title: Hyperinsulinemic Normoglycemia Does Not Meaningfully Improve Myocardial Performance during Cardiac Surgery: A Randomized Trial.
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. The authors extended previous GIK investigations by (1) targeting normoglycemia while administering a GIK infusion (HNC); (2) using improved echocardiographic measures of myocardial deformation, specifically myocardial longitudinal strain and strain rate; and (3) assessing the activation of glucose metabolic pathways.
  
  
  METHODS
  A total of 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). The 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 to 0.5%; P = 0.11). Strain rate was significantly better, but by a clinically unimportant amount: -0.16 s (-0.30 to -0.03 s; P = 0.007). There was no evidence of increased glycolytic, pyruvate oxidation, or hexosamine biosynthetic pathway activation in right atrial samples (HNC, n = 20; standard therapy, 22).
  
  
  CONCLUSIONS
  Administration of glucose and insulin while targeting normoglycemia during aortic valve replacement did not meaningfully improve myocardial function.
authors.affiliation: From the Departments of Cardiothoracic Anesthesia (A.E.D., A.A., S. Sale), Outcomes Research (A.E.D., B.K.K., S. Sarwar, A.S., D.Y., D.I.S.), Molecular Cardiology (O.S.-A., S.C.), Quantitative Health Sciences (D.Y.), Cardiovascular Medicine (J.D.T.), and Cardiac Surgery (M.G.), Cleveland Clinic, Cleveland, Ohio. Current affiliations: Department of Anesthesiology, Northwestern University, Chicago, Illinois (B.K.K.); Department of Family Medicine, Case Medical Center, University Hospitals of Cleveland, Cleveland, Ohio (S.Sarwar); Hepatobiliary Anesthesia, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada (A.S.); Case Western Reserve University, Cleveland, Ohio (S.C.); and Bluhm Cardiovascular Institute, Northwestern Memorial Hospital, Chicago, Illinois (J.D.T.).
authors.forename: Andra E
authors.initials: AE
authors.lastname: Duncan
authors.forename: Babak
authors.initials: B
authors.lastname: Kateby Kashy
authors.forename: Sheryar
authors.initials: S
authors.lastname: Sarwar
authors.forename: Akhil
authors.initials: A
authors.lastname: Singh
authors.forename: Olga
authors.initials: O
authors.lastname: Stenina-Adognravi
authors.forename: Steffen
authors.initials: S
authors.lastname: Christoffersen
authors.forename: Andrej
authors.initials: A
authors.lastname: Alfirevic
authors.forename: Shiva
authors.initials: S
authors.lastname: Sale
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Yang
authors.forename: James D
authors.initials: JD
authors.lastname: Thomas
authors.forename: Marc
authors.initials: M
authors.lastname: Gillinov
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Sessler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001024:Aortic Valve Stenosis / Q000097:blood / Q000188:drug therapy* / Q000601:surgery*; D006348:Cardiac Surgical Procedures / Q000639:trends; D005260:Female; D019918:Heart Valve Prosthesis Implantation / Q000639:trends*; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000188:drug therapy*; D007328:Insulin / Q000008:administration & dosage*; D007430:Intraoperative Care / Q000379:methods / Q000639:trends*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D007328:Insulin