Rosman N P, Colton T, Labazzo J, Gilbert P L, Gardella N B, Kaye E M, Van Bennekom C, Winter M R
Department of Pediatrics, Tufts University School of Medicine, Boston, MA.
N Engl J Med. 1993 Jul 8;329(2):79-84. doi: 10.1056/NEJM199307083290202.
Phenobarbital, once widely prescribed to prevent febrile seizures, is now in disfavor because of its side effects and lack of efficacy. Diazepam, administered only during episodes of fever, may be a safe, effective agent to prevent the recurrence of febrile seizures.
We conducted a randomized, double-blind, placebo-controlled trial among 406 children (mean age, 24 months) who had at least one febrile seizure. Diazepam (0.33 mg per kilogram of body weight) or placebo was administered orally every eight hours during all febrile illnesses.
During a mean follow-up of 1.9 years (a period during which 90 percent of febrile seizures recur), our intention-to-treat analysis showed a reduction of 44 percent in the risk of febrile seizures per person-year with diazepam (relative risk = 0.56; 95 percent confidence interval, 0.38 to 0.81; P = 0.002). A survival analysis of the length of time to the first recurrent febrile seizure did not show a significant difference between the treatment groups (P = 0.064 by the log-rank test), but after adjustment for covariates, diazepam was found to have a benefit (P = 0.027 by Cox regression analysis). An analysis restricted to children who had seizures while actually receiving the study medication (7 in the diazepam group and 29 in the placebo group) showed an 82 percent reduction in the risk of febrile seizures with diazepam (relative risk = 0.18; 95 percent confidence interval, 0.09 to 0.37; P < 0.001). Of the 153 children who took at least one dose of diazepam, 39 percent had ataxia, lethargy, or irritability or at least one other moderate side effect that was reversed after a reduction in the dose. There were no severe side effects.
Oral diazepam, given only when fever is present, is safe and reduces the risk of recurrent febrile seizures.
苯巴比妥曾被广泛用于预防热性惊厥，但由于其副作用及疗效欠佳，现已不再受青睐。仅在发热期间给予地西泮，可能是预防热性惊厥复发的一种安全、有效的药物。
我们对406名至少有一次热性惊厥的儿童（平均年龄24个月）进行了一项随机、双盲、安慰剂对照试验。在所有发热性疾病期间，每8小时口服一次地西泮（0.33毫克/千克体重）或安慰剂。
在平均1.9年的随访期间（在此期间90%的热性惊厥会复发），我们的意向性分析显示，地西泮使每人每年热性惊厥的风险降低了44%（相对风险=0.56；95%置信区间，0.38至0.81；P=0.002）。对首次复发性热性惊厥的发作时间进行的生存分析显示，治疗组之间没有显著差异（对数秩检验P=0.064），但在对协变量进行调整后，发现地西泮有获益（Cox回归分析P=0.027）。一项仅限于在实际接受研究药物治疗时发生惊厥的儿童的分析（地西泮组7例，安慰剂组29例）显示，地西泮使热性惊厥的风险降低了82%（相对风险=0.18；95%置信区间，0.09至0.37；P<0.001）。在153名至少服用一剂地西泮的儿童中，39%出现共济失调、嗜睡或易怒或至少一种其他中度副作用，在剂量减少后这些副作用得到缓解。没有严重副作用。
仅在发热时口服地西泮是安全的，并可降低复发性热性惊厥的风险。
