Recent developments in treatment of status epilepticus: a review

Considering that status epilepticus (SE) is a medical emergency associated with significant morbidity and mortality, there are surprisingly few evidence-based data to guide management decisions. The purpose of this review is to give an overview of the incidence and classification of SE and to summarise the recent developments in the treatment of generalized tonic clonic status epilepticus (GTCSE). These consist in two prospective randomised studies indicating that SE should be treated as soon as possible, even out-of hospital, by intravenous (IV) benzodiazepine. Lorazepam is probably the best choice for the initial therapy. However, the differences in efficacy as compared to diazepam, diazepam associated to phenytoin or phenobarbital were not significant. There is no Class I evidence to help us choose which drug to give in SE that is not responsive to the initial lorazepam. Traditionally, based on a long clinical experience, IV phenytoin is given as the second drug. Recently, phenytoin is being increasingly substituted by fosphenytoin, even though no formal, comparative tolerability studies have been performed to study this compound in GTCSE. Starting in the 1980's, the use of injectable valproic acid (IV VPA) has been reported in an increasing number of uncontrolled case series initiated by doctors, indicating relative easy use, relative good tolerability and suggesting that it may be efficacious. Finally, we have very little data concerning the treatment of SE refractory to a benzodiazepine and phenytoin. Despite this lack of data many centres today use midazolam or propofol rather than phenobarbital or pentobarbital in this setting because these compounds have short half-lives and are, therefore, easier to handle.