地西泮预防热性惊厥复发的疗效与安全性的系统评价和Meta分析

摘要

Objective To systematically review the efficacy and safety of intermittent use of diazepam to prevent recurrence of febrile seizure(FS)using meta-analysis methods. Methods The Cochrane Library(Issue 7,2014),PubMed,EMBASE,CBM, CNKI,VIP and Wanfang Data were searched for the randomized controlled trails( RCTs)about prophylactic use of dizapam to control FS relapse in children up to July 2014. Two reviewers independently screened literature according to the inclusion and exclusion criteria,extracted data and evaluated the methodological quality of included studies. Then meta-analysis was performed using RevMan 5. 2 software,in subjects with low-,moderate- and high-risk of FS recurrence respectively. Results Nine studies involving 1 578 patients were included. The methodological quality evaluation defined generation of random sequences for randomization,allocation concealment,and blinding as high bias risk;selective result reporting,loss of follow up,and alternative sources of bias as low bias risk. Meta-analysis showed no significant difference in FS recurrence rate in 6-month treatment group and intermittent diazepam compared with the control group(RR=0. 62,95% CI:0. 34 to 1. 13,P=0. 12;RD= _0. 07,95%CI:_0. 16 to 0. 02). However,FS relapse rate was markedly decreased at 12 months treatment(RR=0. 59,95%CI:0. 38~0. 91, P=0. 02;RD= _0. 12,95%CI:_0. 22~ _0. 02)and 24 months treatment(RR=0. 54,95%CI:0. 37 to 0. 78,P=0. 001;RD= _0. 17,95%CI:_0. 27 to _0. 07),compared with the control group. The results of subgroup analysis by FS recurrence risk factors indicated that reduced FS recurrence rate was found in the moderate-risk group(6 months:RR=0. 31,95%CI:0. 15 to 0. 62,P=0. 000 9;12 months:RR=0. 39,95%CI:0. 20 to 0. 75 ,P=0. 005;24 months:RR=0. 43,95%CI:0. 24 to 0. 77,P=0. 005)and high-risk group(6 months:RR=0. 24,95%CI:0. 10 to 0. 15;12 months:RR=0. 27,P=0. 00 09. 95%CI:0. 13 to 0. 58,P=0. 000 7;24 months:RR=0. 35,95%CI:0. 19 to 0. 62,P=0. 000 4)but not in the low-risk group (6 months:RR=0. 69,95%CI:0. 40 to 1. 21,P=0. 20;12 months:RR=0. 81,95%CI:0. 47 to 1. 42,P=0. 46;24 months:RR=0. 71,95%CI:0. 45 to 1. 11,P=0. 14). No serious complications about diazepam was reported in the included studies. Conclusion Intermittent diazepam for 12 months or 24 months can effectively reduce FS recurrence rate,and shows good efficacy for moderate-risk and high-risk patients. Additional high quality studies are still expected to verify the above conclusion.%目的：采用Meta分析方法评价间歇使用地西泮预防热性惊厥（ FS）复发的疗效及安全性。方法计算机检索The Cochrane Library（2014年第7期）、PubMed、EMBASE、中国生物医学文献数据库、中国知网、维普中文期刊数据库和万方数据库，收集使用地西泮预防儿童FS复发的RCT文献，检索时限均为建库至2014年7月。由2位研究者按照纳入与排除标准筛选文献，提取数据和评价纳入文献的方法学质量。根据FS复发危险因素行亚组分析。采用RevMan 5.2软件进行Meta分析。结果9篇RCT文献（ n=1578）进入Meta分析。纳入文献的随机序列产生、分配隐藏和盲法为高度偏倚，选择性报告研究结果、结果的完整性和其他偏倚来源为低度偏倚。①随访6个月地西泮组与对照组FS复发率差异无统计学意义，RR=0.62（95% CI：0.34~1.13），P=0.12；RD=_0.07（95%CI：_0.16~0.02）；对FS复发危险因素行亚组分析：地西泮低危险亚组与对照组FS复发率差异无统计学意义，RR=0.69（95%CI：0.40~1.21），P=0.20，中危险亚组与高危险亚组FS复发率显著低于对照组，RR分别为0.31（95%CI：0.15~0.62）和0.24（95%CI：0.10~0.56）。②随访12和24个月地西泮组FS复发率显著低于对照组，RR分别为0.59（95%CI：0.38~0.91）和0.54（95%CI：0.37~0.78）；RD分别为_0.12（95%CI：_0.22~_0.02）和_0.17（95%CI：_0.27~_0.07）。对FS复发危险因素行亚组分析：地西泮低危险亚组与对照组FS复发率差异无统计学意义，RR分别为0.81（95% CI：0.47~1.42）和0.71（95%CI：0.45~1.11），中危险亚组与高危险亚组FS复发率显著低于对照组，12个月：RR分别为0.39（95% CI：0.20~0.75）和0.27（95%CI：0.13~0.58）；24个月：RR分别为0.43（95%CI：0.24~0.77）和0.35（95%CI：0.19~0.62）。③纳入文献均无地西泮严重不良事件的报告。结论地西泮间歇给药可有效降低12和24个月FS复发率，对于FS中高危人群显示出较好疗效的趋势，但仍需进一步补充研究明确。