2258 PART 8 Critical Care Medicine

low-income neighborhoods, is likely a contributing factor but does not

appear to account for the entirety of the elevated SCD rate in blacks.

Alternatively, individuals of Hispanic ethnicity appear to have lower

rates of SCD, despite having a higher prevalence of cardiac risk factors.

It appears that the incidence of SCD may be relatively low among Asian

populations as well, both within the United States and globally. These

gender and racial differences in SCD/SCA incidence and survival are

poorly understood and warrant further research.

TABLE 306-1 Distinction between Cardiovascular Collapse, Cardiac Arrest, and Death

TERM DEFINITION QUALIFIERS MECHANISMS

Cardiovascular collapse Sudden loss of effective circulation due to cardiac

and/or peripheral vascular factors that may reverse

spontaneously (e.g., neurocardiogenic syncope,

vasovagal syncope) or require interventions (e.g.,

cardiac arrest).

Broad term that includes cardiac

arrest and transient events that

characteristically revert spontaneously

presenting as syncope.

Same as cardiac arrest, plus

vasodepressor syncope or other causes

of transient loss of blood flow.

Cardiac arrest Abrupt cessation of cardiac function resulting in

loss of effective circulation that may be reversible by

prompt emergency medical intervention but will lead

to death in its absence.

Rare spontaneous reversions; likelihood

of successful intervention relates to

mechanism of arrest, clinical setting,

availability of emergency medical

services, and prompt return of circulation.

Ventricular fibrillation, ventricular

tachycardia, asystole, bradycardia,

pulseless electrical activity, noncardiac

mechanical factors (e.g., pulmonary

embolism).

Sudden cardiac death Sudden unexpected death attributed to cardiac

arrest, which if witnessed occurs within 1 h of

symptom onset.

In unwitnessed cases, the definition is

often expanded to include unexpected

deaths where the subject was

documented to be well within the

preceding 24 h.

Same as cardiac arrest.

Source: Modified from RJ Myerburg, A Castellanos: Cardiovascular collapse, cardiac arrest, and sudden cardiac death, in Harrison’s Principles of Internal Medicine,

19th ed, DL Kasper et al (eds). New York, McGraw-Hill Education, 2015, pp. 1764–1771, Table 327-1.

0 3 HCM, ARVC 5

Coronary heart disease ~ 40–70%

White Men: 70%

Women and Black Men 40–50%

Asians < 40%

Valvular heart disease

1–5%

Idiopathic

VF/Others

A

Inherited arrhythmia

syndrome

(LQTS, BrS, CPVT, ERS, etc.)

1–2% in Western countries

10% in Asia Myocardial Substrates:

Myocardial scar

Hypertrophy

Fibrosis

Myocardial stretch

Electrical heterogeneity

Ion channel functional modification

Abnormal calcium handling

Cardiomyopathies

(NIDCM, HCM, ARVC, etc.)

10–15% in Western countries

30–35% in Asia

Triggers

Heart failure/Stretch

Ischemia

Myocardial inflammation

Vigorous exertion

Electrolyte abnormality

Environmental stress

Psychological stress/Depression

CPVT, LQTS

B

Age of SCD onset NIDCM

BrS, ERS

Coronary Heart Disease

Valvular Heart Disease

Population‐Based Risk Factors

Male sex

Black race

Diabetes

Current smoking

Hypertension

Chronic kidney disease

ECG features (QT, QRS prolongation, early repolarization, LVH)

Family history of SCD (genetics)

Diet low in N-3 PUFA

Atrial fibrillation

Obstructive sleep apnea

Heavy alcohol intake

Low magnesium levels

Sudden Cardiac Death

Causes

FIGURE 306-1 A. Proportionate causes, substrates, risk factors, and triggers of sudden cardiac death (SCD). B. Variation of causes by age of onset. (Reproduced with

permission from M Hayashi et al: The spectrum of epidemiology underlying sudden cardiac death. Circ Res 116:1887, 2015.)

■ RISK FACTORS (SEE FIG. 306-1)

The presence of overt structural heart disease and/or certain types

of inherited arrhythmia syndromes markedly elevates SCD risk (see

Chaps. 254 and 255). Preexisting CHD and HF are the most prevalent

predisposing cardiac conditions and are associated with a four- to

tenfold increase in SCD risk. Correspondingly, SCD shares many

of the same risk factors with CHD and HF, including hypertension,

diabetes, hypercholesterolemia, obesity, and smoking. Diabetes is a

2259Cardiovascular Collapse, Cardiac Arrest, and Sudden Cardiac Death CHAPTER 306

particularly strong risk factor for SCD even in patients with established

CHD. Hypertension and resultant left ventricular hypertrophy (LVH)

appear to be particularly important markers of SCD risk in blacks, in

whom the prevalence of these conditions is greater. Smoking markedly

elevates risk, and smoking cessation lowers risk particularly among

individuals who have not yet developed overt CHD. Serum cholesterol

appears to be more strongly related to SCD at younger ages, and the

benefits of cholesterol lowering on SCD incidence have not been firmly

established. There also appears to be a genetic component to SCD

risk that is distinct from that associated with other manifestations of

atherosclerosis. A history of SCD in a first-degree relative is associated

with an increased risk for SCD, and with the occurrence of ventricular fibrillation (VF) during acute MI, but is not associated with an

increased risk for acute MI. These data suggest that genetic factors may

predispose to fatal ventricular arrhythmia in the setting of ischemia,

rather than to CHD in general.

Obstructive sleep apnea and seizure disorders are also associated

with increased SCD risk; the underlying mechanism is not clear but

may be due to hypoxia-induced cardiac arrest. Atrial fibrillation also

appears to be associated with an increased risk of SCD, which is partly,

but not entirely, accounted for by its association with underlying heart

disease. Patients with chronic kidney disease are also at higher SCD

risk with annualized SCD rates approaching 5.5% in patients undergoing dialysis. Electrolyte shifts and LVH, which are common in this

population, have been suggested to play a role. There are also potential dietary influences on SCD risk. Individuals with higher intakes

of polyunsaturated fatty acids, particularly n-3 fatty acids, and other

components of a Mediterranean-style diet have lower SCD risks in

observational studies, possibly due to antiarrhythmic effects of dietary

components. Low levels of alcohol intake may be beneficial, but heavy

intake (>3 drinks/day) appears to elevate risk.

■ PRECIPITATING FACTORS

SCD/SCA occurs with higher frequency at certain times, locations,

and in association with certain activities and exposures. Although not

consistently observed across all studies, there does appear to be circadian variations in the incidence of SCD and cardiac arrest, with peaks

in incidence in the morning hours and again in the later afternoon.

There is also seasonal variability in SCD rates, which may be related to

temperature and light exposure. Rates are highest during winter in the

northern hemisphere and summer in the southern hemisphere. SCD

rates also acutely peak during disasters such as earthquakes and terrorist attacks. SCA arrests are more likely to occur in certain locations as

well, with notable clustering around train stations, airports, and other

public places where there is significant population transit. SCD rates

tend to be higher in urban areas and individuals that live near major

roadways are at elevated SCD risk. There is also a well-recognized

acute elevation in SCD risk that occurs during or shortly after bouts

of vigorous exertion, and men appear to be more susceptible. Habitual exercise and training lower this acute risk but do not eliminate it

entirely. Exertion-associated SCDs are particularly tragic and highly

publicized when they occur in highly trained athletes; however, the

majority of such deaths actually occur in the general population. The

common thread amongst these precipitating factors is likely heightened autonomic tone, which can promote ischemia and has direct

proarrhythmia and electrophysiologic actions that lower the threshold

for sustained VF.

CAUSES OF SUDDEN CARDIAC DEATH

■ UNDERLYING HEART DISEASE (FIG. 306-1)

Our understanding regarding the diseases that contribute to SCD is

derived primarily from autopsy series and cardiac evaluations in cardiac arrest survivors, which are highly variable in level of detail. Despite

the limitations of these data, it is generally accepted that sudden death

due to cardiac causes is most commonly due to CAD, although the

proportion with CAD varies markedly by age, race, and sex. It is estimated that ~70% of SCDs in white men are due to CAD, as compared

with only 40–50% in women and blacks. The proportion of SCDs with

underlying CAD may be even lower in Asian ethnicities. Recent data

suggest that the proportion of SCDs with CAD on autopsy may be

declining in some parts of Europe (Fig. 306-2A) and the United States,

and, at the same time, increasing in parts of Japan and other parts of

Asia. Beyond CAD, nonischemic cardiomyopathies (hypertrophic,

dilated, and infiltrative) are the second most frequent cause of SCD in

the United States and European countries. Other less common causes

include valvular heart disease, myocarditis, myocardial hypertrophy

(often from hypertension), and rare primary electrical heart diseases

such as long QT and Brugada syndromes. On average, 5–10% of SCA

victims do not have a significant cardiac abnormality at the time of

autopsy or after extensive premortem cardiac evaluation, and this also

varies by gender and race. Before 35 years of age, atherosclerotic CAD

accounts for a much smaller proportion of deaths, with hypertrophic

cardiomyopathy (HCM), coronary artery anomalies, myocarditis,

arrhythmogenic right ventricular cardiomyopathy, and primary ion

channelopathies accounting for a significant number of these deaths.

■ CARDIAC RHYTHMS AND SUDDEN DEATH

The initial rhythm found when EMS arrive at the scene of an outof-hospital cardiac arrest is an important indication of the potential

cause of the arrest and of the prognosis. In the early days of EMS systems, over half of victims were found in VF, giving rise to the hypothesis that ischemic VF or ventricular tachycardia (VT) degenerating to

VF was the most common event. The proportion of cardiac arrests

found in VF has decreased markedly since the 1970s, to only 20–25%

in more recent studies, and PEA or asystole are now the most common

scenarios (Fig. 306-2B). However, the vast majority of cardiac arrests

are not monitored at the time of collapse, and since arrhythmias are

inherently unstable once hemodynamic collapse occurs, the rhythm

at the time of EMS arrival may not reflect the rhythm that initially

precipitated the SCA as VF and primary bradycardias can degenerate

into asystole. Nonetheless, VF as an initial rhythm still predominates

in public locations or in other situations when there is a short time

frame between witnessed arrest and arrival of EMS, suggesting that

VF remains a common initial precipitating rhythm. However, there

are also data to support an absolute decrease in VF incidence. Proposed explanations include decreases in underlying CHD incidence,

increased used of beta blockers in CHD, and implantable cardioverter

defibrillators (ICD) in high-risk patients. There also appears to be an

increase of PEA incidence over the past several years, suggesting that

the proportion of SCD due to abrupt hemodynamic collapse in the

absence of preceding fatal arrhythmia may be increasing. Proposed

explanations for these proportional changes in PEA versus VF include

the aging of the population and the increased prevalence of end-stage

cardiovascular disease and other severe comorbidities. These older,

sicker patients may be more likely to have arrests in the home and to

have acute precipitants leading to PEA (i.e., respiratory, metabolic, vascular), and/or be less likely to sustain VF up to the point of EMS arrival.

■ DISEASE-SPECIFIC MECHANISMS

CAD can cause SCD through several mechanisms (Table 306-2). The

most common cause is acute MI or transient myocardial ischemia that

leads to polymorphic VT and VF (see Chap. 255). Other primary

mechanisms include severe bradyarrhythmias such as heart block

with a slow escape rhythm, or PEA due to a massive MI or associated

myocardial rupture. Areas of ventricular scar from prior infarcts

increase the predisposition to reentrant VT, which often degenerates

to VF. Once patients have suffered an MI, their risk of SCD elevates

up to tenfold, with the highest absolute rates in the first 30 days after

MI. The mechanisms underlying SCD vary at different time points

after MI, with nonarrhythmic causes such as myocardial rupture

and/or extensive reinfarction predominating early, within the first

1–2 months, and ischemic polymorphic VT and/or scar-related ventricular arrhythmias prevailing later. VT and sudden death can, and

often do, occur years after an initial MI.

Cardiomyopathies and Other Forms of Structural Heart

Disease Scar-mediated reentrant VT can also occur in a host of

2260 PART 8 Critical Care Medicine

0%

2005–06 2007

Overall VT or VF Asystole or PEA

2008 2009 2010 2011 2012

35%

Survival to Discharge

5%

10%

15%

20%

25%

30%

Temporal Changes in Causes of Sudden

Cardiac Death on Autopsy

Proportion of Treated Cardiac Arrest

with Ventricular Fibrillation as Initial

Rhythm

A B

60%

80%

100%

74% 73%

66%

Ischemic

Non-Ischemic

40%

50%

60%

70%

0%

20%

40% 26% 27%

34%

0%

10%

20%

30%

1979–1980 1989–1990 1999–2000 2006–2007

20%

Proportion of Acute MI Patients with Low

LVEF (<30–35%)

C D

10%

15%

0%

5%

Bauer EHJ 2009 Voller H Europace

2011

Jordaens EHJ 2001 Avezum AJC 2008

17%

8.3%

5%

2.5%

60%

47%

40%

25%

1998–2002 2003–2007 2008–2012

FIGURE 306-2 Changing epidemiology of sudden cardiac death/arrest. A. The proportion of sudden cardiac deaths attributable to coronary artery disease among individuals

without a history of heart disease in Finland over time. Postmortem examinations are mandatory in Finland, which has the highest autopsy rate in the Western world.

(J Junttila et al: Circ Arrhythm Electrophysiol 2016). B. Proportion of treated cardiac arrest with ventricular fibrillation as first recorded rhythm in Seattle, Washington,

United States, over time. (Data from L Cobb et al: JAMA 288:3008, 2002, and G Nichol et al: JAMA 300:1423, 2008.) C. Rates of overall survival and survival from shockable and

nonshockable rhythms to hospital discharge among 70,027 out-of-hospital cardiac arrests across the United States from 2005 to 2012 (Cardiac Arrest to Enhance Survival

Registry). (Reproduced with permission from P Chan et al: Recent trends in survival from out-of-hospital cardiac attacks in United States. Circulation 130:1876, 2014.)

D. Proportion of myocardial infarction patients with left ventricular ejection fractions <30–35% in myocardial infarction registries over time.

nonischemic cardiomyopathies in which replacement fibrosis and/or

inflammatory ventricular infiltrates occur (Chap. 254). In congenital

heart disease, surgical scars created during corrective surgery, such as

those performed to correct ventricular septal defects in tetralogy of

Fallot, can also serve as the substrate for ventricular reentry. Other

common predisposing processes such as LVH, ventricular stretch due

to fluid overload, and cardiomyocyte dysfunction can result in electrical heterogeneity and other electrophysiologic changes that predispose

to ventricular arrhythmias, including ion channel alterations that

prolong action potential duration, impair cellular calcium handling,

and diminish cellular coupling. These processes occur in a wide variety of diseases associated with depressed ventricular function and/or

hypertrophy, including CAD, valvular heart disease, myocarditis, and

nonischemic cardiomyopathies.

Absence of Structural Heart Disease In the absence of structural heart disease, VF can be due to an inherited ion channel abnormality, as in long QT and Brugada syndromes (Chap. 255), rapid atrial

fibrillation associated with Wolff-Parkinson-White syndrome (Chap.

249), or drug toxicities, such as polymorphic VT due to drugs that

prolong the QT interval (Chap. 255). PEA can result from pulmonary

emboli, exsanguination, or the terminal phase of respiratory arrest.

MANAGEMENT OF CARDIAC ARREST

As the ability to predict SCA in the population is very limited, community approaches to reduce death focus on the rapid identification

of victims and implementation of resuscitation measures by those

who first encounter the victim, most likely the lay public, who ideally

summon EMS and initiate basic life-support measures with chest

compressions. The approach is codified in the “out-of-hospital chain

of survival,” which includes: (1) initial evaluation and recognition of

the SCA; (2) rapid initiation of cardiopulmonary resuscitation (CPR)

with an emphasis on chest compressions; (3) defibrillation as quickly

as possible usually with an automatic external defibrillation applied

by the lay rescuer or EMT; (4) advanced life support and postcardiac

arrest care. There have been major advances in each of these areas

and survival rates to hospital discharge for out-of-hospital cardiac

arrest have increased, particularly for patients found in VT or VF,

where survival rates can approach 30% in some regions (Fig. 306-2C).

Overall survival rates for out-of-hospital cardiac arrest are also higher

for patients receiving CPR, with recent studies in Europe reporting

survival rates of 16%. Multiple studies have pointed to socioeconomic

disparities in the administration of CPR and application of automatic

external defibrillators (AEDs) contributing to reduced survival rates

from out-of-hospital cardiac arrest in black and Hispanic populations

in the United States.

The initial goal of resuscitation is to achieve the return of spontaneous circulation (ROSC). Success is strongly related to the time

between collapse and initiation of resuscitation, decreasing markedly

after 5 min, and the rhythm at the time of EMT arrival, being best for

VT, worse for VF, and poor for PEA and asystole. Outcomes are also

determined by the age, clinical state, and comorbidities of the victim

prior to the arrest.

■ INITIAL EVALUATION AND INITIATION OF CPR

The rescuer should check for a response from the victim, shout for

help, and call or ask someone else to call their local emergency number

(e.g., 911), ideally on a cell phone that can be placed on speaker mode

2261Cardiovascular Collapse, Cardiac Arrest, and Sudden Cardiac Death CHAPTER 306

TABLE 306-2 Causes of Cardiovascular Collapse and Sudden Cardiac Arrest

CAUSE PATHOPHYSIOLOGIC SUBSTRATE RHYTHM PRESENTATION

Cardiac Causes

Coronary artery disease

 Atherosclerotic, coronary spasm, congenital anomalies

Acute myocardial ischemia/infarction, ventricular

rupture, tamponade

Ventricular scar from healed infarction

Polymorphic VT/VF

Bradyarrhythmia

Pulseless electrical activity

VT

VF

Cardiomyopathies

 Dilated, hypertrophic, ARVC, infiltrative disease, valvular

disease with LV failure

Ventricular scar

Ventricular hypertrophy

Pump failure

VT

Polymorphic VT/VF

Pulseless electrical activity

Bradyarrhythmia

Congenital heart disease

(tetralogy of Fallot, VSD, others)

Ventricular scar from surgical repair

Hypertrophy

VT

Bradyarrhythmias

Polymorphic VT/VF

Aortic stenosis Obstruction to outflow

Ventricular hypertrophy

Bradyarrhythmia

Pulseless electrical activity

Bradyarrhythmia

Polymorphic VT/VF

Mitral valve prolapse/mitral regurgitation Pump failure

Ventricular scar

VT

Polymorphic VT/VF

Arrhythmia syndromes without structural heart disease:

Genetic:

 Long QT

 Brugada

 CPVT

 Idiopathic VF, early repolarization

 Drug toxicities (acquired long QT, others)

 Electrolyte abnormalities (severe hypokalemia)

Abnormal cellular electrophysiology Polymorphic VT/VF

Wolff-Parkinson-White syndrome Accessory atrioventricular connection Preexcited AF/VF

Noncardiac Causes of Cardiovascular Collapse

Pulmonary embolism PEA

Stroke PEA, bradyarrhythmia

Aortic dissection PEA, VF

Exsanguination PEA

Tension pneumothorax PEA

Sepsis PEA

Neurogenic PEA, bradyarrhythmia

Drug overdose PEA, bradyarrhythmia

Abbreviations: AF, atrial fibrillation; ARVC, arrhythmogenic right ventricular cardiomyopathy; CPVT, catecholaminergic polymorphic ventricular tachycardia; LV, left ventricle;

PEA, pulseless electrical activity; VF, ventricular fibrillation; VSD, ventricular septal defect; VT, ventricular tachycardia.

■ RHYTHM-BASED MANAGEMENT (SEE FIG. 306-3)

The rapidity with which defibrillation/cardioversion is achieved is an

important predictor of outcome. A defibrillator, most often an AED,

should be applied as soon as available. AEDs are easily used by lay rescuers and trained first responders, such as police officers and trained

security guards. When the arrest is witnessed, the use of AEDs by lay

responders can improve cardiac arrest survival rates. Once patches are

applied to the chest, a brief pause in chest compressions is required to

allow the AED to record the rhythm. An AED will advise delivery of a

shock if the recorded rhythm meets criteria for VF or VT. Chest compressions are continued while the defibrillator is being charged. As soon

as a diagnosis of VF or VT is established, a 200 joule biphasic waveform

shock should be delivered. Chest compressions are resumed immediately and continue for 2 min until the next rhythm check. If VT/VF is

still present, a second maximal energy shock is delivered. This sequence

is continued until personnel to administer advanced life support are

available or ROSC is achieved. Electrocardiogram (ECG) rhythm strips

produced by the AED should be retrieved, as the initial rhythm can be

an important consideration in determining the cause of the arrest and

to guide further therapy and evaluation if resuscitation is successful.

at the patient’s side such that the responding dispatcher can provide

instructions and queries to the rescuer. Consideration of aspiration or

airway obstruction is important and if suspected a Heimlich maneuver

may dislodge the obstructing body. A trained health care provider

would also check for a pulse (taking no longer than 10 s so as not to

delay initiation of chest compressions) and assess breathing. Gasping

respirations and brief seizure activity are common during SCA and

may be misinterpreted as breathing and responsiveness. Chest compressions should be initiated without delay and administered at a rate

of 100–120/min depressing the sternum by 5 cm (2 in.) and allowing

full chest recoil between compressions. Chest compressions generate

forward cardiac output with sequential filling and emptying of the cardiac chambers, with competent valves maintaining forward direction

of flow. Interruption of chest compressions should be minimized to

reduce end organ ischemia. Ventilation may be administered with two

breaths for every 30 compressions if a trained rescuer is present, but for

lay rescuers without training, chest compressions alone (“hands only

CPR”) are more likely to be effectively applied and of similar benefit.

If a second rescuer is present, they should be sent to seek out an AED,

which are now widely available in many public areas.

2262 PART 8 Critical Care Medicine

FIGURE 306-3 Algorithm for approach to cardiac arrest due to VT or VF (shockable rhythm). A. Chest compressions with ventilation and defibrillation or cardioversion

should be initiated as soon as possible. Defibrillation should be repeated with minimal interruption of chest compressions. Once an intravenous or intraosseous access is

established, administration of epinephrine defibrillation and amiodarone and defibrillation are performed. Further therapy can be guided by possible causes as suggested

by the initial or recurrent cardiac rhythm as shown. CPR, cardiopulmonary resuscitation; I.O., intraosseous; I.V., intravenous; PCI, percutaneous coronary intervention;

ROSC, return of spontaneous circulation. B. Algorithm for approach to cardiac arrest due to bradyarrhythmias/asystole and pulseless electrical activity. Chest compressions

with ventilation (and intubation) should be initiated as soon as possible, and IV access should be obtained. Once an intravenous or intraosseous access is established,

administration of epinephrine is performed. At the same time, an investigation for potential reversible causes should be made and any such causes should be treated if

present. For bradycardic rhythms, atropine 1 mg IV and external subcutaneous or transvenous pacing are also performed. Defibrillation should be repeated with minimal

interruption of chest compressions. Further therapy can be guided by possible causes. CPR, cardiopulmonary resuscitation; I.O., intraosseous; I.V., intravenous; M.I.,

myocardial infarction.

Chest compressions at 100–120/min

Immediate defibrillation

and resume CPR for 2 min

Ventricular Fibrillation or Pulseless Ventricular Tachycardia

A

2 min of chest compressions/ventilation and repeat shock

No ROSC

No ROSC

Continue chest compressions, I.V. or I.O. access, advanced airway

Epinephrine 1 mg q 3–5 min

Repeat shock

I.V. amiodarone 300 mg (may repeat 150 mg), continue CPR

Repeat shock

No ROSC

Specific therapies

Polymorphic VT/VF

Acute coronary syndrome:

lidocaine, PCI

Acquired long QT: Mg,

transvenous pacing,

isoproterenol.

Brugada syndrome, idiopathic VF:

isoporterenol, quinidine.

Monomorphic

VT

lidocaine

procainamide

Sinusoidal VT

Hyperkalemia:

Ca, NaHCO3.

Acute coronary

syndrome

Drug toxicity

Pulseless electrical

activity

Asystole

Bradyarrhythmia/Asystole Pulseless Electrical Activity

B

[Confirm asystole] [Assess pulse]

Identify and treat reversible causes

Epinephrine — 1 mg I.V. {repeat 3–5 min}

For Bradycardia:

Atropine 1 mg I.V.

Pacing — external or pacing wire

* Pulmonary embolus

* Drug overdose

* Hyperkalemia

* Severe acidosis

* Massive acute M.I.

* Hypovolemia

* Hypoxia

* Tamponade

* Pneumothorax

* Hypothermia

CPR, intubate, I.V. access

* Hypoxia

* Hyper- /hypokalemia

* Severe acidosis

* Drug overdose

* Hypothermia

2263Cardiovascular Collapse, Cardiac Arrest, and Sudden Cardiac Death CHAPTER 306

When advanced cardiac life support is available, an intravenous or

intraosseous line is established for administration of medication and

consideration given to placement of an advanced airway (endotracheal

tube or supraglottic airway device). Epinephrine 1 mg every 3–5 min

may be administered intravenously or intraosseously. If circulation is

not restored or the patient is less than fully conscious despite return

of circulation, confirmation that acidosis and hypoxia are adequately

addressed should be assessed with arterial blood gas analysis. If metabolic acidosis persists after successful defibrillation and with adequate

ventilation, 1 meqE/kg NaHCO3

 may be administered.

The cardiac rhythm guides resuscitation when monitoring is available. VT is treated with external shocks synchronized to the QRS when

VT is monomorphic, and asynchronous shocks for polymorphic VT or

VF. If VT/VF recurs after one or more shocks, amiodarone 300 mg can

be administered as a bolus via intravenous or intraosseous route in the

hope that arrhythmia recurrence will be prevented after the next shock,

followed by a 150-mg bolus if the arrhythmia recurs. If amiodarone

fails, lidocaine can be administered.

Consideration of etiology should also guide therapy (Chaps. 254

and 255). Commonly encountered causes of recurrent VT/VF may be

due to ongoing myocardial ischemia or infarction that would benefit

from emergent coronary angiography and revascularization, or QT

prolongation causing the polymorphic VT torsades des pointes that

may respond to administration of magnesium. Hyperkalemia should

respond to administration of calcium, while other measures are implemented to reduce serum potassium.

PEA/asystole should be managed with CPR, ventilation, and administration of epinephrine. Causes of PEA/asystole that require specific

therapy should be considered including airway obstruction, hypoxia,

hypovolemia, acidosis, hyperkalemia, hypothermia, toxins, cardiac

tamponade, tension pneumothorax, pulmonary embolism, and MI.

Naloxone should be administered if opiate overdose is suspected.

■ POSTCARDIAC ARREST ACUTE MANAGEMENT

Following restoration of effective circulation, the possibility of acute

MI should be immediately assessed. The majority of patients who have

ST elevation consistent with acute MI will be found to have a culprit

coronary stenosis/occlusion and emergent coronary angiography with

percutaneous angioplasty, and stenting is recommended. Angiography

should also be considered if an acute coronary syndrome is suspected,

even if ST segment elevation is absent, as approximately half of selected

patients undergoing angiography for this concern are found to have a

coronary lesion as a potential cause of sudden cardiac arrest (SCA).

However, immediate angiography has not been found to result in better

outcomes compared to delayed angiography in patients presenting with

out-of-hospital cardiac arrest due to a VT/VF with no ECG evidence

of ST-segment elevation. Thus, decisions regarding which patients

without ST segment elevation should undergo urgent angiography are

complex and factors such as hemodynamic or electrical instability and

evidence of ongoing ischemia are taken into consideration.

Hemodynamic instability is often present following resuscitation

and further ischemic end organ damage is a major consideration.

Optimizing ventilation with consideration of acidosis, hypoxemia,

and electrolyte abnormalities is important. Maintaining systolic BP at

>90 mmHg and mean BP >65 mmHg is desirable and may require

administration of vasopressors and adjustment of volume status.

Potentially treatable reversible causes including hyperkalemia, severe

hypokalemia, and drug toxicity with QT prolongation causing torsades

des pointes should be identified and treated (Chap. 255).

After stable spontaneous circulation is achieved, brain injury due

to ischemia and reperfusion is a major determinant of survival and

accounts for over two-thirds of deaths. The probability of successful

neurologic recovery decreases rapidly with time from collapse to ROSC

and is <30% at 5 min in the absence of bystander CPR. The time between

collapse and restoration of circulation is generally imprecise, and some

patients have a period of hypotensive VT prior to complete collapse, such

that a reported long period prior to arrival of rescuers does not always

preclude good neurologic recovery. Therapeutic hypothermia (targeted

temperature management) has been shown to improve the likelihood of

survival and neurologic recovery in patients who present with shockable

(VT or VF) rhythms and is recommended for all cardiac arrest patients

who remain comatose, regardless of presenting rhythm, who have lack

of purposeful response to verbal commands following return of spontaneous circulation. A constant target temperature of 32–36°C for at least

24 h is recommended, although a recent trial failed to demonstrate benefit compared with a strategy of targeted normothermia with early and

aggressive treatment of fever. Shivering suppression with analgesics and

sedatives may be needed. Induction of hypothermia should be started

in-hospital, as no benefit was shown for implementation before hospital arrival, and administration of large volumes of cold saline for this

purpose increased the risk of pulmonary edema. Brain injury is often

accompanied by seizures and status epilepticus that may have further

deleterious effects, warranting periodic or continuous electroencephalography (EEG) monitoring and treatment. A number of other therapies

hoped to improve post arrest outcomes have been assessed but have not

been shown to be beneficial, including administration of corticosteroids,

hemofiltration, and efforts to tightly control blood glucose.

Hypothermia and sedation preclude reliable prognostication for

neurologic recovery. Functional neurologic assessment for neurologic

recovery is generally deferred for at least 72 h after return to normothermia, typically 4–5 days after the cardiac arrest. Features that predict

poor outcome include absence of pupillary reflex to light, status myoclonus, absence of EEG reactivity to external stimuli, and persistent

burst suppression on EEG.

■ LONG-TERM MANAGEMENT AFTER SURVIVAL OF

OUT-OF-HOSPITAL CARDIAC ARREST

For patients who survive cardiac arrest and have neurologic recovery,

the likely underlying cause of the arrest guides further treatment. For

arrests not due to an obvious noncardiac cause, a full evaluation for the

forms of structural heart disease outlined in Fig. 306-1 and Table 306-2

should be performed including an assessment for underlying CAD and

ischemia as well as echocardiography and/or cardiac MRI to look for

evidence of prior MI, valvular disease, nonischemic cardiomyopathies,

and to provide an assessment of left ventricular ejection fraction (LVEF).

If the initial evaluation is not definitive or is suggestive of an inflammatory cardiomyopathy (i.e., sarcoidosis, myocarditis), a cardiac PET scan

and/or endomyocardial biopsy may also be performed. Patients without

obvious structural abnormalities should undergo an evaluation for primary electrical disease (long QT syndrome [LQTS], Brugada syndrome,

early repolarization syndrome, or Wolff-Parkinson-White syndrome).

In cases where a heritable syndrome is suspected, further genetic evaluation should be considered. Diagnostic electrophysiology studies are

warranted in selected patients to assess inducible arrhythmias, or provocative testing, such as with epinephrine challenge for LQTS, or sodium

channel blocker (e.g., procainamide) challenge for Brugada syndrome.

Patients with shockable rhythms at arrest (VF and VT) that are not

deemed to have been due to a transient reversible cause and have reasonable life expectancy should undergo insertion of an implantable cardiac defibrillator (ICD) for secondary prevention of SCA/SCD. Most of

these patients will be found to have CAD. Patients with a VF arrest that

occurs within the first 48 h of a documented acute MI generally do not

require an ICD because they have a similar risk of sudden death over

the next 5 years as infarct survivors who did not have a cardiac arrest.

However, patients who have a large infarction with acutely depressed

LV ejection fraction (e.g., <35%) have an increased risk for future development of life-threatening ventricular arrhythmias related to reentry in

the infarct scar (Chap. 252). The percentage of patients with such large

infarcts has been declining due to improved revascularization strategies for acute MI (Fig. 306-2D). Implantation of an ICD early after MI

in these patients does not, however, improve overall survival, in part

because a significant number of sudden deaths in the first 3 months

are due to recurrent myocardial ischemia or myocardial rupture, rather

than cardiac arrhythmias. For patients with large infarcts, a wearable

defibrillator that will treat VT/VF if it occurs may be used while left

ventricular remodeling is taking place, followed by reevaluation of

arrhythmia risk after the infarct is healed to determine if an ICD is

warranted. Patients who experience VF in-hospital >48 h after MI or

2264 PART 8 Critical Care Medicine

in the setting of myocardial ischemia without infarction may be at risk

for recurrent VT/VF. These patients should be evaluated and optimally

treated for ischemia. If there is evidence that clearly implicates ischemia

immediately preceding the onset of VF without evidence of a prior

MI, coronary revascularization may be adequate therapy. Others may

warrant ICD implantation. When the cardiac arrest is due to sustained

monomorphic VT, a prior infarct scar is often present and the recurrence rate is significant regardless of whether the arrest occurred in

association with elevated serum troponin. In this circumstance, even

when revascularization is performed for ischemia, an ICD is usually

warranted owing to the risk of recurrence of scar-related VT.

Patients who have cardiac arrest due to a treatable reversible cause,

such as hyperkalemia or drug toxicity with QT prolongation causing

torsades des pointes (Chap. 255), which can be adequately addressed

and prevented by other means, do not usually need an ICD. An ICD

is usually recommended for cardiac arrest due to VT or VF without a

clearly reversible cause, particularly when structural heart disease, such

as hypertrophic or dilated cardiomyopathy, arrhythmogenic cardiomyopathy, cardiac sarcoidosis, or a cardiac syndrome associated with sudden death, including Brugada syndrome, or LQTS is present (Chaps.

254 and 255). In patients with structural heart disease, it is important

to recognize that life-threatening arrhythmias can be an indication of

terminal, end-stage heart disease with minimal prospect for meaningful survival despite successful resuscitation, and ICDs will not alter the

course of these patients and should not be implanted in this situation,

unless there is a prospect for cardiac replacement therapy with future

cardiac transplantation or a ventricular assist device.

PREVENTION OF SCD

Although advances in CPR and postresuscitation care have improved

survival rates after cardiac arrest, 90% of patients will not survive to be

discharged from the hospital. Of those that do survive, a proportion

(~20%) are left with severe neurologic and/or physical disability. The

majority of cardiac arrests do not occur in public places where AEDs

and rapid defibrillation have the greatest impact. Patients who suffer

an arrest at home also have longer EMS response times and are much

less likely to be found in VF. Finally, 50% of cardiac arrests are not

witnessed precluding effective resuscitation efforts. Thus, preventive

efforts are critical to reducing mortality from cardiac arrest.

■ SCD RISK STRATIFICATION

The presence of overt structural heart disease and/or primary electrical

heart disease is associated with an increased risk of SCD that varies with

the severity and type of disease. For patients with structural heart disease,

depressed left ventricular function is the best validated marker for risk, and

clinical HF elevates risk further. After MI, SCD risk increases gradually as

the LVEF decreases to 40% and then exponentially thereafter. In addition

to LVEF and CHF, other potential markers of increased SCD risk in the

setting of structural heart disease include unexplained syncope, sustained

VT induced at electrophysiology study (EP study), left ventricular scar

size and heterogeneity on cardiac magnetic resonance, markers of altered

autonomic function and altered repolarization, and QRS prolongation.

The majority of these tests, with the exception of the EP study in post-MI

patients, broadly predict death from cardiovascular causes and are not

able to discriminate patients who will die suddenly from an arrhythmia

and those who will die of other cardiac causes. For instance, patients with

the greatest degree of systolic HF and/or lowest LVEF, although at elevated

risk for SCD, are more likely to die from HF. Although sustained VT at EP

study does identify individuals at a higher risk of SCA versus non-SCA in

certain subsets of patients, the sensitivity of the test is generally inadequate

when LV function is significantly reduced.

■ PREVENTIVE THERAPIES FOR SCD IN HIGH-RISK

POPULATIONS

Therapy with beta-adrenergic blockers has been demonstrated to

reduce SCD risk in a multitude of settings including after MI, among

patients with ischemic and nonischemic cardiomyopathy, and in

LQTS. Angiotensin-converting enzyme inhibitors, aldosterone antagonists, and most recently angiotensin-receptor/neprilysin inhibitors

have been associated with reductions in SCD in subsets of patients

with structural heart disease, primarily ischemic and nonischemic

cardiomyopathy accompanied by HF. Coronary artery bypass grafting

has also been associated with reductions in SCD risk, and revascularization in general may lower SCD risk through reduction in ischemic

events and resultant improvements in left ventricular systolic function

by reducing areas of hibernating myocardium.

For patients whose disease continues to confer substantial risk of

sustained VT or VF on optimal medical therapy, an ICD is recommended (Table 306-3). The ICD indication in these patients is referred

to as “primary prevention of sudden death.” The indications for primary

prevention ICDs vary depending on the type of underlying structural

heart disease and its severity, and the strength of evidence varies by

indication. In patients with a history of MI more than 40 days ago, primary prevention ICDs are indicated for those with Class II–III NYHA

HF and LVEF <35%, and those who are NYHA functional Class I with

LVEF <30%. Although ICDs have not been found to be beneficial when

implanted within 40 days of an MI, those with recent or old MI, nonsustained VT, LVEF <40%, and inducible sustained VT at EP study also

warrant an ICD. In general, these criteria are not applied to patients

who are within 90 days of myocardial revascularization, since some will

experience improvement in ventricular function and older trial data

suggested there was no benefit with ICDs in these patents. High-risk

patients with low LVEFs may be considered for a wearable defibrillator

with later reassessment of ventricular function and ICD placement.

ICDs for primary prevention of sudden death are also recommended for patients with diseases other than CAD that put them at

risk for SCD. Primary prevention ICDs are currently indicated in select

high-risk patients with HCM, arrhythmogenic right ventricular dysplasia, cardiac sarcoidosis, and Brugada syndrome, as well, and some

patients with congenital LQTS with high-risk features or who have

failed therapy with beta-adrenergic blocking agents. ICDs are currently

also recommended for those with nonischemic DCM who have an

LVEF ≤35% and who have NYHA functional Class II or III symptoms

on guideline-directed medical therapy.

Data from a recent randomized trial, the Danish Study to Assess the

Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure

on Mortality (DANISH), performed in patients with nonischemic

DCM and LVEF ≤35%, who also had elevated NT-proBNP levels and

NYHA Class II–IV HF, have resulted in some debate regarding these

latter guidelines. This trial did not demonstrate an overall mortality

benefit of the ICD despite a reduction in the incidence of SCD. In subgroup analyses, mortality benefits were observed in younger patients

in whom the competing risk of dying from other causes of death was

lower. These data underscore the importance of considering competing

risks for other causes of mortality when deciding to implant a primary

prevention ICD. Patients who are likely to die from other causes are

unlikely to benefit from an ICD. Patients who do not have a reasonable

expectation of survival with an acceptable functional status for at least

1 year, should not undergo ICD placement. There are also other circumstances where an ICD is not indicated even if there is a significant

sudden death risk (Table 306-4).

■ THE CHALLENGE OF SCD PREVENTION

(FIG. 306-4)

The Greatest Number of Sudden Deaths Occur in “LowRisk” Patients While patients with reduced left ventricular function and HF are at substantially elevated SCD risk, only ~20% of all

SCDs occur in patients with poor left ventricular function. Most SCDs

occur in individuals with preserved ventricular function who would

not qualify for a primary prevention ICD. Although SCD rates are

elevated compared to the general population, the absolute SCD risk in

patients with CHD or HF who have an LVEF >35% is not high enough

to warrant consideration of ICD therapy. While the incidence of SCD is

lower in patients with preserved LVEF, SCD accounts for a greater proportion of cardiac deaths, and active efforts are being made to advance

SCD risk stratification in this segment of the population. However,

at the present time, SCD prevention primarily involves cardiac risk

factor modification and standard medical therapy for the underlying

condition.

2265Cardiovascular Collapse, Cardiac Arrest, and Sudden Cardiac Death CHAPTER 306

TABLE 306-3 Implantable Cardioverter Defibrillator (ICD) Indications

INDICATION

CLASS OF

RECOMMENDATION*

LEVEL OF

EVIDENCE**

Secondary Prevention

All disease states

VT or VF

ICD therapy is indicated in patients who are survivors of cardiac arrest due to VF or

hemodynamically unstable sustained VT after evaluation to define the cause of the

event and to exclude any completely reversible causes.

ICD therapy is indicated in patients with structural heart disease and spontaneous

sustained VT, whether hemodynamically stable or unstable.

ICD implantation is reasonable for patients with sustained VT and normal or nearnormal ventricular function.

Class I

Class I

Class IIa

A

B

C

Syncope ICD therapy is indicated in patients with syncope of undetermined origin with

clinically relevant, hemodynamically significant sustained VT or VF induced at

electrophysiological study.

ICD therapy may be considered in patients with syncope and advanced structural

heart disease in whom invasive and noninvasive investigations have failed to

determine a cause.

Class I

Class IIb

B

C

Primary Prevention

Ischemic cardiomyopathy ICD therapy is indicated in patients with LVEF ≤35% due to prior MI who are at least

40 days post-MI and are in NYHA functional Class II or III.

ICD therapy is indicated in patients with LV dysfunction due to prior MI who are at

least 40 days post-MI, have an LVEF ≤30%, and are in NYHA functional Class I.

ICD therapy is indicated in patients with nonsustained VT due to prior MI, LVEF ≤40%,

and inducible VF or sustained VT at electrophysiological study.

Class I

Class I

Class I

B

A

B

Nonischemic

cardiomyopathy

ICD therapy is indicated in patients with nonischemic DCM who have an LVEF ≤35%

and who are in NYHA functional Class II or III.

ICD implantation is reasonable for patients with unexplained syncope, significant LV

dysfunction, and nonischemic DCM.

ICD therapy can be considered in patients with nonischemic heart disease and NYHA

functional Class I.

Class I

Class IIa

Class IIb

B

C

C

Hypertrophic

cardiomyopathy

ICD implantation is reasonable for patients with HCM who have one or more major

risk factors for SCD.

Class IIa C

Arrhythmogenic right

ventricular dysplasia

ICD implantation is reasonable for the prevention of SCD in patients with ARVC who

have one or more risk factors for SCD.

Class IIa C

Cardiac sarcoidosis ICD implantation is reasonable for the prevention of SCD in patients with cardiac

sarcoidosis who have one or more risk factors for SCD.

Class IIa C

Brugada syndrome ICD implantation is reasonable for patients with Brugada syndrome who have had

syncope.

ICD implantation is reasonable for patients with Brugada syndrome who have

documented VT that has not resulted in cardiac arrest.

Class IIa

Class IIa

C

C

Long-QT syndrome ICD implantation is reasonable to reduce SCD in patients with long QT syndrome who

are experiencing syncope and/or VT while receiving beta blockers.

ICD may be considered as primary therapy in patients with long QT syndrome who

are deemed to be at very high risk, especially those with a contraindication to beta

blocker therapy.

Class IIa

Class IIb

B

B

Catecholaminergic

polymorphic VT (CPVT)

ICD implantation is reasonable for patients with catecholaminergic polymorphic VT

who have syncope and/or documented sustained VT while receiving beta blockers.

Class IIa C

Familial cardiomyopathy ICD therapy may be considered in patients with a familial cardiomyopathy associated

with SCD.

Class IIa C

LV noncompaction ICD therapy may be considered. Class IIa C

CLASS OF RECOMMENDATION* LEVEL OF EVIDENCE**

Class I

Procedure/treatment

SHOULD be performed/

administered

Class IIa

Additional studies with focused

objectives needed.

IT IS REASONABLE to

perform procedure/administer

treatment.

Level A

Multiple populations evaluated.

Data derived from multiple randomized clinical trials

or meta-analyses.

Level B

Limited populations

evaluated.

Data derived from a

single randomized trial or

nonrandomized studies.

Level C

Very limited

populations

evaluated.

Only consensus

opinion of experts,

case studies, or

standard of care.

Abbreviations: VF, ventricular fibrillation; VT, ventricular tachycardia.

Preventing Sudden Death in the General Population Only

about one-half of men and one-third of women who suffer SCA are

recognized to have heart disease prior to the event, and only half

have warning symptoms prior to the event. SCD often occurs without

warning as the first manifestation of cardiac disease. In order to prevent these SCDs, preventive interventions would need to be employed

broadly to the general population. Although several risk scores have

recently been developed with the intent to stratify SCD risk in low-risk

populations, the clinical utility to date is limited by the low absolute

incidence of SCD, which is estimated to be only 50–90 per 100,000 in

the general adult population. Therefore, current efforts aimed at preventing SCD in general populations primarily focus on modification

of the SCD risk factors outlined previously. Individuals who adhere

to a low-risk, healthy lifestyle that includes avoidance of smoking,

2266 PART 8 Critical Care Medicine

TABLE 306-4 Implantable Cardioverter Defibrillator (ICD) Not

Indicated

Patients who do not have a reasonable expectation of survival with an

acceptable functional status for at least 1 year, even if they meet ICD

implantation criteria.

Patients with incessant VT or VF.

Patients with significant psychiatric illnesses that may be aggravated by device

implantation or that may preclude systematic follow-up.

Patients with drug-refractory New York Heart Association Class IV congestive

heart failure who are not candidates for cardiac transplantation or cardiac

resynchronization therapy.

Syncope of undetermined cause in a patient without inducible ventricular

tachyarrhythmias and without structural heart disease.

VF or VT is amenable to surgical or catheter ablation in patients without other

disease predisposing to SCA (e.g., atrial arrhythmias associated with WolffParkinson-White syndrome, RV or LV outflow tract VT, idiopathic VT, or fascicular

VT in the absence of structural heart disease).

Patients with ventricular tachyarrhythmias due to a completely reversible

disorder in the absence of structural heart disease (e.g., electrolyte imbalance,

drugs, or trauma).

Abbreviations: LV, left ventricular; RV, right ventricular; VF, ventricular fibrillation; VT,

ventricular tachycardia.

Source: Adapted from AE Epstein et al: 2012 ACCF/AHA/HRS focused update

incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy

of cardiac rhythm abnormalities: A report of the American College of Cardiology

Foundation/American Heart Association Task Force on Practice Guidelines and the

Heart Rhythm Society. Circulation 127:e283, 2013.

LVEF <30–35%

15%

Sustained VT/VF 5%

No known heart

disease

50%

Other

80%

Patients

treated

with ICDs

A

B

7.2%

Absolute Risk of Sudden Cardiac Death by Clinical Subgroups

6.0%

3.0%

Threshold for

ICD

Demonstrate

benefit 1.5% 1.5%

1.0% 0.8%

0.08%

Sustained

VT/VF

Arrest

Ischemic CM,

LVEF<30%

(MADIT)

POST-MI,

LVEF>35%

Multiple

Cardiac

Risk Factors

General

Population

Proportion of Sudden Cardiac Death by Clinical Subgroups

Post-MI, CHD,

CM, or HF with

LVEF>35%

SCD Rate Per Year (%)

3% Year:

Heart Failure

with

Preserved

Ejection

Fraction

(HFPEF)

Non-Ischemic

CM, LVEF

≤35% NYHA

HF Class IIIV, NTproBNP>200

(DANISH Trial)

Ischemic +

Non-Ischemic

CM, LVEF

≤35%, NYHA

HF Class II-III

(SCD-HEFT)

FIGURE 306-4 A. Proportion of sudden cardiac deaths that occur in clinical subgroups of the population treated and not treated with ICDs. B. Absolute risk of sudden cardiac

death within clinical subgroups in comparison to the threshold of risk where ICDs demonstrated benefit.

maintaining a healthy body weight, participating in moderate exercise,

and a Mediterranean-type dietary pattern have markedly lower rates

of SCD. A substantial number of SCDs are likely to be preventable

through lifestyle modifications and treatment of risk factors.

Acknowledgment

William G. Stevenson contributed to this chapter in the 20th edition and

some material from that chapter has been retained here.

■ FURTHER READING

Al-Khatib SM et al: 2017 AHA/ACC/HRS Guideline for Management

of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death. A Report of the American College of Cardiology/

American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. 72:e91, 2018.

Callaway CW et al: Part 8: Post-Cardiac Arrest Care: 2015 American

Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 132:S465, 2015.

Dankiewicz J et al: Hypothermia versus normothermia after out-ofhospital cardiac arrest. N Engl J Med 384:2283, 2021.

Deo R, Albert CM: Epidemiology and genetics of sudden cardiac

death. Circulation 125:620, 2012.

Fishman GI et al: Sudden cardiac death prediction and prevention

report from a National Heart, Lung, and Blood Institute and Heart

Rhythm Society workshop. Circulation 122:2335, 2010.

Hayashi M et al: The spectrum of epidemiology underlying sudden

cardiac death. Circ Res 116:1887, 2015.

2267 Nervous System Disorders in Critical Care CHAPTER 307

Link MS et al: Part 7: Adult advanced cardiovascular life support: 2015

American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation

132:S444, 2015.

Myerburg RJ et al: Pulseless electric activity: Definition, causes,

mechanisms, management, and research priorities for the next

decade: Report from a National Heart, Lung, and Blood Institute

Workshop. Circulation 128:2532, 2013.

Neumar RW et al: Part 1: Executive summary. 2015 American Heart

Association guidelines update for cardiopulmonary resuscitation and

emergency cardiovascular care. Circulation 132:S315, 2015.

Stecker EC et al: Public health burden of sudden cardiac death in the

United States. Circ Arrhythm Electrophysiol 7:212, 2014.

Zipes DP et al: ACC/AHA/ESC 2006 Guidelines for management of

patients with ventricular arrhythmias and the prevention of sudden

cardiac death: A report of the American College of Cardiology/

American Heart Association Task Force and the European Society of

Cardiology Committee for Practice Guidelines (writing committee

to develop guidelines for management of patients with ventricular

arrhythmias and the prevention of sudden cardiac death): Developed

in collaboration with the European Heart Rhythm Association and

the Heart Rhythm Society. Circulation 114:e385, 2006.

Life-threatening neurologic illness may be caused by a primary disorder affecting any region of the neuraxis or may occur as a consequence

of a systemic disorder such as hepatic failure, multisystem organ failure, or cardiac arrest (Table 307-1). Neurologic critical care focuses

on preservation of neurologic tissue and prevention of secondary

brain injury caused by ischemia, hemorrhage, edema, herniation,

and elevated intracranial pressure (ICP). Encephalopathy is a general

term describing brain dysfunction that is diffuse, global, or multifocal.

Severe acute encephalopathies represent a group of various disorders

due to different neurologic or systemic etiologies but that share the

common themes of primary and secondary brain injury.

■ PATHOPHYSIOLOGY

Brain Edema Swelling, or edema, of brain tissue occurs with many

types of brain injury. The two principal types of edema are vasogenic

and cytotoxic. Vasogenic edema refers to the influx of fluid and solutes

into the brain through an incompetent blood-brain barrier (BBB). In

the normal cerebral vasculature, endothelial tight junctions associated

with astrocytes create an impermeable barrier (the BBB), through

which access into the brain interstitium is dependent upon specific

transport mechanisms. The BBB may be compromised in ischemia,

trauma, infection, and metabolic derangements, and typically develops rapidly following injury. Cytotoxic edema results from cellular

swelling, membrane breakdown, and ultimately cell death. Clinically

significant brain edema usually represents a combination of vasogenic

and cytotoxic components. Edema can lead to increased ICP as well

as tissue shifts and brain displacement or herniation from focal processes (Chap. 28). These tissue shifts can cause injury by mechanical

Section 3 Neurologic Critical Care

307 Nervous System

Disorders in Critical

Care

J. Claude Hemphill, III, Wade S. Smith,

S. Andrew Josephson, Daryl R. Gress

TABLE 307-1 Neurologic Disorders in Critical Illness

LOCALIZATION ALONG

NEUROAXIS SYNDROME

Central Nervous System

Brain: Cerebral

hemispheres 

Global encephalopathy

Delirium

Sepsis

Organ failure—hepatic, renal

 Medication related—sedatives, hypnotics,

analgesics, H2

 blockers, antihypertensives

Drug overdose

 Electrolyte disturbance—hyponatremia,

hypoglycemia

Hypotension/hypoperfusion

Hypoxia

Meningitis

Subarachnoid hemorrhage

Wernicke’s disease

 Seizure—postictal or nonconvulsive status

epilepticus

Hypertensive encephalopathy

Hypothyroidism—myxedema

Focal deficits

Ischemic stroke

Tumor

Abscess, subdural empyema

Intraparenchymal hemorrhage

Subdural/epidural hematoma

Brainstem/cerebellum Mass effect and compression

Basilar artery thrombosis

Intraparenchymal hemorrhage

Central pontine myelinolysis

Spinal cord Mass effect and compression

Disk herniation

Epidural hematoma

Epidural abscess

Ischemia—hypotension/embolic

Trauma

Myelitis

Peripheral Nervous System

Peripheral nerve

Axonal Critical illness polyneuropathy

Neuromuscular blocking agent complications

Metabolic disturbances, uremia, hyperglycemia

Medication effects—chemotherapeutic,

antiretroviral

Demyelinating Guillain-Barré syndrome

Chronic inflammatory demyelinating

polyneuropathy

Neuromuscular junction Prolonged effect of neuromuscular blockade

Medication effects—aminoglycosides

Myasthenia gravis, Lambert-Eaton syndrome,

botulism

Muscle Critical illness myopathy

Cachectic myopathy

Acute necrotizing myopathy

Thick-filament myopathy

Electrolyte disturbances—hypokalemia/

hyperkalemia, hypophosphatemia

Rhabdomyolysis

2268 PART 8 Critical Care Medicine

distention and compression in addition to the ischemia of impaired

perfusion consequent to the elevated ICP.

Ischemic Cascade and Cellular Injury When delivery of substrates, principally oxygen and glucose, is inadequate to sustain cellular function, a series of interrelated biochemical reactions known

as the ischemic cascade is initiated (see Fig. 426-2). The release of

excitatory amino acids, especially glutamate, leads to influx of calcium

and sodium ions, which disrupt cellular homeostasis. An increased

intracellular calcium concentration may activate proteases and lipases,

which then lead to lipid peroxidation and free radical–mediated cell

membrane injury. Cytotoxic edema ensues, and ultimately necrotic

cell death and tissue infarction occur. This pathway to irreversible cell

death is common to ischemic stroke, global cerebral ischemia, and

traumatic brain injury.

Penumbra refers to areas of ischemic brain tissue that have not

yet undergone irreversible infarction, implying that these regions are

potentially salvageable if ischemia can be reversed. Factors that may

exacerbate ischemic brain injury include systemic hypotension and

hypoxia, which further reduce substrate delivery to vulnerable brain

tissue, and fever, seizures, and hyperglycemia, which can increase

cellular metabolism, outstripping compensatory processes. Clinically,

these events are known as secondary brain insults because they lead to

exacerbation of the primary brain injury. Prevention, identification,

and treatment of secondary brain insults are fundamental goals of

management.

An alternative pathway of cellular injury is apoptosis. This process

implies programmed cell death, which may occur in the setting of

Mean Arterial Pressure (MAP), mmHg

Cerebral Blood Flow (CBF), mL/100 g/min

50 150

55

), g

B

Mean Arterial Pressure (MAP), mmHg

Cerebral Blood Flow (CBF), mL/100 g/min

0 50 150

55

F), mL/100 g/

min ), g

A

FIGURE 307-1 Pressure autoregulation of cerebral blood flow. In the normal state where autoregulation is intact A, cerebral perfusion is constant over a wide range

of systemic blood pressures (BP). This is mediated by dilation and constriction of small cerebral arterioles (round circles). Below the BP threshold for maximal dilation,

cerebral blood flow becomes pressure-dependent and decreases, whereas above the threshold for maximum constriction, cerebral blood flow increases with increasing

systemic BP. In severe brain injury, autoregulatory mechanisms may be impaired and cerebral blood flow becomes pressure-dependent throughout (B). At the extremes of

BP, there may be vascular collapse (very low BP) or forced vasodilation (very high BP).

ischemic stroke, global cerebral ischemia, traumatic brain injury, and

possibly intracerebral hemorrhage. Apoptotic cell death can be distinguished histologically from the necrotic cell death of ischemia and is

mediated through a different set of biochemical pathways; apoptotic

cell death occurs without cerebral edema and therefore is often not

seen on brain imaging. At present, interventions for prevention and

treatment of apoptotic cell death remain less well defined than those

for ischemia.

Cerebral Perfusion and Autoregulation Brain tissue requires

constant perfusion in order to ensure adequate delivery of substrate.

The hemodynamic response of the brain has the capacity to preserve

perfusion across a wide range of systemic blood pressures. Cerebral

perfusion pressure (CPP), defined as the mean systemic arterial pressure (MAP) minus the ICP, provides the driving force for circulation

across the capillary beds of the brain. Autoregulation refers to the physiologic response whereby cerebral blood flow (CBF) is regulated via

alterations in cerebrovascular resistance in order to maintain perfusion

over wide physiologic changes such as neuronal activation or changes

in hemodynamic function. If systemic blood pressure drops, cerebral

perfusion is preserved through vasodilation of arterioles in the brain;

likewise, arteriolar vasoconstriction occurs at high systemic pressures

to prevent hyperperfusion, resulting in fairly constant perfusion across

a wide range of systemic blood pressures (Fig. 307-1). At the extreme

limits of MAP or CPP (high or low), flow becomes directly related to

perfusion pressure. These autoregulatory changes occur in the microcirculation and are mediated by vessels below the resolution of those

seen on angiography. CBF is also strongly influenced by pH and Paco2

.