Alfaxalone

To compare two immobilisation protocols for the restraint of urban red foxes: medetomidine-midazolam (MM) and alfaxalone-midazolam (AM).

Prospective, randomised clinical trial.

Fourteen urban red foxes (Vulpes vulpes) captured in the Dublin metropolitan area.

Foxes were randomly assigned to receive either MM [medetomidine 0.07 mg kg^-1, midazolam 0.8 mg kg^-1 intramuscularly (IM)] or AM (alfaxalone 3 mg kg^-1, midazolam 0.8 mg kg^-1 IM). Sedation and recovery were scored. Recovery times and physiological variables [heart rate, respiratory rate (f_R), oscillometric arterial blood pressure, arterial haemoglobin oxygen saturation (SpO₂) and rectal temperature] were measured. Hair and blood samples were collected for cortisol analysis. Sedation was reversed with atipamezole (0.35 mg kg^-1 IM) and/or flumazenil (0.01 mg kg^-1 IM). Recovery ended when foxes walked with coordinated movements. Data were analysed using linear and mixed-effects models.

Seven foxes were given MM and seven AM. Median sedation scores were higher in MM (14.5 versus 12.5; p = 0.048), with shorter reversal times (25 versus 54 minutes; p = 0.009). Heart rate was lower (80 versus 216 beats per minute^-1; p < 0.001) and mean arterial blood pressure higher (147 versus 110 mmHg; p < 0.001) in MM. SpO₂ was higher in AM (95 versus 91%; p = 0.015). Rectal temperature was higher in MM (38.6 versus 36.5 °C; p < 0.001), with a faster decrease in AM (p = 0.006). f_R did not differ between groups (p = 0.492) but increased with higher ambient temperature (p = 0.04) and decreased with higher hair cortisol levels (p = 0.02).

Both protocols provided sufficient sedation for intended procedures. MM resulted in higher sedation scores and faster recovery after antagonist administration, while AM provided higher SpO₂ and heart rates and lower rectal temperature values.

Injectable anesthetics are commonly used in murine experimental procedures. However, these agents may result in neurotoxicity, which should be considered in interpretation of experimental results. We evaluated acute effects of 2 different anesthetic combinations on juvenile mouse brain development using structural MRI to assess impact on the brain. We compared the use of ketamine-xylazine, a commonly used injectable anesthetic combination in mice, to alfaxalone-xylazine in the context of noninvasive procedures requiring immobilization (that is, not a surgical plane of anesthesia). In this longitudinal study, we used MRI to produce three-dimensional scans of mouse brains at 2 time points (postnatal days 14 and 23), analogous to early childhood to prepubescence in humans. At postnatal day 16, mice were either dosed with ketamine-xylazine, alfaxalone-xylazine, or left untreated. From the scans, we quantified whole brain and structure volumes across the brain, comparing growth between time points and modeling the effect of both anesthetics compared with controls. Anesthetic parameters were measured, and general health and welfare were monitored during and after each injectable anesthesia drug condition. Results indicate that systemic and brain toxicity were reduced in mice treated with alfaxalone-xylazine compared with ketamine-xylazine. In addition, both ketamine-xylazine and alfaxalone-xylazine reliably anesthetized all mice, although mice administered ketamine-xylazine showed increased weight loss compared with the alfaxalone-xylazine in the postanesthetic period. These findings highlight alfaxalone-xylazine as a convenient and possibly safer alternative anesthetic for mouse brain development studies when compared with ketamine-xylazine and as a viable option as an injectable anesthetic in juvenile mice.