Erickson Rebecca L, Terzi Matthew C, Jaber Samer M, Hankenson F Claire, McKinstry-Wu Andrew, Kelz Max B, Marx James O
University Laboratory Animal Resources, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Pathobiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
J Am Assoc Lab Anim Sci. 2016;55(5):548-57.
Intraperitoneal injectable anesthetics are often used to achieve surgical anesthesia in laboratory mice. Because bolus redosing of injectable anesthetics can cause unacceptably high mortality, we evaluated intraperitoneal continuous-rate infusion (CRI) of ketamine with or without xylazine for maintaining surgical anesthesia for an extended period of time. Anesthesia was induced in male C57BL/6J mice by using ketamine (80 mg/kg) and xylazine (8 mg/kg) without or with acepromazine at 0.1 mg/kg or 0.5 mg/kg. At 10 min after induction, CRI for 90 min was initiated and comprised 25%, 50%, or 100% of the initial ketamine dose per hour or 50% of the initial doses of both ketamine and xylazine. Anesthetic regimens were compared on the basis of animal immobility, continuous surgical depth of anesthesia as determined by the absence of a pedal withdrawal reflex, and mortality. Consistent with previous studies, the response to anesthetics was highly variable. Regimens that provided the longest continuous surgical plane of anesthesia with minimal mortality were ketamine-xylazine-acepromazine (0.1 mg/kg) with CRI of 100% of the initial ketamine dose and ketamine-xylazine-acepromazine (0.5 mg/kg) with CRI of 50% of the initial ketamine and xylazine doses. In addition, heart rate and respiratory rate did not increase consistently in response to a noxious stimulus during CRI anesthesia, even when mice exhibited a positive pedal withdrawal reflex, suggesting that these parameters are unreliable indicators of anesthetic depth during ketamine-xylazine anesthesia in mice. We conclude that intraperitoneal CRI anesthesia in mice prolongs injectable anesthesia more consistently and with lower mortality than does bolus redosing.
腹腔注射麻醉剂常用于实验室小鼠的手术麻醉。由于注射麻醉剂的大剂量重复给药会导致不可接受的高死亡率,我们评估了腹腔持续输注(CRI)氯胺酮(加或不加赛拉嗪)以长时间维持手术麻醉的效果。使用氯胺酮(80mg/kg)和赛拉嗪(8mg/kg),不加或加0.1mg/kg或0.5mg/kg的乙酰丙嗪,对雄性C57BL/6J小鼠进行麻醉诱导。诱导后10分钟,开始90分钟的CRI,每小时的剂量为初始氯胺酮剂量的25%、50%或100%,或氯胺酮和赛拉嗪初始剂量的50%。根据动物的不动状态、由无足趾退缩反射确定的持续手术麻醉深度以及死亡率对麻醉方案进行比较。与先前的研究一致,对麻醉剂的反应高度可变。提供最长持续手术麻醉平面且死亡率最低的方案是氯胺酮-赛拉嗪-乙酰丙嗪(0.1mg/kg),CRI为初始氯胺酮剂量的100%,以及氯胺酮-赛拉嗪-乙酰丙嗪(0.5mg/kg),CRI为初始氯胺酮和赛拉嗪剂量的50%。此外,在CRI麻醉期间,即使小鼠表现出阳性足趾退缩反射,心率和呼吸频率对有害刺激的反应也没有持续增加,这表明这些参数在小鼠氯胺酮-赛拉嗪麻醉期间不是可靠的麻醉深度指标。我们得出结论,与大剂量重复给药相比,小鼠腹腔CRI麻醉能更持续地延长注射麻醉时间,且死亡率更低。