Department of Pediatric Critical Care, Seattle Children's Hospital, Seattle, WA, USA.
Pediatr Crit Care Med. 2011 Jul;12(4):455-8. doi: 10.1097/PCC.0b013e318207097e.
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.
综述严格血糖控制在儿童中的研究结果并探讨其意义。
对一项随机对照试验进行批判性评价。
这是迄今为止最大的前瞻性随机对照试验，比较了强化胰岛素治疗（血糖目标：50.4-79.2mg/dL[2.8-4.4mmol/L]和70.2-99mg/dL[3.9-5.5mmol/L] [分别用于婴儿和儿童]）和常规胰岛素治疗（目标：180-215mg/dL[10-11.9mmol/L]）在危重病儿童中的应用。两组在入组时相似，营养和葡萄糖输注率相当。未比较类固醇使用和血管活性-正性肌力药物评分。强化胰岛素治疗降低儿科重症监护病房的住院时间（主要结局指标）和衰减 C 反应蛋白浓度>5 天。强化胰岛素治疗对次要结局的影响是精确的，显著降低了继发性感染的发生（绝对风险降低=7.6%[95%置信区间：0.6-14.4]，需要治疗的人数=14[95%置信区间：7-179]）和需要血管活性支持超过 2 天（绝对风险降低=10.4%[95%置信区间：3-17]，需要治疗的人数=10[95%置信区间：6-30]）。强化胰岛素治疗可降低死亡率（p=0.038）；然而，这一发现并不精确（绝对风险降低=3.1%[95%置信区间：0.2-5.4]，需要治疗的人数=33[95%置信区间：18.6-597.3]）。强化胰岛素治疗的低血糖发生率显著升高（绝对风险增加=23.5%[95%置信区间：20-25%]，需要治疗的人数=4[95%置信区间：4-5]）。未评估对长期结局的影响，作者认识到需要进行此类随访研究。本研究在进行成人强化胰岛素治疗试验的同一机构证明了强化胰岛素治疗的疗效，但它可能不能证明在除术后心脏病患者以外的人群中或在没有高度经验丰富的护理人员来管理强化胰岛素治疗的机构中有效。
这是一项设计良好的单中心试验，为概念验证提供了依据。强化胰岛素治疗对死亡率的影响需要进一步研究，其应用可能需要改进以降低低血糖风险。同时，不能常规推荐在危重病儿童中靶向年龄调整的空腹血糖范围。
