Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial

Lancet. 1999 Feb 20;353(9153):623-6. doi: 10.1016/S0140-6736(98)06425-3.


Background: Convulsive status epilepticus is the most common neurological medical emergency and has high morbidity and mortality. Early treatment before admission to hospital is best with an effective medication that can be administered safely. We aimed to find out whether there are differences in efficacy and adverse events between buccal administration of liquid midazolam and rectal administration of liquid diazepam in the acute treatment of seizures.

Methods: At a residential school with on-site medical facilities 42 young people with severe epilepsy were enrolled. Continuous seizures of more than 5 min duration were randomly treated with buccal midazolam or rectal diazepam. If the seizure did not stop within 10 min additional medication chosen by the attending physician was administered. We monitored oxygen saturation and blood pressure for 30 min after treatment. The main outcome measures were efficacy, time from arrival of the nurse to drug administration, time from drug administration to end of seizure, and incidence of adverse cardiorespiratory events.

Findings: Buccal midazolam was used to treat 40 seizures in 14 students, and rectal diazepam 39 seizures in 14 students. Midazolam stopped 30 (75%) of 40 seizures and diazepam 23 (59%) of 39 (p=0.16). The median time from arrival of the nurse to administration of medication was 2 min. Time from administration to end of seizure did not differ significantly between the two treatments. No clinically important adverse cardiorespiratory events were identified in the two groups. Buccal midazolam was universally acceptable to the nursing and care staff.

Interpretation: Buccal midazolam is at least as effective as rectal diazepam in the acute treatment of seizures. Administration via the mouth is more socially acceptable and convenient and may become the preferred treatment for long seizures that occur outside hospital.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Buccal
  • Administration, Rectal
  • Adolescent
  • Adult
  • Anti-Anxiety Agents / administration & dosage*
  • Anti-Anxiety Agents / adverse effects
  • Anticonvulsants / administration & dosage*
  • Anticonvulsants / adverse effects
  • Blood Pressure / drug effects
  • Child
  • Child, Preschool
  • Diazepam / administration & dosage*
  • Diazepam / adverse effects
  • Epilepsy, Complex Partial / drug therapy
  • Epilepsy, Generalized / drug therapy
  • Epilepsy, Tonic-Clonic / drug therapy
  • Female
  • Humans
  • Incidence
  • Male
  • Midazolam / administration & dosage*
  • Midazolam / adverse effects
  • Oxygen / blood
  • Seizures / drug therapy
  • Status Epilepticus / drug therapy*
  • Time Factors
  • Treatment Outcome


  • Anti-Anxiety Agents
  • Anticonvulsants
  • Diazepam
  • Midazolam
  • Oxygen