Aortic Stenosis, Aortic Valve Replacement, Cardiac Surgery, Hyperglycemia
Conditions
Keywords
Hyperglycemia, open heart surgery, bypass
Brief summary
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
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).
Interventions
OTHERhyperinsulinemic normoglycemic clamp (HNC)
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.
OTHERcontrol group
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.
Sponsors
National Institutes of Health (NIH)
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 84 Years
Healthy volunteers
No
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.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Myocardial Function: Left Ventricular Global Longitudinal Strain (%) | end of surgery (closure), an average of 5 minutes | 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. |
| Intraoperative Left Ventricular (LV) Global Longitudinal Strain Rate | end of surgery (closure) an average of 5 minutes | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intraoperative Right Ventricular (RV) Systolic Longitudinal Strain | end of surgery (closure) an average of 5 minutes | 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. |
| Intraoperative Right Ventricular (RV) Systolic Longitudinal Strain Rate | end of surgery (closure) an average of 5 minutes | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hyperinsulinemic Normoglycemic Clamp (HNC) Patients will be randomized to receive treatment with HNC during cardiac surgery.
hyperinsulinemic normoglycemic clamp (HNC): 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. | 49 |
| Standard Glucose Management Patients will be randomized to receive treatment with standard glucose management during cardiac surgery.
control group: 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. | 48 |
| Total | 97 |
Baseline characteristics
| Characteristic | Hyperinsulinemic Normoglycemic Clamp (HNC) | Standard Glucose Management | Total |
|---|---|---|---|
| Age, Continuous | 70 years STANDARD_DEVIATION 9 | 70 years STANDARD_DEVIATION 11 | 70 years STANDARD_DEVIATION 10 |
| Sex: Female, Male Female | 13 Participants | 17 Participants | 30 Participants |
| Sex: Female, Male Male | 36 Participants | 31 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 48 |
| other Total, other adverse events | 0 / 49 | 0 / 48 |
| serious Total, serious adverse events | 0 / 49 | 0 / 48 |
Outcome results
Primary
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
Time frame: end of surgery (closure) an average of 5 minutes
Population: some patient's echocardiography were low quality and can not be used
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hyperinsulinemic Normoglycemic Clamp (HNC) | Intraoperative Left Ventricular (LV) Global Longitudinal Strain Rate | -1.1 Percent / sec | Standard Deviation 0.3 |
| Standard Glucose Management | Intraoperative Left Ventricular (LV) Global Longitudinal Strain Rate | -1.0 Percent / sec | Standard Deviation 0.3 |
p-value: 0.00797.5% CI: [-0.3, -0.01]t-test, 2 sided
Primary
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.
Time frame: end of surgery (closure), an average of 5 minutes
Population: some patient's echocardiography were low quality and can not be used
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hyperinsulinemic Normoglycemic Clamp (HNC) | Myocardial Function: Left Ventricular Global Longitudinal Strain (%) | -16.8 percentage of myocardial shortening | Standard Deviation 4.6 |
| Standard Glucose Management | Myocardial Function: Left Ventricular Global Longitudinal Strain (%) | -15.9 percentage of myocardial shortening | Standard Deviation 4.6 |
p-value: 0.1197.5% CI: [-2.87, 0.48]t-test, 2 sided
Secondary
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.
Time frame: end of surgery (closure) an average of 5 minutes
Population: some patient's echocardiography were low quality and can not be used
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hyperinsulinemic Normoglycemic Clamp (HNC) | Intraoperative Right Ventricular (RV) Systolic Longitudinal Strain | -17.2 percentage of myocardial shortening | Standard Deviation 4.3 |
| Standard Glucose Management | Intraoperative Right Ventricular (RV) Systolic Longitudinal Strain | -17.3 percentage of myocardial shortening | Standard Deviation 3.7 |
p-value: 0.5795% CI: [-2.6, 1.5]t-test, 2 sided
Secondary
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
Time frame: end of surgery (closure) an average of 5 minutes
Population: some patient's echocardiography were low quality and can not be used
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hyperinsulinemic Normoglycemic Clamp (HNC) | Intraoperative Right Ventricular (RV) Systolic Longitudinal Strain Rate | -1.1 Percent / sec | Standard Deviation 0.3 |
| Standard Glucose Management | Intraoperative Right Ventricular (RV) Systolic Longitudinal Strain Rate | -1.1 Percent / sec | Standard Deviation 0.4 |
p-value: 0.4595% CI: [-0.2, 0.1]t-test, 2 sided