Effects of a low dose infusion of racemic and S-ketamine on the nociceptive withdrawal reflex in standing ponies.

The study investigates the impact of low dose constant rate infusion of two variations of ketamine – racemic and S-ketamine – on the pain reflex, or nociceptive withdrawal reflex (NWR), in standing ponies.

Methodology

• The study was a prospective, blinded, cross-over with six healthy 5-year-old Shetland ponies as the subjects.
• The ponies were given either 0.6 mg kg(-1) racemic ketamine or 0.3 mg kg(-1) S-ketamine through intravenous (IV) routes.
• This was followed by an infusion rate of 20 microg kg(-1)minute(-1) for racemic ketamine and 10 microg kg(-1)minute(-1) for S-ketamine lasting 59 minutes.
• The Nociceptive Withdrawal Reflex (NWR) was evoked through transcutaneous electrical stimulation of a peripheral nerve before the drug administration, 15 and 45 minutes after the start of the bolus injection and 15 minutes after the end of the CRI.
• They monitored the reactions using electromyographic responses and took arterial blood to measure plasma concentrations of ketamine and norketamine. They used capillary electrophoresis for enantioselective analysis.
• They also recorded video of the ponies and monitored their behaviour, heart rate, arterial blood pressure, and respiratory rate.

Results

• The results showed that the NWR was significantly depressed in the group of ponies that received racemic ketamine with plasma concentrations between 20 and 25 ng mL(-1) of each enantiomer.
• The ponies that received S-ketamine did not exhibit a significant depression of the NWR.
• Plasma concentrations of S-ketamine were lower compared to those in the group that received racemic ketamine but the difference was not statistically significant.
• Minor changes in behaviour, heart rate, and mean arterial blood pressure were only observed within the first 5-10 minutes after the bolus drug administration in both groups.

Conclusion

• The study concluded that the suppression of the NWR, or antinociceptive activity in standing ponies, could only be observed after treatment with racemic ketamine.
• The researchers suggest that the lack of this effect in S-ketamine could have been due to its lower plasma concentration, a more rapid metabolism, or that it has a lower potency in Equidae (horse family animals). They recommend further research to fully understand these outcomes.