Benzodiazepine Administration for Seizure Emergencies: A Review (P4.250)

Abstract

OBJECTIVE: Review literature describing benzodiazepine administration for treatment of seizure emergencies by routes other than those FDA approved. BACKGROUND: Benzodiazepines are considered effective rescue therapies for seizure emergencies. Current FDA-approved routes of administration (intravenous and rectal) can be associated with administration challenges, and several alternative routes have been reported. Here we present a review of published data on safety, efficacy, and tolerability of benzodiazepines administered by various routes for treatment of seizure emergencies. DESIGN/METHODS: Systemic review of Scopus, using “English language,” “human subject,” and “article” filters. Search terms: Acute Seizures; Acute Repetitive Seizures; Prolonged Seizure; Seizure Clusters; Seizure Emergency; Seizure + Out of Hospital; Status Epilepticus + individual benzodiazepines (clobazam, clonazepam, diazepam, lorazepam, midazolam). Studies using benzodiazepines for maintenance therapy, as second-line treatment, or in combination with other antiepileptic drugs were excluded. RESULTS: In total, 100 unique citations were identified. Of these, 61 were in children, 28 were in adults, and 11 in children and adults. Intranasal, buccal, and intramuscular benzodiazepines were faster to administer to pediatric subjects than IV and rectal. Time from benzodiazepine administration to termination of seizure activity was generally rapid with no significant difference between routes of administration (IV, 1.0-5.0 minutes (min); rectal, 1.3-15.0 min; buccal, 2.8-10.0 min; IM, .25-7.8 min; IN, 2.3-15.0 min). In some studies, caregivers found buccal and intranasal methods more acceptable than rectal administration. Respiratory adverse events (persistent O₂ saturation <92% or <12 breaths/min) were more frequently found with IV administration versus other routes (IV: 0-20.6%; rectal, 0-6.0%; buccal/oral, 0-5.0%; IM, 0-12.0%; IN, 2.0% [reported only in one study]). CONCLUSION: Emerging benzodiazepine administration methods appear to offer a rapid and convenient alternative to IV or rectal routes. The literature supports that these methods are safe and effective alternative routes of benzodiazepine administration for rapid treatment of seizures in children and adults.

Disclosure: Dr. Haut has received personal compensation for activities with Upsher Smith, Acorda, and Impax. Dr. Seinfeld has nothing to disclose. Dr. Pellock has received personal compensation for activities with the National Institutes of Health, Acorda Therapeutics, Catalyst, Eisai Inc., GlaxoSmithKline Inc., King Pharmaceuticals, Marinus Pharmaceuticals, Medscape, Neuropace, Lundbeck Research USA Inc., Pfizer Inc., Questcor Pharmaceuticals Inc., Sepracor Inc., UCB Pharma, Upsher-Smith Laboratories, Inc., and Valeant Pharmaceuticals Inc. Dr. Pellock has received research support from the National Institutes of Health, Center for Disease Control, Eisai Inc., Lundbeck Research USA Inc., Marinus Pharamceuticals, Pfizer Inc., Questcor Pharmaceuticals, UCB Pharma, and Upsher-Smith Laboratories, Inc.