Hadi IMANI RASTABI, Hadi NADDAF, Bahman MOSALLANEJAD, Ahmad KHAJEH

Evaluation of the Feasibility, Reversibility and Cardiorespiratory Effcts of Epidural Dexmedetomidine in Sedated Dogs Undergoing Orchiectomy

The objective of the present study was to evaluate whether epidural dexmedetomidine (DEX) produces sufficient anti-nociception with reversible sedation and cardiorespiratory changes in sedated dogs undergoing orchiectomy. Twelve male dogs weighing 21.7±5.2 kg were used. Dogs received acepromazine (0.025 mg/kg) and morphine (0.25 mg/kg) intramuscularly and a second dose of morphine (0.125 mg/kg) intravenously (IV). DEX (3 µg/kg) was administered epidurally to all dogs (n=12). After confirming complete sensory blockade of the prescrotal region, orchiectomy was performed. If any discomfort was detected during surgery, 2-3 mL lidocaine 1% (maximum two times) was applied into the painful area. Sixty minutes after epidural application, dogs were randomly assigned to receive either treatment of atipamezole (ATP; n=6) or saline (SAL; n=6) IV. None of the dogs required general anesthesia; however, nine out of twelve dogs received lidocaine. The duration of sensory blockade was significantly shorter in ATP than that of SAL. Heart rate, respiratory rate, and rectal temperature showed significantly lower values compared with base after administration of DEX. Administration of atipamezole reversed sedation, sensory blockade and cardiorespiratory changes. In conclusion, epidural DEX did not produce adequate anti-nociception during orchiectomy in sedated dogs. Sedation, sensory blockade and cardiorespiratory changes induced by epidural DEX can be reversed by IV administration of atipamezole.

Orşiektomi Yapılan Sedasyonlu Köpeklerde Epidural Deksmedetomidinin Fizibilite, Reverzibilite ve Kardiyorespiratuvar Etkilerinin Değerlendirilmesi

Bu çalışmanın amacı; orşiektomi yapılan sedasyonlu köpeklerde epidural deksmedetomidinin (DEX) geri dönüşlü sedasyon ve kardiyorespiratuvar değişiklikleri ile yeterli anti-nosisepsiyon üretip üretmediğini değerlendirmekti. Çalışmada ortalama ağıtlıkları 21.7±5.2 kg olan on iki erkek köpek kullanıldı. Köpeklere intramüsküler yolla asepromazin (0.025 mg/kg) ve morfin (0.25 mg/kg) ardından intravenöz yolla (IV) ikinci bir doz morfin (0.125 mg/kg) uygulandı. Tüm köpeklere (n=12) epidural yolla DEX (3 µg/kg) uygulandı. Prescrotal bölgenin tam duyusal blokajı sağlandıktan sonra orşiektomi operasyonu yapıldı. Ameliyat sırasında herhangi bir rahatsızlık tespit edilirse, ağrılı bölgeye 2-3 mL %1’lik lidokain (en fazla iki kez) uygulandı. Epidural uygulamadan altmış dakika sonra, köpekler IV atipamezol (ATP; n=6) veya salin (SAL; n=6) tedavisi alacak şekilde rastgele gruplandırıldı. Köpeklerin hiçbirinde genel anestezi uygulanması gerekmedi; ancak, on iki köpekten dokuzuna lidokain uygulandı. ATP'de duyusal blokajın süresi, SAL'dan daha kısaydı. Kalp atış hızı, solunum hızı ve rektal sıcaklık, DEX uygulamasından sonraki ölçümler ile karşılaştırıldığında önemli ölçüde düşüş gösterdi. Atipamezol uygulaması, sedasyon, duyusal blokaj ve kardiyorespiratuvar değişiklikleri tersine çevirdi. Sonuç olarak, epidural DEX, sedasyon uygulanan köpeklerde orşiektomi sırasında yeterli anti-nosisepsiyon etki üretmediği belirlendi. Epidural DEX'in neden olduğu sedasyon, duyusal blokaj ve kardiyorespiratuvar değişiklikler IV atipamezol uygulamasıyla tersine çevrilebilir.

PDF

___

1. Lorena SE, Luna SP, Lascelles BDX, Corrente JE: Current attitudes regarding the use of perioperative analgesics in dogs and cats by Brazilian veterinarians. Vet Anaesth Analg, 41 (1): 82-89, 2014. DOI: 10.1111/vaa.12104

2. Nickell J, Barter LS, Dechant JE: Effcts of intratesticular and incisional local anesthetic administration for castration of alpacas anesthetized with intramuscular ketamine-xylazine-butorphanol. Vet Surg, 44 (2): 168- 173, 2015. DOI: 10.1111/j.1532-950X.2014.12285.x

3. Park SJ, Piao M, Kim H, Kang HJ, Seo J, Lee S, Baik M: Effects of castration and a lidocaine-plus-flnixin treatment on growth and indicators of pain, inflmmation, and liver function in Korean cattle bull calves. Livest Sci, 216, 61-66, 2018. DOI: 10.1016/j.livsci.2018.07.010

4. Racine J, Vidondo B, Ramseyer A, Koch C: Complications associated with closed castration using the H enderson equine castration instrument in 300 standing equids. Vet Surg, 48 (1): 21-28, 2019. DOI: 10.1111/ vsu.12960

5. Campoy L, Martin-Flores M, Ludders JW, Gleed RD: Procedural sedation combined with locoregional anesthesia for orthopedic surgery of the pelvic limb in 10 dogs: Case series. Vet Anaesth Analg, 39 (4): 436- 440, 2012. DOI: 10.1111/j.1467-2995.2012.00712.x

6. Kushnir Y, Toledano N, Cohen L, Bdolah-Abram T, Shilo-Benjamini Y: Intratesticular and incisional line infiltration with ropivacaine for castration in medetomidine-butorphanol-midazolam sedated dogs. Vet Anaesth Analg, 44 (2): 346-355, 2017. DOI: 10.1016/j.vaa.2016.03.007

7. Yayla S, Kaçar C, Kılıç E, Kaya S, Kuru M, Ermutlu CŞ, Özaydın İ, Hüseyinoğlu Ü, Öğün M: The effcts of intrathecal administration of bupivacaine or ropivacaine following administration of propofol in dogs undergoing ovariohysterectomy. Kafkas Univ Vet Fak Derg, 23 (3): 363-367, 2017. DOI: 10.9775/kvfd.2016.16665

8. Campoy L, Read M, Peralta S: Canine and Feline Local Anesthetic and Analgesic Techniques. In, Grimm KA, Lamont LA, Tranquilli WJ, Greene SA, Robertson SA (Eds): Veterinary Anesthesia and Analgesia, The Fifth Edition of Lumb and Jones., 827-856, John Wiley & Sons, Pondicherry, India, 2015.

9. Jones RS: Epidural analgesia in the dog and cat. Vet J, 161 (2): 123-131, 2001. DOI: 10.1053/tvjl.2000.0528

10. Steagall PVM, Simon BT, Teixeira Neto FJ, Luna SPL: An update on drugs used for lumbosacral epidural anesthesia and analgesia in dogs. Front Vet Sci, 4:68, 2017. DOI: 10.3389/fvets.2017.00068

11. Kuusela E, Raekallio M, Anttila M, Falck I, Molsa S, Vainio O: Clinical effcts and pharmacokinetics of medetomidine and its enantiomers in dogs. J Vet Pharmacol Ther, 23 (1): 15-20, 2000. DOI: 10.1046/j.1365- 2885.2000.00245.x

12. Bennett RC, Restitutti F: Dexmedetomidine or medetomidine: Which should veterinary surgeons select? Companion Anim, 21 (3): 128- 137, 2016. DOI: 10.12968/coan.2016.21.3.128

13. Bloor BC, Frankland M, Alper G, Raybould D, Weitz J, Shurtlif M: Hemodynamic and sedative effects of dexmedetomidine in dog. J Pharmacol Exp Ther, 263 (2): 690-697, 1992.

14. Pascoe PJ, Raekallio M, Kuusela E, McKusick B, Granholm M: Changes in the minimum alveolar concentration of isoflrane and some cardiopulmonary measurements during three continuous infusion rates of dexmedetomidine in dogs. Vet Anaesth Analg, 33 (2): 97-103, 2006. DOI: 10.1111/j.1467-2995.2005.00236.x

15. Smith CK, Seddighi R, Cox SK, Sun X, Knych HK, Doherty TJ: Effct of dexmedetomidine on the minimum infusion rate of propofol preventing movement in dogs. Vet Anaesth Analg, 44 (6): 1287-1295, 2017. DOI: 10.1016/j.vaa.2017.07.004

16. Vasiljević M, Krstić V, Stanković S, Zrimšek P, Svete AN, Seliškar A: Cardiac troponin I in dogs anaesthetized with propofol and sevoflrane: The Inflence of medetomidine premedication and inspired oxygen fraction. Vet Anaesth Analg, 45 (6): 745-753, 2018. DOI: 10.1016/j. vaa.2018.07.003

17. Campagnol D, Neto FJT, Giordano T, Ferreira TH, Monteiro ER: Effcts of epidural administration of dexmedetomidine on the minimum alveolar concentration of isoflrane in dogs. Am J Vet Res, 68 (12): 1308- 1318, 2007. DOI: 10.2460/ajvr.68.12.1308

18. Rector E, Kramer S, Kietzmann M, Hart S, Nolte I: Evaluation of the antinociceptive effct of systemic and epidurally applied xylazine in general anesthesia with isoflrane in dogs and the effct of atipamezole infection on postoperative analgesia. Berl Munch Tierarztl Wochenschr, 111 (11-12): 438-451, 1998.

19. Lee I, Yamagishi N, Oboshi K, Yamada H: Antagonistic effcts of intravenous or epidural atipamezole on xylazine-induced dorsolumbar epidural analgesia in cattle. Vet J, 166 (2): 194-197, 2003. DOI: 10.1016/ S1090-0233(03)00026-1

20. Sullivan AF, Kalso EA, McQuay HJ, Dickenson AH: The antinociceptive actions of dexmedetomidine on dorsal horn neuronal responses in the anaesthetized rat. Eur J Pharmacol, 215 (1): 127-133, 1992. DOI: 10.1016/0014-2999(92)90617-D

21. Sullivan AF, Dashwood MR, Dickenson AH: α2-adrenoceptor modulation of nociception in rat spinal cord: Location, effects and interactions with morphine. Eur J Pharmacol, 138 (2): 169-177, 1987. DOI: 10.1016/0014-2999(87)90430-4

22. Sabbe MB, Penning JP, Ozaki GT, Yaksh TL: Spinal and systemic action of the alpha 2 receptor agonist dexmedetomidine in dogs. Antinociception and carbon dioxide response. Anesthesiology, 80 (5): 1057-1072, 1994.

23. Pohl VH, Carregaro AB, Lopes C, Gehrcke MI, Muller D, Garlet CD: Epidural anesthesia and postoperatory analgesia with alpha-2 adrenergic agonists and lidocaine for ovariohysterectomy in bitches. Can J Vet Res, 76 (3): 215-220, 2012.

24. Nishimura LT, Auckburally A, Santilli J, Vieira BHB, Garcia DO, Honsho CS, de Mattos-Junior E: Effcts of dexmedetomidine combined with commonly administered opioids on clinical variables in dogs. Am J Vet Res, 79 (3): 267-275, 2018. DOI: 10.2460/ajvr.79.3.267

25. Raillard M, Michaut-Castrillo J, Spreux D, Gauthier O, TouzotJourde G, Holopherne-Doran D: Comparison of medetomidine-morphine and medetomidine-methadone for sedation, isoflrane requirement and postoperative analgesia in dogs undergoing laparoscopy. Vet Anaesth Analg, 44 (1): 17-27, 2017. DOI: 10.1111/vaa.12394

26. Murrell JC, Hellebrekers LJ: Medetomidine and dexmedetomidine: A review of cardiovascular effcts and antinociceptive properties in the dog. Vet Anaesth Analg, 32 (3): 117-127, 2005. DOI: 10.1111/j.1467-2995. 2005.00233.x

27. Maze M, Tranquilli W: Alpha-2 adrenoceptor agonists: Defining the role in clinical anesthesia. Anesthesiology, 74, 581-605, 1991.

28. Ko JCH, Fox SM, Mandsager RE: Sedative and cardiorespiratory effcts of medetomidine, medetomidine-butorphanol, and medetomidineketamine in dogs. J Am Vet Med Assoc, 216 (10): 1578-1583, 2000. DOI:10.2460/javma.2000.216.1578

29. Kuusela E, Vainio O, Short CE, Leppäluoto J, Huttunen P, Ström S, Huju V, Valtonen A, Raekallio M: A comparison of propofol infusion and propofol/isoflrane anaesthesia in dexmedetomidine premedicated dogs. J Vet Pharmacol Ther, 26 (3): 199-204, 2003. DOI: 10.1046/j.1365- 2885.2003.00465.x

30. Ansah O, Raekallio M, Vainio O: Comparison of three doses of dexmedetomidine with medetomidine in cats following intramuscular administration. J Vet Pharmacol Ther, 21, 380-387, 1998. DOI: 10.1046/j. 1365-2885.1998.00155.x

31. Souza SS, Intelisano TR, De Biaggi CP, Moura CA, Selmi AL, Dias RA, Cortopassi SRG: Cardiopulmonary and isoflrane‐sparing effcts of epidural or intravenous infusion of dexmedetomidine in cats undergoing surgery with epidural lidocaine. Vet Anaesth Analg, 37 (2): 106-115, 2010. DOI: 10.1111/j.1467-2995.2009.00512.x

32. Haskins SC, Patz JD, Farver TB: Xylazine and xylazine-ketamine in dogs. Am J Vet Res, 47 (3): 636-641, 1986.

33. Granholm M, McKusick BC, Westerholm FC, Aspegrén JC: Evaluation of the clinical efficacy and safety of dexmedetomidine or medetomidine in cats and their reversal with atipamezole. Vet Anaesth Analg, 33 (4): 214-223, 2006. DOI: 10.1111/j.1467-2995.2005.00259.x

34. Pypendop BH, Verstegen JP: Cardiovascular effcts of romifidine in dogs. Am J Vet Res, 62 (4): 490-495, 2001. DOI: 10.2460/ajvr.2001.62.490

35. Virtanen R: Pharmacological profiles of medetomidine and its antagonist, atipamezole. Acta Vet Scand Suppl, 85, 29-37, 1989.

36. Väisänen M, Raekallio M, Kuusela E, Huttunen P, Leppäluoto J, Kirves P, Vainio O: Evaluation of the perioperative stress response in dogs administered medetomidine or acepromazine as part of the preanesthetic medication. Am J Vet Res, 63 (7): 969-975, 2002. DOI: 10.2460/ajvr.2002.63.969