Although some general therapeutic considerations are applicable to all patients in cardiogenic shock, treatment is most effective when the cause is identified. In many situations, this identification allows rapid correction of the underlying problem. In fact, survival in most forms of shock requires a quick, accurate diagnosis. The patient is so critically ill that only prompt, directed therapy can reverse the process. The already high mortality rates in cardiogenic shock are even higher in patients for whom treatment is delayed. Therefore, although measures aimed at temporarily stabilizing the patient may provide enough time to start definitive therapy, potentially life-saving treatment can be carried out only when the cause is known (Table 9–2).
Acute Myocardial Infarction
In patients with cardiogenic shock caused by a large amount of infarcted or ischemic myocardium, the most effective treatment for decreasing mortality is prompt revascularization, with either PCI or coronary artery bypass grafting (CABG) surgery. A number of pharmacologic and nonpharmacologic measures may be helpful in stabilizing the patient prior to revascularization.
Because respiratory failure usually accompanies cardiogenic shock, every effort should be made to ensure adequate ventilation and oxygenation. Adequate oxygenation is essential to avoid hypoxia and further deterioration of oxygen delivery to tissues. Patients with cardiogenic shock should receive supplemental oxygen, and many require mechanical ventilation. Hypoventilation can lead to respiratory acidosis, which could exacerbate the metabolic acidosis already caused by tissue hypoperfusion. Acidosis worsens cardiac function and makes the heart less responsive to inotropic agents. A substantial proportion of the cardiac output in patients with cardiogenic shock is devoted to the “work of breathing,” so mechanical ventilation is also advantageous in this regard.
Although hypovolemia is not the primary defect in cardiogenic shock, a number of patients may be relatively hypovolemic when shock develops following MI. The causes of decreased intravascular volume include increased hydrostatic pressure and increased permeability of blood vessels as well as patients simply being volume depleted for many hours. The physical examination may not always be helpful in determining the adequacy of the left ventricular filling pressure. In selected patients, invasive monitoring with a pulmonary artery catheter can be helpful in determining the optimal volume status. Some patients with cardiogenic shock will actually have improved hemodynamics with slightly higher than normal filling pressures. Ventricular compliance is reduced in acute ischemia; the pressure–volume relationship changes such that cardiac output may be optimized at slightly higher filling pressures. In general, a PCWP of 18–22 mm Hg is considered adequate; further increases will lead to pulmonary congestion without a concomitant gain in cardiac output. Fluid administration, when indicated by low or normal PCWP, should be undertaken in 200–300 mL boluses of saline, followed by careful reassessment of hemodynamic parameters, especially cardiac output and PCWP, and generally should not be undertaken in patients with marginal oxygenation or in those not already mechanically ventilated.
A variety of drugs are available for intravenous administration to increase the contractility of the heart, the heart rate, and peripheral vascular tone. It is important to note that these agents also increase myocardial oxygen demand; improvements in hemodynamics and blood pressure therefore come at a cost, which can be deleterious in patients with ongoing ischemia. Furthermore, β-agonists can precipitate tachyarrhythmias, and α-agonists can lead to dangerous vasoconstriction and ischemia in vital organ beds. When using these agents, attention should be given to the patient as a whole rather than focusing solely on a desired arterial pressure.
Although digoxin benefits patients with chronic congestive heart failure, it is of less benefit in cardiogenic shock because of its delayed onset of action and relatively mild potency (compared with other available agents).
Dopamine is an endogenous catecholamine with qualitatively different effects at varying doses. At low doses (> 3 mcg/kg/min), it predominantly stimulates dopaminergic receptors that dilate various arterial beds, the most important being the renal vasculature. Although used frequently in low doses to improve renal perfusion, there is scant evidence to support the clinical usefulness of this strategy. Intermediate doses of 3–6 mcg/kg/min cause β1-receptor stimulation and enhanced myocardial contractility. Further increases in dosage lead to predominant α-receptor stimulation (peripheral vasoconstriction) in addition to continued β1 stimulation and tachycardia. Dopamine increases cardiac output, and its combination of cardiac stimulation and peripheral vasoconstriction may be beneficial as initial treatment of hypotensive patients in cardiogenic shock.
Dobutamine is a synthetic sympathomimetic agent that differs from dopamine in two important ways: It does not cause renal vasodilatation, and it has a much stronger β2 (arteriolar vasodilatory) effect. The vasodilatory effect may be deleterious in hypotensive patients because a further drop in blood pressure may occur. On the other hand, many patients with cardiogenic shock experience excessive vasoconstriction with a resultant elevation in afterload (SVR) as a result of either the natural sympathetic discharge or the treatment with inotropic agents, such as dopamine, that also have prominent vasoconstrictor effects. In such patients, the combination of cardiac stimulation and decreased afterload with dobutamine may improve cardiac output without a loss of arterial pressure.
Other agents that are used include isoproterenol and norepinephrine. Isoproterenol is also a synthetic sympathomimetic agent. It has very strong chronotropic and inotropic effects, resulting in a disproportionate increase in oxygen consumption and ischemia. It is therefore not generally recommended for cardiogenic shock except occasionally for patients with bradyarrhythmias. Norepinephrine has even stronger α and β1 effects than dopamine and may be beneficial when a patient continues to be hypotensive despite large doses of dopamine (> 20 mcg/kg/min). A recent randomized trial suggests that norepinephrine may be superior to dopamine in the treatment of cardiogenic shock.
Vasodilation (especially of the arterioles to reduce SVR) can be effective in increasing cardiac output in patients with heart failure by countering the peripheral vasoconstriction caused by endogenous catecholamines. Although these agents have a role in treating acute, decompensated heart failure, they are rarely used in patients with cardiogenic shock given the risk of worsening hypotension. The IABP (see below) is generally more effective for reducing SVR without the risk of untoward hypotension.
Circulatory Support Devices
Among the mechanical devices developed to assist the left ventricle until more definitive therapy can be undertaken, the IABP has been in use the longest and is the most well studied. The IABP is placed in the descending aorta, usually via the femoral artery. Its inflation and deflation are timed to the cardiac cycle (generally synchronized with the ECG). The balloon inflates in diastole immediately following aortic valve closure. The augmentation of diastolic pressure that occurs when the balloon inflates increases coronary perfusion as well as that of other organs. The balloon deflates at the end of diastole, immediately before left ventricular contraction, abruptly decreasing afterload and thereby enhancing left ventricular ejection. Unlike β-agonists, these benefits come without increases in myocardial demand.
Indications for use of the IABP include cardiogenic shock, especially when caused by ventricular septal rupture and acute mitral regurgitation. In both ventricular septal rupture and mitral regurgitation, the principle benefit is the decrease in afterload that occurs as the balloon deflates; this results in a larger fraction of the left ventricular volume being ejected forward into the aorta rather than into the left atrium (mitral regurgitation) or the right ventricle (ventricular septal rupture). An IABP should be placed as soon as possible in an effort to support these patients until emergency surgery can be performed. The most common side effects of the IABP are local vascular complications, but these have diminished substantially with the smaller caliber devices used currently. Nonrandomized data have shown that patients in cardiogenic shock treated with an IABP fare better than those not treated with an IABP. Recently, a randomized trial (IABP SHOCK II) showed similar outcomes with or without IABP use following revascularization. The IABP is therefore most useful as a temporizing agent, either to keep patients alive until revascularization or until more aggressive support can be initiated in patients who may be transplant candidates.
A number of other circulatory support devices have been developed in recent years with the ability to provide even more circulatory support than the IABP. Devices can be implanted surgically (such as the left ventricular assist device [LVAD]) or percutaneously and are capable of creating flow rates of 3–5 L/min (close to a normal cardiac output). These devices can be used until cardiac transplantation can be facilitated or occasionally to support patients who ultimately recover. Large-scale, randomized data to support their use are lacking as of this time.
Revascularization, either by PCI or CABG surgery, decreases mortality in patients in whom cardiogenic shock develops following MI. The multicenter, randomized SHOCK trial (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock) showed a trend toward improved survival at 30 days in patients randomized to early revascularization (either PCI or CABG within 6 hours of enrollment). The survival benefit for early revascularization became significant at 6 months, a benefit that persisted to 6 years. Although the mortality of patients treated with a strategy of early revascularization was still high, the absolute reduction in mortality was substantial (13% at 1 year); stated alternatively, the “number needed to treat” with revascularization was approximately eight to prevent one death at 1 year, which is low and provides strong support for revascularization in these circumstances. Of note, patients 75 years of age and older did not benefit from revascularization at 1 year in the randomized trial but did benefit in the nonrandomized but much larger SHOCK registry. Many experts believe that the SHOCK trial was underpowered to show a mortality difference at 30 days and, based on the 6-month and now 6-year data, American College of Cardiology (ACC)/American Heart Association (AHA) guidelines recommend emergency revascularization for patients (especially those under the age of 75) with cardiogenic shock complicating acute MI.
Percutaneous Coronary Intervention
Patients undergoing PCI in the SHOCK trial had a similar benefit to those having bypass surgery. Mortality from cardiogenic shock has decreased over the past decade in parallel with increasing use of PCI for these patients. Although retrospective, other studies from large populations have shown that PCI use is associated with lower mortality in patients with cardiogenic shock.
Despite the marked absolute reduction in mortality observed among patients treated with bypass surgery in the SHOCK trial, only a small proportion of patients with cardiogenic shock undergo urgent bypass surgery (approximately 3% in the National Registry of Myocardial Infarction 2004 database). Nevertheless, patients with multivessel disease in cardiogenic shock should be evaluated for bypass surgery, and for patients with mechanical complications of MI, surgery offers the best hope for survival at present.
Fibrinolytic therapy refers to treating patients with acute ST segment elevation MIs with drugs that have fibrinolytic properties (that dissolve occlusive thrombus within coronary arteries or grafts). Although PCI is superior therapy to fibrinolysis for ST segment elevation MI, fibrinolysis is the recommended therapy if there will be a considerable delay in facilitating PCI. Most trials of fibrinolytic therapy excluded patients with cardiogenic shock. In earlier trials that included patients with cardiogenic shock, there was no benefit to fibrinolytic therapy over placebo. It has been suggested that the low-flow state present in shock may contribute to the limited efficacy of fibrinolytic therapy. In contrast to these older studies, in the SHOCK trial and registry, patients treated medically with fibrinolytic therapy fared better than those medically treated without fibrinolytic therapy. Additional evidence comes from meta-analyses of more recent fibrinolytic trials that revealed improved survival among hypotensive patients treated with fibrinolytics. Fibrinolytic therapy for patients with an acute MI complicated by cardiogenic shock may be useful for patients early in their presentation in whom there will be a delay in timely cardiac catheterization and revascularization.
Aspirin and heparin are indicated in patients with MIs and cardiogenic shock, provided mechanical complications requiring surgery are not present. β-Blockers are contraindicated in patients in cardiogenic shock. Platelet glycoprotein (GP) IIbIIIa inhibitors block the final pathway of platelet activation and aggregation and are beneficial in patients with acute coronary syndromes. Several clinical trials of GP IIbIIIa inhibitors included patients with cardiogenic shock. Patients in cardiogenic shock treated with the GP IIbIIIa inhibitor eptifibatide had improved survival in the PURSUIT trial, and patients in cardiogenic shock at presentation who undergo PCI and are treated with the GP IIbIIIa inhibitor abciximab have improved survival. These agents are probably most effective when initiated during cardiac catheterization, after the coronary anatomy is defined, but may have a role for patients who must be transferred for cardiac catheterization. For patients who eventually stabilize and in whom hypotension is no longer a concern, most clinicians would recommend other medical therapies benefiting patients with heart failure including angiotensin-converting enzyme inhibitors.
Acute mitral regurgitation secondary to papillary muscle dysfunction, myocardial free wall rupture, and VSD are true emergencies. The definitive therapy for these catastrophes is surgical repair, although there are reports of using percutaneously placed devices to successfully repair VSDs. If the patient is to survive, all efforts must be made to get the patient to the operating room as soon as possible after the diagnosis is made. Pharmacologic agents and the IABP (see previous section on circulatory support devices) are useful as temporizing measures.
Right Ventricular Infarction
Cardiogenic shock may occur with right ventricular MI and no or only minimal left ventricular dysfunction. Recent data have questioned the long-accepted notion that patients with shock from an isolated right ventricular MI have a better prognosis than those with primarily left ventricular dysfunction. In the SHOCK registry, patients with a right ventricular MI and shock fared similarly to those with primarily left ventricular dysfunction. Hemodynamic data suggesting right ventricular dysfunction out of proportion to left ventricular dysfunction and ST elevation in lead RV4 on a right-sided ECG are helpful in establishing the diagnosis, and assessment of right ventricular function on echocardiography can confirm the diagnosis. In cases of shock from right ventricular failure, initial treatment is aggressive fluid resuscitation to increase right ventricular preload and output. Significant amounts of fluid (1–2 L or more) may be required to develop an adequate preload for the failing right ventricle. Inotropic agents are usually necessary when the right ventricular failure is so profound that shock continues despite adequate volume administration, and the IABP may be helpful in this situation. Heart block is common in patients with right ventricular MIs. Patients with right ventricular infarction are relatively dependent on right atrial contraction. As a result, single-chamber right ventricular pacing may be inadequate in patients who require pacing, and atrioventricular sequential pacing may be required to improve cardiac output.
Arrhythmias contributing to cardiogenic shock are readily recognized with ECG monitoring and should be promptly treated. Tachyarrhythmias (ventricular tachycardia and supraventricular tachycardia) should be treated with electrical cardioversion in patients with hemodynamic compromise. Bradyarrhythmias may respond to pharmacologic agents (atropine, isoproterenol) in some circumstances, but external or transvenous pacing may be required.
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