• Daren K Heyland, Lucy Wibbenmeyer, Jonathan A Pollack, Bruce Friedman, Alexis F Turgeon, Niknam Eshraghi, Marc G Jeschke, Sylvain Bélisle, Daisy Grau, Samuel Mandell, Sai R Velamuri, Gabriel Hundeshagen, Naiem Moiemen, Kayvan Shokrollahi, Kevin Foster, Fredrik Huss, Declan Collins, Alisa Savetamal, Jennifer M Gurney, Nadia Depetris, Christian Stoppe, Luis Ortiz-Reyes, Dominique Garrel, Andrew G Day, and RE-ENERGIZE Trial Team.
• From the Clinical Evaluation Research Unit (D.K.H., L.O.-R.) and the Research Institute (A.G.D.), Kingston Health Sciences Centre, and the Departments of Critical Care Medicine (D.K.H., L.O.R.) and Public Health Sciences (D.K.H.), Queen's University, Kingston, ON, the Division of Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Faculty of Medicine, Université Laval, and the Population Health and Optimal Health Practices Unit (Trauma-Emergency-Critical Care Medicine) and the Canada Research Chair in Critical Care Neurology and Trauma, Centre Hospitalier Universitaire de Québec-Université Laval Research Center, Quebec, QC (A.F.T.), the Department of Surgery, Division of Plastic Surgery, Department of Immunology, and Institute of Medical Science, University of Toronto, Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre, and Sunnybrook Research Institute, Toronto (M.G.J.), and the Departments of Medicine and Anesthesiology (S.B.) and the Department of Nutrition, Faculty of Medicine (D. Garrel), University of Montreal, Montreal - all in Canada; the University of Iowa, Iowa City (L.W.); Mercy Hospital Burn Center, Mercy Hospital, St. Louis (J.A.P.); Joseph M. Still Research Foundation, Augusta, GA (B.F.); Legacy Oregon Burn Center and Oregon Health and Science University, Portland (N.E.); Internal Medicine, Centro Nacional de Quemaduras y Cirugía Reconstructiva, Asunción, Paraguay (D. Grau); UT Southwestern Medical Center, Dallas (S.M.), and Joint Base San Antonio-Fort Sam Houston, San Antonio (J.M.G.) - both in Texas; University of Tennessee Health Science Center and Firefighters Burn Center, Memphis (S.R.V.); the Department of Hand, Plastic, and Reconstructive Surgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Heidelberg (G.H.), and the Department of Anesthesiology, Intensive Care Medicine, and Pain Therapy, University Hospital Würzburg, Würzburg (C.S.) - both in Germany; Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham (N.M.), Mersey Regional Burn Centre, St. Helens and Knowesley NHS Trust, Whiston Hospital, Prescot (K.S.), Manchester Metropolitan University, Manchester (K.S.), and Plastic Surgery and Burns, Chelsea and Westminster Hospital London, London (D.C.) - all in the United Kingdom; Arizona Burn Center Valleywise Health, Maricopa Medical Center, Phoenix (K.F.); the Department of Surgical Sciences, Plastic Surgery, Uppsala University, and the Burn Center, Department of Plastic and Maxillofacial Surgery, Uppsala University Hospital, Uppsala, Sweden (F.H.); Connecticut Burn Center, Yale New Haven Health/Bridgeport Hospital, Bridgeport (A.S.); and Centro Traumatologico Ortopedico, Azienda Ospedaliera Universitaria, Città della Salute e della Scienza di Torino, Turin, Italy (N.D.).
• N. Engl. J. Med. 2022 Sep 15; 387 (11): 1001-1010.

BackgroundGlutamine is thought to have beneficial effects on the metabolic and stress response to severe injury. Clinical trials involving patients with burns and other critically ill patients have shown conflicting results regarding the benefits and risks of glutamine supplementation.MethodsIn a double-blind, randomized, placebo-controlled trial, we assigned patients with deep second- or third-degree burns (affecting ≥10% to ≥20% of total body-surface area, depending on age) within 72 hours after hospital admission to receive 0.5 g per kilogram of body weight per day of enterally delivered glutamine or placebo. Trial agents were given every 4 hours through a feeding tube or three or four times a day by mouth until 7 days after the last skin grafting procedure, discharge from the acute care unit, or 3 months after admission, whichever came first. The primary outcome was the time to discharge alive from the hospital, with data censored at 90 days. We calculated subdistribution hazard ratios for discharge alive, which took into account death as a competing risk.ResultsA total of 1209 patients with severe burns (mean burn size, 33% of total body-surface area) underwent randomization, and 1200 were included in the analysis (596 patients in the glutamine group and 604 in the placebo group). The median time to discharge alive from the hospital was 40 days (interquartile range, 24 to 87) in the glutamine group and 38 days (interquartile range, 22 to 75) in the placebo group (subdistribution hazard ratio for discharge alive, 0.91; 95% confidence interval [CI], 0.80 to 1.04; P = 0.17). Mortality at 6 months was 17.2% in the glutamine group and 16.2% in the placebo group (hazard ratio for death, 1.06; 95% CI, 0.80 to 1.41). No substantial between-group differences in serious adverse events were observed.ConclusionsIn patients with severe burns, supplemental glutamine did not reduce the time to discharge alive from the hospital. (Funded by the U.S. Department of Defense and the Canadian Institutes of Health Research; RE-ENERGIZE ClinicalTrials.gov number, NCT00985205.).Copyright © 2022 Massachusetts Medical Society.

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