Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
Division of Pharmacokinetics and Drug Therapy, Department of Pharmaceutical Biosciences, Faculty of Pharmacy, Uppsala University, Uppsala, Sweden.
Can J Neurol Sci. 2019 Nov;46(6):702-710. doi: 10.1017/cjn.2019.278.
Status epilepticus (SE) is a neurological emergency associated with significant morbidity and mortality. The objective of this study was to review the critical care management of patients with SE focusing on antiepileptic drugs (AEDs) as well as to determine the optimal dosing strategies of phenytoin (PHT) and predictors of its effectiveness.
A retrospective chart review of adult patients with SE admitted to the University of Alberta Hospital, Canada, was conducted.
Fifty-six admissions were included. Benzodiazepines (BDZs) were initially given in 89% of our patients. Following BDZs, PHT and levetiracetam were the most commonly initiated AEDs as first- and second-line agents and were deemed effective in 30/44 and 5/11 patients, respectively. Patients who received a PHT loading dose (LD) of 1000 mg were less likely to reach target levels compared with a weight-based LD ≥15 mg/kg (29% vs. 60%). Likewise, patients who received a maintenance dose (MD) of 300 mg/day were less likely to reach target compared with 400 mg/day or >5 mg/kg per day; however, this did not reach statistical significance. Three variables were found to be associated with PHT effectiveness: tonic-clonic SE (OR 5.01, 95% CI 1.02-24.7, p = 0.048), history of seizures and BMI <30 kg/m2 (OR 0.16, 95% CI 0.03-1.07, p = 0.059).
Further studies of the predictors of PHT effectiveness, specifically obesity, are necessary to help individualize care. Finally, we suggest that PHT should be loaded according to the guidelines as 20 mg/kg followed by an MD of at least 400 mg/day or >5 mg/kg per day.
癫痫持续状态（SE）是一种与显著发病率和死亡率相关的神经急症。本研究旨在回顾 SE 患者的重症监护管理，重点关注抗癫痫药物（AEDs），并确定苯妥英钠（PHT）的最佳剂量策略及其有效性的预测因素。
对加拿大阿尔伯塔大学医院收治的成人 SE 患者进行回顾性病历分析。
共纳入 56 例患者。在我们的患者中，89%的患者最初给予苯二氮䓬类药物（BDZ）。在 BDZ 之后，PHT 和左乙拉西坦作为一线和二线药物最常被使用，分别在 30/44 和 5/11 例患者中被认为有效。与接受基于体重的 LD≥15mg/kg（29%对 60%）的患者相比，接受 PHT 负荷剂量（LD）1000mg 的患者更不可能达到目标水平。同样，接受 300mg/天维持剂量（MD）的患者与接受 400mg/天或>5mg/kg/天的患者相比，更不可能达到目标水平；然而，这并未达到统计学意义。有三个变量与 PHT 的有效性相关：强直阵挛性 SE（OR 5.01，95%CI 1.02-24.7，p=0.048）、癫痫发作史和 BMI<30kg/m2（OR 0.16，95%CI 0.03-1.07，p=0.059）。
需要进一步研究 PHT 有效性的预测因素，特别是肥胖症，以帮助实现个体化治疗。最后，我们建议根据指南以 20mg/kg 给予 PHT 负荷剂量，然后给予至少 400mg/天或>5mg/kg/天的 MD。
