Lessons from the RAMPART study--and which is the best route of administration of benzodiazepines in status epilepticus

Epilepsia. 2013 Sep;54 Suppl 6(0 6):74-7. doi: 10.1111/epi.12284.


Early treatment of prolonged seizures with benzodiazepines given intravenously by paramedics in the prehospital setting had been shown to be associated with improved outcomes, but the comparative efficacy and safety of an intramuscular (IM) route, which is faster and consistently achievable, was previously unknown. RAMPART (the Rapid Anticonvulsant Medication Prior to Arrival Trial) was a double-blind randomized clinical trial to determine if the efficacy of intramuscular (IM) midazolam is noninferior by a margin of 10% to that of intravenous (IV) lorazepam in patients treated by paramedics for status epilepticus (SE). In children and adults with >5 min of convulsions and who are still seizing at paramedic arrival, midazolam administered by IM autoinjector was noninferior to IV lorazepam on the primary efficacy outcome with comparable safety. Patients treated with IM midazolam were more likely to have stopped seizing at emergency department (ED) arrival, without emergency medical services (EMS) rescue therapy, and were less likely to require any hospitalization or admission to an intensive care unit. Lessons from the RAMPART study's findings and potential implications on clinical practice, on the potential role of other routes of administration, on the effect of timing of interventions, and on future clinical trials are discussed.

Trial registration: ClinicalTrials.gov NCT00809146.

Keywords: Comparative efficacy; Emergency medical services; Intramuscular; Lorazepam; Midazolam.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Allied Health Personnel / trends
  • Anticonvulsants / administration & dosage*
  • Anticonvulsants / therapeutic use
  • Benzodiazepines / administration & dosage*
  • Benzodiazepines / therapeutic use
  • Child
  • Double-Blind Method
  • Drug Administration Routes*
  • Emergency Medical Services / trends
  • Humans
  • Injections, Intramuscular / methods
  • Seizures / drug therapy*
  • Status Epilepticus / drug therapy*
  • Treatment Outcome


  • Anticonvulsants
  • Benzodiazepines

Associated data

  • ClinicalTrials.gov/NCT00809146