ORIGINAL_ARTICLE 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. https://macvetrev.mk/Files/Article/2021/10.2478/macvetrev-2021-0025/macvetrev-2021-0025.pdf 2020-03-15T09:00:00 203 209 10.2478/macvetrev-2021-0025 alfaxalone isobolographic analysis therapeutic index chicks anesthesia Amjed Najem Alatrushi false 1 Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Mosul, Mosul, Iraq AUTHOR Ahmed Salah Naser ahmadphd0@gmail.com false 2 Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Mosul, Mosul, Iraq LEAD_AUTHOR Lierz, M., Korbel, R. (2012). Anesthesia and analgesia in birds. J Exot Pet Med. 21(1): 44-58. 1 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. 2 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 3 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 4 Duke-Novakovski, T. (2015). Ten intravenous anesthetic induction drugs. Quest Answers Small Anim Anesth. 73. Philadelphia: Elsevier Saunders 5 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. 6 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. 7 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. 8 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. 9 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 10 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. 11 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. 12 10.1016/0300-483X(95)03210-7 Dixon, W.J. (1980). Efficient analysis of experimental observations. Annu Rev Pharmacol Toxicol. 20(1): 441-462. 13 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. 14 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. 15 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. 16 10.21608/ejvs.2021.60507.1215 Gupta, P.K. (2016). Fundamentals of toxicology:essential concepts and applications. (pp. 22–41).Academic Press. Amsterdam: Elsevier 17 Naser, A.S., Mohammad, F.K. (2014). Central depressant effects and toxicity of propofol in chicks. Toxicol Reports. 1, 562-568. 18 10.1016/j.toxrep.2014.08.003 Tallarida, R.J. (1992). Statistical analysis of drug combinations for synergism. Pain 49(1): 93-97. 19 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. 20 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. 21 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. 22 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. 23 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. 24 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. 25 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. 26 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. 27 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. 28 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. 29 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. 30 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. 31 10.1016/S0305-0491(96)00182-4