Detomidine and the combination of detomidine and MK-467, a peripheral alpha-2 adrenoceptor antagonist, as premedication in horses anaesthetized with isoflurane.
Abstract: To investigate MK-467 as part of premedication in horses anaesthetized with isoflurane. Methods: Experimental, crossover study with a 14 day wash-out period. Methods: Seven healthy horses. Methods: The horses received either detomidine (20 μg kg(-1) IV) and butorphanol (20 μg kg(-1) IV) alone (DET) or with MK-467 (200 μg kg(-1) IV; DET + MK) as premedication. Anaesthesia was induced with ketamine (2.2 mg kg(-1) ) and midazolam (0.06 mg kg(-1) ) IV and maintained with isoflurane. Heart rate (HR), mean arterial pressure (MAP), end-tidal isoflurane concentration, end-tidal carbon dioxide tension, central venous pressure, fraction of inspired oxygen (FiO2 ) and cardiac output were recorded. Blood samples were taken for blood gas analysis and to determine plasma drug concentrations. The cardiac index (CI), systemic vascular resistance (SVR), ratio of arterial oxygen tension to inspired oxygen (Pa O2 /FiO2 ) and tissue oxygen delivery (DO2 ) were calculated. Repeated measures anova was applied for HR, CI, MAP, SVR, lactate and blood gas variables. The Student's t-test was used for pairwise comparisons of drug concentrations, induction times and the amount of dobutamine administered. Significance was set at p < 0.05. Results: The induction time was shorter, reduction in MAP was detected, more dobutamine was given and HR and CI were higher after DET+MK, while SVR was higher with DET. Arterial oxygen tension and Pa O2 /FiO2 (40 minutes after induction), DO2 and venous partial pressure of oxygen (40 and 60 minutes after induction) were higher with DET+MK. Plasma detomidine concentrations were reduced in the group receiving MK-467. After DET+MK, the area under the plasma concentration time curve of butorphanol was smaller. Conclusions: MK-467 enhances cardiac function and tissue oxygen delivery in horses sedated with detomidine before isoflurane anaesthesia. This finding could improve patient safety in the perioperative period. The dosage of MK-467 needs to be investigated to minimise the effect of MK-467 on MAP.
© 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.
Publication Date: 2014-12-22 PubMed ID: 25529045DOI: 10.1111/vaa.12238Google Scholar: Lookup
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- Controlled Clinical Trial
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates the effects of the drug MK-467 in combination with detomidine as a premedication for horses undergoing anaesthesia with isoflurane. Findings suggest that MK-467 enhances cardiac function and tissue oxygen delivery during anaesthesia, potentially improving patient safety, although the precise dosage requires further exploration.
Objective of the Experiment
- The key objective of the experiment was to explore the potential benefits of using MK-467 combined with detomidine as pre-anaesthetic medication for horses that were to be anaesthetized with isoflurane.
Methods
- Seven healthy horses were involved in this experimental, crossover study.
- Horses received either detomidine and butorphanol alone or with MK-467, with a two-week wash-out period in between treatments.
- Anaesthesia was induced with ketamine and midazolam, and maintained with isoflurane.
- Several health-indicators in the subjects were monitored – heart rate, mean arterial pressure, end-tidal isoflurane concentration, blood gas composition, central venous pressure, inspired oxygen fraction and cardiac output.
- Blood samples were taken for further analysis, and various other data were calculated, including cardiac index, systemic vascular resistance, ratio of arterial oxygen tension to inspired oxygen, and tissue oxygen delivery.
Results
- The results suggest that induction times were shorter when MK-467 was used, and more dobutamine was administered. Additionally, both heart rate and cardiac index were higher, while systemic vascular resistance was higher in horses pre-administered with just detomidine.
- Arterial oxygen tension and tissue oxygen delivery showed increases 40 and 60 minutes after induction with DET + MK compared to DET alone. Furthermore, plasma concentrations of detomidine were found to be reduced in the group given MK-467.
- The research suggests that MK-467 serves to enhance cardiac function and tissue oxygen delivery in horses sedated with detomidine before isoflurane anaesthesia.
Conclusion
- The research concludes that the use of MK-467 in combination with detomidine as a premedication before isoflurane anaesthesia results in improved cardiac function and tissue oxygen delivery.
- This has potential implications for improving patient safety during the perioperative period.
- However, the researchers note that further study is needed to determine the optimal dose of MK-467 to ensure its effect on mean arterial pressure is minimised.
Cite This Article
APA
Pakkanen SA, Raekallio MR, Mykkänen AK, Salla KM, de Vries A, Vuorilehto L, Scheinin M, Vainio OM.
(2014).
Detomidine and the combination of detomidine and MK-467, a peripheral alpha-2 adrenoceptor antagonist, as premedication in horses anaesthetized with isoflurane.
Vet Anaesth Analg, 42(5), 527-536.
https://doi.org/10.1111/vaa.12238 Publication
Researcher Affiliations
- Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
- Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
- Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
- Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
- Animal Health Trust, Newmarket, Suffolk, UK.
- Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
- Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland.
- Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
- Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland.
- Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
MeSH Terms
- Adrenergic alpha-2 Receptor Antagonists / administration & dosage
- Anesthesia, Inhalation / veterinary
- Anesthetics, Intravenous / administration & dosage
- Animals
- Arthroscopy / veterinary
- Cross-Over Studies
- Female
- Heart Rate / drug effects
- Horses / physiology
- Horses / surgery
- Imidazoles / administration & dosage
- Isoflurane / administration & dosage
- Male
- Premedication / veterinary
- Quinolizines / administration & dosage
- Treatment Outcome
Citations
This article has been cited 4 times.- Verhaar N, Kopp V, Pfarrer C, Neudeck S, König K, Rohn K, Kästner S. Alpha(2) Antagonist Vatinoxan Does Not Abolish the Preconditioning Effect of Dexmedetomidine on Experimental Ischaemia-Reperfusion Injury in the Equine Small Intestine. Animals (Basel) 2023 Aug 30;13(17).
- Savvas I, Pavlidou K, Braun C, Schauvliege S, Staffieri F, Moens Y. Evaluation of the Effect of the Inspired Oxygen Fraction on Blood Oxygenation during Inhalant Anaesthesia in Horses: A Systematic Review with Meta-Analysis. Animals (Basel) 2021 Jul 30;11(8).
- Williams MD, Long CT, Durrant JR, McKeon GP, Shive HR, Griffith EH, Messenger KM, Fish RE. Oral Transmucosal Detomidine Gel in New Zealand White Rabbits (Oryctolagus cuniculus). J Am Assoc Lab Anim Sci 2017 Jul 1;56(4):436-442.
- Taylor PM, Hoare HR, de Vries A, Love EJ, Coumbe KM, White KL, Murrell JC. A multicentre, prospective, randomised, blinded clinical trial to compare some perioperative effects of buprenorphine or butorphanol premedication before equine elective general anaesthesia and surgery. Equine Vet J 2016 Jul;48(4):442-50.
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