The additive pulmonary vasodilatory effects of inhaled prostacyclin and inhaled milrinone in postcardiac surgical patients with pulmonary hypertension

Selective pulmonary vasodilation is an advantageous therapeutic strategy fo r cardiac surgical patients with increased pulmonary vascular resistance (P VR) and right ventricular failure. We hypothesized that milrinone, an adeno sine-3 ' ,5 ' -cyclic monophosphate (cAMP)-selective phosphodiesterase enzy me (PDE) inhibitor may, when nebulized and inhaled, cause selective pulmona ry vasodilation and potentiate the vasodilation by inhaled prostacyclin (iP GI(2)). Consequently, we investigated the hemodynamic effects of inhaled mi lrinone or the combination iPGI(2) + inhaled milrinone in cardiac surgical patients (MPAP) > 25 mm. Hg and PVR > 200 dynes . s(-1). cm(-5). During mec hanical ventilation and using a conventional nebulizing system, 9 patients inhaled incremental concentrations of milrinone (0.25, 0.5 and 1 mg/mL) in subsequent 10-min periods (Study Part 1). In the same manner, 11 patients r eceived iPGI(2) (10 mug/mL) followed by the combination of iPGI(2) (10 mug/ mL) and inhaled milrinone (1 mg/mL) (Study Part 2). Inhaled milrinone reduc ed PVR with a maximal effect (- 20%, P < 0.001) at the largest concentratio n. As compared with iPGI(2) alone, iPGI(2) + inhaled milrinone caused a fur ther and prolonged reduction of PVR (-8%, P < 0.05) and increased stroke vo lume (+5%, P < 0.05). Systemic vascular resistance or mean arterial pressur e was not affected by inhalation of either drug(s). The authors conclude th at inhalation of the cAMP-selective PDE-inhibitor milrinone selectively dil ates the pulmonary vasculature without systemic effects in cardiac surgical patients with pulmonary hypertension. Furthermore, inhaled milrinone appea rs to potentiate and prolong the pulmonary selective vasodilatory effect of iPGI(2). Inhaled milrinone alone or combined with iPGI(2) may be an import ant therapeutic option in the treatment of patients with pulmonary hyperten sion and right ventricular failure.