In this episode, I’ll discuss whether levetiracetam, fosphenytoin, or valproate is better for status epilepticus unresponsive to benzodiazepines.
A recent randomized, blinded, adaptive trial was published in New England Journal of Medicine comparing levetiracetam, fosphenytoin, or valproate in pediatric and adult patients for status epilepticus unresponsive to benzodiazepines. The primary outcome was absence of clinically evident seizures and improvement in the level of consciousness by 60 minutes after the start of drug infusion, without additional anticonvulsant medication.
Almost 400 patients were enrolled and randomized between the 3 medication groups. The trial was stopped early for futility at an interim analysis.
Levetiracetam, fosphenytoin, and valproate all had response rates nearing 50%. There were no statistically significant differences in adverse events between groups although there were numerically more episodes of hypotension and intubation in the fosphenytoin group and more deaths in the levetiracetam group.
The doses studied were levetiracetam at a dose of 60 mg per kilogram (maximum, 4500 mg), fosphenytoin at a dose of 20 mg phenytoin equivalents (PE) per kilogram (maximum, 1500 mg PE), and valproate at a dose of 40 mg per kilogram (maximum, 3000 mg).
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