Tight glycemic control versus standard care after pediatric cardiac surgery

Abstract

Background: In some studies, tight glycemic control with insulin improved outcomes in adults undergoing cardiac surgery, but these benefits are unproven in critically ill children at risk for hyperinsulinemic hypoglycemia. We tested the hypothesis that tight glycemic control reduces morbidity after pediatric cardiac surgery.

Methods: In this two-center, prospective, randomized trial, we enrolled 980 children, 0 to 36 months of age, undergoing surgery with cardiopulmonary bypass. Patients were randomly assigned to either tight glycemic control (with the use of an insulin-dosing algorithm targeting a blood glucose level of 80 to 110 mg per deciliter [4.4 to 6.1 mmol per liter]) or standard care in the cardiac intensive care unit (ICU). Continuous glucose monitoring was used to guide the frequency of blood glucose measurement and to detect impending hypoglycemia. The primary outcome was the rate of health care-associated infections in the cardiac ICU. Secondary outcomes included mortality, length of stay, organ failure, and hypoglycemia.

Results: A total of 444 of the 490 children assigned to tight glycemic control (91%) received insulin versus 9 of 490 children assigned to standard care (2%). Although normoglycemia was achieved earlier with tight glycemic control than with standard care (6 hours vs. 16 hours, P<0.001) and was maintained for a greater proportion of the critical illness period (50% vs. 33%, P<0.001), tight glycemic control was not associated with a significantly decreased rate of health care-associated infections (8.6 vs. 9.9 per 1000 patient-days, P=0.67). Secondary outcomes did not differ significantly between groups, and tight glycemic control did not benefit high-risk subgroups. Only 3% of the patients assigned to tight glycemic control had severe hypoglycemia (blood glucose <40 mg per deciliter [2.2 mmol per liter]).

Conclusions: Tight glycemic control can be achieved with a low hypoglycemia rate after cardiac surgery in children, but it does not significantly change the infection rate, mortality, length of stay, or measures of organ failure, as compared with standard care. (Funded by the National Heart, Lung, and Blood Institute and others; SPECS ClinicalTrials.gov number, NCT00443599.).

Figure 1. Assessment, Randomization, and Follow-up of the Study Patients

CPB denotes cardiopulmonary bypass.

Figure 2. Glucose, Insulin, and Nutrition, According to Treatment Group

Data in all the panels are for full 24-hour days during the period of critical illness. Panel A shows time-weighted blood glucose averages calculated from all blood glucose samples on the day of postoperative admission to the cardiac intensive care unit (ICU) (day 1) and the subsequent 6 days (7 a.m. to 6:59 a.m.). Panel B shows total daily insulin delivery. Panel C shows average daily glucose infusion rates. Panel D shows the daily percentage of nutrition delivered through the enteral route. Panel E shows total kilocalories of nutrition per kilogram of body weight per day. In each panel, the boxes represent the interquartile range (25th percentile to 75th percentile) and the horizontal lines the median; the whiskers extend to the 5th and 95th percentiles. To convert the values for glucose to millimoles per liter, multiply by 0.05551.