Effects of Ketamine Compared with Urethane Anesthesia on Vestibular Sensory Evoked Potentials and Systemic Physiology in Mice

The injectable anesthetic mixture ketamine–xylazine is commonly used for electrophysiologic experiments in laboratory animals, especially rodents. General anesthesia can induce significant changes in systemic physiology, including those that compromise neural function, thus introducing research confounds. The extent of such concerns varies by agent. Here in mice, we compared the effects of ketamine–xylazine and urethane–xylazine anesthesia on systemic physiologic parameters and the vestibular sensory evoked potential (VsEP), a tool used commonly to assess peripheral vestibular function. Urethane–xylazine anesthesia provided longer anesthesia, prolonged survival times, and less compromised respiratory and cardiovascular function, compared with ketamine–xylazine. In the absence of countermeasures, mice anesthetized with either ketamine–xylazine or urethane–xylazine showed evidence of hypoxemia and fluctuations in brain temperature, heart rate, respiration rate, and VsEP response latency. The levels of hypoxemia had no effect on VsEP response parameters over the period of study (2 to 5 h). Hypoxemia was effectively countered with O₂ supplementation, which stabilized respiratory rates and improved mean survival times by 160% in mice anesthetized with ketamine–xylazine. Monitoring and controlling brain temperature reduced variation in VsEP latency. VsEP thresholds, latencies, and amplitudes did not differ between mice under ketamine–xylazine compared with urethane–xylazine when the brain temperature was held at the same set point. These findings demonstrate that urethane–xylazine provides improved systemic physiologic conditions during anesthesia in mice and may be substituted for ketamine–xylazine in studies using the VsEP to evaluate peripheral vestibular function. Such advantages may prove useful to research in other neuroscience areas and might reduce the number of animals used to achieve adequate sample sizes.