Midazolam attenuates ketamine-induced abnormal perception and thought process but not mood changes

Purpose: To determine the effects of midazolam, 30 ng.mL(-1), on altered perception, mood, and cognition induced by ketamine. Methods: After ketamine was administered to achieve target concentrations of 50, 100, or 150 ng.mL(-1) in 11 volunteers, perception, mood, and thought process were assessed by a visual analog scale. Mini-Mental State examination (MMSE) assessed cognition. Boluses of midazolam, 30, 14.5, and 12 mu g.kg(-1), were injected every 30 min to maintain the plasma concentration at 30 ng.mL(-1), which was reached 30 min after each injection. Results: Ketamine produced changes in perception about the body (P < 0.01, 0.001, and 0.0001 at 30, 60, and 90 min), surroundings (P < 0.01 and 0.0001 at 60 and 90 min), time (P < 0.002 and 0.0001 at 60 and 90 min), reality (P < 0.001 and 0.0001 at 60 and 90 min), sounds (P < 0.002 at 90 min), and meaning(P < 0.05 at 30 min), Subjects felt less energetic and clearheaded (P < 0.02 and 0.05) during ketamine, midazolam, and their coadministration. Ketamine impaired thought process (P < 0.003 and 0.0001 at 60 and 90 min). Ketamine and midazolam decreased mean total MMSE and recall scores (P < 0.001 for both). Go-administration reduced the number of subjects with perceptual (body, P < 0.01 and 0.001 at 30 and 60 min) and thought process abnormalities. Within the range of observation, co-administration did not affect the changes in mood or recall. Conclusion: Midazolam attenuates ketamine-induced changes in perception and thought process.