Study of anesthetics for euthanasia in rats and mice: A systematic review and meta-analysis on the impact upon biological outcomes (SAFE-RM)

Tobar Leitão, S. A. and Soares, D. D. S. and Carvas Junior, N. and Zimmer, R. and Ludwig, N. F. and Andrades, M.

Life Sci (2021) 284: 119916

DOI: 10.1016/j.lfs.2021.119916

Abstract

AIM: To summarize the knowledge on the effect of anesthetics employed right before euthanasia on biological outcomes. DATA SOURCE: A systematic review of the literature to find studies with isoflurane, ketamine, halothane, pentobarbital, or thiopental just before euthanasia of laboratory rats or mice. STUDY SELECTION: Controlled studies with quantitative data available. DATA EXTRACTION: The search, data extraction, and risk of bias (RoB) were performed independently by two reviewers using a structured form. For each outcome, an effect size (ES) was calculated relative to the control group. Meta-analysis was performed using robust variance meta-regression for hierarchical data structures, with adjustment for small samples. DATA SYNTHESIS: We included 20 studies with 407 biological outcomes (110 unique). RoB analysis indicated that 87.5% of the domains evaluated showed unclear risk, 2% high risk, and 10.5% low risk. The effect size for all anesthetics considered together was 0.99 (CI(95%) = 0.75-1.23; p \textless 0.0001). Sub-analyses indicate high effect sizes for pentobarbital (1.14; CI(95%) = 0.75-1.52; p \textless 0.0001), and isoflurane (1.01; CI(95%) = 0.58-1.44; p = 0.0005) but not for ketamine (1.49; CI(95%) = -7.95-10.9; p = 0.295). CONCLUSION: We showed that anesthetics interfere differently with the majority of the outcomes assessed. However, our data did not support the use of one anesthetic over others or even the killing without anesthetics. We conclude that outcomes cannot be compared among studies without considering the killing method. This protocol was registered at Prospero (CRD42019119520). FUNDING: There was no direct funding for this research.

Citation

Tobar Leitão, S. A., Soares, D. D. S., Carvas Junior, N., Zimmer, R., Ludwig, N. F., & Andrades, M. (2021). Study of anesthetics for euthanasia in rats and mice: A systematic review and meta-analysis on the impact upon biological outcomes (SAFE-RM). Life Sci, 284, 119916. https://doi.org/10.1016/j.lfs.2021.119916 *Euthanasia, Anesthetics, Anesthetics/*pharmacology, Animals, Dose-Response Relationship, Drug, Halothane, Isoflurane, Ketamine, Mice, Pentobarbital, Publication Bias, Rats, Risk, Thiopental

Keywords

• *Euthanasia
• Anesthetics
• Anesthetics/*pharmacology
• Animals
• Dose-Response Relationship
• Drug
• Halothane
• Isoflurane
• Ketamine
• Mice
• Pentobarbital
• Publication Bias
• Rats
• Risk
• Thiopental