Buccal midazolam may be a useful alternative to rectal diazepam for treating acute seizures in refractory epilepsyPDF
ACP J Club. 2000 Jan-Feb;132:22. doi:10.7326/ACPJC-2000-132-1-022
Scott RC, Besag FM, Neville BG. Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial. Lancet. 1999;353:623-6. [PubMed ID: 10030327]
In children and adolescents with refractory epilepsy, is buccal midazolam in solution as effective and safe as rectal diazepam in solution for treating acute seizures?
Randomized (allocation concealed*), unblinded,* controlled trial with follow-up to end of seizure.
A residential center for children and young people with severe epilepsy and other needs in Lingfield, Surrey, England, United Kingdom.
18 of 42 enrolled students with refractory epilepsy (mean age 15 y, 50% girls) who had previously received rectal diazepam for acute seizures and who had a seizure that lasted ≥ 3 minutes during the study period. Follow-up was complete.
When a seizure occurred, the student was allocated to receive either midazolam, 2 mL (10 mg) in a 2-mL syringe given buccally (n = 40 seizures in 14 patients), or diazepam, 10 mg given rectally (n = 39 seizures in 14 patients).
Main outcome measures
Clinical response (seizure stopped within 10 min), time taken for nurse to give medication, time to clinical response, and incidence of adverse events.
In the midazolam group, 24 seizures were generalized tonic-clonic, 8 were complex partial, 6 were myoclonic, and 2 were tonic. In the diazepam group, 22 seizures were tonic-clonic, 9 were complex partial, 4 were myoclonic, and 4 were tonic. The treatment groups did not differ for clinical response (P = 0.16) (Table), time required for nurse to give medication (median time 2 min in each group, P = 0.81), time to clinical response (median time 6 min for midazolam vs 8 min for diazepam, P = 0.31), and incidence of adverse events (none occurred in either group). When patients rather than seizures were the units of analysis, the groups did not differ for any of the outcomes.
In children and adolescents with refractory epilepsy, buccal midazolam was as effective and safe as rectal diazepam for treating acute seizures.
Source of funding: No external funding.
For correspondence: Dr. R.C. Scott, Wolfson Centre, Mecklenburgh Square, London WC1N 2AP, England, UK. FAX 44-171-833-9469.
Table. Buccal midazolam vs rectal diazepam for acute seizures in children and adolescents with refractory epilepsy†
|Outcome at 10 min||Midazolam||Diazepam||RBI (95% CI)||NNT|
|End of seizure||75%||59%||27% (−7 to 79)||Not significant|
†Abbreviations defined in Glossary; RBI, NNT, and CI calculated from data in article. Results refer to proportions of seizures (not patients).
Although rectal diazepam is effective in prolonged acute seizures (1), it has practical problems. Scott and colleagues’ promising evidence of the effectiveness of buccal midazolam is welcome. However, clinicians should consider some issues before adopting it.
Study patients had severe epilepsy and had received diazepam. Would patients receiving a benzodiazepine for the first time respond similarly? A nurse gave midazolam, and medical care was available. Neither of these is normally present in the community. Efficacy, safety, and the optimal doses for young children and elderly persons remain to be determined. Finally, patients with prolonged seizures, not status epilepticus, were treated.
The study methods deserve comment. Seizures (not patients) were randomized, and 50% of seizures occurred in 2 of 18 patients. Data from more patients would reassure clinicians. Blinding would have required concurrent buccal and rectal administration. I believe, however, that it is feasible in this context, and it would have strengthened the findings.
Buccal midazolam offers definitive advantages over rectal diazepam and may be used as an alternative for young persons with prolonged, complex partial, and generalized motor seizures. However, its safety and efficacy in the community require further exploration.
Samuel Wiebe, MD, MSc
University of Western Ontario
London, Ontario, Canada
1. Dreifuss FE, Rosman NP, Cloyd JC, et al. A comparison of rectal diazepam gel and placebo for acute repetitive seizures. N Engl J Med. 1998;338:1869-75. [PubMed ID: 9637805]