Effects of dexmedetomidine, with or without vatinoxan (MK-467), on minimum alveolar concentration of isoflurane in cats

Abstract

ObjectiveTo characterize the effects of dexmedetomidine, with or without vatinoxan, on the minimum alveolar concentration of isoflurane (MACISO) in cats. Study designRandomized crossover experimental study. AnimalsA group of six adult healthy male neutered cats. MethodsCats were anesthetized with isoflurane in oxygen and instrumented. Dexmedetomidine was administered using a target-controlled infusion system to achieve 10 target plasma concentrations ranging from 0 to 40 ng mL–1. Additionally, vatinoxan or an equivalent volume of saline was administered using a target-controlled infusion system to achieve a target plasma concentration of 4 μg mL–1. Pulse rate (PR), respiratory rate, systolic arterial pressure (SAP), hemoglobin oxygen saturation, body temperature, end-tidal partial pressure of carbon dioxide and drug concentrations were measured. MACISO was determined at each target plasma dexmedetomidine concentration using the bracketing method and the tail clamp technique. Pharmacodynamic models were fitted to the plasma dexmedetomidine concentration-MACISO. Pharmacodynamic parameters were tested for equivalence, and if rejected, for difference. ResultsDexmedetomidine alone decreased MACISO in a plasma concentration-dependent manner. Maximum reduction was 77 ± 4%; the dexmedetomidine concentration producing 50% of the maximum decrease (IC50) was 0.77 ng mL–1. Vatinoxan increased MACISO in the absence of dexmedetomidine, decreased the potency of dexmedetomidine for its MACISO-reducing effect (IC50 = 12 ng mL–1) and lessened the maximum MACISO reduction (60 ± 14%). PR decreased less and SAP increased less when dexmedetomidine was administered with vatinoxan compared with saline. Conclusion and clinical relevanceVatinoxan altered the effect of dexmedetomidine on MACISO. A high plasma dexmedetomidine concentration in the presence of vatinoxan resulted in a large decrease in MACISO, with attenuation of dexmedetomidine-induced cardiovascular effects. The vatinoxan–dexmedetomidine combination may provide clinical benefits in isoflurane-anesthetized cats.