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Medetomidine

Grade

Medetomidine + Alfaxalone


Medetomidine-Alfaxalone | Suitability


  • Multimodal Use: Multimodal use alongside additional agents is RECOMMENDED. Medetomidine is commonly employed as part of a  premedication protocol before, or alongside,  additional induction  agents.  Medetomidine is usually administered at modest dose alongside alfaxalone, ketamine, benzodiazepines and opiates.

  • Sole Agent Use: Sole agent use as an induction agent is NOT RECOMMENDED. Medetomidine is rarely employed as a sole agent  in  the rabbit because with sole use muscle rigidity and a long irreversible dose  related recovery time are commonplace. 


Medetomidine-Alfaxalone | Dosing Recommendations



[Medetomidine-Alfaxalone] | Intramuscular Sedation

Evidence Base: (Marsh et al., 2009)


  1. Induce: Medetomidine: 0.25 mg/kg and Alfaxalone 3-5 mg/kg; Administer together, slow IM

  2. Preoxygenate: Place in an oxygen chamber as sedation commences (Approx 5 mins)

  3. Intubation: Consider intubation and maintenance through the use of a volatile agent (e.g. Isoflurane) with supplementary oxygen. Intubation is recommended during all painful or significant procedures.

  4. Reversal: Optional. *Reversal with Atipamezole (2.5 X Medetomidine dose = half Medetomidine volume)

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[Medetomidine-Butorphanol]+Alfaxalone | Intravenous Anaesthesia

Evidence Base: (Navarrete-Calvo et al.)


  1. Induce: Medetomidine 0.04 mg/kg + Butorphanol 0.4 mg/kg + Alfaxalone 2.5 mg/kg, together, slow IM

  2. Preoxygenate: Place in an oxygen chamber as sedation commences (Approx 5 mins)

  3. Induce: One sedation, analgesia, and preoxygenation (5 mins) have taken effect to induce with Alfaxalone at 3-5 mg/kg slow IV to effect (Range 1-10 mg/kg)

  4. Intubation: Subsequent intubation and maintenance through the use of a volatile agent (e.g. Isoflurane) with supplementary oxygen is recommended for all painful or significant procedures.

  5. Reversal: Optional. *Reversal with Atipamezole (2.5 X Medetomidine dose = half Medetomidine volume)

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[Medetomidine -Morphine] +Alfaxalone | Intravenous Anaesthesia

Evidence Base: (Navarrete-Calvo et al.)


  1. Premedicate: Medetomidine 0.2 mg/kg + Morphine 1 -2 mg/kg, together, IV or IM.

  2. Preoxygenate: Place in an oxygen chamber as sedation commences (Approx 5 mins)

  3. Induce: One sedation, analgesia and preoxygenation (5 mins) have taken effect to induce with Alfaxalone 3-5 mg/kg, slow IV to effect (Range 1-10 mg/kg)

  4. Intubation: Subsequent intubation and maintenance through the use of a volatile agent (e.g. Isoflurane) with supplementary oxygen is recommended for all painful or significant procedures.

  5. Reversal: Optional. *Reversal with Atipamezole (2.5 X Medetomidine dose = half Medetomidine volume)

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Medetomidine-Alfaxalone Reversal


  • Atipamezole 0.25mg/kg IM per 0.1mg/kg of previously administered Medetomidine (2.5 X Medetomidine dose = half Medetomidine volume)


Evidence Base: (Baumgartner et al., 2010; Botman et al., 2020; Grint and Murison, 2008; Hellebrekers et al., 1997; Kaartinen et al., 2007; Kim et al., 2004; Kirihara et al., 2019; Orr et al., 2005; Williams and Wyatt, 2007)

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Therapeutics

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Therapeutic Considerations

  1. Administration Advice: Animals should have IV access and be preoxygenated before induction. This can be before or after premedication with medetomidine and additional agents. Ensure rabbits are kept away from predator contact, smell and excessive noise. In clinical settings, animals are usually intubated, or a supraglottic device is placed to allow volatile agents to be employed for anaesthetic maintenance.

  2. Multimodal Use: The protocols provided are all multimodal use.

  3. Adverse Effects Profile: Post-induction apnoea, defined as the cessation of breathing for 30 seconds, is possible if alfaxalone is administered intravenously. This appears more likely with rapid administration or high doses. Anxiolytic premedication and sensitive patient handling will reduce induction tachycardia associated with catecholamine release. Preoxygenation will extend the period where patients showing post-induction issues can be safely supported. Neurological signs (convulsions, myoclonus, tremor, prolonged anaesthesia), cardiorespiratory signs (cardiac arrests, bradycardia, bradypnea) and behavioural signs (hyperactivity, vocalisation) are reported as very rare adverse effects on product datasheets.

  4. Reproductive Safety: According to a product datasheet, studies using alfaxalone in pregnant mice, rats and rabbits have demonstrated no harmful effects on the treated animals' gestation or on their offspring's reproductive performance.

  5. Treatment Goals: Profound sedation or surgical anaesthesia.

  6. Treatment Endpoints: Surgical anaesthesia and positive surgical outcomes.

  7. Efficacy Profile: The comparative risk of death or other adverse outcomes such as inadequate depth or duration of surgical anaesthesia or sedation remain poorly investigated and therefore most information located is regarded as expert opinion only.

  8. Alternative Products: A range of options are presented in this formulary. These include multimodal use of medetomidine, dexmedetomidine, propofol and alfaxalone. Additional options are located in opiate monographs, such as buprenorphine and butorphanol.

  9. Alternative Protocols: A range of options are presented in this formulary. These include multimodal use of medetomidine, dexmedetomidine, propofol and alfaxalone. Additional options are located in opiate monographs, such as buprenorphine and butorphanol.

  10. Clinical Review: Medetomidine and alfaxalone are readily available in most developed countries.

Evidence

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Medetomidine | Rabbit | Literature Review

  1. Antończyk, A., Liszka, B., Skrzypczak, P., Kiełbowicz, Z., 2019. Comparison of analgesia provided by lidocaine or morphine delivered epidurally in rabbits undergoing hindlimb orthopedic surgery. Pol J Vet Sci 22, 31–35. https://doi.org/10.24425/pjvs.2018.125604

  2. Avsaroglu, H., Bull, S., Maas-Bakker, R.F., Scherpenisse, P., Van Lith, H.A., Bergwerff, A.A., Hellebrekers, L.J., Van Zutphen, L.F.M., Fink-Gremmels, J., 2008. Differences in hepatic cytochrome P450 activity correlate with the strain-specific biotransformation of medetomidine in AX/JU and IIIVO/JU inbred rabbits. J Vet Pharmacol Ther 31, 368–377. https://doi.org/10.1111/j.1365-2885.2008.00969.x

  3. Avsaroglu, H., Versluis, A., Hellebrekers, L.J., Haberham, Z.L., van Zutphen, L.F.M., van Lith, H.A., 2003. Strain differences in response to propofol, ketamine and medetomidine in rabbits. Vet Rec 152, 300. https://doi.org/10.1136/vr.152.10.300

  4. Baumgartner, C., Bollerhey, M., Ebner, J., Schuster, T., Henke, J., Erhardt, W., 2010. Effects of medetomidine-midazolam-fentanyl IV bolus injections and its reversal by specific antagonists on cardiovascular function in rabbits. Can J Vet Res 74, 286–298.

  5. Botman, J., Hontoir, F., Gustin, P., Cambier, C., Gabriel, F., Dugdale, A., Vandeweerd, J.-M., 2020. Postanaesthetic effects of ketamine-midazolam and ketamine-medetomidine on gastrointestinal transit time in rabbits anaesthetised with isoflurane. Vet Rec 186, 249. https://doi.org/10.1136/vr.105491

  6. Bradley, M.P., Doerning, C.M., Nowland, M.H., Pasloske, K., Lester, P.A., 2022. Evaluation of alfaxalone total intravenous anesthesia in rabbits (Oryctolagus cuniculus) premedicated with dexmedetomidine or dexmedetomidine and buprenorphine. Veterinary Anaesthesia and Analgesia 49, 308–312. https://doi.org/10.1016/j.vaa.2022.01.006

  7. Difilippo, S.M., Norberg, P.J., Suson, U.D., Savino, A.M., Reim, D.A., 2004. A comparison of xylazine and medetomidine in an anesthetic combination in New Zealand White Rabbits. Contemp Top Lab Anim Sci 43, 32–34.

  8. DiGeronimo, P.M., da Cunha, A.F., 2022. Local and Regional Anesthesia in Zoological Companion Animal Practice. Veterinary Clinics of North America: Exotic Animal Practice, Sedation and Anesthesia of Zoological Companion Animals 25, 321–336. https://doi.org/10.1016/j.cvex.2021.08.015

  9. Ebenhan, T., Zeevaart, J.R., Venter, J.D., Govender, T., Kruger, G.H., Jarvis, N.V., Sathekge, M.M., 2014. Preclinical evaluation of 68Ga-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid-ubiquicidin as a radioligand for PET infection imaging. J Nucl Med 55, 308–314. https://doi.org/10.2967/jnumed.113.128397

  10. Fontes-Sousa, A.P.N., Brás-Silva, C., Moura, C., Areias, J.C., Leite-Moreira, A.F., 2006. M-mode and Doppler echocardiographic reference values for male New Zealand white rabbits. Am J Vet Res 67, 1725–1729. https://doi.org/10.2460/ajvr.67.10.1725

  11. Gardhouse, S., Sanchez, A., 2022. Rabbit Sedation and Anesthesia. Veterinary Clinics of North America: Exotic Animal Practice 25, 181–210. https://doi.org/10.1016/j.cvex.2021.08.012

  12. González-Gil, A., Villa, A., Millán, P., Martínez-Fernández, L., Illera, J.C., 2015. Effects of Dexmedetomidine and Ketamine-Dexmedetomidine with and without Buprenorphine on Corticoadrenal Function in Rabbits. J Am Assoc Lab Anim Sci 54, 299–303.

  13. Grint, Nicola 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, 113–121. https://doi.org/10.1111/j.1467-2995.2007.00362.x

  14. Grint, Nicola J., Murison, P.J., 2008. A comparison of ketamine-midazolam and ketamine-medetomidine combinations for induction of anaesthesia in rabbits. Vet Anaesth Analg 35, 113–121. https://doi.org/10.1111/j.1467-2995.2007.00362.x

  15. Grint, N.J., Murison, P.J., 2007a. Peri-operative body temperatures in isoflurane-anaesthetized rabbits following ketamine-midazolam or ketamine-medetomidine. Vet Anaesth Analg 34, 181–189. https://doi.org/10.1111/j.1467-2995.2006.00319.x

  16. Grint, N.J., Murison, P.J., 2007b. Peri-operative body temperatures in isoflurane-anaesthetized rabbits following ketamine-midazolam or ketamine-medetomidine. Vet Anaesth Analg 34, 181–189. https://doi.org/10.1111/j.1467-2995.2006.00319.x

  17. Hedenqvist, P., Edner, A., Fahlman, Å., Jensen-Waern, M., 2013. Continuous intravenous anaesthesia with sufentanil and midazolam in medetomidine premedicated New Zealand White rabbits. BMC Vet Res 9, 21. https://doi.org/10.1186/1746-6148-9-21

  18. Hedenqvist, P., Edner, A., Jensen-Waern, M., 2014. Anaesthesia in medetomidine premedicated New Zealand White rabbits: a comparison between intravenous sufentanil-midazolam and isoflurane anaesthesia for orthopaedic surgery. Lab Anim 48, 155–163. https://doi.org/10.1177/0023677213516311

  19. Hedenqvist, P., Jensen-Waern, M., Fahlman, Å., Hagman, R., Edner, A., 2015. Intravenous sufentanil-midazolam versus sevoflurane anaesthesia in medetomidine pre-medicated Himalayan rabbits undergoing ovariohysterectomy. Vet Anaesth Analg 42, 377–385. https://doi.org/10.1111/vaa.12207

  20. Hedenqvist, P., Orr, H.E., Roughan, J.V., Antunes, L.M., Flecknell, P.A., 2002. Anaesthesia with ketamine/medetomidine in the rabbit: influence of route of administration and the effect of combination with butorphanol. Vet Anaesth Analg 29, 14–19. https://doi.org/10.1046/j.1467-2987.2001.00058.x

  21. Hedenqvist, P., Roughan, J., Orr, H., Antunes, L.M., 2001. Assessment of ketamine/medetomidine anaesthesia in the New Zealand White rabbit. Vet Anaesth Analg 28, 18–25. https://doi.org/10.1046/j.1467-2995.2001.00019.x

  22. Hellebrekers, L.J., de Boer, E.J., van Zuylen, M.A., Vosmeer, H., 1997. A comparison between medetomidine-ketamine and medetomidine-propofol anaesthesia in rabbits. Lab Anim 31, 58–69. https://doi.org/10.1258/002367797780600215

  23. Henke, J., Astner, S., Brill, T., Eissner, B., Busch, R., Erhardt, W., 2005a. Comparative study of three intramuscular anaesthetic combinations (medetomidine/ketamine, medetomidine/fentanyl/midazolam and xylazine/ketamine) in rabbits. Vet Anaesth Analg 32, 261–270. https://doi.org/10.1111/j.1467-2995.2005.00242.x

  24. Henke, J., Astner, S., Brill, T., Eissner, B., Busch, R., Erhardt, W., 2005b. Comparative study of three intramuscular anaesthetic combinations (medetomidine/ketamine, medetomidine/fentanyl/midazolam and xylazine/ketamine) in rabbits. Vet Anaesth Analg 32, 261–270. https://doi.org/10.1111/j.1467-2995.2005.00242.x

  25. Hess, L., Votava, M., Schreiberová, J., Málek, J., 2009. The effect of the novel alpha-2-adrenoceptor agonist naphthylmedetomidine on pulse rate, arterial blood pressure and sedation in rabbits. Vet Anaesth Analg 36, 144–150. https://doi.org/10.1111/j.1467-2995.2008.00442.x

  26. Hoffmann, J.N., Steinhagen, S., Kast, C., Scheuber, H.P., Jochum, M., Gippner-Steppert, C., Inthorn, D., Schildberg, F.W., Nolte, D., 2002. Chronic left heart catheterization for microvascular blood flow determination in the rabbit: a minimally invasive technique using specially designed port devices. J Surg Res 102, 119–125. https://doi.org/10.1006/jsre.2001.6280

  27. Jin, Y., Wilson, S., Elko, E.E., Yorio, T., 1991. Ocular hypotensive effects of medetomidine and its analogs. J Ocul Pharmacol 7, 285–296. https://doi.org/10.1089/jop.1991.7.285

  28. Kim, M.S., Jeong, S.M., Park, J.H., Nam, T.C., Seo, K.M., 2004a. Reversal of medetomidine-ketamine combination anesthesia in rabbits by atipamezole. Exp Anim 53, 423–428. https://doi.org/10.1538/expanim.53.423

  29. Kim, M.S., Jeong, S.M., Park, J.H., Nam, T.C., Seo, K.M., 2004b. Reversal of medetomidine-ketamine combination anesthesia in rabbits by atipamezole. Exp Anim 53, 423–428. https://doi.org/10.1538/expanim.53.423

  30. Kirihara, Y., Takechi, M., Kurosaki, K., Matsuo, H., Kajitani, N., Saito, Y., 2019. Effects of an anesthetic mixture of medetomidine, midazolam, and butorphanol and antagonism by atipamezole in rabbits. Exp Anim 68, 443–452. https://doi.org/10.1538/expanim.18-0183

  31. Ko, J.C., Thurmon, J.C., Tranquilli, W.J., Benson, G.J., Olson, W.A., 1992. A comparison of medetomidine-propofol and medetomidine-midazolam-propofol anesthesia in rabbits. Lab Anim Sci 42, 503–507.

  32. Lee, L.Y., Lee, D., Ryu, H., Han, J.H., Ko, J., Tyler, J.W., 2019. Capnography-guided Endotracheal Intubation as an Alternative to Existing Intubation Methods in Rabbits. J Am Assoc Lab Anim Sci 58, 240–245. https://doi.org/10.30802/AALAS-JAALAS-17-000150

  33. Mero, M., Vainionpää, S., Vasenius, J., Vihtonen, K., Rokkanen, P., 1989. Medetomidine--ketamine--diazepam anesthesia in the rabbit. Acta Vet Scand Suppl 85, 135–137.

  34. Murphy, Kathy L, Roughan, J.V., Baxter, M.G., Flecknell, P.A., 2010. Anaesthesia with a combination of ketamine and medetomidine in the rabbit: effect of premedication with buprenorphine. Veterinary Anaesthesia and Analgesia 37, 222–229. https://doi.org/10.1111/j.1467-2995.2009.00525.x

  35. Murphy, Kathy L., Roughan, J.V., Baxter, M.G., Flecknell, P.A., 2010. Anaesthesia with a combination of ketamine and medetomidine in the rabbit: effect of premedication with buprenorphine. Vet Anaesth Analg 37, 222–229. https://doi.org/10.1111/j.1467-2995.2009.00525.x

  36. Navarrete-Calvo, R., Gómez-Villamandos, R.J., Morgaz, J., Manuel Domínguez, J., Fernández-Sarmiento, A., Muñoz-Rascón, P., López Villalba, I., Del Mar Granados, M., 2014. Cardiorespiratory, anaesthetic and recovery effects of morphine combined with medetomidine and alfaxalone in rabbits. Vet Rec 174, 95. https://doi.org/10.1136/vr.101293

  37. Nevalainen, T., Pyhälä, L., Voipio, H.M., Virtanen, R., 1989. Evaluation of anaesthetic potency of medetomidine-ketamine combination in rats, guinea-pigs and rabbits. Acta Vet Scand Suppl 85, 139–143.

  38. Ogidigben, M.J., Potter, D.E., 1993. Comparative effects of alpha-2 and DA-2 agonists on intraocular pressure in pigmented and nonpigmented rabbits. J Ocul Pharmacol 9, 187–199. https://doi.org/10.1089/jop.1993.9.187

  39. Orr, H.E., Roughan, J.V., Flecknell, P.A., 2005a. Assessment of ketamine and medetomidine anaesthesia in the domestic rabbit. Vet Anaesth Analg 32, 271–279. https://doi.org/10.1111/j.1467-2995.2005.00211.x

  40. Orr, H.E., Roughan, J.V., Flecknell, P.A., 2005b. Assessment of ketamine and medetomidine anaesthesia in the domestic rabbit. Veterinary Anaesthesia and Analgesia 32, 271–279. https://doi.org/10.1111/j.1467-2995.2005.00211.x

  41. Potter, D.E., Ogidigben, M.J., 1991. Medetomidine-induced alterations of intraocular pressure and contraction of the nictitating membrane. Invest Ophthalmol Vis Sci 32, 2799–2805.

  42. Raekallio, M., Ansah, O.B., Kuusela, E., Vainio, O., 2002. Some factors influencing the level of clinical sedation induced by medetomidine in rabbits. J Vet Pharmacol Ther 25, 39–42. https://doi.org/10.1046/j.1365-2885.2002.00382.x

  43. Raillard, M., Michaut-Castrillo, J., Spreux, D., Gauthier, O., Touzot-Jourde, G., Holopherne-Doran, D., 2017. Comparison of medetomidine—morphine and medetomidine—methadone for sedation, isoflurane requirement and postoperative analgesia in dogs undergoing laparoscopy. Veterinary Anaesthesia and Analgesia 44, 17–27. https://doi.org/10.1111/vaa.12394

  44. Rockwell, K., 2019. Buprenorphine. Journal of Exotic Pet Medicine 30, 12–16. https://doi.org/10.1053/j.jepm.2018.10.002

  45. Rózańska, D., 2009. Evaluation of medetomidine-midazolam-atropine (MeMiA) anesthesia maintained with propofol infusion in New Zealand White rabbits. Pol J Vet Sci 12, 209–216.

  46. Saito, T., Nakajima, Y., Taniguchi, Y., Saito, N., Tanuma, K., Yamada, K., Ogawa, R., 1995. [Endothoracic anesthesia for artificial anus formation in rabbits]. Masui 44, 130–132.

  47. Schroeder, C.A., Smith, L.J., 2011. Respiratory Rates and Arterial Blood Gas Tensions in Healthy Rabbits Given Buprenorphine, Butorphanol, Midazolam, or Their Combinations. Journal of the American Association for Laboratory Animal Science 50, 205–211.

  48. Shimizu, S., Akiyama, T., Kawada, T., Kamiya, A., Turner, M.J., Yamamoto, H., Shishido, T., Shirai, M., Sugimachi, M., 2014. Medetomidine suppresses cardiac and gastric sympathetic nerve activities but selectively activates cardiac vagus nerve. Circ J 78, 1405–1413. https://doi.org/10.1253/circj.cj-13-1456

  49. Shimizu, S., Akiyama, T., Kawada, T., Sata, Y., Mizuno, M., Kamiya, A., Shishido, T., Inagaki, M., Shirai, M., Sano, S., Sugimachi, M., 2012. Medetomidine, an α(2)-adrenergic agonist, activates cardiac vagal nerve through modulation of baroreflex control. Circ J 76, 152–159. https://doi.org/10.1253/circj.cj-11-0574

  50. Szreder, Z., 1993. Comparison between thermoregulatory effects mediated by alpha 1- and alpha 2-adrenoceptors in normothermic and febrile rabbits. Gen Pharmacol 24, 929–941. https://doi.org/10.1016/0306-3623(93)90171-s

  51. Van der Veeken, L., Van der Merwe, J., Devroe, S., Inversetti, A., Galgano, A., Bleeser, T., Meeusen, R., Rex, S., Deprest, J., 2019. Maternal surgery during pregnancy has a transient adverse effect on the developing fetal rabbit brain. Am J Obstet Gynecol 221, 355.e1-355.e19. https://doi.org/10.1016/j.ajog.2019.07.029

  52. Vartiainen, J., MacDonald, E., Urtti, A., Rouhiainen, H., Virtanen, R., 1992. Dexmedetomidine-induced ocular hypotension in rabbits with normal or elevated intraocular pressures. Invest Ophthalmol Vis Sci 33, 2019–2023.

  53. Verbruggen, A.M., Akkerdaas, L.C., Hellebrekers, L.J., Stades, F.C., 2000. The effect of intravenous medetomidine on pupil size and intraocular pressure in normotensive dogs. Vet Q 22, 179–180. https://doi.org/10.1080/01652176.2000.9695052

  54. Weiland, L.C., Kluge, K., Kutter, A.P.N., Kronen, P.W., 2017a. Clinical evaluation of intranasal medetomidine-ketamine and medetomidine-S(+)-ketamine for induction of anaesthesia in rabbits in two centres with two different administration techniques. Vet Anaesth Analg 44, 98–105. https://doi.org/10.1111/vaa.12408

  55. Weiland, L.C., Kluge, K., Kutter, A.P.N., Kronen, P.W., 2017b. Clinical evaluation of intranasal medetomidine-ketamine and medetomidine-S(+)-ketamine for induction of anaesthesia in rabbits in two centres with two different administration techniques. Vet Anaesth Analg 44, 98–105. https://doi.org/10.1111/vaa.12408

  56. Williams, A.M., Wyatt, J.D., 2007a. Comparison of subcutaneous and intramuscular ketamine-medetomidine with and without reversal by atipamezole in Dutch belted rabbits (Oryctolagus cuniculus). J Am Assoc Lab Anim Sci 46, 16–20.

  57. Williams, A.M., Wyatt, J.D., 2007b. Comparison of subcutaneous and intramuscular ketamine-medetomidine with and without reversal by atipamezole in Dutch belted rabbits (Oryctolagus cuniculus). J Am Assoc Lab Anim Sci 46, 16–20.

Monograph Details

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