What is the treatment for status epilepticus?

From the Guidelines

The treatment for status epilepticus requires immediate intervention with benzodiazepines as first-line therapy, followed by second-line therapy with valproate (40 mg/kg) if seizures persist, as recommended by the most recent guidelines 1.

First-Line Therapy

The initial management of status epilepticus typically involves intravenous lorazepam (0.1 mg/kg, maximum 4 mg) or diazepam (0.15-0.2 mg/kg, maximum 10 mg), or midazolam (0.2 mg/kg, maximum 10 mg) which can be given intramuscularly or buccally if IV access is unavailable, as supported by earlier studies 1.

Second-Line Therapy

If seizures persist after 5-10 minutes, second-line therapy should be initiated with valproate (40 mg/kg), which has been shown to be effective in refractory status epilepticus with potentially fewer adverse effects compared to phenytoin 1.

Refractory Status Epilepticus

For refractory status epilepticus, continuous infusions of midazolam, propofol, or pentobarbital may be necessary with EEG monitoring in an ICU setting, as recommended by the Neurocritical Care Society’s Status Epilepticus Guideline Writing Committee and the European Federation of Neurological Societies’ evidence-based guideline for status epilepticus in adults 1.

Key Considerations

Throughout treatment, it's essential to:

• Maintain airway protection
• Provide oxygen
• Monitor vital signs
• Address potential underlying causes such as electrolyte abnormalities, infection, stroke, or medication withdrawal Rapid treatment is crucial as prolonged seizures can lead to neuronal damage, with mortality increasing significantly after 30 minutes of continuous seizure activity, highlighting the importance of prompt and effective management 1.

From the FDA Drug Label

For Status Epilepticus and Non-emergent Loading Dose: Adult loading dose is 10 to 15 mg/kg at a rate not exceeding 50 mg/min. Pediatric loading dose is 15 to 20 mg/kg at a rate not exceeding 1 to 3 mg/kg/min or 50 mg/min, whichever is slower. The loading dose should be followed by maintenance doses of oral or intravenous Phenytoin Sodium Injection every 6 to 8 hours. Other measures, including concomitant administration of an intravenous benzodiazepine such as diazepam, or an intravenous short-acting barbiturate, will usually be necessary for rapid control of seizures because of the required slow rate of administration of phenytoin If administration of parenteral Phenytoin Sodium Injection does not terminate seizures, the use of other anticonvulsants, intravenous barbiturates, general anesthesia, and other appropriate measures should be considered.

The treatment for status epilepticus involves administering a loading dose of 10 to 15 mg/kg of phenytoin intravenously in adults, and 15 to 20 mg/kg in pediatric patients, at a rate not exceeding 50 mg/min in adults and 1 to 3 mg/kg/min or 50 mg/min in pediatric patients. This should be followed by maintenance doses of 100 mg orally or intravenously every 6 to 8 hours. Additionally, other measures such as concomitant administration of an intravenous benzodiazepine or an intravenous short-acting barbiturate may be necessary for rapid control of seizures. If seizures are not terminated, other anticonvulsants, intravenous barbiturates, general anesthesia, and other measures should be considered 2.

From the Research

Treatment for Status Epilepticus

The treatment for status epilepticus typically involves the administration of antiseizure medications, with the goal of promptly terminating seizures.

• The first-line treatment for status epilepticus is benzodiazepines, such as lorazepam, diazepam, or midazolam, as demonstrated by studies 3, 4, 5, 6.
• These medications can be administered through various routes, including intravenous, intramuscular, rectal, or intranasal, depending on the specific situation and the availability of intravenous access 3, 5.
• If seizures persist after the initial treatment, second-line treatments such as phenytoin, fosphenytoin, valproate, or levetiracetam may be warranted 5, 6, 7.
• In cases of refractory and super-refractory status epilepticus, intravenous anesthetics, including ketamine and γ-aminobutyric acid-mediated (GABA-ergic) medications, may be necessary 5, 6.

Administration and Timing

• The timing of treatment is crucial, and clinical response to benzodiazepines is lost with prolonged status epilepticus 3, 5.
• Administering appropriate doses of antiseizure medication in a timely manner is vital for halting seizure activity 5.
• A patient-specific approach framework, consisting of four axes: semiology, etiology, EEG correlate, and age, can help guide the management of status epilepticus 5.

Outcome and Prognosis

• The outcome of status epilepticus depends on the underlying etiology, age, rapidity of treatment, and adequacy of care 4, 6.
• Mortality and morbidity are highest with status epilepticus associated with CNS infections, which is the most important cause of status epilepticus in some countries 4.
• Adherence to a time-framed protocol in the emergency department can help improve the final outcome 4.