Development of a romifidine constant rate infusion with or without butorphanol for standing sedation of horses

To determine constant rate infusion (CRI) protocols for romifidine (R) and romifidine combined with butorphanol (RB) resulting in constant sedation and romifidine plasma concentrations. Blinded randomized crossover study. Ten adult research horses. Part I: After determining normal height of head above ground (HHAG = 100%), loading doses of romifidine (80 μg kg−1) with butorphanol (RB: 18 μg kg−1) or saline (R) were given intravenously (IV). Immediately afterwards, a butorphanol (RB: 25 μg kg−1 hour−1) or saline (R) CRI was administered for 2 hours. The HHAG was used as marker of sedation depth. Sedation was maintained for 2 hours by additional romifidine (20 μg kg−1) whenever HHAG > 50%. The dose rate of romifidine (μg kg−1 hour−1) required to maintain sedation was calculated for both treatments. Part II: After loading doses, the romifidine CRIs derived from part I were administered in parallel to butorphanol (RB) or saline (R). Sedation and ataxia were evaluated periodically. Romifidine plasma concentrations were measured by HPLC-MS-MS at 0, 5, 10, 15, 30, 45, 60, 90, 105, and 120 minutes. Data were analyzed using paired t-test, Fisher's exact test, Wilcoxon signed rank test, and two-way anova for repeated measures (p < 0.05). There was no significant difference in romifidine requirements (R: 30; RB: 29 μg kg−1 hour−1). CRI protocols leading to constant sedation were developed. Time to first additional romifidine bolus was significantly longer in RB (mean ± SD, R: 38.5 ± 13.6; RB: 50.5 ± 11.7 minutes). Constant plasma concentrations of romifidine were achieved during the second hour of CRI. Ataxia was greater when butorphanol was added. Romifidine bolus, followed by CRI, provided constant sedation assessed by HHAG. Butorphanol was ineffective in reducing romifidine requirements in unstimulated horses, but prolonged the sedation caused by the initial romifidine bolus. Both protocols need to be tested under clinical conditions.