Chapter 50: Cardiogenic Shock

Cardiogenic shock is an acute state of decreased cardiac output resulting in inadequate tissue perfusion despite adequate circulating volume. Cardiogenic shock is the leading cause of in-hospital death in patients with acute myocardial infarction (AMI).¹ The true incidence of cardiogenic shock is unknown because many patients die before arrival and escape estimates. Cardiogenic shock is seen in 4% to 8% of patients with ST-segment elevation myocardial infarction (STEMI).^2,3 The incidence is declining in part as a result of the increased use of percutaneous intervention for AMI.^3,4,5,6 Cardiogenic shock occurs less frequently (2.5%) in those with non–ST-segment elevation myocardial infarction (NSTEMI) compared with those with STEMI.^7,8 Only ~10% of AMI patients who will develop cardiogenic shock have it at ED presentation, with the median time of onset after arrival being approximately 6 hours.^2,9 This underscores the therapeutic opportunity that exists by thwarting ongoing myocardial ischemia.

During the past decade, a strategy of early revascularization by percutaneous coronary intervention or coronary artery bypass surgery improved survival of cardiogenic shock patients with acute ischemia compared to medical therapy alone.^3,10,11,12 Despite these advances, the mortality remains high (~50%), with half of the deaths occurring within the first 48 hours after presentation.^3,13,14,15 Early recognition of cardiogenic shock or ongoing myocardial ischemia is the key for emergency physicians. Prompt and successful efforts to restore perfusion optimize patient outcomes.

The more risk factors that are present (Table 50-1), the greater is the amount of vulnerable myocardium and the greater is the likelihood of cardiogenic shock.

The most common cause of cardiogenic shock is extensive myocardial infarction that depresses myocardial contractility. Additional causes are listed in Table 50-2. Regardless of the precipitating cause, cardiogenic shock is primarily "pump failure," which results in reduced cardiac output. The systolic blood pressure drops due to poor cardiac output, and vital organ perfusion is limited. Absent a rise in systemic vascular resistance, the diastolic blood pressure also drops, resulting in coronary artery hypoperfusion. This creates a cycle of worsening myocardial ischemia and pump dysfunction, and eventual decompensation.

Historically, many believed cardiogenic shock was associated with a reflex compensatory vasoconstriction that would increase systemic vascular resistance. Contemporary data refute this belief, showing the average systemic vascular resistance was not elevated in cardiogenic shock patients, even with vasopressor use.¹⁶ Furthermore, the average left ventricular ejection fraction (EF) was only moderately depressed (~30%),¹⁷ and diastolic dysfunction was seen early and frequently, and was associated with greater depression of EF and an increased need for mechanical support.^18,19

A systemic inflammatory response syndrome occurs after AMI and in cardiogenic shock, due to complement system activation and release of systemic inflammatory mediators, including cytokines and inducible nitric oxide synthase.^20,21 The inflammatory response also depresses pump function, dilates the peripheral vasculature, and increases the risk of death.²² However, targeting nitric oxide with tilarginine does not alter mortality, although it improves blood pressure.²³ The monoclonal c5 antibody pexelizumab has been studied as an adjunct to percutaneous intervention in an effort to blunt the activation of the complement cascade associated with infarction. The largest trial of pexelizumab failed to show a mortality benefit compared to placebo.²⁴

Resolution of severe ischemia, neurohormonal, and inflammatory abnormalities may explain the reversible nature of cardiogenic shock in some patients. The wide variations in EF, ventricular size, and vascular resistance suggest that the pathophysiology of cardiogenic shock is diverse and poorly understood.

HISTORY

History can be difficult to obtain if the patient is severely ill. EMS personnel, family, or the medical record may offer additional historical information, notably of existing ischemic heart disease. Patients commonly complain of shortness of breath, chest pain, or weakness. Through history, try to exclude other causes of shock, such as sepsis, massive pulmonary embolism, hemorrhage, or a viral prodrome suggesting myocarditis. Ask about a history of preexisting valvular disease, recent illnesses, hypercoagulable states, substance abuse, or other risk factors for cardiogenic shock as outlined in Table 50-1. Assess for other causes of shock because treatment differs depending on the cause of cardiovascular system failure (Table 50-3).

PHYSICAL EXAMINATION

Cardiogenic shock is characterized by hypoperfusion; this is not always accompanied by hypotension.⁹ Systolic blood pressure is usually <90 mm Hg, although it can be higher with preexisting hypertension. A pulse pressure <20 mm Hg is another finding if systemic resistance has not plummeted, and sinus tachycardia is common unless the patient is on medications that block a tachycardic response. Unless the patient has advanced to the stage of respiratory fatigue or agonal respirations, tachypnea is common. The lung examination demonstrates rales due to the presence of pulmonary edema, except in cases of isolated right-sided failure. Jugular venous distention and a positive hepatojugular reflex are usually present. Patients are usually pale or cyanotic and may have cool skin and mottled extremities or other signs of hypoperfusion. Peripheral edema suggests preexisting heart failure. Diaphoresis indicates activation of the sympathetic nervous system. Cerebral hypoperfusion may result in altered mental status, and renal hypoperfusion may decrease urine output.

If the cardiac point of maximal impulse is normally located, shock is likely due to an acute event. If the point of maximal impulse is laterally shifted and diffuse from cardiac remodeling and enlargement, long-standing cardiac disease with acute decompensation can be presumed. About 10% of cardiogenic shock after AMI is caused by mechanical complications.¹⁴ A new murmur may be the only physical exam finding of mechanical catastrophe; carefully seek any loud or new systolic murmurs. Acute mitral regurgitation can occur from chordae tendineae rupture or papillary muscle dysfunction, accompanied by a soft holosystolic murmur at the apex radiating to the axilla with rales. With papillary muscle dysfunction, the murmur starts with the first heart sound but terminates before the second. An acute ventral septal defect is associated with a new loud holosystolic left parasternal murmur, often with a palpable thrill, that decreases in intensity as the intraventricular pressures equalize. Acute aortic insufficiency is characterized by a soft diastolic murmur and a softer S₁ sound.

Clinical signs of cardiogenic shock include evidence of poor cardiac output with tissue hypoperfusion (hypotension, mental status changes, cool mottled skin) and evidence of volume overload (dyspnea, rales, jugular venous distention). Hemodynamic criteria for cardiogenic shock include (1) sustained hypotension (systolic blood pressure <90 mm Hg), (2) reduced cardiac index (<2.2 L/min/m²), and (3) an elevated (>18 mm Hg) pulmonary artery occlusion pressure. The causes and differential diagnosis of cardiogenic shock are listed in Tables 50-2 and 50-3.

LABORATORY TESTING

There are no laboratory markers specific for the diagnosis of cardiogenic shock. Cardiac biomarkers (primarily troponin) may not be elevated upon initial presentation from an acute myocardial ischemic triggering event, but will eventually elevate. A CBC excludes anemia, which can contribute to cardiac ischemia. The clinical presentation guides the need for specific drug levels (e.g., digoxin, ethanol, or illicit drugs). Hypoperfusion commonly results in an elevated serum lactate, so checking serum lactate may aid diagnosis when overt hypotension is absent. Serum electrolytes and renal and hepatic studies can identify end-organ dysfunction.

The level of serum B-type natriuretic peptide (BNP) is an indicator of left ventricular dysfunction. Because of its high negative predictive value, a normal BNP level (<100 picograms/mL) eliminates cardiogenic shock as the cause of hypoperfusion unless very early after onset or with isolated right heart failure. Conversely, an elevated BNP does not diagnose cardiogenic shock.^25,26

Although elevated inflammatory markers such as C-reactive protein have some prognostic value, these are rarely needed in the acute phase of care.²⁷ Arterial blood gas measurements help identify those at risk of carbon dioxide retention, quantify the presence and severity of acidosis, and determine the contribution of metabolic or respiratory components to acidosis.

IMAGING AND ANCILLARY STUDIES

Electrocardiogram

The ECG helps detect ischemia or STEMI, evaluates for rhythm abnormalities, and provides evidence of electrolytic abnormalities (e.g., hypokalemia) or drug toxicity (e.g., digoxin).

It is important to assess for right ventricle (RV) involvement whenever ischemia is considered because RV infarction is associated with an increased risk for cardiogenic shock and death.²⁸ RV infarction is best evaluated by obtaining right-sided ECG leads (usually V₄R and V₅R) (Figure 50-1). RV infarction complicating inferior myocardial infarction is detected by ST elevation in lead V₁ with depression in V₂.

Chest Radiography

Obtain a portable chest radiograph in all patients. Chest x-ray typically shows pulmonary congestion or edema, alveolar infiltrates, and pleural effusion. These findings may lag by hours, so their absence does not exclude cardiogenic shock. Another confounder to interpreting the chest radiograph is underlying preexisting cardiopulmonary disease; pulmonary edema is difficult to detect on chest radiography in patients with severe chronic obstructive lung disease or interstitial lung disease. Cardiomegaly is the end result of long-standing myocardial remodeling, and its presence may not explain the acute symptoms. The chest radiograph can suggest alternative or confounding diagnoses, such as pneumonia, pneumothorax, aortic dissection, or progressive pericardial effusion (globular cardiac shape).

Bedside Echocardiography

In the setting of cardiogenic shock, emergency bedside echocardiography can help exclude alternative etiologies of shock, identify some mechanical complications, and guide therapy. Assessment should include evaluation of the inferior vena cava (IVC) to determine volume status and estimate right atrial pressure. A subcostal four-chamber view is helpful to visualize pericardial effusion and identify cardiac tamponade. When tamponade is present, there is a pericardial effusion with associated dilation of the IVC and diastolic collapse of the RV with systolic collapse of the right atrium. When cardiac rupture has occurred, there may be a visible clot in the pericardial space. Subcostal, parasternal, and apical views together can help estimate EF and cardiac contractility. An aortic root measurement greater than 3 cm is concerning for ascending aortic dissection, especially when associated with a pericardial effusion. Also assess mitral valve morphology and motion. Apical four-chamber views are helpful for evaluating chamber size. In cases of acute right heart failure due to ischemia, the RV will be dilated and the left ventricle (LV) will appear to be smaller than expected due to low filling pressures. In left heart failure there will be dilation of the LV secondary to decreased cardiac output and increased filling pressure.

Bedside echocardiography is not a substitute for emergent formal transthoracic echocardiography. Formal echocardiography is better able to use color and spectral Doppler to identify mechanical complications and to characterize the nature of cardiac impairment. Echocardiography can detect regional wall motion abnormalities and identify a lack of compensatory hyperkinesis in uninvolved cardiac segments. Loss of RV contractility, RV dilatation, and normal estimated pulmonary pressures occur more commonly with RV infarction.

Color flow Doppler transthoracic echocardiography can identify mechanical causes of cardiogenic shock, such as acute mitral regurgitation or ventricular septal defect. Echocardiography can detect other causes of decreased cardiac output, notably pulmonary embolism. Acute RV dilatation, tricuspid insufficiency, paradoxical systolic septal motion, and high estimated pulmonary artery and RV pressures suggest pulmonary hypertension from an acute pulmonary embolus.

Mechanical Catastrophe Diagnosis

If mechanical catastrophe is suspected, consult cardiothoracic surgery immediately while obtaining a bedside echocardiogram. In the case of myocardial free wall rupture, death is probable unless a pseudoaneurysm forms. Pseudoaneurysm is detected as an acute pericardial effusion on echocardiography. An acute ventricular septal defect is confirmed by color Doppler echocardiography or right heart catheterization demonstrating oxygen saturation step-up from the right atrium to the RV. Acute mitral regurgitation, from papillary muscle rupture or dysfunction, can complicate AMI.

Hemodynamic Monitoring

Patients in cardiogenic shock typically have low cardiac index (<2.2 L/min/m²) and elevated LV end-diastolic pressure (pulmonary artery occlusion pressure >18 mm Hg).²⁹ Invasive hemodynamic monitoring with a pulmonary artery catheter can provide data and guide treatment but is unavailable in most EDs.²⁹ Central venous pressure measurements can help guide fluid resuscitation, with the trend in venous pressures being more important than absolute values. Most patients will require continuous blood pressure monitoring, often with an indwelling catheter.

The most important intervention for ischemic-related cardiogenic shock is emergent revascularization.^10,11,14,30 ED stabilization is a temporizing measure while arranging for definitive therapy such as revascularization in the cardiac catheterization laboratory or surgical intervention for mechanical catastrophe. In the prehospital setting, EMS should direct any suspected cardiogenic shock patient to a facility that has 24-hour emergency cardiac revascularization capability (i.e., cardiac bypass team).³¹

Initial management focuses on airway stability and improving myocardial pump function to maintain end-organ perfusion. Diagnosis, therapy, and arrangements for definitive cardiac care must proceed simultaneously.

AIRWAY

Give supplemental oxygen, and monitor closely for impending or acute respiratory failure that will require immediate mechanical ventilation. Continuous positive airway pressure or bilevel positive airway pressure can provide temporary airway support, but these methods require a hemodynamically stable, cooperative patient—a set of conditions rare in those with cardiogenic shock.

Endotracheal intubation is often necessary to maintain oxygenation and ventilation. However, the change to positive pressure ventilation may further decrease preload and cardiac output and worsen hypotension. Be prepared to administer a fluid bolus in the absence of pulmonary congestion, initiate an appropriate inotrope if congested with a compensated blood pressure, or start a vasopressor if hypotension exists.

STABILIZATION

Cardiac monitoring and IV access are necessary. Correct any hypoxemia, hypovolemia, rhythm disturbances, electrolyte abnormalities, and acid-base alterations rapidly. Place a urinary drainage catheter to monitor urine output in response to therapy.

In AMI, give aspirin early (if not already taking long term) unless there is an absolute contraindication.³² If blood pressure is >90 mm Hg systolic, chest pain may be relieved by careful use of IV nitroglycerin or morphine. Do not use a-blockers in patients with myocardial infarction in cardiogenic shock or who are at risk for cardiogenic shock (Table 50-1).³² Withhold angiotensin-converting enzyme inhibitors or other vasodilators.

HYPOTENSION

Initial therapy is guided by clinical findings. Give crystalloid fluid boluses (250 to 500 cc) for an RV infarct with hypotension, if pulmonary congestion is absent. If there is no improvement with the fluid bolus or if pulmonary congestion develops, vasopressors or inotropes are indicated (Table 50-4).

Inotropes do not change outcome alone but can temporize while ED personnel arrange interventions to restore coronary artery perfusion and LV function.³³ In the absence of profound hypotension, dobutamine is a mainstay of initial pharmacologic treatment. Dobutamine may increase cardiac contractility and should be considered as an individual agent if systolic blood pressure is ≥90 mm Hg without signs of overt shock or organ dysfunction. Avoid the use of dobutamine alone when the systolic blood pressure is <90 mm Hg because of its vasodilatory potential. Often, a vasoconstrictor is needed in addition to dobutamine. Dopamine may increase cardiac work by increasing heart rate and may also increase LV end-diastolic pressure by its β-agonist effect. Combination therapy with a vasopressor (dopamine) and an inotrope (dobutamine) may be more effective than either agent alone. Norepinephrine when combined with dobutamine may have more of an effect on peripheral vasoconstriction than dopamine when combined with dobutamine. If the systolic blood pressure is <70 mm Hg, norepinephrine is preferred over dobutamine due to its antithrombotic effect.³⁴ If shock persists despite use of these agents, an intra-aortic balloon pump is typically placed, although long-term evidence of benefit is lacking.^{25,35,36,37,38,39}

Epinephrine is an alternative to norepinephrine/dobutamine when dobutamine is not available; however, it is associated with increased systemic acidosis, tachycardia, and dysrhythmias compared to the combination of norepinephrine and dobutamine.⁴⁰

Patients on β-blocker therapy may have an attenuated response to dobutamine, making norepinephrine a better choice. Milrinone (a selective phosphodiesterase inhibitor) can be substituted for the catecholamine if dobutamine is ineffective.

Pure vasoconstrictors and α₁-adrenergic receptor agonists, such as phenylephrine, are contraindicated because they increase cardiac afterload without augmenting cardiac contractility.

EARLY REVASCULARIZATION

In ischemic cardiogenic shock, early revascularization by percutaneous coronary intervention or coronary artery bypass grafting is the treatment of choice. The greatest short-term benefit is reported in patients <75 years old, those without previous myocardial infarction, and those treated within 6 hours of symptom onset. However, patients >75 years old who receive revascularization have improved survival over those >75 years old who have delayed or no revascularization, even though those >75 years old are less likely to receive revascularization.⁴¹ Coronary artery bypass grafting requires extensive surgical and medical resources and poses operative risk for seriously ill patients. The cardiac surgeon will make an overall judgment, with operative intervention chosen often for those with good prior functional status and less severe, early presentation of shock. Survival is higher in those receiving early revascularization compared with medical stabilization, even when elderly.⁴¹ Current guidelines do not have an age cutoff for percutaneous coronary intervention.^27,38,39,42

THROMBOLYTIC THERAPY

Emergency coronary intervention in the catheterization laboratory or operating suite is the preferred definitive treatment for cardiogenic shock.^43,44 Thrombolytic therapy is not as effective in establishing reperfusion in AMI with cardiogenic shock as it is in uncomplicated AMI. Survival from cardiogenic shock is highest with emergency coronary intervention, followed by intra-aortic balloon pump combined with thrombolytic therapy; thrombolytic therapy alone is least effective in reducing mortality. Rescue percutaneous coronary intervention does not convey the same mortality benefit as primary percutaneous coronary intervention for these patients.⁴⁵ If no other definitive treatment modalities for cardiogenic shock are available, if the hospital does not have a catheterization laboratory, or if there is prolonged transport time for coronary intervention, thrombolytic therapy should be given to reduce mortality compared to supportive treatment alone.

INTRA-AORTIC BALLOON PUMP COUNTERPULSATION

Intra-aortic balloon pump counterpulsation provides hemodynamic support by decreasing afterload (which lowers myocardial oxygen consumption) and increasing diastolic blood pressure (which augments coronary perfusion).^38,42 Intra-aortic balloon pump improves survival after thrombolytic therapy by augmenting diastolic perfusion pressure and unloading the LV.^11,46,47 Outside of those receiving reperfusion, the long-term benefits of intra-aortic balloon pump use are not clear.^36,37

Resolution of hemodynamic instability with intra-aortic balloon pump support has positive prognostic value.⁴⁸ In hospitals without direct angioplasty capability, stabilization with intra-aortic balloon pump and thrombolysis followed by transfer to a tertiary care facility may be the best management option.^38,42

PERCUTANEOUS LEFT VENTRICULAR ASSIST DEVICES

If cardiogenic shock persists despite revascularization and maximal medical therapy, a left ventricular assist device may augment cardiac output. This device is currently approved by the U.S. Food and Drug Administration only as a bridge to transplantation, and most cardiogenic shock patients are not such candidates. Case studies have described successful support and weaning of patients suffering from cardiogenic shock in the setting of acute infarction.^{49,50,51,52,53} A recent meta-analysis failed to demonstrate a mortality benefit for left ventricular assist devices compared with intra-aortic balloon pumps in patients with cardiogenic shock refractory to inotropic and vasopressor support.⁵⁴

EXTRACORPOREAL MEMBRANE OXYGENATION

Extracorporeal membrane oxygenation can provide almost total circulatory support for a failing heart. Extracorporeal membrane oxygenation is typically instituted in emergency situations when maximum medical therapy has failed. The treating physician must consider the likelihood of recovery before instituting extracorporeal membrane oxygenation; patients with a very poor prognosis are not appropriate for extracorporeal membrane oxygenation. In the best cases, extracorporeal membrane oxygenation can provide support until percutaneous coronary intervention can be performed or until the heart begins to recover after intervention. In other cases, it can provide a "bridge to decision" for transplant or permanent left ventricular assist device placement.

All patients with cardiogenic shock require admission to the intensive care unit at an institution with invasive revascularization capability.^10,30 In noncapable institutions, transfer should be accomplished as quickly as possible.^55,56 If no other definitive treatment modalities for cardiogenic shock are available, if the hospital does not have a catheterization laboratory, or if there is prolonged transport time for coronary intervention, thrombolytic therapy should be given.

Compliance with guidelines for AMI has improved over the last two decades, although compliance in patients with cardiogenic shock may be less.^3,57,58 Some populations continue to face barriers to effective care, especially the elderly and minorities.^58,59 Compliance with recommended guidelines is needed in order to improve outcomes. The most recent American College of Cardiology/American Heart Association guidelines from 2011 recommend aggressive management of patients in cardiogenic shock. Class 1 recommendations include percutaneous coronary intervention or coronary artery bypass graft for STEMI patients in shock (level of evidence B), percutaneous coronary intervention or coronary artery bypass graft for NSTEMI patients in shock (level of evidence B), and transfer for rescue or facilitated percutaneous coronary intervention in patients with persistent ischemia or shock despite lytic therapy (level of evidence B). European guidelines reflect the same treatment priorities.⁶⁰

Acknowledgment: We thank Jim Edward Weber and W. Frank Peacock for their contributions to the prior edition of this chapter.