纳洛酮治疗中重度新生儿缺氧缺血性脑病的Meta分析

Treatment of Naloxone for Moderate and Se vere Neonatal Hypoxia-ischemic Encephalopathy: A Meta-analysis

目的系统评价纳洛酮治疗中重度新生儿缺氧缺血性脑病(HIE)的有效性和安全性。方法计算机检索Cochrane图书馆、Pub Med、Web of Science、中国学术文献总库、中文科技期刊数据库、万方数字化期刊库,检索时限为从建库至2015年6月,2名评价员按纳入与排除标准选择随机对照试验,评价质量,提取资料,并用Rev Man 5.2软件进行数据的Meta分析。结果最终纳入20个随机对照试验,治疗组783例患儿,对照组736例患儿,共计1 519例患儿。Meta分析结果显示,纳洛酮治疗中重度HIE的有效率优于对照组[OR=5.07,95%CI(3.61,7.12),P<0.000 01]。纳洛酮治疗5、7、10、14 d的新生儿行为神经评分优于对照组,差异有统计学意义[WMD=6.61分,95%CI(5.70,7.51)分,P<0.000 01;WMD=4.27分,95%CI(2.63,5.91)分,P<0.000 01;WMD=2.40分,95%CI(1.47,3.34)分,P<0.000 01;WMD=2.58分,95%CI(1.00,4.16)分,P=0.001],但治疗3 d的新生儿行为神经评分与对照组相当[WMD=0.00分,95%CI(-0.76,0.77)分,P=0.99]。纳洛酮治疗临床症状及体征的消失时间(呼吸改善时间、苏醒时间、惊厥消失时间、体征全部消失时间)均优于对照组,差异有统计学意义[WMD=-3.78 h,95%CI(-6.93,-0.64)h,P=0.02;WMD=-9.66 h,95%CI(-14.25,-5.06)h,P<0.000 1;WMD=-2.81 h,95%CI(-5.28,-0.35)h,P=0.03;WMD=-1.02 d,95%CI(-1.84,-0.20)d,P=0.01]。结论纳洛酮可有效治疗中重度HIE,但以上结论仍需高质量的随机对照试验进行进一步的论证。

Objective To objectively evaluate the effect and safety of naloxone for the treatment of moderate and severe neonatal hypoxia-ischemic encephalopathy （HIE）. Methods Research articles published from inception to June 2015 on Cochrane library, PubMed, Web of science, Chinese Science and Technology Journal Full-text Database, Digital Full-text Journal Database and Chinese Journal Full-text Database were searched, which were relevant to naloxone in the treatment of moderate and severe neonatal HIE. And two authors extracted information via standardized data extraction form and assessed the quality of included studies independently. RevMan 5.2 software was used for Meta-analysis. Results At last, 20 randomized controlled trials （involving 1 519 neonates; 783 in the treatment group and 736 in the control group） were included. The results of meta-analysis showed that the effect of naloxone for moderate and severe HIE was significantly superior to the control group [OR=5.07, 95%CI （3.61, 7.12）, P 〈 0.000 01]. The neurobehavioral scores in neonates treated by naloxone after 5, 7, 10, and 14 days were higher than those in the control group [WMD=6.61 points, 95%CI （5.70, 7.51） points, P 〈 0.000 01; WMD=4.27 points, 95%CI （2.63, 5.91） points, P 〈 0.000 01; WMD=2.40 points, 95%CI （1.47, 3.34） points, P 〈0.000 01; WMD=2.58 points, 95%CI （1.00, 4.16） points, P=0.001], respectively; while the neurobehavioral scores after 3-day treatment between the two groups had no statistically difference [WMD=0.00 points, 95%CI（-0.76, 0.77） points, P=0.99]. What＇s more, the disappeared time of clinical symptoms and signs （breathing improvement time, recovery time, convulsions disappearance time, and signs disappearance time） in naloxone group was superior to the control groups [WMD=-3.78 hours, 95%CI （-6.93, -0.64） hours, P=0.02; WMD=-9.66 hours, 95%CI （-14.25, -5.06） hours, P 〈 0.001; WMD=-2.81 hours, 95%CI （-5.28, -0.35） hours, P=0.03; WMD= -1.02 days, 95%CI （-1.84, -0.20） days, P=0.01], respectively. Conclusions Naloxone has certain therapeutic on moderate and severe HIE. Further high-quality randomized controlled trials should be carried out to provide more reliable evidence.