Refractory and Super-refractory Status Epilepticus

Refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE) are neurological emergencies with considerable mortality and morbidity. In this paper, we provide an overview of causes, evaluation, treatment, and consequences of RSE and SRSE, reflecting the lack of high-quality evidence to inform therapeutic approach.

This is a narrative review based on personal practice and experience. Nevertheless, we searched MEDLINE (using PubMed and OvidSP vendors) and Cochrane central register of controlled trials, using appropriate keywords to incorporate recent evidence.

Refractory status epilepticus is commonly defined as an acute convulsive seizure that fails to respond to two or more anti-seizure medications including at least one non-benzodiazepine drug. Super-refractory status epilepticus is a status epilepticus that continues for ≥24 hours despite anesthetic treatment, or recurs on an attempted wean of the anesthetic regimen. Both can occur in patients known to have epilepsy or de novo, with increasing recognition of autoimmune and genetic causes. Electroencephalography monitoring is essential to monitor treatment response in refractory/super-refractory status epilepticus, and to diagnose non-convulsive status epilepticus. The mainstay of treatment for these disorders includes anesthetic infusions, primarily midazolam, ketamine, and pentobarbital. Dietary, immunological, and surgical treatments are viable in selected patients. Management is challenging due to multiple acute complications and long-term adverse consequences.

We have provided a synopsis of best practices for diagnosis and management of refractory/super-refractory status epilepticus and highlighted the lack of sufficient high-quality evidence to drive decision making, ending with a brief foray into avenues for future research.