INTRATHECAL MIDAZOLAM REDUCES ISOFLURANE MAC AND INCREASES THE APNEICTHRESHOLD IN RATS

The purpose of this study was to examine the anaesthetic requirement o f intrathecal midazolam in a dose-response fashion in isoflurane-anaes thetized, tracheostomized rats, and to evaluate the apnoeic threshold after each intrathecal midazolam dose. Intrathecal midazolam, 5, 10, 2 0, and 30 mu g, was administered to 25 anaesthetized tracheotomized ra ts. Isoflurane MAC war determined by the tail-clamp method. The effect of intrathecal midazolam on the apnoeic threshold was evaluated and l ight and electron microscopy studies were performed on cervical, thora cic and lumbar sections of the spinal cord to investigate possible mid azolam-induced neurotoxic effects. Intrathecal midazolam 5, 10, 20 and 30 mu g decreased isoflurane MAC by 16%, 31%, 42%, and 53% respective ly (P < 0.05). The apnoeic threshold was increased by midazolam 5 mu g (from a PaCO2 of 4.25 +/- 0.55 to 5.28 +/- 0.76 kPa, P < 0.05) when c ompared with baseline values, but not further by additional doses. Lig ht and electron microscopy studies on sections taken from the spinal c ord of four animals did not show any morphological changes suggestive of midazolam-induced neurotoxicity when compared with similar preparat ions obtained from controls. These data suggest that intrathecal midaz olam possesses dose-dependent antinociceptive properties which, associ ated with the ceiling effect of the apnoeic threshold obtained al the lowest midazolam dose and the lack of neurotoxic effects, may potentia te inhalational anaesthesia without producing marked respiratory depre ssion.