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Intramuscular versus intravenous benzodiazepines for status epilepticus.

To the Editor: In an double-blind, randomized trial comparing the efficacy of intramuscular midazolam with that of intravenous lorazepam for the treatment of prehospital status epilepticus, Silbergleit et al. (Feb. 16 issue) 1 report that the median time from active midazolam treatment to cessation of convulsions was 3.3 minutes. The pharmacokinetic studies revealed that after intramuscular injection of midazolam, the median time to reach the peak plasma concentration was about 30 minutes.2,3 These results suggest that the antiepileptic effect of intramuscular midazolam appears before the peak plasma concentration, and the plasma midazolam concentration that is required for termination of seizures is significantly lower than the peak plasma concentration. It has been shown that the plasma concentration and efficacy of intramuscular midazolam are directly proportional to the drug dose.3,4 Considering that midazolam had a treatment failure rate of 26.6% in this study, we think that the doses of midazolam that were used (10 mg) were smaller than the doses required for termination of prehospital seizure. It is anticipated that a fixed dose of 20 mg (two autoinjectors) of midazolam is the effective dose in humans.2 Moreover, the authors should provide the sites of intramuscular injection, because these can influence absorption of intramuscular benzodiazepines.5 Fu S. Xue, M.D. Xu Liao, M.D. Yi Cheng, M.D.