Treiman D M, Meyers P D, Walton N Y, Collins J F, Colling C, Rowan A J, Handforth A, Faught E, Calabrese V P, Uthman B M, Ramsay R E, Mamdani M B
Neurology Services of the Veterans Affairs Medical Center in West Los Angeles, Calif, USA.
N Engl J Med. 1998 Sep 17;339(12):792-8. doi: 10.1056/NEJM199809173391202.
Although generalized convulsive status epilepticus is a life-threatening emergency, the best initial drug treatment is uncertain. We conducted a five-year randomized, double-blind, multicenter trial of four intravenous regimens: diazepam (0.15 mg per kilogram of body weight) followed by phenytoin (18 mg per kilogram), lorazepam (0.1 mg per kilogram), phenobarbital (15 mg per kilogram), and phenytoin (18 mg per kilogram). Patients were classified as having either overt generalized status epilepticus (defined as easily visible generalized convulsions) or subtle status epilepticus (indicated by coma and ictal discharges on the electroencephalogram, with or without subtle convulsive movements such as rhythmic muscle twitches or tonic eye deviation). Treatment was considered successful when all motor and electroencephalographic seizure activity ceased within 20 minutes after the beginning of the drug infusion and there was no return of seizure activity during the next 40 minutes. Analyses were performed with data on only the 518 patients with verified generalized convulsive status epilepticus as well as with data on all 570 patients who were enrolled.
Three hundred eighty-four patients had a verified diagnosis of overt generalized convulsive status epilepticus. In this group, lorazepam was successful in 64.9 percent of those assigned to receive it, phenobarbital in 58.2 percent, diazepam plus phenytoin in 55.8 percent, and phenytoin in 43.6 percent (P=0.02 for the overall comparison among the four groups). Lorazepam was significantly superior to phenytoin in a pairwise comparison (P=0.002). Among the 134 patients with a verified diagnosis of subtle generalized convulsive status epilepticus, no significant differences among the treatments were detected (range of success rates, 7.7 to 24.2 percent). In an intention-to-treat analysis, the differences among treatment groups were not significant, either among the patients with overt status epilepticus (P=0.12) or among those with subtle status epilepticus (P=0.91). There were no differences among the treatments with respect to recurrence during the 12-hour study period, the incidence of adverse reactions, or the outcome at 30 days.
As initial intravenous treatment for overt generalized convulsive status epilepticus, lorazepam is more effective than phenytoin. Although lorazepam is no more efficacious than phenobarbital or diazepam plus phenytoin, it is easier to use.
虽然全身性惊厥性癫痫持续状态是一种危及生命的急症，但最佳的初始药物治疗尚不确定。我们进行了一项为期五年的随机、双盲、多中心试验，比较四种静脉用药方案：地西泮（0.15毫克/千克体重）后接苯妥英（18毫克/千克）、劳拉西泮（0.1毫克/千克）、苯巴比妥（15毫克/千克）以及苯妥英（18毫克/千克）。患者被分为明显全身性癫痫持续状态（定义为易于观察到的全身性惊厥）或隐匿性癫痫持续状态（通过脑电图上的昏迷和发作期放电来指示，伴有或不伴有细微的惊厥动作，如节律性肌肉抽搐或强直性眼球偏斜）。当在药物输注开始后20分钟内所有运动和脑电图癫痫活动停止，且在接下来的40分钟内无癫痫活动复发时，治疗被视为成功。分析仅使用518例确诊为全身性惊厥性癫痫持续状态患者的数据以及所有570例入组患者的数据进行。
384例患者被确诊为明显全身性惊厥性癫痫持续状态。在该组中，接受劳拉西泮治疗的患者有64.9%治疗成功，苯巴比妥为58.2%，地西泮加苯妥英为55.8%，苯妥英为43.6%（四组总体比较P = 0.02）。在两两比较中，劳拉西泮显著优于苯妥英（P = 0.002）。在134例确诊为隐匿性全身性惊厥性癫痫持续状态的患者中，各治疗组之间未检测到显著差异（成功率范围为7.7%至24.2%）。在意向性治疗分析中，治疗组之间的差异在明显癫痫持续状态患者中不显著（P = 0.12），在隐匿性癫痫持续状态患者中也不显著（P = 0.91）。在12小时研究期间，各治疗组在复发情况、不良反应发生率或30天结局方面无差异。
作为明显全身性惊厥性癫痫持续状态的初始静脉治疗，劳拉西泮比苯妥英更有效。虽然劳拉西泮并不比苯巴比妥或地西泮加苯妥英更有效，但它使用起来更方便。
