UMEM Educational Pearls

Category: Neurology

Title: When Benzodiazepines Fail in Status Epilepticus

Keywords: ESETT, benzodiazepine, fosphenytoin, valproate, levetiracetam, status epilepticus (PubMed Search)

Posted: 11/27/2019 by WanTsu Wendy Chang, MD (Updated: 4/6/2020)
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  • Up to 1/3 of status epilepticus do not respond to benzodiazepines.
  • Fosphenytoin, valproate, and levetiracetam are 3 antiepileptic medications commonly used to treat benzodiazepine-resistant status epilepticus, though it is unclear which is more effective.
  • Results from the long awaited Established Status Epilepticus Treatment Trial (ESETT) has just been released.
  • Fosphenytoin, valproate, and levetiracetam each achieved seizure cessation within 1 hour in approximately 50% of patients.
    • 80% of responders had seizure cessation within 20 minutes.
  • Seizure recurrence was observed in 10% of each treatment group.
  • It is important to note the dosages of antiepileptic medications used were:
    • Fosphenytoin 20 mg PE/kg, max 1500 mg 
    • Valproate 40 mg/kg, max 3000 mg
    • Levetiracetam 60 mg/kg, max 4500 mg

Bottom Line: Fosphenytoin, valproate, and levetiracetaim have similar efficacy in treatment of benzodiazepine-resistant status epilepticus.


Kapur J, Elm J, Chamberlain JM, et al. Randomized trial of three anticonvulsant medications for status epilepticus. N Engl J Med2019;381:2013-13.

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