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

Manzo Suzuki, MD^*, Kentaro Tsueda, MD^*, Peter S. Lansing, MD^*, Merritt M. Tolan, MD^*, Thomas M. Fuhrman, MD^*, Rachel A. Sheppard, BS^*, Harrell E. Hurst, PhD and Steven B. Lippmann, MD

^* From the Departments of Anesthesiology,
Pharmacology and Toxicology and,
Psychiatry, University of Louisville School of Medicine, Louisville, KY, USA.

Address correspondence to: Kentaro Tsueda MD, Department of Anesthesiology, University of Louisville, Louisville, KY 40292, USA. Phone: 502-852-5851; Fax: 502-852-6056; E-mail: rashep01{at}gwise.louisville.edu

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 in11 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 changes in perception and thought process.

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