Benzodiazepine-refractory status epilepticus: A narrative review

Introduction

Seizures are a common complaint in the emergency department, with status epilepticus (SE) associated with significant morbidity and mortality. While the typical first-line therapy for seizures includes benzodiazepines, patients with SE may be refractory to benzodiazepines. Seizures of longer duration are harder to break, and SE becomes a self-sustaining cycle; thus, benzodiazepine-refractory SE is a particularly challenging condition facing emergency clinicians.

Objectives

This narrative review provides a focused evaluation of SE refractory to first-line therapy, highlighting potential underlying causes and management strategies.

Discussion

SE may occur in 22 % of seizure cases presenting to the emergency department, and up to 40 % of these patients will have seizure activity refractory to benzodiazepine therapy. Prolonged seizure activity is associated with long-term neurologic consequences. Potential underlying causes of SE include endocrine, metabolic, infectious, neurologic, obstetric, toxicologic, and traumatic etiologies. Reversing these underlying causes can help terminate seizure activity. Benzodiazepines (lorazepam, diazepam, and midazolam) are considered first-line anti-seizure medications (ASMs) and must be administered in adequate doses to reach their maximum therapeutic potential. Patients who continue seizing should receive a second dose of benzodiazepines at the 5-min mark, combined with a second-line ASM, such as fosphenytoin (preferred over phenytoin), levetiracetam, or valproic acid. Patients who continue seizing are considered to have refractory SE and should receive third-line agents, such as ketamine, pentobarbital, propofol, or thiopental, as the clinician prepares for intubation. Continuous electroencephalography (EEG) should be considered when moving from second- to third-line ASMs or when intubation is necessary. Early aggressive therapy is key for terminating seizure activity.

Conclusion

Recognizing and treating SE early is critical for preserving neurologic function. Emergency clinicians must be prepared to reverse the underlying causes of SE and utilize second- and third-line ASMs to abort seizure activity when necessary.