Clinical trial NCT00394303: Tight Intra-Operative Glucose Control During Coronary Artery Bypass Surgery
Official title: Tight Intra-Operative Glucose Control Using Continuous Insulin Infusion During Coronary Artery Bypass Surgery: Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Coronary Artery Bypass
Keywords: Open heart surgery
Diabetes mellitus
Hyperglycemia
Surgical site infection
Normoglycemia
Lead sponsor: Rabin Medical Center
Sponsor class: OTHER
First posted: 2006-11-01
Enrollment: 1400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 30-day all-cause mortality.
timeFrame: 30-day
measure: Deep or organ/ space (mediastinitis) surgical site infections.
timeFrame: 90 days
measure: 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.
timeFrame: 30 days
measure: Perioperative cerebrovascular event defined as any new, temporary or permanent, focal or global neurological deficit.
timeFrame: 30 days
Secondary outcomes:
measure: Individual components of the composite primary outcome
timeFrame: 30 days
measure: 6-months and long-term survival.
timeFrame: 6 ans 12 months
measure: Other infectious complications during ICU stay including pneumonia and bloodstream infections according to CDC criteria
timeFrame: ICU stay
measure: Antibiotic use
timeFrame: 30 days
measure: Durations of intubation, ICU and hospital stay
timeFrame: hospital stay
measure: Other post-operative complications occurring during ICU stay, including re-intubation, re-operation
timeFrame: ICU stay
measure: Occurrence of hypoglycemia, defined as blood glucose level of 50mg/ dl or less, during surgery and up to the first glucose measurement in ICU.
timeFrame: during surgery
measure: Occurrence of severe hypokalemia, defined as K<2.5 mEq/l, during surgery
timeFrame: during surgery
measure: Glucose control in ICU, during the first 2 post-operative days
timeFrame: 2 post-operative days
measure: Neurological status before surgery, at discharge and 3 months following surgery:
timeFrame: 3 months
measure: Adverse cardiac events occurring during ICU stay
timeFrame: ICU stay
measure: Re-hospitalizations
timeFrame: 30 days
Other outcomes:
Locations:
city: Petah Tikvah
country: Israel
facility: Rabin Medical Center, Beilinson Hospital
Study officials:
affiliation: Rabin Medical Center
name: Mical Paul, MD
role: PRINCIPAL_INVESTIGATOR
References: