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Buccal midazolam as an alternative to rectal diazepam for prolonged seizures in childhood and adolescence

Three Part Question

In [children with prolonged seizures] does [buccal midazolam or rectal diazepam] lead to [quicker resolution of seizures]?

Clinical Scenario

An 11 year-old girl, known to be epileptic, is brought to the Emergency Department with a prolonged seizure. You have no intravenous access at this point. A colleague recently mentioned that buccal midazolam is an available alternative to rectal diazepam. You are aware that this would be more socially acceptable in the situation, but wonder if it would be as efficacious.

Search Strategy

Medline 1966-01/2005 using the OVID interface and the
Cochrane Library, Issue 4, 2004.
Medline: [exp status epilepticus OR status OR exp seizures/ OR exp seizures, febrile/ or OR fit$.mp] AND [exp midazolam/ OR OR exp Benzodiazepines] AND [exp Mouth Mucosa/ OR OR exp administration, buccal/] AND [exp diazepam OR] AND [ OR exp Rectum/ OR per OR exp Administration, Rectal] LIMIT to human AND English language
Cochrane: buccal AND diazepam

Search Outcome

Altogether 8 papers were identified, two of which were relevant to the three-part question. Cochrane 9 hits, none of which were relevant

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
Scott RC, Besag FM, Neville BG
United Kingdom
79 seizure episodes in 24 young people aged 5-22 years with severe epilepsy living at a residential centre Randomised to receive either 2ml (10mg) buccal midazolam or 10mg rectal diazepam upon having a seizure lasting longer than 3 minutesPRCTTermination of seizure within 10 minutes of drug administrationResponse to midazolam in 30 (75%) of 40 episodes; response to rectal diazepam in 23 (59%) of 39 episodes (p=0.016)Small sample size (no power calculation) Nearly half the seizure episodes occurred in the same two patients
Mean time to termination of seizure6 minutes for midazolam and 8 minutes for diazepam (p=0.31)
Wilson MT, Macleod S, O'Regan ME
United Kingdom
53 young people aged 3-21 years Identified from hospital prescriptions for nasal/buccal midazolam over a 16-month periodTelephone surveyParental preference24 of 40 families had used both rectal diazepam and buccal/nasal midazolam: 20/24 (83%) preferred midazolamAims of the study were to evaluate effectiveness and convenience of nasal/buccal midazolam in terminating prolonged seizures in the community. The study was not appropriately designed to investigate either outcome. Patient group selected having already had midazolam prescribed. This may be because they had already stated a preference for midazolam, introducing selection bias. Further, not all prescriptions may have been identified. No sample size calculation and no statistical analysis Not all results were reported (for example parents were asked to grade ease of use from 1 to 5, no results were given)
Termination of seizures33/40 who used midazolam (83%)


Buccal midazolam is gaining in popularity as a treatment for prolonged seizures in children. It overcomes many of the disadvantages associated with rectal diazepam, including difficulty of administration in wheelchair users and in tonic seizures, potentially unpredictable absorption with constipation and bowel movements and social unacceptability, particularly in older children. Nasal midazolam has also been used (Carley and Smith), although the greater surface area of the buccal mucosa could potentially confer advantages with regard to absorption. One small trial suggests that buccal midazolam is at least as effective as rectal diazepam and one suboptimally designed telephone survey suggested a degree of parental satisfaction with the drug. However, the patient group in the randomised controlled trial is very different from that presenting to emergency departments. There remains a paucity of evidence regarding this topic.

Editor Comment

2010 update at BET 2288

Clinical Bottom Line

Buccal midazolam may be equal or superior to rectal diazepam for treatment of prolonged seizures in children but more evidence is needed for emergency patients.


  1. Scott RC, Besag FMC, Neville BGR. Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial. The Lancet 1999; 353(9153): 623-6.
  2. Wilson MT, Macleod T, O'Regan ME. Nasal/buccal midazolam use in the community. Archives of Disease in Childhood 2004; 89(1):50-51.
  3. Carley S, Smith M. Intranasal midazolam or rectal diazepam in patients with fits [Online] Available at (accessed 15/05/05)
  4. Lee J, Dollery W. Buccal Midazolam vs Rectal Diazepam: Which is more effective in the treatment of acute seizures in children in Accident and emergency department.Update [Online]. BestBETs 2010