Welfare Implications of Low-Dose Atipamezole Reversal of Tiletamine/Zolazepam/Xylazine Anaesthesia in Pigs

Overview

Journal Animals (Basel)

Date 2025 Jan 25

PMID 39858258

Authors

Rachel Layton

David S Beggs

Andrew Fisher

Peter Mansell

Daniel Layton

Peter A Durr

Teegan Allen

Grace Taylor

Michael L Kelly

David T Williams

Kelly J Stanger

Affiliations

Soon will be listed here.

Abstract

Anaesthesia is sometimes required for the effective restraint of laboratory pigs for sample collection. Yet, anaesthesia can initiate a range of physiological disruptions that can increase variability in study data and lead to poorer animal welfare. Judicious use of anaesthesia can mitigate experimental, human safety, and animal welfare concerns, but it does not eliminate the potential for adverse effects. The use of reversal agents can shorten recovery time and reduce the physiological impacts of anaesthesia but can also cause additional side effects. We, therefore, trialled the use of low-dose atipamezole (0.12 mg/kg) for the antagonism of xylazine in laboratory pigs anaesthetised using a combination of xylazine and zolazepam/tiletamine. We measured time to recovery, selected clinical variables, recovery characteristics, and behaviours to investigate if a low dose of antagonist decreased recovery time and reduced the physiological impacts of anaesthesia whilst avoiding adverse negative side effects. We categorised side effects and behaviours as having either a low or high negative welfare impact based on the potential risk of injury and whether behaviours were displayed before or after return to consciousness. Collectively, our results indicated that while the use of low-dose atipamezole decreased recovery time and improved thermoregulation in most pigs, it introduced and exacerbated adverse side effects and behaviours that can lead to poorer welfare outcomes for laboratory pigs.

References

Zhang Z, Bai H, Zhang B, Shen M, Gao L . Comparison of cardiorespiratory and anesthetic effects of ketamine-midazolam-xylazine-sufentanil and tiletamine-zolazepam-xylazine in miniature pigs. PLoS One. 2022; 17(7):e0271325. PMC: 9275679. DOI: 10.1371/journal.pone.0271325. View

Haskins S . General guidelines for judging anesthetic depth. Vet Clin North Am Small Anim Pract. 1992; 22(2):432-4. DOI: 10.1016/s0195-5616(92)50659-3. View

Lin H, Thurmon J, Benson G, Tranquilli W . Telazol--a review of its pharmacology and use in veterinary medicine. J Vet Pharmacol Ther. 1993; 16(4):383-418. DOI: 10.1111/j.1365-2885.1993.tb00206.x. View

Dent B, Stevens K, Clymer J . Forced-Air Warming Provides Better Control of Body Temperature in Porcine Surgical Patients. Vet Sci. 2017; 3(3). PMC: 5606582. DOI: 10.3390/vetsci3030022. View

OMalley C, Hubley R, Tambadou H, Turner P . Refining restraint techniques for research pigs through habituation. Front Vet Sci. 2022; 9:1016414. PMC: 9541109. DOI: 10.3389/fvets.2022.1016414. View

Swindle M, Makin A, Herron A, Clubb Jr F, Frazier K . Swine as models in biomedical research and toxicology testing. Vet Pathol. 2011; 49(2):344-56. DOI: 10.1177/0300985811402846. View

Yang H, Galang K, Gallegos A, Ma B, Isseroff R . Sling Training with Positive Reinforcement to Facilitate Porcine Wound Studies. JID Innov. 2022; 1(2):100016. PMC: 8669512. DOI: 10.1016/j.xjidi.2021.100016. View

Haapalinna A, Viitamaa T, Macdonald E, Savola J, Tuomisto L, Virtanen R . Evaluation of the effects of a specific alpha 2-adrenoceptor antagonist, atipamezole, on alpha 1- and alpha 2-adrenoceptor subtype binding, brain neurochemistry and behaviour in comparison with yohimbine. Naunyn Schmiedebergs Arch Pharmacol. 1997; 356(5):570-82. DOI: 10.1007/pl00005092. View

Lee J, Jee H, Jeong S, Park C, Kim M . Comparison of anaesthetic and cardiorespiratory effects of xylazine or medetomidine in combination with tiletamine/zolazepam in pigs. Vet Rec. 2010; 167(7):245-9. DOI: 10.1136/vr.c3611. View

10.

Nishimura R, Kim H, Matsunaga S, Sakaguchi M, Sasaki N, Tamura H . Antagonism of medetomidine sedation by atipamezole in pigs. J Vet Med Sci. 1992; 54(6):1237-40. DOI: 10.1292/jvms.54.1237. View

11.

Ruetzler K, Kurz A . Consequences of perioperative hypothermia. Handb Clin Neurol. 2018; 157:687-697. DOI: 10.1016/B978-0-444-64074-1.00041-0. View

12.

Swindle M, Nolan T, Jacobson A, Wolf P, Dalton M, Smith A . Vascular access port (VAP) usage in large animal species. Contemp Top Lab Anim Sci. 2005; 44(3):7-17. View

13.

Rushen J, Schwarze N, Ladewig J, Foxcroft G . Opioid modulation of the effects of repeated stress on ACTH, cortisol, prolactin, and growth hormone in pigs. Physiol Behav. 1993; 53(5):923-8. DOI: 10.1016/0031-9384(93)90270-p. View

14.

Layton R, Layton D, Beggs D, Fisher A, Mansell P, Stanger K . The impact of stress and anesthesia on animal models of infectious disease. Front Vet Sci. 2023; 10:1086003. PMC: 9933909. DOI: 10.3389/fvets.2023.1086003. View

15.

Lee J, Kim M . Anesthesia of growing pigs with tiletamine-zolazepam and reversal with flumazenil. J Vet Med Sci. 2011; 74(3):335-9. DOI: 10.1292/jvms.10-0501. View

16.

Kim M, Park C, Jun M, Kim M . Antagonistic effects of yohimbine in pigs anaesthetised with tiletamine/zolazepam and xylazine. Vet Rec. 2007; 161(18):620-4. DOI: 10.1136/vr.161.18.620. View

17.

Klages C . IACUC and Veterinary Considerations for Review of ABSL3 and ABSL4 Research Protocols. ILAR J. 2021; 61(1):3-9. PMC: 8083656. DOI: 10.1093/ilar/ilab009. View

18.

Guo L, Kaustov L, Brenna C, Patel V, Zhang C, Choi S . Cognitive deficits after general anaesthesia in animal models: a scoping review. Br J Anaesth. 2022; 130(2):e351-e360. DOI: 10.1016/j.bja.2022.10.004. View

19.

Copps J . Issues related to the use of animals in biocontainment research facilities. ILAR J. 2005; 46(1):34-43. PMC: 7108559. DOI: 10.1093/ilar.46.1.34. View

20.

Smith A, Swindle M . Preparation of swine for the laboratory. ILAR J. 2006; 47(4):358-63. DOI: 10.1093/ilar.47.4.358. View