Dezocrine-MAC reduction and evidence for myocardial depression in the presence of enflurane

The effect of dezocine, an agonist-antagonist opioid analgesic, on enflurane MAC (EMAC) was measured in dogs and, in a separate study, the hemodynamic effects of IV bolus doses of dezocine in the presence of a stable end-tidal enflurane concentration were measured. Study 1 (n = 8) - EMAC Reduction: Dezocine reduced EMAC in a dose-dependent fashion by a maximum of 58 ± 3% (mean ± SEM) after injection of 20 mg/kg. Cardiac toxicity prevented administration of higher doses. Study 2 - Hemodynamics: Group 1 (n = 7) received dezocine 0.2, 1.5, 5, and 20 mg/kg IV each as a bolus over 30 sec. Group 2 (n = 5) was studied in exactly the same manner except that instead of dezocine, each dog received drug carrier solution alone (carrier). Significant hemodynamic differences between carrier and drug groups were observed only at the 20 mg/kg dose level, which produced death in one dog and a decrease in mean aortic pressure to 39 ± 5% of baseline, in cardiac output to 60 ± 9% of baseline, and in stroke volume to 69 ± 9% of baseline in the remaining dogs. It is concluded that dezocine produces a dose-dependent reduction in EMAC limited by cardiovascular toxicity. This toxicity appears to be related to direct myocardial depression by high doses of dezocine in the presence of enflurane.