Should phenytoin or barbiturates be used as second-line anticonvulsant therapy for toxicological seizures?
Should phenytoin or barbiturates be used as second-line anticonvulsant therapy for toxicological seizures?
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DOI：
10.3109/15563650.2010.521506
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发表时间：
2010-10-01
影响因子：
3.3
通讯作者：
Eddleston, Michael
中科院分区：
文献类型：
--
作者：
Shah, Anoop S. V.;Eddleston, Michael
导论.癫痫发作是自我中毒的常见后遗症。然而，其机制不同于其他病因的癫痫发作。毒物性癫痫发作是由于正常神经元兴奋性和抑制性平衡的改变引起的。相比之下，特发性或创伤相关的癫痫发作通常始于异常神经元的病灶。对于这两种形式的癫痫发作，推荐苯二氮卓类药物作为一线治疗;然而，关于使用苯妥英或巴比妥类药物作为二线治疗存在争议。方法和结果。在这篇文章中，我们系统地回顾了使用这些药物作为毒性癫痫发作的二线治疗的证据。巴比妥类药物通过增加氯离子通道开放的持续时间，补充苯二氮卓类药物对GABAA受体的抗惊厥作用;苯妥英阻断电压依赖性钠通道，以抑制活性电灶的传播，这种作用对非毒性癫痫发作更有用。我们没有发现比较苯妥英钠和巴比妥类药物治疗苯二氮卓类药物难治性毒性癫痫发作的随机对照试验;同样，也没有发现比较这些药物在非中毒患者中使用的试验。动物研究表明，苯巴比妥对许多毒物比苯妥英更有效;少数病例报告表明患者的反应更好。结论尽管缺乏高质量的临床试验数据，药理学知识和动物研究表明，苯巴比妥或硫喷妥钠应作为控制毒性癫痫发作的二线药物。由于缺乏临床或动物研究，新药物如丙泊酚和左乙拉西坦在毒理学癫痫发作中的作用目前尚不清楚。
Introduction. Seizures are a common sequela of self-poisoning. However, their mechanism differs from seizures of other etiologies. Toxicological seizures result from alterations in the excitatory and inhibitory balance of otherwise normal neurons. In contrast, idiopathic or trauma related seizures usually start with a focus of abnormal neurons. For both forms of seizures, benzodiazepines are recommended as first-line therapy; however, there is debate about the use of phenytoin or barbiturates for second-line therapy. Methods and Results. In this article, we systematically review the evidence for the use of these drugs as second-line therapy for toxicological seizures. Barbiturates complement the anticonvulsant effect of benzodiazepines at the GABAA receptor by increasing the duration of chloride channel opening; phenytoin blocks voltage-dependent sodium channels to inhibit propagation from active electrical foci, an effect more useful for nontoxicological seizures. We found no randomized controlled trial comparing phenytoin and barbiturates in toxicological seizures refractory to benzodiazepines; similarly no trial was found comparing the use of these drugs in nonpoisoned patients. Animal studies indicate that phenobarbital has greater effectiveness than phenytoin for many poisons; a few case reports suggest a better response in patients. Conclusion. Despite the lack of high-quality clinical trial data, pharmacological knowledge and animal studies suggest that phenobarbital or thiopentone should be second-line agents for controlling toxicological seizures. The role of newer agents such as propofol and levetiracetam in toxicological seizures is currently unclear because of a lack of clinical or animal studies.