Refractory status epilepticus: new insights in presentation, treatment, and outcome

Refractory status epilepticus (RSE), defined as status epilepticus that fails to respond to the acute administration of two antiepileptic medications, occurs in approximately a third of patients with status epilepticus, and is associated with increased hospital length of stay, mortality, and functional disability. Common presentations include: (1) generalized convulsive status epilepticus or complex partial status epilepticus that continue despite initial therapies; (2) stupor or coma following a generalized convulsive or complex partial seizure; or (3) stupor or coma following brain surgery or acute brain injury. When status epilepticus continues or recurs 24 hours or more after the initiation of anesthetic therapy, or recurs on the reduction or withdrawal of anesthesia, it is termed super RSE. Published evidence on optimal management of RSE consists largely of case reports or small series. The mainstay of treatment is the administration of anesthetic agents titrated to electrographic seizure control. Adjunctive therapies include hypothermia and immunosuppression and less commonly, surgery, electrical stimulation therapies, and induction of ketosis. Patients with cardiopulmonary complications and prolonged duration of drug-induced coma tend to have worse post-treatment functional outcomes. However, significant improvement over time can occur in survivors, and thus treatment is justified even in patients who require prolonged anesthetic coma. The strongest predictors of outcome are duration of anesthetic coma, etiology, and development of cardiopulmonary complications.