Status epilepticus in children is a common and life-threatening complication that challenges practitioners worldwide, from primary to tertiary care. Whilst there is strong evidence to support first-line intervention with benzodiazepines, the medical world has been holding its breath waiting for the definitive outcome of various multicenter studies exploring optimal second-line interventions. Until this information is established, management beyond the recommended two doses of benzodiazepines remains diverse, with multiple, strongly advocated protocols enforced across different centres, countries, and training courses. Challenges to provide optimal care go beyond the drugs used to include the compounding complications from the underlying aetiologies, the time taken to present to medical services for intervention, accessibility to services, and the capacity to provide acute emergency care inclusive of monitoring, airway protection, and drugs. This is in addition to access to trained practitioners. In resource-equipped settings, children with refractory seizures are admitted to intensive care units and can undergo rapid sequence induction. In most regions of the world this level of support is not possible. As such, studies to assess second-line interventions should ideally relate to real-time clinical care across the world, to reflect areas with limited monitoring resources and with health structures that cannot support expensive treatments or interventions. These centres cannot be expected to establish and follow unsustainable guidelines. Clinicians based in these centres cannot advocate unrealistic facilities in the setting of other major healthcare demands. Based on this, it was important that the most recent multicenter, second-line status studies compared agents that can be realistically implemented as common practice world-wide. The three most recent well-designed major studies, ConSEPT (Australia and New Zealand, 13 centres), EcLiPSE (UK, 30 centres), and the ESETT (USA, adults and children, 74 sites) compared, primarily, phenytoin or fosphenytoin with levetiracetam while one study also included an arm for valproate. The studies found no evidence that levetiracetam performed better than phenytoin, or valproate (in the the case of the ESETT study). This was at variance with anecdotal expectations and increasing common practice trends for the use of levetiracetam. The EcLiPSE study noted that the administration and adverse response profile was better for levetiracetam. None of these funded studies were based in lowand middle-income countries (LMICs). None addressed the common challenges faced in these countries. None included phenobarbital in the study arms. Parenteral phenobarbital has been proposed to be an ideal second-line treatment in areas with limited resources. Unless over-dosage with benzodiazepines occurs or there are complications from underlying aetiology, this agent is welltolerated, can be administered via various routes, and patients receiving it appear more resilient to requiring intensive care unit support. In resource-limited settings, benzodiazepine-resistance is not infrequent, and is most typically exacerbated by delayed presentations. As such, effective intervention with viable second-line therapy is often urgently needed. Phenytoin cannot be repeated, it requires cardiac monitoring and infusion through a large vein in a glucose free solution, fosphenytoin is costly, valproate requires monitoring for hepatic dysfunction, and levetiracetam is not currently available across most LMICs at the point of entry for a child presenting with status epilepticus. Even at LMIC tertiary centres, very few can afford to supply levetiracetam. It is frustrating that after all the expertise, financial investment, and effort invested in the identification of optimal, second-line intervention for status epilepticus, phenobarbital was not included in any of these major studies. A multicentre comparison study which includes phenobarbital is needed to understand if this treatment does have a role in status epilepticus management protocols.

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儿童癫痫持续状态的治疗：我们现在在哪里？

儿童癫痫持续状态是一种常见且危及生命的并发症，对全世界从初级保健到三级保健的从业者提出了挑战。虽然有强有力的证据支持苯二氮卓类药物的一线干预，但医学界一直在等待各种探索最佳二线干预措施的多中心研究的最终结果。在此信息确定之前，超过推荐的两个剂量的苯二氮卓类药物的管理仍然多种多样，在不同的中心、国家和培训课程中实施了多种强烈提倡的协议。提供最佳护理的挑战超出了所使用的药物，包括潜在病因的复合并发症、向医疗服务提供干预所需的时间、服务的可及性、以及提供紧急紧急护理的能力，包括监测、气道保护和药物。这是对训练有素的从业者的补充。在资源充足的环境中，难治性癫痫儿童入住重症监护病房，可以进行快速序列诱导。在世界上的大多数地区，这种支持水平是不可能的。因此，理想情况下，评估二线干预措施的研究应与世界各地的实时临床护理相关，以反映监测资源有限的地区以及无法支持昂贵治疗或干预措施的卫生结构。不能指望这些中心建立和遵循不可持续的指导方针。在这些中心的临床医生不能在其他主要医疗保健需求的环境中提倡不切实际的设施。基于此，重要的是，最近的多中心、二线状态研究比较了可以在世界范围内作为普遍做法实际实施的药物。最近三项精心设计的主要研究 ConSEPT（澳大利亚和新西兰，13 个中心）、EcLiPSE（英国，30 个中心）和 ESETT（美国，成人和儿童，74 个中心）主要比较了苯妥英或磷苯妥英与左乙拉西坦，而一项研究还包括丙戊酸盐的手臂。研究发现没有证据表明左乙拉西坦的表现优于苯妥英或丙戊酸盐（就 ESETT 研究而言）。这与轶事预期和使用左乙拉西坦的常见实践趋势不一致。EcLiPSE 研究指出，左乙拉西坦的给药和不良反应曲线更好。这些获得资助的研究都不是基于低收入和中等收入国家 (LMIC)。没有一个涉及这些国家面临的共同挑战。研究组中没有包括苯巴比妥。在资源有限的地区，肠外苯巴比妥已被提议作为理想的二线治疗药物。除非发生苯二氮卓类药物过量或潜在病因引起并发症，否则这种药物耐受性良好，可以通过多种途径给药，并且接受它的患者似乎更能适应需要重症监护病房的支持。在资源有限的环境中，苯二氮卓类耐药并不罕见，最常见的是因就诊延迟而加剧。因此，通常迫切需要对可行的二线治疗进行有效干预。苯妥英不能重复，它需要在无葡萄糖溶液中通过大静脉进行心脏监测和输注，磷苯妥英价格昂贵，丙戊酸盐需要监测肝功能障碍，并且目前大多数 LMIC 无法在大多数 LMIC 儿童出现癫痫持续状态时使用左乙拉西坦。即使在 LMIC 三级中心，也很少有人能够负担得起左乙拉西坦的供应。令人沮丧的是，在确定癫痫持续状态的最佳二线干预措施方面投入了所有专业知识、资金投入和努力之后，苯巴比妥并未被纳入任何这些主要研究中。需要进行包括苯巴比妥在内的多中心比较研究，以了解这种治疗是否确实在癫痫持续状态管理方案中起作用。丙戊酸盐需要监测肝功能障碍，目前在大多数 LMIC 中，对于出现癫痫持续状态的儿童，左乙拉西坦在入院时不可用。即使在 LMIC 三级中心，也很少有人能够负担得起左乙拉西坦的供应。令人沮丧的是，在确定癫痫持续状态的最佳二线干预措施方面投入了所有专业知识、资金投入和努力之后，苯巴比妥并未包括在任何这些主要研究中。需要进行包括苯巴比妥在内的多中心比较研究，以了解这种治疗是否确实在癫痫持续状态管理方案中起作用。丙戊酸盐需要监测肝功能障碍，目前在大多数 LMIC 中，对于出现癫痫持续状态的儿童，左乙拉西坦在入院时不可用。即使在 LMIC 三级中心，也很少有人能够负担得起左乙拉西坦的供应。令人沮丧的是，在确定癫痫持续状态的最佳二线干预措施方面投入了所有专业知识、资金投入和努力之后，苯巴比妥并未被纳入任何这些主要研究中。需要进行包括苯巴比妥在内的多中心比较研究，以了解这种治疗是否确实在癫痫持续状态管理方案中起作用。即使在 LMIC 三级中心，也很少有人能够负担得起左乙拉西坦的供应。令人沮丧的是，在确定癫痫持续状态的最佳二线干预措施方面投入了所有专业知识、资金投入和努力之后，苯巴比妥并未被纳入任何这些主要研究中。需要进行包括苯巴比妥在内的多中心比较研究，以了解这种治疗是否确实在癫痫持续状态管理方案中起作用。即使在 LMIC 三级中心，也很少有人能够负担得起左乙拉西坦的供应。令人沮丧的是，在确定癫痫持续状态的最佳二线干预措施方面投入了所有专业知识、资金投入和努力之后，苯巴比妥并未被纳入任何这些主要研究中。需要进行包括苯巴比妥在内的多中心比较研究，以了解这种治疗是否确实在癫痫持续状态管理方案中起作用。