ACUTE “TOLERANCE” TO THE CENTRAL RESPIRATORY EFFECTS OF MIDAZOLAM IN THE DOG

Abstract

The effect of repeated doses of midnTinlam 0.1 mg kg⁻¹ on efferent activity in the phrenic nerve was observed in seven artificially ventilated dogs, anaesthetized with chloralose and paralysed with suxamethonium. PaO₂, .PaCo₂ arterial pH and core temperature were adjusted to constant values throughout each experiment. The first dose of midazolam caused a relatively prolonged reduction in phrenic activity, after complete recovery a second dose was administered and so on for four doses. Peak phrenic efferent activity returned to initial values on average 69 4min after the first dose of miHnTnlam The effects of successive subsequent doses lasted progressively shorter times (mean values 49.4, 38.7 and 25.3min). In four preparations, 2 h after recovery from the fourth doses a second “train” of four doses was administered. The response to the first dose of this second “train” showed that 90% recovery had occurred from the effect of the first “train” and there wts a similar sequence of decreasing responses to successive doses. This study demonstrated acute tolerance to the central respiratory effects of midazolam.