title: Anesthetic Activity of Alfaxalone Compared with Ketamine in Mice.
abstract: Alfaxalone encased in hydroxypropyl-β -cyclodextrin is a neuroactive steroid compound that has recently been approved in the United States for use as an anesthetic in dogs and cats. We evaluated the use of alfaxalone compared with ketamine, both alone and in combination with xylazine, for anesthesia of C57BL/6 mice. We assessed time to onset of anesthesia, duration of action, reflex responses, respiratory rate, and clinical signs. Alfaxalone (80 mg/kg IP) induced a light surgical plane of anesthesia in all mice, with a time to onset of 2.2 ± 0.2 min and duration of 57.1 ± 3.8 min, whereas ketamine (80 mg/kg IP) provided only sedative effects (time to onset, 5.4 ± 0.4 min; duration, 6.9 ± 0.8 min). Clinically, alfaxalone caused a spectrum of activities, including popcorn-like jumping movements after injection, intense scratching of the face, hyperresponsiveness to noise or touch, and marked limb jerking during recovery. Adding xylazine to the single-agent protocols achieved deep surgical anesthesia (duration: alfaxalone + xylazine, 80.3 ± 17.8 min; ketamine + xylazine, 37.4 ± 8.2 min) and ameliorated the adverse clinical signs. Our preliminary analysis suggests that, because of its side effects, alfaxalone alone is not a viable anesthetic option for mice. Although alfaxalone combined with xylazine appeared to be a more viable option, some mice still experienced mild adverse reactions, and the long duration of action might be problematic regarding the maintenance of body temperature and monitoring of recovery. Further studies evaluating different routes of administration and drug combinations are warranted.
authors.affiliation: Department of Pharmaceutical and Natural Products, Thailand Institute of Scientific and Technological Research, Pathumtani, Thailand.
authors.forename: Parkpoom
authors.initials: P
authors.lastname: Siriarchavatana
authors.affiliation: Laboratory Animal Resources Department, Colorado State University, Fort Collins, Colorado, USA. Jessica.ayers@colostate.edu.
authors.forename: Jessica D
authors.initials: JD
authors.lastname: Ayers
authors.affiliation: Laboratory Animal Resources Department, Colorado State University, Fort Collins, Colorado, USA.
authors.forename: Lon V
authors.initials: LV
authors.lastname: Kendall
mesh_terms: D000758:Anesthesia / Q000662:veterinary*; D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D018592:Cross-Over Studies; D004338:Drug Combinations; D005260:Female; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011277:Pregnanediones / Q000494:pharmacology*; D011897:Random Allocation; D012018:Reflex / Q000187:drug effects; D014991:Xylazine / Q000494:pharmacology
chemical_list: D000777:Anesthetics; D004338:Drug Combinations; D011277:Pregnanediones; D014991:Xylazine; D007649:Ketamine; C006477:alphaxalone