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Inhaled milrinone in cardiac surgical patients: a pilot randomized controlled trial of jet vs. mesh nebulization
Anne Quynh-Nhu Nguyen1, André Y Denault2, Yves Théoret3
1Faculty of Pharmacy, Université de Montréal, Montreal, Canada.
Abstract:
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.
Insights
Inhaled milrinone effectively treats pulmonary hypertension during cardiac surgery. Mesh nebulizers deliver a higher dose and achieve greater plasma concentrations than jet nebulizers, remaining within the therapeutic range without causing hypotension.
Area of Science:
- Pharmacology
- Cardiovascular Medicine
- Respiratory Medicine
Background:
- Inhaled milrinone is used to reduce pulmonary hypertension during cardiac surgery.
- The pharmacokinetics of inhaled milrinone are not well-established.
- Understanding dosing and plasma concentrations is crucial for optimizing inhaled milrinone therapy.
Purpose of the Study:
- To compare the in vitro inhaled dose delivered by jet and mesh nebulizers.
- To determine early in vivo plasma concentrations of milrinone after nebulization.
- To assess the safety and therapeutic range of inhaled milrinone in patients undergoing cardiac surgery.
Main Methods:
- In vitro experiments to quantify inhaled drug delivery.
- Randomized trial in 12 pulmonary hypertensive patients undergoing cardiac surgery.
- Administration of 5 mg inhaled milrinone via jet or mesh nebulizer before cardiopulmonary bypass.
- Hemodynamic monitoring and serial blood sampling for 15 minutes post-inhalation.
Main Results:
- Mesh nebulization delivered a significantly higher inhaled dose (46.4%) compared to jet nebulization (16.6%).
- Early plasma concentrations were 2-3 fold higher following mesh nebulization.
- Milrinone plasma levels remained within the therapeutic range, and no systemic hypotension occurred.
Conclusions:
- Mesh nebulization is more efficient for delivering inhaled milrinone than jet nebulization.
- Inhaled milrinone, via either nebulizer type, is safe and achieves therapeutic plasma concentrations in cardiac surgery patients.
- Further pharmacokinetic studies may be warranted to optimize dosing regimens.
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