Tolerability of extended duration intravenous milrinone in patients hospitalized for advanced heart failure and the usefulness of uptitration of oralangiotensin-converting enzyme inhibitors

Milrinone is a phosphodiesterase inhibitor that has been shown to improve h emodynamic parameters in patients with class III to IV heart failure when a dministered intravenously for less than or equal to 48 hours. This study ex amines the tolerability of long-term intravenous milrinone therapy and asse sses its utility in allowing upward titration of oral vasodilator agents. A retrospective review of hospital records identified 63 patients who underw ent hemodynamic monitoring and received intravenous milrinone for >24 hours in a critical care setting. Hemodynamics and medications were recorded bef ore and after 24 hours of milrinone therapy. Additional medications, as wel l as any adverse events, were recorded throughout milrinone therapy. The me an dose of milrinone was 0.43 +/- 0.10 mu g/kg/min, with a mean duration of 12 +/- 15 days (range 1 to 70). Therapy was continued for >48 hours in 89% of patients, After 24 hours of milrinone therapy, patients exhibited signi ficant improvements in pulmonary artery pressures, pulmonary capillary wedg e pressures, and cardiac index. When compared with baseline, significantly more patients received angiotensin-converting enzyme (ACE) inhibitors after 24 hours of:milrinone and at the end of milrinone therapy (67% vs 86%, p < 0.01). Likewise, significantly more patients also received oral hydralazine and/or nitrates at the end of milrinone therapy (38% vs 65%, p <0.01) when compared with baseline. The mean doses of most oral medications at the 3 t ime periods were similar. The ACE inhibitor dose was significantly higher a t the end of milrinone therapy when compared with baseline, and hydralazine dose was significantly higher at the end of therapy when compared with 24 hours. Few adverse effects were noted, with only 10% of patients experienci ng symptomatic ventricular tachycardia and 2 patients with significant hypo tension requiring discontinuation of the drug. The adverse events were simi lar in the group of patients who received milrinone For greater than or equ al to 7 days compared with the entire cohort. Milrinone was well tolerated over the long term in a controlled inpatient setting, and allowed uptitrati on of oral vasodilator therapy. (C) 1999 by Excerpta Medica, Inc.