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Randomized Controlled Trial
. 2020 Feb 7;10(1):2069.
doi: 10.1038/s41598-020-58902-x.

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

Anne Quynh-Nhu Nguyen  1 , André Y Denault  2 , Yves Théoret  3 , Louis P Perrault  4 , France Varin  5
Affiliations
Randomized Controlled Trial

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

Anne Quynh-Nhu Nguyen et al. Sci Rep. .

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Milrinone plasma concentration-time profiles for 12 cardiac surgical patients after limited sampling (n = 4) following the administration of a 5 mg dose using jet or mesh nebulization.
Figure 2
Figure 2
Jet nebulizer (Airlife Misty Max 10 Nebulizer; Salter Labs, Arvin, CA, USA). (A) Mesh nebulizer (Aeroneb Professional Nebulizer System; Aerogen Ltd., Galway, Ireland) (B).
Figure 3
Figure 3
In vitro settings for estimation of milrinone dose recovery (mesh nebulizer displayed). Setting 1 (A) was used to determine the emitted dose (filter A). Setting 2 (B) was used to determine the inhaled dose (filter B) and exhaled dose (filter C). The residual dose (nebulizer cup) and wasted dose (nebulizer T-piece) were also measured.
See this image and copyright information in PMC

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