Hospital treatment of congestive heart failure

Hospital Treatment of Congestive Heart Failure Management According to Hemodynamic Profile,

JAMES S. FORRESTER. M.D. DAVID

D. WATERS”

LOS Angeles, California

Selection of therapy for subjects with acute congestive cardiac failure usually involves a choice among a diuretic, a vasodllator and an inotropic agent. Three principal questions are involved in the decision: (1) Is cardiac output normal or depressed? (2) Is blood pressure normal or depressed? (3) Is regional myocardial ischemia present? Diuretics are safe and easy to administer, but they do not increase cardiac output or relieve hypoperfusion. lnotropic agents increase cardiac output but differ widely in their effects on blood pressure: selection of specific agents is influenced by their blood pressure effect. All inotropic agents, however, potentially aggravate regional myocardiai ischemia. In ischemic heart failure, therefore, vasodilators which also increase cardiac output, may be chosen. Vasodilator admtnlstration Is in turn limited by the decrease In arterial pressure which accompanies increasing infusion rate. When these three questlons are considered in combfnation, an effective therapeutic regimen can be identified. Thus, congestion without hypoperfusion requires a diuretic if blood pressure is normal; and a vasodilator when blood pressure is increased. In the presence of congestion with hypoperfusion, a vasodilator is employed if blood pressure is normal; and a posftive inotroptc drug when blood pressure is depressed. The use of hemodynamic monitoring in coronary care units during the last decade [l] has led to identification of subsets of patients with various degrees of circulatory impairment and to the recognition that the hemodynamic and metabolic effects of therapeutic agents vary substantially within each subset [2,3]. Since the effects of therapeutic agents can be predicted with reasonable accuracy within a given subset, there is now a rational basis for inpatient therapy of cardiac failure. The purpose of this article is to describe these subsets and the different responses to drug therapy that each subset exhibits. SUBSETS: THEIR IDENTIFICATION AND IMPORTANCE

From the Division of Cardiology, Cedars-Sinai Medical Center, Los Angeles, California. Requests for reprints should be addressed to Dr. James S. Forrester, Cedars-Sinai Medical Center, Division of Cardiology, 8700 Beverly Boulevard, Los Angeles, California 90048. Present address: lnstitut de Cardiologie de Montreal, 500 est, rue Belanger. Montreal, Quebec. Canada HlT lC8. l

In practice, heart failure is best described in terms of its two primary sets of clinical manifestations, pulmonary congestion and peripheral hypoperfusion, each of which has a specific and independently variable hemodynamic cause. An increase in pulmonary capillary pressure results in pulmonary congestion, and a reduction in cardiac index causes peripheral hypoperfusion. Since pulmonary congestion and peripheral hypoperfusion can occur either independently or together, four subsets of patients can be recognized:

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TABLE I

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Relationship of Hemodynamics to Clinical Subsets NORMAL (SUBSET I)

PULMONARY CONGESTION (SUBSET II)

PERIPHERAL HYPOPERFUSION (SUBSET Ill)

CONGESTION HYPOPERFUSION (SUBSET IV

Cl 2.2

18 PCP NOTE: Cl = cardiac index (liters/min/m*); PCP = pulmonary illary pressure, mm Hg (left ventricular filling pressure).

I = No pulmonary congestion or peripheral perfusion II = Pulmonary congestion

cap-

hypo-

without hypoperfusion

Ill = Peripheral hypoperfusion

without

congestion

IV = Combined pulmonary congestion and peripheral hypoperfusion Subset classification is clinically relevant in three ways. First, the hemodynamic determinants of pulmonary congestion and peripheral hypoperfusion, pulmonary capillary pressure and cardiac index, respectively, represent the two axes of the Starling relationship (performance versus preload): thus, the four subsets represent different levels of cardiac function (Table I). Second, since survival in acute heart failure is directly related to the level of cardiac function, the subsets are of major prognostic value (Table II). Third, both the primary goals of therapy and the response to drugs are different in each subset of cardiac function, thus identification of a patient as within a given subset provides a direction for therapy. The two primary goals of therapy in patients with acute heart failure are (1) to reduce pulmonary congestion by lowering pulmonary capillary pressure when it is increased and (2) to reduce hypoperfusion by increasing cardiac output when it is reduced. If heart

TABLE II

Mortality Rates in Clinical and Hemodynamic Subsets

subset

Pulmonary Congestion (PCP > t8 mm Hg)

I II Ill IV

5 +

Peripheral Hypopertudon (Cl < 2.2 ittsrsl mlnlm2)

174

July 1979

1 11 18 60

+ +

NOTE: PCP = pulmonary

capillary

Per Cenl Mortality Hsmodynamlc Clinical

pressure:

Cl = cardiac

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Volume 65

failure is secondary to acute myocardial infarction, a third goal is added. Since therapy directed at improving cardiac performance by altering cardiac output and pulmonary capillary pressure may substantially affect both myocardial oxygen supply and demand, attention should also be given to the effects of therapeutic agents upon the degree of myocardial ischemia. Therapy which increases contractility, afterload (arterial systolic pressure), preload (pulmonary capillary pressure) or heart rate, increases myocardial oxygen demand. Because drug therapy seldom increases perfusion of ischemic areas in the presence of fixed proximal coronary artery stenosis, an increase in oxygen demand carries a substantial risk for increasing infarct size. PHARMACOLOGIC INTERVENTIONS IN HEART FAILURE Therapeutic agents employed to improve cardiac function are usefully considered in three classes: diuretics, vasodilators and inotropic agents. This classification is particularly suitable in clinical practice, for although there are substantial variations in the magnirude of effects, the direction of the hemodynamic response to various drugs within each subset is similar. Diuretic Agents. Diuretic agents cause a reduction in pulmonary capillary pressure with little change in cardiac output or heat-t rate in patients with heart failure [4-61. There are two mechanisms by which increased pulmonary capillary pressure is reduced by these agents. The most immediate effect is extrarenal: these agents produce a substantial increase in venous capacitance with resultant redistribution of venous blood away from the lungs toward the periphery and a decrease in pulmonary capillary pressure. An important characteristic of this effect is that it occurs approximately within 5 minutes of the drug administration, thus preceding the diuretic effect and making these drugs useful in acutely ill patients. The second mechanism of action is through increasing sodium and water excretion by the kidney. The resultant diuresis produces a decrease in intravascular volume, and a consequent decrease in left ventricular volume and pressure, which in turn causes a reduction in pulmonary capillary pressure and relief of pulmonary congestion. If left ventricular volume is excessively reduced, however, a substantial decrease in cardiac output may occur. Therefore, in patients with pulmonary congestion (subset II) improvement is secondary to decreased pulmonary capillary pressure with no change in cardiac index; in patients without pulmonary congestion (subsets I and ill), clinical deterioration may occur secondary to diminished cardiac index. In subset IV (both pulmonary congestion and peripheral hypo-

HOSPITAL

TABLE iii Diuretic Furosemide Ethacrynic acid Thiazides Aldosterone antagonists

THERAPY

OF HEART

FAILURE--FORRESTER,

Diuretics

WATERS

_-_____Disadvantages

Advantages High potency; rapid action; safe High potency; rapid action; safe Moderate potency; rapid action No potassium toss

Initial Dose

May cause sudden hypotension; tendency rebound phenomenon after withdrawal; May cause sudden hypotension; tendency rebound phenomenon after withdrawal; Kaluresis; tendency to refractoriness

40 mg, intravenous or oral 50 mg. intravenous or oral 25-50 mg, oral

to refractoriness; kaluresis to refractoriness; kaluresis

Immediate effectiveness is less than with furosemide, ethacrynic acid or thiazides

perfusion) diuretics relieve pulmonary congestion but have no effect on the signs and symptoms of peripheral hypoperfusion, since cardiac index does not increase. The advantages and disadvantages, and the doses of the most commonly used diuretics are shown in Table III. These agents are dramatiPeripheral Vasodllators. cally effective in improving cardiac hemodynamics in patients with heart failure. Cardiac output increases substantially, pulmonary capillary pressure decreases and there is little change in heart rate. The mechanism responsible for these hemodynamic changes is extracardiac. Reduction in peripheral arteriolar resistance to ejection results in an increase in the ejection fraction, which is translated into an increase in stroke volume and cardiac output. The increase in systolic emptying leads to a decreased left ventricular diastolic volume and decreased pulmonary capillary pressure. Like diuretic agents, the effect of peripheral vasodilators differs between patients in the pulmonary congestion subsets and those with normal pulmonary capillary pressure. Peripheral vasodiiators increase stroke volume in patients with increased pulmonary capillary pressure (subsets II and IV), but decrease stroke volume and increase heart rate in patients with normal left ventricular filling pressures (subsets I and iii). Mechanisms responsible for these differences are illustrated in Table IV. Patients with normal cardiac function (subset I) have a normal ejection fraction. Therefore, there is no margin to increase ejection fraction by the mechanism of reduced peripheral vascular resistance. Since peripheral vasodilators also dilate peripheral veins, resulting in peripheral venous pooling, reduction in stroke volume occurs due to the Starling effect. In contrast, patients with increased pulmonary capillary pressure due to heart failure exhibit an increase in ejection fraction with a reduction in peripheral vascular resistance which, in turn, lead to an increase in stroke volume and a decrease in pulmonary capillary pressure [7]. The advantages and disadvantages, and the doses of specific peripheral vasodiiators used in the hospi-

25-100

mg, oral

talized patient are shown in Table V. Nitroglycerin [ 81 exerts its effect primarily on the venous system, phentolamine [9-161 primarily on the arterial system, and nitroprusside [7,17] has an action intermediate between the two. The most potent agents are nitroprusside and phentoiamine. Phentoiamine is seldom used because it is considerably more expensive than nitroprusside. The use of nitroprusside to improve cardiac performance has several major advantages. its effect on hemodynamics is immediate, and its half-life is extremely short (about 30 seconds in the systemic circulation). Its major disadvantage isthat intravascular hemodynamic monitoring is required to control drug administration. Of the nitrates which have thus far been studied, isosorbide dinitrate [ 181 and nitroglycerin ointment [ 191 have received the most attention. These two agents are of approximately equal potency. Sublingual isosorbide dinitrate carries the major disadvantage in that its action is of relatively short duration, about 11/2 hours, and therefore requires frequent administration. Nitroglycerin ointment and oral isosorbide [ 201 are exceptionally effective drugs for the treatment of both acute and chronic heart failure and have a medium range duration (4 to 6 hours). The use of vasodilating agents is limited by their propensity to induce or aggravate hypotension in patients with severe heart failure. The response to infusion of a peripheral vasodiiator, however, generally follows a three step progression determined by dose level. At low doses, cardiac output increases and pulmonary TABLE IV

Peripheral Vasodilator Effects in Presence of Normal Versus Abnormal Pulmonary Capillary Pressure (PCP) Abnormal PCP

JArterial resistance f Venouscapacitance Hemodynamic result

Normal PCP

f EF

NOAEF

1;” ILVFP

IZFP JLVFP

NOTE: EF = ejection fraction; CO = cardiac output; LVFP = left ventricular filling pressure.

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HOSPITAL THERAPY OF HEART FAILURE-FORRESTER,

TABLE V

WATERS

Vasodilators

Vasodllalor

Advantages

Disadvantages

Phentolamine

High potency; immediate effect; half-life extremely short High potency; rapid action

lsosorbide dinitrate

Sublingual or oral administration

Nitroglycerin ointment

Prolonged duration of action (UP to 6 hours); removable

Nitroprusside

Requires hemodynamic monitoring Requires hemodynamic monitoring Less potent than nitroprusside and phentolamine Topical use may not be well accepted bv oatients

capillary pressure decreases with little change in arterial pressure. If the infusion rate is then increased, a further increase in cardiac output and decrease in pulmonary capillary pressure occurs, but arterial pressure also begins to decrease. If the infusion rate is again increased, profound vasodilation occurs, and cardiac output, pulmonary capillary pressure and arterial pressure all decrease. At this infusion rate, peripheral vasodilating agents are potentially lethal. For this reason, to avoid overdosage, two guidelines are employed in vasodilator therapy: (1) pulmonary capillary pressure should not be decreased below 15 to 18 mm Hg (if the patient is being evaluated clinically, these drugs should not be administered in the absence of rales) and (2) arterial pressure should be kept within the physiologic range (generally, greater than 100 mm Hg peak systolic pressure). lnotroplc Agents. lnotropic agents increase cardiac output and decrease pulmonary capillary pressure by improving myocardial contractility. These agents, therefore, are quite effective in the treatment of patients in subsets II (isolated pulmonary congestion) and IV (both pulmonary congestion and peripheral hypoperfusion). Because increased myocardial contractility also increases myocardial oxygen demand, these agents are of limited value, however, when acute myocardial ischemia accompanies acute heart failure. Table VI illustrates the advantages and disadvantages, mechanisms of action and dose levels of the commonly used inotropic agents. Digitalis compounds [ 2 l-271 have three important

TABLE VI

Hemodynamic Subsets as a Basis of Therapy SEDATIVE (SUBSET I)

DIURETIC, VASODILATOR (SUBSET II)

VOLUME, PACING (SUBSET Ill)

+ INOTROPIC AGENT, VASDDILATDB (SUBSET IV)

Cl 2.2

18 PCP

176

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DoseRange 15-400 pg/min, intravenously 0.25-1.0

mg/min intravenously

2.5-5 mg sublingually; lo-30 orally (ingested) 1 J-4.0 inches (cutaneous)

mg

cardiovascular effects: they increase myocardial contractility, slow atrioventricular conduction and therefore heart rate, and constrict both peripheral arterioles and venules. They are effective agents for increasing cardiac output and decreasing pulmonary capillary pressure in patients with heart failure, but they have little effect on cardiac output in normal persons. Dlgoxin is currently the most commonly used digitalis preparation in patients with heart failure. It is approximately 80 per cent absorbed in the gastrointestinal tract, and its serum half-life is approximately one and a half days. Most digoxin is excreted by the kidneys at a rate proportional to the glomerular filtration rate, but small percentages are metabolized by the liver. When given intravenously, the effect of digoxin can be detected at 10 minutes; its peak effect is attained at approximately 30 minutes to an hour. Little therapeutic advantage can be gained by using a more rapidly acting digitalis preparation. Few drugs have a more narrow therapeutic to toxic dose ratio than digitalis: the prevalence of digitalis toxicity in hospitalized patients has been reported to be as high as 20 to 30 per cent. Therefore, the dosage employed and the rate of administration should be governed by the clinical circumstances. For instance, in a situation of moderate urgency, such as rapid atrial fibrillation associated with moderate pulmonary congestion, it would be appropriate to administer 1 mg of digoxin intravenously followed by 0.25 mg intravenously every 4 hours until the ventricular rate decreases to less than 100 beats/min. The loading dose of digitalis should be related to body size; the maintenance dose should be related to renal function. An average maintenance dose for an average size individual with normal renal function is 0.25 mg of digoxin a day. Catecholamines, including isoproterenol [ 28-341, norepinephrine [35,36], glucagon [37-401 and dopamine [41-501, all reduce pulmonary capillary pressure and increase cardiac output in patients with heart failure. The differences in mechanisms of action relate predominantly to the magnitude of effects of these agents upon the so-called (Y- and fl- adrenergic receptors. The cu-receptors are responsible for adrenergic-mediated peripheral vasoconstriction and the p-

HOSPITAL THERAPY OF HEART FAILURE-FORRESTER,

receptors are responsible for cardiac stimulation (0, receptors) and sympathetic vasodilation (& receptors). lsoproterenol and glucagon are peripheral vasodilators and can increase cardiac output by this mechanism, whereas both dopamine and norepinephrine are dominantly P-adrenergic at low doses and cY-adrenergic at high doses. The hemodynamic effects of inotropic agents, therefore, differ predominantly in their effect upon arterial pressure: in the clinical dosage usually employed, dopamine and norepinephrine increase arterial pressure, and isoproterenol and glucagon either cause no change or decrease arterial pressure. Because it is the most potent inotropic agent, isoproterenol is probably the most effective in increasing cardiac output and decreasing pulmonary capillary pressure, but it is also most prone to aggravate myocardial ischemia when it is present. Dopamine may be used for the patient with concomitant hypotension in subset IV, norepinephrine should be utilized when immediate restoration of arterial systolic pressure takes precedence over all other considerations. Other Agents. Morphine is perhaps the most important agent used in the treatment of acute pulmonary edema. It has three important actions: it is a potent peripheral vasodilator, it has minor inotropic effects, and it is a central nervous system sedative. Given intravenously to a patient with acute pulmonary edema, its peripheral venous and arterial vasodilating effects cause a substantial reduction in pulmonary capillary pressure and may increase cardiac output if it is depressed. As with other peripheral vasodilating agents, excessive drug administration can result in a decrease in cardiac output and arterial pressure. Although the drug is a respiratory depressant, when cautiously administered, it neither produces respiratory failure nor aggravates carbon dioxide retention associated with acute pulmonary edema. Oxygen increases peripheral vascular resistance and can lead to a reduction in cardiac output. This disadvantage, however, is outweighed by its beneficial effects. Acute pulmonary edema is associated with hypoxemia due to venoarterial intrapulmonary shunting. Administration of oxygen, therefore, serves partially to reduce hypoxemia and thereby increase oxygen delivery to ischemic tissues. Recent experimental evidence also suggests that oxygen administration during acute myocardial infarction may reduce the severity of ischemic injury to the myocardium. APPROACH TO THE INPATIENT TREATMENT HEART FAILURE

OF

In the most acutely ill patients, two series of treatment decisions are required. The first concerns selection of an appropriate treatment within the first several minutes; of necessity, this must follow the most cursory of

WATERS

evaluations. The second set of treatment decisions involves those made within the first several hours or days, in which both a more careful evaluation is required and a greater range of therapeutic alternatives is presented. When a patient is first seen with severe acute heart failure, the predominant symptoms are either those associated with a marked increase in pulmonary capillary pressure (signs of severe pulmonary congestion) or the symptoms of an acute reduction in cardiac output (signs of peripheral hypoperfusion). This initial distinction provides the basis for treatment within the first several minutes. Immediate Treatment. Acute pulmonary edema: Prior to administering therapy, one critical question must be answered: is there clear evidence that the patient has pulmonary congestion and not acute respiratory failure secondary to other causes? The administration of morphine to a patient with primary respiratory failure, for instance, can substantially aggravate this disorder, whereas it may be life-saving in a patient with acute pulmonary congestion secondary to heart failure. Within the first minutes of seeing the patient, three emergency procedures are indicated for treatment of acute severe pulmonary congestion: (1) administration of oxygen, (2) placement of a large bore intravenous line, (3) administration of 5 to 10 mg morphine sulphate intravenously, slowly over several minutes. If these therapies are not immediately effective, phlebotomy (range 100 to 500 cc) may be performed, or rotating tourniquets may be employed. Peripheral hypoperfusion: As with pulmonary congestion, one critical question must be answered prior to administration of therapy: is the acute hypoperfusion due to a cardiac or noncardiac cause; specifically, is either cardiogenic shock or hypovolemia present? Critical to this distinction is a rapid evaluation for evidence of pulmonary congestion, most importantly the presence of rales on auscultation. Although this distinction may seem to be relatively straightforward, it can be deceptively difficult in a patient with severe peripheral hypoperfusion who has shallow breathing, or when only a few rales are audible. If hypovolemia is present, fluid replacement takes immediate priority. In all other cases with associated hypotension, three procedures must be initiated immediately: (1) Placement of both an intravenous cannula and intraarterial line. (2) A continuous infusion of a pressor agent through the intravenous line (nonrepinephrine, 5 Fg/min or dopamine, 5 to 10 pg/kg/min are both suitable). Systolic arterial pressure should be titrated to a level of 90 to 120 mm Hg. (3) Oxygen administration by face mask, nasal cannula or endotracheal intubation. These therapies are administered as emergency measures, without regard to the etiology of the pre-

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senting symptoms and are dominantly directed toward immediate reduction of pulmonary capillary pressure in acute pulmonary congestion and toward an increase in cardiac output or arterial pressure in acute peripheral hypoperfusion. As soon as these emergency procedures have been completed, the second phase of emergency treatment for acute failure should begin. Inpatient Management of Heart Failure. After emergency treatment, the process of subsequent therapeutic decision making depends predominantly upon subset identification (Table VI). Subset I (normal function) is not germane to this discussion. Subset II is characterized by isolated pulmonary congestion, i.e., an isolated increase in pulmonary capillary pressure. Although an increase in pulmonary capillary pressure is most commonly due to depressed function, cardiac index is not necessarily decreased. Most compensatory mechanisms are geared to preserve cardiac output, even at the expense of pulmonary capillary pressure: for instance, dilatation, hypertrophy and renal mechanisms can all increase cardiac index but also increase pulmonary capillary pressure. Thus, the clinical manifestations of increased pulmonary capillary pressure precede those of decreased cardiac index in heart failure. Isolated pulmonary congestion is probably the most common of the subsets of heart failure. Treatment in this subset is directed primarily at the reduction of pulmonary capillary pressure. The treatment of choice in this subset is most commonly a diuretic because these agents can be readily administered with few side effects. When diuretics are ineffective in relieving pulmonary congestion in the absence of acute myocardial ischemia, digitalis is also effective, but it carries a greater risk of toxicity than the diuretics. Other inotropic agents are of limited value in this subset. If diuretics are ineffective and acute ischemia is present, a trial of oral or topical nitrates is appropriate. Intravenous vasodilators, although effective, are less appropriate because hemodynamic monitoring is required. Patients in subset Ill have circulatory failure, often with a cardiac abnormality. There are three major causes. The majority of patients in this subset demonstrate reduction in stroke volume with a compensatory tachycardia. Such patients often exhibit substantial improvement with volume loading or blood replacement. The amount of volume administration is controlled by the hemodynamic response. In general, cardiac output will increase with volume infusion until the level of pulmonary capillary pressure reaches approximately 15 to 18 mm Hg after which a further increase in cardiac output is minimal. In acutely hypovolemic patients with a long-standing history of pulmonary congestion, higher levels of pulmonary capillary pressure may be required (e.g., postoperative bleeding in patient with mitral valve

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replacement). Depending upon the etiology of the signs of peripheral hypoperfusion, cardiac function may or may not return to normal. For instance, the patient in subset Ill who presents with bleeding as the etiology for peripheral hypoperfusion will respond quite well to volume replacement therapy; on the other hand, a patient with acute myocardial infarction may still exhibit substantial reduction in cardiac output after the pulmonary capillary pressure is brought to the high normal range. In such patients this condition may then be identified as part of subset IV (combined peripheral hypoperfusion and pulmonary congestion) and treated with additional modalities, such as peripheral vasodilators, but only with continuing adequate volume replacement. A small group of patients in this subset have a slow or normal heart rate in the face of a severely reduced cardiac output. This group of patients may respond quite favorably to a therapeutic increase in heart rate, the most substantial increases in cardiac output being observed in patients with heart rates in the range of 50 to 70 beats/min, with little response in cardiac index beyond 90 to 100 beats/min. In units equipped with temporary transvenous pacemaking capability, this is the therapy of choice because the clinical and cardiac output response can be titrated directly to heart rate. In the absence of pacemaking capability, intravenously administered atropine may increase heart rate and cardiac output in this group of patients in a dramatic fashion, a fact well recognized by anesthesiologists facing this situation in the operating theater. The third group of patients presenting with clinical subset Ill are those with marked reduction in peripheral vascular resistance, frequently secondary to arteriovenous shunting. The most common representatives are patients with anaphylaxis and alcoholics with septic shock. In this group, cardiac output may be within the normal range, although peripheral perfusion is markedly reduced. Appropriate therapy for this group has not been clearly defined. The most effective therapy for these patients is that directed against the underlying disease itself (e.g., specific antibiotic therapy for septic shock, epinephrine and steroids for anaphylaxis). In subset IV, attention should center upon the level of arterial pressure. If arterial pressure is in the physiologic range, the choice of therapies lies between inotropic agents and peripheral vasodilators, which are of comparable effectiveness in improving cardiac function. Both groups are limited by the side effects which they produce. In the presence of acute myocardial infarction, the use of peripheral vasodilators is much to be preferred, since these agents reduce myocardial oxygen requirement and by so doing may decrease infarct size and arrhythmias. Vasodilator administration is limited by the inevitable development of hypotension

HOSPITAL

as the infusion rate is increased. In the absence of both myocardial ischemia and hypotension, isoproterenol is the most potent inotropic agent, but it should be used with caution in patients with known heart disease of any type. Digitalis is most commonly the inotropic agent of choice in the absence of myocardial ischemia, although its potency is not as great as other inotropic agents or intravenous peripheral vasodilators. The potency of peripheral vasodilators varies widely between the intravenous agents (nitroprusside and phentolamine) which increase cardiac output by as much as 75 per cent [8] and the sublingual, oral or topical agents (nitroglycerin, isosorbide) which increase cardiac output by about 25 per cent when optimally administered. There is no similar important difference between vasodilators in effectiveness for reducing pulmonary capillary pressure. When arterial pressure is less than 100 mm Hg, an inotropic agent with a pressor action is the drug of choice. Dopamine offers considerable advantage in this situation. It has a mild pressor action which is readily titratable, and it also increases cardiac index. In addition, its selective action on important vascular beds promotes distribution of blood flow to desired areas: specifically, it increases renal and mesenteric perfusion. Two constraints must be observed: low dose dopamine infusion produces hypotension (the drug is usually a vasodilator below 2 mg/min) and induces tachycardia at higher infusion rates. This latter side effect frequently limits the infusion rate.

THERAPY

OF HEART

FAILURE-FORRESTER.

WATERS

In contrast, norepinephrine offers more potency for increasing arterial pressure, but it is more difficult to titrate. The increased arterial pressure generally is a reflection of a more substantial increase in peripheral vascular resistance than in cardiac output and the agent may be less effective than dopamine in increasing flow to vital organs. For this reason, administration of agents such as norepinephrine seldom is of lasting benefit and should be viewed primarily as a temporizing measure to obtain control of arterial pressure until a more effective therapy can be administered. As in patients with normal arterial pressure, digitalis may also be effectively employed to increase the cardiac index in the hypotensive patients in subset IV, although a substantial increase in arterial pressure should not be expected. In summary, there are two fundamental principles to recognize in the therapy of heart failure: (1) Acute heart failure represents several hemodynamic subsets, which are clinically identifiable. (2) The response to therapy varies with each subset. These variations in prognosis and response to therapy reflect the complex interaction between normal and injured myocardium, central nervous system stimuli, the peripheral vasculature and intravascular volume. With thorough understanding of the limited number of hemodynamic outcomes that these complex interactions produce, it is possible to select an effective therapy in most patients hospitalized with disordered cardiac performance.

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cardial infarction. Am J Cardiol 33: 37, 1974. Gould L, Ettinger S, Carmichael A, et al.: The use of phentolamine in experimental hemorrhagic shock. Angiology 21: 330,197o. Gould L: Phentolamine. Am Heart J 78: 276, 1969. Taylor SH, Sutherland GR, MacKenzie GJ, et al.: The circulatory effects of phentolamine in man with particular respect to changes in forearm blood flow. Clin Sci 28: 265, 1965. Gould L. Zahir M, Ettinger S: Phentolamine and cardiovascular performance. Br Heart J 31: 154, 1969. Taylor SH, Sutherland GR, MacKenzie Gl, et al.: The circulatory effects of intravenous phentolamine in man. Circulation 31: 741, 1965. Kelly DT, Delgado CE, Taylor OR, et al.: Use of phentolamine in acute myocardiil infarction associated with hypertension and left ventricular failure. Circulation 47: 729, 1973. fvlajidPA, Sharma B, Taylor SH: Phentolamine for vasodilator treatment of severe heart failure. Lancet 2: 7 19, 197 1. Franciosa JA, Guiha NH, Limas CJ, et al.: Improved left ventricular function during nitroprusside infusion in acute myocardial infarction. Lancet 1: 650, 1972. Gray R, Chatterjee K, Vyden JK. et al.: Hemodynamic and metabolic effects of isosorbide dinitrate in chronic congestive heart failure. Am Heart J 90: 346, 1972. Taylor WR, Forrester JS, Magnusson P, et al.: Hemodynamic effects of nitroglycerin ointment in congestive heart failure. Am J Cardiol 38: 469, 1976.

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