadine, rocuronium)].
Honorarium: CR Bard [lecture at the 2015 Asia TTM course]. Clifton W Callaway, MD, PhD Nothing
to disclose Ron M Walls, MD, FRCPC, FAAEM Other Financial Interest: Airway Management
Education Center [Healthcare provider education and resources (Cook Melker Universal
Cricothyrotomy kit, the Difficult Airway course)]. Jonathan Grayzel, MD, FAAEM Nothing to disclose

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