André Y Denault1, Jean S Bussières2, Ramiro Arellano3, Barry Finegan4, Paul Gavra5, François Haddad6, Anne Q N Nguyen5, France Varin5, Annik Fortier7, Sylvie Levesque7, Yanfen Shi8, Mahsa Elmi-Sarabi9, Jean-Claude Tardif8, Louis P Perrault10, Jean Lambert11. 1. Department of Anesthesia, Montreal Heart Institute, Université de Montréal, 5000 Bélanger Street, Montreal, QC, H1T 1C8, Canada. andre.denault@gmail.com. 2. Department of Anesthesiology, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, QC, Canada. 3. Department of Anesthesiology, Kingston General Hospital, Queen's University, Kingston, ON, Canada. 4. Department of Anesthesiology, Edmonton Heart Institute, University of Alberta, Edmonton, AB, Canada. 5. Faculty of Pharmacy, Université de Montréal, Montreal, QC, Canada. 6. Department of Cardiology, Stanford Cardiovascular Institute, Stanford, CA, USA. 7. Montreal Health Innovations Coordinating Center (MHICC), Montreal, QC, Canada. 8. Department of Medicine, Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada. 9. Department of Anesthesia, Montreal Heart Institute, Université de Montréal, 5000 Bélanger Street, Montreal, QC, H1T 1C8, Canada. 10. Department of Cardiac Surgery, Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada. 11. Department of Social and Preventive Medicine, School of Public Health, Université de Montréal, Montreal, QC, Canada.
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.
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.
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