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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

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

Conditions
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Hyperglycemia, Aortic Valve Replacement, Aortic Stenosis, Cardiac Surgery

Intervention / Treatment
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* Other: hyperinsulinemic normoglycemic clamp (HNC)
* Other: control group


Participation Criteria
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Eligibility Criteria
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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.)

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 84 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: hyperinsulinemic normoglycemic clamp (HNC)<br>Patients will be randomized to receive treatment with HNC during cardiac surgery. | Other: hyperinsulinemic normoglycemic clamp (HNC)<br>* 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.<br>|
| Placebo Comparator: standard glucose management<br>Patients will be randomized to receive treatment with standard glucose management during cardiac surgery. | Other: control group<br>* 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.<br>* Other names: standard of care;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial Function: Left Ventricular Global Longitudinal Strain (%) | 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. | end of surgery (closure), an average of 5 minutes | 
| Intraoperative Left Ventricular (LV) Global Longitudinal Strain Rate | 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 | end of surgery (closure) an average of 5 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraoperative Right Ventricular (RV) Systolic Longitudinal Strain | 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. | end of surgery (closure) an average of 5 minutes | 
| Intraoperative Right Ventricular (RV) Systolic Longitudinal Strain Rate | 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 | end of surgery (closure) an average of 5 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperglycemia, open heart surgery, bypass