Temkin N R, Dikmen S S, Wilensky A J, Keihm J, Chabal S, Winn H R
Department of Neurological Surgery, University of Washington, Seattle 98104.
N Engl J Med. 1990 Aug 23;323(8):497-502. doi: 10.1056/NEJM199008233230801.
Antiepileptic drugs are commonly used to prevent seizures that may follow head trauma. However, previous controlled studies of this practice have been inconclusive.
To study further the effectiveness of phenytoin (Dilantin) in preventing post-traumatic seizures, we randomly assigned 404 eligible patients with serious head trauma to treatment with phenytoin (n = 208) or placebo (n = 196) for one year in a double-blind fashion. An intravenous loading dose was given within 24 hours of injury. Serum levels of phenytoin were maintained in the high therapeutic range (3 to 6 mumol of free phenytoin per liter). Follow-up was continued for two years. The primary data analysis was performed according to the intention to treat.
Between drug loading and day 7, 3.6 percent of the patients assigned to phenytoin had seizures, as compared with 14.2 percent of patients assigned to placebo (P less than 0.001; risk ratio, 0.27; 95 percent confidence interval, 0.12 to 0.62). Between day 8 and the end of year 1, 21.5 percent of the phenytoin group and 15.7 percent of the placebo group had seizures; at the end of year 2, the rates were 27.5 percent and 21.1 percent, respectively (P greater than 0.2 for each comparison; risk ratio, 1.20; 95 percent confidence interval, 0.71 to 2.02). This lack of a late effect could not be attributed to differential mortality, low phenytoin levels, or treatment of some early seizures in patients assigned to the placebo group.
Phenytoin exerts a beneficial effect by reducing seizures only during the first week after severe head injury.
抗癫痫药物常用于预防头部创伤后可能发生的癫痫发作。然而，此前关于这种做法的对照研究尚无定论。
为了进一步研究苯妥英钠（大仑丁）预防创伤后癫痫发作的有效性，我们将404例符合条件的重度头部创伤患者以双盲方式随机分为苯妥英钠治疗组（n = 208）或安慰剂组（n = 196），治疗一年。在受伤后24小时内给予静脉负荷剂量。苯妥英钠的血清水平维持在高治疗范围内（每升游离苯妥英3至6微摩尔）。随访持续两年。主要数据分析按意向性治疗进行。
在药物负荷期至第7天，分配到苯妥英钠组的患者中有3.6%发生癫痫发作，而分配到安慰剂组的患者中有14.2%发生癫痫发作（P<0.001；风险比，0.27；95%置信区间，0.12至0.62）。在第8天至第1年末，苯妥英钠组有21.5%的患者发生癫痫发作，安慰剂组为15.7%；在第2年末，发生率分别为27.5%和21.1%（每次比较P>0.2；风险比，1.20；95%置信区间，0.71至2.02）。这种后期无效应不能归因于死亡率差异、苯妥英钠水平低或安慰剂组中一些早期癫痫发作的治疗。
苯妥英钠仅在重度头部损伤后的第一周通过减少癫痫发作发挥有益作用。
