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However, milrinone pharmacokinetics has not been determined for this route of administration. The objective of this study was to investigate inhaled milrinone dosing <jats:italic>in vitro<\/jats:italic> and early plasma concentrations <jats:italic>in vivo<\/jats:italic> after jet and mesh nebulization. Twelve pulmonary hypertensive patients scheduled for cardiac surgery were randomized to receive milrinone (5\u2009mg) by inhalation before CPB using a jet or mesh nebulizer. <jats:italic>In vitro<\/jats:italic> experiments were conducted to determine the inhaled dose delivered with either jet or mesh nebulization. <jats:italic>In vivo<\/jats:italic> experiments involved hemodynamic monitoring and blood samples drawn from patients for the first 15\u2009min after the end of inhalation to determine early plasma concentrations. After mesh nebulization, the mean <jats:italic>in vitro<\/jats:italic> 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; <jats:italic>P<\/jats:italic>\u2009=\u20090.006). Consistent with this, the early plasma concentrations <jats:italic>in vivo<\/jats:italic> were also 2\u20133 fold higher after mesh nebulization (<jats:italic>P<\/jats:italic>\u2009=\u20090.002\u20130.005). After inhalation (jet or mesh nebulization), milrinone early plasma concentrations remained within the therapeutic range. No systemic hypotension was reported in our patients.<\/jats:p>","DOI":"10.1038\/s41598-020-58902-x","type":"journal-article","created":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T11:03:42Z","timestamp":1581073422000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Inhaled milrinone in cardiac surgical patients: a pilot randomized controlled trial of jet vs. mesh nebulization"],"prefix":"10.1038","volume":"10","author":[{"given":"Anne Quynh-Nhu","family":"Nguyen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 Y.","family":"Denault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Th\u00e9oret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis P.","family":"Perrault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"France","family":"Varin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,7]]},"reference":[{"key":"58902_CR1","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/S1053-0770(97)90250-0","volume":"11","author":"LA Doolan","year":"1997","unstructured":"Doolan, L. 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