Clinical trial NCT02349152: Remifentanil and Glycemic Response in Cardiac Surgery
Official title: The Effect of Intraoperative Continuous Remifentanil Infusion on Glycemic Response and Variability in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass: A Prospective, Randomized, Open Label Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Diseases
Hyperglycemia
Keywords: Cardiopulmonary bypass
Heart surgery
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Mylan Inc.
First posted: 2015-01-28
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Blood Glucose Values (More Than One ) > 180 mg%
timeFrame: Intraoperative period
Secondary outcomes:
measure: Insulin Requirement
timeFrame: Intraoperative period; Induction to end of surgery
measure: Number of Blood Glucose Values > 180 mg%
timeFrame: Intraoperative period, Induction to end of surgery
measure: Mean, Peak and Trough Intraoperative Blood Glucose (mg/dl)
timeFrame: Intraoperative period; Induction to end of surgery
measure: Postoperative Blood Glucose
timeFrame: From ICU Admission (After Surgery) Until 24 hours postoperatively
measure: Total Postoperative Regular Insulin
timeFrame: From ICU Admission (After Surgery) Until 24 hours postoperatively
measure: Intraoperative Pre-cardiopulmonary Bypass Hemodynamic Stability
timeFrame: induction of anesthesia till systemic heparinization before cardiopulmonary bypass
measure: Stress Hormone Levels-Cortisol (µg/dl)
timeFrame: Perioperative period (Intraoperatively and 8 hours postoperatively)
measure: Inflammatory Mediator Levels, Interleukin-1b, Interleukin 6 and Tumor Necrosis Factor (TNF) (pg/ml)
timeFrame: Perioperative period (Intraoperatively and 8 hours postoperatively)
measure: Stress Hormone Levels-ACTH, GH, Glucagon (pg/ml)
timeFrame: Perioperative period (Intraoperatively and 8 hours postoperatively)
measure: Society of Thoracic Surgery Patient Outcomes
timeFrame: 30 day outcomes
measure: Postoperative Pain
timeFrame: Every day 6 hour for 48 hours postoperative period
measure: Emergence From Anesthesia
timeFrame: Immediate postoperative period until 30 days post-operatively
measure: Wound Hyperalgesia
timeFrame: 96 hours postoperatively
measure: Development of Chronic Pain
timeFrame: 1, 3, 6 and 12 months after discharge from the hospital
measure: Glycemic Variability
timeFrame: From the start of induction till 24 hours postoperatively
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: UPMC Presbyterian Hospital
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh Medical Center
name: Kathrivel Subramaniam, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Doenst T, Wijeysundera D, Karkouti K, Zechner C, Maganti M, Rao V, Borger MA. Hyperglycemia during cardiopulmonary bypass is an independent risk factor for mortality in patients undergoing cardiac surgery. J Thorac Cardiovasc Surg. 2005 Oct;130(4):1144. doi: 10.1016/j.jtcvs.2005.05.049.
citation: Ihn CH, Joo JD, Choi JW, Kim DW, Jeon YS, Kim YS, Jung HS, Kwon SY. Comparison of stress hormone response, interleukin-6 and anaesthetic characteristics of two anaesthetic techniques: volatile induction and maintenance of anaesthesia using sevoflurane versus total intravenous anaesthesia using propofol and remifentanil. J Int Med Res. 2009 Nov-Dec;37(6):1760-71. doi: 10.1177/147323000903700612.
citation: Subramaniam B, Lerner A, Novack V, Khabbaz K, Paryente-Wiesmann M, Hess P, Talmor D. Increased glycemic variability in patients with elevated preoperative HbA1C predicts adverse outcomes following coronary artery bypass grafting surgery. Anesth Analg. 2014 Feb;118(2):277-287. doi: 10.1213/ANE.0000000000000100.
citation: Shinoda T, Murakami W, Takamichi Y, Iizuka H, Tanaka M, Kuwasako Y. Effect of remifentanil infusion rate on stress response in orthopedic surgery using a tourniquet application. BMC Anesthesiol. 2013 Jul 10;13:14. doi: 10.1186/1471-2253-13-14. eCollection 2013.
citation: Cok OY, Ozkose Z, Pasaoglu H, Yardim S. Glucose response during craniotomy: propofol-remifentanil versus isoflurane-remifentanil. Minerva Anestesiol. 2011 Dec;77(12):1141-8. Epub 2011 May 20.
citation: Lazar HL, McDonnell M, Chipkin SR, Furnary AP, Engelman RM, Sadhu AR, Bridges CR, Haan CK, Svedjeholm R, Taegtmeyer H, Shemin RJ; Society of Thoracic Surgeons Blood Glucose Guideline Task Force. The Society of Thoracic Surgeons practice guideline series: Blood glucose management during adult cardiac surgery. Ann Thorac Surg. 2009 Feb;87(2):663-9. doi: 10.1016/j.athoracsur.2008.11.011. No abstract available.
citation: Subramaniam K, Sciortino C, Ruppert K, Monroe A, Esper S, Boisen M, Marquez J, Hayanga H, Badhwar V. Remifentanil and perioperative glycaemic response in cardiac surgery: an open-label randomised trial. Br J Anaesth. 2020 Jun;124(6):684-692. doi: 10.1016/j.bja.2020.01.028. Epub 2020 Apr 2.