Diplomate European College of Equine Internal Medicine Utrecht University Vianen, Utrecht, Netherlands
Disclosure(s):
Anne L. Hendrikx, DVM, DECEIM: No financial relationships to disclose
Introduction Prolongation of the dosing interval of exogenous glucocorticoids such as dexamethasone can reduce the risk for side effects like laminitis in horses. Plasma cortisol concentrations can be used as biomarker to determine the duration of the suppressive effect of dexamethasone on the hypothalamic-pituitary-adrenal axis. This study determined the effect of prolonging the dosing interval of intravenous administered dexamethasone from 24 to 48 hours on plasma cortisol concentrations in healthy horses.
Methods Five healthy adult warmblood mares received intravenous dexamethasone (0.06 mg/kg) twice every 24 hours (day 1+2) or twice every 48 hours (day 1+3) in a crossover design. Plasma cortisol and dexamethasone concentrations were measured repeatedly for eight days via a validated UPLC-MS/MS analysis method. A mixed effect model was applied on log-transformed plasma cortisol concentrations. Results After the first dexamethasone injection mean plasma cortisol concentration reduced from baseline (100%) to 7% (range 2-30%) at 24 hours and to 43% (range 27-59%) at 48 hours. Plasma cortisol concentrations returned to baseline at day 6 with once daily injections (day 1+2) and at day 7 with bidiurnal injections (day 1+3). Two hours after concentrate feeding in the evening, some horses showed a short plasma cortisol peak.
Discussion Both dosing intervals of dexamethasone resulted in a significant decrease in plasma cortisol concentrations. The circadian rhythm of plasma cortisol disappeared in all horses during the first days of dexamethasone treatment. The food-related plasma cortisol response that was observed in some horses might be similar to the meal-stimulated high-cortisol responder phenomenon described in humans.
Clinical relevance Bidiurnal dexamethasone injections should be considered as a treatment option in horses based on suppressive effects on the hypothalamic-pituitary-adrenal axis. However, it is unclear if cortisol response is a suitable biomarker for anti-inflammatory effects of dexamethasone.
Learning Objectives:
explain the rationale for prolonging dexamethasone dosing intervals in horses to reduce adverse effects such as laminitis.
differentiate the magnitude plasma cortisol suppression between 24-hour and 48-hour dexamethasone dosing intervals in healthy horses.
