Cardiogenic Shock

Background: Cardiogenic shock is a major, and frequently fatal, complication of a variety of acute and chronic disorders that impair the ability of the heart to maintain adequate tissue perfusion. Cardiac failure with cardiogenic shock continues to be a frustrating clinical problem; the management of this condition requires a rapid and well-organized approach.

Cardiogenic shock is a physiologic state in which inadequate tissue perfusion results from cardiac dysfunction, most commonly following acute myocardial infarction (MI). The clinical definition of cardiogenic shock is a decreased cardiac output and evidence of tissue hypoxia in the presence of adequate intravascular volume. Hemodynamic criteria for cardiogenic shock are sustained hypotension (systolic blood pressure <90 mm Hg for at least 30 minutes) and a reduced cardiac index (<2.2 L/min/m²) in the presence of an elevated pulmonary capillary occlusion pressure (>15 mm Hg).

The diagnosis of cardiogenic shock sometimes can be made at the bedside by observing hypotension and clinical signs of poor tissue perfusion, including oliguria, cyanosis, cool extremities, and altered mentation. These signs usually persist after attempts at correcting hypovolemia, arrhythmia, hypoxia, and acidosis have been made.

Historical Aspects

Myocardial infarction is the most common cause of cardiogenic shock in modern times. Morgagni first recognized myocardial infarction in 1761, subsequently described by Caleb Parry in 1788 and by Heberden in 1802. John Hunter, a surgeon at St. George𠏋 Hospital, London, described his personal experience with myocardial infarction in 1773. Adam Hammer, a physician in Mannheim, identified the role of coronary thrombosis in causation of myocardial infarction in 1878. The clinical features of acute myocardial infarction and survival of patients after such an event were reported in 1912 in the Journal of the American Medical Association by James Herrick, a Chicago physician. In the late 20th century, clinicians recognized cardiogenic shock as a low cardiac output state, secondary to extensive left ventricular infarction, development of a mechanical defect (eg, ventricular septal or papillary muscle rupture), and right ventricular infarction.

Pathophysiology: Disorders that can result in the acute deterioration of cardiac function leading to cardiogenic shock include MI or ischemia, acute myocarditis, sustained arrhythmia, acute valvular catastrophe, and decompensation of end-stage cardiomyopathy from multiple etiologies. Autopsy studies show that cardiogenic shock generally is associated with the loss of more than 40% of the left ventricular myocardial muscle. The pathophysiology of cardiogenic shock, which is well understood in the setting of coronary artery disease, is described below.

Myocardial pathology

Cardiogenic shock is characterized by both systolic and diastolic dysfunction. In patients who develop cardiogenic shock from acute MI, progressive myocardial necrosis with infarct extension is consistently observed and is accompanied by decreased coronary perfusion pressure and increased myocardial oxygen demand. These patients often have multi-vessel coronary artery disease with limited coronary flow reserve. Ischemia remote from the infarcted zone is an important contributor to shock. Myocardial diastolic function also is impaired as ischemia causes decreased myocardial compliance, thereby increasing left ventricular filling pressure, which may lead to pulmonary edema and hypoxemia.

Cellular pathology

Tissue hypoperfusion, with consequent cellular hypoxia, causes anaerobic glycolysis, the accumulation of lactic acid, and intracellular acidosis. Failure of myocyte membrane transport pumps also occurs, which decreases transmembrane potential and causes intracellular accumulation of sodium and calcium, resulting in myocyte swelling. If ischemia is severe and prolonged, myocardial cellular injury becomes irreversible and leads to myonecrosis, which includes mitochondrial swelling, the accumulation of denatured proteins and chromatin, and lysosomal breakdown, resulting in fracture of the mitochondria, nuclear envelopes, and plasma membranes. Additionally, apoptosis (programmed cell death) may be found in peri-infarcted areas and may contribute to myocyte loss. Activation of inflammatory cascades, oxidative stress, and stretching of the myocytes produces mediators that overpower inhibitors of apoptosis, thus activating the apoptosis.

Reversible myocardial dysfunction

Myocardial stunning represents post-ischemic dysfunction that persists despite restoration of normal blood flow. By definition, myocardial dysfunction from stunning eventually resolves completely. The mechanism of myocardial stunning involves a combination of oxidative stress, abnormalities of calcium homeostasis and circulating myocardial depressant substances.

It is extremely important to understand that large areas of dysfunctional but viable myocardium can contribute to the development of cardiogenic shock in patients with myocardial infarction. This potentially reversible dysfunction often is described as myocardial stunning or hibernating myocardium. Myocardial stunning represents postischemic dysfunction that persists despite restoration of normal blood flow. By definition, myocardial dysfunction from stunning eventually resolves completely. The mechanism of myocardial stunning involves a combination of oxidative stress, abnormalities of calcium homeostasis, and circulating myocardial-depressant substances.

Hibernating myocardium is a state of persistently impaired myocardial function at rest, which occurs because of the severely reduced coronary blood flow. Hibernation appears to be an adaptive response to hypoperfusion that may minimize the potential for further ischemia or necrosis. Revascularization of hibernating or stunned myocardium generally leads to improved myocardial function. Consideration for the presence of myocardial stunning and hibernation is vital in patients with cardiogenic shock because of the therapeutic implications of these conditions. Hibernating myocardium improves with revascularization, whereas the stunned myocardium retains inotropic reserve and can respond to inotropic stimulation. Although hibernation is considered a different physiologic process than that of myocardial stunning, the conditions are difficult to distinguish in the clinical setting and often coexist.

Cardiovascular mechanics of cardiogenic shock

The main mechanical defect in cardiogenic shock is that the left ventricular end-systolic pressure-volume curve is shifted to the right because of a marked reduction in contractility. As a result, at a similar or even lower systolic pressure, the ventricle is able to eject less blood volume per beat. Therefore, the end-systolic volume usually is greatly increased in cardiogenic shock, and the stroke volume is decreased. To compensate for the decrease in stroke volume, the curvilinear diastolic pressure-volume curve shifts to the right, with a decrease in diastolic compliance. This leads to increased diastolic filling that is associated with an increase in end-diastolic pressure. The increase in cardiac output by this mechanism comes at the cost of having a higher left ventricular diastolic filling pressure, which ultimately increases myocardial oxygen demand and causes pulmonary edema.

As a result of decreased contractility, the patient develops elevated left and right ventricular (RV) filling pressures and a low cardiac output. Mixed venous oxygen saturation falls because of the increased tissue oxygen extraction, which is due to the low cardiac output. This, combined with intrapulmonary shunting that often is present, contributes to substantial arterial desaturation.

Systemic effects

When a critical mass of left ventricular myocardium becomes ischemic and fails to pump effectively, stroke volume and cardiac output decrease. Ischemia is further exacerbated by compromised myocardial perfusion due to hypotension and tachycardia. The pump failure increases ventricular diastolic pressures concomitantly, causing additional wall stress, hence elevating myocardial oxygen requirements. Systemic perfusion is compromised by decreased cardiac output, with tissue hypoperfusion causing increased anaerobic metabolism, leading to the formation of lactic acid, which further deteriorates the systolic performance of the myocardium.

Depressed myocardial function also leads to the activation of several physiologic compensatory mechanisms. These include sympathetic stimulation, which increases heart rate and contractility and renal fluid retention, which increases the left ventricular preload. The raised heart rate and contractility increases myocardial oxygen demand, further worsening myocardial ischemia. Fluid retention and impaired left ventricular diastolic filling caused by tachycardia and ischemia contribute to pulmonary venous congestion and hypoxemia. Sympathetic-mediated vasoconstriction to maintain systemic blood pressure increases myocardial afterload, which impairs cardiac performance. Increased myocardial oxygen demand with simultaneous inadequate myocardial perfusion worsens myocardial ischemia, initiating a vicious cycle that ultimately ends in death if uninterrupted.

Usually, both systolic and diastolic myocardial dysfunction are present in patients with cardiogenic shock. Metabolic derangements that impair myocardial contractility further compromise systolic ventricular function. Myocardial ischemia decreases myocardial compliance, thereby elevating left ventricular filling pressure at a given end-diastolic volume (diastolic dysfunction). This further leads to pulmonary congestion and congestive heart failure.

Shock state

Shock state, irrespective of the etiology, is described as a syndrome initiated by acute systemic hypoperfusion that leads to tissue hypoxia and vital organ dysfunction. A maldistribution of blood flow to end organs leads to cellular hypoxia and end-organ damage, the well-described multisystem organ dysfunction syndrome. All forms of shock are characterized by inadequate perfusion to meet the metabolic demands of the tissues. Three organs are of vital importance, the brain, heart, and kidneys.

Decline in higher cortical function may indicate diminished perfusion of the brain, which leads to an altered mental status ranging from confusion and agitation to flaccid coma. The heart plays a central role in perpetuating shock. Depressed coronary perfusion leads to worsening cardiac dysfunction and a cycle of self-perpetuating progression of global hyperperfusion. Renal compensation for reduced perfusion results in diminished glomerular filtration, causing oliguria and subsequent renal failure.

Frequency:
　

In the US: The incidence of cardiogenic shock ranges from 5-10% in patients with acute myocardial infarction. In the Worcester Heart Attack Study, a community-wide analysis, an incidence of 7.5% was reported.
The literature contains few data on cardiogenic shock in nonischemic patients.

Internationally: Several multicenter thrombolytic trials in Europe reported a prevalence of cardiogenic shock following MI of approximately 7%.

Mortality/Morbidity: The historic mortality rate from cardiogenic shock is 80-90%; recent studies have reported somewhat less in-hospital mortality, in the range of 56-67%. With the advent of thrombolytics, improved interventional coronary procedures, and better medical therapies for heart failure, the overall incidence of cardiogenic shock is likely to decline from historic highs.

Sex: The overall incidence of cardiogenic shock is higher in men because of the increased incidence of coronary artery disease in males. However, the percentage of female patients with MI who develop cardiogenic shock is higher than that of their male counterparts.

CLINICAL

History: Cardiogenic shock is a medical emergency. Performance of a complete clinical assessment is critical to understanding the cause of the shock and for targeting therapy towards correcting the cause.

Cardiogenic shock following acute myocardial infarction generally develops after admission to the hospital, although a small number of patients are in shock at presentation. Patients demonstrate clinical evidence of low cardiac output, which is manifested by sinus tachycardia, low urine output, and cool extremities. Systemic hypotension, defined as systolic blood pressure below 90 mm Hg or a decrease in mean blood pressure by 30 mm Hg, ultimately develops and further propagates tissue hypoperfusion.

Most patients who develop acute myocardial infarction present with abrupt onset of squeezing or heavy substernal chest pain; the pain may radiate to left arm or to the neck. The chest pain may be atypical, the location being epigastric or the neck or the arm only. The pain quality may be burning, sharp, or stabbing. The pain may be absent in persons with diabetes or elderly individuals.

Associated autonomic symptoms including nausea, vomiting, and sweating also may occur.

A history of previous cardiac disease, use of cocaine, previous myocardial infarction or previous cardiac surgery should be obtained. A patient thought to have myocardial ischemia should have assessment of cardiac risk factors. The evaluation should include history of hyperlipidemia, left ventricular hypertrophy, family history of premature coronary artery disease, history of hypertension, and cigarette smoking. Presence of two or more risk factors increases the likelihood of acute myocardial infarction.

Other associated symptoms are diaphoresis, exertional dyspnea, or dyspnea at rest. The feeling of presyncope or syncope, palpitations, generalized anxiety, or depression are other features indicative of poor cardiac function.

Physical: Cardiogenic shock is diagnosed after documentation of myocardial dysfunction and exclusion of alternative causes of hypotension, such as hypovolemia, hemorrhage, sepsis, pulmonary embolism, pericardial tamponade, aortic dissection, and preexisting valvular disease. Shock is present if evidence of multisystem organ hypoperfusion is detected on physical examination.

Patients in shock usually appear ashen or cyanotic and have cool skin and mottled extremities.

Peripheral pulses are rapid and faint and may be irregular if arrhythmias are present.

Jugular venous distention and crackles in the lungs are usually (but not always) present. Peripheral edema may be present, as well.

Heart sounds usually are distant, and both third and fourth heart sounds (S₃ and S₄) may be present.

The pulse pressure may be low, and patients usually are tachycardic.

Patients show signs of hypoperfusion, such as altered mental status and decreased urine output.

A systolic murmur may be heard in patients with acute mitral regurgitation or ventricular septal rupture. The associated parasternal thrill indicates ventricular septal defect, whereas murmur of mitral regurgitation may be limited to early systole. The systolic murmur, which becomes louder on Valsalva and prompt standing, suggests hypertrophic obstructive cardiomyopathy (idiopathic hypertropic subaortic stenosis).

Causes: Acute or acute on chronic left ventricular failure is a classic scenario in cardiogenic shock.

The causes of cardiogenic shock can be divided into the following sections, based on etiology:

Systolic dysfunction: The primary abnormality in systolic dysfunction is decreased myocardial contractility. Acute MI or ischemia is the most common cause; cardiogenic shock is more likely to be associated with anterior MI. The other causes of systolic dysfunction leading to cardiogenic shock are severe myocarditis, end-stage cardiomyopathy (including valvular causes), myocardial contusion, and prolonged cardiopulmonary bypass.
　
Diastolic dysfunction: Increased left ventricular diastolic chamber stiffness contributes to cardiogenic shock commonly during myocardial ischemia, but also in the late stages of hypovolemic shock and septic shock. Increased diastolic dysfunction is particularly detrimental when systolic contractility is also depressed. The causes of cardiogenic shock primarily due to the diastolic dysfunction are listed at the end of this section.
　
Valvular dysfunction: Valvular dysfunction may lead to cardiogenic shock acutely or may aggravate other etiologies of shock. Acute mitral regurgitation secondary to papillary muscle rupture or dysfunction is caused by ischemic injury. Rarely, acute obstruction of the mitral valve by left atrial thrombus also may result in cardiogenic shock by means of severely decreased cardiac output. Aortic and mitral regurgitation reduce forward flow, raise end-diastolic pressure and aggravate shock associated with other etiologies.
　
Cardiac arrhythmia: Ventricular tachyarrhythmias often are associated with cardiogenic shock. Furthermore, bradyarrhythmias may cause or aggravate shock due to another etiology. Sinus tachycardia and atrial tachyarrhythmias contribute to hypoperfusion and aggravate shock.
　
Coronary artery disease: Cardiogenic shock generally is associated with the loss of more than 40% of the left ventricular myocardium, although predominantly RV infarction or the mechanical complications of MI (eg, acute mitral regurgitation, ventricular septal rupture, free wall rupture) also may lead to cardiogenic shock. In patients with previously compromised left ventricular function, even a small infarction may precipitate shock. Cardiogenic shock is more likely to develop in people who are elderly or diabetic or in those who have had a previous inferior infarction.

Other causes: Mechanical complications such as acute mitral regurgitation, large RV infarction, and rupture of the interventricular septum or left ventricular free wall are other causes of cardiogenic shock.

Causes of cardiogenic shock include the following:

Left ventricular failure
- Systolic dysfunction䤥ecreased contractility
- Ischemia/MI
- Global hypoxemia
- Valvular disease (see below)
- Myocardial depressant drugs (eg, beta-blockers, calcium channel blockers, antiarrhythmics)
- Myocardial contusion
- Respiratory acidosis
- Metabolic derangements (eg, acidosis, hypophosphatemia, hypocalcemia)

Diastolic dysfunction/increased myocardial diastolic stiffness
- Ischemia
- Ventricular hypertrophy
- Restrictive cardiomyopathy
- Consequence of prolonged hypovolemic or septic shock
- Ventricular interdependence
- External compression by pericardial tamponade

Greatly increased afterload
- Aortic stenosis
- Hypertrophic cardiomyopathy
- Dynamic aortic outflow tract obstruction
- Coarctation of the aorta
- Malignant hypertension

Valvular or structural abnormality
- Mitral stenosis
- Endocarditis
- Mitral aortic regurgitation
- Obstruction due to atrial myxoma or thrombus
- Papillary muscle dysfunction or rupture
- Ruptured septum or free wall arrhythmias

Decreased contractility
- RV infarction
- Ischemia
- Hypoxia
- Acidosis

Right ventricular failure

Greatly increased afterload
- Pulmonary embolism
- Pulmonary vascular disease (eg, pulmonary arterial hypertension, veno-occlusive disease)
- Hypoxic pulmonary vasoconstriction
- Peak end-expiratory pressure (PEEP)
- High alveolar pressure
- Acute respiratory distress syndrome
- Pulmonary fibrosis
- Sleep disordered breathing
- Chronic obstructive pulmonary disease
Arrhythmias
- Atrial and ventricular arrhythmias (tachycardia-mediated cardiomyopathy)
- Conduction abnormalities (eg, atrioventricular blocks, sinus bradycardia)

DIFFERENTIALS

Myocardial Infarction
Myocardial Ischemia
Myocardial Rupture
Myocarditis
Pulmonary Edema, Cardiogenic
Pulmonary Embolism
Sepsis, Bacterial
Septic Shock
Shock, Distributive
Shock, Hemorrhagic
Systemic Inflammatory Response Syndrome
　

Other Problems to be Considered:

Approach to the initial clinical evaluation of a patient in shock

Any patient presenting with shock must have an early working diagnosis, an approach to urgent resuscitation, and confirmation of the working diagnosis. Shock is identified in most patients by hypotension and inadequate organ perfusion, which may be caused either by low cardiac output or by low systemic vascular resistance. Circulatory shock can be subdivided into 4 distinct classes on the bases of underlying mechanism and characteristic hemodynamics. These classes of shock should be considered and systemically differentiated before establishing a definite diagnosis of septic shock.

Hypovolemic shock

Hypovolemic shock results from loss of blood volume caused by conditions such as gastrointestinal bleeding, extravasation of plasma, major surgery, trauma, and severe burns.

Obstructive shock

Obstructive shock results from impedance of circulation by an intrinsic or extrinsic obstruction. Pulmonary embolism, dissecting aneurysm, and pericardial tamponade all result in obstructive shock.

Distributive shock

Distributive shock is caused by conditions such as direct arteriovenous shunting and is characterized by decreased resistance or increased venous capacity from the vasomotor dysfunction. These patients have high cardiac output hypotension, large pulse pressure, low diastolic pressure, and warm extremities with good capillary refill. Such findings on physical examination strongly suggest a working diagnosis of septic shock.

Cardiogenic shock

Cardiogenic shock is characterized by primary myocardial dysfunction resulting in the inability of the heart to maintain adequate cardiac output. These patients demonstrate clinical signs of low cardiac output, with evidence of adequate intravascular volume. The patients have cool and clammy extremities, poor capillary refill, tachycardia, narrow pulse pressure, and low urine output.

WORKUP

Lab Studies:
　

Biochemical profile: Measurement of routine biochemistry, such as electrolytes, renal function (urea and creatinine), and liver function tests (eg, bilirubin, aspartate aminotransferase [AST], alanine aminotransferase [ALT], and lactic acid dehydrogenase [LDH]) all are useful in appraisal of proper functioning of vital organs.

Complete blood count: Measurement of CBC generally is helpful to exclude anemia; a high white cell count may indicate an underlying infection, and platelet count may be lowered secondary to coagulopathy of sepsis.

Cardiac enzymes

Diagnosis of acute myocardial infarction is aided by a variety of serum markers, which include creatine kinase (CK) and its subclasses, troponin, myoglobin, and lactate dehydrogenase. The CK-MB is most specific but may be falsely elevated in myopathy, hypothyroidism, renal failure, and skeletal muscle injury.

Cardiac troponins T and I are widely used for diagnosis of myocardial injury. The rapid release and metabolism of myoglobin occurs in myocardial infarction. A 4-fold rise of myoglobin over 2 hours appears to be a sensitive test for myocardial infarction. Serum lactate dehydrogenase (LDH) increases approximately 10 hours after onset of myocardial infarction, peaks at 24-48 hours, and gradually returns to normal in 6-8 days. LD-1 isoenzyme is primarily released by the heart but also may come from kidney, stomach, pancreas, and red blood cells.

Arterial blood gases: Arterial blood gases indicate overall acid-base homeostasis and level of arterial blood oxygenation. Base deficit elevation (normal is +3 to ? mmol/L) correlates with the occurrence and severity of shock. Base deficit also is an important marker to follow during resuscitation of a patient from shock.

Lactate: Serial lactate measurements are useful markers of hypoperfusion and also are used as indicators of prognosis. Elevated lactate in a patient with signs of hypoperfusion indicates a poor prognosis; rising lactate during resuscitation portends a very high mortality rate.

Imaging Studies:
　

Echocardiography should be performed early to establish the cause of cardiogenic shock.

Echocardiography provides information on global and regional systolic function, as well as diastolic dysfunction.

Echocardiography also can lead to a rapid diagnosis of mechanical causes of shock, such as papillary muscle rupture causing acute myocardial regurgitation, acute ventricular septal defect, free myocardial wall rupture, and pericardial tamponade.

Chest x-ray: Chest x-ray is useful in excluding other causes of shock or chest pain. A widened mediastinum may indicate aortic dissection; tension pneumothorax or pneumomediastinum may present as low-output shock. Most patients with established cardiogenic shock exhibit findings of left ventricular failure. These radiological features include pulmonary vascular redistribution, interstitial pulmonary edema, enlarged hilar shadows, presence of Kerley-B lines, cardiomegaly, bilateral pleural effusions, and, finally, the alveolar edema manifests as bilateral perihilar opacities in a so-called butterfly distribution.

Other Tests:
　

Electrocardiogram: Acute myocardial ischemia is diagnosed by the presence of ST segment elevation, ST segment depression, or the presence of Q waves. T wave inversion, although less sensitive, is seen in myocardial ischemia. Therefore, perform electrocardiography immediately to diagnose MI and/or ischemia.

Procedures:
　

Invasive hemodynamic monitoring

Invasive hemodynamic monitoring (right heart catheterization) is very useful for excluding other causes of shock, eg, volume depletion, or obstructive and septic shock.

The hemodynamic measurements of cardiogenic shock are a pulmonary capillary wedge pressure (PCWP) greater than 15 mm Hg and a cardiac index of less than 2.2 L/min/m².

The presence of large V waves on the pulmonary capillary wedge pressure tracing suggests severe mitral regurgitation.

A step-up in oxygen saturation between the right atrium and the RV is diagnostic of ventricular septal rupture.

High right-sided filling pressures in the absence of an elevated pulmonary capillary wedge pressure, when accompanied with electrocardiographic criteria, indicates RV infarction.

Coronary artery angiography

Coronary angiography is urgently indicated in patients with myocardial ischemia or MI who also develop cardiogenic shock. Angiography is required to assess the anatomy of the coronary arteries and the need for urgent revascularization.

Coronary angiography often demonstrates multivessel coronary artery disease in cardiogenic shock. In these patients, a compensatory hyperkinesis cannot occur in the noninfarct territory because of the severe coronary artery atherosclerosis. The most common cause of cardiogenic shock is extensive MI, although a smaller infarction in a previously compromised left ventricle also may precipitate shock. Following MI, large areas of nonfunctional but viable myocardium (hibernating myocardium) also can cause or contribute to cardiogenic shock.

TREATMENT

Medical Care: Initial management includes fluid resuscitation to correct hypovolemia and hypotension, unless pulmonary edema is present. Central venous and arterial lines often are required; right heart catheterization and oximetry are routine. Oxygenation and airway protection are critical; intubation and mechanical ventilation commonly are required. Correction of electrolyte and acid-base abnormalities, such as hypokalemia, hypomagnesemia, and acidosis, are essential.

In patients with inadequate tissue perfusion and adequate intravascular volume, initiation of an inotropic and/or vasopressor drug may be necessary. Dopamine increases myocardial contractility and supports the blood pressure; however, it may increase myocardial oxygen demand. Dobutamine may be preferable if the systolic blood pressure is higher than 80 mm Hg and has the advantage of not affecting myocardial oxygen demand. However, the resulting tachycardia may preclude the use of this inotrope in some patients.

Thrombolytic therapy

Although thrombolytic therapy reduces mortality rates in patients with acute MI, its benefits for patients with cardiogenic shock secondary to MI are less certain. When used early in the course of MI, thrombolytic therapy reduces the likelihood of subsequent development of cardiogenic shock after the initial event.

In the Gruppo Italiano Per lo Studio Della Streptokinase Nell𥕜nfarto Miocardio (GISSI) trial, 30-day mortality rates were 69.9% in patients with cardiogenic shock who received streptokinase, compared to 70.1% in patients who received a placebo. Similarly, other studies with a tissue plasminogen activator did not show any benefit in mortality rates from cardiogenic shock. Lower rates of reperfusion of the infarct-related artery in patients with cardiogenic shock might explain the disappointing results from thrombolytic therapy. The other reasons for decreased efficacy of thrombolytic therapy in cardiogenic shock are a result of hemodynamic, mechanical, and metabolic factors that are unaffected by such therapy.

Intra-aortic balloon pump

The use of the intra-aortic balloon pump (IABP) reduces systolic left ventricular afterload and augments the diastolic coronary perfusion pressure, thereby increasing cardiac output and improving coronary artery blood flow. Intra-aortic balloon pumping is effective for the initial stabilization of patients with cardiogenic shock. However, intra-aortic balloon pumping is not a definitive therapy; the IABP stabilizes the patients so that definitive diagnostic and therapeutic maneuvers can be performed.
　
Intra-aortic balloon pumping also may be a useful adjunct to thrombolysis for initial stabilization and transfer of patients to a tertiary care facility. Some studies have shown lower mortality in patients with MI treated with intra-aortic balloon pumping and subsequent revascularization.
　
Complications may be documented in up to 30% of patients who undergo intra-aortic balloon pumping and mainly relate to local vascular problems, emboli, infection, and hemolysis. The impact of intra-aortic balloon pumping on long-term survival is controversial and depends on the hemodynamic status and etiology of cardiogenic shock. Patient selection is the key issue; the early insertion of the IABP may result in clinical benefit rather than waiting until full-blown cardiogenic shock has developed.

Ventricular assist devices
　
- These devices function as prosthetic ventricles but most require a sternotomy for insertion. Assist devices may be used to support left ventricular performance, RV performance, or a combination, depending on the underlying condition. The Pierce-Donachy left ventricular assist device has been used as a bridge to cardiac transplantation. Insertion of this device allowed survival to transplant in 75% of 29 patients.
  The Nimbus Hemopump circumvents the problem associated with median sternotomy and allows a percutaneous placement of cannula across the aortic valve, which is coupled to an extracorporeal power source. The major complications of this device are ventricular arrhythmias and embolic phenomenon.
  
  　
- The indications for insertion of a ventricular assist device are controversial. Thus, aggressive approach to support the circulatory system may be used after failure of medical treatment and intra-aortic balloon pumping; and in the presence of the potentially reversible cause of cardiogenic shock.

Surgical Care: The retrospective and prospective data favor aggressive mechanical revascularization in patients with cardiogenic shock secondary to MI.

Percutaneous transluminal coronary angioplasty

Reestablishing blood flow in the infarct-related artery may improve left ventricular function and survival following MI. In acute MI, studies show that percutaneous transluminal coronary angioplasty (PTCA) can achieve adequate flow in 80-90% of patients, compared with 50-60% of patients after thrombolytic therapy.

Several retrospective clinical trials have shown that patients with cardiogenic shock due to myocardial ischemia benefitted from a reduction in 30-day mortality rates when treated with angioplasty. A recent study of direct (primary) PTCA in patients with cardiogenic shock reports lower mortality rates in patients treated with angioplasty combined with the use of stents, compared to medical therapy.

Coronary artery bypass grafting

Critical left main artery disease and 3-vessel coronary artery disease are common findings in patients who develop cardiogenic shock. The potential contribution of ischemia in the noninfarcted zone contributes to deterioration of already compromised myocardial function.

Coronary artery bypass grafting (CABG) in the setting of cardiogenic shock generally is associated with high surgical morbidity and mortality. Because the results of percutaneous interventions can be favorable, routine bypass surgery for these patients often is discouraged.

Shock trial

A recent study known as the Shock Trial addressed the question of revascularization in patients with cardiogenic shock. Patients were assigned to receive either optimal medical management, including an IABP and thrombolytic therapy, or cardiac catheterization followed by revascularization using PTCA or CABG.

The mortality rates at 30 days were 46.7% in the early intervention group, compared with 56% in patients treated with optimal medical management. Although this did not reach a statistical significance at 1 month, the mortality at 6 months was significantly lower in the early intervention group. This study supports the superiority of a strategy that combines early revascularization with medical management in patients with cardiogenic shock.

Consultations: Consultation with a cardiologist and/or an intensivist should be done early in the patient's clinical course. The patient usually is admitted to a coronary care unit or intensive care unit.

MEDICATION

Vasopressors augment the coronary and cerebral blood flow during the low-flow state associated with shock. Sympathomimetic amines with both alpha- and beta-adrenergic effects are indicated in cardiogenic shock. Dopamine and dobutamine are the drugs of choice to improve cardiac contractility, with dopamine the preferred agent in hypotensive patients.

Vasodilators relax vascular smooth muscle and reduce the systemic vascular resistance (SVR), allowing for improved forward flow, which improves cardiac output. Adequate pain control is essential for quality patient care and patient comfort. Diuretics are used to decrease plasma volume and peripheral edema. The reduction in plasma volume and stroke volume associated with diuresis may decrease cardiac output and, consequently, blood pressure, with a compensatory increase in peripheral vascular resistance. With continuing diuretic therapy, the volumes of the extracellular fluid and of the plasma return to near pretreatment levels, and the peripheral vascular resistance usually falls below its pretreatment baseline.
　

Drug Category: Vasopressors/inotropes -- These drugs augment both the coronary and the cerebral blood flow during the low-flow state associated with cardiogenic shock.

Drug Name	Dopamine (Intropin) -- Stimulates both adrenergic and dopaminergic receptors. Hemodynamic effect depends on the dose. Lower doses stimulate mainly dopaminergic receptors that produce renal and mesenteric vasodilation. Cardiac stimulation and vasoconstriction is produced by higher doses.
Adult Dose	5-20 mcg/kg/min IV continuous infusion; dose may be increased by 1-4 mcg/kg/min q10-30min until the optimal response is achieved; >50% of patients are maintained satisfactorily on doses <20 mcg/kg/min
Pediatric Dose	Administer as in adults.
Contraindications	Documented hypersensitivity; pheochromocytoma; ventricular fibrillation
Interactions	Phenytoin, alpha- and beta-adrenergic blockers, general anesthesia, and MAOIs increase and prolong effects of dopamine
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Must be administered via central vein Closely monitor urine flow, cardiac output, pulmonary wedge pressure, and blood pressure during infusion; prior to infusion, correct hypovolemia with either whole blood or plasma, as indicated; monitoring central venous pressure or left ventricular filling pressure may be helpful in detecting and treating hypovolemia

Drug Name	Dobutamine (Dobutrex) -- Sympathomimetic amine with stronger beta than alpha effects. Produces systemic vasodilation and increases the inotropic state. Higher dosages may cause an increase in heart rate, exacerbating myocardial ischemia.
Adult Dose	5-20 mcg/kg/min IV continuous infusion, titrate to desired response; not to exceed 40 mcg/kg/min
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity to the agent, hypertrophic cardiomyopathy, atrial fibrillation or flutter, severe tachycardia
Interactions	Beta-adrenergic blockers antagonize the effects of dobutamine; general anesthetics may increase its toxicity.
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Following a myocardial infarction, use dobutamine with extreme caution; correct hypovolemic state before using May exacerbate hypotension Cautious use indicated when ventricular or life-threatening tachyarrhythmias are present

Drug Category: Phosphodiesterase enzyme inhibitors -- Induce peripheral vasodilation and provide inotropic support.

Drug Name	Milrinone (Primacor) -- Positive inotrope and vasodilator with little chronotropic activity. Different in mode of action from either cardiac glycosides (digoxin) or catecholamines.
Adult Dose	50 mcg/kg IV loading dose over 10 min, followed by 0.375-0.75 mcg/kg/min continuous IV infusion
Pediatric Dose	Administer as in adults; although DOC in many pediatric ICUs, safety and efficacy are not well established
Contraindications	Documented hypersensitivity
Interactions	May precipitate if infused in the same IV line as furosemide
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Monitor fluid, electrolyte changes, and renal function during therapy; excessive diuresis may cause an increase in potassium loss and predispose digitalized patients to arrhythmias (correct hypokalemia by potassium supplementation prior to treatment); slow or stop the infusion in patients showing excessive decreases in blood pressure; if vigorous diuretic therapy has caused significant decreases in cardiac filling pressure, cautiously administer the drug and monitor blood pressure, heart rate, and clinical symptomatology

Drug Name	Inamrinone - formerly amrinone (Inocor) -- Phosphodiesterase inhibitor with positive inotropic and vasodilator activity. Produces vasodilation and increases inotropic state. More likely to cause tachycardia than dobutamine and may exacerbate myocardial ischemia.
Adult Dose	Initial dose: 0.75 mg/kg IV bolus slowly over 2-3 min Maintenance infusion: 5-10 mcg/kg/min; not to exceed 10 mg/kg; adjust dose according to patient response
Pediatric Dose	Administer as in adults; safety and efficacy not well established
Contraindications	Documented hypersensitivity
Interactions	Diuretics may cause significant hypovolemia and a decrease in filling pressure; inamrinone has additive effects with cardiac glycosides
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Causes thrombocytopenia in 2-3% of patients; hypotension may occur following a loading dose; requires adequate preload; ventricular dysrhythmias may occur but may be related to the underlying condition; do not use in patients with cardiac outlet obstruction (eg, aortic stenosis, pulmonic stenosis, hypertrophic cardiomyopathy); discontinue therapy if clinical symptoms of liver toxicity occur; correct hypokalemic states before using inamrinone

Drug Category: Vasodilators -- Decrease preload and/or afterload

Drug Name	Nitroglycerin (Nitro-Bid) -- Causes relaxation of vascular smooth muscle by stimulating intracellular cyclic guanosine monophosphate production. The result is a decrease in preload and blood pressure (afterload).
Adult Dose	10-200 mcg/min IV continuous infusion
Pediatric Dose	0.1-1 mcg/kg/min IV infusion
Contraindications	Documented hypersensitivity; severe anemia, shock, postural hypotension, head trauma, closed-angle glaucoma, cerebral hemorrhage
Interactions	Aspirin may increase nitrate serum concentrations; marked symptomatic orthostatic hypotension may occur with coadministration of calcium channel blockers (dose adjustment of either agent may be necessary)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in 3-vessel, left main coronary artery disease, aortic stenosis, or low systolic blood pressure

Drug Category: Analgesics

Drug Name	Morphine sulfate (Duramorph, Astramorph, MS Contin) -- DOC for narcotic analgesia due to its reliable and predictable effects, safety profile, and ease of reversibility with naloxone. Various IV doses are used, commonly titrated until the desired effect is obtained.
Adult Dose	Starting dose: 0.1 mg/kg IV/IM/SC Maintenance dose: 5-20 mg/70 kg IV/IM/SC q4h Relatively hypovolemic patients: start with 2 mg IV/IM/SC, reassess hemodynamic effects of the dose
Pediatric Dose	0.1-0.2 mg/kg/dose IV/IM/SC q2-4h prn; not to exceed 15 mg/dose; may initiate at 0.05 mg/kg/dose
Contraindications	Documented hypersensitivity; hypotension, potentially compromised airway where establishing rapid airway control would be difficult
Interactions	Phenothiazines may antagonize analgesic effects of opiate agonists; tricyclic antidepressants, MAOIs, and other CNS depressants may potentiate the adverse effects of morphine.
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Avoid in hypotension, respiratory depression, nausea, emesis, constipation, and urinary retention; caution in atrial flutter and other supraventricular tachycardias; has vagolytic action and may increase ventricular response rate

Drug Category: Diuretics -- Decrease plasma volume and peripheral edema. Excessive reduction in plasma volume and stroke volume associated with diuresis may decrease cardiac output and, consequently, blood pressure.

Drug Name	Furosemide (Lasix) -- Increases excretion of water by interfering with chloride-binding cotransport system, which in turn inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule. Individualize dose to patient. Depending on response, administer at increments of 20-40 mg no sooner than 6-8 h after the previous dose, until desired diuresis occurs. When treating infants, titrate with 1 mg/kg/dose increments until a satisfactory effect is achieved.
Adult Dose	20-80 mg/d PO/IV/IM; titrate up to 600 mg/d for severe edematous states; may be administered as a continuous infusion as well
Pediatric Dose	1 mg/kg IV/IM slowly under close supervision; not to exceed 6 mg/kg
Contraindications	Documented hypersensitivity, hepatic coma, anuria, and a state of severe electrolyte depletion
Interactions	Metformin decreases furosemide concentrations; furosemide interferes with the hypoglycemic effect of antidiabetic agents and antagonizes the muscle-relaxing effect of tubocurarine; auditory toxicity appears to be increased with the coadministration of aminoglycosides and furosemide; hearing loss of varying degrees may occur; the anticoagulant activity of warfarin may be enhanced when taken concurrently with this medication; increased plasma lithium levels and toxicity are possible when taken concurrently with this medication
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Observe for blood dyscrasias, liver or kidney damage, or idiosyncratic reactions; perform frequent serum electrolyte, carbon dioxide, glucose, uric acid, calcium, creatinine, and BUN determinations during the first few months of therapy and periodically thereafter; loop diuretics may increase urinary excretion of magnesium and calcium

FOLLOW-UP

Further Inpatient Care:
　

Cardiogenic shock is an emergency requiring immediate resuscitative therapy, before shock irreversibly damages vital organs. Simultaneously, elucidating the cause of shock is important so that therapy can be directed to correcting the cause.

Transfer:
　

Immediately transfer a patient who develops cardiogenic shock to an institution where invasive monitoring, coronary revascularization, and skilled personnel are available to provide expert care to the patient.

Prognosis:
　

In the absence of aggressive, highly experienced technical care, mortality among patients with cardiogenic shock is exceedingly high (up to 70-90%). The key to achieving a good outcome is rapid diagnosis, prompt supportive therapy, and expeditious coronary artery revascularization in patients with myocardial ischemia and infarction. The mortality rate in patients treated aggressively can be lowered to 40-60%. The prognosis of patients who survive cardiogenic shock is not well studied but may be reasonable, if the underlying cause of shock is corrected.

MISCELLANEOUS

Medical/Legal Pitfalls:
　

Cardiogenic shock has a very high mortality rate (60-80%), although mortality rates have decreased over the last 2 decades.

Areas of nonfunctioning but viable (hibernating) myocardium can cause or contribute to the development of cardiogenic shock.

The key to a good outcome in cardiogenic shock is an organized approach, with rapid diagnosis and prompt initiation of therapy to maintain blood pressure and cardiac output. Early and definitive restoration of coronary blood flow is the most important intervention for producing improvement in survival, and it represents standard therapy at present for patients with cardiogenic shock due to myocardial ischemia.

The development of cardiogenic shock may be prevented with early revascularization in patients with myocardial infarction when accompanied with appropriate pharmacological management; and with required intervention in patients with structural heart disease.

Special Concerns:
　

Right ventricular infarction

RV infarction occurs in up to 30% of patients with inferior MI and becomes hemodynamically unstable in 10% of those patients. Diagnosis is made by identifying ST segment elevation in the right precordial leads (V₃ or V₄R) and/or typical hemodynamic findings on right heart catheterization (elevated right atrial and RV end-diastolic pressures with normal to low pulmonary artery wedge pressure and low cardiac output). Echocardiography also can be very helpful in the diagnosis of RV infarction. Patients with cardiogenic shock from RV infarction have a better prognosis when compared to those with cardiogenic shock due to left ventricular systolic failure.
　
Management of cardiogenic shock from right ventricular infarction: Supportive therapy for patients with RV infarction begins with the restoration and maintenance of RV preload with fluid administration. However, excessive fluid resuscitation may compromise left ventricular filling by introducing interventricular septal shift. Inotropic therapy with dobutamine may be effective in increasing cardiac output in patients with RV infarction. Maintenance of systemic arterial pressure in order to maintain adequate coronary artery perfusion may require vasoconstricting agents, such as norepinephrine. In unstable patients, IABP may be useful for ensuring adequate blood supply to the already compromised right ventricle. Revascularization of the occluded coronary artery, preferably by PTCA is crucial for management and has shown to dramatically improved outcome.

Acute mitral regurgitation

Acute mitral regurgitation usually is associated with inferior myocardial infarction due to ischemia or infarction of the papillary muscle. The incidence is approximately 1% of MIs, posteromedial papillary muscle is involved more frequently than the anterolateral muscle. Acute mitral regurgitation usually occurs 2-7 days following acute MI and presents with abrupt onset of pulmonary edema, hypotension, and cardiogenic shock.
　
Echocardiography is extremely useful in making a diagnosis. The 2-dimensional echocardiogram will show the malfunctioning mitral valve, and the Doppler study can be used to document the severity of mitral regurgitation. Right heart catheterization often is required for stabilizing the patient. Tall V waves identified on pulmonary arterial and wedge pressure waveforms indicate acute mitral regurgitation. However, the diagnosis must be confirmed by echocardiography or left ventriculography before definite therapy or surgery.
　
Hemodynamic stabilization by reducing afterload either with nitroprusside or IABP often is instituted. Definitive therapy requires revascularization, if ischemia is present, and/or surgical valve repair or replacement, if structural valvular lesion is present. The mortality in the presurgical era was reported at 50% in the first 24 hours, with 2-months survival reported at 6%.

Cardiac rupture

Rupture of the free wall of the left ventricle occurs within 2 weeks of the MI and may occur within the first 24 hours. The rupture may involve the anterior or posterior or lateral wall of the ventricle.
　
Cardiac rupture often presents as sudden cardiac death. Premortem symptoms include chest pain, agitation, tachycardia, and hypotension. This diagnosis should be considered in patients with electromechanical dissociation who have a history of anginal pain. Patients rarely, if ever, survive cardiac rupture.

Ventricular septal rupture

Approximately 1-3% of acute MIs are associated with ventricular septal rupture. Most septal ruptures occur within the week following MI. Patients with acute ventricular septal rupture develop acute heart failure and/or cardiogenic shock, with physical findings of a harsh holosystolic murmur and left parasternal thrill. A left-to-right intracardiac shunt as demonstrated by a step-up (>5% increase in oxygen saturation) between the right atrium and right ventricle confirms the diagnosis. Alternatively, 2-dimensional and Doppler echocardiography can be used to identify the location and severity of the left-to-right shunt.
　
Rapid stabilization using IABP and pharmacologic measures, followed by emergent surgical repair, is life saving. The timing of surgical intervention is controversial, but most experts suggest operative repair within 48 hours of the rupture. Ventricular septal rupture portends a poor prognosis unless an aggressive approach to management is utilized. Immediate surgical repair of patients with ventricular septal rupture is reported to be associated with survival rates of 42-75%; therefore, it is imperative that prompt surgical therapy be undertaken as soon as possible after the diagnosis of ventricular septal rupture is confirmed.

Reversible myocardial dysfunction

Other causes of severe reversible myocardial dysfunction are sepsis-associated myocardial depression, myocardial depression following cardiopulmonary bypass, or inflammatory myocarditis. This presentation is often referred to as cold septic shock in older literature. In these situations, myocardial dysfunction occurs from the effects of inflammatory cytokines, such as tumor necrosis factor (TNF) and interleukin (IL)-1.
　
Myocardial dysfunction may vary from mild to severe and may lead to cardiogenic shock. For patients in cardiogenic shock, cardiovascular support with inotropic agents may be required until recovery, which generally occurs after the underlying disease process resolves.

PICTURES

Caption: Picture 1. This ECG shows an extensive anterolateral myocardial infarction; this patient subsequently developed cardiogenic shock.

Picture Type: ECG

Caption: Picture 2. The above patient's ECG shows further evolutionary changes.

Picture Type: ECG

Caption: Picture 3. In contrast, another patient developed cardiogenic shock secondary to pericarditis and pericardial tamponade.

Picture Type: ECG

Caption: Picture 4. A 63-year-old man admitted to ED with clinical features of cardiogenic shock. The ECG revealed wide-complex tachycardia, likely ventricular tachycardia. Following cardioversion, the shock state improved. The cause of ventricular tachycardia was myocardial ischemia.

Picture Type: ECG

Caption: Picture 5. This patient presented with an acute anterolateral myocardial infarction, then developed cardiogenic shock. Coronary angiography showed a severe stenosis of the left anterior descending coronary artery, which was dilated by percutaneous transluminal coronary angioplasty (PTCA).

Picture Type: Photo

Caption: Picture 6. A coronary angiogram of a patient with cardiogenic shock demonstrates severe stenosis of the left anterior descending coronary artery.

Picture Type: Photo

Caption: Picture 7. Following angioplasty of the critical stenosis, coronary flow is reestablished. The patient recovered from cardiogenic shock.

Picture Type: Photo

Caption: Picture 8. This echocardiogram of a patient with cardiogenic shock shows enlarged cardiac chambers; the motion study showed poor left ventricular function. (Courtesy of R Hoeschen, MD)

Picture Type: Image

BIBLIOGRAPHY

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