Effect of constant rate infusion of detomidine with and without vatinoxan on blood glucose and insulin concentrations in horses

Objective: To assess the effects of an α₂-adrenoceptor agonist (detomidine) constant rate infusion (CRI) with and without an α₂-adrenoceptor antagonist (vatinoxan) CRI on blood insulin and glucose concentrations, heart rate, intestinal borborygmi, and sedation during and after infusion in horses. Study design: Randomized, blinded, crossover, experimental study. Animals: A total of nine healthy, adult Finnhorse mares. Methods: Horses were treated with an intravenous (IV) detomidine loading dose (0.01 mg kg^–1), followed by CRI (0.015 mg kg^–1 hour^–1), and the same doses of detomidine combined with an IV vatinoxan loading dose (0.15 mg kg^–1), followed by CRI (detomidine and vatinoxan; 0.05 mg kg^–1 hour^–1) with an 18 day washout period. Infusion time was 60 minutes and horses were monitored for 240 minutes after the infusion. Heart rate, borborygmi score and sedation were assessed, and blood glucose, insulin and triglyceride concentrations were measured. Data were analyzed using repeated measures ANCOVA and Wilcoxon signed-rank tests. Values of p < 0.05 were considered statistically significant. Results: Insulin concentration decreased during (median nadir 1.7, range 0.0–2.9 μIU mL^–1 at 60 minutes, p < 0.0001) and increased after detomidine CRI (median 36.6, range 11.7–78.4 μIU mL^–1 at 180 minutes, p = 0.0001) significantly compared with detomidine and vatinoxan CRI. A significant elevation of blood glucose (peak 11.5 ± 1.6 mmol L^–1 at 60 minutes, p < 0.0001) was detected during detomidine CRI. Vatinoxan alleviated the insulin changes and abolished the significant increase in blood glucose. Vatinoxan alleviated the decrease in heart rate (p = 0.0001) during detomidine infusion. No significant differences were detected in sedation scores between treatments. Conclusions and clinical relevance: Vatinoxan attenuated the negative adverse effects of detomidine CRI and thus is potentially beneficial when used in combination with an α₂-adrenoceptor agonist CRI in horses.