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Clinical application of different constant rate infusions of detomidine and methadone in standing horses

Grant number: 17/01425-6
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): June 01, 2017
Effective date (End): February 28, 2018
Field of knowledge:Agronomical Sciences - Veterinary Medicine - Animal Clinics and Surgery
Principal researcher:Stelio Pacca Loureiro Luna
Grantee:Miguel Gozalo Marcilla
Supervisor abroad: Stijn Schauvliege
Home Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Research place: Ghent University (UGent), Belgium  
Associated to the scholarship:14/00474-5 - Antinociceptive effects and farmacokinetics in horses treated with different low doses of methadone and detomidine, BP.PD


There is currently an increasing tendency in equine practice to avoid the risks of general anaesthesia by applying standing sedation protocols for procedures lasting longer than 45 to 60 minutes. The use of intravenous (IV) constant rate infusions (CRIs) is mandatory to produce steady-state plasma concentrations, avoiding the peaks and troughs associated with bolus administrations. The use of detomidine CRIs for standing sedation in horses has been reported mainly as a sole infusion, after sedation with detomidine alone, or associated with opioids, such as morphine and buprenorphine, with the aim of potentiating sedation and providing analgesia. Up to date, there are no clinical studies reporting the co-administration of a detomidine CRI combined with an opioid infusion, such as methadone. Our post-doctoral research has shown, up to now, that an IV bolus of methadone (0.2 mg/kg) potentiated the antinociception produced by detomidine at 5 and 10 µg/kg. It was clear that the adverse effects such as deep sedation, ataxia and prolonged intestinal hypomotiliy were diminished when methadone was combined with 5 µg/kg detomidine compared to the higher dose. Pharmacokinetic data were obtained in the last semester of 2016 and modelling of the pharmacokinetic and pharmacodynamic data will be performed in February 2017, during the visit of the applicant to the Royal Veterinary College (RVC) of London. With that data, different protocols for medium and long-term sedation will be determined and their sedative and antinociceptive properties tested under experimental circumstances (March to May 2017). With those results, and with the absence of large clinical studies, we are applying for this BEPE grant to test our protocols in a well-known institution, with a large caseload that may be applicable for our research. This international cooperation would allow us to finalize our project testing our techniques in a real-life scenario. Furthermore, as explained in the project, additional research is proposed, which involves the design of a scale of post-operative pain in horses recently published by the supervisor of this project, Prof. Dr. Stelio Pacca Loureiro Luna. This work was supported by the FAPESP (2010/08967-0 and 2010/00786-6) and the stay of the applicant in Ghent may be used for the validation of that scale too.

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Scientific publications (7)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
GOZALO-MARCILLA, MIGUEL; LOUREIRO LUNA, STELIO PACCA; GASTHUYS, FRANK; SCHAUVLIEGE, STIJN. Thermal, mechanical and electrical stimuli in antinociceptive studies in standing horses: an update. VETERINARY ANAESTHESIA AND ANALGESIA, v. 47, n. 1, p. 15-27, JAN 2020. Web of Science Citations: 0.
GOZALO-MARCILLA, MIGUEL; DA SILVA, RODRIGO MOREIRA; LOUREIRO LUNA, STELIO PACCA; DE OLIVEIRA, ALICE RODRIGUES; FONSECA, MARIANA WERNECK; LOPES, NORBERTO PEPORINE; TAYLOR, POLLY M.; PELLIGAND, LUDOVIC. A possible solution to model nonlinearity in elimination and distributional clearances with alpha(2)-adrenergic receptor agonists: Example of the intravenous detomidine and methadone combination in sedated horses. JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS, v. 42, n. 6, p. 738-744, NOV 2019. Web of Science Citations: 0.
GOZALO-MARCILLA, M.; DE OLIVEIRA, A. R.; FONSECA, M. W.; POSSEBON, F. S.; PELLIGAND, L.; TAYLOR, P. M.; LUNA, S. P. L. Sedative and antinociceptive effects of different detomidine constant rate infusions, with or without methadone in standing horses. EQUINE VETERINARY JOURNAL, v. 51, n. 4, p. 530-536, JUL 2019. Web of Science Citations: 3.
GOZALO-MARCILLA, M.; LUNA, S. P. L.; MOREIRA DA SILVA, R.; CROSIGNANI, N.; LOPES, N. P.; TAYLOR, P. M.; PELLIGAND, L. Characterisation of the in vivo interactions between detomidine and methadone in horses: Pharmacokinetic and pharmacodynamic modelling. EQUINE VETERINARY JOURNAL, v. 51, n. 4, p. 517-529, JUL 2019. Web of Science Citations: 3.
GOZALO-MARCILLA, MIGUEL; LUNA, STELIO P. L.; GASTHUYS, FRANK; POLLARIS, ELKE; VLAMINCK, LIEVEN; MARTENS, ANN; HASPESLAGH, MAARTEN; SCHAUVLIEGE, STIJN. Clinical applicability of detomidine and methadone constant rate infusions for surgery in standing horses. VETERINARY ANAESTHESIA AND ANALGESIA, v. 46, n. 3, p. 325-334, MAY 2019. Web of Science Citations: 1.
SCHAUVLIEGE, STIJN; CUYPERS, CHARLOTTE; MICHIELSEN, ANNELEEN; GASTHUYS, FRANK; GOZALO-MARCILLA, MIGUEL. How to score sedation and adjust the administration rate of sedatives in horses: a literature review and introduction of the Ghent Sedation Algorithm. VETERINARY ANAESTHESIA AND ANALGESIA, v. 46, n. 1, p. 4-13, JAN 2019. Web of Science Citations: 2.
GOZALO-MARCILLA, M.; GASTHUYS, F.; LUNA, S. P. L.; SCHAUVLIEGE, S. Is there a place for dexmedetomidine in equine anaesthesia and analgesia? A systematic review (2005-2017). JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS, v. 41, n. 2, p. 205-217, APR 2018. Web of Science Citations: 5.

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