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Veterinary journal (London, England : 1997)2014; 202(3); 489-497; doi: 10.1016/j.tvjl.2014.09.007

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 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.
Publication Date: 2014-09-16 PubMed ID: 25266648DOI: 10.1016/j.tvjl.2014.09.007Google Scholar: Lookup
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  • Clinical Trial
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The study explored the pain-relief effects, plasma concentrations, and sedative effects of various doses of dexmedetomidine and lignocaine in horses. The researchers found that both drugs increased pain thresholds, though individual responses to dexmedetomidine varied considerably.

Research Objectives

  • The study aimed to investigate the impact of different doses of dexmedetomidine and lignocaine, both clinically used for analgesia in horses. The focus was on their antinociceptive (pain relief) effects, changes in plasma concentrations, and sedative effects.
  • To provide a comprehensive picture, researchers tested three escalating doses for each drug administered intravenously using a continuous rate infusion (CRI).

Methodology

  • Three dosage rates for dexmedetomidine and lignocaine were administered to 10 Swiss Warmblood horses using CRI, each preceded by a bolus, which is an initial large dose intended to quickly elevate plasma drug concentration.
  • Pain reactions or thresholds were evaluated using electromyography following single and repeated stimulation. The withdrawal reflexes of horses to the given pain stimuli were quantified using an ingenious method – electrically induced nociceptive withdrawal reflex.
  • In addition to evaluating nociceptive thresholds (pain sensitivity), the researchers also looked at the nociceptive tolerance, or how much pain a horse can tolerate before eliciting a pain response.
  • Plasma drug concentrations and levels of sedation were also monitored and recorded. The plasma concentration was analyzed using liquid chromatography and mass spectrometry, which are standard methods for detecting and quantifying substances in a mixture. Sedation levels were measured using a visual analogue scale.

Findings

  • All doses of dexmedetomidine increased pain thresholds to both single and repeated stimulation, exceptions being at the lowest dose where an increase in pain threshold to single stimulation did not occur.
  • Dexmedetomidine enhanced tolerance of the horses to the induced pain at every dose rate. However, a notable amount of individual variability was recorded in dexmedetomidine plasma concentrations and the levels of sedation.
  • On a similar note, lignocaine enhanced pain thresholds and tolerance at the two higher dosages. At a lower dosage, it only increased tolerance to repeated stimulation.
  • The study identified that the lowest doses to result in consistent antinociception were dexmedetomidine at 4 µg/kg/h and lignocaine at 40 µg/kg/min.
  • Unlink dexmedetomidine, lignocaine did not induce significant sedation in the horses.

Cite This Article

APA
Risberg A, Spadavecchia C, Ranheim B, Krontveit R, Haga HA. (2014). Antinociceptive effects of three escalating dexmedetomidine and lignocaine constant rate infusions in conscious horses. Vet J, 202(3), 489-497. https://doi.org/10.1016/j.tvjl.2014.09.007

Publication

ISSN: 1532-2971
NlmUniqueID: 9706281
Country: England
Language: English
Volume: 202
Issue: 3
Pages: 489-497
PII: S1090-0233(14)00376-1

Researcher Affiliations

Risberg, A
  • Department of Veterinary Medicine and Life Sciences, Norwegian University of Life Sciences, 0454 Oslo, Norway. Electronic address: aase.risberg@nmbu.no.
Spadavecchia, C
  • Vetsuisse Faculty, Department of Clinical Veterinary Sciences, 3012 Berne, Switzerland.
Ranheim, B
  • Department of Food Safety and Infection Biology, Faculty of Veterinary Medicine and Life Sciences, Norwegian University of Life Sciences, 0454 Oslo, Norway.
Krontveit, R
  • Faculty of Veterinary Medicine and Life Sciences, Centre for Epidemiology and Biostatistics, Norwegian University of Life Sciences, 0454 Oslo, Norway.
Haga, H A
  • Department of Veterinary Medicine and Life Sciences, Norwegian University of Life Sciences, 0454 Oslo, Norway.

MeSH Terms

  • Analgesics / blood
  • Analgesics / pharmacology
  • Animals
  • Chromatography, Liquid / veterinary
  • Cross-Over Studies
  • Dexmedetomidine / blood
  • Dexmedetomidine / pharmacology
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • Horses / metabolism
  • Hypnotics and Sedatives / blood
  • Hypnotics and Sedatives / pharmacology
  • Infusions, Intravenous / veterinary
  • Lidocaine / blood
  • Lidocaine / pharmacology
  • Male
  • Mass Spectrometry / veterinary
  • Random Allocation
  • Reflex / drug effects

Citations

This article has been cited 4 times.
  1. Verhaar N, Hoppe S, Grages AM, Hansen K, Neudeck S, Kästner S, Mazzuoli-Weber G. Dexmedetomidine Has Differential Effects on the Contractility of Equine Jejunal Smooth Muscle Layers In Vitro. Animals (Basel) 2023 Mar 10;13(6).
    doi: 10.3390/ani13061021pubmed: 36978562google scholar: lookup
  2. Mühlemann S, Leandri M, Risberg ÅI, Spadavecchia C. Comparison of Threshold and Tolerance Nociceptive Withdrawal Reflexes in Horses. Animals (Basel) 2021 Nov 26;11(12).
    doi: 10.3390/ani11123380pubmed: 34944157google scholar: lookup
  3. de Oliveira AR, Gozalo-Marcilla M, Ringer SK, Schauvliege S, Fonseca MW, Trindade PHE, Puoli Filho JNP, Luna SPL. Development, Validation, and Reliability of a Sedation Scale in Horses (EquiSed). Front Vet Sci 2021;8:611729.
    doi: 10.3389/fvets.2021.611729pubmed: 33665216google scholar: lookup
  4. Di Giminiani P, Sandercock DA, Malcolm EM, Leach MC, Herskin MS, Edwards SA. Application of a handheld Pressure Application Measurement device for the characterisation of mechanical nociceptive thresholds in intact pig tails. Physiol Behav 2016 Oct 15;165:119-26.
    doi: 10.1016/j.physbeh.2016.07.006pubmed: 27422675google scholar: lookup