Elaboration of a xylazine and dexmedetomidine infusion regime which provides a constant level of sedation in horses

Abstract

The study was performed to elaborate equipotent constant rate infusion regimes of xylazine and dexmedetomidine in awake horses, which provide a constant level of sedation and may be suitable for constant rate infusion to be used as part of a total intravenous anaesthesia (TIVA) protocol in horses. Five adult, healthy university-owned horses were sedated three times for two hours with a washout period of 2 weeks between treatments. In group X the horses were sedated with 0.5 mg/kg bwt of xylazine IV, followed by a constant rate infusion (CRI) of 1 mg/kg bwt/h xylazine. In group D1 horses received a bolus of 3.5 µg/kg bwt IV dexmedetomidine and a CRI of 5 µg/kg bwt/h. In D2 horses were treated as horses in group D1 but received additional boli of 0.5 mg per horse of dexmedetomidine to reach the same reduction of nose-to-ground-distance of group X. Heart rate (HR), respiratory rate (RR) and nose-to-ground-distance were recorded every five minutes. Reaction to thermal stimulation of the skin over the nostrils and thermal threshold was tested. A two-way analysis of variance with repeated measurements was used to analyse data with an alpha of 5%. The dosage of dexmedetomidine used in group D1 (3.5 µg/kg bwt, IV and 5 µg/kg bwt/h) was not equipotent to the xylazine dosage used in group X (0.5 mg/kg bwt, IV and 1 mg/kg bwt/h) and a calculated CRI of 7 µg/kg bwt/h was necessary in group D2 to receive equisedation. All horses developed signs of mild to deep sedation including moderate ataxia. HR and nose-to-ground distance decreased significantly from baseline to sedation in all groups. RR decreased significantly from baseline to sedation in group D2. Thermal thresholds increased significantly above baseline from time 15 to 120 minutes in group X and D1 and from time 15 to 150 minutes in group D2. We concluded that all three dosing regimes are suitable to maintain a constant level of sedation with moderate signs of ataxia. A calculated CRI of 7 µg/kg bwt/h dexmedetomidine after a bolus of 3.5 µg/kg bwt was equisedative to a CRI of 1 mg/kg bwt/h xylazine after a bolus of 0.5 mg/kg bwt.

Effects of dexmedetomidine and xylazine on cardiovascular function during total intravenous anaesthesia with midazolam and ketamine and recovery quality and duration in horses

“…The doses of xylazine and dexmedetomidine were determined to be equisedative from a previous study (Mueller et al. ).…”

Pharmacokinetics of xylazine after 2‐, 4‐, and 6‐hr durations of continuous rate infusions in horses

“…Horses in all groups showed signs of deep and stable sedation after bolus administration of XYL, and this lasted for the entire duration of drug infusion. Head height or nose‐to‐ground distance is commonly used in horses to assess degree of sedation (Muller et al., 2012; Ringer et al, 2013). The degree of sedation (no response to tactile or acoustic stimuli) suggests that horses would have had a lower head position for the entire infusion periods.…”

“…The dose regimens used for a CRI range from 0.7 to 1 mg kg −1 hr −1 after an i.v. bolus (Muller, Hopster, Hopster‐Iversen, Rohn, & Kastner, 2012; Ringer, Portier, Fourel, & Bettschart‐Wolfensberger, 2012; Ringer, Portier, Torgerson, Castagno, & Bettschart‐Wolfensberger, 2013). Xylazine causes sedation primarily by stimulating the central nervous system presynaptic α 2 ‐adrenergic receptors.…”

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

“…Therefore, based on its PK profile, dexmedetomidine may be useful for both short‐ and long‐term standing procedures. Rates of 7 μg kg −1 hr −1 after a bolus of 3.5 μg/kg were proven to be equisedative to a sedation dose of xylazine at 0.5 mg/kg followed by a 1 mg kg −1 hr −1 CRI (Müller et al., ). Antinociception was present at rates of 4 and 6 μg kg −1 hr −1 (Risberg et al., ).…”

“…In an experimental, randomized, cross‐over study involving five adult healthy horses, Müller, Hopster, Hopster‐Iversen, Rohn, and Kästner () compared the sedative and antinociceptive effects of a dexmedetomidine protocol consisting of a bolus of 3.5 μg/kg followed by an infusion of 5 or 7 μg kg −1 hr −1 , with a xylazine regime (0.5 mg/kg plus 1 mg kg −1 hr −1 CRI), for 120 min. The lower dexmedetomidine infusion rate (5 μg kg −1 hr −1 ) produced less reduction in HHAG, around 30%–50%, whereas the higher (7 μg kg −1 hr −1 ) produced similar steady reductions as xylazine, around 70% for the duration of the CRIs.…”