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危重患儿的严格血糖控制
Tight Glycemic Control in Critically Ill Children


Michael S.D. Agus ... 其他 • 2017.02.23

重视血糖控制目标,改善危重患儿预后

 

韩峻峰,贾伟平*

上海交通大学附属第六人民医院内分泌代谢科;上海市糖尿病临床医学中心;上海市糖尿病重点实验室;上海市糖尿病研究所;上海市代谢病临床医学中心

* 通讯作者

 

2009年美国临床内分泌医师学会(American Association of Clinical Endocrinologists,AACE)和美国糖尿病学会(American Diabetes Association,ADA)联合发表共识,提出不可忽视危重患者和重症监护治疗病房(intensive care unit,ICU)患者的血糖控制1。国际上围绕成人血糖控制目标的研究结论并不一致。最初比利时Leuven研究显示将血糖严格控制在4.4~6.1 mmol/L,比常规控制组10~11.1 mmol/L能够减少成年危重患者的死亡率,缩短ICU住院时间,降低ICU住院>3日者的死亡率2。但之后多个临床试验结果并不支持这个结论。大型多中心的随机对照研究NICE-SUGAR(Normal Glycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation)结果证实:强化治疗组(血糖控制目标:4.5~6.0 mmol/L)90日死亡率显著高于常规治疗组(血糖控制目标:8~10 mmol/L);且源于心血管的死亡和严重低血糖在强化治疗组中更多见3。因此,2010年ADA推荐院内危重患者的血糖控制目标为7.8~10 mmol/L;最新颁布的《中国住院患者血糖管理专家共识》对成人危重患者血糖要求宽松控制,具体目标为空腹7.8~10.0 mmol/L,餐后2小时血糖或随机血糖7.8~13.9 mmol/L4。由于儿科患者血糖控制证据不充分,共识申明此目标不一定适合重症儿童。

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摘要


背景

在多中心研究中,以达到正常血糖水平为目标的严格血糖控制未能改善心脏手术后危重成人或患儿的结局。而有关未接受心脏手术的危重患儿的研究尚缺乏。

 

方法

在这项35个中心的试验中,我们将确定合并高血糖(排除接受心脏手术的患者)的危重患儿随机分配至两种血糖控制范围中的一组:即80~110 mg/dL(4.4~6.1 mmol/L;较低控制目标组)或150~180 mg/dL(8.3~10.0 mmol/L;较高控制目标组)。临床医师接受持续葡萄糖监测及胰岛素调整确切方法的指导。主要结局是28日内不在重症监护治疗病房(ICU)的天数。

 

结果

该试验根据数据和安全性监察委员会建议提前终止,原因是获益的可能性低,以及有证据表明可能存在伤害。在713例患者中,360例随机分配至较低控制目标组,353例则至较高控制目标组。在意向治疗分析中,不在ICU的(ICU-free)中位天数在较低控制目标组和较高控制目标组之间没有显著差异(分别为19.4日[四分位距,0~24.2]以及19.4日[四分位距,6.7~23.9];P=0.58)。在符合方案分析中,在中位时间加权的平均葡萄糖水平方面,较低控制目标组(109 mg/dL [四分位距,102~118];6.1 mmol/L [四分位距,5.7~6.6])显著低于较高控制目标组(123 mg/dL [四分位距,108~142];6.8 mmol/L [四分位距,6.0~7.9];P<0.001)。较低控制目标组中的患者与较高控制目标组相比,具有较高的医疗相关感染率(349例患者中的12名[3.4%]对349例患者中的4名[1.1%],P=0.04),以及较高的重度低血糖发生率,定义为血糖水平低于40 mg/dL(2.2 mmol/L)(18例患者[5.2%]对7例[2.0%],P=0.03)。在死亡率、器官功能障碍的严重程度或是不使用通气机的天数方面,没有发现显著差异。

 

结论

与较高的血糖控制目标(血糖水平150~180 mg/dL)相比,合并高血糖的危重患儿未从严格血糖控制(以较低的血糖水平80~110 mg/dL为控制目标)中获益(由美国国立心肺血液研究所[National Heart,Lung,and Blood Institute]等资助;HALF-PINT研究在ClinicalTrials.gov注册号为NCT01565941)。





作者信息

Michael S.D. Agus, M.D., David Wypij, Ph.D., Eliotte L. Hirshberg, M.D., Vijay Srinivasan, M.D., E. Vincent Faustino, M.D., Peter M. Luckett, M.D., Jamin L. Alexander, B.A., Lisa A. Asaro, M.S., Martha A.Q. Curley, R.N., Ph.D., Garry M. Steil, Ph.D., and Vinay M. Nadkarni, M.D., for the HALF-PINT Study Investigators and the PALISI Network*
From the Division of Medicine Critical Care (M.S.D.A., J.L.A., G.M.S.) and the Department of Cardiology (D.W., L.A.A.), Boston Children’s Hospital and Harvard Medical School, Boston; the Division of Pediatric Critical Care, University of Utah Medical School, Primary Children’s Hospital, Salt Lake City, and Intermountain Medical Center, Murray — both in Utah (E.L.H.); Children’s Hospital of Philadelphia (V.S., V.M.N.) and the Perelman School of Medicine (V.S., M.A.Q.C., V.M.N.) and the School of Nursing (M.A.Q.C.), University of Pennsylvania — all in Philadelphia; Yale School of Medicine, New Haven, CT (E.V.F.); and Children’s Medical Center Dallas and the University of Texas Southwestern Medical School, Dallas (P.M.L.). Address reprint requests to Dr. Agus at Boston Children’s Hospital, 300 Longwood Ave., Boston, MA 02115, or at michael.agus@childrens.harvard.edu. *A complete list of the Heart and Lung Failure–Pediatric Insulin Titration (HALF-PINT) study investigators and a description of the involvement of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) network are provided in the Supplementary Appendix, available at NEJM.org.

 

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