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

Abstract

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.