在儿童发热性疾病期间应用地西泮以预防热性惊厥复发

Diazepam treatment to prevent recurrence of febrile seizures during the febrile disease in children

目的探讨地西泮在儿童发热性疾病中对热性惊厥复发的预防作用。方法研究共纳入406例患儿(平均年龄24个月),进行随机、双盲的安慰剂对照试验,纳入患儿均至少发生1次热性惊厥,在所有发热性疾病期间,参与者每8 h口服地西泮0.33 mg/kg体重或安慰剂。结果在平均1.9年的随访期间(90%的患儿出现热性惊厥复发),服用地西泮后每人每年热性惊厥的风险降低了44%(RR=0.56,95%CI 0.38~0.81,P=0.002)。对首次复发的热性惊厥的时间长度的生存分析显示,两组比较差异无统计学意义(P=0.064),但是在调整协变量后,发现地西泮对减少热性惊厥复发具有益处(P=0.027)。对热性惊厥发作时接受研究药物的患儿(地西泮组7例,安慰剂组29例)的分析结果显示,使用地西泮后热性惊厥的风险降低82%(RR=0.18,95%CI0.09~0.37,P<0.001)。在至少服用1次地西泮的153例患儿中,39%出现运动失调、嗜睡或易怒等并发症,所有患儿均没有严重不良反应发生。结论儿童仅在发热时口服地西泮是安全的,可降低热性惊厥复发的风险。

Objective To explore the preventive effect of diazepam on recurrence of febrile seizures in children with febrile diseases. Methods A total of 406 children（ 24 months） were enrolled in a randomized,double-blind placebo-controlled trial,in which children had at least one episode of febrile seizures. During all febrile illnesses,patients were given diazepam（ 0. 33 mg/kg body weight） or placebo every 8 hours. Results During an average of 1. 9-year follow-up（ 90% of children experienced recurrence of febrile seizures during the period）,the risk of febrile seizures per person per year after diazepam treatment was decreased by 44%（ RR = 0. 56,95% CI 0. 38 ~ 0. 81,P =0. 002）. The survival analysis of the length of the first recurrent febrile seizures did not showsignificant differences between the two groups（ P = 0. 064）. However,after adjusting the covariates,diazepam was found to reduce the risk of febrile seizures with a benefit（ P = 0. 027）. The children who received the study drug at the onset of febrile seizures（ 7 cases in diazepam group and 29 cases in placebo group） showed a 82% reduction in the risk of febrile seizures after radiotherapy（ RR = 0. 18,95% CI,0. 09 ~ 0. 37,P = 0. 001）. Of the 153 children who had at least 1 time of diazepam,39% of them had complications,such as dyskinesia,lethargy or irritability,and all children had no serious adverse reaction. Conclusion Diazepam is safe for children only when they have fever,and it can reduce the risk of recurrence of febrile seizures.