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

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 = 0.75-1.23; p < 0.0001). Sub-analyses indicate high effect sizes for pentobarbital (1.14; CI = 0.75-1.52; p < 0.0001), and isoflurane (1.01; CI = 0.58-1.44; p = 0.0005) but not for ketamine (1.49; CI = -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.