Milrinone in Advanced Heart Failure: Dose and Therapeutic Monitor Outside Intensive Care Unit

Advanced chronic heart failure (ACHF) patients often require inotropes before transplantation or ventricular assist device implantation. Milrinone, an inotrope and vasodilator, may accumulate in cardiorenal syndrome with serious adverse effects. We investigated the potential for therapeutic drug monitoring of milrinone levels using High Performance Liquid Chromatography Mass Spectrometry (HPLC-MS). 22 ACHF patients (15 males, 49 +/- 9 years) received milrinone 50 mu g/kg intravenously (i.v.) during heart catheterization. Milrinone levels were 216 +/- 71 ng/ml (within the reported therapeutic range: 100-300 ng/ml), followed by improvements in cardiac index, pulmonary artery and wedge pressures (p < 0.005). 18 ACHF patients (17 males, 50 +/- 12 years, 13 had renal dysfunction) received continuous i.v. milrinone (5-26 days) at 0.1-0.2 mu g/kg/min, titrated according to plasma milrinone levels. No adverse events occurred. Therapeutic levels were achieved with doses of 0.2 +/- 0.06 mu g/Kg/min, below those recommended in Summary of Product Characteristics. Milrinone therapy can be noninvasively monitored by HPLC-MS, while avoiding toxicity in ACHF.