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Inhaled milrinone administered before cardiopulmonary bypass (CPB) reduces the severity of pulmonary hypertension during cardiac surgery. However, milrinone pharmacokinetics has not been determined for this route of administration. The objective of this study was to investigate inhaled milrinone dosing  in vitro  and early plasma concentrations  in vivo  after jet and mesh nebulization. Twelve pulmonary hypertensive patients scheduled for cardiac surgery were randomized to receive milrinone (5 mg) by inhalation before CPB using a jet or mesh nebulizer.  In vitro  experiments were conducted to determine the inhaled dose delivered with either jet or mesh nebulization.  In vivo  experiments involved hemodynamic monitoring and blood samples drawn from patients for the first 15 min after the end of inhalation to determine early plasma concentrations. After mesh nebulization, the mean  in vitro  inhaled dose was almost 3-fold higher compared to jet nebulization (46.4% vs 16.6% for mesh and jet, respectively; mean difference, 29.8%; 95% CI, 14.1 to 45.5;  P  = 0.006). Consistent with this, the early plasma concentrations  in vivo  were also 2–3 fold higher after mesh nebulization ( P  = 0.002–0.005). After inhalation (jet or mesh nebulization), milrinone early plasma concentrations remained within the therapeutic range. No systemic hypotension was reported in our patients.

Inhaled milrinone in cardiac surgical patients: a pilot randomized controlled trial of jet vs. mesh nebulization