To review findings and discuss implications of strict glycemic control in children.
Critical appraisal of a randomized controlled trial.
This is the largest prospective randomized controlled trial to date, comparing intensive insulin therapy (glycemic targets: 50.4–79.2 mg/dL [2.8–4.4 mmol/L] and 70.2–99 mg/dL [3.9–5.5 mmol/L] [for infants and children, respectively]) and conventional insulin therapy (target: 180–215 mg/dl [10–11.9 mmol/L]) among critically ill children. Groups were similar at enrollment and had comparable forms of nutrition and glucose infusion rates. Steroid use and vasoactive-inotrope scores were not compared. Intensive insulin therapy reduced pediatric intensive care unit length of stay (primary outcome measure) and attenuated C-reactive protein concentrations >5 days. The effect of intensive insulin therapy on secondary outcome measures was precise in regards to significant reductions in secondary infection occurrence (absolute risk reduction = 7.6% [95% confidence interval: 0.6–14.4], number needed to treat = 14 [95% confidence interval: 7–179]) and need for vasoactive support beyond 2 days (absolute risk reduction = 10.4% [95% confidence interval: 3–17], number needed to treat = 10 [95% confidence interval: 6–30]). Mortality decreased with intensive insulin therapy (p = .038); however, this finding was imprecise (absolute risk reduction = 3.1% [95% confidence interval: 0.2–5.4], number needed to treat = 33 [95% confidence interval: 18.6–597.3]). The incidence of hypoglycemia was significantly higher with intensive insulin therapy (absolute risk increase = 23.5% [95% confidence interval: 20–25%], number needed to harm = 4 [95% confidence interval: 4–5]). Long-term effects on outcomes were not evaluated, and the authors recognize the need for such follow-up studies. This study demonstrated efficacy of intensive insulin therapy at the same institution where the original adult intensive insulin therapy trial was conducted, but it may not demonstrate effectiveness in populations other than postoperative cardiac patients, which composed the majority of patients enrolled or in institutions without a highly experienced nursing staff to manage intensive insulin therapy.
This was a well-designed single-center trial that serves as proof of concept. The effects of intensive insulin therapy on mortality require further investigation, and its practice may need refinement to reduce the risk of hypoglycemia. In the meantime, targeting age-adjusted fasting glucose ranges cannot be routinely recommended in critically ill children.