亚低温治疗新生儿缺氧缺血性脑病远期临床效果的Meta分析

Long-term clinical efficacy of mild hypothermia therapy in neonates with hypoxic-ischemic encephalopathy: a Meta analysis

摘要:

目的 系统评价亚低温治疗新生儿缺氧缺血性脑病(HIE)的远期疗效及安全性.方法 计算机检索PubMed、EMBASE、Cochrane、中国期刊全文数据库、万方数据库及维普中文科技期刊数据库等,收集符合纳入标准的亚低温治疗新生儿HIE的研究,检索时限均为从建库至2014年3月.采用RevMan5.1软件进行Meta分析.结果 共纳入8个随机对照研究.Meta分析结果显示,随访至12~24个月时,与对照组相比,全身亚低温治疗能显著降低病死率、生长发育延迟发生率(分别RR=0.73,95%CI:0.61~0.89;RR=0.70,95%CI:0.54~0.93);选择性头部或全身亚低温治疗能显著降低脑瘫发生率(分别RR= 0.65,95%CI:0.46~0.94;RR=0.67,95%CI:0.52~0.86).1个随访至6~7岁的研究显示,与对照组比较,亚低温治疗降低了病死率及死亡/严重伤残合并发生率(P<0.05).亚低温治疗组窦性心动过缓、血小板减少、低血糖等不良反应发生率较对照组增高,而心律失常、低血压、血栓或出血、低血钾、脓毒症、肝功能异常发生率两组间差异无统计学意义.结论 亚低温治疗HIE患儿随访至12~24月龄时其疗效明显,但其对患儿儿童期的影响尚待深入研究.该治疗不良反应发生率低,临床耐受性好.

Abstract:

Objective To systematically evaluate the long-term clinical efficacy and safety of mild hypothermia therapy in neonates with hypoxic-ischemic encephalopathy (HIE). Methods All randomized controlled trials (RCTs) of mild hypothermia therapy for neonatal HIE from inception to March 2014 were retrieved from databases including Cochrane Library, PubMed, Embase, CBMdisc, and Wanfang Data. Meta analysis was performed using RevMan 5.1 Software. Results Eight RCTs met the search criteria. The results of Meta analysis showed that, compared with the control group, systemic hypothermia significantly reduced the mortality rate and the incidence of growth delay (RR=0.73, 95% CI: 0.61-0.89; RR=0.70, 95%CI: 0.54-0.93); selective head or systemic hypothermia therapy significantly reduced the incidence of cerebral palsy (RR=0.65, 95%CI: 0.46-0.94; RR=0.67, 95%CI: 0.52-0.86) up to 12-24 months of age. One study reported that hypothermia reduced the mortality rate and the rate of a composite end point of death or severe disability compared with the control group at 6 to 7 years of age. The incidence of adverse events including sinus bradyarrhythmia, thrombocytopenia and hypoglycemia was significantly higher in the hypothermia group than in the control group, whereas the incidence of cardiac arrhythmia, hypotension, thrombosis or bleeding, hypokalemia, sepsis, and liver dysfunction showed no significant differences between the two groups. Conclusions Mild hypothermia therapy demonstrates a significant efficacy in children with HIE up to 12-24 months of age, but there is still a need for further research on childhood outcomes after mild hypothermia for neonatal HIE. This therapy has few adverse effects and a high clinical tolerability.