• Andra E Duncan, Daniel I Sessler, Hiroaki Sato, Tamaki Sato, Keisuke Nakazawa, George Carvalho, Roupen Hatzakorzian, Takumi Codere-Maruyama, Alaa Abd-Elsayed, Somnath Bose, Tamer Said, Maria Mendoza-Cuartas, Hyndhavi Chowdary, Edward J Mascha, Dongsheng Yang, A Marc Gillinov, and Thomas Schricker.
• From the Departments of Cardiothoracic Anesthesia (A.E.D.) Outcomes Research (A.E.D., D.I.S., A.A.-E., S.B., T. Said, M.M.-C., H.C., E.J.M., D.Y.) Quantitative Health Sciences (E.J.M., D.Y.) Thoracic and Cardiovascular Surgery (A.M.G.), Cleveland Clinic, Cleveland, Ohio the Department of Anesthesia, Royal Victoria Hospital, McGill University, Montreal, Canada (H.S., T. Sato, K.N., G.C., R.H., T.C.-M., T. Schricker) Current positions: Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (A.A.-E.) Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center, Boston, Massachusetts (S.B.) Departments of Family Medicine and Geriatric Medicine, Metro Health Medical Center, Cleveland, Ohio (T. Said) Southern Arizona Anesthesia, Tucson, Arizona (M.M.-C.) the Department of Anesthesiology, University of Cincinnati, Cincinnati, Ohio (H.C.).
• Anesthesiology. 2018 Jun 1; 128 (6): 1125-1139.

BackgroundHyperinsulinemic normoglycemia augments myocardial glucose uptake and utilization. We tested the hypothesis that hyperinsulinemic normoglycemia reduces 30-day mortality and morbidity after cardiac surgery.MethodsThis dual-center, parallel-group, superiority trial randomized cardiac surgical patients between August 2007 and March 2015 at the Cleveland Clinic, Cleveland, Ohio, and Royal Victoria Hospital, Montreal, Canada, to intraoperative glycemic management with (1) hyperinsulinemic normoglycemia, a fixed high-dose insulin and concomitant variable glucose infusion titrated to glucose concentrations of 80 to 110 mg · dl; or (2) standard glycemic management, low-dose insulin infusion targeting glucose greater than 150 mg · dl. The primary outcome was a composite of 30-day mortality, mechanical circulatory support, infection, renal or neurologic morbidity. Interim analyses were planned at each 12.5% enrollment of a maximum 2,790 patients.ResultsAt the third interim analysis (n = 1,439; hyperinsulinemic normoglycemia, 709, standard glycemic management, 730; 52% of planned maximum), the efficacy boundary was crossed and study stopped per protocol. Time-weighted average glucose concentration (means ± SDs) with hyperinsulinemic normoglycemia was 108 ± 20 versus 150 ± 33 mg · dl with standard glycemic management, P < 0.001. At least one component of the composite outcome occurred in 49 (6.9%) patients receiving hyperinsulinemic normoglycemia versus 82 (11.2%) receiving standard glucose management (P < efficacy boundary 0.0085); estimated relative risk (95% interim-adjusted CI) 0.62 (0.39 to 0.97), P = 0.0043. There was a treatment-by-site interaction (P = 0.063); relative risk for the composite outcome was 0.49 (0.26 to 0.91, P = 0.0007, n = 921) at Royal Victoria Hospital, but 0.96 (0.41 to 2.24, P = 0.89, n = 518) at the Cleveland Clinic. Severe hypoglycemia (less than 40 mg · dl) occurred in 6 (0.9%) patients.ConclusionsIntraoperative hyperinsulinemic normoglycemia reduced mortality and morbidity after cardiac surgery. Providing exogenous glucose while targeting normoglycemia may be preferable to simply normalizing glucose concentrations.

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