A Comparative Evaluation of the Anesthetic Efficacy and Hepatic Safety of Tiletamine-Zolazepam and Ketamine-Diazepam in New Zealand White Rabbits
DOI:
https://doi.org/10.52331/v30i3pr13Keywords:
Rabbit, Tiletamine-Zolazepam, Ketamine-Diazepam, Toxicity, Anesthesia, Hepatic SafetyAbstract
This study aimed to compare the anesthetic efficacy, physiological stability, and hepatic effects of tiletamine-zolazepam (TZ) versus ketamine-diazepam (KD) in rabbits. Forty healthy male New Zealand White rabbits (2–3 kg) were randomly assigned into five groups: a saline control, three tiletamine-zolazepam (TZ) dose groups (32, 7.5, and 3.5 mg/kg IV), and a ketamine-diazepam (KD) group (20 + 1 mg/kg IV). Anesthetic depth, duration, and physiological parameters were monitored for 60 minutes. Blood samples were collected before anesthesia and on days 1, 3, 5, and 7 post-injection to assess liver function. The TZ-High group (32 mg/kg) exhibited the longest duration of anesthesia but also showed severe cardiorespiratory depression, characterized by a significant drop in respiratory rate and heart rate. Furthermore, this group displayed marked elevations in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at 24 and 72 hours, indicating significant hepatotoxicity. In contrast, the KD and TZ-Mid groups provided adequate anesthesia with better physiological stability and minimal biochemical alterations. It is concluded that while high-dose tiletamine-zolazepam provides prolonged anesthesia, it induces severe and unacceptable hepatotoxicity and cardiorespiratory distress in rabbits. The combination of ketamine-diazepam or a mid-range dose of tiletamine-zolazepam offers a safer alternative for procedures in rabbits.
References
1. Miller, I.; Rogel-Gaillard, C.; Spina, D.; Fontanesi, L.; De Almeida, A. The Rabbit as an Experi-mental and Production Animal: From Genomics to Proteomics. Curr. Protein Pept. Sci. 2014, 15, 134–145. doi:10.2174/1389203715666140221115135.
2. Mapara, M.; Thomas, B.S.; Bhat, K.M. Rabbit as an animal model for experimental research. Dent. Res. J. (Isfahan) 2012, 9, 111–118. doi:10.4103/1735-3327.92960.
3. Brodbelt, D. Perioperative mortality in small animal anaesthesia. Vet. J. 2009, 182, 152–161. doi:10.1016/j.tvjl.2008.06.011.
4. Schmid, M.L.; Werner, J.; Saller, A.M.; Reiser, J.; Zablotski, Y.; Ostertag, J.; et al. Evaluation of dif-ferent intramuscular injectable anesthetic combinations in rabbits: Impact on anesthetic depth, physi-ological parameters, and EEG recordings. PLoS One 2025, 20, e0319106. doi:10.1371/journal.pone.0319106.
5. Marín, P.; Belda, E.; Laredo, F.G.; Torres, C.A.; Hernandis, V.; Escudero, E. Pharmacokinetics and sedative effects of alfaxalone with or without dexmedetomidine in rabbits. Res. Vet. Sci. 2020, 129, 6–12.
6. Turner Giannico, A.; Ayres Garcia, D.A.; Lima, L.; de Lara, F.A.; Corona Ponczek, C.A.; Shaw, G.C.; et al. Determination of Normal Echocardiographic, Electrocardiographic, and Radiographic Cardiac Parameters in the Conscious New Zealand White Rabbit. J. Exot. Pet Med. 2015, 24, 223–234.
7. Henao-Guerrero, N.; Riccó, C.H. Comparison of the cardiorespiratory effects of a combination of ketamine and propofol, propofol alone, or a combination of ketamine and diazepam before and after induction of anesthesia in dogs sedated with acepromazine and oxymorphone. Am. J. Vet. Res. 2014, 75, 231–239.
8. Limprasutr, V.; Sharp, P.; Jampachaisri, K.; Pacharinsak, C.; Durongphongtorn, S. Tileta-mine/zolazepam and dexmedetomidine with tramadol provide effective general anesthesia in rats. Anim. Model Exp. Med. 2021, 4, 40–46.
9. Khokhlova, O.N.; Borozdina, N.A.; Sadovnikova, E.S.; Pakhomova, I.A.; Rudenko, P.A.; Korol-kova, Y.V.; et al. Comparative Study of the Aftereffect of CO₂ Inhalation or Tiletamine–Zolazepam–Xylazine Anesthesia on Laboratory Outbred Rats and Mice. Biomedicines 2022, 10, 512.
10. Topal, A.; Satar, N.Y.G.; Ates, O.; Uckan, E.M.; Yavas, O.; Cangul, I.T. Comparison of the effects of ketamine-diazepam, tiletamine-zolazepam and propofol infusion anesthesia in rabbit. Kafkas Univ. Vet. Fak. Derg. 2023, 29, 137–144.
11. Sokolowski, K.; Turner, P.V.; Lewis, E.; Wange, R.L.; Fortin, M.C. Exploring rabbit as a nonrodent species for general toxicology studies. Toxicol. Sci. 2024, 199, 29–39.
12. Harcourt-Brown, F. The rabbit consultation and clinical techniques. In Textbook of Rabbit Medicine; Harcourt-Brown, F., Ed.; Elsevier: Oxford, UK, 2002; pp. 52–93.
13. Wenger, S. Anesthesia and analgesia in rabbits and rodents. J. Exot. Pet Med. 2012, 21, 7–16.
14. Kianian, S.; Bansal, J.; Lee, C.; Zhang, K.; Bergese, S.D. Perioperative multimodal analgesia: a re-view of efficacy and safety of the treatment options. Anesthesiol. Perioper. Sci. 2024, 2, 9.
15. Karasu, A.; Altug, N.; Aslan, L.; Bakir, B.; Yuksek, N. Evaluation of the anesthetic effects of xylazine-ketamine, xylazine-tiletamine-zolazepam and tiletamine-zolazepam using clinical and labor-atory parameters in rabbits. Medycyna Wet. 2018, 74, 646–652.
16. Lester, P.A.; Moore, R.M.; Shuster, K.A.; Myers, D.D. Anesthesia and Analgesia. In The Laboratory Rabbit, Guinea Pig, Hamster, and Other Rodents; Suckow, M.A., Stevens, K.A., Wilson, R.P., Eds.; Academic Press: Boston, MA, USA, 2012; pp. 33–56.
17. Kabakchiev, C.; Valverde, A.; Singh, A.; Beaufrère, H. Cardiovascular and respiratory effects of carbon dioxide pneumoperitoneum in the domestic rabbit (Oryctolagus cuniculus). Can. J. Vet. Res. 2020, 84, 108–114.
18. Buckley, G.J.; DeCubellis, J.; Sharp, C.R.; Rozanski, E.A. Cardiopulmonary Resuscitation in Hospi-talized Rabbits: 15 cases. J. Exot. Pet Med. 2011, 20, 46–50. doi:10.1053/j.jepm.2010.11.010.
19. Gardhouse, S.; Sanchez, A. Rabbit Sedation and Anesthesia. Vet. Clin. North Am. Exot. Anim. Pract. 2022, 25, 181–210. doi:10.1016/j.cvex.2021.08.012.
20. Lennox, A.M. Care of the Geriatric Rabbit. Vet. Clin. North Am. Exot. Anim. Pract. 2010, 13, 123–133.
21. Lee, H.W.; Machin, H.; Adami, C. Peri-anaesthetic mortality and nonfatal gastrointestinal complica-tions in pet rabbits: a retrospective study on 210 cases. Vet. Anaesth. Analg. 2018, 45, 520–528.
22. Kiani, A.K.; Pheby, D.; Henehan, G.; Brown, R.; Sieving, P.; Sykora, P.; et al. Ethical considerations regarding animal experimentation. J. Prev. Med. Hyg. 2022, 63, E255–E266. doi:10.15167/2421-4248/jpmh2022.63.2S3.2768.
23. Kaye, A.D.; Urman, R.D.; Rappaport, Y.; Siddaiah, H.; Cornett, E.M.; Belani, K.; et al. Multimodal analgesia as an essential part of enhanced recovery protocols in the ambulatory settings. J. Anaesthe-siol. Clin. Pharmacol. 2019, 35, S40–S45.
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Copyright (c) 2026 Flavia Pradhan, Rajesh Tharu, Jyoti Chaudhary, Akash Adhikari, Sujan Adhikari, Dibina Kaini, Roshik Shrestha, Khema Pandey, Sanjay Paudel

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