Benefits of GIK in Cardiac Surgery Patients

Myocardial Protection of Glucose - Insulin - Potassium in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass

The purpose of this study is to evaluate the effects of modified glucose - insulin - potassium (GIK) therapy in cardiac surgery patients undergoing cardiopulmonary bypass (CPB).

Study Overview

• Status: Unknown
• Conditions: Cardiac Surgery; Cardiopulmonary Bypass
• Intervention / Treatment: Drug: GIK; Drug: Control

Detailed Description

Cardiopulmonary bypass (CPB) is a necessary technique to maintain the circulation during cardiac surgery. But CPB itself is associated with a series of problems of organs, such as hyperglycemia induced by neuroendocrine stress. The research showed that hyperglycemia induced by stress would cause a worsened hospital outcome for patients undergoing cardiac surgery. Intraoperative and postoperative glucose control is beneficial for patients.

It has been for more than 40 year since the first application of glucose - insulin - potassium (GIK) in cardiac surgery but the clinical application of GIK shows controversial results. The beginning time of application and the ratio of glucose and insulin may be the key reasons for the controversy. In our pilot trial of 40 valve replacement cases, we found that perioperative treatment of GIK with an insulin-glucose ratio of 1:3 showed beneficial effects during heart surgery. Therefore, the investigators are planning to continue to test this modified GIK regimen for more heart surgery patients and determine whether GIK may have cardioprotective effects on patients undergoing CPB surgery.

Myocardial biopsies for biological mechanism analysis will be performed prior to CPB, 15 min after aortic cross clamp application and 15 min after reperfusion only in a small cohort. Myocardial biopsies will be snap frozen or fixed.

• Study Type: Interventional
• Enrollment (Actual): 930
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Deparment of Cardiovascular surgery,Xijing Hospital, Fourth Military Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Between 18 and 70 years of age
• Elective cardiac surgery with first time cardiopulmonary bypass
• Left ventricular ejection fraction(LVEF) ≥ 30%
• Informed agreement signed

Exclusion Criteria:

• Previous cardiac surgery
• Emergent surgery
• Cardiac surgery without the use of cardiopulmonary bypass
• Diabetes mellitus
• Severe renal insufficiency
• Severe respiratory insufficiency
• Serious preoperative illness (sepsis, active infection or active malignancy requiring treatment)
• Pregnant woman or positive pregnancy test
• History of drug abuse
• Subject has a history of bleeding diathesis, coagulopathy, or refuses blood transfusion
• Enrollment in another clinical study
• Lack of informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: GIK; glucose-insulin-potassium (GIK) consists of 20% glucose (200 g/L), 66.7 U/L regular insulin and 80 mmol/L potassium chloride (KCl).	Drug: GIK; Intravenous solution was started at about 10 minutes before general anesthesia, running at a rate of 1 mL/kg/h for 12.5 hours.; Other Names: Glucose-insulin-potassium
Placebo Comparator: Control; 6.12 g/L sodium acetate, 5.85 g/L sodium chloride, 0.3 g/L potassium chloride and 0.33 g/L calcium chloride	Drug: Control; Intravenous solution was started at about 10 minutes before general anesthesia, running at a rate of 1 mL/kg/h for 12.5 hours.; Other Names: Balanced salt solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants of the major adverse cardiac events	The composite of major adverse cardiac events included acute myocardial infarction, cardiac arrest with successful resuscitation, low cardiac output syndrome, congestive heart failure, arrhythmia and all-cause death.	Stay in hospital

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mortality		until the study ends
Length of stay in intensive care unit and hospital	Length of stay in intensive care unit and hospital	Stay in intensive care unit and hospital
Number of patients of postoperative complications	Postoperative complications included prolonged ventilation, the use of inotropes, sepsis/infection, renal complications, stroke and reoperation.	Stay in hospital

Other Outcome Measures

Outcome Measure	Time Frame
Left ventricular ejection fraction (LVEF)	24h after operation and before discharge
Creatine kinase-myocardial bands (CK-MB)	during 48 h after surgery

Collaborators and Investigators

• Sponsor: Xijing Hospital
• Investigators: Study Chair: Dinghua Yi, MD,PhD, Deparment of cardiovascular surgery, XiJing hospital, Fourth Military Medical University; Principal Investigator: Qin Cui, MD,PhD, Deparment of cardiovascular surgery,XiJing hospital,Fourth Military Medical University; Principal Investigator: Jia Li, MD,PhD, Deparment of Physiology, Fourth Military Medical University; Principal Investigator: Feng Gao, MD,PhD, Deparment of Physiology, Fourth Military Medical University; Principal Investigator: Kun Zhao, MD, Deparment of cardiovascular surgery, XiJing hospital,Fourth Military Medical University; Principal Investigator: Shiqiang Yu, MD,PhD, Deparment of cardiovascular surgery, XiJing hospital, Fourth Military Medical University

Publications and helpful links

General Publications

• Zhao K, Zhang Y, Li J, Cui Q, Zhao R, Chen W, Liu J, Zhao B, Wan Y, Ma XL, Yu S, Yi D, Gao F. Modified Glucose-Insulin-Potassium Regimen Provides Cardioprotection With Improved Tissue Perfusion in Patients Undergoing Cardiopulmonary Bypass Surgery. J Am Heart Assoc. 2020 Mar 17;9(6):e012376. doi: 10.1161/JAHA.119.012376. Epub 2020 Mar 10.

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): March 1, 2013
• Study Completion (Anticipated): February 1, 2022

Study Registration Dates

• First Submitted: January 8, 2012
• First Submitted That Met QC Criteria: January 23, 2012
• First Posted (Estimate): January 24, 2012

Study Record Updates

• Last Update Posted (Estimate): October 31, 2014
• Last Update Submitted That Met QC Criteria: October 30, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Cardiac surgery; Glucose-insulin-potassium
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: XJcuiqin_2012