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Open Access Research article

A comparison of medetomidine and its active enantiomer dexmedetomidine when administered with ketamine in mice

Wesley M Burnside12, Paul A Flecknell1, Angus I Cameron3 and Aurélie A Thomas1*

Author Affiliations

1 Comparative Biology Centre, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, United Kingdom

2 School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Bearsden Road, Glasgow, G61 1QH, United Kingdom

3 Boyd Orr Centre for population and ecosystem health, Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, United Kingdom

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BMC Veterinary Research 2013, 9:48  doi:10.1186/1746-6148-9-48

Published: 13 March 2013

Abstract

Background

Medetomidine-ketamine (MK) and dexmedetomidine-ketamine (DK) are widely used to provide general anaesthesia in laboratory animals, but have not been compared directly in many of these species, including rodents. This study aimed to compare the onset and depth of anaesthesia, and changes in vital signs, after intraperitoneal (IP) or subcutaneous (SC) administration of ketamine (75 mg kg-1) combined with medetomidine (1 mg kg-1) or dexmedetomidine (0.5 mg kg-1) using a randomised semi-crossover design with ≥ 48 hours between treatments in 10 male and 10 female mice. Each mouse was anaesthetised twice using the same administration route (IP or SC): once with each drug-ketamine combination. Anaesthetised mice were monitored on a heating pad without supplemental oxygen for 89 minutes; atipamezole was administered for reversal. The times that the righting reflex was lost post-injection and returned post-reversal were analysed using general linear models. Tail-pinch and pedal reflexes were examined using binomial generalized linear models. Pulse rate (PR), respiratory rate (fr), and arterial haemoglobin saturation (SpO2) were compared using generalized additive mixed models.

Results

There were no significant differences among treatments for the times taken for loss and return of the righting reflex, or response of the tail-pinch reflex. The pedal withdrawal reflex was abolished more frequently with MK than DK over time (P = 0.021). The response of PR and SpO2 were similar among treatments, but fr was significantly higher with MK than DK (P ≤ 0.0005). Markedly low SpO2 concentrations occurred within 5 minutes post-injection (83.8 ± 6.7%) in all treatment groups and were most severe after 89 minutes lapsed (66.7 ± 7.5%). No statistical differences were detected in regards to administration route (P ≤ 0.94).

Conclusions

This study failed to demonstrate clinical advantages of the enantiomer dexmedetomidine over medetomidine when combined with ketamine to produce general anaesthesia in mice. At the doses administered, deep surgical anaesthesia was not consistently produced with either combination; therefore, anaesthetic depth must be assessed before performing surgical procedures. Supplemental oxygen should always be provided during anaesthesia to prevent hypoxaemia.

Keywords:
Alpha-2 agonists; Dexmedetomidine; Drug administration route; General anaesthesia; Hypoxaemia; Ketamine; Mouse; Medetomidine; Subcutaneous injection; Supplemental oxygen