Preoperative and postoperative use of inotropes in cardiac surgery

Preoperative and postoperative use of inotropes in cardiac surgery

Preoperative and Postoperative Use of Inotropes in Cardiac Surgery Roberta Hines, MD T RADITIONALLY, the pharmacological management of myocardial dy...

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Preoperative and Postoperative Use of Inotropes in Cardiac Surgery Roberta Hines, MD


RADITIONALLY, the pharmacological management of myocardial dysfunction has been focused on the intraoperative period. In particular, during cardiac surgery, the greatest use of vasoactive agents occurs during weaning from cardiopulmonary bypass (CPB). However, as a result of the changing demographics of the patient population, the need for inotropic support during the preoperative and postoperative periods is increasing. Classically, inotropic agents are administered to increase myocardial contractility and myocardial performance. Although contractility is a vital component of normal cardiac function, the importance of preload, afterload, and heart rate (HR) must not be overlooked. All four of these variables must be considered when selecting an inotrope in the perioperative period (Fig 1). The etiology of perioperative myocardial dysfunction is often multifactorial. Reductions in myocardial performance occur as a result of increased systemic vascular resistance (SVR), increased HR, decreased contractility (dP/dt), and/or increased pulmonary vascular resistance (PVR) (Fig 2). Therefore, an appropriate pharmacological strategy must be developed based on the specific hemodynamic derangements involved. Choices for the management of perioperative myocardial dysfunction include pharmacological agents (a-adrenergic agonists, nonadrenergic agents, fi-adrenergic agonists) and/or mechanical assist devices. The phosphodiesterase-III (PDE-III) inhibitors are the most recent addition to the class of nonadrenergic agents/ inotropic pharmacological agents. Unlike the catecholamines that exert their positive inotropic effect by stimulating /3-adrenergic receptors, the PDE-III inhibitors such as amrinone work by inhibiting fraction III phosphodiesterase. Because the PDE-III inhibitors are nonadrenergic compounds, they do not rely on stimulation of either (Y-or @-adrenergic receptors. They may be particularly beneficial in patients suffering from congestive heart failure (CHF) with secondary down-regulation of their P-receptors. In addition,

the combined use of P-agonists and PDE-III inhibitors results in a synergistic increase in myocardial performance.’ The primary hemodynamic features of this class of agents are listed in Table 1. Amrinone produces an increase in cardiac output (CO) and decreases in SVR, PVR, and pulmonary capillary wedge pressure (PCWP). Clinically, these effects occur with minimal changes in HR or myocardial oxygen consumption (MVO;?). Amrinone also improves renal blood flow, although indirectly (ie, it does not stimulate dopadrenergic receptors). By increasing CO, amrinone improves renal perfusion, usually by a secondary increase in the glomerular filtration rate. The PDE-III inhibitors provide positive inotropic support combined with systemic and pulmonary vasodilation, and are extremely valuable in the management of impaired myocardial performance during the preoperative and postoperative periods. PERIOPERATIVE USES OF AMRINONE IN CARDIAC SURGERY

When decreased cardiac contractility is associated with increased SVR, amrinone results in an increase in CO combined with a decrease in SVR. Clinically, this is demonstrated in the perioperative stabilization of patients with CHF, acute or chronic. Benotti et al were the first to document the clinical effectiveness of amrinone in the management of CHF.’ In this study, following the administration of amrinone, cardiac index increased by 53%, PCWP decreased by 29%, and SVR decreased by 29%. Of note, in spite of an increase in contractility, changes in HR and mean arterial pressure were minimal (+3% and -6%, respectively). Amrinone’s ability

From the Department of Anesthesiology, Yale Vniversity School of Medicine, New Haven, CT. Address reprint requests to Roberta Hines, MD, Department of Anesthesiology, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06510. 0 1990 by W.B. Saunders Company. OSSS-6296/90/0406-SOO6$03.00/0

Journal of CardiothoracicAnesthesia, Vol 4, No 6, Suppl 5 (December), 1990: pp 29-33



30 Increased SVR



I Increased PVR


Myocardial Dysfunction


Increased Heart Rate

Decreased Contractility Fig 2. Etiology of perioperative myocardial dysfunction involves decreased contractiliw, increased SVR. increased PVR, and increased HR. Fig 1. Four variables affecting myocardial performancrt-contractility, HR. preload, and afterload-to be considered in selection of an inotrope during the perioperative


to increase CO without significantly increasing HR may be of particular importance in patients suffering from coronary artery disease (CAD).3 With the advent of more sophisticated angioplasty techniques, high-risk patients (ie, those with multiple-vessel disease) are now frequently subjected to procedures in the cardiac catheterization laboratory. Unfortunately, 5% to 10% of these procedures result in complications requiring urgent or emergent operative intervention. An acute reduction in myocardial performance consisting of decreased CO, elevations in left ventricular end-diastolic pressure, increased HR and MVOz are frequently encountered following a failed angioplasty. As a result of significant underlying CAD, dysrhythmias are also commonly observed during this period. The stabilization of patients following failed coronary angioplasty represents a major therapeutic challenge. Certainly, definitive treatment for these patients is myocardial revascularization, but what can be done to optimize myocardial performance in the immediate perioperative period? Inotropes (ie, fiagonists), vasodilators, and the intraaortic balloon pump have served as the principal modes oftherapy to optimize cardiac performance prior to urgent revascularization. Amrinone’s ability to augment myocardial performance with minimal changes in HR and MVO, provides a useful pharmacological mechanism for obtaining hemodynamic stability in this patient population. TREATMENT



Use of amrinone for the management of patients with mitral valve disease and pulmonary hypertension was evaluated by Hess et al, who studied 21 patients with mitral valve stenosis (NYHA classification III or IV) whose surgery for mitral valve replacement was complicated by pulmonary hypertension.4 Following amrinone administered as an intravenous (IV) loading dose of 1.5 mg/kg, cardiac index increased from 1.4 L/min/ m* to 1.9 L/mitt/m*, SVR was reduced throughout the study period, the mean pulmonary artery pressure (PAP) declined approximately 20%, and the PVR dropped significantly by 30% to 50%. In addition, a significant increase in intrapulmonary right-to-left shunt was observed during treatment with amrinone, confirming its ability to dilate the pulmonary arterial vasculature. In a subsequent study performed by Hess et aL4 pulmonary vasodilating properties of amrinone were compared with sodium nitroprusside in 17 patients with aortic or mitral valve stenosis and pulmonary hypertension (NYHA classification IV) who required cardiac surgery. In the anesthetic steady state prior to surgery, SVR was lowered by 20% with both agents. The mean dose of drug required for this reduction was 8 &kg/ min for amrinone and 1.O&kg/min for sodium nitroprusside. Of note, only amrinone produced a significant decrease (25%) in PVR. Likewise, venous admixture increased significantly only in patients receiving amrinone. In both groups, the mean PCWP and mean PAP changed to the same extent. The pressure decrease in the pulmonary circulation induced by the nitroprusside was atTable 1. Primaw Hemodvnamic Features of Amrinone Increases contractility

Amrinone’s combined inotropic and vasodilating effects have proven to be effective in the treatment of pulmonary hypertension associated with decreased myocardial contractility.

Produces vasodilation, decreases PVR, decreases SVR Increases CO No change in HR Decreases Mi/O,



tributed to peripheral venodilation. The decrease in PAP observed with amrinone was attributed to pulmonary vasodilation. The pulmonary vasodilating effects of amrinone have also been described in patients with pulmonary hypertension awaiting heart/lung transplantation. Deeb et al have studied the effect of amrinone in 27 patients who had evidence of pulmonary hypertension (PVR > 6 Woods units [WUJ) who did not respond to a challenge of sodium nitroprusside to lower pulmonary pressures.’ In this study, 87% (24/27) of previously unresponsive pulmonary hypertensive patients responded to amrinone administration (PVR < 5 WU). In a second study,6 the same group compared amrinone with conventional therapy (ie, diuretics, digoxin, captopril) in 38 potential transplant candidates with pulmonary hypertension. Although in both groups the pulmonary hemodynamics improved enough for the patient to be considered eligible for transplantation (PVR < 5 WV), the decrease in PVR noted with amrinone was more pronounced than that observed with conventional therapy (amrinone PVR = 2.49 WU; conventional therapy PVR = 3.34 WV). Amrinone’s effects on the pulmonary vasculature have been well documented in a wide variety of clinical studies. Although the precise mechanism (direct 21indirect) of this pulmonary vasodilation has not been determined, significant reductions in PVR are observed in a wide variety of disease states. RIGHT VENTRICULAR FAILURE

Under normal conditions, right ventricular (RV) performance is governed by end-diastolic volume (preload), contractility, pulmonary vascular impedance (afterload), and coronary perfusion. However, in pathological conditions, such as pulmonary hypertension, the most important factor governing RV function is status of the pulmonary vascular impedance (ie, afterload) (Fig 3). Indeed, the contractility of the RV appears to be more dependent on the maintenance of a normal afterload than does the left ventricle. The thin-walled RV will not compensate for changes in afterload, particularly if these changes are acute. In situations in which pulmonary vascular impedance is acutely increased, RV performance is dramatically affected.7 In situations in which



Is Dependent


In Normal Conditions

L-7 \




Contractility Pulmonary Impedance


Volume /



In Pathological Conditions

Fig 3. Under normal circumstances, RV performance is governed by preload, contractilii, and pulmonary vascular impedance (afterload). In pathological conditions such as pulmonary hypertension, afterload becomes the most important factor governing RV performance.

this increase in afterload occurs gradually (ie, clinical obstruction), a pulmonary disease compensatory mechanism develops (ie, hypertrophy) and the RV remains normal at rest. However, in situations in which pulmonary impedance is increased acutely, these compensatory mechanisms are no longer adequate and RV failure ensues.8 Clinical studies that result in an increased PVR include positive-pressure ventilation, valvular heart disease, sepsis, adult respiratory distress syndrome, hypoxia, and pulmonary emboli. In these situations prompt and effective reductions in RV afterload will result in maintenance of normal RV function. A variety of pharmacological agents are available as pulmonary vasodilators (Table 2). All these compounds will effectively reduce PVR. Unfortunately, presently there is no available selective pulmonary vasodilator. Initially, prostaglandin, particularly PGE, , offered promise in this area. D’Ambra et al demonstrated the ability of PGEi to reduce PVR following CPB in patients with severe pulmonary hypertension undergoing mitral valve replacement.’ Although PGE, was effective in treating the pulmonary hypertension, left atria1 injection of norepinephrine was required to maintain an adequate systemic perfusion pressure. The need for concomitant left-sided administration of vasopressors severely restricts the clinical utility of PGE,. The PDE-III inhibitor provides pulmonary vasodilation without the need for simultaneous infusion of left atrial vasopressors.3’4 Konstam et al compared the ability of amrinone with sodium nitroprusside (SNP) to de-



crease PVR and augment RV function.” Data from this study show that amrinone was as effective as SNP in reducing PVR and augmenting RV ejection fraction. In addition, elevations in PVR frequently result in, or are accompanied by, decreases in RV contractility. In such cases, a combination of pulmonary vasodilation and positive inotropic support is necessary. Amrinone offers the advantage of providing both of these hemodynamic properties simultaneously. Clinically this combination of decreased cardiac performance and increased PVR may be observed in patients with mitral and/or aortic valve disease, primary pulmonary hypertension, chronic obstructive pulmonary disease (COPD), and car pulmonale. As previously mentioned, Hess et al demonstrated amrinone’s ability to decrease PVR and augment biventricular performance in patients with mitral and aortic valvular disease.4 Although no definitive laboratory data are available, clinical experience in patients suffering from pulmonary hypertension secondary to COPD demonstrates a reduction in PVR and increased RV performance following amrinone administration. Similarly, the population with primary pulmonary hypertension has been shown to benefit with sustained reduction in PVR following amrinone therapy.‘g6 POSTOPERATIVE USES OF AMRINONE

Alone or in combination with catecholamine therapy, amrinone has been shown to be an effective treatment modality in the cardiothoracic intensive care unit. Historically, Goenen et al were the first to report on the effectiveness of amrinone in the management of depressed ventricular function following cardiac surgery.” The hemodynamic effects of amrinone were measured in cardiac surgical patients who developed significant decreases in CO and increases in PCWP. Amrinone therapy was instituted as a loading dose of 2 mg/kg followed by an infusion of 20 pg/kg/min for 12 hours. At these doses amrinone Table 2.


Nitroglycerin Sbdium nitroprusside Hydralazine Terbutaline Aminophylline Amrinone Prostaglandins

produced significant improvement in CO, accompanied by decreases in PCWP, SVR, and right atria1 pressure (RAP). In a subsequent study, 14 patients with low CO syndrome following bypass were treated with amrinone.12 In these patients, cardiac index increased from 1.7 to 2.5 L/ min/min2, mean HR decreased from 91 to 84 beats/min, and mean arterial pressure increased from 85/57 to 100/72 mm Hg. More recent investigations have focused on the combined use of amrinone plus catecholamines to augment ventricular performance in the postoperative period following cardiac surgery. Olsen et al also used a combination of amrinone and dopamine for the management of moribund cardiogenic shock following open heart surgery.‘3 Robinson and Tchervenkov reported the combined use of norepinephrine and amrinone as a treatment for low CO after aortocoronary artery bypass surgery.14 Finally, Nakatuska and Mobley combined norepinephrine with amrinone and nitroglycerin to successfully manage a patient who developed low CO, high PCWP, and hypotension.15 Ongoing investigations are focusing on the postoperative use of amrinone in conjunction with &agonists, intraaortic balloon counterpulsation, and a-agonists. The synergistic effect on contractility noted with dual therapy (catecholamines plus PDE-111s) is the principal reason for the active clinical interest in using combination therapy. The precise choice of adrenergic agents (LY-or P-agonists) to use in combination with amrinone will be governed by the particular clinical situation. SUMMARY

Amrinone’s unique ability to combine positive inotropic support with systemic and pulmonary vasodilation makes it an extremely valuable agent in the perioperative management of cardiac surgical patients (Fig 4). In the perioperative stabilization of patients with CHF, these properties combined with minimal changes in heart rate and MV02 make amrinone a particularly useful therapeutic agent.231’3’2In patients with pulmonary hypertension and/or RV dysfunction, the pulmonary vasodilating effects of amrinone have been shown to be clinically beneficial.4,5 In the postoperative period, following cardiac surgery, SVR is often elevated and CO de-





??Decreased ??Right

Ventricular Contractility

Ventricular Dysfunction




Peripheral Perfusion

??Congenital ??Valvular

Heart Disease

Heart Disease

Fig 4. Amrinone provides positive inotropic support with systemic and pulmonary vasodilation in perioperative

management of cardiac surgical patients.


pressed. Here the systemic vasodilatory effects of amrinone, combined with its positive inotropic effects have been shown to treat successfully the low CO syndrome.” As a result of the synergistic effect observed with the combined use of PDEIII inhibitor and the adrenergic agents (ie, catecholamines), most postoperative therapy now consists of a combined approach (using amrinone plus an CYor P-agonist). The particular adrenergic agonist chosen will depend on the clinical setting. Clinical experience and research data continue to document the effectiveness of the PDE-III inhibitors, either alone or in combination, as a valuable adjuvant in the pharmacological management of the cardiac surgical patient.

REFERENCES 1. Gage J, Rutman H, Lucid0 D, et al: Additive effects of dobutamine and amrinone on myocardial contractility and ventricular performance in patients with severe heart failure. Circ Res 74:367-373, 1986 2. Benotti JR, Grossman W, Braunwald E, et al: Effects of amrinone on myocardial energy metabolism and hemodynamics in patients with severe congestive heart failure due to coronary artery disease. Circulation 62:28-34, 1980 3. Slogoff S, Keats AS: Does perioperative myocardial &hernia lead to postoperative myocardial infarction? Anesthesiology 62:107-l 14, 1985 4. Hess W, Arnold B, Veit S: The hemodynamic effects of amrinone in patients with mitral stenosis and pulmonary hypertension. Eur Heart J 7:800-807, 1986 5. Deeb GM, Bolling SF, Guynn TP, et al: Amrinone versus conventional therapy in pulmonary hypertensive patients awaiting cardiac transplantation. Ann Thorac Surg (in press) 6. Bolling SF, Deeb GM, Crowley DC, et al: Prolonged amrinone therapy prior to orthotopic cardiac transplantation in patients with pulmonary hypertension. Transplant Proc 20~753-756, 1989 7. Sibbald WJ, Driedger AA: Right ventricular function in acute disease states: Pathophysiologic considerations. Crit Care Med 11:339-345, 1983 8. Matthay RA, Berger HJ, Davies R, et al: Right and left ventricular exercise performance in chronic obstructive

pulmonary disease, radionuclide assessment. Ann Intern Med 93~234-239, 1980 9. D’Ambra M, LaRaia P, Phellan D, et al: Prostaglandin Ei-A new therapy for refracting right heart failure and pulmonary hypertension after mitral valve replacement. J Thorac Cardiovasc Surg 89:567-572, 1985 IO. Konstam MA, Cohen SR, Salem DN, et al: Effect of amrinone on right ventricular function: Predominance of afterload reduction. Circulation 74:359-366, 1986 11. Goenen M, Pedemonte 0, Baele P, et al: Amrinone in the management of low cardiac output after open heart surgery. Am J Cardiol 56:33B-38B, 1985 12. Gunnicker M, Hess W: Preliminary results with amrinone in perioperative low cardiac output syndromes. J Thorac Cardiovasc Surg 35:219-225, 1987 13. Olsen K, Kloya J, Fieldman A: Combination high dose amrinone and dopamine in the management of moribund cardiogenic shock after open heart surgery. Chest 94:503-507, 1988 14. Robinson RJS, Tchervenkov C: Treatment of low cardiac output after aortocoronary artery bypass surgery using a combination of norepinephrine and amrinone. J Cardiothorac Anesth 1:229-233, 1987 15. Nakatuska M, Mobleg R: The combined use of noradrenaline, am&one and nitroglycerin in the management of severe low cardiac output after coronary artery surgery. Anaesth Intens Care 16:458-487, 1988