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Veterinary anaesthesia and analgesia2017; 44(5); 1116-1127; doi: 10.1016/j.vaa.2017.03.009

Sedative and antinociceptive effects of different combinations of detomidine and methadone in standing horses.

Abstract: To evaluate intravenous (IV) detomidine with methadone in horses to identify a combination which provides sedation and antinociception without adverse effects. Methods: Randomized, placebo-controlled, blinded, crossover. Methods: A group of eight adult healthy horses aged (mean ± standard deviation) 7 ± 2 years and 372 ± 27 kg. Methods: A total of six treatments were administered IV: saline (SAL); detomidine (5 μg kg; DET); methadone (0.2 mg kg; MET) alone or combined with detomidine [2.5 (MLD), 5 (MMD) or 10 (MHD) μg kg]. Thermal, mechanical and electrical nociceptive thresholds were measured, and sedation, head height above ground (HHAG), cardiopulmonary variables and intestinal motility were evaluated at 5, 15, 30, 45, 60, 75, 90, 120 and 180 minutes. Normal data were analyzed by mixed-model analysis of variance and non-normal by Kruskal-Wallis (p < 0.05). Results: Nociceptive thresholds in horses administered methadone with the higher doses of detomidine (MMD, MHD) were increased above baseline to a greater degree and for longer duration (MMD: 15-30 minutes, MHD: 30-60 minutes) than in horses administered low dose with methadone or detomidine alone (MLD, DET: 5-15 minutes). No increases in nociceptive thresholds were recorded in SAL or MET. Compared with baseline, HHAG was lower for 30 minutes in MMD and DET, and for 45 minutes in MHD. No significant sedation was observed in SAL, MET or MLD. Intestinal motility was reduced for 75 minutes in MHD and for 30 minutes in all other treatments. Conclusions: Methadone (0.2 mg kg) potentiated the antinociception produced by detomidine (5 μg kg), with minimal sedative effects. Conclusions: Detomidine (5 μg kg) with methadone (0.2 mg kg) produced antinociception without the adverse effects of higher doses of detomidine.
Publication Date: 2017-04-17 PubMed ID: 29050998DOI: 10.1016/j.vaa.2017.03.009Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial

Summary

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The study explores the combination of two drugs, detomidine and methadone, administered intravenously in horses, with the aim of providing pain relief and sedation without associated adverse effects.

Experimental Design

  • The research involved eight healthy, adult horses, aged around 7 years and weighing roughly 372 kg.
  • The study was conducted as a randomized, blinded, placebo-controlled crossover trial.
  • The team administered six different treatments intravenously: saline as a placebo, detomidine alone, methadone alone, and three different combinations of methadone with detomidine, varying by dosage.

Measurements and Methods

  • Nociceptive thresholds (pain response levels) were assessed using thermal, mechanical, and electrical stimuli.
  • The evaluation also included the degree of sedation, head height above ground (as a measure of sedation), cardiopulmonary variables, and intestinal motility.
  • These measures were taken at various intervals, ranging from 5 minutes to 180 minutes post-administration
  • Statistical analysis was carried out using mixed-model analysis of variance for normal data and the Kruskal-Wallis test for non-normal distributions.

Key Findings

  • The combination of methadone and higher doses of detomidine led to a more significant and longer-lasting increase in pain threshold than lower doses or the individual drugs.
  • However, no such increases in pain threshold were recorded with the saline placebo or methadone alone.
  • Head height above the ground, reflecting sedation, was lower for longer durations with the higher doses of detomidine combined with methadone.
  • Intestinal motility was reduced for longer periods in the treatment involving the highest dose of detomidine.
  • No apparent sedation was recorded with the saline placebo, methadone alone, or the lowest dosage of the methadone-detomidine combination.

Conclusions

  • It was observed that a specific dosage of methadone (0.2 mg kg) potentiated the pain-relieving effects of detomidine (5 μg kg), with only minimal sedative effects.
  • The same dosage of detomidine, when combined with methadone, provided pain relief without the adverse effects associated with higher doses of detomidine.

Cite This Article

APA
Gozalo-Marcilla M, Luna SP, Crosignani N, Filho JNP, Possebon FS, Pelligand L, Taylor PM. (2017). Sedative and antinociceptive effects of different combinations of detomidine and methadone in standing horses. Vet Anaesth Analg, 44(5), 1116-1127. https://doi.org/10.1016/j.vaa.2017.03.009

Publication

ISSN: 1467-2995
NlmUniqueID: 100956422
Country: United States
Language: English
Volume: 44
Issue: 5
Pages: 1116-1127
PII: S1467-2987(17)30174-5

Researcher Affiliations

Gozalo-Marcilla, Miguel
  • Department of Veterinary Surgery and Anaesthesiology, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, SP, Brazil. Electronic address: miguelgozalomarcilla@gmail.com.
Luna, Stelio Pl
  • Department of Veterinary Surgery and Anaesthesiology, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, SP, Brazil.
Crosignani, Nadia
  • Department of Veterinary Surgery and Anaesthesiology, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, SP, Brazil.
Filho, José Np Puoli
  • Department of Animal Production, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, SP, Brazil.
Possebon, Fábio S
  • Department of Veterinary Hygiene and Public Health, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, SP, Brazil.
Pelligand, Ludovic
  • Departments of Clinical Services and Sciences and Comparative Biomedical Sciences, Royal Veterinary College, Hatfield, UK.
Taylor, Polly M
  • Taylor Monroe, Ely, UK.

MeSH Terms

  • Analgesia / methods
  • Analgesia / veterinary
  • Anesthetics, Combined / administration & dosage
  • Animals
  • Conscious Sedation / methods
  • Conscious Sedation / veterinary
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Female
  • Horses
  • Imidazoles / administration & dosage
  • Imidazoles / pharmacology
  • Injections, Intravenous / veterinary
  • Male
  • Methadone / administration & dosage
  • Methadone / pharmacology

Citations

This article has been cited 9 times.
  1. Cock G, Blakeney Z, Hernandez JA, DeNotta S. Opioid-free sedation for atlantoaxial cerebrospinal fluid collection in adult horses. J Vet Intern Med 2022 Sep;36(5):1812-1819.
    doi: 10.1111/jvim.16450pubmed: 35639966google scholar: lookup
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  3. Gozalo-Marcilla M, Bettschart-Wolfensberger R, Johnston M, Taylor PM, Redondo JI. Data Collection for the Fourth Multicentre Confidential Enquiry into Perioperative Equine Fatalities (CEPEF4) Study: New Technology and Preliminary Results. Animals (Basel) 2021 Aug 30;11(9).
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  5. de Oliveira AR, Gozalo-Marcilla M, Ringer SK, Schauvliege S, Fonseca MW, Esteves Trindade PH, Prospero Puoli Filho JN, Luna SPL. Development and validation of the facial scale (FaceSed) to evaluate sedation in horses. PLoS One 2021;16(6):e0251909.
    doi: 10.1371/journal.pone.0251909pubmed: 34061878google scholar: lookup
  6. 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.
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    doi: 10.5455/OVJ.2025.v15.i7.5pubmed: 41036345google scholar: lookup
  9. Maldonado Moreno N, Alves Moreira J, Araujo De Oliveira L, Sanches Gontijo A, Castilho Baldi ML, Rocha Wenceslau R, Beier SL. Analgesic and Gastrointestinal Effects of Methadone in Horses Undergoing Orchiectomy. Animals (Basel) 2025 Aug 11;15(16).
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