Effect of Butorphanol and Buprenorphine use on cardiac Troponin I and C-reactive protein concentrations in Ketamine-Dexmedetomidine-Midazolam anesthesia in rabbits
Abstract
The purpose of this study was to evaluate the effects of two anesthetic combinations, ketamine–dexmedetomidine–midazolam–butorphanol and ketamine–dexmedetomidine–midazolam–buprenorphine, on cardiac troponin I and C-reactive protein concentrations during short- term anesthesia in rabbits. Sixteen adult New Zealand White rabbits (8 males and 8 females) were included in the study and randomly divided into two groups, each consisting of four males and four females. Group 1 received ketamine (20 mg/kg IM), dexmedetomidine (35 μg/kg IM), midazolam (0.5 mg/kg IM) and buprenorphine (0.02 mg/kg IM), while Group 2 received ketamine (20 mg/kg IM), dexmedetomidine (35 μg/kg IM), midazolam (0.5 mg/kg IM) and butorphanol (0.2 mg/kg IM). Reflex responses (standing, ear and rear pedal reflex) and cardiopulmonary parameters (heart rate, respiratory rate and peripheral oxygen saturation) were recorded before anesthesia and at 5, 10, 15, 30, 45 and 60 min after drug administration. Blood samples for C-reactive protein and cardiac troponin I analysis were collected before anesthesia induction, at 30 min of anesthesia, and at 6, 12 and 24 h after anesthesia. Both anesthetic combinations provided adequate anesthesia for short surgical procedures in rabbits within the tested dose ranges. However, the butorphanol combination produced a longer duration of surgical anesthesia and deeper sedation compared with buprenorphine. Neither protocol caused significant increases in serum C-reactive protein or cardiac troponin I concentrations, suggesting that both anesthetic combinations can be safely used for short-term anesthesia in rabbits.
Downloads
References
O’Brien PJ, Smith D, Knechtel TJ, Pruimboom-Brees I, Brees DJ, Spratt DP, Archer FJ, Butler P, Potter AN, Provost JP, Richard J, Snyder PA, Reagan WJ. Cardiac troponin I is a sensitive, specific biomarker of cardiac injury in laboratory animals. Lab. Anim. [Internet]. 2006; 40(2):153-171. doi: https://doi.org/d7r3bj DOI: https://doi.org/10.1258/002367706776319042
Oohashi E, Kimura Y, Matsumoto K. Pilot study on serum C-reactive protein in pet rabbits: clinical usefulness. Vet. Rec. Open. [Internet]. 2019; 6(1):e000272. doi: https://doi.org/gqttzt DOI: https://doi.org/10.1136/vetreco-2017-000272
Schultz JJ, Hsu AK, Gross GJ. Ischemic preconditioning and morphine-induced cardioprotection involve the delta (δ)-opioid receptor in the intact rat heart. J. Mol. Cell. Cardiol. [Internet]. 1997; 29(8):2187-2195. doi: https://doi.org/b3bfdb DOI: https://doi.org/10.1006/jmcc.1997.0454
Henke J, Astner S, Brill T, Eissner B, Busch R, Erhardt W. Comparative study of three intramuscular anaesthetic combinations (medetomidine/ketamine, medetomidine/ fentanyl/midazolam and xylazine/ketamine) in rabbits. Vet. Anaesth. Anal. [Internet]. 2005; 32(5):261-270. doi: https://doi.org/c72pzh DOI: https://doi.org/10.1111/j.1467-2995.2005.00242.x
Zaugg M, Schaub MC, Foex P. Myocardial injury and its prevention in the perioperative setting. Br. J. Anaesth. [Internet]. 2004; 93(1):21-33. doi: https://doi.org/bnw4tx DOI: https://doi.org/10.1093/bja/aeh150
Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. [Internet]. 1986; 74(5):1124-1136. doi: https://doi.org/b5xzrf DOI: https://doi.org/10.1161/01.CIR.74.5.1124
Savola, JM. Cardiovascular actions of medetomidine and their reversal by atipamezole. Acta Vet. Scand. Suppl. [Internet]. 1989 [20 dec 2025]; 85:39-47. PMID: 2571276. Available in: https://goo.su/ti0q
Thurmon JC, Tranquilli WJ, Benson GJ. Considerations for general anesthesia. In: Thurmon JC, Tranquilli WJ, Benson GJ,eds. Lumb and Jones’ Veterinary Anesthesia, 3rd ed. Hagerstown, Marylan, USA: Williams and Wilkins, 1996. p. 5–34.
Virtanen R, Savola JM, Saano V, Nyman L. Characterization of the selectivity, specificity and potency of medetomidine as an α2-adrenoceptor agonist. Eur. J. Pharmacol. [Internet]. 1988; 150(1-2):9-14. doi: https://doi.org/c247pr DOI: https://doi.org/10.1016/0014-2999(88)90744-3
Cromheecke S, Pepermans V, Hendrickx E, Lorsomradee S, Ten Broecke PW, Stockman BA, Rodrigus IE, De Hert SG. Cardioprotective properties of sevoflurane in patients undergoing aortic valve replacement with cardiopulmonary bypass. Anesth. Analg. [Internet]. 2006; 103(2):289-296. doi: https://doi.org/dbhmpg DOI: https://doi.org/10.1213/01.ane.0000226097.22384.f4
Malagon I, Hogenbirk K, Van Pelt J, Hazekamp MG, Bovill JG. Effect of three different anaesthetic agents on the postoperative production of cardiac troponin T in paediatric cardiac surgery. Br. J. Anaesth. [Internet]. 2006; 94(6):805-809. doı: https://doi.org/ds464r DOI: https://doi.org/10.1093/bja/aei142
Cason BA, Gamperl AK, Slocum RE, Hickey RF. Anesthetic-induced preconditioning: previous administration of isoflurane decreases myocardial infarct size in rabbits. Anesthesiology. [Internet]. 1997; 87(5):1182-1190. doi: https://doi.org/dcs5rb DOI: https://doi.org/10.1097/00000542-199711000-00023
Shizukuda Y, Mallet RT, Lee SC, Downey HF. Hypoxic preconditioning of ischaemic canine myocardium. Cardiovasc. Res. [Internet]. 1992; 26(5):534-542. doı: https://doi.org/bhhmxj DOI: https://doi.org/10.1093/cvr/26.5.534
Kiliç N. A comparison between medetomidine-ketamine and xylazine-ketamine anaesthesia in rabbits. Turk. J. Vet. Anim. Sci. [Internet]. 2004 [cited 11 Nov 2025]; 28(5):921-926. Available in: https://goo.su/HqKcftK
Ko JC, Austin BR, Barletta M, Weil AB, Krimins RA, Payton ME. Evaluation of dexmedetomidine and ketamine in combination with various opioids as injectable anesthetic combinations for castration in cats. J. Am. Vet. Med. Assoc. [Internet]. 2011; 239(11):1453-1462. doi: https://doi.org/dtwd95 DOI: https://doi.org/10.2460/javma.239.11.1453
Barletta M, Austin BR, Ko JC, Payton ME, Weil AB, Inoue, T. Evaluation of dexmedetomidine and ketamine in combination with opioids as injectable anesthesia for castration in dogs. J. Am. Vet. Med. Assoc. [Internet]. 2011; 238(9):1159-1167. doi: https://doi.org/dzmsmj DOI: https://doi.org/10.2460/javma.238.9.1159
Santangelo B, Micieli F, Mozzillo T, Reynaud F, Marino F, Auletta L, Vesce G. Transnasal administration of a combination of dexmedetomidine, midazolam and butorphanol produces deep sedation in New Zealand White rabbits. Vet. Anaesth. Anal. [Internet]. 2016; 43(2):209-214. doi: https://doi.org/f8j5px DOI: https://doi.org/10.1111/vaa.12278
Kılıç N, Kozacı LD, Kibar B, Şen ZB, Bellek CG, Bulut O. Effect (s) of Long-Term Anaesthesia Induced by Isoflurane, Sevoflurane, Propofol-Fentanyl, Medetomidin-Midozolam-Ketamine or Xylazine-Ketamine Combinations on the Acut Phase Proteins and Cardiac Troponins Levels in Rabbits. FÜ Sağ. Bil. Vet. Derg. [Internet]. 2018 [cited 16 Jan 2026]; 32(1):7-12. Available in: https://goo.su/kmakm
Kirazoğlu E. Tavşanlarda deksmedetomidin-ketamin ve ksilazin-ketamin anestezilerinin hematolojik ve klinik parametrelere etkisinin karşılaştırılması. [Dissertation master thesis on the Internet]. Şanlıurfa, Türkiye: University of Harran; 2019 [cited 6 May 2025]. 173 p. Turkish. Available in: https://goo.su/UJP3
Slingsby LS, Murrell JC, Taylor PM. Combination of dexmedetomidine with buprenorphine enhances the antinociceptive effect to a thermal stimulus in the cat compared with either agent alone. Vet. Anaesth. Anal. [Internet]. 2010; 37(2):162-170. doi: https://doi.org/dqj9h3 DOI: https://doi.org/10.1111/j.1467-2995.2009.00519.x
Leppänen MK, McKusick BC, Granholm MM, Westerholm FC, Tulamo R, Short CE. Clinical efficacy and safety of dexmedetomidine and buprenorphine, butorphanol or diazepam for canine hip radiography. J. Small Anim. Pract. [Internet]. 2006; 47(11):663-669. doi: https://doi.org/fvqk48 DOI: https://doi.org/10.1111/j.1748-5827.2006.00030.x
Lammintausta R. The alpha-2 adrenergic drugs in veterinary anaesthesia. J. Vet. Anaesth. [Internet]. 1991; 18(1):3-8. doi: https://doi.org/dh2bj5 DOI: https://doi.org/10.1111/j.1467-2995.1991.tb00504.x
Hedenqvist P, Edner A, Fahlman Å, Jensen-Waern M. Continuous intravenous anaesthesia with sufentanil and midazolam in medetomidine premedicated New Zealand White rabbits. BMC Vet. Res. [Internet]. 2013; 9:21. doi: https://doi.org/f23wfw DOI: https://doi.org/10.1186/1746-6148-9-21
Cardoso CG, Ayer IM, Jorge AT, Honsho CS, Mattos-Junior E. A comparative study of the cardiopulmonary and sedative effects of a single intramuscular dose of ketamine anesthetic combinations in rabbits. Res. Vet. Sci. [Internet]. 2020; 128:177-182. doi: https://doi.org/gpfqgj DOI: https://doi.org/10.1016/j.rvsc.2019.11.016
Ferreira FS, Barretto FL, Fabres A, Silveira LS, Carvalho CB. Cardiacmarkers in five different breeds of rabbits (Oryctolagus cuniculus Linnaeus, 1758) used for cardiovascular research. Pesq. Vet. Bras. [Internet]. 2016; 36(8):737-742. doi: https://doi.org/qz4h DOI: https://doi.org/10.1590/S0100-736X2016000800010
Chaniotakis I, Antoniou E, Kostomitsopoulos N, Karapsias S, Mirilas P, Salakos C. Stress response to ovariohysterectomy in rabbits: role of anaesthesia and surgery. J. Obstet. Gynaecol. [Internet]. 2018; 38(5):697-701. doi: https://doi.org/qz4j DOI: https://doi.org/10.1080/01443615.2017.1400523
Deveci V. Tavşanlarda medetomidin-ketamin ve propofol-fentanil ile oluşturulan anestezinin bazı hemodinamik parametreler ile kardiyak troponin-I ve serum C-reaktif protein konsantrasyonları üzerine etkisi. [Dissertation doctoral thesis on the Internet]. Aydın, Türkiye: University of Adnan Menderes; 2015 [cited 6 Jan 2026]. 123 p. Available in: https://goo.su/DywRbnZ
Saunders AB, Hanzlicek AS, Martinez EA, Stickney MJ, Steiner JM, Suchodolski JS, Fosgate GT. Assessment of cardiac troponin I and C-reactive protein concentrations associated with anesthetic protocols using sevoflurane or a combination of fentanyl, midazolam, and sevoflurane in dogs. Vet. Anaesth. Anal. [Internet]. 2009; 36(5):449-456. doi: https://doi.org/bbzn6d DOI: https://doi.org/10.1111/j.1467-2995.2009.00483.x
Singletary GE, Saunders AB, Saunders WB, Suchodolski JS, Steiner JM, Fosgate GT, Hartsfield SM. Cardiac troponin I concentrations following medetomidine butorphanol sedation in dogs. Vet. Anaesth. Anal. [Internet]. 2010; 37(4):342-346. doi: https://doi.org/ckvkzf DOI: https://doi.org/10.1111/j.1467-2995.2010.00540.x
