Remarks y Status epilepticus is a medical emergency which can lead to profound systemic and neurological damage and is associated with significant short-term and long-term mortality. Timely control of status epilepticus is of paramount importance to improve the outcomes. y A staged treatment protocol for management of status epilepticus is recommended.

• Approximately 30–40% of all individuals fail to respond to initial treatment with benzodiazepines (benzodiazepine-resistant or established status epilepticus) and need further treatment with other intravenous antiseizure medicines (ASMs). The treatment of established status epilepticus is the focus of this recommendation with the above medicines initiated when seizures persist after two doses of benzodiazepines. y Advantages of levetiracetam and sodium valproate include lesser risk of adverse effects as compared with fosphenytoin. Both levetiracetam and sodium valproate are broad spectrum medicines active against all types of seizures, and hence may be a good agent for maintenance therapy after the acute control of seizures in adults with genetic generalized epilepsy or when the type of seizure/epilepsy syndrome is not clear. y There is low- to moderate-quality evidence that the safety profile of levetiracetam was better than fosphenytoin, in terms of lesser cardiovascular adverse events. y Sodium valproate has been associated with hepatic side-effects, in terms of raised transaminases and elevated ammonia levels. It is contraindicated in individuals with liver disease, which may not be evident when the person is brought in convulsing and needs emergency treatment. y There is low-quality evidence that phenobarbital has a higher risk of respiratory depression and cardiovascular adverse effects as compared with sodium valproate. y Phenobarbital and diazepam infusion carries the potential risk of sedation and respiratory depression, which may be increased if it is used after benzodiazepines. y Phenytoin has associated risks of arrhythmia and hypotension and can be difficult to administer in adults with comorbid cardiac conditions. y Most trials excluded women known to be pregnant. Seizures in pregnant women can be due to eclampsia which requires different treatment. Fosphenytoin or levetiracetam may be a better choice for women with epilepsy who have status epilepticus. y The recommendation that sodium valproate is not recommended in women and girls of childbearing potential because of potential harm to the fetus, is not included in this question. Since this recommendation covers the short-term use of sodium valproate, the teratogenic effects may vary.

Implementation considerations y The choice of medicine is affected by a number of factors, including availability, cost and side-effects. y There are feasibility and affordability issues; intravenous fosphenytoin is not currently on the WHO EML (13). y Adults treated for established status epilepticus require monitoring and may require ventilatory support; thus, secondary care is necessary. y Delay in initiation and underdosing has been observed in treatment of status epilepticus. To terminate status epilepticus as quickly as possible drugs should be given in recommended dosages. There is a need to increase awareness of quick intervention, adequate initial benzodiazepine dosing and timely initiation of second-line treatment in benzodiazepine-resistant cases. y Time to get medical attention is likely to be longer in LMICs, so advocacy is needed for better pre-hospital management of seizures.