Comparison of intramuscular administration of alfaxalone-ketamine-dexmedetomidine and alfaxalone-butorphanol-midazolam in naked mole-rats (Heterocephalus glaber)

David Eshar 1Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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Gail L. Huckins 1Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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Trenton C. Shrader 2Lincoln Children's Zoo, 122 S 27th St, Lincoln, NE 68502.

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Hugues Beaufrère 3Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON NIG 2WI, Canada.

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Abstract

OBJECTIVE

To compare anesthetic effects of alfaxalone-ketamine-dexmedetomidine (AKD) and alfaxalone-butorphanol-midazolam (ABM) in naked mole-rats (Heterocephalus glaber).

ANIMALS

20 naked mole-rats.

PROCEDURES

Naked mole-rats received AKD (alfaxalone, 2 mg/kg; ketamine, 20 mg/kg; and dexmedetomidine, 0.02 mg/kg; n = 10) or ABM (alfaxalone, 2 mg/kg; butorphanol, 2 mg/kg; and midazolam, 1 mg/kg; 9) IM; 1 animal was removed from the study. Atipamezole (I mg/kg) and flumazenil (0.1 mg/kg) were administered 40 minutes after anesthetic induction (defined as loss of the righting reflex) with AKD and ABM, respectively. Heart rate, respiratory rate, oxygen saturation, and reflexes were recorded every 5 minutes.

RESULTS

The ABM group had significantly longer median times for induction and recovery than the AKD group. Administration of ABM resulted in significantly lower respiratory rates than administration of AKD from time of anesthetic induction to 10 minutes after induction. Respiratory rate significantly decreased in the AKD group from I0 minutes after induction through the end of the anesthetic period but did not change over time in the ABM group. Males had higher respiratory rates in both groups. Loss of the righting reflex was still evident 40 minutes after induction in both groups. In the AKD group, all tested reflexes were absent from I0 to 40 minutes after induction; the ABM group had variable reflexes that recovered within individual animals over time.

CONCLUSIONS AND CLINICAL RELEVANCE

Both AKD and ABM provided effective immobilization in naked mole-rats, but AKD appeared to provide more consistent and deeper anesthesia, compared with administration of ABM.

Abstract

OBJECTIVE

To compare anesthetic effects of alfaxalone-ketamine-dexmedetomidine (AKD) and alfaxalone-butorphanol-midazolam (ABM) in naked mole-rats (Heterocephalus glaber).

ANIMALS

20 naked mole-rats.

PROCEDURES

Naked mole-rats received AKD (alfaxalone, 2 mg/kg; ketamine, 20 mg/kg; and dexmedetomidine, 0.02 mg/kg; n = 10) or ABM (alfaxalone, 2 mg/kg; butorphanol, 2 mg/kg; and midazolam, 1 mg/kg; 9) IM; 1 animal was removed from the study. Atipamezole (I mg/kg) and flumazenil (0.1 mg/kg) were administered 40 minutes after anesthetic induction (defined as loss of the righting reflex) with AKD and ABM, respectively. Heart rate, respiratory rate, oxygen saturation, and reflexes were recorded every 5 minutes.

RESULTS

The ABM group had significantly longer median times for induction and recovery than the AKD group. Administration of ABM resulted in significantly lower respiratory rates than administration of AKD from time of anesthetic induction to 10 minutes after induction. Respiratory rate significantly decreased in the AKD group from I0 minutes after induction through the end of the anesthetic period but did not change over time in the ABM group. Males had higher respiratory rates in both groups. Loss of the righting reflex was still evident 40 minutes after induction in both groups. In the AKD group, all tested reflexes were absent from I0 to 40 minutes after induction; the ABM group had variable reflexes that recovered within individual animals over time.

CONCLUSIONS AND CLINICAL RELEVANCE

Both AKD and ABM provided effective immobilization in naked mole-rats, but AKD appeared to provide more consistent and deeper anesthesia, compared with administration of ABM.

Contributor Notes

Address correspondence to Dr. Eshar (deshar@vet.k-state.edu).
  • 1. Artwohl J, Hill T, Comer C, et al. Naked mole-rats: unique opportunities and husbandry challenges. Lab Anim (NY) 2002;31:32–36.

  • 2. Donnelly TM, Bergin I, Ihrig M. Biology and diseases of other rodents. In: Fox JG, Anderson LC, Otto GM, et al, eds. Laboratory animal medicine. 3rd ed. Amsterdam: Elsevier, 2015;328–330.

    • Search Google Scholar
    • Export Citation
  • 3. Garcia Montero A, Burda H, Begall S. Chemical restraint of African mole-rats (Fukomys sp.) with a combination of ketamine and xylazine. Vet Anaesth Analg 2015;42:187–191.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4. Widmer HR, Hoppeler H, Nevo E, et al. Working underground: respiratory adaptations in the blind mole rat. Proc Natl Acad Sci U S A 1997;94:2062–2067.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5. Crish SD, Dengler-Crish CM, Catania KC. Central visual system of the naked mole-rat (Heterocephalus glaber). Anat Rec A Discov Mol Cell Evol Biol 2006;288:205–212.

    • Search Google Scholar
    • Export Citation
  • 6. Henry EC, Sarko DK, Catania KC. Central projections of trigeminal afferents innervating the face in naked mole-rats (Heterocephalus glaber). Anat Rec (Hoboken) 2008;291:988–998.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7. Hetling JR, Baig-Silva MS, Comer CM, et al. Features of visual function in the naked mole-rat Heterocephalus glaber. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 2005;191:317–330.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8. Negroni J, Nevo E, Cooper HM. Neuropeptidergic organization of the suprachiasmatic nucleus in the blind mole rat (Spalax ehrenbergi). Brain Res Bull 1997;44:633–639.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9. Nemec P, Burda H, Peichl L. Subcortical visual system of the African mole-rat Cryptomys anselli: to see or not to see? Eur J Neurosci 2004;20:757–768.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10. Park KK, Luo X, Mooney SJ, et al. Retinal ganglion cell survival and axon regeneration after optic nerve injury in naked mole-rats. J Comp Neurol 2017;525:380–388.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11. Streicher S, Boyles JG, Oosthuizen MK, et al. Body temperature patterns and rhythmicity in free-ranging subterranean Damaraland mole-rats, Fukomys damarensis. PLoS One 2011;6:e26346.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12. Arenillas M, Gomez de Segura IA. Anaesthetic effects of alfaxalone administered intraperitoneally alone or combined with dexmedetomidine and fentanyl in the rat. Lab Anim 2018;52:588–598.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13. Flecknell PA, Thomas AA. Comparative anesthesia and analgesia of laboratory animals. In: Grimm KA, Lamont LA, Tranquilli WJ, et al, eds. Veterinary anesthesia and analgesia. Oxford, England: Wiley Blackwell, 2015;754–763.

    • Search Google Scholar
    • Export Citation
  • 14. Hahn N, Eisen RJ, Eisen L, et al. Ketamine-medetomidine anesthesia with atipamezole reversal: practical anesthesia for rodents under field conditions. Lab Anim (NY) 2005;34:48–51.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15. Molina AM, Moyano MR, Serrano-Rodriguez JM, et al. Analyses of anaesthesia with ketamine combined with different sedatives in rats. Vet Med Czech 2015;60:368–375.

    • Search Google Scholar
    • Export Citation
  • 16. Browning GR, Eshar D, Beaufrère H. Comparison of dexmedetomidine-ketamine-midazolam and isoflurane for anesthesia of black-tailed prairie dogs (Cynomys ludovicianus). J Am Assoc Lab Anim Sci 2019;58:50–57.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17. Fox L, Snyder LB, Mans C. Comparison of dexmedetomidine-ketamine with isoflurane for anesthesia of chinchillas (Chinchilla lanigera). J Am Assoc Lab Anim Sci 2016;55:312–316.

    • Search Google Scholar
    • Export Citation
  • 18. Higuchi S, Yamada R, Hashimoto A, et al. Evaluation of a combination of alfaxalone with medetomidine and butorphanol for inducing surgical anesthesia in laboratory mice. Jpn J Vet Res 2016;64:131–139.

    • Search Google Scholar
    • Export Citation
  • 19. Parkinson L, Mans C. Anesthetic and postanesthetic effects of alfaxalone-butorphanol compared with dexmedetomidine-ketamine in chinchillas (Chinchilla lanigera). J Am Assoc Lab Anim Sci 2017;56:290–295.

    • Search Google Scholar
    • Export Citation
  • 20. Doerning CM, Bradley MP, Lester PA, et al. Effects of subcutaneous alfaxalone alone and in combination with dexmedetomidine and buprenorphine in guinea pigs (Cavia porcellus). Vet Anaesth Analg 2018;45:658–666.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21. Bradley MP, Doerning CM, Nowland MH, et al. Intramuscular administration of alfaxalone alone and in combination for sedation and anesthesia of rabbits (Oryctolagus cuniculus). J Am Assoc Lab Anim Sci 2019;58:216–222.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22. Ribas T, Bublot I, Junot S, et al. Effects of intramuscular sedation with alfaxalone and butorphanol on echocardiographic measurements in healthy cats. J Feline Med Surg 2015;17:530–536.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23. Khenissi L, Nikolayenkova-Topie O, Broussaud S, et al. Comparison of intramuscular alfaxalone and ketamine combined with dexmedetomidine and butorphanol for castration in cats. J Feline Med Surg 2017;19:791–797.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24. Lee J, Suh S, Choi R, et al. Cardiorespiratory and anesthetic effects produced by the combination of butorphanol, medetomidine and alfaxalone administered intramuscularly in Beagle dogs. J Vet Med Sci 2016;77:1677–1680.

    • Search Google Scholar
    • Export Citation
  • 25. Seo JI, Han SH, Choi R, et al. Cardiopulmonary and anesthetic effects of the combination of butorphanol, midazolam and alfaxalone in Beagle dogs. Vet Anaesth Analg 2015;42:304–308.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26. d'Ovidio D, Marino F, Noviello E, et al. Sedative effects of intramuscular alfaxalone in pet guinea pigs (Cavia porcellus). Vet Anaesth Analg 2018;45:183–189.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27. Siriarchavatana P, Ayers JD, Kendall LV. Anesthetic activity of alfaxalone compared with ketamine in mice. J Am Assoc Lab Anim Sci 2016;55:426–430.

    • Search Google Scholar
    • Export Citation
  • 28. Muñoz KA, Robertson SA, Wilson DV. Alfaxalone alone or combined with midazolam or ketamine in dogs: intubation dose and select physiologic effects. Vet Anaesth Analg 2017;44:766–774.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29. Lemke KA. Perioperative use of selective alpha-2 agonists and antagonists in small animals. Can Vet J 2004;45:475–480.

  • 30. Turner PV, Brabb T, Pekow C, et al. Administration of substances to laboratory animals: routes of administration and factors to consider. J Am Assoc Lab Anim Sci 2011;50:600–613.

    • Search Google Scholar
    • Export Citation
  • 31. Lau C, Ranasinghe MG, Shiels I, et al. Plasma pharmacokinetics of alfaxalone after a single intraperitoneal or intravenous injection of Alfaxan® in rats. J Vet Pharmacol Ther 2013;36:516–520.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32. Italiano M, Robinson R. Effect of benzodiazepines on the dose of alfaxalone needed for endotracheal intubation in healthy dogs. Vet Anaesth Analg 2018;45:720–728.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33. Zapata A, Laredo FG, Escobar M, et al. Effects of midazolam before or after alfaxalone for co-induction of anaesthesia in healthy dogs. Vet Anaesth Analg 2018;45:609–617.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34. Lagos-Carvajal A, Queiroz-Williams P, da Cunha A, et al. Determination of midazolam dose as co-induction with alfaxalone in sedated cats. Vet Anaesth Analg 2019;46:299–307.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35. Rodrigo-Mocholí D, Belda E, Bosmans T, et al. Clinical efficacy and cardiorespiratory effects of intramuscular administration of alfaxalone alone or in combination with dexmedetomidine in cats. Vet Anaesth Analg 2016;43:291–300.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36. Erickson RL, Blevins CE, Souza Dyer CD, et al. Alfaxalone-xylazine anesthesia in laboratory mice (Mus musculus). J Am Assoc Lab Anim Sci 2019;58:30–39.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37. Ramoo S, Bradbury LA, Anderson GA, et al. Sedation of hyperthyroid cats with subcutaneous administration of a combination of alfaxalone and butorphanol. Aust Vet J 2013;91:131–136.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38. Chan ED, Chan MM, Chan MM. Pulse oximetry: understanding its basic principles facilitates appreciation of its limitations. Respir Med 2013;107:789–799.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 39. White KL, Paine S, Harris J. A clinical evaluation of the pharmacokinetics and pharmacodynamics of intravenous alfaxalone in cyclodextrin in male and female rats following a loading dose and constant rate infusion. Vet Anaesth Analg 2017;44:865–875.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 40. Fink G, Sarkar DK, Dow RC, et al. Sex difference in response to alphaxalone anaesthesia may be oestrogen dependent. Nature 1982;298:270–272.

  • 41. Bencze M, Behuliak M, Zicha J. The impact of four different classes of anesthetics on the mechanisms of blood pressure regulation in normotensive and spontaneously hypertensive rats. Physiol Res 2013;62:471–478.

    • Search Google Scholar
    • Export Citation
  • 42. Ferré PJ, Pasloske K, Whittem T, et al. Plasma pharmacokinetics of alfaxalone in dogs after an intravenous bolus of Alfaxan-CD RTU. Vet Anaesth Analg 2006;33:229–236.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 43. Muir W, Lerche P, Wiese A, et al. Cardiorespiratory and anesthetic effects of clinical and supraclinical doses of alfaxalone in dogs. Vet Anaesth Analg 2008;35:451–462.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 44. Maddern K, Adams VJ, Hill NA, et al. Alfaxalone induction dose following administration of medetomidine and butorphanol in the dog. Vet Anaesth Analg 2010;37:7–13.

    • Crossref
    • Search Google Scholar
    • Export Citation

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