Consensus Protocol for the Treatment of Super-Refractory Status Epilepticus

Abstract

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