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Effects of a low dose infusion of racemic and S-ketamine on the nociceptive withdrawal reflex in standing ponies |
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| Authors: | Peterbauer Christoph Larenza Paula M Knobloch Monika Theurillat Regula Thormann Wolfgang Mevissen Meike Spadavecchia Claudia |
| Affiliation: | Anaesthesiology Section, Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University Berne, Switzerland; Department of Clinical Pharmacology, University of Berne, Switzerland; Division of Veterinary Pharmacology &Toxicology, Vetsuisse Faculty, University of Berne, Switzerland; Department of Companion Animal Clinical Sciences, Norwegian School of Veterinary Science, Oslo, Norway |
| Abstract: | ObjectiveTo investigate the effect of plasma concentrations obtained by a low dose constant rate infusion (CRI) of racemic ketamine or S-ketamine on the nociceptive withdrawal reflex (NWR) in standing ponies.Study designProspective, blinded, cross-over study.AnimalsSix healthy 5-year-old Shetland ponies.MethodsPonies received either 0.6 mg kg−1 racemic ketamine (group RS) or 0.3 mg kg−1 S-ketamine (group S) intravenously (IV), followed by a CRI of 20 μg kg−1minute−1 racemic ketamine (group RS) or 10 μg kg−1minute−1 S-ketamine (group S) for 59 minutes. The NWR was evoked by transcutaneous electrical stimulation of a peripheral nerve before drug administration, 15 and 45 minutes after the start of the bolus injection and 15 minutes after the end of the CRI. Electromyographic responses were recorded and analysed. Arterial blood was collected before stimulation and plasma concentrations of ketamine and norketamine were measured enantioselectively using capillary electrophoresis. Ponies were video recorded and monitored to assess drug effects on behaviour, heart rate (HR), mean arterial blood pressure (MAP) and respiratory rate.ResultsThe NWR was significantly depressed in group RS at plasma concentrations between 20 and 25 ng mL−1 of each enantiomer. In group S, no significant NWR depression could be observed; plasma concentrations of S-ketamine (9–15 ng mL−1) were lower, compared to S-ketamine concentrations in group RS, although this difference was not statistically significant. Minor changes in behaviour, HR and MAP only occurred within the first 5–10 minutes after bolus drug administration in both groups.ConclusionAntinociceptive activity in standing ponies, demonstrated as a depression of the NWR, could only be detected after treatment with racemic ketamine. S-ketamine may have lacked this effect as a result of lower plasma concentrations, a more rapid metabolism or a lower potency of S-ketamine in Equidae so further investigation is necessary. |
| Keywords: | capillary electrophoresis constant rate infusion nociceptive withdrawal reflex plasma concentration pony racemic ketamine S-ketamine |
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