Ketamıne/xylazine anesthesia ıs safe in hemorheological point of view: a preliminary report

Abstract

Purpose: Some anesthetic drugs are known to have influence on circulation due to hemorheological effects. We aimed to investigate the possible effects of ketamin-xylazine anesthesia, which is extensively used in experimental animal laboratories on hemorheological parameters. Materials and methods: Adult, male Wistar-Albino rats were divided into two as control (pre-anesthesia) and post-anesthesia (n=17). Ketamin-HCl/Xylazine-HCl (90 mg/kg-10 mg/kg) were injected intraperitoneally. Intracardiac heparinized blood was collected either without anesthesia (control group) or after anesthesia (post-anesthesia group) following the loss of reflexes such as righting, cornea and withdrawal. Erythrocyte deformability was determined by an ektacytometer, while WBV (at shear rates of 38, 76 and 190 s–1) and PV (at 190 s–1 shear rate) at standard (40%) and otolog hematocrit (Hct) were measured via a cone-plate rotational viscometer. Results: Mean time taken for the disappearance of righting reflex was 4 ± 3.6, corneal reflex 8 ± 6.8 and for withdrawal reflex 10 ± 6.7 min. 90 mg/kg Ketamin-10 mg/kg Xylazine administration did not affect RBC deformability, WBV and PV of the rats. Conclusion: These results demonstrate that, use of Ketamin/Xylazine anesthesia may be recommended especially when dealing with hemorheological, cardiovascular and hematological parameters.

Keywords

• ketamin/xylazine
• anesthesia
• erythocyte deformability
• viscosity
• rat

Ketamin/ksilazin anestezi hemoreolojik bakış açısından güvenlidir: bir ilk rapor

Abstract

Amaç: Bazı anestezik ilaçların hemoreolojik etkileri nedeniyle dolaşımı etkilediği bilinmektedir. Deney hayvan laboratuarlarında yaygın olarak kullanılan ketamin-ksilazin anestezisinin hemoreolojik parametreler üzerine olası etkilerini araştırmayı amaçladık. Gereç ve yöntem: Yetişkin, erkek Wistar-Albino sıçanlar kontrol (anestezi öncesi) ve anestezi sonrası (n = 17) olarak ikiye ayrıldı. Ketamin-HCl / Xylazine-HCl (90 mg / kg-10 mg / kg) intraperitoneal olarak enjekte edildi. İntrakardiyak heparinize kan anestezi olmadan alındı ​​(kontrol grubu) veya anestezi sonrası (anestezi sonrası grup) düzeltme, kornea ve geri çekme gibi reflekslerin kaybını takiben. Eritrosit deformabilitesi bir ektasitometre ile belirlendi, WBV ise (38, 76 ve 190 s – 1 kesme hızlarında) ve PV (190 sn – 1 kesme hızında) standartta (% 40) ve otolog hematokrit (Hct) bir koni plakalı rotasyonel viskometre ile ölçülmüştür. Bulgular: Doğrultma refleksinin kaybolması için alınan ortalama süre 4 ± 3.6, kornea refleksi 8 ± 6.8 ve geri çekilme refleksi 10 ± 6.7 dakika idi. 90 mg / kg Ketamin-10 mg / kg Xylazine uygulaması, sıçanların RBC deforme olabilirliğini, WBV ve PV'sini etkilememiştir. Sonuç: Bu sonuçlar, Ketamin / Xylazine anestezisinin özellikle hemoreolojik, kardiyovasküler ve hematolojik parametrelerle uğraşırken önerilebileceğini göstermektedir.

Keywords

• ketamin/ksilazin
• anestezi
• eritrosit deformobilite
• viskozite
• sıçan

References

1. G.R. Lauretti, I.C. Lima, M.P. ReiS, W.A. Prado and N.L. Pereira, Oral ketamine and transdermal nitroglycerin as analgesic adjuvants to oral morphine therapy for cancer pain management. Anesthesiology. 1999;90(6):1528-33. https://doi.org/10.1097/00000542-199906000-00005
2. V.M. Azevedo, G.R. Lauretti, N.L. Pereira and M.P. Reis, Transdermal ketamine as an adjuvant for postoperative analgesia after abdominal gynecological surgery using lidocaine epidural blockade, Anesth Analg. 2000;91(6):1479-82. https://doi.org/10.1097/00000539-200012000-00034.
3. I.S. Grant, W.S Nimmo and J.A. Clements, Pharmacokinetics and analgesic effects of i.m. and oral ketamine. Br J Anaesth. 1981;53(8):805-10. https://doi.org/10.1093/bja/53.8.805.
4. R.S. Duman, The Dazzling Promise of Ketamine. Cerebrum. 2018;cer-04-18.
5. D.L. Anghelescu and J.M. Tesney. Neuropathic Pain in Pediatric Oncology: A Clinical Decision Algorithm. Paediatr Drugs. 2019;21(2):59-70. https://doi.org/10.1007/s40272-018-00324-4.
6. S. Chomchai, J. Phuditshinnapatra, P. Mekavuthikul and C. Chomchai. Effects of unconventional recreational drug use in pregnancy. Semin Fetal Neonatal Med. 2019;24(2):142-148. https://doi.org/10.1016/j.siny.2019.01.010.
7. R. Louer, R.C. McKinney, S. Abu-Sultaneh, R. Lutfi and K. Abulebda. Safety and Efficacy of a Propofol and Ketamine Based Procedural Sedation Protocol in Children with Cerebral Palsy Undergoing Botulinum Toxin A Injections. PM R. 2019;11(12):1320-1325. https://doi.org/ 10.1002/pmrj.12146
8. J.M. Malinovsky, J.Y. Lepage, A. Cozian, J.M. Mussini, M. Pinaudt and R. Souron. Is ketamine or its preservative responsible for neurotoxicity in the rabbit?. Anesthesiology. 1993;78(1):109-15. https://doi.org/10.1097/00000542-199301000-00016.

9. C. Grant and R.N. Upton. Cardiovascular and haemodynamic effects of intramuscular doses of xylazine in conscious sheep. Aust Vet J. 2001;79(1):58-60. https://doi.org/ 10.1111/j.1751-0813.2001.tb10642.x.
10. H.C. Lin, R.C. Purohit and T.A. Powe. Anesthesia in sheep with propofol or with xylazine-ketamine followed by halothane. Vet Surg. 1997;26(3):247-52. https://doi.org/ 10.1111/j.1532-950x.1997.tb01494.x.
11. J. Stuart and G.B. Nash. Red cell deformability and haematological disorders. Blood Rev. 1990;4(3):141-7. https://doi.org/ 10.1016/0268-960x(90)90041-p.
12. P. Gyawali, R.S. Richards, P.T. Bwititi and E.U. Nwose, Association of abnormal erythrocyte morphology with oxidative stress and inflammation in metabolic syndrome. Blood Cells Mol Dis. 2015;54(4):360-3. https://doi.org/ 10.1016/j.bcmd.2015.01.005.
13. F.C. Mokken, C.P. Henny and A.W. Gelb.The effects of propofol compared to high-dose fentanyl anesthesia on rheologic parameters in coronary artery surgery. J Cardiothorac Vasc Anesth. 1993;7(1):10-6. https://doi.org/ 10.1016/1053-0770(93)90111-w.
14. A. Yesilkaya, Z. Ertug, A. Yegin, M. Melikoglu and O.K. Baskurt. Deformability and oxidant stress in red blood cells under the influence of halothane and isoflurane anesthesia. Gen Pharmacol. 1998 Jul;31(1):33-6. https://doi.org/ 10.1016/s0306-3623(97)00426-6.
15. X. Nie, Z.Y. Wen, Z.Y. Yan, L. Huang, D. Sun and B. Cheng. Effects of morphine on rheological properties of rat red blood cells. Clin Hemorheol Microcirc. 2000;22(3):189-95.
16. A.I. Alet, S.S. Basso, H.V. Castellini, M. Delannoy, N. Alet, M. D'Arrigo and B.D. Riquelme. Hemorheological in vitro action of propofol on erythrocytes from healthy donors and diabetic patients. Clin Hemorheol Microcirc. 2016;25;64(2):157-165. https://doi.org/ 10.3233/CH-162054.
17. S.F. Afshar, A. Baniadam and P.S. Marashıpour. Effect of xylazine-ketamine on arterial blood pressure, arterial blood pH, blood gases, rectal temperature, heart and respiratory rates in goats. Bull Vet Inst Pulawy. 2005; 49: 481-484.
18. E. Fish, M.J. Brown and P.J. Danneman. Anesthesia and Analgesia in Laboratory Animals, 2nd ed. In: San Diego: American College of Laboratory Animal Medicine Series: Academic Press, 2008.
19. M.C. Giroux, P. Hélie, P. Burns and P. Vachon. Anesthetic and pathological changes following high doses of ketamine and xylazine in Sprague Dawley rats. Exp Anim. 2015; 64(3): 253–260. https://doi.org/ 10.1538/expanim.14-0088.
20. M.R. Hardeman and P.T. Goedhart. Methods in Hemorheology. in: Handbook of Hemorheology and Hemodynamics, O.K. Baskurt, M.R. Hardeman, M.R. Rampling and H.J. Meiselman, eds, IOS Press: Netherlands: 2007.
21. S.C. Haskins. Anaesthetic Management of Patients with Cardiopulmonary Disorders, in: World Veterinary Congress Proceedings, Tokyo:1995; 195.
22. H. Rohrbach, T. Korpivaara, U. Schatzmann and C. Spadavecchia. Comparison of the effects of the alpha-2 agonists detomidine, romifidine and xylazine on nociceptive withdrawal reflex and temporal summation in horses. Vet. Anaesth. Analg. 2009;36(4):384-95. https://doi.org/ 10.1111/j.1467-2995.2009.00466.x.
23. L.W. Hall and K.W.Clarke, Veterinary anaesthesia. 9th ed. London: Baillière Tindall. 1991; 25-29.
24. R.R. Paddleford and R.C. Harvey. Alpha 2 agonists and antagonists. Vet. Clin. North. Am. Small. Anim. Pract. 1999;29(3):737-45. https://doi.org/ 10.1016/s0195-5616(99)50058-2.
25. K. Clarke and L.A. Hall. Survey of Anaesthesia in Small Animal Practice: AVA/BSAVA Report. Vet. Anaesth. Analg. 1990;17(1):4–10. https://doi.org/10.1111/j.1467-2995.1990.tb00380.x
26. G.A. Gokhan, I.E. Gurer, M. Akyuz and R. A. Tuncer. A case of extraventricular neurocytoma of the spinal cord. Neuropathology. 2008;28(3):322-5. https://doi.org/ 10.1111/j.1440-1789.2007.00843.x.
27. R.N. Cassu, A. Melchert, J.T. Canoa and P.D. Martins. Sedative and clinical effects of the pharmacopuncture with xylazine in dogs. Acta. Cir. Bras. 2014;29(1):47-52. https://doi.org/ 10.1590/S0102-86502014000100007.
28. M.D. Sinclair. A review of the physiological effects of alpha2-agonists related to the clinical use of medetomidine in small animal practice. Can. Vet. J. 2003;44(11):885-97.
29. J.S. Gaynor and W. Muir. Handbook of Veterinary Pain Management. London: Mosby; 2000.
30. C.F. Janssen, P. Maiello, M.J. Wright, K.B. Kracinovsky and J.T. Newsome. Comparison of Atipamezole with Yohimbine for Antagonism of Xylazine in Mice Anesthetized with Ketamine and Xylazine. J. Am. Assoc. Lab. Anim. Sci. 2017; 56(2): 142–147.
31. M.C. Giroux, R. Santamaria, P. Hélie, P. Burns, F. Beaudry and P. Vachon. Physiological, pharmacokinetic and liver metabolism comparisons between 3-, 6-, 12- and 18-month-old male Sprague Dawley rats under ketamine-xylazine anesthesia. Exp. Anim. 2016;65(1):63-75. https://doi.org/ 10.1538/expanim.15-0039.
32. I.H. Akbudak, V. Kucukatay, O. Kilic-Erkek, Y. Ozdemir and M. Bor-Kucukatay. Investigation of the effects of major ozone autohemotherapy application on erythrocyte deformability and aggregation. Clin. Hemorheol. Microcirc. 2019;71(3):365-372. https://doi.org/ 10.3233/CH-180417.
33. S. Chien. Biophysical behavior of red cells in suspensions in: The Red Blood Cell, , In : Surgenor DM( Eds), New York:1975; Academic Press. 1031-1133
34. O.K. Baskurt and H.J. Meiselman, Blood rheology and hemodynamics. Semin. Thromb. Hemost. 2003;29(5):435-50. https://doi.org/ 10.1055/s-2003-44551.
35. M.S. El-Sayed. Effects of exercise and training on blood rheology. Sports. Med. 998;26(5):281-92. https://doi.org/ 10.2165/00007256-199826050-00001.
36. P.I. Bagher and S.S. Segal. Regulation of blood flow in the microcirculation: role of conducted vasodilation. Acta. Physiol(Oxf). 2011;202(3):271-84. https://doi.org/ 10.1111/j.1748-1716.2010.02244.x.
37. Y. Hellsten, M. Nyberg, L.G. Jensen, S.P. Mortensen. Vasodilator interactions in skeletal muscle blood flow regulation. J. Physiol. 2012:15;590(24):6297-305. https://doi.org/ 10.1113/jphysiol.2012.240762.
38. G.N. Herńandez, C. Dabin, del M.C. Gayol and M.L. Rasia. Haemorheological variables in a rat model of hypertriglyceridaemic obesity and diabetes. Vet. Res. Commun. 2002;26(8):625-35. https://doi.org/10.1023/a:1020920820767.
39. Y.H. Kim, H.G. Chung and S.A. Myung. In vitro effect of clinical propofol concentrations on red blood cell aggregation and deformability. Clin. Hemorheol. Microcirc. 2012;51(4):287-92. https://doi.org/ 10.3233/CH-2012-1535.
40. N. Antonova, E. Zvetkova, I. Ivanov and Y. Savov. Hemorheological changes and characteristic parameters derived from whole blood viscometry in chronic heroin addicts. Clin. Hemorheol. Microcirc. 2008;39(1-4):53-61.