Analyze Diet
Journal of veterinary pharmacology and therapeutics2020; 43(4); 369-376; doi: 10.1111/jvp.12855

Pharmacokinetics and clinical effects of xylazine and dexmedetomidine in horses recovering from isoflurane anesthesia.

Abstract: This study determined the pharmacokinetics and compared the clinical effects of xylazine and dexmedetomidine in horses recovering from isoflurane anesthesia. Six healthy horses aged 8.5 ± 3 years and weighing 462 ± 50 kg were anesthetized with isoflurane for 2 hr under standard conditions on two occasions one-week apart. In recovery, horses received 200 μg/kg xylazine or 0.875 μg/kg dexmedetomidine intravenously and were allowed to recover without assistance. These doses were selected because they have been used for postanesthetic sedation in clinical and research studies. Serial venous blood samples were collected for quantification of xylazine and dexmedetomidine, and the pharmacokinetic parameters were calculated. Two individuals blinded to treatment identity evaluated recovery quality with a visual analog scale. Times to stand were recorded. Results (mean ± SD) were compared using paired t tests or Wilcoxon signed-ranked test with p < .05 considered significant. Elimination half-lives (62.7 ± 21.8 and 30.1 ± 8 min for xylazine and dexmedetomidine, respectively) and steady-state volumes of distribution (215 ± 123 and 744 ± 403 ml/kg) were significantly different between xylazine and dexmedetomidine, whereas clearances (21.1 ± 17.3 and 48.6 ± 28.1 ml/minute/kg), times to stand (47 ± 24 and 53 ± 12 min) and recovery quality (51 ± 24 and 61 ± 22 mm VAS) were not significantly different. When used for postanesthetic sedation following isoflurane anesthesia in healthy horses, dexmedetomidine displays faster plasma kinetics but is not associated with faster recoveries compared to xylazine.
Publication Date: 2020-03-12 PubMed ID: 32166760DOI: 10.1111/jvp.12855Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article
  • Randomized Controlled Trial
  • Veterinary

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article focuses on a comparative study of the pharmacokinetics and clinical effects of two anaesthetic drugs in horses: xylazine and dexmedetomidine. These drugs were administered to horses recovering from isoflurane anaesthesia, with the aim to understand their effects on recovery periods, how the body processes these drugs, and any significant differences between them.

Study Design

  • The research was conducted on six healthy horses, each around eight and a half years old and with an average weight of 462 kg.
  • Each horse was anesthetized with isoflurane for two hours under standard conditions on two separate occasions, with a gap of a week in between.
  • During recovery from anesthesia, the horses were injected with either 200 μg/kg xylazine or 0.875 μg/kg dexmedetomidine, doses chosen based on prior usage in postanesthetic sedation studies.
  • The horses were left to recover without assistance, and venous blood samples were systematically collected to ascertain the concentration of xylazine and dexmedetomidine present overtime.
  • Pharmacokinetic parameters, such as elimination half-lives and steady-state volumes of distribution, were calculated for both drugs based on these blood sample data.
  • Lastly, recovery quality was assessed by using a visual analog scale by two individuals who were unaware of the treatment given to each horse.

Results and Findings

  • The research found significant differences between xylazine and dexmedetomidine on certain parameters. Dexmedetomidine had a faster elimination half-life (30.1±8 minutes) and larger volume of distribution (744±403 ml/kg) than xylazine (62.7±21.8 minutes and 215±123 ml/kg, respectively).
  • However, other parameters such as clearances, times to stand, and recovery quality assessment showed no significant difference between the two drugs.
  • The research concludes that while dexmedetomidine has faster plasma kinetics, it does not necessarily contribute to faster recovery periods compared to xylazine post-isoflurane anesthesia in healthy horses.

Cite This Article

APA
Guedes A, Knych H, Tucker L, Almeida DC, Baldo CF, Wendt-Hornickle E, Allweiler S. (2020). Pharmacokinetics and clinical effects of xylazine and dexmedetomidine in horses recovering from isoflurane anesthesia. J Vet Pharmacol Ther, 43(4), 369-376. https://doi.org/10.1111/jvp.12855

Publication

ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 43
Issue: 4
Pages: 369-376

Researcher Affiliations

Guedes, Alonso
  • Veterinary Clinical Sciences Department, College of Veterinary Medicine, University of Minnesota, Minneapolis, MN, USA.
Knych, Heather
  • K. L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.
Tucker, Laura
  • Veterinary Clinical Sciences Department, College of Veterinary Medicine, University of Minnesota, Minneapolis, MN, USA.
Almeida, Daniel C
  • Veterinary Clinical Sciences Department, College of Veterinary Medicine, University of Minnesota, Minneapolis, MN, USA.
Baldo, Caroline F
  • Veterinary Clinical Sciences Department, College of Veterinary Medicine, University of Minnesota, Minneapolis, MN, USA.
Wendt-Hornickle, Erin
  • Veterinary Clinical Sciences Department, College of Veterinary Medicine, University of Minnesota, Minneapolis, MN, USA.
Allweiler, Sandra
  • Veterinary Clinical Sciences Department, College of Veterinary Medicine, University of Minnesota, Minneapolis, MN, USA.

MeSH Terms

  • Analgesics / administration & dosage
  • Analgesics / pharmacokinetics
  • Analgesics / pharmacology
  • Anesthesia Recovery Period
  • Anesthetics, Inhalation / administration & dosage
  • Anesthetics, Inhalation / pharmacokinetics
  • Anesthetics, Inhalation / pharmacology
  • Animals
  • Cross-Over Studies
  • Dexmedetomidine / administration & dosage
  • Dexmedetomidine / pharmacokinetics
  • Dexmedetomidine / pharmacology
  • Female
  • Horses / blood
  • Hypnotics and Sedatives / administration & dosage
  • Hypnotics and Sedatives / pharmacokinetics
  • Isoflurane / pharmacology
  • Male
  • Xylazine / administration & dosage
  • Xylazine / pharmacokinetics
  • Xylazine / pharmacology

References

This article includes 33 references
  1. Altman DG. Some common problems in medical research. (pp. 404-408).
  2. Bettschart-Wolfensberger R, Freeman SL, Bowen IM, Aliabadi FS, Weller R, Huhtinen M, Clarke KW. Cardiopulmonary effects and pharmacokinetics of i.v. dexmedetomidine in ponies. Equine Veterinary Journal 37(1), 60-64.
  3. Bidwell LA, Bramlage LR, Rood WA. Equine perioperative fatalities associated with general anaesthesia at a private practice-a retrospective case series. Veterinary Anaesthesia and Analgesia 34(1), 23-30.
  4. Clark-Price SC. Recovery of horses from anesthesia. The Veterinary Clinics of North America. Equine Practice 29(1), 223-242.
  5. Creighton CM, Lemke KA, Lamont LA, Horney BS, Doyle AJ. Comparison of the effects of xylazine bolus versus medetomidine constant rate infusion on the stress response, urine production, and anesthetic recovery characteristics in horses anesthetized with isoflurane. Journal of the American Veterinary Medical Association 240(8), 998-1002.
    doi: 10.2460/javma.240.8.998google scholar: lookup
  6. DrugBank. Dexmedetomidine. .
  7. Dugdale AH, Obhrai J, Cripps PJ. Twenty years later: A single-centre, repeat retrospective analysis of equine perioperative mortality and investigation of recovery quality. Veterinary Anaesthesia and Analgesia 43(2), 171-178.
    doi: 10.1111/vaa.12285google scholar: lookup
  8. Dugdale AH, Taylor PM. Equine anaesthesia-associated mortality: Where are we now?. Veterinary Anaesthesia and Analgesia 43(3), 242-255.
    doi: 10.1111/vaa.12372google scholar: lookup
  9. Dyer DC, Hsu WH, Lloyd WE. Pharmacokinetics of xylazine in ponies: Influence of yohimbine. Archives Internationales De Pharmacodynamie Et De Therapie 289(1), 5-10.
  10. Dyke TM, Hubbell JA, Sams RA, Hinchcliff KW. Hepatic blood flow in horses during the recuperative period from maximal exercise. American Journal of Veterinary Research 59(11), 1476-1480.
  11. FDA. Guidance for industry: Bioanalytical method validation. .
  12. Garcia-Villar R, Toutain PL, Alvinerie M, Ruckebusch Y. The pharmacokinetics of xylazine hydrochloride: An interspecific study. Journal of Veterinary Pharmacology and Therapeutics 4(2), 87-92.
  13. Gozalo-Marcilla M, Hopster K, Gasthuys F, Hatz L, Krajewski AE, Schauvliege S. Effects of a constant-rate infusion of dexmedetomidine on the minimal alveolar concentration of sevoflurane in ponies. Equine Veterinary Journal 45(2), 204-208.
  14. Gozalo-Marcilla M, Steblaj B, Schauvliege S, Duchateau L, Gasthuys F. Comparison of the influence of two different constant-rate infusions (dexmedetomidine versus morphine) on anaesthetic requirements, cardiopulmonary function and recovery quality in isoflurane anaesthetized horses. Research in Veterinary Science 95(3), 1186-1194.
  15. Guedes AGP, Tearney CC, Cenani A, Aristizabal F, Nieto J. Comparison between the effects of postanesthetic xylazine and dexmedetomidine on characteristics of recovery from sevoflurane anesthesia in horses. Veterinary Anaesthesia and Analgesia 44(2), 273-280.
    doi: 10.1016/j.vaa.2016.04.002google scholar: lookup
  16. Hinkle DE, Wiersma W, Jurs SG. Applied statistics for the behavioral sciences. .
  17. Hubbell JA. Recovery from anaesthesia in horses. Equine Veterinary Education 11(3), 160-167.
  18. Johnston GM, Eastment JK, Wood JLN, Taylor PM. The confidential enquiry into perioperative equine fatalities (CEPEF): Mortality results of phases 1 and 2. Veterinary Anaesthesia and Analgesia 29(4), 159-170.
  19. Kuusela E, Raekallio M, Anttila M, Falck I, Molsa S, Vainio O. Clinical effects and pharmacokinetics of medetomidine and its enantiomers in dogs. Journal of Veterinary Pharmacology and Therapeutics 23(1), 15-20.
  20. Marcilla MG, Schauvliege S, Duchateau L, Gasthuys F. Cardiopulmonary effects of two constant rate infusions of dexmedetomidine in isoflurane anaesthetized ponies. Veterinary Anaesthesia and Analgesia 37(4), 311-321.
  21. Marcilla MG, Schauvliege S, Segaert S, Duchateau L, Gasthuys F. Influence of a constant rate infusion of dexmedetomidine on cardiopulmonary function and recovery quality in isoflurane anaesthetized horses. Veterinary Anaesthesia and Analgesia 39(1), 49-58.
  22. Matthews NS, Hartsfield SM, Mercer D, Beleau MH, MacKenthun A. Recovery from sevoflurane anesthesia in horses: Comparison to isoflurane and effect of postmedication with xylazine. Veterinary Surgery 27(5), 480-485.
  23. PubChem. Xylazine. .
  24. Pypendop BH, Ilkiw JE. Pharmacokinetics of dexmedetomidine after intravenous administration of a bolus to cats. American Journal of Veterinary Research 75(5), 441-445.
    doi: 10.2460/ajvr.75.5.441google scholar: lookup
  25. Rezende ML, Grimsrud KN, Stanley SD, Steffey EP, Mama KR. Pharmacokinetics and pharmacodynamics of intravenous dexmedetomidine in the horse. Journal of Veterinary Pharmacology and Therapeutics 38(1), 15-23.
    doi: 10.1111/jvp.12138google scholar: lookup
  26. Santonastaso A, Hardy J, Cohen N, Fajt V. Pharmacokinetics and pharmacodynamics of xylazine administered by the intravenous or intra-osseous route in adult horses. Journal of Veterinary Pharmacology and Therapeutics 37(6), 565-570.
    doi: 10.1111/jvp.12136google scholar: lookup
  27. Santos M, Fuente M, Garcia-Iturralde R, Herran R, Lopez-Sanroman J, Tendillo FJ. Effects of alpha-2 adrenoceptor agonists during recovery from isoflurane anaesthesia in horses. Equine Veterinary Journal 35(2), 170-175.
  28. Schwartz DD, Clark TP. Affinity of detomidine, medetomidine and xylazine for alpha-2 adrenergic receptor subtypes. Journal of Veterinary Pharmacology and Therapeutics 21(2), 107-111.
  29. Steffey EP, Howland D Jr, Giri S, Eger EI II. Enflurane, halothane, and isoflurane potency in horses. American Journal of Veterinary Research 38(7), 1037-1039.
  30. Valente AC, Brosnan RJ, Guedes AG. Desflurane and sevoflurane elimination kinetics and recovery quality in horses. American Journal of Veterinary Research 76(3), 201-207.
    doi: 10.2460/ajvr.76.3.201google scholar: lookup
  31. Virtanen R, Savola JM, Saano V, Nyman L. Characterization of the selectivity, specificity and potency of medetomidine as an alpha 2-adrenoceptor agonist. European Journal of Pharmacology 150(1-2), 9-14.
  32. Whitehair KJ, Steffey EP, Willits NH, Woliner MJ. Recovery of horses from inhalation anesthesia. American Journal of Veterinary Research 54(10), 1693-1702.
  33. Yamaoka K, Nakagawa T, Uno T. Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations. Journal of Pharmacokinetics and Biopharmaceutics 6(2), 165-175.
    doi: 10.1007/bf01117450google scholar: lookup

Citations

This article has been cited 5 times.
  1. Tucker L, Almeida D, Wendt-Hornickle E, Baldo CF, Allweiler S, Guedes AGP. Effect of 15° Reverse Trendelenburg Position on Arterial Oxygen Tension during Isoflurane Anesthesia in Horses. Animals (Basel) 2022 Feb 1;12(3).
    doi: 10.3390/ani12030353pubmed: 35158676google scholar: lookup
  2. Cunneen A, Pratt S, Perkins N, McEwen M, Truchetti G, Rainger J, Farry T, Kidd L, Goodwin W. Total Intravenous Anaesthesia with Ketamine, Medetomidine and Midazolam as Part of a Balanced Anaesthesia Technique in Horses Undergoing Castration. Vet Sci 2021 Jul 26;8(8).
    doi: 10.3390/vetsci8080142pubmed: 34437464google scholar: lookup
  3. Gozalo-Marcilla M, Ringer SK. Recovery after General Anaesthesia in Adult Horses: A Structured Summary of the Literature. Animals (Basel) 2021 Jun 14;11(6).
    doi: 10.3390/ani11061777pubmed: 34198637google scholar: lookup
  4. Di Cesare F, Rabbogliatti V, Draghi S, Amari M, Brioschi FA, Villa R, Ravasio G, Cagnardi P. Pharmacokinetics of dexmedetomidine in anaesthetized horses following repeated subcutaneous administration and intravenous constant rate infusion. BMC Vet Res 2023 Dec 9;19(1):264.
    doi: 10.1186/s12917-023-03831-wpubmed: 38071301google scholar: lookup
  5. Ruíz-López P, Cuypers C, Schauvliege S. Xylazine Infusion during Equine Colic Anesthesia with Isoflurane and Lidocaine: A Retrospective Study. Animals (Basel) 2023 Sep 13;13(18).
    doi: 10.3390/ani13182902pubmed: 37760302google scholar: lookup