CHAPTER 84 PHARMACOLOGIC SUPPORT OF CARDIAC FAILURE
Cardiovascular disease affects more than 70 million people, according to statistics from the American Heart Association in 2002. Congestive heart failure affects approximately 4.9 million of these Americans, resulting in about 1 million admissions and costs of about $27.9 billion annually.1 Admission for acute decompensated heart failure (ADHF) often results from exacerbation of pre-existing disease or following any number of events, including acute myocardial infarction, valvular disease, and arrhythmias. Additionally, patients today are older and sicker and may be undergoing cardiac and noncardiac surgery as well as developing other causes of acute heart failure such as from sepsis or pulmonary embolus. Patients with ADHF are often triaged to the medical intensive care unit (ICU); however, these patients are also presenting for urgent exploratory and elective surgery. Whether presenting with acute or chronic heart disease, this sicker population represents an increasingly difficult challenge for the surgical intensivist. Diagnosing and treating the initiating cause is imperative; the mainstay of therapy is optimal pharmacologic hemodynamic management.
PATHOPHYSIOLOGY
The pathophysiologic mechanisms leading to ADHF, as well as the goals of pharmacologic treatment, must be identified in order to successfully treat patients with ADHF. Understanding the complex nature of each specific disease process and its physiologic response is crucial for improving function and outcome. Cardiac failure is usually a result of derangement in any number of physiologic factors, including preload, afterload, contractility, heart rate, and heart rhythm.2
Increased preload is common in ADHF and is usually secondary to volume overload but can also occur with myocardial ischemia and valvular dysfunction. The body’s natural compensatory response is to increase filling pressures to improve myocardial contractility by increasing wall stress on the ventricle (moving up on the Frank-Starling curve).3 Heart failure generally causes a decrease in renal blood flow and subsequently activates the renin-angiotensin-aldosterone axis (RAAA). The end results of these compensatory mechanisms are vasoconstriction by angiotensin II with increased renal blood flow, release of aldosterone, which increases sodium absorption in exchange for potassium, and promotion of ventricular hypertrophy, fibrosis, and remodeling that ultimately leads to increased ventricular stiffness.4
Increased cardiac afterload is common in the perioperative setting due to multiple causes such as pre-existing hypertension, catecholamine surge, postoperative hypertension, and release of cytokines and inflammatory mediators. Moreover, pulmonary artery hypertension is increased due to similar causes, but can be exacerbated as well by relative hypoxic vasoconstriction and acidosis. In the failing heart, the sympathetic nervous system (SNS) is stimulated as the body acts to increase systemic vascular resistance to maintain normal perfusion to vital organs. The failing heart is further strained as it attempts to increase cardiac output against higher outflow pressures.3 The increased sympathetic tone also stimulates the release of renin, further activating the RAAA and its inherent problems in heart failure. Subsequently, there is an increase in myocardial oxygen demand, worsening sodium and water retention and a heightened potential to exacerbate lethal cardiac arrhythmias.3 Furthermore, higher plasma levels of circulating catecholamine have been correlated with worse prognosis.
Myocardial contractility is largely affected by stimulation of the SNS. Adrenergic agents increase intracellular adenosine monophosphate (cAMP), which in turn, increases calcium influx and strengthens the contraction. However, with chronically increased sympathetic tone, the failing heart becomes less responsive to circulating catecholamines, seemingly protecting the myocytes from the excessive catecholamines and their resulting inotropic and chronotropic drive. This dampened response is due to decreased sensitivity and down regulation of the β-receptors from the chronically elevated catecholamine levels that persist in congestive heart failure.2 Contractility becomes impaired and is less responsive to physiologic needs as well as to pharmacologic agents that act at the β-receptors. In addition, the failing heart responds inadequately to volume overload. The Frank-Starling mechanism is blunted, and significant increases in preload are poorly tolerated, further exacerbating congestive symptoms.
Right ventricular (RV) failure is becoming increasingly recognized as a significant cause of morbidity and mortality in the ICU.5,6 The RV is thin-walled and compliant relative to the left ventricle (LV) and is designed to function in a low-pressure, low-resistance environment. Contraction occurs in three stages: papillary muscle contraction, RV movement toward the interventricular septum, and LV contraction with twisting of the RV. There is minimal time spent in isovolemic contraction and relaxation, resulting in almost continuous flow to the lungs.5 The RV is vulnerable to elevation in pulmonary vascular resistance, which will increase the time spent in isovolemic contraction and relaxation, decreasing overall forward blood flow. The RV is perfused primarily from the right coronary artery (RCA), with perfusion occurring in systole and diastole as long as the low-pressure system remains intact. Both ventricles are dependent on movement of the interventricular septum, which can shift toward either the RV or LV, both of which can impair adequate filling and increase end diastolic pressures.
Following cardiac surgery, ventricular function is transiently impaired even in patients with normal preoperative ventricular function. This is due to several factors, including aortic cross clamping, inadequate myocardial protection, hypothermia and cardioplegia, reperfusion injury, as well as excessive levels of inotropes in the perioperative setting. There is a biphasic pattern, with initial recovery following weaning from cardiopulmonary bypass, a nadir at about 3–6 hours, and then full recovery at 8–24 hours. This pattern can obviously be delayed by poor preoperative ventricular function.7 Pharmacologic support is frequently necessary until adequate function returns.
TREATMENT
Diuretics
Diuretics are the mainstay and building block in treating patients with ADHF, as volume overload is a common occurrence. However, there are no randomized clinical trials demonstrating the efficacy of diuretics on mortality in ADHF. Nonetheless, diuretics remain an effective therapy for the volume-overloaded patient; they act by decreasing preload and intravascular volume and relieving the symptoms of dyspnea and pulmonary congestion.3 Also, hypervolemia is common in the surgical patient who has pre-existing congestive heart failure due to volume resuscitation from trauma, sepsis, major surgery, or perioperative fluid management. Loop diuretics such as furosemide are commonly used; more potent alternatives such as bumetanide or torasemide are useful in the diuretic-resistant patient. Intravenous boluses can be used, but continuous drips have been shown to be as effective and produce a more “gentle” diuresis. Continuous infusions have been shown to be less toxic and even more efficacious in patients with renal insufficiency.8 Volume status should be addressed clinically or with invasive monitoring if needed, as overdiuresis or diuresis of the normovolemic patient can cause hypotension or hypoperfusion of end organs. Diuretics may be detrimental in the face of an acute myocardial infarction or other organ dysfunction, as well as in the early postoperative setting in the presence of capillary leak and third space fluid sequestration. Other concerns include the use of high-dose diuretics, which can activate the RAAA and the SNS, and which have their own adverse long-term effects.
Vasodilators
Nitroglycerin can be an effective agent for the rapid treatment of cardiogenic pulmonary edema and ADHF and provides rapid relief of symptoms. The primary effect of nitroglycerin (NTG) is venodilation, with vasodilation occurring at higher dosing (>30 mcg/min). Nitroglycerin has minimal effects on cardiac and skeletal muscle and causes smooth muscle relaxation mainly in the venous system, allowing for increased venous capacitance. It effectively and rapidly reduces ventricular filling pressures (preload), relieving unwanted ventricular wall stress and, more importantly, reduces myocardial oxygen demand. In addition, NTG can improve coronary blood flow by reducing coronary artery resistance and prolonging diastole. The half-life of NTG is short, allowing for rapid escalation and discontinuation of the drug, but tachyphylaxis occurs and often requires persistently increasing dosage. Other unwanted side effects include headache and abdominal pain related to the powerful vasodilation.3 Volume status must be determined, and diuretics can be helpful in negating the increasing resistance to nitrates.
