Hyperinsulinemic Normoglycemia Does Not Meaningfully Improve Myocardial Performance during Cardiac Surgery

Abstract

Background Glucose-insulin-potassium (GIK) administration during cardiac surgery inconsistently improves myocardial function, perhaps because hyperglycemia negates the beneficial effects of GIK. The hyperinsulinemic normoglycemic clamp (HNC) technique may better enhance the myocardial benefits of GIK. We extended previous GIK investigations by: 1) targeting normoglycemia while administering a glucose-insulin-potassium infusion (HNC); 2) using improved echocardiographic measures of myocardial deformation, specifically myocardial longitudinal strain and strain rate; and, 3) assessing activation of glucose metabolic pathways. Methods 100 patients having aortic valve replacement for aortic stenosis were randomly assigned to HNC (high-dose insulin with concomitant glucose infusion titrated to normoglycemia) versus standard therapy (insulin treatment if glucose >150 mg/dL). Our primary outcomes were left ventricular longitudinal strain and strain rate, assessed using speckle-tracking echocardiography. Right atrial tissue was analyzed for activation of glycolysis/pyruvate oxidation and alternative metabolic pathways. Results Time-weighted mean glucose concentrations were lower with HNC (127±19 mg/dL) than standard care (177±41 mg/dL; P<0.001). Echocardiographic data were adequate in 72 patients for strain analysis and 67 patients for strain rate analysis. HNC did not improve myocardial strain, with an HNC minus standard therapy difference of −1.2 (97.5%CI: −2.9, 0.5)%; P=0.11. Strain rate was significantly better, but by a clinically unimportant amount: −0.16 (−0.30, −0.03) sec−1, P = 0.007. There was no evidence of increased glycolytic, pyruvate oxidation, or hexosamine biosynthetic pathway activation in right atrial samples (n = 20, HNC; 22, standard therapy). Conclusions Administration of glucose and insulin while targeting normoglycemia during aortic valve replacement did not meaningfully improve myocardial function.

Early Left and Right Ventricular Response to Aortic Valve Replacement

“…27 Briefly, patients who were considered to be at increased risk for myocardial injury induced by cardioplegic arrest (patients with aortic stenosis and LV hypertrophy) 28,29 were randomized to intraoperative glucose control using standard glucose control (insulin treatment for blood glucose >150 mg/dL) versus hyperinsulinemic normoglycemia. Hyperinsulinemic normoglycemia involves a high-dose insulin infusion at a fixed rate (5 mU/kg/min) with a concomitant variable glucose (dextrose 20%) infusion supplemented with potassium (40 mEq/L) and phosphate (30 mmol/L), titrated to a target glucose concentration of 80 – 110 mg/dL.…”

“…Hyperinsulinemic normoglycemia involves a high-dose insulin infusion at a fixed rate (5 mU/kg/min) with a concomitant variable glucose (dextrose 20%) infusion supplemented with potassium (40 mEq/L) and phosphate (30 mmol/L), titrated to a target glucose concentration of 80 – 110 mg/dL. 27 Because the primary results did not find a meaningful difference in myocardial function between groups (minimal change in LV strain rate which was statistically significant [−0.16 (−0.30, −0.03) sec −1 , P = 0.007], but not clinically meaningful, and no difference in LV strain, RV strain or strain rate), 27 the study groups were combined for this supplementary analysis to assess change in LV and RV myocardial deformation during AVR surgery.…”

“…27 Epinephrine was administered for low cardiac index (< 2.0 L·min −1 ·m −2 ) and/or norepinephrine was given for low systemic vascular resistance (<700 dyn·sec·cm −5 ) following separation from CPB to maintain mean arterial blood pressures higher than 80 mmHg and cardiac index greater than 2.0 L·min −1 ·m −2 .…”

“…27 Briefly, Vivid S6 or Vivid E9 Ultrasound systems (GE Healthcare Vingmed Ultrasound AS, Horten, Norway) with a multiplane phased array GE 6Tc-RS 2.9–8.0 MHz transducer or an active matrix 4D volume phased array 3.0–8.0 MHz transducer were used to collect echocardiographic data for off-line analysis using dedicated analysis software (EchoPAC v.112, GE Healthcare Vingmed Ultrasound AS, Horten, Norway).…”

Experience using high-dose glucose-insulin-potassium (GIK) in critically ill patients

“…GIK has been studied in acute myocardial infarction [11,36,37] and cardiac surgery [38][39][40], albeit with variable results and thus no overall benefit [41]. Possible reasons include use of different doses of insulin, failure to maintain normoglycaemia, and introduction after thrombolysis where high blood sugar levels may have enhanced the degree of reperfusion injury.…”