Remifentanil and Glycemic Response in Cardiac Surgery

Phase 4

Completed

Conditions: Hyperglycemia
Heart Diseases

Interventions: Drug: Remifentanil
Drug: Fentanyl

Registration Number: NCT02349152

Lead Sponsor: Kathirvel Subramaniam

Brief Summary: This study evaluates the effect of using remifentanil during cardiopulmonary bypass surgery to supress the hyperglycemic response in perioperative period. Half of the participants will receive continuous intravenous remifentanil during surgery, while the other half will receive intermittent intravenous fentanyl during surgery. Intermittent intravenous fentanyl administration is this institution's standard of care.

Detailed Description: Stress-induced hyperglycemia is a well-known phenomena that occurs during cardiopulmonary bypass surgery. Hyperglycemia increases the incidence of major adverse events and mortality in patients undergoing cardiac surgery.

Remifentanil, an ultra-short acting opioid analgesic, has been shown to reduce the stress response to cardiopulmonary bypass when compared to intermittent fentanyl and inhalation anesthesia. This in turn, will reduce the occurence of perioperative hyperglycemia, glycemic variability and insulin requirements in patients undergoing cardiac surgery.

NOTE;

Primary Outcome changed on 06/15/2015-Change Approved by University of Pittsburgh IRB on 06/22/2015- First patient enrolled January 2016.

Primary outcome measure; Percentage of patients with two or more than two intraoperative blood glucose levels more than 180 mg% in both groups will be estimated and the difference in this parameter between the two groups will form the primary outcome measure of this study.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 116

Inclusion Criteria

Open cardiac surgery through sternotomy approach (coronary artery bypass, valve surgery, and any other open heart surgeries)
Surgery with use of cardiopulmonary bypass
Patients over 18 years of age
Both female and male genders
All races

Exclusion Criteria

Minimally invasive heart surgery through thoracotomy approach
Patients receiving regional analgesia such as intrathecal morphine
Patients undergoing procedures under deep hypothermic circulatory arrest
Patients with active infections such as acute infective endocarditis
Emergency surgery
Patients undergoing transplantations and ventricular assist device insertion
Patients on any mechanical circulatory support preoperatively
Patient's refusal
Allergy to remifentanil
Positive pregnancy test
Morbid obesity
End stage liver and kidney disease

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Remifentanil group	Remifentanil	Half of subjects enrolled will be randomized to the remifentanil group
Fentanyl group	Fentanyl	Half of subjects enrolled will be randomized to the fentanyl group

Primary Outcome Measures

Name	Time	Method
Blood Glucose Values (More Than One ) > 180 mg%	Intraoperative period	Percentage of patients with two or more intraoperative blood glucose levels greater than 180 mg/dl. Percentage in both groups will be estimated, then the difference in this statistic will form the primary outcome measure of this study. (Primary Outcome changed on 06/15/2015-Change Approved by University of Pittsburgh IRB on 06/22/2015- First patient enrolled January 2016)

Secondary Outcome Measures

Name	Time	Method
Number of Blood Glucose Values > 180 mg%	Intraoperative period, Induction to end of surgery	Blood glucose values that exceed 180 mg% will be counted
Mean, Peak and Trough Intraoperative Blood Glucose (mg/dl)	Intraoperative period; Induction to end of surgery	Blood glucose measured every hour
Total Postoperative Regular Insulin	From ICU Admission (After Surgery) Until 24 hours postoperatively	Total units of regular insulin required post-operatively
Glycemic Variability	From the start of induction till 24 hours postoperatively	Coefficient of variation in blood glucose levels. Denotes how large the fluctuations in blood glucose are. Higher numbers indicate increased variation.
Emergence From Anesthesia	Immediate postoperative period until 30 days post-operatively	Time to extubation after completion of surgery in the operating room and intensive care unit
Intraoperative Pre-cardiopulmonary Bypass Hemodynamic Stability	induction of anesthesia till systemic heparinization before cardiopulmonary bypass	Blood pressure (systolic, diastolic and mean), Heart rate every 5 minutes from induction of anesthesia till systemic heparinization before cardiopulmonary bypass
Wound Hyperalgesia	96 hours postoperatively	Von frey hair objective testing
Development of Chronic Pain	1, 3, 6 and 12 months after discharge from the hospital	Telephonic call Numeric pain scale; Scale is 0-10, with 10 being the highest pain.
Stress Hormone Levels-Cortisol (µg/dl)	Perioperative period (Intraoperatively and 8 hours postoperatively)	Serum cortisol levels (measured as µg/dl) taken at: Prebypass, cardiopulmonary bypass (2 samples: at start of bypass and end of bypass), postbypass, ICU 8 hours postoperative period
Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml)	Perioperative period (Intraoperatively and 8 hours postoperatively)	Inflammatory mediator levels, Interleukin-1b (IL-1b), Interleukin 6 (IL-6) and Tumor Necrosis Factor Alpha (TNFa) (all measured in pg/ml) taken at: Prebypass, cardiopulmonary bypass (2 samples:30 min start of bypass (CPB-30) and end of bypass (CPB-END), postbypass, ICU 8 hours postoperative period
Society of Thoracic Surgery Patient Outcomes	30 day outcomes	Postoperative outcomes collected from the Society of Thoracic Surgery (STS) database. 30 day Mortality (outcome 1) and 30 day Readmission (outcome 2) cerebral vascular accident(outcome 3), prolonged mechanical ventilation (outcome 4), renal failure (outcome 5), atrial fibrillation (outcome 6), cardiac arrest (outcome 7)
Postoperative Blood Glucose	From ICU Admission (After Surgery) Until 24 hours postoperatively	Mean and peak blood glucose levels postoperatively
Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml)	Perioperative period (Intraoperatively and 8 hours postoperatively)	Adreno-corticotrophic hormone (ACTH), Growth Hormone (GH) and Glucagon (measured as pg/ml) taken at: Prebypass, cardiopulmonary bypass (2 samples: 30 mins after start of bypass (CPB 30) and end of bypass (CPB END), post-bypass and ICU 8 hours postoperative period
Postoperative Pain	Every day 6 hour for 48 hours postoperative period	Pain scores; Every day 6 hour for 48 hours postoperative period
Insulin Requirement	Intraoperative period; Induction to end of surgery	Average dose of insulin (Units/ml) calculated for each group in the intraoperative period