Cardiopulmonary effects and pharmacokinetics of i.v. dexmedetomidine in ponies

Reasons for performing study: Currently available sedatives depress cardiopulmonary function considerably; therefore, it is important to search for new, less depressive sedatives. The study was performed to assess duration and intensity of cardiopulmonary side effects of a new sedative, dexmedetomidine (DEX), in horses. Objectives: To study pharmacokinetics and cardiopulmonary effects of i.v.. DEX. Methods: Pharmacokinetics of 3.5 mug/kg bwt i.v. DEX were studied in a group of 8 mature (mean age 4.4 years) and 6 old ponies (mean age 20 years). Cardiopulmonary data were recorded in mature ponies before and 5, 10, 20, 30, 45 and 60 mins after administration of DEX 3.5 mug/kg bwt i.v. Data were analysed using ANOVA for repeated measures, and where appropriate Dunnett's t test was used to detect differences from resting values (P < 0.05). Results: Within 2 h after DEX administration, plasma levels were beyond limits of quantification (0.05 ng/ml). Mean values for kinetic parameters for mature and old ponies were: Cmax (ng/ml) 4.6 and 3.8, t(1/2) (min) 19.8 and 28.9 and AUC (ng.min/ml) 34.5 and 44.3, respectively. Heart rate, central venous pressure, pulmonary artery pressure and pulmonary capillary wedge pressure did not change significantly compared to presedation values throughout the 60 min observation period. Compared to presedation values, stroke volume and mixed venous PO2 were reduced for the first 5 mins, paralleled by an increase in systemic and pulmonary vascular resistance. Cardiac index was reduced for the first 10 mins, arterial blood pressures at 20, 30 and 45 mins and respiratory rate throughout the 60 min observation period, but no change in arterial PO2 or PCO2 occurred. Conclusions: DEX administration i.v. causes similar cardiopulmonary changes to those caused by other alpha-(2) adrenoceptor agonists, but of very short duration. DEX is redistributed particularly rapidly. Potential relevance: DEX might be safer for sedation of horses because of its very short-lasting cardiopulmonary side effects. For long duration sedation, its kinetics favour its use as a continuous infusion.