title: A multicentre randomized-controlled trial of inhaled milrinone in high-risk cardiac surgical patients.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anesthesia, Montreal Heart Institute, Université de Montréal, 5000 Bélanger Street, Montreal, QC, H1T 1C8, Canada. andre.denault@gmail.com.
authors.forename: André Y
authors.initials: AY
authors.lastname: Denault
authors.affiliation: Department of Anesthesiology, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, QC, Canada.
authors.forename: Jean S
authors.initials: JS
authors.lastname: Bussières
authors.affiliation: Department of Anesthesiology, Kingston General Hospital, Queen's University, Kingston, ON, Canada.
authors.forename: Ramiro
authors.initials: R
authors.lastname: Arellano
authors.affiliation: Department of Anesthesiology, Edmonton Heart Institute, University of Alberta, Edmonton, AB, Canada.
authors.forename: Barry
authors.initials: B
authors.lastname: Finegan
authors.affiliation: Faculty of Pharmacy, Université de Montréal, Montreal, QC, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Gavra
authors.affiliation: Department of Cardiology, Stanford Cardiovascular Institute, Stanford, CA, USA.
authors.forename: François
authors.initials: F
authors.lastname: Haddad
authors.affiliation: Faculty of Pharmacy, Université de Montréal, Montreal, QC, Canada.
authors.forename: Anne Q N
authors.initials: AQN
authors.lastname: Nguyen
authors.affiliation: Faculty of Pharmacy, Université de Montréal, Montreal, QC, Canada.
authors.forename: France
authors.initials: F
authors.lastname: Varin
authors.affiliation: Montreal Health Innovations Coordinating Center (MHICC), Montreal, QC, Canada.
authors.forename: Annik
authors.initials: A
authors.lastname: Fortier
authors.affiliation: Montreal Health Innovations Coordinating Center (MHICC), Montreal, QC, Canada.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Levesque
authors.affiliation: Department of Medicine, Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Anesthesia, Montreal Heart Institute, Université de Montréal, 5000 Bélanger Street, Montreal, QC, H1T 1C8, Canada.
authors.forename: Mahsa
authors.initials: M
authors.lastname: Elmi-Sarabi
authors.affiliation: Department of Medicine, Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
authors.affiliation: Department of Cardiac Surgery, Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.
authors.forename: Louis P
authors.initials: LP
authors.lastname: Perrault
authors.affiliation: Department of Social and Preventive Medicine, School of Public Health, Université de Montréal, Montreal, QC, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Lambert
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D002302:Cardiac Output / Q000187:drug effects; D006348:Cardiac Surgical Procedures / Q000379:methods*; D002407:Catheterization, Swan-Ganz; D004311:Double-Blind Method; D017548:Echocardiography, Transesophageal; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000517:prevention & control; D008297:Male; D020105:Milrinone / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016343:Monitoring, Intraoperative; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D014665:Vasodilator Agents; D020105:Milrinone