Auditory and electroencephalographic effects of midazolam and alpha-hydroxy-midazolam in healthy subjects

Aims Whereas cortical EEG effects of benzodiazepines are well characterized , information about benzodiazepine effects in other areas of the central ne rvous system is sparse. This study investigated the action of midazolam and its active metabolite alpha-hydroxy-midazolam on different parts of the au ditory pathway in six healthy volunteers in a randomized, double-blind, thr ee-way cross-over study. Methods Acoustically evoked short (SLP) and middle (MLP) latency potentials , transitory evoked otoacoustic emissions (TEOAE), and EEG power spectra we re analysed after short i.v. injections of placebo, or 0.15 mg kg(-1) midaz olam, or alpha-hydroxy-midazolam, respectively. Results All subjects fell asleep during the 4 min infusion of active drug. SLP showed a significant transient increase of Jewett wave V 10 min after i njection for midazolam and alpha-hydroxy-midazolam while the latency of wav e I was unchanged. Both benzodiazepines induced a marked and long-lasting M LP amplitude decrease for 240 min with slow recovery over the following 360 min. No changes of TEOAE were observed. In agreement with earlier reports, increases in EEG beta activity and decreases in alpha activity were observ ed after administration of either drug. Conclusions Systemically administered benzodiazepines modulate the auditory pathway above the level of the cochlea. While SLP changes were closely ass ociated with sedation and high plasma benzodiazepine concentrations, MLP ef fects persisted for hours after sedation even at low benzodiazepine plasma levels. Evoked potentials may therefore be more sensitive than EEG as a too l to monitor benzodiazepine effects.