Midazolam attenuates ketamine-induced abnormal perception and thought process but not mood changes.
OBJECTIVE
To determine the effects of midazolam, 30 ngxmL(-1), on altered perception, mood, and cognition induced by ketamine.


METHODS
After ketamine was administered to achieve target concentrations of 50, 100, or 150 ngxmL 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 microgxkg(-1), were injected every 30 min to maintain the plasma concentration at 30 ngxmL(-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.


CONCLUSIONS
Midazolam attenuates ketamine-induced changes in perception and thought process.
Suzuki
M
M
Department of Anesthesiology, University of Louisville School of Medicine, KY 40292, USA.
Tsueda
K
K
Lansing
P S
PS
Tolan
M M
MM
Fuhrman
T M
TM
Sheppard
R A
RA
Hurst
H E
HE
Lippmann
S B
SB
D000328:Adult; D000339:Affect / Q000187:drug effects*; D000778:Anesthetics, Dissociative / Q000009:adverse effects* / Q000097:blood; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced / Q000517:prevention & control* / Q000523:psychology; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007649:Ketamine / Q000009:adverse effects* / Q000097:blood; D008297:Male; D008874:Midazolam / Q000627:therapeutic use*; D008875:Middle Aged; D009483:Neuropsychological Tests; D010465:Perception / Q000187:drug effects*; D011597:Psychomotor Performance / Q000187:drug effects; D012894:Sleep Stages / Q000187:drug effects; D013850:Thinking / Q000187:drug effects*
D000778:Anesthetics, Dissociative; D014151:Anti-Anxiety Agents; D007649:Ketamine; D008874:Midazolam