Assessment of long-term therapy with milrinone and the effects of milrinone withdrawal

To assess the long-term efficacy of milrinone in patients with severe congestive heart failure, we obtained hemodynamic measurements (systemic arterial and right heart catheterization) in 13 patients at baseline and after intravenous administration of milrinone. After continuous oral milrinone therapy of 8 ± 4 months duration, repeat hemodynamic study was performed in patients on oral milrinone therapy, after withdrawal of milrinone, and after readministration of milrinone intravenously. Comparison of initial baseline and withdrawal hemodynamic measurements for the group as a whole showed no interval progression of heart failure, as reflected by the pulmonary capillary wedge pressure (27 ± 8 to 24 ± 12 mm Hg, NS) or the cardiac index (2.0 ± 0.4 to 2.1 ± 0.8 liters/min/m², NS). Individual comparisons of milrinone-free hemodynamics revealed that five patients had improved hemodynamically, three patients were unchanged, and five patients had deteriorated, four of whom manifested dependence on milrinone with a progressive hemodynamic decline after milrinone withdrawal which required readministration of milrinone on an emergency basis. Continued efficacy of milrinone was observed on readmission after withdrawal: pulmonary capillary wedge pressure fell from 27 ± 8 to 16 ± 10 mm Hg (p = .001) initially and from 24 ± 12 to 13 ± 11 mm Hg (p = .001) at readministration, while cardiac index rose from 2.0 ± 0.4 to 2.8 ± 0.5 liters/min/m² (p = .001) initially and from 2.1 ± 0.8 to 2.7 ± 0.5 liters/min/m² (p = .005) upon readministration. Long-term therapy with oral milrinone in these patients was not associated with an accelerated rate of progression in underlying heart failure, and there was no evidence of the development of tachyphylaxis to milrinone.