Abstract
The purpose of this study was to examine the anaesthetic requirement of intrathecal midazolam in a dose-response fashion in isoflurane-anaesthetized, tracheostomized rats, and to evaluate the apnoeic threshold after each intrathecal midazolam dose. Intrathecal midazolam, 5, 10, 20, and 30 μg, was administered to 25 anaesthetized tracheotomized rats. Isoflurane MAC was determined by the tail-clamp method. The effect of intrathecal midazolam on the apnoeic threshold was evaluated, and light and electron microscopy studies were performed on cervical, thoracic and lumbar sections of the spinal cord to investigate possible midazolam-induced neurotoxic effects. Intrathecal midazolam 5, 10, 20 and 30 μg decreased isoflurane MAC by 16%, 31%, 42%, and 53% respectively (P < 0.05). The apnoeic threshold was increased by midazolam 5 μg (from a PaCO2 of 4.25 ± 0.55 to 5.28 ± 0.76 kPa, P < 0.05) when compared with baseline values, but not further by additional doses. Light and electron microscopy studies on sections taken from the spinal cord of four animals did not show any morphological changes suggestive of midazolam-induced neurotoxicity when compared with similar preparations obtained from controls. These data suggest that intrathecal midazolam possesses dose-dependent antinociceptive properties which, associated with the ceiling effect of the apnoeic threshold obtained at the lowest midazolam dose and the lack of neurotoxic effects, may potentiate inhalational anaesthesia without producing marked respiratory depression.
Résumé
Ce travail vise à déterminer la relation dose-effet du midazolam intra-thécal chez le rat trachéotomisé, anesthésié à l’isoflurane et de rechercher le seuil apnéique après chaque dose intrathécale de midazolam. Des doses de midazolam intra-thécal de 5, 10, 20 et 30 μg sont administrées à 25 rats anesthésiés et trachéotomisés. Le MAC de l’isoflurane est déterminé par la méthode de clampage de la queue. L’effet du midazolam sur le seuil apnéique est évalué et des études de microscopie optique et électronique réalisées sur des sections de moelle cervicale, thoracique et lombaire pour vérifier la neurotoxicité du midazolam. Les doses de midazolam intra-thécal de 5, 10, 20, et 30 μg réduisent le MAC de l’isoflurane de 16%, 31%, 42% et 53% respectivement (P < 0,05). Le seuil apnéique est augmenté par le midazolam 5 μg (d’une PaCO2 de 4,25 ± 0,55 à 5,28 ± 0.76 kPa, P < 0,05) comparativement aux valeurs de base, sans autres modifications après des doses additionnelles. Les coupes étudiées à la microscopie optique et électronique n’ont pas montré de changements morphologiques évocateurs de neurotoxicité lorsqu’elles sont comparées à des spécimens identiques prélevés sur les contrôles. Ces données suggèrent que le midazolam intra-thécal possède des propriétés antinociceptives qui, associées au plafonnement des effets sur le seuil apnéique de la dose inférieure de midazolam et à l’absence de neurotoxicité, pourraient potentialiser l’anesthésie inhalatoire sans produire de dépression respiratoire notable.
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Supported by the Swiss National Science Fund no 32-28958.90.
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Schwieger, I.M., Jorge-Costa, M., Pizzolato, G.P. et al. Intrathecal midazolam reduces isoflurane MAC and increases the apnoeic threshold in rats. Can J Anaesth 41, 144–148 (1994). https://doi.org/10.1007/BF03009809
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DOI: https://doi.org/10.1007/BF03009809