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

Abstract

Summary 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 μg/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 μg/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, t1/2 (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.

Blood glucose, acid–base and electrolyte changes during loading doses of alpha2-adrenergic agonists followed by constant rate infusions in horses

“…However pH values remained within physiologically normal limits. An increase in pH has not been reported previously after single doses of the different alpha 2 -adrenergic agonists (Clarke et al, 1991;Bueno et al, 1999;Yamashita et al, 2000;Freeman et al, 2002;Bettschart-Wolfensberger et al, 2005) or during CRI of medetomidine and detomidine (Daunt et al, 1993;Bettschart-Wolfensberger et al, 1999;van Dijk et al, 2003) in horses. Conversely, a decrease in pH in face of an increase in HCO À 3 was reported during a CRI of medetomidine-morphine (Solano et al, 2009).…”

Antinociceptive effects of three escalating dexmedetomidine and lignocaine constant rate infusions in conscious horses

“…For dexmedetomidine, boluses of 0.96 μg/kg were administered by hand over 1 min and the infusion rates were 2, 4 and 6 μg/kg/h. The sizes of boluses were calculated on the basis of available pharmacokinetic data (Bettschart-Wolfensberger et al, 2005). Boluses of 550 μg/kg lignocaine were administered over 10 min and infusion rates were 20, 40 and 60 μg/kg/min.…”

Is there a place for dexmedetomidine in equine anaesthesia and analgesia? A systematic review (2005–2017)

“…Bettschart‐Wolfensberger et al. () first studied the PK of an i.v. 3.5 μg/kg bolus in 14 ponies, eight mature (4.4 ± 1.1 years) and six old adults (20 ± 3.2 years), by means of capillary gas chromatography with negative ion chemical ionization mass spectrometry.…”

“…Based on Bettschart‐Wolfensberger et al. (), Marcilla, Schauvliege, Duchateau, and Gasthuys () designed an experimental study with six adults, healthy ponies. Each pony was anaesthetized once for 150 min, with periods of 30 min alternating saline with low and high doses of dexmedetomidine.…”