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Journal of equine veterinary science2026; 106109; doi: 10.1016/j.jevs.2026.106109

Comparison of xylazine-ketamine-guaifenesin and xylazine-tiletamine-zolazepam protocols for constant rate infusion anesthesia in horses undergoing field castration.

Abstract: The common use of "triple drip" (xylazine, ketamine, and guaifenesin; XKG) is a popular protocol for constant rate infusion (CRI) in equine practice. However, due to restrictions on ketamine and guaifenesin in many countries, tiletamine-zolazepam (TZ) could serve as an alternative. To date, there have been limited studies evaluating the use of xylazine in combination with TZ (XTZ) administered via CRI to maintain surgical anesthesia in equine field practice. Objective: To compare the effectiveness and safety of XTZ infusion with the classical XKG protocol for field anesthesia. Methods: Twelve healthy stallions were randomly allocated to two groups (XKG and XTZ) for castration. All horses were premedicated with xylazine at 1 mg/kg intravenously (IV). The XKG group received ketamine at 2 mg/kg IV for induction, followed by maintenance with xylazine 1.375 mg/kg/h, ketamine 2.75 mg/kg/h and guaifenesin 68.75 mg/kg/h The XTZ group was induced with TZ at 1 mg/kg IV and maintained with xylazine 0.75 mg/kg/h and TZ 1.5 mg/kg/h RESULTS: No clinically significant differences of anesthetic effects and cardiorespiratory parameters were observed between the XTZ and XKG formulation. Conclusions: The preparation of the CRI XTZ might be effectively alternated the triple drip for maintaining anesthesia in equine field practice.
Publication Date: 2026-08-03 PubMed ID: 42546860DOI: 10.1016/j.jevs.2026.106109Google Scholar: Lookup
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Summary

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Overview

  • This study evaluated and compared two anesthesia protocols for horses undergoing castration in the field: the traditional xylazine-ketamine-guaifenesin (XKG) “triple drip” and an alternative xylazine-tiletamine-zolazepam (XTZ) protocol.
  • The study found that the XTZ protocol provided similar anesthetic effectiveness and cardiorespiratory stability to the classical XKG protocol, suggesting XTZ could be a viable alternative where ketamine and guaifenesin use is restricted.

Background and Rationale

  • Constant rate infusion (CRI) anesthesia using a combination of drugs is common in equine surgeries, particularly in field conditions where equipment and facilities are limited.
  • The “triple drip” protocol—xylazine, ketamine, and guaifenesin (XKG)—is widely used for maintaining surgical anesthesia because of its balanced effects and safety profile.
  • However, many countries impose legal restrictions on the use of ketamine and guaifenesin, limiting the use of the standard triple drip approach.
  • Tiletamine-zolazepam (TZ), a combination of dissociative anesthetic and benzodiazepine, is a potential alternative anesthetic agent that could replace ketamine and guaifenesin in CRI protocols.
  • Prior to this study, limited research had assessed how well xylazine combined with TZ (XTZ) worked for CRI anesthesia in equines in field settings.

Study Objective

  • The main goal was to compare the anesthetic effectiveness and safety of the XTZ protocol against the classical XKG triple drip protocol in horses undergoing field castration.

Methods

  • Twelve healthy stallions were randomly assigned to one of two groups (6 horses per group): XKG or XTZ.
  • All horses were premedicated with intravenous xylazine at 1 mg/kg to induce sedation.
  • For induction:
    • XKG group received ketamine 2 mg/kg IV.
    • XTZ group received tiletamine-zolazepam (TZ) 1 mg/kg IV.
  • For maintenance anesthesia via CRI:
    • XKG group: xylazine 1.375 mg/kg/h, ketamine 2.75 mg/kg/h, guaifenesin 68.75 mg/kg/h.
    • XTZ group: xylazine 0.75 mg/kg/h, tiletamine-zolazepam 1.5 mg/kg/h.
  • Parameters measured included anesthetic depth and cardiorespiratory functions to assess safety and effectiveness.

Results

  • No clinically significant differences were observed between the two groups in terms of anesthetic effects.
  • Cardiorespiratory parameters, such as heart rate, respiratory rate, and blood pressure, were comparable between XKG and XTZ protocols.
  • This indicates that both protocols maintained stable anesthesia and vital signs during the surgical procedure.

Conclusions

  • The tiletamine-zolazepam based CRI combined with xylazine (XTZ) effectively maintained anesthesia in horses undergoing castration in field conditions.
  • The XTZ protocol may serve as a practical alternative to the classical triple drip (XKG), particularly in regions where ketamine and guaifenesin availability is restricted.
  • This alternative could allow veterinarians greater flexibility in anesthetic protocols without compromising safety or efficacy during field surgeries.

Implications and Future Directions

  • The study supports the adoption of XTZ CRI protocols for equine field anesthesia when traditional drugs are unavailable or restricted.
  • Further larger-scale studies could confirm these findings and optimize dosing and administration protocols.
  • Additional research into recovery quality, long-term safety, and applicability in other types of equine surgeries would help validate the broader use of XTZ.

Cite This Article

APA
Maneephan P, Thepparat K, Suwanekkasit B, Limrodpai J, Sangbunjong A, Karkkaew P, Chantong B, Vinijkumthorn R. (2026). Comparison of xylazine-ketamine-guaifenesin and xylazine-tiletamine-zolazepam protocols for constant rate infusion anesthesia in horses undergoing field castration. J Equine Vet Sci, 106109. https://doi.org/10.1016/j.jevs.2026.106109

Publication

ISSN: 0737-0806
NlmUniqueID: 8216840
Country: United States
Language: English
Pages: 106109
PII: S0737-0806(26)00344-8

Researcher Affiliations

Maneephan, Photchanun
  • Equine Clinic, Prasu Arthorn Veterinary Teaching Hospital, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom, Thailand. Electronic address: photchanun.man@mahidol.ac.th.
Thepparat, Krittima
  • 6(th) year student, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom, Thailand. Electronic address: krittima.bon@student.mahidol.edu.
Suwanekkasit, Benjawan
  • 6(th) year student, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom, Thailand. Electronic address: benjawan.suw@student.mahidol.edu.
Limrodpai, Jirakarn
  • 6(th) year student, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom, Thailand. Electronic address: jirakarn.lim@student.mahidol.edu.
Sangbunjong, Athicha
  • 6(th) year student, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom, Thailand. Electronic address: athicha.sag@student.mahidol.edu.
Karkkaew, Prem
  • 6(th) year student, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom, Thailand. Electronic address: prem.kar@student.mahidol.edu.
Chantong, Boonrat
  • Department of Pre-Clinic and Applied Animal Science, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom, Thailand. Electronic address: boonrat.cha@mahidol.ac.th.
Vinijkumthorn, Ruethaiwan
  • Department of Clinical Sciences and Public Health, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom, Thailand,. Electronic address: ruethaiwan.vin@mahidol.ac.th.

Conflict of Interest Statement

Declaration of competing interest I have nothing to declare.

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