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

To elaborate constant rate infusion (CRI) protocols for xylazine (X) and xylazine/butorphanol (XB) which will result in constant sedation and steady xylazine plasma concentrations. Blinded randomized experimental study. Ten adult research horses. Part I: After normal height of head above ground (HHAG = 100%) was determined, a loading dose of xylazine (1 mg kg−1) with butorphanol (XB: 18 μg kg−1) or saline (X: equal volume) was given slowly intravenously (IV). Immediately afterwards, a CRI of butorphanol (XB: 25 μg kg−1 hour−1) or saline (X) was administered for 2 hours. The HHAG was used as a marker of depth of sedation. Sedation was maintained for 2 hours by additional boluses of xylazine (0.3 mg kg−1) whenever HHAG >50%. The dose of xylazine (mg kg−1 hour−1) required to maintain sedation was calculated for both groups. Part II: After the initial loading dose, the calculated xylazine infusion rates were administered in parallel to butorphanol (XB) or saline (X) and sedation evaluated. Xylazine plasma concentrations were measured by HPLC-MS-MS at time points 0, 5, 30, 45, 60, 90, and 120 minutes. Data were analyzed using paired t-test, Wilcoxon signed rank test and a 2-way anova for repeated measures (p < 0.05). There was no significant difference in xylazine requirements (X: 0.69, XB: 0.65 mg kg−1 hour−1) between groups. With treatment X, a CRI leading to prolonged sedation was developed. With XB, five horses (part I: two, part II: three) fell down and during part II four horses appeared insufficiently sedated. Xylazine plasma concentrations were constant after 45 minutes in both groups. Xylazine bolus, followed by CRI, provided constant sedation. Additional butorphanol was ineffective in reducing xylazine requirements and increased ataxia and apparent early recovery from sedation in unstimulated horses. Data were obtained on unstimulated healthy horses and extrapolation to clinical conditions requires caution.