Pharmacodynamic effects of milrinone with and without a bolus loading infusion

Milrinone is a positive inotropic agent with vasodilatory and lusitropic activity. Milrinone dosed as a 50 microg/kg bolus followed by a continuous infusion provides an immediate and sustained hemodynamic response. The comparative pharmacodynamics of a placebo bolus and a milrinone bolus followed by a continuous milrinone infusion in patients with decompensated heart failure are unknown.

Nineteen patients with decompensated heart failure underwent right heart catheterization and were randomized to receive an intravenous infusion of milrinone at a rate of 0.50 microg/kg/min with (n = 9) or without (n = 10) a preceding 50 microg/kg bolus. Pulmonary capillary wedge pressure, cardiac index, and plasma milrinone levels were measured serially over 24 hours.

In the milrinone bolus group, maximal effects on plasma concentration (352.3 ng/mL), cardiac index (+0.97 L/min/m(2), P =.02), and pulmonary capillary wedge pressure (-11.25 mm Hg, P <.001) were seen after the loading dose. In the placebo loading dose group, significant hemodynamic effects were observed starting at 30 minutes after the start of the continuous infusion. Changes in pulmonary capillary wedge pressure (placebo -8.6 vs milrinone -8.78 mm Hg, P not significant [NS]) were similar in both groups at 2 hours, whereas changes in cardiac index (placebo loading +0.81 vs milrinone loading +0.78 L/min/m(2), P NS) and milrinone levels (placebo loading 168.0 vs milrinone loading 165.6 ng/mL, P NS) were similar at 3 hours. One patient randomized to a milrinone bolus demonstrated a marked decrease in blood pressure and was discontinued from therapy.

A milrinone infusion without a bolus appears to be a rapidly effective inotropic strategy that may have an improved safety profile during the initiation of therapy compared with a continuous infusion strategy initiated with a bolus.