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血浆神经生物标志物作为儿科牙科全身麻醉神经毒性的衡量指标:一项前瞻性观察可行性研究。

Plasma neurological biomarkers as a measure of neurotoxicity in pediatric dental general anesthesia: a prospective observational feasibility study.

机构信息

Pediatric Anaesthesiology Department, Sidra Medicine, Doha, Qatar.

Hamad Dental Centre, Hamad Medical Corporation (HMC), Doha, Qatar.

出版信息

Eur Arch Paediatr Dent. 2024 Apr;25(2):267-275. doi: 10.1007/s40368-024-00884-9. Epub 2024 Apr 22.

Abstract

PURPOSE

Neurotoxicity concerns have been raised over general anesthesia and sedation medication use in children. Such concerns are largely based on animal studies, historical anesthetic agents, and assessment tools, thus warranting further investigations. Blood biomarkers in detecting neuronal inflammation and apoptosis are novel methods for detecting neuronal damage. Therefore, the aim of this feasibility study was to assess the usefulness of the levels of four plasma biomarkers in dental general anesthesia (DGA) as surrogate markers of neurotoxicity in children. The secondary aim was to compare changes in motor manipulative skills pre- and post-anesthetic exposure.

METHODS

This single-center prospective observational study included 22 healthy children aged between 3 and 6 years old who underwent DGA. Subclinical neurotoxicity was measured with a panel of four plasma biomarkers: Caspase-3, neuron-specific enolase (NSE), neurofilament light chain, and S100B at three time points (1; at start, 2; end and 3; on recovery from DGA). The Skillings-Mack test was used to identify the difference in the biomarker levels at three time points. Motor manipulative score assessment, prior and two weeks after DGA was also performed.

RESULTS

A total of 22 study participants (mean age = 5 ± 1 years) were included with a median DGA duration of 106 ± 28 min. A reduction in Caspase-3 levels was recorded, with pairwise comparison over three time points, reporting a statistical significance between time point 2 vs. 1 and time point 3 vs. 1. Although fluctuations in NSE levels were recorded, no significant changes were found following pairwise comparison analysis. Among other biomarkers, no significant changes over the three periods were recorded. Furthermore, no significant changes in manipulative motor scores were reported.

CONCLUSION

Caspase-3 reduced significantly in the short time frames during day-care DGA; this might be due to the relatively short anesthesia duration associated with dental treatment as compared with more extensive medical-related treatments. Therefore, further studies on Caspase-3 as a potential biomarker in pediatric DGA neurotoxicity are required to further ascertain results of this study.

摘要

目的

人们对儿童全身麻醉和镇静药物的使用提出了神经毒性的担忧。这些担忧主要基于动物研究、历史麻醉剂和评估工具,因此需要进一步研究。血液生物标志物在检测神经元炎症和细胞凋亡方面是检测神经元损伤的新方法。因此,本可行性研究的目的是评估四种血浆生物标志物在儿童牙科全身麻醉(DGA)中的水平作为神经毒性的替代标志物的有用性。次要目的是比较麻醉前和麻醉后运动操作技能的变化。

方法

这项单中心前瞻性观察性研究纳入了 22 名年龄在 3 至 6 岁之间的健康儿童,他们接受了 DGA。亚临床神经毒性通过一组四种血浆生物标志物来衡量:Caspase-3、神经元特异性烯醇化酶(NSE)、神经丝轻链和 S100B,在三个时间点(1;开始时,2;结束时和 3;从 DGA 恢复时)进行测量。Skillings-Mack 测试用于确定三个时间点之间生物标志物水平的差异。还在 DGA 之前和之后两周进行了运动操作评分评估。

结果

共纳入 22 名研究参与者(平均年龄=5±1 岁),DGA 持续时间中位数为 106±28 分钟。记录到 Caspase-3 水平降低,三个时间点的配对比较显示,时间点 2 与时间点 1 以及时间点 3 与时间点 1 之间存在统计学意义。尽管 NSE 水平波动,但通过配对比较分析未发现明显变化。其他生物标志物在三个时期均无明显变化。此外,运动操作评分无明显变化。

结论

日间牙科全身麻醉期间,Caspase-3 在短时间内显著降低;这可能是由于与更广泛的医学相关治疗相比,与牙科治疗相关的麻醉时间相对较短。因此,需要进一步研究 Caspase-3 作为儿科 DGA 神经毒性的潜在生物标志物,以进一步确定本研究的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129d/11058848/8e124d203791/40368_2024_884_Fig1_HTML.jpg

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