Canadian Journal of Anaesthesia

, Volume 47, Issue 9, pp 866–874 | Cite as

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

  • Manzo Suzuki
  • Kentaro Tsueda
  • Peter S. Lansing
  • Merritt M. Tolan
  • Thomas M Fuhrman
  • Rachel A. Sheppard
  • Harrell E. Hurst
  • Steven B. Lippmann
Reports Of Investigation


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 12µg·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 0.001 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 and 60 and 90 min). Ketamine and midazolam decreased mean total MMSE and recall scores (P<0.001 for both). Co-administraion 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.


Ketamine Midazolam Thought Process Keta Ketamine Infusion 
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Objectif: Déterminer les effets de 30 ng·mL−1 de midazolam sur les changements de perception, d’humeur et de fonction cognitive induits par la kétamine.

Méthode: Après l’administration de kétamine visant à obtenir des concentrations cibles de 50, 100, ou 150 ng·mL−1 chez 11 volontaires, la perception, l’humeur et la fonction cognitive ont été évaluées à l’aide d’une échelle visuelle analogique. L’examen MMS de Folstein et coll. (MMS) a servi à évaluer la fonction cognitive. Des bolus de midazolam de 30, 14,5 et 12µg·kg−1 ont été injectés à toutes les 30 min afin de maintenir la concentration plasmatique à 30 ng·mL−1, concentration atteinte 30 min après chaques injection.

Résultats: La kétamine a modifié la perception du corps (P<0,01; 0,001 et 0,0001 à 30, 60 et 90 min), de l’environnement (P<0,01 et 0,0001 à 60 et 90 min), du temps (P<0,002 et 0,0001 à 60 et 90 min), de la réalité (P<0,001 et 0,0001 à 60 et 90 min), des sons (P <0,002 à 90 min) et du sens (P<0,05 à 90 min). Les sujets se sentaient moins énergiques et moins lucides (P<0,02 et 0,05) pendant l’administration de kétamine, de midazolam et pendant leur co-administration. La kétamine a altéré le processus cognitif (P<0,003 et 0,0001 à 60 et 90 min). La kétamine et le midazolam ont fait baisser les scores totaux moyens de MMS et de mémoire (P<0,001 pour les deux). La co-administration a réduit le nombre de sujets dont les perceptions (corps,P<0,01 et 0,001 à 30 et 60 min) et la fonction cognitive étaient modifiées. Pendant le temps d’observation, la co-administration n’a pas eu d’effet sur les changements d’humeur ou de mémoire.

Conclusion: Le midazolam diminue les changements de perception et de cognition induits par la kétamine.


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Copyright information

© Canadian Anesthesiologists 2000

Authors and Affiliations

  • Manzo Suzuki
    • 1
  • Kentaro Tsueda
    • 1
  • Peter S. Lansing
    • 1
  • Merritt M. Tolan
    • 1
  • Thomas M Fuhrman
    • 1
  • Rachel A. Sheppard
    • 1
  • Harrell E. Hurst
    • 2
  • Steven B. Lippmann
    • 3
  1. 1.From the Department of AnesthesiologyUniversity of Louisville School of MedicineLouisvilleUSA
  2. 2.Department of Pharmacology and ToxicologyUniversity of Louisville School of MedicineLouisvilleUSA
  3. 3.Department of PsychiatryUniversity of Louisville School of MedicineLouisvilleUSA

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