A RANDOMIZED, DOUBLE-BLIND-STUDY OF PHENYTOIN FOR THE PREVENTION OF POSTTRAUMATIC SEIZURES
A RANDOMIZED, DOUBLE-BLIND-STUDY OF PHENYTOIN FOR THE PREVENTION OF POSTTRAUMATIC SEIZURES
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DOI：
10.1056/nejm199008233230801
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发表时间：
1990-08-23
影响因子：
158.5
通讯作者：
WINN, HR
中科院分区：
文献类型：
--
作者：
TEMKIN, NR;DIKMEN, SS;WINN, HR
背景：抗癫痫药物通常用于预防头部外伤后的癫痫发作。然而，以前对这种做法的对照研究没有结论。研究方法：为了进一步研究苯妥英钠（苯妥英钠）预防创伤后癫痫发作的有效性，我们将404例符合条件的严重头部创伤患者随机分为苯妥英钠组（n = 208）和安慰剂组（n = 196），以双盲方式治疗1年。受伤后24小时内给予静脉负荷剂量。苯妥英的血清水平维持在高治疗范围（3至6 μ mol游离苯妥英/升）。随访持续两年。结果：在药物负荷和第7天之间，3.6%的苯妥英钠组患者发生癫痫发作，而安慰剂组患者为14.2%（P < 0.001;风险比为0.27; 95%置信区间为0.12 ~ 0.62）。从第8天到第1年结束，苯妥英组和安慰剂组分别有21.5%和15.7%的人癫痫发作;在第2年结束时，癫痫发作率分别为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）。这种迟发效应的缺乏不能归因于死亡率差异、苯妥英钠水平低或安慰剂组患者对某些早期癫痫发作的治疗。结论：苯妥英钠仅在重型颅脑损伤后第一周内通过减少癫痫发作发挥有益作用。
Background: Antiepileptic drugs are commonly used to prevent seizures that may follow head trauma. However, previous controlled studies of this practice have been inconclusive. Methods: To study further the effectivneess 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 .mu.mol of free phenytoin per liter). Follow-up was continued for two years. The primary data analysis was performed according to the intention to treat. Results: 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 < 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 > 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. Conclusions: Phenytoin exerts a beneficial effect by reducing seizures only during the first week after severe head injury.