The detrimental effects of hyperglycemia in critically ill patients has been well described in the literature. However, the benfefits of maintaining normoglycemia using insulin infusions has been controversial. In 2009, The New England Journal of Medicine published a study by the NICE-SUGAR Study Investigators that appeared to answer the question about risks and benefits of intensive insulin therapy. Studying more than 6,000 subjects, the authors showed an increase in mortality in critically ill adults who underwent intensive glucose control, compared to those who underwent conventional control of their blood sugars. Interestingly, in the same year, a pediatric study was published in Lancet by Vlasselaers et al that demonstrated a decrease in mortality and length of pediatric intensive care unit (PICU) stay in those patients who had intensive glucose control, compared to the conventional therapy. Though it should be noted that while this study randomized 700 children, it was a single-center trial whose subjects were primarily children who had undergone cardiac surgery (around 75%).
In this study by Macrae et al, the authors randomized more than 1,300 critically ill children from 13 centers to undergo either tight glucose control (maintaining blood glucose levels between 72-126 mg/dl) or conventional therapy (infusing insulin only in patients whose blood glucose levels were over 216 mg/dl until they dropped to 180 mg/dl). The authors recruited children between the ages of 36 weeks of corrected gestational age and 16 years of age. Like the the Vlasselaers study, a predominance of subjects underwent cardiac surgery compared to other reasons for PICU admission (around 60% and 40%, respectivley). The aims of this study were to assess whether tight glycemic control could reduce morbidity and mortality rates and associated costs for critically ill children compared to conventional therapy.
The results of this trial were mixed. When examining the data for the primary outcome, the number of days the subjects were alive and free from mechanical ventilation, the authors clearly demonstrated that tight glycemic control did not demonstrate a benefit. However, some of the secondary examined outcomes revealed a “complex relationship of potential benefit and harms.” Like most of the other studies that examined this topic, this trial demonstrated a statistically significant increase in episodes of moderate and severe hypoglycemia in the tight glycemic control group.Part of the reason for this may be related to the frequency of glucose measurements that were taken. The protocol initially called for hourly checks at the beginning of an insulin infusion until the levels were stable for 6 hours, which then allowed for every 2 hour checks.
In the subgroup of patients who underwent cardiac surgery, hypoglycemia was associated with in increase in mortality (10.6% vs. 2.1% in those without hypoglycemia). However, tight glycemic control was also associated with a decreased incidence of renal replacement therapy compared to conventional therapy. In addition, in the subgroup of critically-ill children who did not undergo cardiac surgery, tight glycemic control was associated with shorter lengths of hospital stay and lower health care costs.
This article is important because it provides clinical direction in a specific patient population and should direct any future studies in this topic. Clearly, the increased mortality associated with hypoglycemia found in cardiac patients in this trial, which was consistent with a similar finding in the NICE-SUGAR trial, should cause practitioners to pause before initiating tight glycemic control in these children. However, in other critically ill children, the positive responses seen with tight glycemic control in this study also deserve attention. Future studies should be done to confirm these findings, but also to provide some insight into the reasons for the differences between hyperglycmia in children after cardiac surgery versus other critically ill children.
This Concise Critical Appraisal is authored by SCCM member Daniel E. Sloniewsky, MD. Each installment highlights journal articles most relevant to the critical care practitioner. Daniel Sloniewsky is an associate professor in the Department of Pediatrics at the Stony Brook Long Island Children’s Hospital in Stony Brook, NY, where he is board certified in pediatrics and pediatric critical care. He completed his fellowship training at Children’s Memorial Hospital and Northwestern University in Chicago. His major interests are in acute pediatric pulmonary disease, transfusion medicine and ethics. He is also actively involved in resident education, Pediatric Advanced Life Support and Pediatric Fundamental Critical Care Support instruction.