Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Eur J Neurol. 2011 Dec;18(12):1391-6. doi: 10.1111/j.1468-1331.2011.03420.x. Epub 2011 May 9.
Evidence-based data to guide the management of status epilepticus (SE) after failure of primary treatment are still scarce and the alternate needs to be found when phenytoin (PHT) is not available or contraindicated. Comparison of intravenous (IV) valproate (VPA) and diazepam (DZP) infusion has not been conducted in adults with SE. This prospective randomized controlled trial is thus designed to evaluate the relative efficacy and safety of IV VPA and continuous DZP infusion as second-line anticonvulsants.
After failure of first-line anticonvulsants treatment, patients with generalized convulsive status epilepticus (GCSE) were randomized to receive either IV VPA or continuous DZP infusion. Primary outcome was the proportion of patients with effective control. Side effects were also evaluated.
There were 66 cases enrolled, with the mean age of 41 ± 21 years. Seizure was controlled in 56% (20/36) of the DZP group and 50% (15/30) of the VPA group (P = 0.652). No patient in the VPA group developed respiratory depression, hypotension, or hepatic dysfunction, whereas in the DZP group, 5.5% required ventilation and 5.5% developed hypotension. Time (hour) for regaining consciousness after control was near-significantly longer in the DZP group [13(3.15-21.5)] than in the VPA group [3(0.75-11)] (P = 0.057). Virus encephalitis and long duration of GCSE were independent risk factors of drug resistance.
Both IV VPA and continuous DZP infusion are effective second-line anticonvulsants for GCSE. IV VPA was well tolerated and free of respiratory depression and hypotension, which may develop in the DZP group. Outcome parameters were not significantly different between groups.
对于苯妥英(Phenytoin,PHT)禁忌或无效的癫痫持续状态(Status Epilepticus,SE)患者,缺乏指导其治疗的循证医学证据,需要寻找替代药物。目前尚未在成人 SE 患者中比较静脉用(Intravenous,IV)丙戊酸钠(Valproate,VPA)和地西泮(Diazepam,DZP)的疗效。因此,本前瞻性随机对照试验旨在评估 IV VPA 和持续 DZP 输注作为二线抗惊厥药物的相对疗效和安全性。
在一线抗惊厥药物治疗失败后,全身性强直阵挛性 SE(Generalized Convulsive Status Epilepticus,GCSE)患者被随机分为接受 IV VPA 或持续 DZP 输注组。主要结局为有效控制的患者比例。同时评估了不良反应。
共纳入 66 例患者,平均年龄为 41 ± 21 岁。DZP 组 56%(20/36)和 VPA 组 50%(15/30)的患者癫痫得到控制(P = 0.652)。VPA 组无呼吸抑制、低血压或肝功能障碍患者,而 DZP 组 5.5%的患者需要通气,5.5%的患者出现低血压。DZP 组控制后意识恢复时间(小时)[13(3.15-21.5)]明显长于 VPA 组[3(0.75-11)](P = 0.057)。病毒脑炎和 GCSE 持续时间较长是药物抵抗的独立危险因素。
IV VPA 和持续 DZP 输注均是 GCSE 的有效二线抗惊厥药物。IV VPA 耐受性良好,无呼吸抑制和低血压,而 DZP 组可能出现这些不良反应。两组间结局参数无显著差异。