Antagonistic Effects of Flumazenil on Tiletamine-Zolazepam Induced Anesthesia in Dogs

Tiletamine-Zolazepam에 의한 개의 마취에서 Flumazenil의 길항효과

  • Won, Heung-Seok (College of Veterinary Medicine, Research Center for Transgenic Cloned Pigs, Chungnam National University) ;
  • Lee, Jae-Yeon (College of Veterinary Medicine, Research Center for Transgenic Cloned Pigs, Chungnam National University) ;
  • Jeong, Seong-Mok (College of Veterinary Medicine, Research Center for Transgenic Cloned Pigs, Chungnam National University) ;
  • Lee, Soo-Jin (College of Veterinary Medicine, Research Center for Transgenic Cloned Pigs, Chungnam National University) ;
  • Park, Chang-Sik (Division of Animal Science & Resources, Research Center for Transgenic Cloned Pigs, Chungnam National University) ;
  • Kim, Myung-Cheol (College of Veterinary Medicine, Research Center for Transgenic Cloned Pigs, Chungnam National University)
  • 원흥석 (충남대학교 수의과대학) ;
  • 이재연 (충남대학교 수의과대학) ;
  • 정성목 (충남대학교 수의과대학) ;
  • 이수진 (충남대학교 수의과대학) ;
  • 박창식 (충남대학교 동물자원학부) ;
  • 김명철 (충남대학교 수의과대학)
  • Accepted : 2010.08.18
  • Published : 2010.08.30

Abstract

The purpose of this study was to determine the antagonistic effects of flumazenil on anesthesia induced with tiletamine/zolazepam in dogs. The anesthetic effects (sedation, analgesic, muscle relaxation, posture and auditory response score), vital signs (heart rate, respiratory rate and rectal temperature) and blood biochemistry (glucose (GLU), total protein (TP), alanine aminotransferase (ALT), aspartate aminotransferase (AST)) were examined as indicators of the antagonistic effects. A total of 6 clinically healthy mongrel dogs were used in this study. The dogs in TZ group received administration of tiletamine/zolazepam 10 mg/kg IV. The dogs in TZF group received administration dose of TZ 10 mg/ kg IV followed by the administration of flumazenil 0.1 mg/kg 20 minutes after administering a TZ 10 mg/kg dose. There were significant differences in the recovery of anesthesia between the groups. The GLU level in the TZF group after the administration of flumazenil was significantly higher than that of the TZ group. There was a larger change in the HR in the TZF group than in the TZ group until 30 minutes after flumazenil administration. The sternal recumbency, standing and walking times of the TZF group were faster than those of the TZ group. In conclusion, flumazenil showed antagonistic effect against tiletamine/zolazepam in dogs. When recovering from anesthesia, flumazenil reduced sternal recumbency, standing and walking times.

본 연구는 tiletamine/zolazepam 대조군과 대조군에 benzodiazepine의 길항제인 flumazenil을 투여한 실험군의 마취 효과와 혈액생화학, Vital sign, 마취회복시간에 대하여 비교하였다. 건강한 6마리의 개들(평균 체중 $5.2{\pm}2.2$)이 실험에 이용 되었다. Tiletamine/zolazepam 을 투여하였고 20분 뒤에 benzodiazepine의 길항제인 flumazenil 0.1 mg을 투여하였다. 마취효과 (Sedation, analgesia, muscle relaxation, posture and auditory response score), Vital sign (심박수, 호흡수, 체온), 혈액 생화학 (GLU, TP, ALT, AST) 검사들이 두 그룹에서 tiletamine/zolazepam 투여전, 투여후 1, 5, 20, 30, 60 그리고 90분에 실시되었다. 또한 마취회복시간 (head up, sternal recumbency, standing and walking times)은 부동화 상태에서 각 행동양식 이 보이는 시간까지 측정되었다. Analgesia score는 투여 후 20분과 30분에, posture score는 투여 후 30분에 그리고 auditory response score는 투여 후 1분과 20분에 TZF그룹이 TZ그룹보다 유의하게 낮아 benzodiazepine에 대한 flumazenil의 길항효과를 나타냈다. 평균 심박수는 두 그룹 모두 투여 후 1분부터 급상승하여 유의하게 정상 심박수 보다 높았다. 평균 호흡수는 TZF그룹이 TZ그룹보다 유의하지 않았으나 높은 호흡수를 보였다. 결론적으로 개에서 flumazenil의 투여는 tiletamine/zolazepam에 대한 길항작용을 나타내었다. 마취로 부터의 회복에 있어서, flumazenil은 sternal recumbency, standing 및 walking times를 단축시켰다.

Keywords

References

  1. Anderson JA. Reversal Agents in Sedation and Anesthesia: A Review. Anesth Prog 1988; 35: 43-47.
  2. Ashton CH. Bezodiazepine overdose: are specific antagonists useful? Br Med J 1985; 16: 805-806.
  3. Christian R, Norman T. Paradoxical Reactions to Benzodiazepines in Intravenous Sedation; A Report of 2 Cases and Review of the Literature. Anesth Prog 2002; 49: 128-132.
  4. Earle RY. The Effect of Flumazenil on the Recovery Time of Dental Patients Sedated with Diazepam. Anesth Prog 1989; 36: 46-51.
  5. James GW. Flumazenil; a benzodiazepine antagonist. Many uses, possibly including withdrawal from benzodiazepines. BMJ 1988; 297.
  6. Kathryn W, Corey B, Robert H, Lloyd D, Mark H. Chemical immobilization of adult female weddell seals with tiletamine and zolazepam; effects of age, condition and stage of lactation. BMC Vet Res 2006; 2: 8 https://doi.org/10.1186/1746-6148-2-8
  7. Kim MJ, Park CS, Jun MH, Kim M. Antagonistic effects of yohimbine in pigs anaesthetised with tiletamine/zolazepam and xylazine. Vet Rec 2007; 161: 620-624. https://doi.org/10.1136/vr.161.18.620
  8. Ko JC, Williams BL, Smith VL, Mcgrath CJ, Jacobson JD. Comparison of telazol, telazol-ketamine, telazol-xylazine, and telazol-ketamine-xylazine as chemical restraint and andesthetic induction combination in swine. Lab Anim Sci 1993; 43: 476-480.
  9. Lin HC, Thurmon JC, Benson GJ, Thanquilli WJ. Telazol-a review of its pharmacology and use in veterinary practice. J Vet Pham Therap 1991; 16: 383-418.
  10. Morris C, James L, Bruce J. Reversal of Central Benzodiazepine Effects by Intravenous Flumazenil. University of Colorado Health Sciences Center, Denver Colorado. Anesth Prog 1991; 38: 12-16
  11. Park MH, Seo KM, Jang KH. Effects of continuous administration of Tiletamine-zolazepam in dogs. Korean J Vet Res 1997; 37: 457-462.
  12. Plumb DC. Plumb's Veterinery Drug Handbook, 5th ed. Ames: Iowa State University Press. 2004; 490-491.
  13. Richard LF, Paul AM, John MC, Flumazenil Reversal of Consious Sedation Induced with Intravenous Fentanyl and Diazepam. Anesth Prog 1995; 42: 11-16.
  14. Toru M, Naoto K, Shunichi O, Koji T, Teruhito K, Akira T. Timing and side effects of flumazenil for dental outpatients receiving intravenous sedation with midazolam. Anesth Prog 1997; 44: 127-131.