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Stress Ulcer Prophylaxis during Invasive Mechanical Ventilation
Deborah Cook1, Adam Deane1, François Lauzier1
1From From the Departments of Medicine (D.C., G.G., W.A., M.M., E.D., J.C.D., J.L.Y.T., B. Rochwerg, T.K.), Health Research Methods, Evidence, and Impact (D.C., N.Z., G.G., D.H.-A., G.R., W.A., M.M., L.H., F.C., J.C.D., B. Rochwerg, F.X., L.T.), and Family Medicine (M.V.), McMaster University, Hamilton, ON, the Department of Medicine, University of British Columbia, Vancouver, BC (B.D.), Population Health and Optimal Health Practice Research Unit, Centre Hospitalier Universitaire de Québec, Université Laval Research Center, Quebec, QC (F. Lauzier), St. Joseph's Healthcare Hamilton Research Institute, Hamilton, ON (D.C., F.C., G.G., L.S., L.T., N.Z.), Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto (J. Marshall, K.B., A. Goffi, M.E.W., R.F., N.K.J.A., S.M.); Queen's University, Kingston, ON (J. Muscedere), the Department of Medicine, Critical Care, University of Ottawa, Ottawa (S.E.), Dalhousie University, Halifax, NS (R.H., O.L.), Niagara Health, St. Catharines, ON (E.D., J.L.Y.T.), Université de Sherbrooke, Sherbrooke, QC (F. Lamontagne, F.D., C.S.A.), Brantford General Hospital, Brantford, ON (B. Reeve), North York General Hospital, Toronto (A. Geagea), the Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB (D.N., K.F.), the University of Manitoba, Winnipeg (G.V.-G., R.Z.), Royal Jubilee Hospital, Victoria, BC (D.O., G.W.), Unity Health Toronto-St. Michael's Hospital, Toronto (K.B., A. Goffi), Vancouver General Hospital, Vancouver, BC (W.H.), Nanaimo Regional General Hospital, Nanaimo, BC (D.F.), the Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto (R.F., N.K.J.A.), Western University, London, ON (I.B., T.M.), William Osler Hospital, Brampton, ON (A.B., S.T.), Mount Sinai Hospital, Toronto (S.M.), Cambridge Memorial Hospital, Cambridge, ON (I.M.), Centre Hospitalier de l'Université de Montréal (E.C.) and Hôpital du Sacré-Coeur de Montréal (E.C., Y.A.C.), University of Montreal (D.W.), Montreal, Université Laval, Quebec, QC (P.A.), the Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton (O.G.R., V.L.), Meakins-Christie Laboratories and Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre (A.S.K.), and the Department of Critical Care, McGill University (A.S.K., K.K.), Montreal, the Ottawa Hospital Research Institute, Ottawa (S. Kanji), the Department of Medicine, University of Saskatchewan, and the Department of Critical Care, Saskatchewan Health Authority, Regina (E.S.), Royal Columbia Hospital, New Westminster, BC (S.R.), Centre Intégré Universitaire de Santé et de Services Sociaux de l'Est-de-l'Île-de-Montréal, Hôpital Maisonneuve-Rosemont, Montreal (F.M.), Université Laval, Faculté de Médecine, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, QC (F. Lellouche), the Department of Medicine, Windsor Regional Hospital, Windsor, ON (A.R.), Grand River Hospital, Kitchener, ON (P.H.), St. Joseph's Hospital, Toronto (R.C.), St. John Regional Hospital, St. John, NB (M.T.) - all in Canada; the University of Melbourne, Melbourne, VIC (A.D.); the George Institute for Global Health, Faculty of Medicine and Health, University of New South Wales (M.H., J. Myburgh, S. Knowles, N.H., B.V., D.R., L.B., S.F.) and St. George Hospital (J. Myburgh), Sydney, Royal Melbourne Hospital, Melbourne, VIC (K.M.B.), and the University of Adelaide, Adelaide, SA (M.C., A.P.) - all in Australia; King Abdullah International Medical Research Center and King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia (Y.M.A.); King's College London (M.O.) and School of Public Health, Faculty of Medicine, Imperial College (S.F.), London; Medical Research Institute of New Zealand, Wellington, New Zealand (P.Y.); the Department of Anesthesia, Critical Care Medicine, and Pain Medicine, Kuwait Extracorporeal Life Support Program, Al-Amiri Hospital, Ministry of Health, Kuwait City, Kuwait (A.A.-F.); Pontifical Catholic University, Belo Horizonte, Brazil (G.R.); the University of Nebraska Medical Center, Omaha (D.J.); the Department of Pulmonary and Critical Care Medicine, Maroof International Hospital, Islamabad, Pakistan (M.I.); and Midwestern University, College of Pharmacy, Glendale, AZ (J.F.B.).
Background:
Whether proton-pump inhibitors are beneficial or harmful for stress ulcer prophylaxis in critically ill patients undergoing invasive ventilation is unclear.
Methods:
In this international, randomized trial, we assigned critically ill adults who were undergoing invasive ventilation to receive intravenous pantoprazole (at a dose of 40 mg daily) or matching placebo. The primary efficacy outcome was clinically important upper gastrointestinal bleeding in the intensive care unit (ICU) at 90 days, and the primary safety outcome was death from any cause at 90 days. Multiplicity-adjusted secondary outcomes included ventilator-associated pneumonia, Clostridioides difficile infection, and patient-important bleeding.
Results:
A total of 4821 patients underwent randomization in 68 ICUs. Clinically important upper gastrointestinal bleeding occurred in 25 of 2385 patients (1.0%) receiving pantoprazole and in 84 of 2377 patients (3.5%) receiving placebo (hazard ratio, 0.30; 95% confidence interval [CI], 0.19 to 0.47; P<0.001). At 90 days, death was reported in 696 of 2390 patients (29.1%) in the pantoprazole group and in 734 of 2379 patients (30.9%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.85 to 1.04; P = 0.25). Patient-important bleeding was reduced with pantoprazole; all other secondary outcomes were similar in the two groups.
Conclusions:
Among patients undergoing invasive ventilation, pantoprazole resulted in a significantly lower risk of clinically important upper gastrointestinal bleeding than placebo, with no significant effect on mortality. (Funded by the Canadian Institutes of Health Research and others; REVISE ClinicalTrials.gov number, NCT03374800.).
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