Abstract:

Objective  To explore the efficiency and safety of drugs to prevent the recurrence of febrile seizures (FS).  Methods  Relevant literatures were searched via PubMed, EMBASE/SCOPUS, EBSCO-CINAHL, Web of Science, Cochrane Database of Systematic Reviews from December 1997 to November 2014 using the following keywords: febrile seizure OR febrile convulsion, recurrence, prevention OR prophylaxis, medicine OR medication. Publication type was limited to Meta-analysis. Extract the relevant information of Meta-analysis, such as characteristics of objects, types of study design, number of clinical trials, number of cases, search strategies, databases, information of methodology (methods of randomization, concealment, blinding, withdrawal and exit), follow-up time, heterogeneity analysis, subgroup analysis and outcome assessment, etc. Quality of Reporting of Meta-analyses (QUOROM) and Oxman-Guyatt Overview Quality Assessment Questionnaire (OQAQ) were used to assess the quality of included Meta-analyses. Jadad decision was used to assess inclusion and exclusion criteria, search strategies, effectiveness evaluation, data extraction and data analysis, to explore reliable evidence of evidence-based medicine.  Results  Eventually, four Meta-analyses were included after screening of all the literatures that can be searched out. Among those Meta-analyses, the Meta-analysis of Offringa and Newton (2012) was relatively more reliable. The results suggesed that no clinically important benefits were found in administering intermittent oral or rectal diazepam, oral phenobarbitone, phenytoin, valproate, pyridoxine, buprofen, diclofenac and acetominophen to children with FE. Only one clinical trial reported that intermittent oral clobazam could reduce the recurrence of FE in comparing with placebo at 6-month follow-up (RR = 0.360, 95% CI: 0.200-0.640; P = 0.000), but it should be verified by more randomized controlled trials (RCTs). Among 4 Meta-analyses included in this study, the Meta-analyses of Rosenbloom (2013), Masuko (2003) and Rantala (1997) did not mention the problems of publication bias; in the Meta-analysis of Offringa and Newton (2012), a funnel plot was applied for evaluation of this problem, however, no quantitative analysis was conducted to evaluate the effect of publication bias on the validity of conclusions and no further processing was mentioned. Conclusions  In view of good prognosis of recurrent FE, unsure efficacy of preventive medicine and high risk of adverse drug reactions, it should not be routinely recommended the use of antiepileptic drugs, antipyretic drugs or pyridoxine to prevent the recurrence of FE.

Key words: Seizures, febrile, Recurrence, Drug therapy, Meta-analysis

摘要：

目的 评价药物预防性治疗热性惊厥复发的有效性和安全性。方法 分别以febrile seizure OR febrile convulsion、recurrence、prevention OR prophylaxis、medicine OR medication 的不同组合为检索式，计算机检索1997 年12 月-2014 年11 月美国国立医学图书馆生物医学信息检索系统、荷兰医学文摘、EBSCO-CINAHL、Web of Science、Cochrane 系统评价数据库中关于药物预防性治疗热性惊厥复发的Meta 分析文献，提取研究对象、研究设计类型、临床试验数目、病例数、检索策略和数据库、研究方法学、随访时间、异质性分析和亚组分析，以及结局评价等资料。采用Meta 分析报告质量评价工具（QUOROM）和Oxman-Guyatt 系统评价质量评价量表（OQAQ）进行质量评价，Jadad 决策工具评价纳入与排除标准、检索策略、有效性评价、数据提取和总和、数据分析等资料。结果 最终纳入4 篇英文Meta 分析文献。其中，Offringa 和Newton（2012 年）的Meta 分析可信度相对较高，提示间断口服或直肠予地西泮、间断口服苯巴比妥、苯妥英钠、丙戊酸钠、维生素B₆、布洛芬、双氯芬酸钠、对乙酰氨基酚等药物对降低热性惊厥复发率无重要临床意义；仅1 项临床试验显示间断口服氧异安定治疗后6 个月时复发率明显降低（RR = 0.360，95%CI：0.200 ~ 0.640；P = 0.000）。4 项Meta 分析中3 项未提及发表偏倚的识别和处理，仅1 项采用漏斗图进行发表偏倚评价，但未行定量分析以评价其对Meta 分析结论科学性的影响，亦未描述对发表偏倚的进一步处理。结论 鉴于热性惊厥患儿复发后预后较好，而药物预防性治疗存在效果不确切、药物不良反应明显等缺陷，故不常规推荐抗癫痫药、解热镇痛药、维生素B₆等作为预防性治疗热性惊厥复发的常规用药。

关键词: 惊厥, 发热性, 复发, 药物疗法, Meta分析