Effects of Medetomidine and Tramadol Administration on the Minimum Alveolar Concentration of Isoflurane in Dogs

Medetomidine과 Tramadol이 개에서 Isoflurane의 최소 폐포 농도에 미치는 영향

  • Kim, Kyung-Mi (College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University) ;
  • Cheong, Jong-Tae (College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University) ;
  • Park, Hyun-Jeong (College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University)
  • 김경미 (제주대학교 수의과대학.수의과학연구소) ;
  • 정종태 (제주대학교 수의과대학.수의과학연구소) ;
  • 박현정 (제주대학교 수의과대학.수의과학연구소)
  • Accepted : 2010.11.18
  • Published : 2010.12.31

Abstract

This study was to evaluate the effects of tramadol and medetomidine administration on minimum alveolar concentration (MAC) of isoflurane in dogs. MAC of isoflurane was determined in four occasions; 1 ml saline (Control), $2{\mu}g$/kg medetomidine (M2), 4 mg/kg tramadol (T4), $2{\mu}g$/kg medetomidine-4 mg/kg tramadol combination (M2T4). Heart rate, blood pressure, respiratory rate, end-tidal carbon dioxide concentration, saturation of hemoglobin with oxygen and body temperature were recorded. After administration of M2 ($0.81{\times}0.18%$), T4 ($0.81{\times}0.14%$) and M2T4 ($0.62{\times}0.12%$), less isoflurane was required than the control value ($1.13{\times}0.19%$). Significantly lower heart rate than the control value was detected after treatment of M2, T4, and M2T4. When only M2T4 was administered, blood pressure was significantly higher than the control value. In conclusion, administrations of tramadol, medetomidine and medetomidine-tramadol combination decreased the MAC of isoflurane in dogs. Especially, medetomidine-tramadol combinations could be useful as a premedication because of the anesthetic sparing effect and moderate changes in cardiovascular system.

본 연구는 tramadol과 medetomidine이 개에서 isoflurane의 최소폐포농도에 미치는 영향에 대해 알아보고자 하였다. Isoflurane의 최소폐포농도는 1 ml의 생리식염수(control), $2{\mu}g$/kg의 medetomidine (M2), 4 mg/kg의 tramadol (T4), $2{\mu}g$/kg medetomidine과 4 mg/kg tramadol (M2T4)의 투여 네 가지 경우에 따라 측정되었다. 실험 중 심박수, 혈압, 호흡수, 호기말 이산화탄소분압, 혈중산소포화도, 체온을 측정하였다. M2, T4, M2T4 투여 후 isoflurane의 최소 폐포농도는 각각 $0.81{\pm}0.17%$, $0.81{\pm}0.14%$, $0.62{\pm}0.13%$로 대조군$1.13{\pm}0.19%$ 에 비해서 낮았다. 심박수는 M2, T4, M2T4 투여 시 낮았고 혈압은 M2T4투여 시에만 유의적으로 높았다. Tramadol 과 medetomidine의 투여 및 두 약물의 혼합투여는 isoflurane의 최소폐포농도를 유의적으로 낮추었다. 특히 tramadol과 medetomidine의 혼합투여는 마취제의 절감효과와 심혈관계에 있어 변화가 적기 때문에 전마취제로서 유용하게 사용될 수 있을 것이다.

Keywords

References

  1. Bertelson MF, Villadsen L. A comparison of the efficacy and cardiorespiratory effects of four medetomidine-based anaesthetic protocols in the red fox (Vulpes vulpes). Vet Anaesth Analge 2009; 36: 328-333. https://doi.org/10.1111/j.1467-2995.2009.00464.x
  2. Coetzee JF, Loggerenberg HV. Tramadol or morphine administered during operation: a study of immediate postoperative effects after abdominal hysterectomy. Br J Anaesth 1998; 81: 737-741. https://doi.org/10.1093/bja/81.5.737
  3. Coetzee JF, Maritz JS, Torr JC. Effect of tramadol on depth of anaesthesia. Br J Anaesth 1996; 76: 415-418. https://doi.org/10.1093/bja/76.3.415
  4. Cullen LK. Medetomidine sedation in dogs and cats: A review of its pharmacology, antagonism and dose. Br Vet J 1996; 152: 519-535. https://doi.org/10.1016/S0007-1935(96)80005-4
  5. Doherty TJ, Will WA, Rohrbach BW, Geiser DR. Effect of morphine and flunixin meglumine on isoflurane minimum alveolar concentration in goats. Vet Anaesth Analge 2004; 31: 97-101. https://doi.org/10.1111/j.1467-2987.2004.00156.x
  6. Duthie DJR. Remifentanil and tramadol. Br J Anaesth 1998; 81: 51-57. https://doi.org/10.1093/bja/81.1.51
  7. Eger EI, Saidman LJ, Brandstater B. Minimum alveolar anesthetic concentration: A standard of anesthetic potency. Anesthesiology 1965; 26: 756-763. https://doi.org/10.1097/00000542-196511000-00010
  8. Egger KA, Power I. Tramadol. Br J Anaesth 1995; 74: 247-249. https://doi.org/10.1093/bja/74.3.247
  9. Ewing KK, Mohammed HO, Scarlett JM, Short CE. Reduction of isoflurane anesthetic requirement by medetomidine and its restoration by atipamezole in dogs. Am J Vet Res 1993; 54: 294-299.
  10. Grint NJ, Burford J, Dugdale AHA. Investigating medetomidine-buprenorphine as preanaesthetic medication in cats. J Small Anim Pract 2009; 50: 73-81. https://doi.org/10.1111/j.1748-5827.2008.00688.x
  11. Ko JCH, Abbo LA, Weil AB, Johnson BM, Inoue T, Payton ME. Effect of orally administered tramadol alone or with an intravenously administered opioid on minimum alveolar concentration of sevoflurane in cats. J Am Vet Med Assoc 2008; 232: 1834-1840. https://doi.org/10.2460/javma.232.12.1834
  12. Ko JCH, Bailey JE, Pablo LS, Heaton-Jones TG. Comparison of sedative and cardiorespiratory effects of medetomidine and medetomidine-butorphanol combination in dogs. Am J Vet Res 1996; 57: 535-540.
  13. Ko JCH, Lange DN, Mandsager RE, Payton ME, Bowen C, Kamata A, Kuo WC. Effects of butorphanol and carprofen on the minimal alveolar concentration of isoflurane in dogs. J Am Vet Med Assoc 2000; 217: 1025-1028. https://doi.org/10.2460/javma.2000.217.1025
  14. Ko JCH, Nicklin CF, Melendaz M, Hamilton P, Kuonen CD. Effects of a microdose of medetomidine on diazepam-ketamine induced anesthesia in dogs. J Am Vet Med Assoc 1998; 213: 215-219.
  15. Ko JCH, Payton ME, White AG, Galloway DS, Inoue T. Effects of intravenous diazepam or microdose medetomidine on propofol-induced sedation in dogs. J Am Anim Hosp Assoc 2006; 42: 18-27.
  16. Ko JCH, Weil AB, Inoue T. Effects of carprofen and morphine on the minimum alveolar concentration of isoflurane in dogs. J Am Anim Hosp Assoc 2009; 45: 19-23.
  17. Kukanich K, Papich Mg. Pharmacokinetics of tramadol and the metabolite O-desmethyltramadol in dogs. J Vet Pharmacol Therap 2004; 27: 239-246. https://doi.org/10.1111/j.1365-2885.2004.00578.x
  18. Machado CEG, Doris HD, Maxie MG. Effects of oxymorphine and hydromorphone on the minimum alveolar concentration of isoflurane in dogs. Vet Anaesth Analge 2006; 33: 70-77. https://doi.org/10.1111/j.1467-2995.2005.00215.x
  19. Mastrocinque S, Fantoni DT. A comparison of preoperative tramadol and morphine for the control of early postoperative pain in canine ovariohysterectomy. Vet Anaesth Analge 2003; 30: 220-228. https://doi.org/10.1046/j.1467-2995.2003.00090.x
  20. Maze M, Vickery RG, Merlone SC, Gaba DM. Anesthetic and hemodynamic effects of the alpha2-adrenergic agonist, axepexole, in isoflurane-anesthetized dogs. Anesthesiology 1988; 68: 689-694. https://doi.org/10.1097/00000542-198805000-00006
  21. McMillan CJ, Livingston A, Clark CR, Dowling PM, Taylor SM, Duke T, Terlinden R. Pharmacokinetics of intravenous tramadol in dogs. Can J Vet Res 2008; 72: 325-331.
  22. Muir WW, Ford JL, Karpa GE, Harrison EE, Gadawski JE. Effects of intramuscular administration of low doses of medetomidine and medetomidine-butorphanol in middle-aged and old dogs. J Am Vet Med Assoc 1999; 215: 1116-1120.
  23. Muller H, Stoyanov M, Brahler A, Hempelmann G. Hemodynamic and respiratory effects of tramadol during nitrous oxide-oxygen-artificial respiration and in the postoperative period. Anaesthesist 1982; 31: 604-610.
  24. Pypendop BH, Verstegen JP. Hemodynamic effects of medetomidine in the dog: A dose titration study. Vet Surg 1998; 27: 612-622. https://doi.org/10.1111/j.1532-950X.1998.tb00539.x
  25. Quasha AL, Eger EI, Tinker JH. Determination and applications of MAC. Anesthesiology 1980; 53: 315-334. https://doi.org/10.1097/00000542-198010000-00008
  26. Santos M, Kunkar V, Garcia-Iturralde P, Tendillo FJ. Meloxicam, a specific COX-2 inhibitor, does not enhance the isoflurane minimum alveolar concentration reduction produced by morphine in the rat. Anesth Anag. 2004; 98: 359-363.
  27. Salmenpera MT, Szlam F, Hug CC. Anesthetic and hemodynamic interaction of dexmedetomidine and fentanyl in dogs. Anesthesiology 1994; 80: 837-846. https://doi.org/10.1097/00000542-199404000-00017
  28. Seddighi MR, Egger CM, Rohrbach BW, Cox SK, Doherty TJ. Effects of tramadol on the minimum alveolar concentration of sevoflurane in dogs. Vet Anaesth Analge 2009; 36: 334-340. https://doi.org/10.1111/j.1467-2995.2009.00468.x
  29. Sinclair MD. A review of the physiological effects of $\alpha_2$- agonists related to the clinical use of medetomidine in small animal practice. Can Vet J 2003; 44: 885-897.
  30. Steffey EP, Howland D Jr. Isoflurane potency in the dog and cat. Am J Vet Res 1977; 38: 1833-1836.
  31. Valverde A, Morey TE, Hernandez J, Davies W. Validation of several types of noxious stimuli for use in determining the minimum alveolar concentration for inhalation anesthetics in dogs and rabbits. Am J Vet Res. 2003; 64: 957-962. https://doi.org/10.2460/ajvr.2003.64.957
  32. Wilson D, Pettifer GR, Hosgood G. Effect of transdermally administered fentanyl on minimum alveolar concentration of isoflurane in normothermic and hypothermic dogs. J Am Vet Med Assoc 2006; 228: 1042-1046. https://doi.org/10.2460/javma.228.7.1042
  33. Wilson J, Doherty TJ, Egger CM, Filder A, Cox S, Rohrbach B. Effects of intravenous lidocaine, ketamine, and the combination on the minimum alveolar concentration of sevoflurane in dogs. Vet Anaesth Analge 2008; 35: 289-296. https://doi.org/10.1111/j.1467-2995.2007.00389.x
  34. Wolff MH, Leather HA, Wouters PF. Effects of tramadol on minimum alveolar concentration (MAC) of isoflurane in rats. Br J Anaesth 1999; 83: 780-783. https://doi.org/10.1093/bja/83.5.780
  35. WU WN, Mckown LA, Gauthier AD, Jones WJ, Raffa RB. Metabolism of the analgesic drug, tramadol hydrochloride, in rat and dog. Xenobiotica 2001; 31: 423-441. https://doi.org/10.1080/00498250110057378
  36. Yamashita K, Okano Y, Yamashita M, Umar MA, Kushiro T, Muir WW. Effects of carprofen and meloxicam with or without butorphanol on the minimum alveolar concentration of sevoflurane in dogs. J Vet Med Sci 2008; 70: 29-35. https://doi.org/10.1292/jvms.70.29