Aggressive Glycemic Control Not Beneficial in Diabetic CABG Patients

Aggressive glycemic control in diabetic patients undergoing coronary artery bypass graft surgery resulted in a sharp upswing in hypoglycemic events while providing no advantage in clinical cardiovascular outcomes, compared with moderate control, according to a randomized, controlled trial.

The impetus for this trial was the fact that the optimal blood glucose level in diabetic patients undergoing CABG surgery isn’t known, according to Dr. Harold L. Lazar. The Society of Thoracic Surgeons recommends that blood glucose be kept below 180 mg/dL during cardiac surgery and afterwards in the ICU (Ann. Thorac. Surg. 2009;87:663-9).

This recommendation is based on solid evidence of benefit; for example, a previous study by Dr. Lazar and his coworkers showed that maintaining blood glucose in the 120-180 mg/dL range in diabetic CABG patients resulted in less atrial fibrillation, fewer sternal wound infections, shorter hospital stays, better left ventricular function, and increased 5-year survival, compared with diabetic patients whose blood glucose was greater than 180 mg/dL (Circulation 2004;109:1497-502).

However, there have subsequently been conflicting reports as to whether maintaining blood glucose levels even lower (below 120 mg/dL) provides added benefit or might actually be harmful.

In the current study, 82 CABG patients with diabetes were randomized to moderate glycemic control if they had a blood glucose level of 120-180 mg/dL, or aggressive control if they had a blood glucose of 90-120 mg/dL. Levels were maintained using continuous intravenous insulin solutions, starting at the induction of anesthesia and continuing for 18 hours after surgery. All patients were on standard cardioprotective medications, including a beta-blocker, statin, and aspirin.

The moderate-control group achieved a mean blood glucose of 135 mg/dL, compared with 103 mg/dL in the tight-control group, Dr. Lazar said at the annual meeting of the American Surgical Association, where he presented the study results.

The primary end point was the 30-day rate of major adverse events, a composite that included death, MI, cerebrovascular accidents, atrial fibrillation, and deep sternal infections. The rate was 40% in the moderate-control group and 35% with aggressive glycemic control, a nonsignificant difference. Rates of each of the individual components of the composite end point were similar in the two groups as well. Nor did the two study arms differ significantly in secondary end points, including time on the ventilator, weight gain, need for inotropic support, or length of hospital or ICU stay, said Dr. Lazar of Boston Medical Center.

One or more hypoglycemic events were experienced by 10% of the moderate-control group vs. 75% of the aggressively managed group, although none of these episodes resulted in a neurologic event.

There was a trend for serum free fatty acid levels (a surrogate marker for a systemic inflammatory response) to be lower in the aggressive-control group than in the moderate-control group when they were measured 18 hours postoperatively.

Audience members questioned whether the 82-patient trial was powered sufficiently to draw firm conclusions regarding major adverse cardiovascular event rates. Dr. Lazar agreed that this is a legitimate concern. He said long-term follow-up of the study participants is planned to determine whether the lower free fatty acid levels in the aggressive glycemic control group will eventually be reflected in better graft patency and fewer ischemic events.

Dr. Lazar declared having no financial conflicts.

Aggressive glycemic control in diabetic patients undergoing coronary artery bypass graft surgery resulted in a sharp upswing in hypoglycemic events while providing no advantage in clinical cardiovascular outcomes, compared with moderate control, according to a randomized, controlled trial.

The impetus for this trial was the fact that the optimal blood glucose level in diabetic patients undergoing CABG surgery isn’t known, according to Dr. Harold L. Lazar. The Society of Thoracic Surgeons recommends that blood glucose be kept below 180 mg/dL during cardiac surgery and afterwards in the ICU (Ann. Thorac. Surg. 2009;87:663-9).

This recommendation is based on solid evidence of benefit; for example, a previous study by Dr. Lazar and his coworkers showed that maintaining blood glucose in the 120-180 mg/dL range in diabetic CABG patients resulted in less atrial fibrillation, fewer sternal wound infections, shorter hospital stays, better left ventricular function, and increased 5-year survival, compared with diabetic patients whose blood glucose was greater than 180 mg/dL (Circulation 2004;109:1497-502).

However, there have subsequently been conflicting reports as to whether maintaining blood glucose levels even lower (below 120 mg/dL) provides added benefit or might actually be harmful.

In the current study, 82 CABG patients with diabetes were randomized to moderate glycemic control if they had a blood glucose level of 120-180 mg/dL, or aggressive control if they had a blood glucose of 90-120 mg/dL. Levels were maintained using continuous intravenous insulin solutions, starting at the induction of anesthesia and continuing for 18 hours after surgery. All patients were on standard cardioprotective medications, including a beta-blocker, statin, and aspirin.

The moderate-control group achieved a mean blood glucose of 135 mg/dL, compared with 103 mg/dL in the tight-control group, Dr. Lazar said at the annual meeting of the American Surgical Association, where he presented the study results.

The primary end point was the 30-day rate of major adverse events, a composite that included death, MI, cerebrovascular accidents, atrial fibrillation, and deep sternal infections. The rate was 40% in the moderate-control group and 35% with aggressive glycemic control, a nonsignificant difference. Rates of each of the individual components of the composite end point were similar in the two groups as well. Nor did the two study arms differ significantly in secondary end points, including time on the ventilator, weight gain, need for inotropic support, or length of hospital or ICU stay, said Dr. Lazar of Boston Medical Center.

One or more hypoglycemic events were experienced by 10% of the moderate-control group vs. 75% of the aggressively managed group, although none of these episodes resulted in a neurologic event.

There was a trend for serum free fatty acid levels (a surrogate marker for a systemic inflammatory response) to be lower in the aggressive-control group than in the moderate-control group when they were measured 18 hours postoperatively.

Audience members questioned whether the 82-patient trial was powered sufficiently to draw firm conclusions regarding major adverse cardiovascular event rates. Dr. Lazar agreed that this is a legitimate concern. He said long-term follow-up of the study participants is planned to determine whether the lower free fatty acid levels in the aggressive glycemic control group will eventually be reflected in better graft patency and fewer ischemic events.

Dr. Lazar declared having no financial conflicts.

Aggressive glycemic control in diabetic patients undergoing coronary artery bypass graft surgery resulted in a sharp upswing in hypoglycemic events while providing no advantage in clinical cardiovascular outcomes, compared with moderate control, according to a randomized, controlled trial.

The impetus for this trial was the fact that the optimal blood glucose level in diabetic patients undergoing CABG surgery isn’t known, according to Dr. Harold L. Lazar. The Society of Thoracic Surgeons recommends that blood glucose be kept below 180 mg/dL during cardiac surgery and afterwards in the ICU (Ann. Thorac. Surg. 2009;87:663-9).

This recommendation is based on solid evidence of benefit; for example, a previous study by Dr. Lazar and his coworkers showed that maintaining blood glucose in the 120-180 mg/dL range in diabetic CABG patients resulted in less atrial fibrillation, fewer sternal wound infections, shorter hospital stays, better left ventricular function, and increased 5-year survival, compared with diabetic patients whose blood glucose was greater than 180 mg/dL (Circulation 2004;109:1497-502).

However, there have subsequently been conflicting reports as to whether maintaining blood glucose levels even lower (below 120 mg/dL) provides added benefit or might actually be harmful.

In the current study, 82 CABG patients with diabetes were randomized to moderate glycemic control if they had a blood glucose level of 120-180 mg/dL, or aggressive control if they had a blood glucose of 90-120 mg/dL. Levels were maintained using continuous intravenous insulin solutions, starting at the induction of anesthesia and continuing for 18 hours after surgery. All patients were on standard cardioprotective medications, including a beta-blocker, statin, and aspirin.

The moderate-control group achieved a mean blood glucose of 135 mg/dL, compared with 103 mg/dL in the tight-control group, Dr. Lazar said at the annual meeting of the American Surgical Association, where he presented the study results.

The primary end point was the 30-day rate of major adverse events, a composite that included death, MI, cerebrovascular accidents, atrial fibrillation, and deep sternal infections. The rate was 40% in the moderate-control group and 35% with aggressive glycemic control, a nonsignificant difference. Rates of each of the individual components of the composite end point were similar in the two groups as well. Nor did the two study arms differ significantly in secondary end points, including time on the ventilator, weight gain, need for inotropic support, or length of hospital or ICU stay, said Dr. Lazar of Boston Medical Center.

One or more hypoglycemic events were experienced by 10% of the moderate-control group vs. 75% of the aggressively managed group, although none of these episodes resulted in a neurologic event.

There was a trend for serum free fatty acid levels (a surrogate marker for a systemic inflammatory response) to be lower in the aggressive-control group than in the moderate-control group when they were measured 18 hours postoperatively.

Audience members questioned whether the 82-patient trial was powered sufficiently to draw firm conclusions regarding major adverse cardiovascular event rates. Dr. Lazar agreed that this is a legitimate concern. He said long-term follow-up of the study participants is planned to determine whether the lower free fatty acid levels in the aggressive glycemic control group will eventually be reflected in better graft patency and fewer ischemic events.

Dr. Lazar declared having no financial conflicts.