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 ASM, i.e. established status epilepticus. 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 Both levetiracetam and sodium valproate are broad spectrum drugs active against all types of seizures, and hence may be a good agent for maintenance therapy after the acute control of seizures in children with genetic generalized epilepsy or when the type of seizure/epilepsy syndrome is not clear. If available, intravenous levetiracetam should be considered because of its superior safety profile. y There is low- to moderate-quality evidence that the safety profile of levetiracetam was better than fosphenytoin in terms of less requirement for intubation. y There is low- to moderate-quality evidence that the safety profile of sodium valproate was better than phenytoin for cardiovascular adverse effects, and better than fosphenytoin in terms of less requirement for intubation. y The advantages of sodium valproate include a smaller risk for cardiorespiratory side-effects. y Sodium valproate has, however, been associated with risks for hepatotoxicity and pancreatitis. It is contraindicated in individuals with liver disease, which may not be evident when the person is brought in convulsing and needs emergency treatment. Also, sodium valproate is contraindicated in inherited metabolic – including mitochondrial
• disorders, which may manifest in children with seizures and status epilepticus. y Phenobarbital may cause sedation and respiratory depression, and the risk may be increased if it is used after benzodiazepines. y Phenytoin is associated with risks for arrhythmia and hypotension, and it is difficult to administer in particular settings. 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 model list of essential medicines for children (EMLc) (132). y Children treated for established status epilepticus require monitoring and may require ventilatory support; thus, tertiary/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 medicines 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.