Medical School, University of Basel, Basel, Switzerland.
CNS Drugs. 2012 Sep 1;26(9):761-72. doi: 10.2165/11633090-000000000-00000.
Refractory status epilepticus (RSE) is the most severe manifestation of status epilepticus (SE), often requiring intensive care and therapeutic coma. It is associated with prolonged intensive care unit (ICU) and hospital stays, as well as increased morbidity and mortality. Treatment involves both intravenous anaesthetics and antiepileptic drugs (AEDs) that can be administrated intravenously, by nasogastric tube or by percutaneous endoscopic gastrostomy. Experience with some of the newer AEDs for the treatment of RSE is restricted and higher-class evidence regarding tolerability and efficacy is lacking. Topiramate is a potent broad-spectrum AED with several modes of action, including blockade of the ionotropic glutamatergic AMPA receptor, which is likely to be an important mechanism for the treatment of SE. While there is no commercially available intravenous formulation, topiramate can be administered enterally, which may make it suitable for the treatment of RSE.
The objective of this study was to evaluate the tolerability, safety profile and efficacy of adjunctive and enterally administered topiramate in patients with RSE.
A medical chart review was performed of all consecutive patients treated for RSE between August 2004 and December 2011 at the ICU of the University Hospital Basel (Basel, Switzerland).
113 (43%) of all consecutive 268 patients with SE developed RSE. Of those, 35 (31%) were treated with topiramate. Median age was 60.5 years. Topiramate was used as an add-on treatment after 1-6 (median 4) prior administered AEDs had failed. It was introduced after a median of 2 (range 2-23) days for a duration of 1-24 (median 3) days. The response rate after topiramate administration as the third AED was 86% (6/7 patients), and remained stable at 67% after administration as the fourth, fifth, sixth or seventh AED when the groups of successfully and probably successfully treated patients were pooled. Overall, RSE was terminated in 71% of patients within 72 hours after first administration of topiramate, in 9% of patients, within 24 hours (none in the 800 mg/day group; 9% in the 400-799 mg/day group; and 11% in the <400 mg/day group). Mortality was 31% and was not strictly dependent on failure to terminate RSE, but also on the underlying aetiology of RSE. There were no serious or fatal adverse events directly attributable to topiramate. Adverse effects included slight hyperchloremic acidosis and hyperammonemia (all associated with co-medication with valproic acid).
Treatment with enterally administered topiramate was feasible, well tolerated and had a good safety profile in patients with RSE in this observational, single-centre, cohort study. Refractory SE was terminated in the majority of patients within 3 days after initiation of topiramate. Prospective studies are warranted to further evaluate topiramate for the treatment of RSE.
难治性癫痫持续状态（RSE）是癫痫持续状态（SE）最严重的表现形式，通常需要重症监护和治疗性昏迷。它与延长的重症监护病房（ICU）和住院时间、增加发病率和死亡率有关。治疗包括静脉麻醉剂和抗癫痫药物（AEDs），这些药物可以通过静脉、鼻胃管或经皮内镜胃造口术给予。一些新的 AED 治疗 RSE 的经验有限，缺乏关于耐受性和疗效的更高等级证据。托吡酯是一种具有多种作用机制的强效广谱 AED，包括阻断离子型谷氨酸能 AMPA 受体，这可能是治疗 SE 的重要机制。虽然没有市售的静脉制剂，但托吡酯可以口服给予，这使其可能适合治疗 RSE。
本研究旨在评估辅助和口服给予托吡酯治疗 RSE 患者的耐受性、安全性和疗效。
对 2004 年 8 月至 2011 年 12 月期间在巴塞尔大学医院 ICU 连续治疗 SE 的所有患者进行了病历回顾。
在 268 例 SE 连续患者中，有 113 例（43%）发展为 RSE。其中，35 例（31%）接受了托吡酯治疗。中位年龄为 60.5 岁。托吡酯作为附加治疗，在之前使用的 1-6 种（中位数 4 种）AED 失败后使用。它在中位数为 2（范围 2-23）天后开始使用，持续 1-24（中位数 3）天。作为第三种 AED 给药后，反应率为 86%（7/7 例患者），当成功和可能成功治疗的患者组被汇总时，作为第四、第五、第六或第七种 AED 给药后，反应率保持稳定为 67%。总体而言，在首次给予托吡酯后 72 小时内，71%的患者 RSE 终止，9%的患者在 24 小时内（800mg/天组无；400-799mg/天组 9%；<400mg/天组 11%）。死亡率为 31%，并不严格取决于 RSE 无法终止，还取决于 RSE 的潜在病因。没有直接归因于托吡酯的严重或致命的不良事件。不良事件包括轻微的高氯性酸中毒和高血氨（均与丙戊酸钠联合用药有关）。
在这项观察性、单中心队列研究中，口服给予托吡酯治疗 RSE 患者是可行的、耐受良好且具有良好的安全性。在开始托吡酯治疗后，大多数患者在 3 天内终止难治性 SE。需要前瞻性研究进一步评估托吡酯治疗 RSE。
