Guo Ling Yi, Kaustov Lilia, Brenna Connor T A, Patel Vikas, Zhang Cheng, Choi Stephen, Halpern Stephen, Wang Dian-Shi, Orser Beverley A
Department of Physiology, University of Toronto, Toronto, ON, Canada.
Department of Anesthesia, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Perioperative Brain Health Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Br J Anaesth. 2023 Feb;130(2):e351-e360. doi: 10.1016/j.bja.2022.10.004. Epub 2022 Nov 17.
It remains controversial whether general anaesthetic drugs contribute to perioperative neurocognitive disorders in adult patients. Preclinical studies have generated conflicting results, likely because of differing animal models, study protocols, and measured outcomes. This scoping review of preclinical studies addressed the question: 'Do general anaesthetic drugs cause cognitive deficits in adult animals that persist after the drugs have been eliminated from the brain?'
Reports of preclinical studies in the MEDLINE database published from 1953 to 2021 were examined. A structured review process was used to assess original studies of cognitive behaviours, which were measured after treatment (≥24 h) with commonly used general anaesthetic drugs in adult animals.
The initial search yielded 380 articles, of which 106 were fully analysed. The most frequently studied animal model was male (81%; n=86/106) rodents (n=106/106) between 2-3 months or 18-20 months of age. Volatile anaesthetic drugs were more frequently studied than injected drugs, and common outcomes were memory behaviours assessed using the Morris water maze and fear conditioning assays. Cognitive deficits were detected in 77% of studies (n=82/106) and were more frequent in studies of older animals (89%), after inhaled anaesthetics, and longer drug treatments. Limitations of the studies included a lack of physiological monitoring, mortality data, and risk of bias attributable to the absence of randomisation and blinding.
Most studies reported cognitive deficits after general anaesthesia, with age, use of volatile anaesthetic drugs, and duration of anaesthesia as risk factors. Recommendations to improve study design and guide future research are presented.
全身麻醉药物是否会导致成年患者围手术期神经认知障碍仍存在争议。临床前研究得出了相互矛盾的结果,这可能是由于动物模型、研究方案和测量结果的不同。这项对临床前研究的范围综述解决了以下问题:“全身麻醉药物是否会导致成年动物出现认知缺陷,且在药物从大脑中清除后这些缺陷仍然存在?”
检索了1953年至2021年发表在MEDLINE数据库中的临床前研究报告。采用结构化综述流程评估认知行为的原始研究,这些研究是在成年动物用常用全身麻醉药物治疗(≥24小时)后进行测量的。
初步检索得到380篇文章,其中106篇进行了全面分析。最常研究的动物模型是2至3个月或18至20个月大的雄性(81%;n = 86/106)啮齿动物(n = 106/106)。与注射药物相比,挥发性麻醉药物的研究更为频繁,常见的结果是使用莫里斯水迷宫和恐惧条件反射试验评估的记忆行为。在77%的研究(n = 82/106)中检测到认知缺陷,在老年动物的研究(89%)、吸入麻醉后以及较长时间的药物治疗中更为常见。研究的局限性包括缺乏生理监测、死亡率数据以及由于缺乏随机化和盲法导致的偏倚风险。
大多数研究报告了全身麻醉后存在认知缺陷,年龄、挥发性麻醉药物的使用和麻醉持续时间是危险因素。本文提出了改进研究设计和指导未来研究的建议。