Intraoperative tight glucose control using hyperinsulinemic normoglycemia increases delirium after cardiac surgery

Abstract

Background: Postoperative delirium is common in patients recovering from cardiac surgery. Tight glucose control has been shown to reduce mortality and morbidity. Therefore, the authors sought to determine the effect of tight intraoperative glucose control using a hyperinsulinemic-normoglycemic clamp approach on postoperative delirium in patients undergoing cardiac surgery.

Methods: The authors enrolled 198 adult patients having cardiac surgery in this randomized, double-blind, single-center trial. Patients were randomly assigned to either tight intraoperative glucose control with a hyperinsulinemic-normoglycemic clamp (target blood glucose, 80 to 110 mg/dl) or standard therapy (conventional insulin administration with blood glucose target, <150 mg/dl). Delirium was assessed using a comprehensive delirium battery. The authors considered patients to have experienced postoperative delirium when Confusion Assessment Method testing was positive at any assessment. A positive Confusion Assessment Method was defined by the presence of features 1 (acute onset and fluctuating course) and 2 (inattention) and either 3 (disorganized thinking) or 4 (altered consciousness).

Results: Patients randomized to tight glucose control were more likely to be diagnosed as being delirious than those assigned to routine glucose control (26 of 93 vs. 15 of 105; relative risk, 1.89; 95% CI, 1.06 to 3.37; P = 0.03), after adjusting for preoperative usage of calcium channel blocker and American Society of Anesthesiologist physical status. Delirium severity, among patients with delirium, was comparable with each glucose management strategy.

Conclusion: Intraoperative hyperinsulinemic-normoglycemia augments the risk of delirium after cardiac surgery, but not its severity.

Figure 1

Trial diagram. Patients missed Confusion Assessment Method (CAM) assessments for the following reasons were considered as missing due to unavailability, including out of the unit, medical reasons (such as, severe pain, shortness of breath, and etc.), asleep, ventilated, intubated, and discharge. POD = postoperative day.

Figure 2

Time-weighted average (TWA) glucose concentration in patients assigned the hyperinsulinemic-normoglycemic clamp and to routine glucose management. Results presented as boxplots: the first quartile, median, and third quartile comprise the boxes; whiskers extend to the most extreme observations within 1.5 times the interquartile range of the first and third quartiles, respectively.

Figure 3

Time-weighted average (TWA) glucose concentration in delirious (both hyperinsulinemic-normoglycemic clamp and routine glucose management) and non-delirious (both hyperinsulinemic-normoglycemic clamp and routine glucose management) patients. Results presented as boxplots: the first quartile, median, and third quartile comprise the boxes; whiskers extend to the most extreme observations within 1.5 times the interquartile range of the first and third quartiles, respectively.

Figure 4

Average and maximum Memorial Delirium Assessment Score (MDAS) score in all assessments of 26 delirious patients assigned the hyperinsulinemic-normoglucemic clamp and in 15 delirious patients assigned to routine glucose management. Results presented as boxplots: the first quartile, median, and third quartile comprise the boxes; whiskers extend to the most extreme observations within 1.5 times the interquartile range of the first and third quartiles, respectively.