2251Cardiogenic Shock and Pulmonary Edema CHAPTER 305

of vital organs and extremities remains a clinical hallmark. Although

ineffective stroke volume is the inciting event, inadequate circulatory

compensation also may contribute to shock. Initial peripheral vasoconstriction may improve coronary and peripheral perfusion at the cost

of increased afterload. However, over the course of CS, the systemic

inflammation response triggered by acute cardiac injury often induces

pathologic vasodilatation. Inflammatory cytokines and endothelial and

inducible nitric oxide (NO) synthase may augment production of NO

and its by-product, peroxynitrite, which has a negative inotropic effect

and is cardiotoxic. Lactic acidosis and hypoxemia contribute to the

vicious circle, as severe acidosis reduces the efficacy of endogenous and

exogenous catecholamines. During ICU or CICU support, bleeding

and/or transfusions may trigger inflammation and are usually associated with higher mortality (Fig. 305-1).

Patient Profile In patients with MI, older age, prior MI, diabetes

mellitus, anterior MI location, and multivessel coronary artery disease with extensive coronary artery stenoses are associated with an

increased risk of CS. Shock associated with a first inferior MI should

prompt a search for a mechanical cause or RV involvement. CS may

rarely occur in the absence of significant stenosis, as seen in takotsubo

syndrome or fulminant myocarditis.

Timing Shock is present on admission in approximately one-quarter

of MI patients who develop CS; of these patients, one-quarter develop

it rapidly thereafter, within 6 h of MI onset, and another quarter

develop shock later on the first day. Later onset of CS may be due to

reinfarction, marked infarct expansion, or mechanical complications.

Diagnosis For these unstable patients, supportive therapy must be

initiated simultaneously with diagnostic evaluation (Fig. 305-3). A

focused history and physical examination should be performed along

with an electrocardiogram (ECG), chest x-ray, arterial blood gas (ABG)

analysis, lactate measurement, and blood specimens for laboratory

analysis. Initial echocardiography is an invaluable tool to elucidate the

underlying cause of CS.

CLINICAL FINDINGS Most patients initially are dyspneic, pale, apprehensive, and diaphoretic, and mental status may be altered. The pulse

is typically weak and rapid, or occasionally, severe bradycardia due

to high-grade heart block may be present. Systolic BP is typically

reduced (<90 mmHg, or catecholamines are required to maintain BP

>90 mmHg), but occasionally, BP may be maintained by very high

systemic vascular resistance. Tachypnea and jugular venous distention

may be present. Typically, there is a weak apical pulse and a soft S1

, and

an S3

 gallop may be audible. Acute, severe MR and VSR usually are

associated with characteristic systolic murmurs (Chap. 275). Crackles

are audible in most patients with LV failure. Oliguria/anuria is common. CS patients often require early mechanical ventilation (~80%)

for management of acute hypoxemia, increased work of breathing, and

hemodynamic instability; vasopressors often are required to maintain

adequate BP.

LABORATORY FINDINGS The white blood cell count and C-reactive

protein typically are elevated. Renal function often is progressively

impaired. Newer renal function markers such as cystatin C or neutrophil gelatinase–associated lipocalin (NGAL) do not add prognostic

information over creatinine. Hepatic transaminases are elevated due

to liver hypoperfusion in ~20% of patients and may be very high. The

arterial lactate level is usually elevated to >2 mmol/L; if higher, it indicates worse prognosis. ABGs usually demonstrate hypoxemia and an

anion gap metabolic acidosis. Glucose levels at admission are often elevated, a strong independent predictor for mortality. Cardiac markers,

creatine kinase and its MB fraction, and troponins I and T are typically

markedly elevated in acute MI.

ELECTROCARDIOGRAM In acute MI with CS, Q waves and/or ST elevation in multiple leads or left bundle branch block are usually present.

Approximately one-half of MIs with CS are anterior infarctions. Global

ischemia due to severe left main stenosis usually is accompanied by

ST-segment elevation in lead aVR and ST depressions in multiple leads.

CHEST ROENTGENOGRAM The chest x-ray typically shows pulmonary vascular congestion and often pulmonary edema but may be

normal in up to a third of patients. The heart size is usually normal

when CS results from a first MI but may be enlarged when it occurs in

a patient with a previous MI.

ECHOCARDIOGRAM An echocardiogram (Chap. 241) should be

obtained promptly in patients with suspected/confirmed CS to help

define its etiology. Echocardiography is able to delineate the extent of

Stage E: Extremis CS. Patients experiencing cardiac arrest with

E ongoing cardiopulmonary resuscitation (CPR) and/or ECMO.

Extremis

D

Deteriorating

C

Classical cardiogenic

shock

B

Beginning cardiogenic shock

A

At risk for cardiogenic shock development

Stage D: CS signals deteriorating or doom. Similar to

stage C but getting worse and failing to respond to

initial interventions.

Stage C: Classic CS. Manifest CS with hypoperfusion

requiring intervention (inotropes, vasopressors, or MCS,

excluding ECMO) beyond volume resuscitation to

restore perfusion.

Stage B: Clinical evidence of relative hypotension

or tachycardia without hypoperfusion being at

“beginning” of CS (preshock).

Stage A: Currently no signs/symptoms

of CS, but being “at risk” for its

development.

FIGURE 305-2 Shock severity definition. Five categories of cardiogenic shock (CS). Stage A: At risk: Patients “at risk” for cardiogenic shock development but not currently

experiencing signs/symptoms of cardiogenic shock. Stage B: Patients with clinical evidence of relative hypotension or tachycardia without hypoperfusion being at

“beginning” of cardiogenic shock. Stage C: Patients in the state of “classic” cardiogenic shock. Stage D: Cardiogenic shock signals deteriorating or “doom.” Stage E:

Patients in “extremis,” such as those experiencing cardiac arrest with ongoing cardiopulmonary resuscitation and/or extracorporeal membrane oxygenation (ECMO)

cardiopulmonary resuscitation. MCS, mechanical circulatory support. (Reproduced with permission from H Thiele et al: Management of cardiogenic shock complicating

myocardial infarction: An update 2019. Eur Heart J 40:2671, 2019.)

2252 PART 8 Critical Care Medicine

infarction/myocardium in jeopardy and the presence of mechanical

complications such as VSR, MR, or cardiac tamponade. Furthermore, valvular obstruction or insufficiency, dynamic LV outflow tract

obstruction, and proximal aortic dissection with aortic regurgitation or

tamponade may be seen, or indirect evidence for pulmonary embolism

may be obtained (Chap. 279) (Table 305-2).

PULMONARY ARTERY CATHETERIZATION The use of pulmonary artery

catheter (PAC) hemodynamic monitoring has declined because clinical

trials have shown no mortality benefit. However, PAC hemodynamic

data and waveforms can be helpful in both diagnosis and management.

PAC data can confirm the presence and severity of CS, involvement of

the right ventricle, left-to-right shunting, pulmonary artery pressures

and transpulmonary gradient, and pulmonary and systemic vascular

resistance. It can help in recognition of acute MR, decreased left atrial

filling pressure, right or left dominance, and secondary septic causes

and also can exclude left-to-right shunts. Equalization of diastolic

pressures suggests cardiac tamponade, but echocardiogram is more

definitive. The detailed hemodynamic profile can be used to individualize and monitor therapy and to provide prognostic information,

such as cardiac index and cardiac power. The use of a PAC is currently

recommended by the American Heart Association for potential utilization in cases of diagnostic or CS management uncertainty or in patients

with severe CS who are unresponsive to initial therapy.

ADVANCED HEMODYNAMIC MONITORING Recently, new central

venous catheter systems linked to computer-based algorithms provide

continuous monitoring of a variety of derived hemodynamic parameters, including cardiac output, stroke volume, stroke volume variation,

and systemic vascular resistance (Table 305-3). When combined with a

femoral arterial catheter, calculated extravascular lung water and pulmonary permeability index can be monitored. The information allows for

more rational therapy and assessment but has not yet shown improved

clinical outcomes in patients with shock or pulmonary edema.

CARDIAC CATHETERIZATION AND CORONARY ANGIOGRAPHY The

definition of the coronary anatomy provides useful information and

is immediately indicated in all patients with CS complicating MI for

further reperfusion treatment. Furthermore, cardiac catheterization

should also be considered for resuscitated cardiac arrest survivors

without ST-segment elevation in CS because ~70% of these patients

have relevant coronary artery disease. However, routine early invasive

coronary angiography did not show a survival benefit in hemodynamically stable patients after resuscitation from cardiac arrest without

ST-segment elevation.

TREATMENT

Acute Myocardial Infarction

GENERAL MEASURES

In addition to the usual treatment of acute MI (Chap. 275), initial

therapy is aimed at maintaining adequate systemic and coronary

perfusion by raising the BP with vasopressors and adjusting volume status to a level that ensures optimum LV filling pressure

(Fig. 305-3). There is some interpatient variability, but generally,

adequate perfusion occurs with a mean arterial BP of 60–65 mmHg

or a systolic BP of ~90 mmHg. Hypoxemia and acidosis need to

be corrected, particularly since acidemia attenuates vasoconstriction by catecholamines. Up to 90% of patients require ventilatory

support, decreasing the stress from increased work of breathing

(see “Pulmonary Edema,” below) (Fig. 305-3). Moderate glucose

control (≤180 mg/dL or 10.0 mmol/L) should be a goal, and hypoglycemia must be avoided. Negative ionotropic agents should be

discontinued. Bradyarrhythmias may require transvenous pacing.

Recurrent ventricular tachycardia or rapid atrial fibrillation may

require immediate treatment (Chap. 246).

REPERFUSION-REVASCULARIZATION

Rapid revascularization of the infarct-related artery is the only

evidence-based treatment strategy for mortality reduction in CS

and forms the mainstay therapeutic intervention for CS due to MI

(Fig. 305-2). In the SHOCK trial, 132 lives were saved per 1000

patients treated with early revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG)

compared with initial medical therapy. Outcome benefit correlates

strongly with the time between symptom onset, first medical contact, and reperfusion. In general, PCI with drug-eluting stents of the

infarct-related artery is the preferred reperfusion strategy. Approximately 80% of CS patients present with multivessel coronary artery

disease. In these patients, culprit-only PCI with possible staged

revascularization is the method of choice because it reduces mortality and requirement for renal replacement therapy at 30 days and

1 year in comparison to immediate multivessel PCI, as shown in the

CULPRIT-SHOCK trial. The major driver for the reduction in the

composite endpoint was a reduction in 30-day mortality. Updated

recent clinical practice guidelines recommend avoiding immediate

nonculprit PCI. Currently, vascular access for diagnostic angiography and PCI via the radial artery are preferred when feasible over

femoral arterial access due to the greater safety of radial artery

access. CABG is currently performed in only 5% of cases, mainly if

coronary anatomy is not amenable to PCI.

TABLE 305-1 Etiologies of Cardiogenic Shocka

 and Cardiogenic

Pulmonary Edema

Etiologies of Cardiogenic Shock or Pulmonary Edema

Acute myocardial infarction/ischemia

Left ventricular failure

Ventricular septal rupture

Papillary muscle/chordal rupture–severe mitral regurgitation

Ventricular free wall rupture

Other conditions complicating large myocardial infarctions

Excess negative inotropic or vasodilator medications

Post–cardiac arrest

Postcardiotomy

Refractory sustained supraventricular or ventricular tachyarrhythmias

Refractory sustained bradyarrhythmias

Acute fulminant myocarditis

End-stage cardiomyopathy

Takotsubo syndrome/apical ballooning syndrome

Hypertrophic cardiomyopathy with severe outflow obstruction

Aortic dissection with aortic insufficiency or tamponade

Severe valvular heart disease

Critical aortic or mitral stenosis

Acute severe aortic regurgitation or mitral regurgitation

Toxic/metabolic

β Blocker or calcium channel antagonist overdose

Pheochromocytoma

Scorpion venom

Hypertensive crisis

Post–cardiac arrest stunning

Myocardial depression in setting of septic shock or systemic inflammatory

response syndrome

Myocardial contusion

Other Etiologies of Cardiogenic Shockb

Right ventricular failure due to:

Acute myocardial infarction

Acute or decompensated chronic cor pulmonale

Pericardial tamponade

Toxic/metabolic

Severe acidosis, severe hypoxemia

a

The etiologies of cardiogenic shock are listed. Most of these can cause pulmonary

edema instead of shock or pulmonary edema with cardiogenic shock. b

These cause

cardiogenic shock but not pulmonary edema.

2253Cardiogenic Shock and Pulmonary Edema CHAPTER 305

VASOPRESSORS AND INOTROPES

Inotropic agents are theoretically appealing in CS treatment. However, current evidence is scarce. Vasoactive medications are often

used in the management of patients with CS, and all have important

disadvantages, including increases in myocardial oxygen consumption, afterload, lethal arrhythmias, and possible myocardial cell

death. As a consequence, catecholamines should be used in the

lowest possible doses for the shortest possible time. Despite their

frequent use, little clinical outcome data prove their benefit or are

available to guide the initial selection of vasoactive therapies in

patients with CS. No vasopressor has been demonstrated to change

outcome in large clinical trials. Norepinephrine is reasonable as

the first-line vasopressor based on randomized trials compared to

dopamine and also epinephrine. Norepinephrine was associated

with fewer adverse events, including arrhythmias, compared to

dopamine in a randomized trial of patients with several etiologies

of circulatory shock and with improved survival in a prespecified

subgroup of CS patients. Norepinephrine dosing is usually begun at

2–4 μg/min and titrated upward based on BP. Norepinephrine was

associated with lower lactate levels and less refractory CS compared

to epinephrine. Dopamine’s hemodynamic effects vary depending

on dose, and there is interpatient variability in responses. Low

doses stimulate renal dopaminergic receptors, and with increasing

doses, there is stimulation of first β-adrenergic receptors and then

α-adrenergic receptors. Dopamine should be avoided as first-line

therapy for MI with CS based on hemodynamic and proarrhythmogenic effects.

Dobutamine is a synthetic sympathomimetic amine with positive inotropic action and minimal positive chronotropic activity at

low doses (2.5 μg/kg per min) but moderate chronotropic activity at

higher doses. Its vasodilating activity often precludes its use when

a vasoconstrictor effect is required. Levosimendan may also be

appealing despite a lack of randomized data but was not beneficial

for organ dysfunction in sepsis and also in high-risk patients undergoing cardiovascular surgery.

MECHANICAL CIRCULATORY SUPPORT

The most commonly used mechanical circulatory support (MCS)

device has been the intraaortic balloon pump (IABP), which is

inserted into the aorta via the femoral artery and provides passive

hemodynamic support. However, routine IABP use in conjunction

with early revascularization (predominantly with PCI) did not reduce

30-day, 12-month, or 6-year mortality in the IABP-SHOCK II trial.

IABP also had no benefit on secondary endpoints (arterial lactate, catecholamine doses, renal function, or intensive care severity of illness

unit scores). IABP is no longer recommended for CS with LV failure.

Surgical/intervent.

closure (IC)

Heart team

Cardiogenic shock complicating infarction (STEMI or NSTEMI)

Emergency invasive angiography (IB)

Immediate echocardiography (IC)

Left ventricular dysfunction (~80%)

Cause of

cardiogenic

shock Catheterization laboratory/ OR Mechanical circulatory support

General measures:

Mean blood pressure goal

65 mmHg, optimal

end-organ perfusion, lactate

clearance

Right ventricular dysfunction (~7%) Mechanical complication (~13%)

VSD (~4%) Mitral reg. (~7%) Free wall rupture (~2%)

Emergency PCI of culprit lesion (IB)

Emergency CABG (if not amenable to PCI) (IB)

No routine PCI of non-IRA lesions (IIIB)

Fluid challenge as first-line therapy if no sign of overt fluid overload (IC)

Invasive blood pressure monitoring (IC)

Pulmonary artery catheter (IIB/C)

Ventilatory support/O2 according to blood gases (IC)

Intravenous inotropes to increase cardiac output (IIB/C)

Vasopressors (norepinephrine preferable over dopamine) in presence of persistent hypotension (IIB/B)

Ultrafiltration in refactory congestion not responding to diuretics (IIB/C)

No routine IABP (IIIB)

Weaning

Weaning

Short-term percutaneous MCS in selected patients/refractory cardiogenic shock (IIB/C)

Yes

Yes

Yes

No

No

No Severe neurologic deficit? Age, comorbidities?

Long-term surgical MCS

Bridge to

recovery

Bridge to

transplant

Destination

therapy

IABP (IIA/C)

Mitral repair/

replacement (IC)

Emergency PCI of culprit lesion in case of interventional treatment

(IB)

Simultaneous CABG in case of surgical treatment (IB)

Surgery (IC)

pericardiocentesis

Stabilization?

Recovery of cardiac function?

FIGURE 305-3 Emergency management of patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI). Treatment algorithm for patients with

CS. The class of recommendation and level of evidence according to European Society of Cardiology guidelines are provided (see “Further Reading”). CABG, coronary

artery bypass grafting; ECG, electrocardiogram; IABP, intraaortic balloon pump; IRA, infarct-related artery; MCS, mechanical circulatory support; NSTEMI, non–ST-segment

elevation myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction; VSD, ventricular septal defect. (Reproduced

with permission from H Thiele et al: Management of cardiogenic shock complicating myocardial infarction: An update 2019. Eur Heart J 40:2671, 2019.)

2254 PART 8 Critical Care Medicine

TABLE 305-2 Utility of the Echocardiogram in Cardiogenic Shock or

Pulmonary Edema

CLINICAL QUESTION INFORMATION

Ventricular function Predominantly left, right, or biventricular

involvement

Etiology Acute Myocardial Infarction

• Extent of infarction/myocardium in jeopardy

• Status of the nonculprit infarct zone

• Presence of mechanical complications

Acute/Chronic Valvular Insufficiency/Obstruction/

Stenosis (Native/Prosthetic)

• Etiology: endocarditis; degenerative valve

disease

• Location and hemodynamic consequences

Dynamic Left Ventricular Tract Obstruction

Takotsubo Syndrome

Cardiac Tamponade

• Circumferential versus localized effusion

• Route of pericardiocentesis if indicated

Acute Pulmonary Embolism

• Right ventricular function

• Pulmonary artery pressure

• Presence of clot in transition/patent foramen

ovale

Acute Aortic Syndrome

• Nature and extent of dissection

• Degree of aortic insufficiency

• Presence of pericardial effusion

Hemodynamics Volume assessment by inferior vena cava diameter

and inspiratory collapse

Estimated pulmonary artery systolic pressure

Estimated left atrial pressure

Therapeutic guidance Guide vasoactive support

Monitor response to therapy

Mechanical circulatory support decisions

Catheter position and guidance

Pulmonary Pleural effusion

Lung edema

Pneumothorax

Pulmonary infiltration

TABLE 305-3 Hemodynamic Patternsa

RA, mmHg RVS, mmHg RVD, mmHg PAS, mmHg PAD, mmHg PCW, mmHg CI, (L/min)/m2 SVR, (dyn · s)/cm5

Normal values <6 <25 0–12 <25 0–12 <6–12 ≥2.5 (800–1600)

MI without pulmonary edemab — — — — — ~13 (5–18) ~2.7 (2.2–4.3) —

Pulmonary edema ↔↑ ↔↑ ↔↑ ↑ ↑ ↑ ↔↓ ↑

Cardiogenic shock

LV failure ↔↑ ↔↑ ↔↑ ↔↑ ↑ ↑ ↓ ↔↑

RV failurec ↑ ↓↔↑d ↑ ↓↔↑d ↔↓↑d ↓↔↑d ↓ ↑

Cardiac tamponade ↑ ↔↑ ↑ ↔↑ ↔↑ ↔↑ ↓ ↑

Acute mitral regurgitation ↔↑ ↑ ↔↑ ↑ ↑ ↑ ↔↓ ↔↑

Ventricular septal rupture ↑ ↔↑ ↑ ↔↑ ↔↑ ↔↑ ↑PBF ↓SBF ↔↑

Hypovolemic shock ↓ ↔↓ ↔↓ ↓ ↓ ↓ ↓ ↑

Septic shock ↓ ↔↓ ↔↓ ↓ ↓ ↓ ↑ ↓

a

There is significant patient-to-patient variation. Pressure may be normalized if cardiac output is low. b

Forrester et al classified non-reperfused MI patients into four

hemodynamic subsets. (From JS Forrester et al: N Engl J Med 295:1356, 1976.) PCW pressure and CI in clinically stable subset 1 patients are shown. Values in parentheses

represent range. c

”Isolated” or predominant RV failure. d

PCW and pulmonary artery pressures may rise in RV failure after volume loading due to RV dilation and right-to-left

shift of the interventricular septum, resulting in impaired LV filling. When biventricular failure is present, the patterns are similar to those shown for LV failure.

Abbreviations: CI, cardiac index; LV, left ventricular; MI, myocardial infarction; P/SBF, pulmonary/systemic blood flow; PAS/D, pulmonary artery systolic/diastolic; PCW,

pulmonary capillary wedge; RA, right atrium; RV, right ventricular; RVS/D, right ventricular systolic/diastolic; SVR, systemic vascular resistance.

Source: Table prepared with the assistance of Krishnan Ramanathan, MD.

Active MCS devices to support the left, right, or both ventricles can be placed percutaneously or surgically. Temporary percutaneous MCS can be used as bridge to recovery, to surgically

implanted devices, or to heart transplantation, or as a temporizing

measure when the neurologic status is uncertain. Percutaneous

MCS, including the TandemHeart and Impella devices, and also

venoarterial extracorporeal membrane oxygenation (VA-ECMO)

have been used in patients not responding to standard treatment

(catecholamines, fluids, and IABP) and also as a first-line treatment.

Active percutaneous MCS results in better hemodynamic support

compared to IABP. However, the appropriate role of MCS is uncertain because a positive impact on clinical outcomes or mortality

has not yet been demonstrated in trials or meta-analyses. More

recent observational data with matched comparisons even showed

higher mortality and more complications with active devices such

as Impella.

Surgically implanted devices can support the circulation as

bridging therapy for cardiac transplant candidates or as destination

therapy (Chap. 260). Assist devices should be used selectively in

suitable patients based on decisions by a multidisciplinary team

with expertise in the selection, implantation, and management of

MCS devices (Fig. 305-3).

Prognosis The expected death rates for patients with MI complicated by CS range widely based on age, severity of hemodynamic

abnormalities, severity of clinical hypoperfusion (arterial lactate,

renal function), and performance of early revascularization. The

recently introduced IABP-SHOCK II score predicts prognosis based

on six readily available variables: age >73 years; prior stroke; glucose

at admission >10.6 mmol/L (191 mg/dL); creatinine at admission

>132.6 μmol/L (1.5 mg/dL); Thrombolysis in Myocardial Infarction

(TIMI) flow grade after PCI <3; and arterial blood lactate at admission

>5 mmol/L. It also may help guide treatment strategies. The SCAI CS

severity definition is also helpful in prognosis estimation.

■ SHOCK SECONDARY TO RIGHT VENTRICULAR

INFARCTION

Persistent CS due to predominant RV failure accounts for only 5%

of CS complicating MI. It often results from proximal right coronary

artery occlusion. The salient features are relatively high right atrial

pressures, RV dilation and dysfunction, and only mildly or moderately

depressed LV function. High right-sided pressures may be absent

without volume loading. However, CS often has overlap combinations

2255Cardiogenic Shock and Pulmonary Edema CHAPTER 305

of both RV and LV ischemia, given a shared septum and the effect of

ventricular interdependence on RV function. Management of isolated

RV CS includes fluid administration to optimize right atrial pressure

(10–15 mmHg); avoidance of excess fluids, which shifts the interventricular septum into the LV; catecholamines; early reestablishment of

infarct-artery flow; and right-sided MCS.

■ MITRAL REGURGITATION

(See also Chap. 275) Acute severe MR due to papillary muscle dysfunction and/or rupture may complicate MI and result in CS and/or

pulmonary edema. This complication most often occurs on the first

day, with a second peak several days later. The diagnosis is confirmed

by echocardiography (Table 305-2). Afterload reduction with IABP

and, if tolerated, vasodilators to reduce pulmonary edema is recommended as a bridge to surgery or interventional treatment. Mitral

valve repair or reconstruction is the definitive therapy and should be

performed early in the course in suitable candidates. Other options

include percutaneous edge-to-edge repair, which has been successful

in small case series (Fig. 305-3).

■ VENTRICULAR SEPTAL RUPTURE

(See also Chap. 275) VSR complicating MI is a relatively rare event

associated with very high mortality if CS is present (>80%). The incidence of infarct-related VSR without reperfusion was 1–2% but has

decreased to 0.2% in the era of reperfusion. VSR occurs a median of

24 h after infarction but may occur up to 2 weeks later. Echocardiography demonstrates shunting of blood from the left to the right ventricle

and may visualize the opening in the interventricular septum. Current

guidelines recommend immediate surgical VSR closure, irrespective

of the patient’s hemodynamic status, to avoid further hemodynamic

deterioration. IABP support as a bridge to surgery is recommended

based on expert opinion. Given high mortality, suboptimal surgical

results, and the ineligibility for surgery of many patients, interventional

percutaneous VSR umbrella device closure has been developed. Results

of interventional VSR closure suggest a similar outcome as surgery. The

heart team should decide how to close the VSR (Fig. 305-3).

■ FREE WALL RUPTURE

Myocardial rupture is a dramatic complication of MI that is most likely

to occur during the first week after the onset of symptoms. The clinical

presentation typically is a sudden loss of pulse, BP, and consciousness

with ongoing sinus rhythm on ECG (pulseless electrical activity) due

to cardiac tamponade (Chap. 270). Free wall rupture may also result in

CS due to subacute tamponade when the pericardium temporarily seals

the rupture sites. Definitive surgical repair is required (Fig. 305-3).

■ ACUTE FULMINANT MYOCARDITIS

(See also Chap. 259) Myocarditis can mimic acute MI with ST abnormalities or bundle branch block on the ECG and marked elevation of

cardiac markers. Acute myocarditis causes CS in a small proportion of

cases. These patients are typically younger than those with CS due to

acute MI and often do not have typical ischemic chest pain. Echocardiography usually shows global LV dysfunction. Initial management is

the same as for CS complicating acute MI but does not involve revascularization. Endomyocardial biopsy is recommended to determine the

diagnosis and need for immunosuppressives for entities such as giant

cell myocarditis. Refractory CS can be managed with MCS.

■ PULMONARY EDEMA

The etiologies and pathophysiology of pulmonary edema are discussed in Chap. 37.

Diagnosis Acute pulmonary edema usually presents with the rapid

onset of dyspnea at rest, tachypnea, tachycardia, and severe hypoxemia.

Crackles and wheezing due to alveolar flooding and airway compression from peribronchial cuffing may be audible. Release of endogenous

catecholamines often causes hypertension.

It is often difficult to distinguish between cardiogenic and noncardiogenic causes of acute pulmonary edema. Echocardiography may

identify systolic and diastolic ventricular dysfunction and valvular

lesions. ECG ST elevation and evolving Q waves are usually diagnostic of acute MI and should prompt immediate institution of MI

protocols and coronary artery revascularization therapy (Chap. 275).

Brain natriuretic peptide levels, when substantially elevated, support

heart failure as the etiology of acute dyspnea with pulmonary edema

(Chap. 257).

The use of a PAC permits measurement of pulmonary capillary

wedge pressures (PCWP) and helps differentiate high-pressure (cardiogenic) from normal-pressure (noncardiogenic) causes of pulmonary edema. Pulmonary artery catheterization is indicated when the

etiology of the pulmonary edema is uncertain, when edema is refractory to therapy, or when it is accompanied by refractory hypotension.

Data derived from use of a PAC often alter the treatment plan, but no

impact on mortality rates has been demonstrated.

TREATMENT

Pulmonary Edema

The treatment of pulmonary edema depends on the specific etiology. As an acute, life-threatening condition, a number of measures must be applied immediately to support the circulation, gas

exchange, and lung mechanics. Simultaneously, conditions that frequently complicate pulmonary edema, such as infection, acidemia,

anemia, and acute kidney dysfunction, must be corrected.

SUPPORT OF OXYGENATION AND VENTILATION

Patients with acute cardiogenic pulmonary edema generally have

an identifiable cause of acute LV failure—such as arrhythmia,

ischemia/infarction, or myocardial decompensation (Chap. 257)—

that may be rapidly treated, with improvement in gas exchange. In

contrast, noncardiogenic edema usually resolves much less quickly,

and most patients require mechanical ventilation.

Oxygen Therapy Support of oxygenation is essential to ensure

adequate O2

 delivery to peripheral tissues, including the heart. Generally, the goal is O2

 saturation of 92% or more, but very high saturation (>98%) may be detrimental. For non-CS acute hypoxemic

respiratory failure patients with normal Paco2

, O2

 administration

by high-flow nasal cannula for acute hypoxemic respiratory failure

has better outcomes than use of bilevel positive airway pressure

(BiPAP).

Positive-Pressure Ventilation Pulmonary edema increases the

work of breathing and the O2

 requirements of this work, imposing

a significant physiologic stress on the heart. When oxygenation or

ventilation is not adequate despite supplemental O2

, positive-pressure

ventilation by face or nasal mask or by endotracheal intubation

should be initiated. Noninvasive ventilation (NIV) (Chap. 302)

can rest the respiratory muscles, improve oxygenation and cardiac

function, and reduce the need for intubation. While NIV is believed

effective for cardiogenic pulmonary edema, Cochrane analyses

have not yet substantiated this benefit. In refractory cases, mechanical ventilation can relieve the work of breathing more completely

than can NIV. Mechanical ventilation with positive end-expiratory

pressure can have multiple beneficial effects on pulmonary edema,

as it: (1) decreases both preload and afterload, thereby improving

cardiac function; (2) redistributes lung water from the intraalveolar

to the extraalveolar space, where the fluid interferes less with gas

exchange; and (3) increases lung volume to avoid atelectasis.

Renal Replacement Therapy For pulmonary edema patients with

refractory volume overload, metabolic acidosis (pH <7.15–7.25),

hypoxemia, and/or persistent hyperkalemia, renal replacement

therapy should be considered. For patients who are hypotensive or

require ionotropic support, continuous renal replacement therapy

usually is better tolerated than intermittent hemodialysis.

REDUCTION OF PRELOAD

In most forms of pulmonary edema, the quantity of extravascular

lung water is determined by a combination of the PCWP, the pulmonary vascular permeability, and the intravascular volume status.

2256 PART 8 Critical Care Medicine

Diuretics The loop diuretics furosemide, bumetanide, and

torsemide are effective in most forms of pulmonary edema, even in

the presence of hypoalbuminemia, hyponatremia, or hypochloremia. Furosemide is also a venodilator that rapidly reduces preload

before any diuresis occurs and is the diuretic of choice. The initial

dose of furosemide should be ≤0.5 mg/kg, but a higher dose (1 mg/

kg) is required in patients with renal insufficiency, chronic diuretic

use, or hypervolemia or after failure of a lower dose. Combinations

of diuretics and/or continuous infusion are helpful to achieve the

desired degree of diuresis in selected patients.

Nitrates Nitroglycerin and isosorbide dinitrate act predominantly

as venodilators but have coronary vasodilating properties as well.

Their onset is rapid, and they are effectively administered by a

variety of routes. Sublingual nitroglycerin (0.4 mg × 3 every 5 min)

is first-line therapy for acute cardiogenic pulmonary edema. If pulmonary edema persists in the absence of hypotension, sublingual

may be followed by IV nitroglycerin, commencing at 5–10 μg/min.

IV nitroprusside (0.1–5 μg/kg per min) is a potent venous and arterial vasodilator. It is useful for patients with pulmonary edema and

hypertension but is not recommended in states of reduced coronary

artery perfusion. It requires close monitoring and titration using an

arterial catheter for continuous BP measurement.

Morphine Given in 2- to 4-mg IV boluses, morphine is a transient

venodilator that reduces preload while relieving dyspnea and anxiety. These effects can diminish stress, catecholamine levels, tachycardia, and ventricular afterload in patients with pulmonary edema

and systemic hypertension. However, some registry trials showed

increased mortality with use of morphine.

Angiotensin-Converting Enzyme (ACE) Inhibitors ACE inhibitors reduce both afterload and preload and are recommended for

hypertensive patients. A low dose of a short-acting agent may be

initiated and followed by increasing oral doses. In acute MI with

heart failure, ACE inhibitors reduce short- and long-term mortality

rates. The optimal starting point of ACE inhibitors has not been

tested so far.

Other Preload-Reducing Agents IV recombinant brain natriuretic

peptide (nesiritide) is a potent arterial and venous vasodilator with

diuretic properties and is effective in the treatment of cardiogenic

pulmonary edema. It should be reserved for refractory patients and

is not recommended in the setting of ischemia or MI. Endothelin

antagonists are being studied as they inhibit vasoconstriction and

can improve cardiac output and decrease PCWP.

Physical Methods In nonhypotensive patients, venous return

can be reduced by use of the sitting position with the legs dangling

along the side of the bed.

Inotropic and Inodilator Drugs The sympathomimetic amines

dopamine and dobutamine (see above) are potent inotropic agents.

The bipyridine phosphodiesterase-3 inhibitors (inodilators), such

as milrinone (50 μg/kg followed by 0.25–0.75 μg/kg per min), stimulate myocardial contractility while promoting peripheral and pulmonary vasodilation. Inodilators may be helpful in selected patients

with cardiogenic pulmonary edema and severe LV dysfunction, but

there is little published clinical data.

Digitalis Glycosides Once a mainstay of treatment because of

their positive inotropic action (Chap. 257), digitalis glycosides are

rarely used at present. However, they may be useful for control of

ventricular rate in patients with rapid ventricular response to atrial

fibrillation or flutter and LV dysfunction with pulmonary edema,

because they do not have the negative inotropic effects of other

drugs that inhibit atrioventricular nodal conduction

Intraaortic Balloon Counterpulsation IABP (Chap. 260) may be

helpful in rare instances of acute MR from infective endocarditis

but is not typically used for pulmonary edema with CS.

Treatment of Tachyarrhythmias and Atrioventricular Resynchronization (See also Chap. 252) Sinus tachycardia or atrial fibrillation

can result from elevated left atrial pressure and sympathetic stimulation. Tachycardia itself can limit LV filling time and raise left

atrial pressure further. Although relief of pulmonary congestion

will slow the sinus rate or ventricular response in atrial fibrillation,

a primary tachyarrhythmia may require cardioversion. In patients

with reduced LV function and without atrial contraction or with

lack of synchronized atrioventricular contraction, placement of

an atrioventricular sequential pacemaker should be considered

(Chap. 244).

Reduction in Pulmonary Vascular Permeability At present, no

clinical therapies have been demonstrated as clinically effective to

reduce the “leakiness” of the pulmonary capillaries.

Stimulation of Alveolar Fluid Clearance A variety of drugs and

cellular therapies can stimulate alveolar epithelial ion transport and

upregulate the clearance of alveolar solute and water, but this strategy has not been proven beneficial in clinical trials thus far.

SPECIAL CONSIDERATIONS

Risk of Iatrogenic Cardiogenic Shock In the treatment of pulmonary edema, vasodilators lower BP, and their use, particularly in

combination, may lead to hypotension, coronary artery hypoperfusion, and shock (Fig. 305-1). In general, patients with a hypertensive

response to pulmonary edema tolerate and benefit from these medications. In normotensive patients, low doses of single agents should

be instituted sequentially, as needed, and with close monitoring.

Acute Coronary Syndromes (See also Chap. 275) Acute STEMI

complicated by pulmonary edema is associated with in-hospital

mortality rates of 20–40%. After immediate stabilization, coronary

artery blood flow must be reestablished rapidly. Early primary PCI

is the method of choice; alternatively, a fibrinolytic agent should be

administered. Early coronary angiography and revascularization by

PCI or CABG also are indicated for patients with non–ST-segment

elevation acute coronary syndrome.

Takotsubo Syndrome Takotsubo syndrome is an acute reversible

heart failure syndrome characterized by acute onset of left-sided

heart failure with reversible ST segment elevation and some

increase in troponin levels, usually triggered by a major physical or

emotional, stressful event. At end systole there often is the appearance of left ventricular apical ‘ballooning’. Most patients recover

and return to normal ventricular function. However, prognosis is

similar or even worse in comparison to patients with acute myocardial infarction.

Extracorporeal Membrane Oxygenation (ECMO) For patients

with acute, severe, noncardiogenic edema with a potential rapidly

reversible cause, ECMO may be considered in highly selected

patients as a temporizing supportive measure to achieve adequate

gas exchange, with current survival to discharge rates of 50–60%.

Usually, venovenous ECMO is used in this setting. ECMO can function as a bridge to transplantation or other interventions.

Unusual Types of Edema Specific etiologies of pulmonary edema

may require particular therapy. Reexpansion pulmonary edema can

develop after removal of longstanding pleural space air or fluid.

These patients may develop hypotension or oliguria with pulmonary edema resulting from rapid fluid shifts into the lung. Diuretics

and preload reduction are contraindicated, and intravascular volume repletion often is needed while supporting oxygenation and

gas exchange.

High-altitude pulmonary edema often can be prevented by use

of dexamethasone, calcium channel–blocking drugs, or long-acting

inhaled β2

-adrenergic agonists. Treatment includes descent from

altitude, bed rest, oxygen, and, if feasible, inhaled NO; nifedipine

may also be effective.

For pulmonary edema resulting from upper airway obstruction,

recognition of the obstructing cause is key because treatment then

is to relieve or bypass the obstruction.

2257Cardiovascular Collapse, Cardiac Arrest, and Sudden Cardiac Death CHAPTER 306

■ FURTHER READING

Alviar CL et al: For the ACC Critical Care Cardiology Working

Group. Positive pressure ventilation in the cardiac intensive care unit.

J Am Coll Cardiol 72:1532, 2018.

Amin AP et al: The evolving landscape of Impella use in the United

States among patients undergoing percutaneous coronary intervention with mechanical circulatory support. Circulation 141:273,

2020.

Baran DA et al: SCAI clinical expert consensus statement on the classification of cardiogenic shock. Cathet Cardiovasc Interv 94:29, 2019.

Dhruva SS et al: Association of use of intravascular microaxial left

ventricular assist device vs intra-aortic balloon pump on in-hospital

mortality and major bleeding among patients with acute myocardial

infarction complicated by cardiogenic shock. JAMA 323:734, 2020.

Hochman Judith S et al: Early revascularization in acute myocardial

infarction complicated by cardiogenic shock. SHOCK investigators.

Should we emergently revascularize occluded coronaries for cardiogenic shock. N Engl J Med 341:625, 1999.

Ingbar DH: Cardiogenic pulmonary edema: Mechanisms and

treatment—An intensivists view. Curr Opin Crit Care 25:371, 2019.

Thiele H et al: Intraaortic balloon support for myocardial infarction

with cardiogenic shock. N Engl J Med 367:1287, 2012.

Thiele H et al: PCI strategies in patients with acute myocardial infarction and cardiogenic shock. N Engl J Med 377:2419, 2017.

Thiele H et al: Percutaneous short-term active mechanical support

devices in cardiogenic shock: A systematic review and collaborative

meta-analysis of randomized trials. Eur Heart J 38:3523, 2017.

Thiele H et al: One-year outcomes after PCI strategies in cardiogenic

shock. N Engl J Med 379:1699, 2018.

Thiele H et al: Management of cardiogenic shock complicating myocardial infarction: An update 2019. Eur Heart J 40:2671, 2019.

van Diepen S et al: Contemporary management of cardiogenic shock:

A scientific statement. Circulation 136:e232, 2017.

OVERVIEW AND DEFINITIONS

(SEE TABLE 306-1)

Cardiovascular collapse is severe hypotension from acute cardiac

dysfunction or loss of peripheral vasculature resistance resulting in

cerebral hypoperfusion and loss of consciousness. This condition can

be the result of a cardiac arrhythmia, severe myocardial or valvular

dysfunction, loss of vascular tone, and/or acute disruption of venous

return. When an effective circulation is restored spontaneously,

patients present with syncope (see Chap. 21). In the absence of spontaneous resolution, then cardiac arrest occurs, ultimately resulting in

death if resuscitation attempts are unsuccessful or not initiated. Underlying etiologies for cardiovascular collapse include benign conditions,

such as neurocardiogenic syncope, but also life-threatening conditions

including: ventricular tachyarrhythmias; severe bradycardia; severely

depressed myocardial contractility, as with massive acute myocardial

infarction (MI) or pulmonary embolus; and other catastrophic events

interfering with cardiac function such as myocardial rupture with

cardiac tamponade or papillary muscle rupture with torrential mitral

regurgitation.

Sudden cardiac arrest (SCA) refers to an abrupt loss of cardiac

function resulting in complete cardiovascular collapse due either to an

306 Cardiovascular Collapse,

Cardiac Arrest, and

Sudden Cardiac Death

Christine Albert, William H. Sauer

acute life-threatening cardiac arrhythmia or abrupt loss of myocardial

pump function that requires emergency medical intervention for restoration of effective circulation. Most SCAs occur outside the hospital,

and fewer than 10% of these victims survive to be discharged from

the hospital despite undergoing attempted resuscitation by emergency

medical services (EMS). For those that die prior to hospital admission,

a cardiovascular cause for the arrest is often presumed based upon the

absence of evidence for a traumatic or other noncardiac cause at the

time of the arrest. If the patient does not survive an SCA, the death is

classified as a sudden cardiac death (SCD). Deaths that occur during

hospitalization or within 30 days after resuscitated cardiac arrest are

usually counted as SCDs in epidemiologic studies.

SCD also includes a broader category of unexplained rapid deaths

thought to be due to cardiac causes where resuscitation was not

attempted. In epidemiologic studies, SCD is usually defined as an

unexpected death without obvious extracardiac cause that occurs in

association with a witnessed rapid collapse or within 1 h of symptom

onset. This definition is based on the presumption that rapid deaths

are often due to an arrhythmia, an assumption that cannot always be

validated. Approximately half of all SCDs are not witnessed. In the

United States, few deaths undergo autopsies, and noncardiac conditions that evolve rapidly such as acute cerebral hemorrhage, aortic

rupture, and pulmonary embolism cannot be excluded without an

autopsy. Therefore, definitive information necessary to establish the

cause of death is usually not available. In unwitnessed cases, the definition is often further expanded to include unexpected deaths where

the subject was documented to be well when last observed within

the preceding 24 h. This expanded definition further decreases the

certainty that the death was due to an arrhythmia or other cardiac

causes, and recent data suggest that noncardiac causes may comprise a

larger than expected percentage of these unwitnessed sudden deaths.

Most countries, including the United States, do not have national

surveillance systems or reporting requirements for SCD; thus the true

incidence and frequency of SCD and its different mechanisms can only

be estimated.

EPIDEMIOLOGY

■ DEMOGRAPHICS

SCA and SCD are major public health problems that account for 15%

of all deaths and comprise 50% of all cardiac deaths. In the United

States alone, there are an estimated 350,000 EMS-attended out-ofhospital cardiac arrests and 210,000 SCDs in the adult population

annually. The estimated societal burden of premature death due to SCD

is 2 million years of potential life lost for men and 1.3 million years of

potential life lost for women, which is greater than most other leading

causes of death. Although cardiac pathology, particularly coronary

heart disease (CHD), underlies the majority of SCDs, up to two-thirds

of all SCDs occur as the first clinical expression of previously undiagnosed heart disease. SCD rates have declined but not as steeply as

rates for CHD in general. Age, gender, race, and geographic region all

influence the incidence of SCD. Rates of out-of-hospital cardiac arrest

are lower in Asia (52.5 per 100,000 person-years) than Europe (86.4 per

100,000 person-years), North America (98.1 per 100,000 person-years),

and Australia (111.9 per 100,000 person-years); and also vary within

geographic regions of the United States. SCD is rare in individuals

younger than 35 years of age (1–3 per 100,000 per year) and increases

markedly with age as the incidence of coronary artery disease (CAD),

heart failure (HF), and other predisposing conditions also increases.

Although absolute SCD rates increase with age, the proportion of

deaths that are due to SCD decreases as other causes of death increase.

Women have a lower incidence of SCD and SCA than men, and

women are more likely to present with pulseless electrical activity

(PEA) and to have their SCD occur at home as compared with men.

Possibly related to these factors, the SCD rate has not declined as much

for younger women compared to men in recent years. Black as opposed

to white Americans have higher rates of SCD, are more likely to have

unwitnessed arrests, to be found with PEA, and have lower rates of survival. Socioeconomic disparities, with resuscitation being less likely in