title: Dose regimens, variability, and complications associated with using repeat-bolus dosing to extend a surgical plane of anesthesia in laboratory mice.
abstract: Extending a surgical plane of anesthesia in mice by using injectable anesthetics typically is accomplished by repeat-bolus dosing. We compared the safety and efficacy of redosing protocols administered either during an anesthetic surgical plane (maintaining a continuous surgical plane, CSP), or immediately after leaving this plane (interrupted surgical plane, ISP) in C57BL/6J mice. Anesthesia was induced with ketamine, xylazine, and acepromazine (80, 8, and 1 mg/kg IP, respectively), and redosing protocols included 25% (0.25K), 50% (0.5K), or 100% (1.0K) of the initial ketamine dose or 25% (0.25KX) or 50% (0.5KX) of the initial ketamine-xylazine dose. In the ISP group, the surgical plane was extended by 13.8 ± 2.1 min (mean ± SEM) after redosing for the 0.25K redose with 50% returning to a surgical plane, 42.7 ± 4.5 min for the 0.5K redose with 88% returning to a surgical plane, and 44.3 ± 15.4 min for the 1.0K redose, 52.8 ± 7.2 min for the 0.25KX redose, and 45.9 ± 2.9 min for the 0.5KX redose, with 100% of mice returning to a surgical plane of anesthesia in these 3 groups. Mortality rates for ISP groups were 0%, 12%, 33%, 12%, and 18%, respectively. Mice in CSP groups had 50% mortality, independent of the repeat-dosing protocol. We recommend redosing mice with either 50% of the initial ketamine dose or 25% of the initial ketamine-xylazine dose immediately upon return of the pedal withdrawal reflex to extend the surgical plane of anesthesia in mice, optimize the extension of the surgical plane, and minimize mortality.
authors: University Laboratory Animal Resources, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: Samer M
authors: SM
authors: Jaber
authors: University Laboratory Animal Resources, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: F Claire
authors: FC
authors: Hankenson
authors: School of Veterinary Medicine, University of California, Davis, California, USA.
authors: Kathleen
authors: K
authors: Heng
authors: Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: Andrew
authors: A
authors: McKinstry-Wu
authors: Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: Max B
authors: MB
authors: Kelz
authors: University Laboratory Animal Resources, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. marx@upenn.edu.
authors: James O
authors: JO
authors: Marx
mesh_terms: D000075:Acepromazine / Q000008:administration & dosage*; D000777:Anesthetics / Q000008:administration & dosage*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014991:Xylazine / Q000008:administration & dosage*
chemical_list: D000777:Anesthetics; D014991:Xylazine; D000075:Acepromazine; D007649:Ketamine
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