Original Scientific Article
The safety profile of the anesthetic effect of alfaxalone and its interaction with xylazine and ketamine in chick’s model (Gallus gallus domesticus)
Correspondence: Ahmed Salah Naser, email@example.com
Received: 18 February 2021
Received in revised form: 07 August 2021
Accepted: 12 August 2021
Available Online First: 06 September 2021
Published on: 15 October 2021
The objective of our research was to estimate the therapeutic index and assess the interaction of alfaxalone (IP) with ketamine or xylazine (IM) in chicks by using isobolographic analysis. The up-and-down technique was involved to calculate the median effective anesthetic dosages (ED50) of alfaxalone, xylazine, and ketamine given separately or at the same time in young chicks. Then the up-and-down technique was involved to estimate the median lethal dosage (LD50) of alfaxalone (IP) to determine the safety profile. The ED50 of all anesthetics was evaluated isobolographically to assess the type of interaction between alfaxalone and xylazine or alfaxalone and ketamine. The alfaxalone ED50 was 32.88 mg/kg (IP), whereas the LD50 was 102.40 mg/kg (IP). The ED50 values for alfaxalone, ketamine, and xylazine were 32.88, 12.24, and 2.45 mg/kg, respectively. The ED50 values of alfaxalone with ketamine or xylazine (25:25 ED50 values) were: 7.39+2.35, and 8.61+0.63 mg/kg, respectively. ED50 values were decreased when the combinations of alfaxalone/ketamine or alfaxalone/xylazine were administered by 22-21% and 26-25%, respectively. The anesthesia of chicks with alfaxalone is safe, produces a surgical stage of anesthesia, and can be used for minor surgical procedures. The use of alfaxalone with ketamine or xylazine has been shown to have a synergistic effect and these findings may be of clinical relevance in poultry or may be extended to mammals following further clinical trials.
Keywords: alfaxalone, isobolographic analysis, therapeutic index, chicks, anesthesia
- Lierz, M., Korbel, R. (2012). Anesthesia and analgesia in birds. J Exot Pet Med. 21(1): 44-58. https://doi.org/10.1053/j.jepm.2011.11.008
- Lichtenberger, M. (2007). Shock and cardiopulmonary-cerebral resuscitation in small mammals and birds. Vet Clin North Am Exot Anim Pract. 10(2): 275-291. https://doi.org/10.1016/j.cvex.2007.02.001
- Zehnder, A.M., Hawkins, M.G., Pascoe, P.J. (2014). Avian anatomy and physiology. In: G. West, D. Heard, N. Caulket (Eds.), Zoo animal and wild life immobilisation and anesthesia (pp. 389-398). New York: Wiley-Blackwell https://doi.org/10.1002/9781118792919.ch23
- Palmer, D. (2019). Veterinary Therapeutics. In:M. Tighe, M. Brown (Eds.), Mosby’s comprehensivereview for veterinary technicians. Part 3 (p. 419).Amsterdam: Elsevier
- Duke-Novakovski, T. (2015). Ten intravenous anesthetic induction drugs. Quest Answers Small Anim Anesth. 73. Philadelphia: Elsevier Saunders https://doi.org/10.1002/9781118912997.ch10
- Child, K.J., Currie, J.P., Davis, B., Dodds, M.G., Pearce, D.R., Twissell, D.J. (1971). The pharmacological properties in animals of CT1341-a new steroid anaesthetic agent. BJA Br J Anaesth. 43(1): 2-13. https://doi.org/10.1093/bja/43.1.2-a
- Brewster, M.E., Estes, K.S., Bodor, N. (1990). An intravenous toxicity study of 2-hydroxypropyl- β-cyclodextrin, a useful drug solubilizer, in rats and monkeys. Int J Pharm. 59(3): 231-243. https://doi.org/10.1016/0378-5173(90)90114-J
- Green, C.J., Knight, J., Precious, S., Simpkin, S. (1981). Ketamine alone and combined with diazepam or xylazine in laboratory animals: a 10 year experience. Lab Anim. 15(2): 163-170. https://doi.org/10.1258/002367781780959107
- Elowni, E.E., Sanhouri, A.A., Dafalla, R.A., Makky, E.A.M., Aldood, M.E., Yassin, M.A. (2019). Evaluation of ketamine as a general anesthetic for domestic fowl chicks. Sudan Journal of Science and Technology 20(2): 22–26. https://doi.org/10.4236/oalib.1106463
- Makky, E.A.M., Aldood, M.E., Dafalla, R.A.H. (2017). Administration of ketamine hydrochloride as general anesthesia in domestic fowl. Sudan University of Science and Technology. http://repository.sustech.edu/handle/123456789/23914
- Samour, J.H., Jones, D.M., Knight, J.A., Howlett, J.C. (1984). Comparative studies of the use of some injectable anaesthetic agents in birds. Vet Rec. 115(1): 6-11. https://doi.org/10.1136/vr.115.1.6
- Gessner, P.K. (1995). Isobolographic analysis of interactions: an update on applications and utility. Toxicology 105(2-3): 161-179. https://doi.org/10.1016/0300-483X(95)03210-7
- Dixon, W.J. (1980). Efficient analysis of experimental observations. Annu Rev Pharmacol Toxicol. 20(1): 441-462. https://doi.org/10.1146/annurev.pa.20.040180.002301
- Naser, A.S., Amin, Y.M. (2019). Analgesic effect of silymarin in chicks. Iraqi J Vet Sci. 33(2): 273-276. https://doi.org/10.33899/ijvs.2019.162906
- Naser, A.S., Albadrany, Y., Shaaban, K.A. (2020). Isobolographic analysis of analgesic interactions of silymarin with ketamine in mice. J Hell Vet Med Soc. 71(2): 2171-2178. https://doi.org/10.12681/jhvms.23653
- Alatrushi, A.N., Naser, A.S. (2021). Evaluation of the anesthetic action of alfaxalone in chicks and compared with alfaxalone/ketamine or alfaxalone/ xylazine. Egypt J Vet Sci. 52(2): 221-228. https://doi.org/10.21608/ejvs.2021.60507.1215
- Gupta, P.K. (2016). Fundamentals of toxicology:essential concepts and applications. (pp. 22–41).Academic Press. Amsterdam: Elsevier
- Naser, A.S., Mohammad, F.K. (2014). Central depressant effects and toxicity of propofol in chicks. Toxicol Reports. 1, 562-568. https://doi.org/10.1016/j.toxrep.2014.08.003
- Tallarida, R.J. (1992). Statistical analysis of drug combinations for synergism. Pain 49(1): 93-97. https://doi.org/10.1016/0304-3959(92)90193-F
- Puig, M.M., Warner, W., Pol, O. (2000). Intestinal inflammation and morphine tolerance alter the interaction between morphine and clonidine on gastrointestinal transit in mice. J Am Soc Anesthesiol. 93(1): 219-230. https://doi.org/10.1097/00000542-200007000-00033
- Naser, A.S., Mohammad, F.K. (2014). Isobolographic analysis of sedative and hypnotic interactions of propofol with ketamine and xylazine in chicks. Hum Vet Med. 6(2): 56-60.
- Punch, P.I.P. (2001). A retrospective study of the success of medical and surgical treatment of wild Australian raptors. Aust Vet J. 79(11): 747-752. https://doi.org/10.1111/j.1751-0813.2001.tb10890.x
- Smith, S., Rodriguez-Barbon, A. (2008). Waterfowl:medicine and surgery. BSAVA Man Farm PetsGloucester, UK Br Small Anim Vet Assoc. 250-273.
- Curtis, R., Jemmett, J.E., Hendy, P.G. (1977). Saffan (CT 1341) as an anaesthetic agent for the budgerigar Melopsittacus undulatus. J Small Anim Pract. 18(7): 465-472. https://doi.org/10.1111/j.1748-5827.1977.tb05914.x
- Erickson, R.L., Blevins, C.E., De Souza Dyer, C., Marx, J.O. (2019). Alfaxalone-xylazine anesthesia in laboratory mice (Mus musculus). J Am Assoc Lab Anim Sci. 58(1): 30-39. https://doi.org/10.30802/AALAS-JAALAS-18-000010
- Siriarchavatana, P., Ayers, J.D., Kendall, L.V.(2016). Anesthetic activity of alfaxalone comparedwith ketamine in mice. J Am Assoc Lab Anim Sci.55(4): 426-430.
- Heng, K., Marx, J.O., Jampachairsi, K., Huss, M.K., Pacharinsak, C. (2020). Continuous rate infusion of alfaxalone during ketamine-xylazine anesthesia in rats. J Am Assoc Lab Anim Sci. 59(2): 170-175. https://doi.org/10.30802/AALAS-JAALAS-19-000122
- Keates, H.L., van Eps, A.W., Pearson, M.R.B. (2012). Alfaxalone compared with ketamine for induction of anaesthesia in horses following xylazine and guaifenesin. Vet Anaesth Analg. 39(6): 591-598. https://doi.org/10.1111/j.1467-2995.2012.00756.x
- Muñoz, K.A., Robertson, S.A., Wilson, D.V. (2017). Alfaxalone alone or combined with midazolam or ketamine in dogs: intubation dose and select physiologic effects. Vet Anaesth Analg. 44(4): 766-774. https://doi.org/10.1016/j.vaa.2017.01.004
- Khenissi, L., Nikolayenkova-Topie, O., Broussaud, S., Touzot-Jourde, G. (2017). Comparison of intramuscular alfaxalone and ketamine combined with dexmedetomidine and butorphanol for castration in cats. J Feline Med Surg. 19(8): 791-797. https://doi.org/10.1177/1098612X16657951
- Tanaka, K., An, B.K., Banno, C., Xia, Z.S., Ohtani, S. (1997). Effects of dietary fat sources on lipid metabolism in growing chicks (Gallus domesticus). Comp Biochem Physiol Part B Biochem Mol Biol. 116(1): 119-125. https://doi.org/10.1016/S0305-0491(96)00182-4
© 2021 Alatrushi A.N. This is an open-access article published under the terms of the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Conflict of Interest Statement
The authors have declared that no competing interests exist.
Macedonian Veterinary Review. Volume 44, Issue 2, Pages 203-209, e-ISSN 1857-7415, p-ISSN 1409-7621, DOI: 10.2478/macvetrev-2021-0025, 2021