Combined Inotropic Effects of Amrinone and Epinephrine After Cardiopulmonary Bypass in Humans

Abstract

Amrinone, a phosphodiesterase inhibitor, and epinephrine, an alpha- and beta-adrenergic receptor agonist, are inotropic drugs used during cardiac surgery to reverse myocardial depression after cardiopulmonary bypass. However, these drugs have not been compared separately, or in combination, in this patient population. We hypothesized that the combination might have complementary actions in improving myocardial function. We, therefore, compared amrinone, epinephrine, and the combination of amrinone and epinephrine in a randomized, blinded, placebo-controlled study in patients undergoing coronary artery bypass grafting. Forty patients with ejection fractions > 0.45 were studied. Right ventricular ejection fraction pulmonary artery catheters and radial arterial catheters were inserted before fentanyl-midazolam anesthesia. After separation from bypass, patients received either a placebo (n = 20) or amrinone bolus (1.5 mg/kg, n = 20) at time 0 and a placebo (n = 20) or epinephrine (30 ng.kg-1.min-1, n = 20) infusion at time 5 min. This resulted in four study groups, n = 10 in each group. Data were collected every 2.5 min for 10 min. Epinephrine, amrinone, and the combination of both drugs significantly increased cardiac output, stroke volume, O2 delivery, and left ventricular stroke work. The increase in stroke volume (P < 0.05) was 12 +/- 6, 16 +/- 4, and 30 +/- 4 mL/beat with epinephrine, amrinone, and the combination of amrinone and epinephrine, respectively. The amrinone-epinephrine combination increased stroke volume as much as the sum of amrinone and epinephrine given separately. Systemic vascular resistance and pulmonary vascular resistance decreased with amrinone and amrinone-epinephrine, but not with epinephrine. Epinephrine increased mean arterial and mean pulmonary arterial pressures. Right ventricular ejection fraction did not significantly increase (P = 0.09) with epinephrine, but increased significantly with amrinone (0.45 to 0.53, P = 0.01), and with the combination (0.43 to 0.55, P = 0.006). These data indicate that amrinone and epinephrine effectively increase myocardial performance during cardiac surgery. Right ventricular function especially was improved with amrinone and the combination of amrinone and epinephrine. The combined effects of amrinone and epinephrine may be useful in patients recovering from the ischemia and reperfusion injury resulting from coronary artery bypass grafting.

Pharmacotherapy Update on the Use of Vasopressors and Inotropes in the Intensive Care Unit

“…14,42,43 Combining milrinone with a direct B1R agonist may additively increase CO in patients with profoundly impaired cardiac function, with an added risk of adverse events. 24,47,48 Dobutamine Versus Milrinone Dobutamine and milrinone produce similar improvements in CO when titrated to full effect in patients with HF, although each individual patient may respond better to one drug or the other. 41,[49][50][51] Dobutamine produces greater stimulation of myocardial contractility, while milrinone produces greater vasodilation and reduction in cardiac filling pressures (Table 2).…”

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“…Two small, randomized controlled trials [5,8] compared epinephrine with the PDI amrinone. In both studies, both drugs significantly increased CI from baseline.…”

Amrinone improves postischemic myocardial metabolism in the rat heart-lung preparation

“…Usually amrinone causes a positive inotropic effect when it is administered to maintain a therapeutic plasma concentration of 1.5-2.0[~g-m1-1 [1][2][3][4]. In ischemia-damaged hearts, 1009g.ml 1 amrinone had an apparent inotropic action, provoking significant increases in cardiac output (11%) and aortic flow (10%) in the isolated working rat heart [20].…”

“…Amrinone may be useful to treat the clinical patients with poor left heart function after cardiopulmonary bypass and patients with heart failure associated with acute myocardial infarction. In previous studies, amrinone was reported to improve cardiac performance in patients undergoing cardiac surgery [1][2][3][4]. In those studies, the effects of amrinone were modified by autonomic sympathetic and parasympathetic reflexes.…”