Tight Intra-Operative Glucose Control During Coronary Artery Bypass Surgery

Tight Intra-Operative Glucose Control Using Continuous Insulin Infusion During Coronary Artery Bypass Surgery: Randomized Controlled Trial

Blood glucose levels increase in response to stress, infection or other conditions faced by patients in the hospital. This occurs commonly among patients with known diabetes, but also among non-diabetic hospitalized patients. Tight glucose control, the maintenance of blood glucose levels within normal limits (80-120 mg/dl), has been shown to improve patient outcomes in the hospital in several settings, mainly among critically ill patients hospitalized in intensive care units.

We plan to assess the importance of tight glucose control during open-heart surgery. The prevalence of hyperglycemia (elevated blood glucose) during this operation is high. Hyperglycemia may be associated with increased vulnerability to surgical site infections, neurological damage, cardiac and renal injury. Conversely, tight glucose control may be associated with hypoglycemia (pathologically low glucose levels) that may results in neurological injury. We hypothesize that tight glucose control will improve patient outcomes following surgery.

Study Overview

• Status: Terminated
• Conditions: Coronary Artery Bypass
• Intervention / Treatment: Drug: Intraoperative continuous insulin infusion; Other: Control

Detailed Description

Current evidence supports intensive glucose control for patients in the intensive care unit post-cardiac surgery. The risk-benefit ratio of tight glucose control using continuous insulin infusion during surgery has not been established. Pros for tight control include the association of hyperglycemia with neurological injury, cardiac ischemia, white blood cell dysfunction and renal failure. The cons include adverse effects, mainly hypoglycemia and hypokalemia. As with any intervention in medicine, tight intra-operative glucose control should be assessed in a randomized controlled trial.

Objectives:to assess whether tight intra-operative tight glucose control using continuous insulin infusion reduces morbidity and mortality following cardiac surgery, defined as the incidence rate of surgical site infections, adverse neurological events, renal failure and 30-day mortality following CABG.

Additional outcomes will include the effect of continuous insulin infusion on longer-term mortality; other infectious complications and antibiotic use during hospitalization; cardiovascular outcomes; the need for re-operations; length of hospital stay; readmission; hypoglycemia and other adverse events.

Design: randomized controlled trial, with blinding of outcome assessors.

Participants: all consecutive patients >18 years undergoing CABG, without or without additional valve or other surgery at Rabin Medical Center; Beilinson campus, providing informed consent.

Exclusion criteria: patients with diabetic ketoacidosis, or hyperosmolar coma.

Intervention: Continuous insulin infusion throughout the operation aimed to maintain normoglycemia using a nomogram

Control: Glucose management according to the discretion of the anesthesiologist (continuous or bolus infusion)

During the early post-operative period (ICU-stay following surgery), all patients will be treated with intensive glucose control targeting glucose levels between 80-110.

• Study Type: Interventional
• Enrollment (Anticipated): 1400
• Phase: Phase 4

Contacts and Locations

Study Locations

• Israel
  • Petah Tikvah, Israel, 49100
    • Rabin Medical Center, Beilinson Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• All consecutive patients >18 years undergoing CABG, without or without additional valve or other surgery at Rabin Medical Center; Beilinson campus, providing informed consent.

Exclusion Criteria:

• Patients with diabetic ketoacidosis, or hyperosmolar coma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Intervention	Drug: Intraoperative continuous insulin infusion; Nomogram specified in appendix
No Intervention: 2; Control	Other: Control; Glucose management according to the discretion of the anesthesiologist aimed to maintain glucose levels <200 mg.dl, reflecting current practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
30-day all-cause mortality.	30-day
Deep or organ/ space (mediastinitis) surgical site infections.	90 days
Acute renal failure during post-operative ICU stay, defined as: doubling of serum creatinine from baseline; or >50% reduction from baseline glomerular filtration rate; or need for renal replacement therapy.	30 days
Perioperative cerebrovascular event defined as any new, temporary or permanent, focal or global neurological deficit.	30 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Individual components of the composite primary outcome	30 days
6-months and long-term survival.	6 ans 12 months
Other infectious complications during ICU stay including pneumonia and bloodstream infections according to CDC criteria	ICU stay
Antibiotic use	30 days
Durations of intubation, ICU and hospital stay	hospital stay
Other post-operative complications occurring during ICU stay, including re-intubation, re-operation	ICU stay
Occurrence of hypoglycemia, defined as blood glucose level of 50mg/ dl or less, during surgery and up to the first glucose measurement in ICU.	during surgery
Occurrence of severe hypokalemia, defined as K<2.5 mEq/l, during surgery	during surgery
Glucose control in ICU, during the first 2 post-operative days	2 post-operative days
Neurological status before surgery, at discharge and 3 months following surgery:	3 months
Adverse cardiac events occurring during ICU stay	ICU stay
Re-hospitalizations	30 days

Collaborators and Investigators

• Sponsor: Rabin Medical Center
• Investigators: Principal Investigator: Mical Paul, MD, Rabin Medical Center

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Study Completion (Anticipated): August 1, 2009

Study Registration Dates

• First Submitted: October 31, 2006
• First Submitted That Met QC Criteria: October 31, 2006
• First Posted (Estimate): November 1, 2006

Study Record Updates

• Last Update Posted (Estimate): April 1, 2009
• Last Update Submitted That Met QC Criteria: March 31, 2009
• Last Verified: June 1, 2007

More Information

Terms related to this study

• Keywords: Hyperglycemia; Diabetes mellitus; Surgical site infection; Normoglycemia; Open heart surgery
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: 4214