Optimization of intraperitoneal injection anesthesia in mice: Drugs, dosages, adverse effects, and anesthesia depth

Purpose. The goals of the study were to find a safe intraperitoneal injecti on anesthesia protocol for medium-duration surgery in mice (e.g., embryo tr ansfer/vasectomy) coupled with a simple method to assess anesthesia depth u nder routine laboratory conditions. Methods: Eight anesthetic protocols consisting of combinations of dissociat ive anesthetics (ketamine, tiletamine), alpha (2)-agonists (xylazine, medet omidine), and/or sedatives (acepromazine, azaperone, zolazepam) were compar ed for their safety and efficacy (death rate, surgical tolerance), using ob servations and reflex tests. The four best protocols were further evaluated during vasectomy: physiologic measurements (respiratory rate, electrocardi ogram, arterial blood pressure, body temperature, blood gas tensions, and a cid-base balance) were used to characterize the quality of anesthesia. The reactions of physiologic parameters to surgical stimuli were used to determ ine anesthesia depth, and were correlated with reflex test results. Results. The protocol with the highest safety margin and the longest time o f surgical tolerance (54 min) was ketamine/xylazine/acepromazine. Three fur ther anesthetic combinations were associated with surgical tolerance: ketam inet xylazine, ketamine/xylazine/azaperone, and tiletamine/xylazine/zolazep am (Telazol/xylazine). The protocols consisting of ketamine/medetomidine an d ketamine/azaperone were not associated with clearly detectable surgical t olerance. The most reliable parameter of surgical tolerance under routine l aboratory conditions was the pedal withdrawal reflex. Conclusions: The best intraperitoneal injection anesthesia regimen consiste d of ketamine/xylazine/acepromazine. The dose must be adapted to the partic ulars of each experimental design (mouse strain, sex, age, mutation). This is best done by measuring surgical tolerance, using the pedal withdrawal re flex.