FDA发出警告,3岁以下儿童反复和长时间使用吸入性麻醉药可能会增加神经系统损害的风险。然而,缺乏支持这一警告的强有力的临床证据。关于异氟烷的所有临床前证据的系统评价,七氟醚,在幼年实验动物中暴露地氟醚和安氟醚对神经变性和行为的影响可能阐明了这种风险实际上有多严重。在2022年11月23日对PubMed和Embase进行了全面搜索。基于预定义的选择标准,由两个独立的审阅者筛选所获得的参考。有关研究设计和结果数据的数据(Caspase-3和TUNEL用于神经变性,莫里斯水迷宫(MWM),高架加迷宫(EPM),提取开场(OF)和恐惧条件(FC),并计算个体效应大小,随后使用随机效应模型进行汇总。亚组分析是预先定义的,并针对物种进行,性别,麻醉年龄,重复或单次暴露以及结果测量的时间。在19.796个参考文献中,筛选出的324个可以包括在审查中。对于安氟醚,很少有研究进行荟萃分析(n=1)。暴露于七氟醚,异氟烷和地氟烷显著增加Caspase-3水平和TUNEL水平。Further,七氟醚和异氟醚也会导致学习和记忆障碍,增加焦虑。地氟醚对学习和记忆影响不大,对焦虑没有影响.七氟醚和异氟醚对神经变性的长期影响无法分析,因为研究太少。对于行为结果,然而,这是可能的,并显示七氟醚在所有三个相关结局中导致学习和记忆受损,在高架迷宫中导致焦虑增加.对于异氟烷,还观察到学习和记忆受损,但只有足够的数据可用于学习和记忆相关的两个结局.Further,单一暴露于七氟醚或异氟醚会增加神经变性和学习和记忆受损。总之,我们显示了暴露于卤代醚引起神经变性和行为改变的证据。这些影响对于七氟烷和异氟烷最明显,并且在单次暴露后已经存在。迄今为止,还没有足够的研究来评估长期神经变性作用的存在。然而,我们在这篇关于以后生活中行为变化的综述中提供了证据,提示一些永久性的神经退行性改变.总之,与FDA发出的警告相反,我们表明单独暴露于异氟烷和七氟烷会对大脑发育产生负面影响。根据本综述的结果,七氟醚和异氟醚的使用应尽可能限制在这一年轻弱势群体中,直到对长期永久性影响进行更多研究。
The FDA issued a warning that repeated and prolonged use of inhalational anaesthetics in children younger than 3 years may increase the risk of neurological damage. Robust clinical evidence supporting this warning is however lacking. A systematic
review of all preclinical evidence concerning isoflurane, sevoflurane, desflurane and enflurane exposure in young experimental animals on neurodegeneration and behaviour may elucidate how severe this risk actually is PubMed and Embase were comprehensively searched on November 23, 2022. Based on predefined selection criteria the obtained references were screened by two independent reviewers. Data regarding study design and outcome data (Caspase-3 and TUNEL for neurodegeneration, Morris water maze (MWM), Elevated plus maze (EPM), Open field (OF) and Fear conditioning (FC)) were extracted, and individual effect sizes were calculated and subsequently pooled using the random effects model. Subgroup analyses were predefined and conducted for species, sex, age at anesthesia, repeated or single exposure and on time of outcome measurement. Out of the 19.796 references screened 324 could be included in the
review. For enflurane there were too few studies to conduct meta-analysis (n = 1). Exposure to sevoflurane, isoflurane and desflurane significantly increases Caspase-3 levels and TUNEL levels. Further, sevoflurane and isoflurane also cause learning and memory impairment, and increase anxiety. Desflurane showed little effect on learning and memory, and no effect on anxiety. Long term effects of sevoflurane and isoflurane on neurodegeneration could not be analysed due to too few studies. For behavioural outcomes, however, this was possible and revealed that sevoflurane caused impaired learning and memory in all three related outcomes and increased anxiety in the elevated plus maze. For isoflurane, impaired learning and memory was observed as well, but only sufficient data was available for two of the learning and memory related outcomes. Further, single exposure to either sevoflurane or isoflurane increased neurodegeneration and impaired learning and memory. In summary, we show evidence that exposure to halogenated ethers causes neurodegeneration and behavioural changes. These effects are most pronounced for sevoflurane and isoflurane and already present after single exposure. To date there are not sufficient studies to estimate the presence of long term neurodegenerative effects. Nevertheless, we provide evidence in this
review of behavioral changes later in life, suggesting some permanent neurodegenerative changes. Altogether, In contrast to the warning issued by the FDA we show that already single exposure to isoflurane and sevoflurane negatively affects brain development. Based on the results of this
review use of sevoflurane and isoflurane should be restrained as much as possible in this young vulnerable group, until more research on the long term permanent effects have been conducted.