Modified Glucose‐Insulin‐Potassium Regimen Provides Cardioprotection With Improved Tissue Perfusion in Patients Undergoing Cardiopulmonary Bypass Surgery

BACKGROUND: Laboratory studies demonstrate glucose‐insulin‐potassium (GIK) as a potent cardioprotective intervention, but clinical trials have yielded mixed results, likely because of varying formulas and timing of GIK treatment and different clinical settings. This study sought to evaluate the effects of modified GIK regimen given perioperatively with an insulin‐glucose ratio of 1:3 in patients undergoing cardiopulmonary bypass surgery. METHODS AND RESULTS: In this prospective, randomized, double‐blinded trial with 930 patients referred for cardiac surgery with cardiopulmonary bypass, GIK (200 g/L glucose, 66.7 U/L insulin, and 80 mmol/L KCl) or placebo treatment was administered intravenously at 1 mL/kg per hour 10 minutes before anesthesia and continuously for 12.5 hours. The primary outcome was the incidence of in‐hospital major adverse cardiac events including all‐cause death, low cardiac output syndrome, acute myocardial infarction, cardiac arrest with successful resuscitation, congestive heart failure, and arrhythmia. GIK therapy reduced the incidence of major adverse cardiac events and enhanced cardiac function recovery without increasing perioperative blood glucose compared with the control group. Mechanistically, this treatment resulted in increased glucose uptake and less lactate excretion calculated by the differences between arterial and coronary sinus, and increased phosphorylation of insulin receptor substrate‐1 and protein kinase B in the hearts of GIK‐treated patients. Systemic blood lactate was also reduced in GIK‐treated patients during cardiopulmonary bypass surgery. CONCLUSIONS: A modified GIK regimen administered perioperatively reduces the incidence of in‐hospital major adverse cardiac events in patients undergoing cardiopulmonary bypass surgery. These benefits are likely a result of enhanced systemic tissue perfusion and improved myocardial metabolism via activation of insulin signaling by GIK. CLINICAL TRIAL REGISTRATION: URL: clinicaltrials.gov. Identifier: NCT01516138.