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

Abstract

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 μg·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 90 min). Subjects felt less energetic and clearheaded (P < 0.02 and 0.05) during ketamine, midazolam, and their co-administration. 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). Co-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 charges in perception and thought process.