AHF is a complex and heterogeneous syndrome, with only a few randomized controlled trials that have assessed treatment approaches. The comorbidities that are common in ICU patients make management more difficult and complicated. The immediate goals of treatment include improvement of tissue perfusion and oxygenation, correction of underlying hemodynamic abnormalities and the causes of cardiac decompensation, and control of symptoms. These short-term goals should then be linked to longer-term management strategies that ideally improve morbidity and mortality rates.
Respiratory Therapy and Ventilatory Support
A priority in treating patients with acute cardiac failure is the maintenance of arterial oxygen saturation (SaO2) within the normal range to improve tissue oxygenation. This can be achieved by using supplemental oxygen in most patients and by the use of noninvasive (see Chap. 33) or invasive (see Chap. 36) ventilatory strategies for patients with greater degrees of respiratory compromise.
Several trials have suggested a benefit of continuous positive airway pressure (CPAP) in patients with AHF, in particular a reduction in the need for endotracheal intubation.52–56 These investigations have been criticized for their small size and a failure to demonstrate a difference in mortality rate, but a recent meta-analysis showed a trend to decreased hospital mortality rate when CPAP was used as a routine measure for patients with AHF.57
Other forms of noninvasive ventilatory support have been studied, most often bilevel support delivered by nasal or full-face mask. Three randomized trials compared this approach with conventional oxygen therapy, large-dose nitrate therapy, or CPAP,58–60 with mixed results. A recent multicenter study of treatment of patients in pulmonary edema secondary to AHF showed no benefit for the general population of patients but did show a trend toward improvement by subset analysis of the more severely compromised patients.61
Analysis of these studies suggests that benefit is likely to be seen in more severely ill patients not stabilized with oxygen therapy alone. One approach is to use CPAP or other forms of support in patients with pulmonary edema, an elevated arterial partial pressure of CO2 (suggesting impending ventilatory failure) and a low pH even when an arterial pressure of CO2 is normal (suggesting more severe hypoperfusion).
Vasodilators are the first line therapy in patients with pulmonary congestion and adequate blood pressure. Nitrates relieve pulmonary congestion by reducing left ventricular preload and afterload. The highest tolerable dose of nitrates with low dose furosemide should be administered since it is more effective than furosemide treatment alone in acute pulmonary edema.62 However, close monitoring during intitiation of therapy is necessary because excessive vasodilation may induce a steep reduction in blood pressure, ischemia, sometimes shock and renal failure. Moreover, rapid development of tolerance to nitrates, especially when they are given intravenously, limits their effectiveness after 16 to 24 hours.
Sodium nitroprusside (SNP) has been also used for patients with acute heart failure and has found its widest application in patients with hypertensive crisis and ventricular decompensation. Controlled trials of its use are lacking in heart failure per se. Use of SNP requires close blood pressure monitoring. Prolonged administration can be associated with thiocyanate and/or cyanide toxicity and patients should be converted early to alternative agents to avoid these problems, particularly when renal and/or hepatic dysfunction are present.
Diuretics are indicated in patients with symptoms secondary to fluid retention. Diuretics increase the urine volume by enhancing the excretion of water and sodium chloride leading to decreased plasma and extracellular fluid volume and a decrease in peripheral and pulmonary edema. The acute hemodynamic effect of the intravenous administration of loop diuretics is vasodilation manifested by a reduction in ventricular filling pressures and in pulmonary vascular resistance.63 With high doses reflex vasoconstriction has been reported. In acutely decompensated heart failure the use of diuretics normalizes loading conditions and may reduce neurohormonal activation in the short term.64,65
Intravenous administration of loop diuretics (furosemide, bumetanide, torasemide) is preferred in acute heart failure. The dose should be titrated according to the diuretic response and relief of congestive symptoms. Administration of a loading dose followed by continuous infusion has been shown to be more effective than bolus alone with a lower incidence of toxicity.65–69 Diuretic resistance has been described and when present alternative means of fluid removal by dialysis or ultrafiltration should be considered.
Morphine can be used in the treatment of patients with pulmonary edema although its effectiveness has not been studied in clinical trials. Morphine induces venodilation and mild arterial dilation, reduces heart rate70 and relieves breathlessness in patients with acute pulmonary edema.
There is no evidence from clinical trials to support the use of anticoagulants in critically ill patients with AHF without myocardial ischemia or atrial flutter/fibrillation. However, the morbidity and mortality from thromboembolic disease in the ICU warrants the consideration of prophylactic anticoagulation in patients with AHF. A placebo controlled study evaluating enoxaparine in acutely ill patients, which included patients with AHF, demonstrated a reduction in the incidence of complicating venous thromboembolism but no improvement in survival or duration of hospitalization.71
Nesiritide, a recombinant human BNP, has been used for the treatment of AHF. Nesiritide reduces right atrial pressure, pulmonary capillary wedge pressure and increases stroke volume. Additional beneficial actions include coronary artery vasodilation, diuresis, natriuresis and neurohormonal suppression.72 The drug has been shown to be more efficacious than placebo in symptom improvement without a pro-arrhythmic effect. When compared to intravenous nitroglycerin neseritide results in a more rapid improvement in hemodynamic profile in patients with AHF.73 In an open-label randomized trial of nesiritide and standard care versus standard care alone, patients treated with nesiritide exhibited a trend toward decreased readmissions and six-month mortality.74 Nesiritide is administered as a 2 μg/kg bolus followed by a fixed dose infusion of 0.01 μg/kg per minute. The dose can be increased every three hours, to a maximum of 0.03 μg/kg/min, if the pulmonary capillary wedge pressure is more than 20 mm Hg and systolic blood pressure is more than 100 mm Hg (using a 1 μg/kg bolus followed by an increase of 0.005 μg/kg/min over the previous infusion rate). If hypotension occurs, the infusion should be discontinued and restarted after blood pressure stabilization, at a 30% lower infusion rate without bolus. Hypotension is a significant adverse effect of the drug, and may persist despite immediate cessation of infusion. Accordingly, nesiritide should not be employed in patients with extremely labile blood pressure dipping below a level of 90 mm Hg systolic.
In the near future, therapies directed at potentiating the beneficial effects of endogenous natriuretic peptides by reducing their degradation may find clinical application. A target under current investigation is neutral endopeptidase, the primary enzyme involved in their degradation. However, preliminary studies of inhibitors of neutral endopeptidase showed increased neurohormonal activation with increased levels of angiotensin II and endothelin-1 after enzyme inhibition.75 Thus, vasopeptidase inhibitors, which could provide simultaneous inhibition of angiotensin converting enzyme and neutral endopeptidase have been developed. Early use of such agents has been confounded by a high incidence of angioedema.76,77
Beta-blocking agents are contraindicated in patients with AHF, at least if it is clear that systolic dysfunction of the left ventricle is significant. Among patients in whom ischemia and tachycardia per se are felt to contribute significantly to their deterioration, beta blockade may be required; under such circumstances a short acting agent such as esmolol or metoprolol may given intravenously to permit cessation of therapy if adverse effects are encountered. Patients admitted to the ICU with AHF already receiving beta blockers should be continued on this therapy unless inotropic support is needed or excessive dosages is suspected.
In the initial management of the patient with acute heart failure, ACE inhibitors are not recommended and calcium antagonists are contraindicated. ACE inhibitors have an important role in the patient with systolic heart failure early after stabilization. Some new compounds with diuretic effect and vasodilating properties are under investigation, including vasopressin receptor antagonists.
Inotropic agents are indicated in the presence of hypotension and low cardiac output, with or without pulmonary congestion, refractory to optimal doses of diuretics and vasodilators (see Table 23-1). Inotropes are potentially harmful in chronic HF as they increase oxygen demand and calcium loading and should be used with caution.78–80 However, in patients with AHF, symptom relief and prognosis appear dependent on correction of grossly deranged hemodynamics. Only a few controlled trials assessing specific inotropic regimens have been performed and thus rigid guidelines for drug administration do not exist.80
Table 23–1. Inotropic Agents ||Download (.pdf)
Table 23–1. Inotropic Agents
|Dobutamine||Hypotension, hypoperfusion||No||2 to 20–40 μg/kg per minute (predominant β-agonist effect throughout this range)|
|Dopamine||Hypotension, hypoperfusion||No||<3 μg/kg per minute: dopaminergic effect 3–5 μg/kg per minute: β-agonist effect predominant >5 μg/kg per minute: α agonist, vasoconstriction predominant|
|Milrinone||Hypoperfusion with preserved blood pressure, patients on β blockers||25–75 μg/kg per minute over 10–20 min||0.375–0.75 μg/kg per minute|
|Norepinephrine||Severe hypotension refractory to dobutamine||0.2–1.0 μg/kg per minute|
Dopamine is an endogenous cathecolamine and a precursor of norepinpehrine. Its effects differ according to dosage. At low doses (≤2 to 3 μg/kg/min) activation of dopaminergic DA1 and DA2 receptors predominates with vasodilation in renal, mesenteric, coronary and cerebral vascular beds. The activation of DA2 receptors inhibits norepinephrine release from nerve terminals, activates the emetic center, decreases prolactin release and inhibits angiotensin II mediated aldosterone secretion. In the past, dopamine was widely used in the ICU to improve renal blood flow and diuresis in AHF patients with hypotension and low urine output. However, administration of low-dose dopamine to critically ill patients at risk of renal failure does not confer clinically significant protection from renal dysfunction.81,82 Small trials suggested some benefit of dopamine at low doses in patients with AHF but this general practice is not strongly supported by existing literature.83 In AHF with hypotension dopamine can be used at higher doses for both inotropic and vasoconstrictive purposes but adverse effects of increased afterload or mismatch of oxygen supply to myocardial demand should be anticipated.
Dobutamine is a synthetic, sympathomimetic agent with substantial beta agonist activity resulting in significant inotropic and chronotropic effects on the heart.84 It is usually initiated with a 2 to 3 μg/kg/min infusion rate without a loading dose. The infusion rate may be progressively titrated according to symptoms, diuretic response or assessments of hemodynamics (cardiac output, mixed venous oxygen saturation). The dose may be initially increased to 20 μg/kg/min as required. When undesirable side effects are encountered (tachycardia, hypotension, chest pain, arrhythmia), discontinuation of the drug is usually associated with reversal of effect due to short half life. Dobutamine may have an additive effect when given concurrently with phosphodiesterase inhibitors (see below). Prolonged infusion of dobutamine (above 48 hours) is associated with tolerance effects.85,86
Type III phosphodiesterase inhibitors (PDEI) are drugs with hemodynamic activity intermediate between that of a pure vasodilator and that of an inotrope.85 They are mainly used in patients with AHF and peripheral hypoperfusion, refractory to optimal diuretic and vasodilating therapy. Milrinone and enoximone are the PDEIs used in clinical practice. They act by inhibiting the breakdown of cyclic-AMP (cAMP) into AMP in both the vascular and myocardial smooth muscle. As a result, contractility improves in cardiomyocytes and relaxation in the smooth muscle cells. Because their site of action is distal to the beta-adrenergic receptors PDEIs maintain their effects even during concomitant beta-blocker therapy. When administered to patients with advanced HF, milrinone improves hemodynamics without tolerance development.86 Hypotension may be caused by excessive peripheral venodilation and is observed mainly in the patients with low intravascular volume. Therefore PDEIs are used in patients with preserved systemic blood pressure. Outcome data regarding PDE-I administration in patients with acute HF are limited but not encouraging especially in patients with ischemic cardiomyopathy. Based on hemodynamic data alone, the combination of milrinone and dobutamine has a greater positive inotropic effect than each drug alone. However, the pharmacokinetic profile of milrinone is not optimal for ICU patients because individual responses to milrinone vary considerably.
A new class of medications which enhance calcium sensitization of the contractile proteins has found application in Europe and agents are in survival clinical trials in Europe and North America. Levosimendan is such an agent, and has been used in patients with symptomatic low cardiac output secondary to cardiac systolic dysfunction without severe hypotension. Levosimendan improves cardiac contractility by increasing the sensitivity of troponin C to calcium although is also type III PDE inhibitor.87–91 Activation of adenosine triphosphate (ATP) sensitive potassium channels are responsible for its vasodilatory properties. Levosimendan has an active, potent, acetylated metabolite with half-life of approximately 80 hours, which probably explain the prolonged hemodynamic effects of a 24-hours levosimendan infusion.88–91 Levosimendan has not been used extensively in patients with AHF. In patients with decompensated chronic systolic HF increases cardiac output, heart rate and stroke volume and decreases the pulmonary capillary wedge pressure and systemic and pulmonary vascular resistance.88–91 An improvement in symptoms and decreased mortality has been shown in trials comparing levosimendan with dobutamine in patients with advanced chronic HF.91 The hemodynamic effect of levosimendan is maintained in heart failure patients on concomitant beta-blocker therapy. Tachycardia and hypotension are its main side effects and levosimendan is not recommended in patients with low systolic blood pressure.
When the combination of inotropic agent and fluid challenge fails to restore organ perfusion and blood pressure, therapy with vasoconstrictors may be needed. Since this treatment may result in excessive afterload applied to a failing ventricle, it should be used as an emergency measure to sustain life and maintain perfusion in the face of life-threatening hypotension. Recent data indicate that if a vasopressor is needed, norepinephrine may be used because epinephrine has more negative effects on splanchnic circulation and on lactate metabolism.92,93
Cardiac glycosides inhibit sodium-potassium ATPase, thereby increasing calcium-sodium exchange with resulting positive inotropic effects. In AHF, cardiac glycosides produce a small increase in cardiac output and a reduction of filling pressures.94,95 However, in patients with heart failure following myocardial infarction, increase of creatine kinase was more pronounced in patients receiving cardiac glycosides,96,97 and in some studies a proarrhythmic effect and an adverse effect on outcome have been described. Accordingly, cardiac glycosides are not recommended for the acute management of AHF especially after acute myocardial infarction.
Mechanical Assist Devices
Mechanical circulatory support may be used in patients with AHF without permanent end-organ dysfunction, non-responding to conventional therapy, as a bridge to recovery or as a bridge to heart transplant. In clinical trials left ventricular assist devices have been used as destination therapy for patients with advanced chronic heart failure but device related complications limit their use for this indication.
Intraaortic Balloon Pump (IABP)
IABP is most frequently used in patients with cardiogenic shock or ongoing severe myocardial ischemia, refractory to initial medical therapy, in preparation for revascularization. It is also useful in patients with acute myocardial infarction complicated by significant mitral regurgitation or rupture of the interventricular septum, to obtain hemodynamic stabilization for definitive diagnostic studies and treatment or after cardiac surgical procedures for patients with low cardiac output states.98 The IABP has obvious advantages over other cardiac assist devices because of the rapidity and ease of insertion, accomplished through a femoral artery and performed at the bedside of the ICU patient. However, IABP does not augment forward flow to the extent achieved with ventricular assist devices (see below).
IABP operation is based on the principle of counterpulsation. A balloon is positioned in the descending aorta just distal to the left sublavian artery. The balloon deflates at the onset of systole immediate prior to the ejection of blood from the left ventricle. Thus reduces afterload, thereby decreasing left ventricular work and myocardial oxygen consumption. It inflates in diastole, increasing diastolic pressure resulting in increased coronary artery perfusion. In the setting of non-ischemic heart failure the afterload reduction may be still useful but the benefits of increased coronary flow are not clear. Vascular complications are common and careful monitoring of lower extremity perfusion is necessary. Intraabdominal (mesenteric ischemia, pancreatitis, splenic infarction), neurologic (stroke, paraplegia) and infectious complications have been described. Balloon rupture with helium embolization and balloon entrapment has been also reported. IABP is contraindicated in patients with aortic dissection or significant aortic insufficiency and its use should be restricted to patients with a correctable underlying condition.
Ventricular Assist Devices
AHF patients not responding to conventional treatment including intra-aortic balloon pumping are candidates for mechanical circulatory support with ventricular assist devices (VAD).99–101 This situation should be understood as one of bridging the patient ventricular function is expected to improve or transplantation is planned. VAD has been used after acute myocardial infarction, in post cardiac surgery low cardiac output syndrome and in acute myocarditis. Specific hemodynamic criteria have been used for patient selection in decompensated chronic heart failure but patient selection is more difficult in AHF. Patients with right heart failure are candidates for biventricular support, patients with aortic valve prosthesis are at increased risk for thromboembolism with some systems and aortic regurgitation is exaggerated after left VAD insertion because of the lowered left ventricular end diastolic pressure. An incompetent aortic valve may need repair or replacement before VAD insertion.
Many VAD are currently available and can be categorized in several different ways including: (a) left versus right VAD; (b) pulsatile versus non pulsatile flow; (c) internal versus external placement. No current single VAD is appropriate for the management of all AHF patients. Selection of the device is determined by the expected duration of support, the specific cardiac pathology, type of support needed (right, left or biventricular), the device availability and surgical team experience. It is not possible for all cardiac surgery centers to use all available systems. Ideally, a center should have access to a short term support system for AHF, a long term support system and a system capable of providing support to the right ventricle.101
The patient with a VAD is a challenge for the ICU team because thromboembolism, bleeding, infection, hemolysis and device malfunction are common complications associated with the use of these systems.