Treatment of refractory status epilepticus: literature review and a proposed protocol

Refractory status epilepticus describes continuing seizures despite adequate initial pharmacologic treatment. This situation is common in children, but few data are available to guide management. We review the literature related to the pharmacologic treatment and overall management of refractory status epilepticus, including midazolam, pentobarbital, phenobarbital, propofol, inhaled anesthetics, ketamine, valproic acid, topiramate, levetiracetam, pyridoxine, corticosteroids, the ketogenic diet, and electroconvulsive therapy. Based on the available data, we present a sample treatment algorithm that emphasizes the need for rapid therapeutic intervention, employs consecutive medications with different mechanisms of action, and attempts to minimize the risk of hypotension. The initial steps suggest using benzodiazepines and phenytoin. Second steps suggest using levetiracetam or valproic acid, which exert few hemodynamic adverse effects and have multiple mechanisms of action. Additional management strategies that could be employed in tertiary-care settings, such as coma induction guided by continuous electroencephalogram monitoring and surgical options, are also discussed.