Dissociative anesthesia using ketamine combined with midazolam, dexmedetomidine, or both, with or without reversal, for orchiectomy in guinea pigs (Cavia porcellus)

Authors

DOI:

https://doi.org/10.5433/1679-0359.2025v46n5p1327

Keywords:

Glucose, Heart rate, Post-anesthetic recovery, Respiratory rate, Sedation.

Abstract

The increasing popularity of guinea pigs as pets and their high reproductive capacity have heightened demand for orchiectomy procedures. This study aimed to evaluate the effects of different anesthetic drug combinations on this species. Eighteen male Cavia porcellus (641 ± 135 g) were randomly assigned to three groups (n = 6) after baseline blood glucose measurement: ketamine (15 mg kg -1) combined with midazolam (1 mg kg -1) (M), dexmedetomidine (10 µg kg -1) (D), or half-doses of each (0.5 mg kg-1 midazolam and 5 µg kg -1 dexmedetomidine) (DM). After intramuscular administration, sedation was scored using two systems that assessed posture, response to stimuli, and muscle relaxation. Orchiectomy was then performed under aseptic conditions, with all animals receiving standardized supportive care, including thermal support via a heating mattress and continuous monitoring of vital parameters. A single veterinarian performed all surgeries to ensure consistency. Anesthesia was maintained with isoflurane (1 vol%) via face mask, adjusted by ± 0.25 vol% in response to manipulation and vital signs. Postoperatively, blood glucose was re-measured, and three animals from each group received antagonists: flumazenil (0.1 mg kg -1) in group M, atipamezole (50 µg kg -1) in group D, or half-doses of both drugs in group DM. Recovery was assessed using the blink reflex, time to ventral recumbency, and time to ambulation, with blood glucose levels measured again at the end of recovery. On one sedation scale, group D (score 19, range 18–19) exhibited significantly deeper sedation than group M (14.5, range 7–18), while group DM (18, range 9–19) did not differ significantly from either. Mean heart rate was highest in group M (249 ± 29) compared with groups D (184 ± 16) and DM (180 ± 21). Isoflurane concentration was lowest in group D (0.8 ± 0.2 vol%) compared with groups M (1.5 ± 0.4 vol%) and DM (1.4 ± 0.4 vol%). Antagonists reduced recovery time by 66% in group M, 30% in group D, and 48% in group DM, with significantly shorter times to ambulation observed in groups M and DM. Blood glucose levels did not differ significantly across groups. In conclusion, ketamine combined with dexmedetomidine provided deeper sedation, reduced isoflurane requirements, and, in the groups receiving dexmedetomidine, lowered heart rate compared with midazolam, whereas antagonist administration accelerated recovery in protocols containing midazolam.

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Author Biographies

Gustavo Antônio Boff, Universidade Federal de Pelotas

PhD Student, Postgraduate Degree in Veterinary Medicine, Universidade Federal de Pelotas, UFPEL, Pelotas, RS, Brazil.

Luã Borges Iepsen, Universidade Federal de Pelotas

M.e Student, Postgraduate Degree in Veterinary Medicine, UFPEL, Pelotas, RS, Brazil.

Ana Paula Morel, Universidade Federal de Pelotas

PhD Student, Postgraduate Degree in Veterinary Medicine, Universidade Federal de Pelotas, UFPEL, Pelotas, RS, Brazil.

Mical Cipriano Felipe, Universidade Federal de Pelotas

Self-employed Veterinarian, Florianopolis, SC, Brazil.

Marta Priscila Vogt, Universidade Federal de Pelotas

Self-employed Veterinarian, Porto Alegre, RS, Brazil.

Fabiane Borelli Grecco, Universidade Federal de Pelotas

Profa. Dra., Undergraduate Degree in Veterinary Medicine, UFPEL, Pelotas, RS, Brazil.

Martielo Ivan Gehrcke, Universidade Federal de Pelotas

Prof. Dr., Undergraduate Degree in Veterinary Medicine, UFPEL, Pelotas, RS, Brazil.

References

Aarnes, T. K., Dent, B. T., Lakritz, J., Kukanich, B., Wavreille, V. A., Lerche, P., Ricco Pereira, C. H., & Bednarski, R. M. (2023). Pharmacokinetics and pharmacodynamics of intramuscular dexmedetomidine in dogs. American Journal of Veterinary Research, 84(4), 1-5. doi: 10.2460/ajvr.22.10.0184

Allweiler, S. I. (2016). How to improve anesthesia and analgesia in small mammals. Veterinary Clinics of North America: Exotic Animal Practice, 19(2), 361-377. doi: 10.1016/j.cvex.2016.01.012

Atalan, G., Erol, H., Atasever, A., Doğan, Z., Güneş, V., Yönez, M. K., & Keleş, I. (2019). Comparison of systemic effects of midazolam, ketamine and isoflurane anaesthesia in rabbits. Journal of Veterinary Research, 63(3), 275-283. doi: 10.2478/jvetres-2019-0035

Avelino, J. A., Walsh, C. A., Wharton, K. N., Ekanayake, D., & Ekanayake-Alper, D. (2024). A comparison of three anesthetic drug combinations for inducing surgical anesthesia in female guinea pigs (Cavia porcellus). Journal of the American Association for Laboratory Animal Science, 63(2), 182-189. doi: 10.30802/AALAS-JAALAS-23-000064

Bailey, R. S., Barter, L. S., Pypendop, B. H., & Wilson, R. P. (2017). Pharmacokinetics of dexmedetomidine in isoflurane-anesthetized New Zealand White rabbits. Veterinary Anaesthesia and Analgesia, 44(6), 876-882. doi: 10.1016/j.vaa.2017.01.003

Bellini, L., Banzato, T., Contiero, B., & Zotti, A. (2014). Evaluation of sedation and clinical effects of midazolam with ketamine or dexmedetomidine in pet rabbits. Veterinary Record, 175(15), 372. doi: 10.1136/vr.102595

Bennett, K., & Lewis, K. (2022). Sedation and anesthesia in rodents. Veterinary Clinics of North America: Exotic Animal Practice, 25(2), 211-255. doi: 10.1016/j.cvex.2021.08.013

Bienert, A., Płotek, W., Wiczling, P., Warzybok, J., Borowska, K., Buda, K., Kulińska, K., Billert, H., Kaliszan, R., & Grześkowiak, E. (2014). The influence of age and dosage on the pharmacodynamics of dexmedetomidine in rabbits. Journal of Medical Science, 83(2), 108-115. doi: 10.20883/medical.e53

Boehm, C. A., Carney, E. L., Tallarida, R. J., & Wilson, R. P. (2010). Midazolam enhances the analgesic properties of dexmedetomidine in the rat. Veterinary Anaesthesia and Analgesia, 37(6), 550-556. doi: 10.1111/j.1467-2995.2010.00565.x

Cantwell, S. L. (2001). Ferret, rabbit, and rodent anesthesia. Veterinary Clinics of North America: Exotic Animal Practice, 4(1), 169-191. doi: 10.1016/S1094-9194(17)30056-7

Connell, A. R., Hookham, M. B., Fu, D., Brazil, D. P., Lyons, T. J., & Yu, J. Y. (2022). Comparisons of α₂-adrenergic agents, medetomidine and xylazine, with pentobarbital for anesthesia: important pitfalls in diabetic and nondiabetic rats. Journal of Ocular Pharmacology and Therapeutics, 38(2), 156-166. doi: 10.1089/jop.2021.0084

Cruz, J. I., Loste, J. M., & Burzaco, O. H. (1998). Observations on the use of medetomidine/ketamine and its reversal with atipamezole for chemical restraint in the mouse. Laboratory Animals, 32(1), 18-22. doi: 10.1258/0023677987805593

Doerning, C. M., Bradley, M. P., Lester, P. A., & Nowland, M. H. (2018). Effects of subcutaneous alfaxalone alone and in combination with dexmedetomidine and buprenorphine in guinea pigs (Cavia porcellus). Veterinary Anaesthesia and Analgesia, 45(5), 658-666. doi: 10.1016/j.vaa.2018.06.004

Fox, L., Snyder, L. B. C., & Mans, C. (2016). Comparison of dexmedetomidine-ketamine with isoflurane for anesthesia of chinchillas (Chinchilla lanigera). Journal of the American Association for Laboratory Animal Science, 55(3), 312-316. PMID: 27177565

Gasparik-Küls, N., Larenza, M. P., & Rocchi, A. (2023). Use of a propofol infusion for anaesthetic maintenance in guinea pigs (Cavia porcellus): a retrospective case series. Veterinary Anaesthesia and Analgesia, 50(4), 498-501. doi: 10.1016/j.vaa.2023.06.005

Grint, N. J., & Murison, P. J. (2008). A comparison of ketamine-midazolam and ketamine-medetomidine combinations for induction of anaesthesia in rabbits. Veterinary Anaesthesia and Analgesia, 35(2), 113-121. doi: 10.1111/j.1467-2995.2007.00362.x

Isaza, N. M., & Isaza, R. (2020). Neutering procedures and considerations in rabbits and other small mammals. In S. White (Ed.), High-quality, high-volume spay and neuter and other shelter surgeries (vol. 1, pp. 295-323). Hoboken. doi: 10.1002/9781119646006

Kaiser, S., Korte, A., Wistuba, J., Baldy, M., Wissmann, A., Dubičanac, M., Richter, S. H., & Sachser, N. (2023). Effects of castration and sterilization on baseline and response levels of cortisol A case study in male guinea pigs. Frontiers in Veterinary Science, 9(6), 1093157. doi: 10.3389/fvets.2022.1093157

Kawano, T., Takahashi, T., Kaminaga, S., Kadono, T., Yamanaka, D., Iwata, H., Eguchi, S., & Yokoyama, M. (2015). A comparison of midazolam and dexmedetomidine for recovery of serotonin syndrome in rats. Journal of Anesthesia, 29(5), 631-634. doi: 10.1007/s00540-014-1973-9

Kint, L. T., Seewoo, B. J., Hyndman, T. H., Clarke, M. W., Edwards, S. H., Rodger, J., Feindel, K. W., & Musk, G. C. (2020). The pharmacokinetics of medetomidine administered subcutaneously during isoflurane anesthesia in Sprague-Dawley rats. Animals, 10(6), 1050. doi: 10.3390/ani10061050

Lennox, A. M., & Capello, V. (2008). Tracheal intubation in exotic companion mammals. Journal of Exotic Pet Medicine, 17(3), 221-227. doi: 10.1053/j.jepm.2008.05.009

Murrell, J. C., & Hellebrekers, L. J. (2005). Medetomidine and dexmedetomidine: a review of cardiovascular effects and antinociceptive properties in the dog. Veterinary Anaesthesia and Analgesia, 32(3), 117-127. doi: 10.1111/j.1467-2995.2005.00233.x

Okur, S., Yanmaz, L. E., Golgeli, A., Senocak, M. G., Ersoz, U., Orhun, O. T., & Gumurcinler, B. (2023). Sedative and cardiopulmonary effects of intranasal butorphanol with midazolam or dexmedetomidine in New Zealand White rabbits. Veterinary Record, 193(1), e2999. doi: 10.1002/vetr.2999

Rabe, H. (2011). Reference ranges for biochemical parameters in guinea pigs for the Vettest® 8008 blood analyzer. Tierärztliche Praxis Ausgabe K: Kleintiere/Heimtiere, 39(3), 170-175. PMID: 22143626

Ríos Álvarez, E., Vilalta Solé, L., & García de Carellán Mateo, A. (2022). Comparison of subcutaneous sedation with alfaxalone or alfaxalone-midazolam in pet guinea pigs (Cavia porcellus) of three different age groups. Journal of the American Veterinary Medical Association, 260(9), 1024-1030. doi: 10.2460/javma.21.02.0104

Rondeau, A., Langlois, I., Pang, D. S., & Leung, V. S. Y. (2020). Development of a sedation assessment scale for comparing the sedative effects of alfaxalone-hydromorphone and ketamine-midazolam-hydromorphone for intravenous catheterization in the domestic rat (Rattus norvegicus). Journal of Exotic Pet Medicine, 35(2), 117-122. doi: 10.1053/j.jepm.2020.09.004

Rousseau-Blass, F., Cribb, A. E., Beaudry, F., & Pang, D. S. J. (2021). A pharmacokinetic-pharmacodynamic study of intravenous midazolam and flumazenil in adult New Zealand White Californian rabbits (Oryctolagus cuniculus). Journal of the American Association for Laboratory Animal Science, 60(3), 319-328. doi: 10.30802/AALAS-JAALAS-20-000084

Scarabelli, S., & Nardini, G. (2019). Basic principles of anaesthesia of small mammals: Part 1. Companion Animal, 24(5), 271-276. doi: 10.12968/coan.2019.24.5.271

Scarabelli, S., & Nardini, G. (2020). Basic principles of anaesthesia of small mammals: Part 2. Companion Animal, 25(1), 1-8. doi: 10.12968/coan.2019.0064

Schmitz, S., Henke, J., Tacke, S., & Guth, B. (2016a). Successful implantation of an abdominal aortic blood pressure transducer and radio-telemetry transmitter in guinea pigs Anaesthesia, analgesic management and surgical methods, and their influence on hemodynamic parameters and body temperature. Journal of Pharmacological and Toxicological Methods, 80(1), 9-18. doi: 10.1016/j.vascn.2016.03.003

Schmitz, S., Tacke, S., Guth, B., & Henke, J. (2016b). Comparison of physiological parameters and anaesthesia-specific observations during isoflurane, ketamine-xylazine or medetomidine-midazolam-fentanyl anaesthesia in male guinea pigs. PLoS One, 11(8), e0161258. doi: 10.1371/journal.pone.0161258

Schmitz, S., Tacke, S., Guth, B., & Henke, J. (2017). Repeated anaesthesia with isoflurane and medetomidine-midazolam-fentanyl in guinea pigs and its influence on physiological parameters. PLoS One, 12(4), e0174423. doi: 10.1371/journal.pone.0174423

Schwartz, M., Muñana, K. R., Nettifee-Osborne, J. A., Messenger, K. M., & Papich, M. G. (2013). The pharmacokinetics of midazolam after intravenous, intramuscular and rectal administration in healthy dogs. Journal of Veterinary Pharmacology and Therapeutics, 36(5), 471-477. doi: 10.1111/jvp.12032

Serighelli, G., Jr., Comassetto, F., Stiehl, M. Z., & Oleskovicz, N. (2024). Evaluation of two protocols for chemical restraint in guinea pigs (Cavia porcellus). Archives of Veterinary Science, 29(3), e96398. doi: 10.5380/avs.v29i3.96398

Shomer, N. H., Holcombe, H., & Harkness, J. E. (2015). Biology and diseases of guinea pigs. In J. G. Fox, L. C. Anderson, G. M. Otto, K. R. Pritchett-Corning, & M. T. Whary (Eds.), Laboratory animal medicine (3nd ed., pp. 247-283). Amsterdam. doi: 10.1016/B978-0-12-409527-4.00006-7

Sixtus, R. P., Pacharinsak, C., Gray, C. L., Berry, M. J., & Dyson, R. M. (2021). Differential effects of four intramuscular sedatives on cardiorespiratory stability in juvenile guinea pigs (Cavia porcellus). PLoS One, 16(12), e0259559. doi: 10.1371/journal.pone.0259559

Wang, X., Xiang, P., Drummer, O. H., Ji, J., Zhuo, Y., Duan, G., & Shen, M. (2021). Pharmacokinetic study of midazolam and α-hydroxymidazolam in guinea pig blood and hair roots after a single dose of midazolam. Journal of Pharmaceutical and Biomedical Analysis, 195, 113890. doi: 10.1016/j.jpba.2021.113890

Wharton, K. N., Walsh, C. A., Haulter, M., Ekanayake, D., & Ekanayake-Alper, D. (2024). Sedation efficacy of midazolam in conjunction with ketamine and alfaxalone in female laboratory guinea pigs (Cavia porcellus). Journal of the American Association for Laboratory Animal Science, 63(5), 572-580. doi: 10.30802/AALAS-JAALAS-24-000028

Zimmerman, K., Moore, D. M., & Smith, S. A. (2015). Hematological assessment in pet guinea pigs (Cavia porcellus): blood sample collection and blood cell identification. Veterinary Clinics of North America: Exotic Animal Practice, 18(1), 33-40. doi: 10.1016/j.cvex.2014.09.002

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Published

2025-09-22

How to Cite

Boff, G. A., Iepsen, L. B., Morel, A. P., Felipe, M. C., Vogt, M. P., Grecco, F. B., & Gehrcke, M. I. (2025). Dissociative anesthesia using ketamine combined with midazolam, dexmedetomidine, or both, with or without reversal, for orchiectomy in guinea pigs (Cavia porcellus). Semina: Ciências Agrárias, 46(5), 1327–1346. https://doi.org/10.5433/1679-0359.2025v46n5p1327

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