Although some studies have portrayed tight blood sugar control as a potential means of lowering infection rates in critically ill adults, the SPECS study, published online Sept. 7 in the New England Journal of Medicine, found no indication that the approach benefits pediatric patients undergoing heart surgery. As a result, the editorialist suggested that the door should be closed on routine use of glucose homeostasis in critically ill children.

Congenital heart defects are the most common birth defects, with approximately 20,000 pediatric cardiothoracic surgical procedures performed in the U.S. each year (J Pediatr 2008;153:807-813). Postoperative morbidity and mortality among infants and young children remain relatively high, according to the study authors; thus, they said the identification of modifiable risk factors during postoperative critical care is “important for continued improvement in outcomes.” Tight glycemic control has emerged as a potential approach to reduce morbidity in adult cardiac medical and surgical populations, but they noted that it has not proved generalizable to all critical care patients.

The two-center, prospective, randomized SPECS (Safe Pediatric Euglycemia in Cardiac Surgery) trial enrolled 980 children, 0 to 36 months of age, undergoing surgery with cardiopulmonary bypass.

Michael S.D. Agus, MD, of Boston Children's Hospital, and colleagues randomly assigned the pediatric patients 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). They used continuous glucose monitoring to guide the frequency of blood glucose measurement and to detect impending hypoglycemia.

The primary outcome was the rate of healthcare-associated infections in the cardiac ICU. Secondary outcomes included mortality, length of stay, organ failure and hypoglycemia.

Based on the study protocol, a total of 444 of the 490 children received tight glycemic control (91 percent) and insulin, while nine of 490 children were assigned to standard care (2 percent).

Although normoglycemia was achieved earlier with tight glycemic control than with standard care (six hours vs. 16 hours) and was maintained for a greater proportion of the critical illness period (50 percent vs. 33 percent), tight glycemic control was not associated with a significantly decreased rate of healthcare-associated infections (8.6 vs. 9.9 per 1,000 patient-days), the SPECS investigators reported.

The secondary outcomes did not differ significantly between groups, and tight glycemic control did not benefit high-risk subgroups, according to Agus et al. Only 3 percent of the patients assigned to tight glycemic control had severe hypoglycemia (blood glucose <40 mg per deciliter [2.2 mmol per liter]).

The researchers concluded that 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.

In the accompanying editorial, Brian P. Kavanagh, MB, of the Hospital for Sick Children in Toronto, said the study offers “key data,” because it “seems that—as in adults—claims for survival benefit in critically ill children are incorrect. Furthermore, there is no reason why the effects of glucose control in children would be opposite to those in adults. In aggregate, the data do not support a basis for embarking on a pediatric megatrial.”

He added that “the most important question” from a decade of studying glucose control in the ICU is how influential practice guidelines advocating tight glucose control were developed yet turned out to be harmful.

“Guideline writers, reflecting on the experience, must accept that there are multiple sources of clinical knowledge and must pay careful attention to trial characteristics—especially study reproducibility—in order to provide advice that genuinely helps clinicians,” Kavanagh wrote. “Clinicians in turn should use guidelines wisely, recognizing that no single source of knowledge is sufficient to guide clinical decisions.

“Is the door closed on studying glucose homeostasis in the critically ill? No, but it should be closed on the routine normalization of plasma glucose in critically ill adults and children,” Kavanagh recommended.

Next, the SPECS researchers said they will conduct a broader study of glycemic control, called HALF-PINT (Heart and Lung Failure – Pediatric Insulin Titration). The randomized, multi-center trial will compare two glucose control ranges in hyperglycemic, critically ill children, ages two weeks through 18 years, who are hospitalized in the pediatric intensive care unit with heart and/or lung failure.

The SPECS study was supported by grants from a National Heart, Lung and Blood Institute (NHLBI) grant, the American Recovery and Reinvestment Act supplement through the NHLBI and the Harvard Catalyst Clinical and Translational Research Center.