Intravenous Antiepileptic Drugs in Adults with Benzodiazepine-Resistant Convulsive Status Epilepticus

Generalized convulsive status epilepticus (GCSE) is a time-dependent medical emergency, which requires to be promptly recognized and treated. First-line benzodiazepines effectively control GCSE in two thirds of patients. After their failure, antiepileptic drugs are administered intravenously. A recent systematic review showed that phenobarbital was the most effective and less tolerated second-line treatment for GCSE in adults. Valproate and levetiracetam were less effective than phenobarbital, but associated with lower risk of respiratory depression and hypotension; lacosamide showed a good safety profile. These results probably reflect the doses used in included trials. Phenytoin ranked worst in the likelihood of reaching GCSE cessation, reflecting the long infusion time required to prevent adverse events. The Established Status Epilepticus Treatment Trial (ESETT) demonstrated equi-effectiveness of levetiracetam, fosphenytoin, and valproate in benzodiazepine - resistant GCSE in adults and children; these drugs had similar incidences of adverse events. Overall, levetiracetam and valproate administered at adequate doses are effective and safe second-line treatments for GCSE in adults. The effectiveness of phenytoin in benzodiazepine-resistant status is hampered by its long infusion time with delayed onset of anticonvulsant activity. Further studies could evaluate the efficacy and safety of second-line drugs administered immediately after benzodiazepines and irrespective of the initial control of GCSE.