Consensus Protocol for the Treatment of Super-Refractory Status Epilepticus

Daniel Gomes, José Pimentel, Carla Bentes, Diana Aguiar de Sousa, Ana Patrícia Antunes, António Alvarez, Zélia Costa e Silva


Introduction: Super-refractory status epilepticus is defined as status epilepticus that persists or recurs 24 hours after anaesthetic therapy onset or after its withdrawal. It is mostly found in intensive care units and carries high mortality but good long-term prognosis for those who survive. In contrast with the initial phases of status epilepticus, treatment lacks strong scientific evidence and is mostly derived from case reports or small case series.
Objective: To propose a protocol for the treatment of super-refractory status epilepticus in level III intensive care units, focusing on the treatment strategies to control clinical and/or electroencephalographic epileptic activity.
Material and Methods: Narrative review of the literature by PubMed search. Available evidence was discussed in consensus meetings by intensive care and neurology experts’ from a level III intensive care unit and one of the Portuguese reference centres for the treatment of refractory epilepsy, respectively.
Results: Anaesthetics with the highest level of evidence are propofol, midazolam, thiopental and ketamine. These represent the basis of the treatment of super-refractory status epilepticus and should be used in combination with antiepileptic drugs. The level of evidence for the latter is lower, however, levetiracetam, topiramate, pregabalin, lacosamide, valproic acid, phenytoin and perampanel may be recommended. Alternative therapeutic strategies with very low level of evidence are recommended in cases of total absence of clinical response, such as magnesium sulphate, pyridoxine, ketogenic diet, therapeutic hypothermia and immunosupression.
Conclusion: We propose a treatment protocol based on a sequential combination of anaesthetics, anti-epileptic drugs and alternative therapies. Strategies to evaluate treatment response and to wean drugs based on clinical results are also proposed.


Clinical Protocols; Consensus; Critical Care; Review Literature; Status Epilepticus

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