Tight Glycemic Control in Critically Ill Children

Abstract

BACKGROUND In multicenter studies, tight glycemic control targeting a normal blood glucose level has not been shown to improve outcomes in critically ill adults or children after cardiac surgery. Studies involving critically ill children who have not undergone cardiac surgery are lacking. METHODS In a 35-center trial, we randomly assigned critically ill children with confirmed hyperglycemia (excluding patients who had undergone cardiac surgery) to one of two ranges of glycemic control: 80 to 110 mg per deciliter (4.4 to 6.1 mmol per liter; lower-target group) or 150 to 180 mg per deciliter (8.3 to 10.0 mmol per liter; higher-target group). Clinicians were guided by continuous glucose monitoring and explicit methods for insulin adjustment. The primary outcome was the number of intensive care unit (ICU)–free days to day 28. RESULTS The trial was stopped early, on the recommendation of the data and safety monitoring board, owing to a low likelihood of benefit and evidence of the possibility of harm. Of 713 patients, 360 were randomly assigned to the lower-target group and 353 to the higher-target group. In the intention-to-treat analysis, the median number of ICU-free days did not differ significantly between the lower-target group and the higher-target group (19.4 days [interquartile range {IQR}, 0 to 24.2] and 19.4 days [IQR, 6.7 to 23.9], respectively; P = 0.58). In per-protocol analyses, the median time-weighted average glucose level was significantly lower in the lower-target group (109 mg per deciliter [IQR, 102 to 118]; 6.1 mmol per liter [IQR, 5.7 to 6.6]) than in the higher-target group (123 mg per deciliter [IQR, 108 to 142]; 6.8 mmol per liter [IQR, 6.0 to 7.9]; P<0.001). Patients in the lower-target group also had higher rates of health care–associated infections than those in the higher-target group (12 of 349 patients [3.4%] vs. 4 of 349 [1.1%], P = 0.04), as well as higher rates of severe hypoglycemia, defined as a blood glucose level below 40 mg per deciliter (2.2 mmol per liter) (18 patients [5.2%] vs. 7 [2.0%], P = 0.03). No significant differences were observed in mortality, severity of organ dysfunction, or the number of ventilator-free days. CONCLUSIONS Critically ill children with hyperglycemia did not benefit from tight glycemic control targeted to a blood glucose level of 80 to 110 mg per deciliter, as compared with a level of 150 to 180 mg per deciliter.

‘We just dilute sugar and give’ health workers’ reports of management of paediatric hypoglycaemia in a referral hospital in Malawi

“…Some interviewees referred to risks related to hyperglycaemia, and there is some evidence that admission hyperglycaemia in critically ill children is associated with increased mortality [28–30]. While tight glycaemic control has been practiced in intensive care units with the assumption that hyperglycaemia in the critically ill worsens outcomes, recent studies have shown no difference in mortality or morbidity between severely sick children assigned to a higher or lower target group [31–33]. Although there is little evidence that dangerous hyperglycaemia or poor outcomes result from treating hypoglycaemia, hyperglycaemia, as well as recurrent hypoglycaemia, may be common after dextrose infusions [34].…”

Use of continuous subcutaneous insulin infusion (CSII) therapy in pediatric diabetes patients in the perioperative period

“…The outcomes of tight glycemic control (TGC) in critically ill children continue to be studied. Multicenter studies have shown that TGC is associated with higher rates of health care associated infections and severe hypoglycemia in critically ill children; others suggest TGC has no significant impact on major clinical outcomes . The landmark NICE‐SUGAR trial demonstrated an increase in mortality among critically ill adults randomized to intensive glucose control (81‐108 mg/dL) compared with conventional glucose control (<180 mg/dL) .…”

The Emperor Has no Clothes? Searching for Dysregulation in Sepsis

“…Because the NICE SUGAR study did not involve children, Agus et al [35] performed a randomized controlled trial of aggressive insulin treatment of hyperglycemia in pediatric patients in intensive care. This was not a study of pediatric sepsis, specifically, but many enrolled patients had infection and sepsis.…”

“…This was not a study of pediatric sepsis, specifically, but many enrolled patients had infection and sepsis. Agus et al [35] enrolled 713 critically ill children and randomly assigned them to a lower target blood sugar group who received more insulin and to a higher target group who received less insulin. The main outcome measure, ICU-free days up to day 28, was similar in both groups.…”