Perioperative Medicine  |   June 2018
Hyperinsulinemic Normoglycemia during Cardiac Surgery Reduces a Composite of 30-day Mortality and Serious In-hospital Complications: A Randomized Clinical Trial
Author Notes
  • 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.), and Thoracic and Cardiovascular Surgery (A.M.G.), Cleveland Clinic, Cleveland, Ohio; and 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.); and the Department of Anesthesiology, University of Cincinnati, Cincinnati, Ohio (H.C.).
  • The primary results of this investigation (the composite outcome of mortality and serious morbidity) have not been previously presented or published. Subinvestigations that were unrelated to the primary outcome have been presented at American Society of Anesthesiologists meetings in October 2008 (Chowdary et al., The influence of diabetes on intraoperative glucose control), in October 2008 (Said et al., Comparison of within-patient glucose variability measures), and in October 2009 (Abd-Elsayed et al., The effect of diabetes on intraoperative glycemic variability).
    The primary results of this investigation (the composite outcome of mortality and serious morbidity) have not been previously presented or published. Subinvestigations that were unrelated to the primary outcome have been presented at American Society of Anesthesiologists meetings in October 2008 (Chowdary et al., The influence of diabetes on intraoperative glucose control), in October 2008 (Said et al., Comparison of within-patient glucose variability measures), and in October 2009 (Abd-Elsayed et al., The effect of diabetes on intraoperative glycemic variability).×
  • Submitted for publication September 18, 2017. Accepted for publication February 1, 2018.
    Submitted for publication September 18, 2017. Accepted for publication February 1, 2018.×
  • Address correspondence to Dr. Duncan: Departments of Cardiothoracic Anesthesia and Outcomes Research, Anesthesiology Institute, Cleveland Clinic, 9500 Euclid Ave – J4, Cleveland, Ohio 44195. duncana@ccf.org. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Perioperative Medicine / Clinical Science / Cardiovascular Anesthesia
Perioperative Medicine   |   June 2018
Hyperinsulinemic Normoglycemia during Cardiac Surgery Reduces a Composite of 30-day Mortality and Serious In-hospital Complications: A Randomized Clinical Trial
Anesthesiology 6 2018, Vol.128, 1125-1139. doi:10.1097/ALN.0000000000002156
Anesthesiology 6 2018, Vol.128, 1125-1139. doi:10.1097/ALN.0000000000002156
Abstract

Background: Hyperinsulinemic normoglycemia augments myocardial glucose uptake and utilization. We tested the hypothesis that hyperinsulinemic normoglycemia reduces 30-day mortality and morbidity after cardiac surgery.

Methods: This 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–1; or (2) standard glycemic management, low-dose insulin infusion targeting glucose greater than 150 mg · dl–1. 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.

Results: At 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–1 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–1) occurred in 6 (0.9%) patients.

Conclusions: Intraoperative hyperinsulinemic normoglycemia reduced mortality and morbidity after cardiac surgery. Providing exogenous glucose while targeting normoglycemia may be preferable to simply normalizing glucose concentrations.