Pharmacokinetics of milrinone in patients with congestive heart failure during continuous venovenous hemofiltration

Abstract

To evaluate the pharmocokinetics of intravenous milrinone in patients with severe congestive heart failure during continuous venovenous hemofiltration (CVVH). Prospective study of patients with congestive heart failure admitted to the intensive care unit (ICU). ICU between September 1997 and August 1999. Six patients with severe congestive heart failure during CVVH: all patients received a continuous infusion of milrinone of 0.25 microg x kg(-1) min(-1). The hemodynamics and plasma concentration of milrinone were measured before and after the infusion. Pharmacokinetics were analyzed with one-compartment model featuring constant rate infusion. The steady-state concentration (Css) was 845 +/- 135 (mean +/- SD) ng/ml, and the half-life time (t1/2) was 20.1 +/- 3.3 h. Cardiac index and stroke volume index after the infusion of milrinone increased significantly compared with pre-infusion levels. Other hemodynamic parameters did not change significantly. All patients died within 1 month after the injection of milrinone because of severe forms of arrhythmia, such as ventricular tachycardia and ventricular fibrillation. We found that the mean Css and the mean t1/2 of milrinone in subjects during CVVH were much higher and longer than those previously reported for subjects with normal renal function. It is therefore essential to adjust the dose or modify the dosing interval of milrinone during renal replacement therapy for patients with severe congestive heart failure. However, further studies are needed to determine the details of pharmacokinetics of milrinone and therapeutic procedures for patients with severe heart failure during CVVH.