The Effect of the Hyperinsulinemic Normoglycemic Clamp on Myocardial Function and Utilization of Glucose

The Effect of the Hyperinsulinemic Normoglycemic Clamp on Myocardial Function and Utilization of Glucose

The Effect of the Hyperinsulinemic Normoglycemic Clamp on Myocardial Function and Utilization of Glucose

The overall research plan is to test the hypothesis that intraoperative treatment of hyperinsulinemic normoglycemic clamp (HNC) in cardiac surgical patients improves myocardial function and short-term outcomes compared with standard glucose management.

Specific Aim #1:To determine whether intraoperative use of HNC affords cardioprotective benefits measured by improved echocardiographic measures of myocardial function, serum markers of cardiomyocyte injury, and hemodynamic indices measured immediately (at end of surgery) and during the short-term (initial hospitalization).

Patients will be randomized to receive treatment with standard glucose management during cardiac surgery.

Prior to anesthetic induction, a baseline blood glucose value will be obtained, followed by an insulin infusion of 5 mU.Kg-1.min-1. When blood glucose is <110 mg/dL, a variable continuous infusion of glucose (dextrose 20%) supplemented with potassium (40 mEq/L) and phosphate (30 mmol/L) is administered to preserve normoglycemia (80-110 mg/dL). The glucose infusion is titrated to target glucose levels by checking blood glucose every 5 - 15 min with Accu-Check (Roche Diagnostics, Switzerland) glucose monitor. At sternal closure, insulin infusion is decreased to 1 mU/Kg/min. On admission to the ICU, insulin treatment follows the ICU protocol. The dextrose infusion is slowly weaned off over 2 - 4 hrs maintaining blood glucose > 80 mg/dL. Arterial blood glucose is measured every 30 - 60 min for 2 hrs, then, as stated in ICU protocol.

Baseline arterial blood glucose will be obtained before anesthetic induction. Repeat measurements are performed every 30-90 min. Glucose >150 on CPB will receive insulin according to intraoperative protocol. After surgery, insulin is given according to ICU protocol. Target glucose < 180 mg/dL.

Left ventricular global longitudinal strain measured by intraoperative transesophageal echocardiography at end of surgery and assessed using off-line speckle-tracking echocardiography. higher values (%) mean a worse outcome.

Left ventricular global longitudinal strain rate measured by intraoperative transesophageal echocardiography at end of surgery and assessed using off-line speckle-tracking echocardiography. higher values mean a worse outcome

Right ventricular global longitudinal strain measured by intraoperative transesophageal echocardiography at end of surgery and assessed using off-line speckle-tracking echocardiography. higher values mean a worse outcome.

Right ventricular global longitudinal strain rate measured by intraoperative transesophageal echocardiography at end of surgery and assessed using off-line speckle-tracking echocardiography. higher values mean a worse outcome

Inclusion Criteria: Age 40 - 84 years old, Aortic stenosis, Scheduled for Aortic valve replacement. Exclusion Criteria: Poor quality echocardiographic images unsuitable for analysis Off -pump surgical procedure Anticipated deep hypothermic circulatory arrest Any contraindications to transesophageal echocardiogram (TEE) or other proposed intervention Unable to give written informed consent (non-English speaking, vulnerable patients, etc.)

Zhang K, Kumar N, Alfirevic A, Sale S, You J, Bauer A, Duncan AE. Left Ventricular Twist Mechanics Before and After Aortic Valve Replacement: A Feasibility Study and Exploratory Analysis. Semin Cardiothorac Vasc Anesth. 2022 Sep;26(3):226-236. doi: 10.1177/10892532221114791. Epub 2022 Jul 18.

Zhang K, Sheu R, Zimmerman NM, Alfirevic A, Sale S, Gillinov AM, Duncan AE. A Comparison of Global Longitudinal, Circumferential, and Radial Strain to Predict Outcomes After Cardiac Surgery. J Cardiothorac Vasc Anesth. 2019 May;33(5):1315-1322. doi: 10.1053/j.jvca.2018.10.031. Epub 2018 Oct 24.

Sonny A, Alfirevic A, Sale S, Zimmerman NM, You J, Gillinov AM, Sessler DI, Duncan AE. Reduced Left Ventricular Global Longitudinal Strain Predicts Prolonged Hospitalization: A Cohort Analysis of Patients Having Aortic Valve Replacement Surgery. Anesth Analg. 2018 May;126(5):1484-1493. doi: 10.1213/ANE.0000000000002684.

Duncan AE, Sarwar S, Kateby Kashy B, Sonny A, Sale S, Alfirevic A, Yang D, Thomas JD, Gillinov M, Sessler DI. Early Left and Right Ventricular Response to Aortic Valve Replacement. Anesth Analg. 2017 Feb;124(2):406-418. doi: 10.1213/ANE.0000000000001108.