Optimization of Ketamine/Xylazine Anesthesia in Geriatric Mice

Aged mice are becoming increasingly important models for human senescence. Many studies require anesthesia. Standard rodent ketamine/xylazine injectable regimens have been associated with increased incidences of death, unreliable surgical planes, and prolonged recoveries in geriatric mice. We hypothesized that the addition of atipamezole reversal and higher doses of ketamine or xylazine would result in a more reliable surgical plane of anesthesia and quicker recovery in geriatric mice without increasing mortality. Mice (n = 6 per group) were subjected to one of 3 anesthetic regimens: 100 mg/kg ketamine and 10 mg/kg xylazine without reversal (Standard); 150 mg/kg ketamine and 10 mg/kg xylazine with 1 mg/kg atipamezole reversal (High Ketamine); or 100 mg/kg ketamine and 15 mg/kg xylazine with 1 mg/kg atipamezole reversal (High Xylazine). While anesthetized, righting reflex, pedal withdrawal reflex, heart rate, respiratory rate, arterial oxygen saturation (SpO2), and temperature were recorded. While both experimental groups provided a more consistent surgical plane of anesthesia, the High Ketamine group had both the longest anesthetic period and the highest mortality (33.3%). The High Xylazine group had moderate mortality (16.6%) and a comparable anesthetic period to the Standard regimen, along with a superior SpO2 to both groups. Atipamezole reversal led to a faster return of righting reflex and an increase in SpO2 but did not affect the total length of recovery compared with the Standard group that did not include a reversal agent. Overall, the High Xylazine group provided a more reliable surgical plane to the Standard group in geriatric mice but increased mortality (16.6%), and the addition of atipamezole as a reversal agent did not significantly change the length of recovery. The information gained from this study can help guide decisions regarding the use of ketamine and xylazine in geriatric mice for surgical procedures or lengthy procedures for which redosing might be necessary.