Centre for Anaesthesia and Cognitive Function, Department of Anaesthesia and Acute Pain Medicine, St. Vincent's Hospital, Melbourne, Australia.
Anaesthesia Perioperative and Pain Medicine Unit, Melbourne Medical School, University of Melbourne, Australia.
JAMA Neurol. 2018 May 1;75(5):542-547. doi: 10.1001/jamaneurol.2017.4913.
Anesthesia and surgery are believed to act on the central nervous system by a fully reversible mechanism innocuous to nerve cells. Evidence that neurological sequelae may follow would challenge this belief and would thereby suggest a need to reassess theories of the mechanism of anesthetic action or the response of the central nervous system to surgery.
To measure 2 biomarkers of neurological injury (neurofilament light and tau) in plasma in a series of timed collections before and after anesthesia and surgery.
DESIGN, SETTING, AND PARTICIPANTS: These 2 related observational studies (CAPACITY and ARCADIAN) recruited patients 60 years and older who were undergoing general anesthesia for surgeries performed within a tertiary hospital. Blood samples were taken immediately before surgical anesthesia was administered and then sequentially after surgery at 30-minute, 6-hour, 24-hour, and 48-hour intervals. Sampling took place from January 2014 to August 2015. Data analysis took place from October 2016 to February 2017.
Plasma neurofilament light and tau.
A total of 30 patients were enrolled (13 from the CAPACITY study and 17 from the ARCADIAN study). The mean (SD) age was 69.1 (7.0) years, and 18 members (59%) of the participant group were female; 22 (73%) were undergoing joint arthroplasty. Mean neurofilament light increased at each measurement from a combined baseline mean (SD) of 22.3 (20.4) pg/mL to a maximal combined mean (SD) level of 35.1 (28.7) pg/mL, a maximum increase of 67% (95% CI, 45%-89%; P < .001), at 48 hours postoperatively. The level of tau increased significantly from baseline at every measurement, from a combined baseline mean (SD) of 3.1 (1.3) pg/mL to a maximal combined mean (SD) of 10.8 (9.5) pg/mL, a peak increase of 257% (95% CI, 154%-361%; P < .001), at 6 hours postoperatively. After 6 hours, the mean level began to return to baseline but remained elevated after 48 hours.
Neurofilament light is a specific marker of axonal injury and has been shown to indicate neuronal damage in a number of diseases. Tau proteins are an integral component of axonal integrity, and increased tau indicates neuronal damage. The increases in both neurofilament light and tau over 48 hours after surgery suggest that general anesthesia and surgery may be associated with neuronal damage in the short term. Further investigations will be required to study any association with clinical outcomes. These preliminary findings demand that we question the prevailing assumption that anesthesia and surgery are innocuous, transient, and without injurious changes to the central nervous system.
人们普遍认为，麻醉和手术通过一种对神经细胞无害的完全可逆机制作用于中枢神经系统。如果有证据表明神经后遗症可能随之而来，这将挑战这一观点，并因此表明有必要重新评估麻醉作用机制或中枢神经系统对手术反应的理论。
在麻醉和手术前和后一系列定时采集的样本中测量血浆中的 2 种神经损伤生物标志物（神经丝轻链和 tau）。
设计、设置和参与者：这 2 项相关的观察性研究（CAPACITY 和 ARCADIAN）招募了 60 岁及以上的患者，他们正在接受全麻下的手术，这些手术在一家三级医院进行。在手术麻醉前立即采集血样，然后在术后 30 分钟、6 小时、24 小时和 48 小时进行连续采样。采样时间为 2014 年 1 月至 2015 年 8 月。数据分析时间为 2016 年 10 月至 2017 年 2 月。
血浆神经丝轻链和 tau。
共纳入 30 名患者（CAPACITY 研究 13 名，ARCADIAN 研究 17 名）。平均（SD）年龄为 69.1（7.0）岁，参与者组中 18 名（59%）为女性；22 名（73%）正在接受关节置换术。神经丝轻链的平均水平从联合基线的 22.3（20.4）pg/mL 增加到联合最大平均（SD）水平 35.1（28.7）pg/mL，最大增加 67%（95%CI，45%-89%；P<0.001），在术后 48 小时。tau 的水平在每个测量点都显著高于基线，从联合基线的 3.1（1.3）pg/mL 增加到联合最大平均（SD）的 10.8（9.5）pg/mL，最大增加 257%（95%CI，154%-361%；P<0.001），在术后 6 小时。6 小时后，平均水平开始恢复到基线，但在 48 小时后仍处于升高状态。
神经丝轻链是轴突损伤的特异性标志物，已被证明在多种疾病中表明神经元损伤。tau 蛋白是轴突完整性的重要组成部分，tau 蛋白的增加表明神经元损伤。手术后 48 小时内神经丝轻链和 tau 的增加表明全身麻醉和手术可能与短期的神经元损伤有关。需要进一步的研究来研究与临床结果的任何关联。这些初步发现要求我们质疑普遍存在的假设，即麻醉和手术是无害的、短暂的，不会对中枢神经系统造成有害的变化。
