Postgraduate Program in Cardiology and Cardiovascular Science, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos, 2400, 90035-903 Porto Alegre, RS, Brazil; Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350 - sala 12113, 90035-903 Porto Alegre, RS, Brazil.
Department of Evidence-Based Health, UNIFESP, Rua Isabel Schmidt, 349, São Paulo 04743-030, Brazil.
Life Sci. 2021 Nov 1;284:119916. doi: 10.1016/j.lfs.2021.119916. Epub 2021 Sep 1.
To summarize the knowledge on the effect of anesthetics employed right before euthanasia on biological outcomes.
A systematic review of the literature to find studies with isoflurane, ketamine, halothane, pentobarbital, or thiopental just before euthanasia of laboratory rats or mice.
Controlled studies with quantitative data available.
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.
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).
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).
There was no direct funding for this research.
总结在安乐死前使用的麻醉剂对生物学结果的影响。
对使用异氟烷、氯胺酮、氟烷、戊巴比妥或硫喷妥钠安乐死的实验室大鼠或小鼠的研究进行系统文献回顾。
具有定量数据的对照研究。
两名审查员使用结构化表格独立进行搜索、数据提取和偏倚风险（RoB）评估。对于每个结果，相对于对照组计算效应大小（ES）。使用稳健方差元回归进行层次数据结构的荟萃分析，并针对小样本进行调整。
我们纳入了 20 项研究，共涉及 407 个生物学结果（110 个独特结果）。RoB 分析表明，评估的 87.5%的领域存在不确定风险，2%存在高风险，10.5%存在低风险。所有考虑的麻醉剂的综合效应大小为 0.99（CI=0.75-1.23；p<0.0001）。亚分析表明戊巴比妥（1.14；CI=0.75-1.52；p<0.0001）和异氟烷（1.01；CI=0.58-1.44；p=0.0005）的效应较大，但氯胺酮（1.49；CI=-7.95-10.9；p=0.295）则不然。
我们表明，麻醉剂对评估的大多数结果的干扰不同。然而，我们的数据并不支持使用一种麻醉剂而不是其他麻醉剂，甚至不使用麻醉剂进行安乐死。我们得出的结论是，如果不考虑杀戮方法，就不能在研究之间比较结果。本研究方案已在 Prospero（CRD42019119520）上注册。
本研究无直接资助。
