口服左乙拉西坦即刻预防儿童热性惊厥的多中心随机对照研究

摘要

目的：热性惊厥（febrile seizure，FS）是最常见的儿童惊厥性疾病，也是全球儿科急诊最常见的就诊原因之一。本研究即为寻求一种新的、安全有效的方法来预防 FS 的发生。方法共115例入组前6个月内有过至少2次或2次以上的 FS 发作患儿，按2∶1的比例随机分配至左乙拉西坦（Levetiracetam，LEV）组及对照组。在发热初始，LEV 组给予 LEV 片15～30 mg/(kg·d)，口服，每天2次，连续服用1周，然后每2天减半量，直到第2周结束时停药；当体温>38.5℃时口服退热药，并根据当地儿科医生建议对症处理。主要效应指标是在随访的48周内与发热相关的惊厥频率以及 FS再发率，次要指标是两组医疗费用比较。结果意向性分析显示 LEV 组78例经历了148次发热事件，其中11例经历了15次 FS 再发。对照组中37例经历了64次发热事件，19例经历了32次 FS 再发。两组间差异有显著性。使用 LEV 预防 FS 再发的医疗费用明显低于对照组。在48周的随访期间，仅一例发生比较严重的嗜睡，未发现其他的严重不良发应。结论口服 LEV 即刻预防儿童 FS 安全有效，并可减少医疗资源的浪费。%Objective Febrile seizure (FS) is the most common form of children seizure disorders. FS is perhaps one of the most frequent causes of admittance to pediatric emergency wards worldwide. We aimed to identify a new, safe, and effective therapy for preventing FS recurrence. Method A total of 115 children with a history of two or more episodes of FS were randomly assigned to levetiracetam (LEV) and control (LEV/control ratio = 2:1) groups. At the onset of fever, LEV group was orally administered with a dose of 15~30 mg/kg per day twice daily for 1 week. Thereafter, the dosage was gradually reduced until totally discontinued in the second week. The primary efficacy variable was seizure frequency associated with febrile events and FS recurrence rate (RR) during 48-weeks follow-up. The second outcome was the cost effectiveness of the two groups. Results The intention-to-treat analysis showed that 78 children in LEV group experienced 148 febrile episodes. Among these 78 children, 11 experienced 15 FS recurrences. In control group, 37 children experienced 64 febrile episodes; among these 37 children, 19 experienced 32 FS recurrences. A significant difference was observed between two groups in FS RR and FS recurrence/fever episode. The cost of LEV group for the prevention of FS recurrence is lower than control group. During 48-week follow-up period, one patient in LEV group exhibited severe drowsiness. No other side effects were observed in the same patient and in other children. Conclusions Intermittent oral LEV can effectively prevent FS recurrence and reduce wastage of medical resources.