A Comparison of Ketamine or Etomidate Combined with Xylazine for Intraperitoneal Anesthesia in Four Mouse Strains

Intraperitoneal (IP) injection is a common route of anesthetic administration in mice. Ketamine-xylazine (KX) anesthesia is one of the most widely used IP protocols, but has limitations. Etomidate is an alternative to ketamine that has been used in both human and veterinary medicine yet has not been widely studied in mice. The purpose of this study was to evaluate etomidate-xylazine (EX) anesthesia as an alternative to KX. We hypothesized that EX would be as safe and effective as KX, with both sex- and strain-dependent differences. Male and female Crl:CD1(ICR), C57BL/6NCrl, BALB/cJ and NU/J mice were given a single IP dose of ketamine 100 mg/kg and xylazine 10 mg/kg or etomidate 20 mg/kg and xylazine 10 mg/kg. Sedation times were similar between KX and EX, with CD1 mice exhibiting shorter sedation times. Surgical anesthesia was achieved in 44% of EX mice, compared with 4% of KX mice. C57BL/6NCrl mice were significantly more likely to achieve surgical anesthesia when given EX (94%) or KX (18%) than were other strains. In all strains except C57BL/6NCrl mice, females were more likely to reach surgical anesthesia than males. Several mice experienced an adverse hyperexcitement response during induction, with BALB/cJ (79%) and NU/J (87%) mice given EX significantly more likely than other strains to experience hyperexcitement. EX and KX protocols had no overall differences in lowest respiration rate, lowest systolic blood pressure, lowest rectal temperature, or levels of acidosis, although the lowest heart rates were significantly higher with EX, indicating that EX and KX have similar safety profiles. Thus, EX and KX administration were associated with several significant physiologic differences when comparing sexes or individual strains. Our results indicate that EX is an equally effective sedative and a more effective surgical anesthetic than KX; however, EX is only recommended for invasive procedures in C57BL/6 mice due to the high rate of hyper-excitement and inconsistent surgical depth seen in other strains. Further study is needed to optimize EX for use in multiple mouse strains.