Background

Refractory status epilepticus (RSE) represents a serious medical condition requiring early and targeted therapy. Given the increasing number of elderly or multimorbid patients with a limitation of life-sustaining therapy (LOT) or within a palliative care setting (PCS), guidelines-oriented therapy escalation options for RSE have to be omitted frequently.

Objectives

This systematic review sought to summarize the evidence for fourth-line antiseizure drugs (ASDs) and other minimally or non-invasive therapeutic options beyond guideline recommendations in patients with RSE to elaborate on possible treatment options for patients undergoing LOT or in a PCS.

Methods

A systematic review of the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focusing on fourth-line ASDs or other minimally or non-invasive therapeutic options was performed in February and June 2020 using the MEDLINE, EMBASE and Cochrane databases. The search terminology was constructed using the name of the specific ASD or therapy option and the term ‘status epilepticus’ with the use of Boolean operators, e.g. “(brivaracetam) AND (status epilepticus)”. The respective Medical Subject Headings (MeSH) and Emtree terms were used, if available.

Results

There is currently no level 1, grade A evidence for the use of ASDs in RSE. The best evidence was found for the use of lacosamide and topiramate (level 3, grade C), followed by brivaracetam, perampanel (each level 4, grade D) and stiripentol, oxcarbazepine and zonisamide (each level 5, grade D). Regarding non-medicinal options, there is little evidence for the use of the ketogenic diet (level 4, grade D) and magnesium sulfate (level 5, grade D) in RSE. The broad use of immunomodulatory or immunosuppressive treatment options in the absence of a presumed autoimmune etiology cannot be recommended; however, if an autoimmune etiology is assumed, steroid pulse, intravenous immunoglobulins and plasma exchange/plasmapheresis should be considered (level 4, grade D). Even if several studies suggested that the use of neurosteroids (level 5, grade D) is beneficial in RSE, the current data situation indicates that there is formal evidence against it.

Conclusions

RSE in patients undergoing LOT or in a PCS represents a challenge for modern clinicians and epileptologists. The evidence for the use of ASDs in RSE beyond that in current guidelines is low, but several effective and well-tolerated options are available that should be considered in this patient population. More so than in any other population, advance care planning, advance directives, and medical ethical aspects have to be considered carefully before and during therapy.

中文翻译：

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姑息治疗或维持生命治疗有限的难治性癫痫持续状态患者的治疗选择：系统评价。

背景

难治性癫痫持续状态 (RSE) 是一种严重的疾病，需要早期针对性治疗。鉴于生命维持治疗 (LOT) 或姑息治疗 (PCS) 受限的老年或多病患者数量不断增加，必须经常忽略以指南为导向的 RSE 治疗升级方案。

目标

本系统综述旨在总结 RSE 患者四线抗癫痫药物 (ASD) 和指南建议之外的其他微创或无创治疗方案的证据，以详细说明接受 LOT 或 PCS 的患者可能的治疗方案。

方法

2020 年 2 月和 2020 年 2 月和 6 月，使用 MEDLINE 对文献进行了系统综述，重点关注四线 ASD 或其他微创或无创治疗方案。 、EMBASE 和 Cochrane 数据库。搜索术语是使用特定 ASD 或治疗选项的名称和术语“癫痫持续状态”并使用布尔运算符构建的，例如“(布瓦西坦) AND (癫痫持续状态)”。使用相应的医学主题标题 (MeSH) 和 Emtree 术语（如果有）。

结果

目前尚无 1 级 A 级证据证明 ASD 在 RSE 中的使用。最好的证据是使用拉科酰胺和托吡酯（3 级，C 级），其次是布瓦西坦、吡仑帕奈（各 4 级，D 级）以及司替戊醇、奥卡西平和唑尼沙胺（各 5 级，D 级）。关于非药物选择，几乎没有证据表明在 RSE 中使用生酮饮食（4 级，D 级）和硫酸镁（5 级，D 级）。在没有推测的自身免疫病因的情况下，不建议广泛使用免疫调节或免疫抑制治疗方案；然而，如果假设为自身免疫病因，则应考虑类固醇脉冲、静脉注射免疫球蛋白和血浆置换/血浆置换术（4 级，D 级）。即使多项研究表明使用神经类固醇（5 级，D 级）对 RSE 有益，但目前的数据情况表明，有正式证据反对它。

结论

接受 LOT 或 PCS 的患者的 RSE 对现代临床医生和癫痫病学家来说是一个挑战。除了当前指南之外，在 RSE 中使用 ASD 的证据很少，但在该患者群体中应该考虑一些有效且耐受性良好的选择。与任何其他人群相比，在治疗前和治疗期间必须仔细考虑预先护理计划、预先指示和医疗伦理方面。