If using rapid-sequence intubation, short-acting paralytics are preferred to prevent masking of ongoing seizure activity.

Antibiotics with or without antivirals should also be considered and adequate oxygenation confirmed because central nervous system infections and anoxic injury are major concerns in patients in status epilepticus.

Benzodiazepines are the first line of treatment and the mainstay of seizure management. Intravascular (including both intravenous and intraosseous routes) options include lorazepam, midazolam, and diazepam.

If IV/IO access cannot be obtained, intramuscular lorazepam or midazolam or rectal diazepam can be used. IV lorazepam has been found to be superior to intravascular diazepam.¹⁴

Lorazepam’s efficacy as compared to midazolam is unclear, but midazolam is possibly superior.15 Perhaps the most common regimen is 2 mg of lorazepam repeated every minute as needed to a maximum of 10 mg.

Phenytoin or fosphenytoin is considered second-line treatment. For status epilepticus, the recommended dose is 20 mg/kg, and another 10 mg/kg bolus can be considered (for a total of 30 mg/kg).⁴ Fosphenytoin is considered safer because of the lack of the propylene glycol diluent and can be given at a faster rate.¹⁶

Failure to respond to benzodiazepine and phenytoin defines refractory status epilepticus. Approximately 9%-30% of status epilepticus becomes refractory and mortality jumps to 50%.¹⁵

Third-line agents to consider at this point include valproic acid, phenobarbital, and levetiracetam. Valproic acid has an excellent safety profile and is recommended at a dose of 20 mg/kg, although doses as high as 45 mg/kg can be used.17 It is contraindicated in patients with hepatic disease or disfunction because of the extremely rare occurrence of fatal idiosyncratic hepatotoxicity.^18,19

Phenobarbital dosing is similar to phenytoin in that it is given at 20 mg/kg, but can be given up to 30 mg/kg for refractory seizures. It is highly sedating and usually causes significant respiratory depression and hypotension requiring intervention.

Levetiracetam is a newer antiepileptic drug currently used for the treatment of seizures that is showing potential for the treatment of status epilepticus. Several case series demonstrated the potential benefit of levetiracetam in patients with status epilepticus.^15,20,21 The mechanism of action is not completely understood, but the benefits of the drug include its wide therapeutic index, ease of administration, lack of interaction with other antiepileptic drugs, and low incidence of side effects (primarily central nervous system effects, sleepiness, and vomiting).