摘要：

目的 评价咪达唑仑非静脉途径单药治疗儿童癫痫持续状态的有效性和安全性。方法 分别以咪达唑仑（midazolam）、癫痫持续状态（status epilepticus）、儿童（children）等中英文词汇为检索词，计算机检索近15 年美国国立医学图书馆生物医学信息检索系统、ScienceDirect数据库，以及中国知网中国知识基础设施工程、维普中文科技期刊数据库、万方数据库；同时辅助手工检索和Google Scholar 等搜索引擎在互联网检索关于咪达唑仑非静脉途径单药治疗癫痫持续状态的随机对照临床试验。采用Jadad 量表和RevMan 5.3 统计软件进行文献质量评价和Meta 分析。结果 经剔除重复和不符合纳入标准者，258篇文献中共纳入6项随机对照临床试验计766例次癫痫持续状态患儿。Meta分析显示：非静脉途径咪达唑仑组与静脉注射地西泮组疗效差异无统计学意义（RD = -0.070，95%CI：-0.200 ~ 0.060；P = 0.290），但疗效优于经直肠地西泮组（RD = 0.170，95%CI：0.030 ~ 0.320；P = 0.020）；经鼻黏膜咪达唑仑组与静脉注射地西泮组急诊入院至癫痫发作停止时间（SMD = -1.570，95%CI：-3.280 ~ 0.140；P = 0.070）和药物显效时间（SMD = 0.240，95%CI：-0.110 ~ 0.590；P = 0.170）差异均无统计学意义；非静脉途径咪达唑仑组与静脉或非静脉途径地西泮组药物不良反应差异亦无统计学意义（RD = -0.010，95%CI：-0.030 ~ 0.200；P = 0.500）。结论 咪达唑仑非静脉途径单药治疗儿童癫痫持续状态安全、有效，但尚待更多高质量多中心大样本随机对照临床试验加以验证。

关键词: 癫痫持续状态, 咪达唑仑, 地西泮, Meta分析, 儿童

Abstract:

Objective  To evaluate the clinical efficacy and safety of non-intravenous midazolam for treating status epilepticus (SE) in children.  Methods  Taking midazolam, status epilepticus and children both in Chinese and English as search terms, retrieve in databases such as PubMed, ScienceDirect, China National Knowledge Infrastructure (CNKI), VIP and Wanfang Data, assisted by manual searching and Google Scholar, in order to collect randomized controlled trials (RCTs) about non-intravenous midazolam for treating SE in children from January 2000 to January 2015. Jadad Scale was used to evaluate the quality of literatures. Meta-analysis was performed by using RevMan 5.3 software.  Results  There were a total of 258 records after preliminary searching, and 6 RCTs involving 766 episodes were finally included after excluding duplicate ones and those which did not meet the inclusion criteria. The results were as follows: 1) midazolam via intranasal administration was as effective as intravenous diazepam in achieving seizure control in children (RD = -0.070, 95%CI: -0.200—0.060, P = 0.290). However, non-intravenous (intranasal or buccal) midazolam showed better effects on seizure control than rectal diazepam (RD = 0.170, 95% CI: 0.030—0.320; P = 0.020). 2) The mean time from arrival at hospital to cessation was not significantly different between intranasal midazolam and intravenous diazepam (SMD = -1.570, 95%CI: -3.280—0.140; P = 0.070). 3) There was no statistical difference between intranasal midazolam and intravenous diazepam for the time from giving drug to cessation (SMD = 0.240, 95%CI: -0.110—0.590; P = 0.170). 4) There was no statistical difference on the occurrence rate of adverse drug reactions between non-intravenous midazolam and intravenous or non-intravenous diazepam (RD = -0.010, 95% CI: -0.030—0.200; P = 0.500).  Conclusions  Non-intravenous midazolam is safe and effective in the treatment for status epilepticus in children. However, the conclusion still needs to be further vertified by more high-quality multi-center large-sample RCTs.

Key words: Status epilepticus, Midazolam, Diazepam, Meta-analysis, Child