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

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 (S(p)O2) 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 S(p)O2 were similar among treatments, but fr was significantly higher with MK than DK (P ≤ 0.0005). Markedly low S(p)O2 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.

Figure 1

Loss and return of the righting reflex. Mean time (seconds) until loss of the righting reflex (LORR) and return of the righting reflex (RORR) after administration of medetomidine-ketamine (MK) or dexmedetomidine-ketamine (DK) by the intraperitoneal (IP) or subcutaneous (SC) route. The time to LORR was not significantly affected by drug (P = 0.29) or administration route (P = 0.71). Similarly, the time until RORR was not significantly affected by drug (P = 0.61) or administration route (P = 0.18).

Figure 2

Tail-pinch and pedal reflexes. Percentage of individuals with present tail-pinch and pedal withdrawal reflexes after administration of medetomidine-ketamine (MK) or dexmedetomidine-ketamine (DK) over time. Loss of the tail-pinch reflex did not significantly differ between drug combination (P = 0.36). Pedal withdrawal reflex loss was not consistently achieved by either drug combination, but was more frequent with MK than DK over time (P = 0.021).

Figure 3

Vital signs. Mean pulse rate (PR) and respiratory rate (fr) after administration of medetomidine-ketamine (MK) or dexmedetomidine-ketamine (DK), and arterial haemoglobin saturation (S_pO₂) after drug administration by the intraperitoneal (IP) or subcutaneous (SC) route over time. Although means were not used to determine statistical significance, they effectively display data trends.