Alldredge B K, Lowenstein D H, Simon R P
Division of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco.
Am J Med. 1989 Dec;87(6):645-8. doi: 10.1016/s0002-9343(89)80397-3.
Despite conflicting experimental and clinical evidence, diphenylhydantoin continues to be used for the treatment of alcohol withdrawal seizures in emergency departments and alcohol detoxification centers. Our goal was to evaluate the effectiveness of intravenous diphenylhydantoin for prevention of alcohol withdrawal seizures in high-risk patients using a prospective, randomized, double-blind, placebo-controlled study design.
Ninety alcoholic patients, enrolled within six hours of the initial alcohol-related seizure in a withdrawal episode, were randomly assigned to treatment with intravenous diphenylhydantoin (1,000 mg) or placebo. Seventy-one patients had a history of seizures during prior alcohol withdrawal episodes. Patients with a history of seizures unrelated to alcohol withdrawal were excluded. Drugs known to affect the seizure threshold or demonstrating cross-tolerance with alcohol were withheld. For each patient, the study endpoint was either (1) seizure recurrence or (2) a minimum 12-hour seizure-free observation period after completion of the study drug infusion.
During the postinfusion observation period, six of 45 diphenylhydantoin-treated patients and six of 45 placebo-treated patients experienced at least one recurrent seizure. Equivalent diphenylhydantoin serum levels were measured in patients with and without subsequent seizures. There was no statistically significant difference between the response rates for the two treatments (p greater than 0.05). The 95% confidence interval for the difference in response probabilities was -14.0%, 14%.
When administered to non-epileptic patients within six hours of the onset of alcohol withdrawal seizures, intravenous diphenylhydantoin failed to show a significant benefit over placebo in the prevention of subsequent seizures. We suggest that the well-documented risks of intravenous diphenylhydantoin therapy outweigh the potential benefit in the short-term treatment of alcohol withdrawal seizures.
尽管存在相互矛盾的实验和临床证据，但苯妥英钠仍继续在急诊科和酒精解毒中心用于治疗酒精戒断性癫痫发作。我们的目标是采用前瞻性、随机、双盲、安慰剂对照研究设计，评估静脉注射苯妥英钠对高危患者预防酒精戒断性癫痫发作的有效性。
90名在戒断发作时首次出现与酒精相关癫痫发作后6小时内入组的酒精性患者，被随机分配接受静脉注射苯妥英钠（1000毫克）或安慰剂治疗。71名患者既往酒精戒断发作时有癫痫发作史。有与酒精戒断无关的癫痫发作史的患者被排除。停用已知会影响癫痫阈值或与酒精有交叉耐受性的药物。对于每位患者，研究终点为以下二者之一：（1）癫痫复发；（2）完成研究药物输注后至少12小时无癫痫发作的观察期。
在输注后观察期内，45名接受苯妥英钠治疗的患者中有6名，45名接受安慰剂治疗的患者中有6名经历了至少一次癫痫复发。有或无后续癫痫发作的患者测得的苯妥英钠血清水平相当。两种治疗的有效率之间无统计学显著差异（p大于0.05）。反应概率差异的95%置信区间为-14.0%，14%。
在酒精戒断性癫痫发作开始后6小时内给予非癫痫患者静脉注射苯妥英钠，在预防后续癫痫发作方面未显示出比安慰剂有显著益处。我们认为，静脉注射苯妥英钠治疗的充分记录的风险超过了在酒精戒断性癫痫发作短期治疗中的潜在益处。
