title: Antinociceptive effects of three escalating dexmedetomidine and lignocaine constant rate infusions in conscious horses.
abstract: Dexmedetomidine and lignocaine IV are used clinically to provide analgesia in horses. The aims of this study were to investigate the antinociceptive effects, plasma concentrations and sedative effects of 2, 4 and 6 µg/kg/h dexmedetomidine IV, with a bolus of 0.96 µg/kg preceding each continuous rate infusion (CRI), and 20, 40 and 60 µg/kg/min lignocaine IV, with a bolus of 550 µg/kg preceding each CRI, in 10 Swiss Warmblood horses. Electrically elicited nociceptive withdrawal reflexes were evaluated by deltoid muscle electromyography. Nociceptive threshold and tolerance were determined by electromyography and behaviour following single and repeated stimulation. Plasma concentrations of drugs were determined by liquid chromatography and mass spectrometry. Sedation was scored on a visual analogue scale. Dexmedetomidine increased nociceptive threshold to single and repeated stimulation for all CRIs, except at 2 µg/kg/h, where no increase in single stimulation nociceptive threshold was observed. Dexmedetomidine increased nociceptive tolerance to single and repeated stimulation at all CRIs. There was large individual variability in dexmedetomidine plasma concentrations and levels of sedation; the median plasma concentration providing antinociceptive effects to all recorded parameters was 0.15 ng/mL, with a range from <0.02 ng/mL (below the lower limit of quantification) to 0.25 ng/mL. Lignocaine increased nociceptive threshold and tolerance to single and repeated stimulation at CRIs of 40 and 60 µg/kg/min, corresponding to plasma lignocaine concentrations >600 ng/mL. Only nociceptive tolerance to repeated stimulation increased at 20 µg/kg/min lignocaine. Lignocaine at 40 µg/kg/min and dexmedetomidine at 4 µg/kg/h were the lowest CRIs resulting in consistent antinociception. Lignocaine did not induce significant sedation.
authors.affiliation: Department of Veterinary Medicine and Life Sciences, Norwegian University of Life Sciences, 0454 Oslo, Norway. Electronic address: aase.risberg@nmbu.no.
authors.forename: A
authors.initials: A
authors.lastname: Risberg
authors.affiliation: Vetsuisse Faculty, Department of Clinical Veterinary Sciences, 3012 Berne, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Spadavecchia
authors.affiliation: Department of Food Safety and Infection Biology, Faculty of Veterinary Medicine and Life Sciences, Norwegian University of Life Sciences, 0454 Oslo, Norway.
authors.forename: B
authors.initials: B
authors.lastname: Ranheim
authors.affiliation: Faculty of Veterinary Medicine and Life Sciences, Centre for Epidemiology and Biostatistics, Norwegian University of Life Sciences, 0454 Oslo, Norway.
authors.forename: R
authors.initials: R
authors.lastname: Krontveit
authors.affiliation: Department of Veterinary Medicine and Life Sciences, Norwegian University of Life Sciences, 0454 Oslo, Norway.
authors.forename: H A
authors.initials: HA
authors.lastname: Haga
mesh_terms: D000700:Analgesics / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D002853:Chromatography, Liquid / Q000662:veterinary; D018592:Cross-Over Studies; D020927:Dexmedetomidine / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006736:Horses / Q000378:metabolism*; D006993:Hypnotics and Sedatives / Q000097:blood / Q000494:pharmacology*; D007262:Infusions, Intravenous / Q000662:veterinary; D008012:Lidocaine / Q000097:blood / Q000494:pharmacology*; D008297:Male; D013058:Mass Spectrometry / Q000662:veterinary; D011897:Random Allocation; D012018:Reflex / Q000187:drug effects*
chemical_list: D000700:Analgesics; D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine; D008012:Lidocaine
keywords: Antinociception; Constant rate infusion; Dexmedetomidine; Equine; Lignocaine