The Clinical Effectiveness of Atipamezole as a Medetomidine-Tiletamine/Zolazepam Antagonist in Dogs

개에서 Medetomidine-Tiletamine/Zolazepam 마취에 대한 Atipamezole의 길항 효과

  • Kwon, Young-sam (College of Veterinary Medicine Kyungpook National University) ;
  • Joo, Eun-jung (College of Veterinary Medicine Kyungpook National University) ;
  • Jang, Kwang-ho (College of Veterinary Medicine Kyungpook National University)
  • Published : 2003.09.01

Abstract

The cardiopulmonary and antagonistic effects of atipamezole, to medetomidine (30 ug/kg, IM)-tiletamine/zolazepam (10 mg/kg, IV) were determined. Twelve healthy mongrel dogs ,(4.00$\pm$0.53 kg, mean$\pm$SD) were randomly assigned to the four experimental groups (control, A30; atipamezole 30 ug/kg, A60; atipamezole 60 ug/kg, A150; atipamezole 150 ug/kg) with 3 dogs in each group. Atropine (0.03 mg/kg, IM), medetomidine, and tiletamine/zolazepam (TZ) were injected 10 minute intervals. Atipamezole was injected intravenously 15 minutes after TZ injection. Mean arousal time (MAT) was 52.50$\pm$4.98, 43.06$\pm$2.60, 32.83$\pm$8.13, and 14.36$\pm$1.60 minutes in control, A30, A60, and Al50 groups respectively. In Al50 group, MAT was significantly reduced (P < 0.05). but mean walking time (MWT) was similar to that in control group. In recovery period, the higher doses of atimapezole, the rougher recovery including head rocking, hypersalivation, and muscle twitching. Five of twelve dogs vomited within 5 minutes after medetomidine injection. In Control group, heart rate significantly decreased in all recording stages except 15 minutes after TZ injection, 10 minutes after medetomidine injection in all groups, and 40 minutes after atipamezole injection in A30 group (P < 0.05). In Al50 group, atipamezole reversed the respiratory depression induced by medetomidine. Arterial blood pressure was significantly decreased 10minutes after medetomidine injection and 15 minutes after TZ injection in almost dogs in this study (P < 0.05). From 10 minutes after atipamezole injection to arousal time, arterial blood pressure was progressively increased in A60 and A150 group. Any value of blood gas analysis and CBC, and serum chemistry values were not significantly changed except pH of Al50 at 10 minutes after medetomidine injection. As shown in present study, atipamezole(150 ug/kg) is considered to exert a useful reversal effect in dogs anesthetized with medetomidine-tiletamine/zolazepam combination.

Medetomidine (30 ug/kg IM) - tiletamine/zolazepam (10 mg/kg IV) 합제를 사용하여 마취한 잡종견(4.00$\pm$0.53kg) 12두에서 atipamezole의 심폐계 영향과 길항효과에 대하여 평가하였다. 4개의 실험군에 각각3두씩 임의로 배당하였다 (대조군: atipamezole 처치를 하지 않은 군, A30군: atipamezole 30 um/kg, A60: atipamezole 60 ug/kg, Al50: atipamezole 150 ug/kg). 모든 실험견은 medetomidine 투여 10분 전 atropine (0.03 mg/kg, IM)으로 전처치하였으며, medetomidine 투여 10분 후 tiletamine/zolazepam (TZ)를 투여하였다. TZ투여 15분 후 atipamezole을 정맥으로 투여하였다. 실험견이 머리를 들 때까지의 평균시간은 대조군 43.06$\pm$2.60분, A30군 43.06$\pm$2.60분, A60군 32.83$\pm$8.13분 Al50군 14.36$\pm$1.60분으로 대조군과 비교할 때 A150군에서 유의성 있게 감소하였으나 (P<0.05) 완전한 보행을 보일 때까지의 평균시간에는 유의성이 나타나지 않았다. 회복기에 보이는 두부의 진전, 과도한 유연, 근육 경련과 같은 부작용은 atipamezole치 용량이 증가할수록 심하게 나타났다. 12두의 실험견중 5두가 medetomidine투여 후 5분 이내에 구토를 하였다. 대조군에서 심박수는 TZ 투여 후 15분을 제외하고, 모든 측정시간대에서 유의성 있는 감소를 나타내었으며, 전 실험군에서 medetomidine 투여 10분 후. A30군에서 atipamezole투여 후 40분에 심박수의 유의성 있는 감소가 나타났다 (P<0.05). Al50군에서는 atipamezole투여 10분 후 심계 항진 및 호흡 항진이 나타났다. 대다수 실험견에서 동맥혈압은 medetomidine과 tiletamine/zolazepam 투여 후 유의성 있게 감소하였으나 (P< 0.05) A60군과 Al50군에서는 atipamezole투여 후 점차적으로 회복되었다. 혈액가스검사와 총 혈구계산치는 유의성 있는 변화가 관찰되지 않았다 본 실험의 결과로 atipamezole 150 mg/kg은 MTZ 병용 마취견 각성에 뛰어난 효과를 나타낸다고 사료된다.

Keywords

References

  1. Vet Anaesth Analge v.27 Evaluation of the analgesic properties of acepromazine maleate, oxymorphone, medeto-midine and a combination of acepromazine-oxymorphone Barnhart,M.D.;Hubbell,J.A. https://doi.org/10.1046/j.1467-2995.2000.00024.x
  2. Vet Med. v.84 The effects of tolazoline, doxapram, and Ro 15-1788 on the depressant action of Telazol Bednarski,R.M.;Muir,W.W.;Tracy,C.H.
  3. Acta Vet Scand v.85 Cardiovascular and pulmonary effects of a new sedative/analgesic (medetomidine) as a preanesthetic drug in the dog Bergstrom,K.
  4. Am. J. Vet. Res. v.43 Cardiodynamics in the rhesus macaque during dissociative anesthesia Booker,J.L.;Heickson,H.H.;Fitzpatrick,E.L.
  5. Lab Anim Sci. v.41 Anesthetic and nephrotoxic effects of Telazol in New Zealand white rabbits Brammer,D.W.;Doerning,B.J.;Chrisp,C.E.;Rush,H.G.
  6. J. Wildlife Dissease v.33 Reversible immobilization of free-ranging polar bears with medetomidine-zolazepam-tiletamine and atipamezole Cattet,M.R.L.;Caulkett,N.A.;Polischuk,S.C.;Ramsay,M.A. https://doi.org/10.7589/0090-3558-33.3.611
  7. Can Vet J. v.41 Anesthesia of wood bison with medetomidine-zolazepam/tiletamine and xylazine-zolazepam/tiletamine combinations Caulkett,N.A.;Cattet,M.R.L.;Cantwell,S.;Cool,N.;Olsen,W.
  8. J. Wildlife Disease v.33 Physiological effects of medetomidine-zolazepamtiletamine immobilization in black bears Caulkett,N.A.;Catter,R.L. https://doi.org/10.7589/0090-3558-33.3.618
  9. J. Vet Pharmacol Therap v.20 The comparative hypoxaemic effect of four 2 adrenoceptor agonists(xylazine, romifidine, detomidine and medetomidine) in sheep Celly,C.S.;McDonell,W.N.;Young,S.S.;Black,W.D. https://doi.org/10.1046/j.1365-2885.1997.00097.x
  10. Korean. J. Vet Res v.38 Comparison of tiletamine-zolazepam, tiletamine-zolazepam-xylazine and ketamine-xylazine anesthesia in dogs Chang,H.S.;Jang,I.H.
  11. Vet Rec. v.140 Effects of tiletamine/zolazepam premedication on propofol aneasthesia in dogs Cullen,L.K.;Reynoldson,J.A. https://doi.org/10.1136/vr.140.14.363
  12. Lab. Anim. Sci. v.42 Nephro-toxicity of tiletamine in New Zealand white rabbits Doerning,N.J.;Brammer,D.W.;Chrisp,C.E.(et al.)
  13. Vet Med v.84 Testing low doses of intravenous Telazol in canine practice Donaldson,L.L.;McGrath,C.J.;Tracy,C.H.
  14. Am J. Vet Res. v.54 Reduction of isoflurane anesthetic requirement by medetomidine and its restoration by atipamezole in dogs Ewing,K.K.;Mobammed,H.O.;Scarlett,J.M.;Short,C.E.
  15. Vet Med v.83 Searching for a safe, effective antagonist to Telazol overdose Hatch,R.C.;Clark,J.D.;Jernigan,A.D.;Tracy,C.H.
  16. Vet Surg v.18 Cardiorespiratory effects of the intravenous administration of tiletamine-zolazepam to dogs. Hellyer,P.;Muir,W.W.;Hubbell,J.A.E.;Sally,J. https://doi.org/10.1111/j.1532-950X.1989.tb01063.x
  17. Am J. Vet Res v.50 Xylazine and tiletamine-zolazepam anesthesia in horses Hubbell,J.A.E.;Bednarski,R.M.;Muir,W.W.
  18. Vet Clin No Am Small Anim Pract v.22 Other protentially useful new injectable anesthetic agents Ilkiw,J.E. https://doi.org/10.1016/S0195-5616(92)50611-8
  19. J. Vet. Clin. v.19 Effects of yohimbine and atipamezole in dogs anesthetized with xylazine-ketamine combination on EEG Jang,H.S.;Jang,K.H.;Lee,M.G.;Jang,I.H.
  20. J. Vet Pharmacol Therap v.23 Clinical effects and pharmacokinetics of medeto-midine and its enantiomers in dogs Kuusela,E.;Raekallio,M.;Anttila,M.;Falck,I.;Molsa,S.;Vainio,O. https://doi.org/10.1046/j.1365-2885.2000.00245.x
  21. Am J. Vet Res v.52 Cardiopulmonary effects of a tiletamine-zolazepam combination in sheep Lagutchik,M.S.;Januszkiewicz,A.J.;Dodd,K.T.;Martin,D.G.
  22. Veterinary anesthesia(3rd ed.) Dissociative anesthetics Lin,H.C.
  23. Am J. Vet Res v.35 Effects of CI 744 on skeletal muscle activity in monkeys(Macaca mulatta) McNamara,J.A.Jr.;Sly,D.L.;Cohen,B.J.
  24. Vet Clin North Am Small Anim Pract v.29 Etomidate and telazol Pablo,L.S.;Bailey,J.E. https://doi.org/10.1016/S0195-5616(99)50060-0
  25. Veterinary drug handbook(3rd ed.) Plumb,D.C.
  26. J. Vet Pharmacol Therap v.21 Pharmacokinetics of medetomidine and atipamezole in dairy calves: an agonist-antagonist interaction Raneim,B.;Soli,N.E.;Ryeng,K.A.;Arnemo,J.M.;Horsberg,T.E.
  27. Vet Med v.84 Talking about Telazol, Roundable Short,C.E.
  28. Vet Rec. v.129 Effects of anticholinergic treatment on the cardiac and respiratory system in dogs sedated with medetomidine Short,C.E. https://doi.org/10.1136/vr.129.14.310
  29. Am J. Vet Res v.36 Absence of sensitization to epinephrine-induced cardiac arrhythmia and fibrillation in dogs and cats anesthetized with CI 744 Smith,R.D.;Pettway,C.E.
  30. Veterinary anesthesia(3rd ed.) Preaneshetics and anesthetic adjuncts Thurmon,J.C.;Tranquilli,W.J.;Benson,G.J.
  31. Vet Med v.83 Comparing the effects of intravenous and intramuscular administration of Telazol Tracy,C.H.;Short,C.E.;Clark,B.C.
  32. J. Vet Pharma Ther v.13 Reversal of medetomidine sedation by atipamezole in dogs Vainio,O.;Vaha-Vahe,T. https://doi.org/10.1111/j.1365-2885.1990.tb00742.x
  33. Vet Rec. v.127 Reversal of medetomidine-induced cardiovascular and respiratory changes with atipamezole in dogs Vainio,O.
  34. Vet Rec. v.128 An evaluation of medetomidine/ketamine and other drug combinations for anaesthesia in cats Verstegen,J.;Fargetton,X.;Donnay,I.;Ectors,F. https://doi.org/10.1136/vr.128.2.32
  35. Vet Rec. v.128 Antagonistic activities of atipamezole, 4-aminopyridine and yohimbine against medetomidine/ketamine-induced anaesthesia in cats Verstegen,J.;Fargetton,X.;Zanker,S.;Donnay,I.;Ectors,F. https://doi.org/10.1136/vr.128.3.57
  36. Arch Int Pharmacodyn Ther v.20 Highly selective and specific antagonism of central and peripheral alpha 2-adrenoceptors by atipamezole Virtanen,R.;Savola,J.M.;Saano,V.
  37. Acta Veterinaria Scandinavica v.85 Pharmacological profiles of medetomidine and its antagonist, atipamezole Virtanen,R.
  38. J. Vet Pharmacol Therap v.13 The clinical effectiveness of atipamezole as a medetomidine antagonist in the dog Vaha-vahe,T. https://doi.org/10.1111/j.1365-2885.1990.tb00769.x