Treiman D M
Neurology Service, VA West Los Angeles Medical Center, CA.
Neurology. 1990 May;40(5 Suppl 2):32-42.
Benzodiazepines are the most potent drugs used in the management of status epilepticus (SE). A number of presynaptic, postsynaptic, and nonsynaptic actions of benzodiazepines have been described. However, only the benzodiazepines' enhancement of gamma-aminobutyric acid (GABA)ergic inhibition and their reduction of repetitive firing occur at concentrations of unbound drug comparable to those that block absence seizures or stop clinical SE in patients. Thus, it is likely that these actions contribute to antiepileptic and anti-SE efficacy of the benzodiazepines. A predictable sequence of progressive electroencephalographic (EEG) changes during the course of generalized convulsive SE, both in humans and in experimental models, has been recently described. The homology of the sequence of EEG patterns in patients and in experimental models supports the concept that animal models should be useful in evaluating the treatment of clinical SE, and benzodiazepines are effective in stopping SE in a number of animal models. Late SE in animals, however, as in humans, is less responsive to treatment than is early SE. Forty-seven clinical studies in which clonazepam, diazepam, or lorazepam was used in the treatment of SE have been reported. Overall, lasting control of SE was achieved in 79% of the 1,346 patients in these noncontrolled studies. However, no data yet exist to differentiate the efficacy of 1 of the benzodiazepines from that of the others. Therefore, the choice of benzodiazepine is best determined by availability and by pharmacokinetic differences. Because of a much smaller volume of distribution of unbound drug, lorazepam appears to have a significantly longer effective duration of action against SE than does diazepam, which is rapidly redistributed to lipid stores in the body after intravenous administration. For this reason, we now use lorazepam in the initial treatment of patients with generalized convulsive SE.
苯二氮䓬类药物是用于治疗癫痫持续状态（SE）的最有效药物。苯二氮䓬类药物的多种突触前、突触后和非突触作用已被描述。然而，只有在未结合药物浓度与阻断失神发作或终止患者临床SE的浓度相当的情况下，苯二氮䓬类药物增强γ-氨基丁酸（GABA）能抑制作用以及减少重复放电才会发生。因此，这些作用可能有助于苯二氮䓬类药物的抗癫痫和抗SE疗效。最近已经描述了在人类和实验模型中，全身性惊厥性SE过程中脑电图（EEG）渐进性变化的可预测序列。患者和实验模型中EEG模式序列的同源性支持了动物模型在评估临床SE治疗中应有用的概念，并且苯二氮䓬类药物在多种动物模型中对终止SE有效。然而，与人类一样，动物的晚期SE对治疗的反应比早期SE小。已经报道了47项使用氯硝西泮、地西泮或劳拉西泮治疗SE的临床研究。总体而言，在这些非对照研究的1346例患者中，79%实现了SE的持久控制。然而，尚无数据区分一种苯二氮䓬类药物与其他药物的疗效。因此，苯二氮䓬类药物的选择最好由可用性和药代动力学差异来决定。由于未结合药物的分布容积小得多，劳拉西泮对SE的有效作用持续时间似乎比地西泮长得多，地西泮静脉给药后会迅速重新分布到体内的脂质储存中。因此，我们现在在全身性惊厥性SE患者的初始治疗中使用劳拉西泮。
