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Abstract
Rabbits present unique anesthetic challenges due to their high metabolic rate, stress susceptibility, and increased perioperative mortality risk. The physiological effects of two injectable anesthetic protocols Midazolam-Ketamine (MK) and Xylazine-Ketamine (XK) in rabbits undergoing orthopedic Surgery (implant removal) are compared in this study. A total of six rabbits were randomly assigned to two groups (n=3 per group) to receive either MK (5 mg/kg midazolam + 20 mg/kg ketamine) or XK (5 mg/kg xylazine + 20 mg/kg ketamine) intramuscularly. At baseline and at 0, 30, 60, 90, and 120 minutes after induction, core temperature, respiratory rate, and pulse rate were measured. The results showed that the XK combination caused severe respiratory depression immediately after induction (mean difference: −23.33 breaths/min, 95% CI: −25.31 to −21.35) and considerable hypothermia, with a mean temperature difference of −3.37°C after 60 minutes (95% CI: −4.51 to −2.22). While the Midazolam-Ketamine (MK) combination provided better physiological stability in maintaining normothermia and respiratory function, the Xylazine-Ketamine (XK) protocol offered more effective postoperative analgesia despite causing significant hypothermia and respiratory depression. These findings suggest MK may be a safer option for routine use, whereas XK may be considered when analgesia is prioritized and adequate supportive care is ensured. Furthermore, in resource-limited circumstances, Xylazine-Ketamine remains a feasible alternative when complemented with active warming and respiratory monitoring.
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References
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References
Brodbelt, D. (2009). Perioperative mortality in small animal anaesthesia. Vet. J., 182(2), 152–161. https://doi.org/10.1016/j.tvjl.2008.06.011
Brodbelt, D. C., Blissitt, K. J., Hammond, R. A., Neath, P. J., Young, L. E., Pfeiffer, D. U., and Wood, J. L. (2008). The risk of death: The confidential enquiry into perioperative small animal fatalities. Vet. Anaesth. Analg., 35(5), 365–373. https://doi.org/10.1111/j.1467-2995.2008.00397.x
Dandea, Ş. M., Peștean, C. P., Melega, I., Codea, R. A., Bel, L. V., Hașaș, A. D., Popovici, C. P., and Sevastre, B. (2025). Anesthetic protocols for enhancing physiological stability in rabbits during hemorrhagic shock. Vet. Med. Int., (2025), 6645642. https://doi.org/10.1155/vmi/6645642
Fitri, W. N., Wahid, H., Jesse, F. F., Sarah, S. A., Mohd-Azmi, M., and Azrolharith, S. (2021). Semen collection in Rusa timorensis under general anaesthesia by using ketamine-xylazine. Iraqi J. Vet. Sci., 35(1), 197–205. https://doi.org/10.33899/ijvs.2020.126614.1350
Flecknell, P. A. (1998). Developments in the veterinary care of rabbits and rodents. In Pract., 20(6), 286–295. https://doi.org/10.1136/inpract.20.6.286
Fusco, A., Douglas, H., Barba, A., Hopster, K., Stefanovski, D., Sinder, B., Cahill, P. J., Snyder, B., and Schaer, T. P. (2021). V-Gel® guided endotracheal intubation in rabbits. Front. Vet. Sci., 8, 684624. https://doi.org/10.3389/fvets.2021.684624 PMID: 34136562; PMCID: PMC8193276
Gardhouse, S., and Sanchez, A. (2022). Rabbit sedation and anesthesia. Vet. Clin. North Am. Exot. Anim. Pract., 25(1), 181–210. https://doi.org/10.1016/j.cvex.2021.08.012
Giovanitti, J. A., Jr, Thoms, S. M., and Crawford, J. J. (2015). Alpha-2 adrenergic receptor agonists: a review of current clinical applications. Anesth. Prog., 62(1), 31–39. https://doi.org/10.2344/0003-3006-62.1.31
Hobbs, B. A., Rolhall, T. G., Sprenkel, T. L., and Anthony, K. L. (1991). Comparison of several combinations for anesthesia in rabbits. Am. J. Vet. Res., 52(5), 669–674. PMID: 2064334
Johnson-Delaney, C. A., and Orosz, S. E. (2011). Rabbit respiratory system: Clinical anatomy, physiology and disease. Vet. Clin. North Am. Exot. Anim. Pract., 14(2), 257–vi. https://doi.org/10.1016/j.cvex.2011.03.002
Lee, V. K., Flynt, K. S., Haag, L. M., and Taylor, D. K. (2010). Comparison of the effects of ketamine, ketamine-medetomidine, and ketamine-midazolam on physiologic parameters and anesthesia-induced stress in rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques. J. Am. Assoc. Lab. Anim. Sci., 49(1), 57–63. PMID: 20122317; PMCID: PMC2826836
Mahmood, M. B. (2022). A comparison between ketamine-xylazine and ketamine-midazolam or all of them to induce balance anesthesia in rabbits. Iraqi J. Vet. Sci., 36(2), 499–506. https://doi.org/10.33899/ijvs.2021.130618.1852
Marín, P., Belda, E., Laredo, F. G., Torres, C. A., Hernandis, V., and Escudero, E. (2020). Pharmacokinetics and sedative effects of alfaxalone with or without dexmedetomidine in rabbits. Res. Vet. Sci., 129, 6–12. https://doi.org/10.1016/j.rvsc.2019.12.015
Mohammed, E., and Abd-Alhafid, Y. (2023). The relationship between heart rate, body weight and heart weight in male rabbits Oryctolagus cuniculus. and domestic chicken males "Gallus gallus". Libyan J. Basic Sci., 20, 117–125.
Schmid, M. L., Werner, J., Saller, A. M., Reiser, J., Zablotski, Y., Ostertag, J., Kreuzer, M., Lendl, C., Potschka, H., & Baumgartner, C. (2025). Evaluation of different intramuscular injectable anesthetic combinations in rabbits: Impact on anesthetic depth, physiological parameters, and EEG recordings. PLoS One, 20(2), e0319106. https://doi.org/10.1371/journal.pone.0319106
Wenger, S. (2012). Anesthesia and analgesia in rabbits and rodents. J. Exot. Pet Med., 21(1), 7–16. https://doi.org/10.1053/j.jepm.2011.11.010