Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus
Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus
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DOI：
10.1056/nejmoa1905795
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发表时间：
2019-11-28
影响因子：
158.5
通讯作者：
Silbergleit, Robert
中科院分区：
文献类型：
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作者：
Kapur, Jaideep;Elm, Jordan;Silbergleit, Robert
背景：对于苯二氮卓类药物治疗难治性癫痫持续状态患者的药物选择尚未有深入的研究。方法：在一项随机、盲法、适应性试验中，我们比较了三种静脉注射抗惊厥药物——左乙拉西坦、磷妥英钠和丙戊酸钠——对苯二氮卓类药物治疗无反应的癫痫持续状态儿童和成人的疗效和安全性。主要结果是在药物输注开始后60分钟没有临床明显的癫痫发作和意识水平的改善，没有额外的抗惊厥药物。计算出每种药物最有效或最无效的后验概率。安全性结果包括危及生命的低血压或心律失常、气管插管、癫痫发作复发和死亡。结果共入组384例患者，随机分配接受左乙拉西坦（145例）、磷苯妥英（118例）和丙戊酸钠（121例）治疗。再入组的第二次癫痫持续状态患者占16个额外的随机化实例。根据预先规定的停止规则，发现一种药物的优势或劣势是徒劳的，计划的中期分析导致试验停止。在纳入的患者中，有10%被确定患有精神性癫痫发作。癫痫持续状态停止和60分钟意识水平改善的主要结局发生在68例左乙西坦组（47%，95%可信区间，39 - 55），53例磷苯妥英组（45%，95%可信区间，36 - 54）和56例丙戊酸组（46%，95%可信区间，38 - 55）。每种药物最有效的后验概率分别为0.41、0.24和0.35。在数值上，磷苯妥英组低血压和插管发生率高于其他组，左乙拉西坦组死亡发生率高于其他组，但这些差异并不显著。结论在苯二氮卓类难治性惊厥癫痫持续状态的情况下，抗惊厥药物左乙拉西坦、磷苯妥英和丙戊酸均能使大约一半的患者癫痫发作停止并提高警觉性60分钟，并且这三种药物的不良事件发生率相似。
BACKGROUNDThe choice of drugs for patients with status epilepticus that is refractory to treatment with benzodiazepines has not been thoroughly studied.METHODSIn a randomized, blinded, adaptive trial, we compared the efficacy and safety of three intravenous anticonvulsive agents - levetiracetam, fosphenytoin, and valproate - in children and adults with convulsive status epilepticus that was unresponsive to treatment with benzodiazepines. The primary outcome was absence of clinically evident seizures and improvement in the level of consciousness by 60 minutes after the start of drug infusion, without additional anticonvulsant medication. The posterior probabilities that each drug was the most or least effective were calculated. Safety outcomes included life-threatening hypotension or cardiac arrhythmia, endotracheal intubation, seizure recurrence, and death.RESULTSA total of 384 patients were enrolled and randomly assigned to receive levetiracetam (145 patients), fosphenytoin (118), or valproate (121). Reenrollment of patients with a second episode of status epilepticus accounted for 16 additional instances of randomization. In accordance with a prespecified stopping rule for futility of finding one drug to be superior or inferior, a planned interim analysis led to the trial being stopped. Of the enrolled patients, 10% were determined to have had psychogenic seizures. The primary outcome of cessation of status epilepticus and improvement in the level of consciousness at 60 minutes occurred in 68 patients assigned to levetiracetam (47%; 95% credible interval, 39 to 55), 53 patients assigned to fosphenytoin (45%; 95% credible interval, 36 to 54), and 56 patients assigned to valproate (46%; 95% credible interval, 38 to 55). The posterior probability that each drug was the most effective was 0.41, 0.24, and 0.35, respectively. Numerically more episodes of hypotension and intubation occurred in the fosphenytoin group and more deaths occurred in the levetiracetam group than in the other groups, but these differences were not significant.CONCLUSIONSIn the context of benzodiazepine-refractory convulsive status epilepticus, the anticonvulsant drugs levetiracetam, fosphenytoin, and valproate each led to seizure cessation and improved alertness by 60 minutes in approximately half the patients, and the three drugs were associated with similar incidences of adverse events.