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Veterinary anaesthesia and analgesia2021; 48(3); 451-460; doi: 10.1016/j.vaa.2020.08.011

Antinociceptive effects of levomethadone in standing horses sedated with romifidine.

Abstract: To evaluate the antinociceptive effect of a bolus of intravenous levomethadone administered to horses during romifidine constant rate infusion (CRI). Methods: Prospective, randomized, masked, crossover experimental study. Methods: A group of eight adult Warmblood horses (seven geldings, one mare) aged 6.6 ± 4.4 years, weighing 548 ± 52 kg [mean ± standard deviation (SD)]. Methods: Levomethadone 0.1 mg kg or an equivalent volume of saline (control) was administered intravenously to standing horses 60 minutes after starting a romifidine CRI. Blood samples to quantify romifidine and levomethadone plasma concentrations by capillary electrophoresis were collected up to 150 minutes after levomethadone administration. The nociceptive withdrawal reflex threshold (NWRT) was determined continuously using an automated threshold tracking device. Sedation and cardiopulmonary variables were assessed at regular intervals. A pharmacokinetic-pharmacodynamic (PK-PD) model was elaborated. Data are presented as mean ± SD or median (interquartile range, 25%-75%) where appropriate. Differences between groups were considered statistically significant for p < 0.05. Results: Horses exhibited higher NWRTs after levomethadone administration than after saline (123 ± 9% versus 101 ± 9% relative to baseline, p < 0.05). The PK-PD model identified a contribution of levomethadone to the NWRT increase. Effect size was variable among individuals. No adverse reactions to levomethadone administration were observed. A slight effect of levomethadone on sedation scores was evident for the 60 minutes following its administration. Conclusions: A single injection of levomethadone has the potential to increase the NWRT during romifidine CRI in horses and can be administered in combination with α-adrencoceptor agonists to enhance antinociception in horses. However, individual variation is marked.
Publication Date: 2021-02-02 PubMed ID: 33685821DOI: 10.1016/j.vaa.2020.08.011Google Scholar: Lookup
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  • Journal Article

Summary

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The research tested the pain-relieving effects of levomethadone when given to horses that were sedated with romifidine. The study found that levomethadone enhanced the pain threshold in these horses, although the effect varied among individuals.

Methodology

  • The experiment was a prospective, randomized, masked, crossover study involving eight adult Warmblood horses, with an average age of 6.6 years and an average weight of 548 kg.
  • The horses were given an intravenous injection of 0.1mg/kg levomethadone or an equivalent volume of saline (as a control). This injection was administered 60 minutes after a romifidine constant rate infusion (CRI) had started while the horses were standing.
  • Blood samples were taken up to150 minutes after the administration of levomethadone. The blood was tested to quantify the plasma concentrations of romifidine and levomethadone. These tests were carried out using capillary electrophoresis.

Data Collection and Analysis

  • The nociceptive withdrawal reflex threshold (NWRT), a measure of the body’s pain response, was continuously monitored using an automated device.
  • The state of the horses’ sedation and cardiopulmonary variables were regularly assessed.
  • The gathered data helped to produce a pharmacokinetic-pharmacodynamic (PK-PD) model. The data was presented as either the mean ± standard deviation or the median with an interquartile range of 25%-75%, based on its suitability.
  • Differences between the groups were classified as statistically significant if the p-value was below 0.05.

Results

  • The horses showed higher NWRTs after receiving levomethadone compared to saline. The average increase was by 123 ± 9% relative to the baseline, as against 101 ± 9% in the saline group.
  • The PK-PD model showed that levomethadone contributed to the increase in the NWRT, but the effect size varied among individuals.
  • No adverse reactions were noted after levomethadone was administered.
  • A minor influence of levomethadone on sedation scores was seen for 60 minutes after its administration.

Conclusion

Levomethadone has the potential to enhance the NWRT in horses under romifidine CRI. It can also be combined with α-adrencoceptor agonists to increase pain relief (antinociception) in horses. There is, however, significant variation in the response of individual horses.

Cite This Article

APA
Studer N, Bernal SD, Thormann W, Levionnois O, Spadavecchia C. (2021). Antinociceptive effects of levomethadone in standing horses sedated with romifidine. Vet Anaesth Analg, 48(3), 451-460. https://doi.org/10.1016/j.vaa.2020.08.011

Publication

ISSN: 1467-2995
NlmUniqueID: 100956422
Country: United States
Language: English
Volume: 48
Issue: 3
Pages: 451-460
PII: S1467-2987(21)00004-0

Researcher Affiliations

Studer, Nicole
  • Department of Anaesthesiology and Pain Therapy, Vetsuisse Faculty, University of Bern, Bern, Switzerland. Electronic address: nicole_studer@gmx.net.
Bernal, Sabina Diez
  • Department of Anaesthesiology and Pain Therapy, Vetsuisse Faculty, University of Bern, Bern, Switzerland; The Royal (Dick) School of Veterinary Studies and the Roslin Institute, The University of Edinburgh, Midlothian, UK.
Thormann, Wolfgang
  • Department of Clinical Pharmacology, University of Bern, Bern, Switzerland.
Levionnois, Olivier
  • Department of Anaesthesiology and Pain Therapy, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Spadavecchia, Claudia
  • Department of Anaesthesiology and Pain Therapy, Vetsuisse Faculty, University of Bern, Bern, Switzerland.

MeSH Terms

  • Analgesics
  • Anesthesia / veterinary
  • Animals
  • Female
  • Horses
  • Imidazoles / pharmacology
  • Male
  • Prospective Studies

Citations

This article has been cited 3 times.
  1. Emanuel D, Kästner SBR, Delarocque J, Grob AJ, Bienert-Zeit A. Influence of Butorphanol, Buprenorphine and Levomethadone on Sedation Quality and Postoperative Analgesia in Horses Undergoing Cheek Tooth Extraction. Vet Sci 2022 Apr 6;9(4).
    doi: 10.3390/vetsci9040174pubmed: 35448672google scholar: lookup
  2. Nannarone S, Giannettoni G, Laurenza C, Giontella A, Moretti G. Methadone or Butorphanol as Pre-Anaesthetic Agents Combined with Romifidine in Horses Undergoing Elective Surgery: Qualitative Assessment of Sedation and Induction. Animals (Basel) 2021 Aug 31;11(9).
    doi: 10.3390/ani11092572pubmed: 34573538google scholar: lookup
  3. Maidanskaia EG, Mirra A, Marchionatti E, Levionnois OL, Spadavecchia C. Antinociceptive, Sedative and Excitatory Effects of Intravenous Butorphanol Administered Alone or in Combination with Detomidine in Calves: A Prospective, Randomized, Blinded Cross-Over Study. Animals (Basel) 2023 Jun 9;13(12).
    doi: 10.3390/ani13121943pubmed: 37370454google scholar: lookup