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Canadian Journal of Anesthesia/Journal canadien d'anesthésie
Published in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie 10/2016

01-10-2016 | Reports of Original Investigations

A multicentre randomized-controlled trial of inhaled milrinone in high-risk cardiac surgical patients

Authors: André Y. Denault, MD, PhD, Jean S. Bussières, MD, Ramiro Arellano, MD, Barry Finegan, MD, Paul Gavra, PhD, François Haddad, MD, Anne Q. N. Nguyen, PhD, France Varin, PhD, Annik Fortier, MSc, Sylvie Levesque, MSc, Yanfen Shi, MD, Mahsa Elmi-Sarabi, MSc, Jean-Claude Tardif, MD, Louis P. Perrault, MD, PhD, Jean Lambert, PhD

Published in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie | Issue 10/2016

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Abstract

Purpose

Inhaled milrinone (iMil) has been used for the treatment of pulmonary hypertension (PH) but its efficacy, safety, and prophylactic effects in facilitating separation from cardiopulmonary bypass (CPB) and preventing right ventricular (RV) dysfunction have not yet been evaluated in a clinical trial. The purpose of this study was to investigate if iMil administered before CPB would be superior to placebo in facilitating separation from CPB.

Methods

High-risk cardiac surgical patients with PH were randomized to receive iMil or placebo after the induction of anesthesia and before CPB. Hemodynamic parameters and RV function were evaluated by means of pulmonary artery catheterization and transesophageal echocardiography. The groups were compared for the primary outcome of the level of difficulty in weaning from CPB. Among the secondary outcomes examined were the reduction in the severity of PH, the incidence of RV failure, and mortality.

Results

Of the 124 patients randomized, the mean (standard deviation [SD]) EuroSCORE II was 8.0 (2.6), and the baseline mean (SD) systolic pulmonary artery pressure (SPAP) was 53 (9) mmHg. The use of iMil was associated with increases in cardiac output (P = 0.03) and a reduction in SPAP (P = 0.04) with no systemic hypotension. Nevertheless, there was no difference in the combined incidence of difficult or complex separation from CPB between the iMil and control groups (30% vs 28%, respectively; absolute difference, 2%; 95% confidence interval [CI], −14 to 18; P = 0.78). There was also no difference in RV failure between the iMil and control groups (15% vs 14%, respectively; difference, 1%; 95% CI, −13 to 12; P = 0.94). Mortality was increased in patients with RV failure vs those without (22% vs 2%, respectively; P < 0.001).

Conclusion

In high-risk cardiac surgery patients with PH, the prophylactic use of iMil was associated with favourable hemodynamic effects that did not translate into improvement of clinically relevant endpoints. This trial was registered at ClinicalTrials.gov; identifier: NCT00819377.
Appendix
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Metadata
Title
A multicentre randomized-controlled trial of inhaled milrinone in high-risk cardiac surgical patients
Authors
André Y. Denault, MD, PhD
Jean S. Bussières, MD
Ramiro Arellano, MD
Barry Finegan, MD
Paul Gavra, PhD
François Haddad, MD
Anne Q. N. Nguyen, PhD
France Varin, PhD
Annik Fortier, MSc
Sylvie Levesque, MSc
Yanfen Shi, MD
Mahsa Elmi-Sarabi, MSc
Jean-Claude Tardif, MD
Louis P. Perrault, MD, PhD
Jean Lambert, PhD
Publication date
01-10-2016
Publisher
Springer US
Published in
Canadian Journal of Anesthesia/Journal canadien d'anesthésie / Issue 10/2016
Print ISSN: 0832-610X
Electronic ISSN: 1496-8975
DOI
https://doi.org/10.1007/s12630-016-0709-8

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