Comparison of sedative recovery time after midazolam versus diazepam administration

OBJECTIVE: To compare the sedative recovery rate pharmacology of intravenous midazolam vs. diazepam when used for short-term sedation. DATA SOURCES: English-language articles were identified through a search of the MEDLINE and InPharma databases. Bibliographies of retrieved articles were examined for relevant articles. STUDY SELECTION: Twenty-eight studies were identified based on a priori inclusion criteria. Eight trials had enough information to combine results for sedative recovery rate. DATA EXTRACTION: The difference in mean time to sedative recovery, weighted by sample size, was determined. DATA SYNTHESIS: Of the 28 trials, eight reported a significantly faster sedation recovery rate from diazepam vs. midazolam, whereas 19 trials reported no difference in sedative recovery time, and a single trial reported that midazolam offered significantly faster recovery from sedation than diazepam. A commonly defined time to sedative recovery event was available for only eight trials. The median dosing ratio for these eight trials was 2.1:1 for diazepam over midazolam. The weighted mean time difference was 4 mins 16 secs in favor of diazepam as the agent from which patients recover more quickly. CONCLUSIONS: These results firmly underscore the understanding that elimination half-lives of benzodiazepines do not necessarily correspond with their sedative pharmacodynamic effects, and we conclude that there are no clinically important sedative recovery rate differences between midazolam and diazepam, while midazolam is a more expensive agent.