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.
Kaplan–Meier curve showing probability of recovery occurring after the corresponding time point postreversal injection in minutes for the Standard (red), High Ketamine (green), and High Xylazine (blue) groups. The y-axis shows probability of recovery occurring after the corresponding time point, and the x-axis shows the time in minutes postreversal injection. At the time of reversal injection (0 min), no mice have recovered; therefore, the probability that recovery occurs after this time point is 1.00. The black dashed lines represent median recovery times for each group. The colored tick marks represent animals that died before recovery. Log-rank P value comparing all groups is shown in the lefthand corner. Because no mice regained RR or recovered between induction and reversal injection, this period was excluded from analyses related to RR and recovery.
Kaplan–Meier curve showing probability of regaining righting reflex occurring after the corresponding time point postreversal injection in minutes for the Standard (red), High Ketamine (green), and High Xylazine (blue) groups. The y-axis shows probability of regaining righting reflex after the corresponding time point, and the x-axis shows the time in minutes postreversal injection. At the time of reversal injection (0 min), no mice have regained righting reflex; therefore, the probability that recovery occurs after this time point is 1.00. The black dashed lines represent median recovery times for each group. Log-rank P value comparing all groups is shown in the lefthand corner. Because no mice regained RR or recovered between induction and reversal injection, this period was excluded from analyses related to RR and recovery.
Kaplan–Meier curve showing probability of recovery occurring after the corresponding time point after regaining righting reflex for the Standard (red), High Ketamine (green), and High Xylazine (blue) groups. The y-axis shows probability of recovery occurring after the corresponding time point and the x-axis shows the time in minutes after regaining righting reflex. At the time that righting reflex is regained (0 min), no mice have recovered; therefore, the probability that recovery occurs after this time point is 1.00. The black dashed lines represent median recovery times for each group. The colored tick marks represent animals that died before recovery, with 2 tick marks overlaid. Log-rank P value comparing all groups is shown in the lefthand corner.
Boxplot comparing time to first loss of PWR from induction in minutes between the Standard, High Ketamine, and High Xylazine groups.
Boxplot comparing the length of longest surgical plane in minutes between the Standard, High Ketamine, and High Xylazine groups.
Line graph showing mean BR on the y-axis every 5 min from induction on the x-axis for the Standard (red), High Ketamine (green), and High Xylazine (blue) groups with points presenting means for each group at each time point. As mice regain righting reflex, their data are omitted, such that the data becomes noisier further along the x-axis as fewer mice are included in the mean. The vertical dashed line shows the time of injection of reversal or sham.
Line graph showing mean HR on the y-axis every 5 min from induction on the x-axis for the Standard (red), High Ketamine (green), and High Xylazine (blue) groups with points presenting means for each group at each time point. As mice regain righting reflex, their data are omitted, such that the data becomes noisier further along the x-axis as fewer mice are included in the mean. The vertical dashed line shows the time of injection of reversal or sham.
Line graph showing mean SpO2 on the y-axis every 5 min from induction on the x-axis for the Standard (red), High Ketamine (green), and High Xylazine (blue) groups with points presenting means for each group at each time point. As mice regain righting reflex, their data are omitted, such that the data becomes noisier further along the x-axis as fewer mice are included in the mean. The vertical dashed line shows the time of injection of reversal or sham.
Contributor Notes
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