背景:术后谵妄(POD)是手术患者最常见的并发症之一。基于血液的生物标志物可能有助于识别有风险的患者。这项研究旨在评估血管和内皮功能以及炎症特异性的血清生物标志物是如何改变的。在随后发生POD的患者手术之前或之后。
方法:这是一项针对德国三级医院PROPDESC单中心试验的连续招募的非心脏和心脏手术患者(年龄>60岁)的亚队列的研究。手术前和手术后的血清样本,并对样品进行基于珠子的17种血清蛋白(IL-3,IL-8,IL-10,Cripto,CCL2,RAGE,Resistin,ANGPT2,TIE2,血栓调节蛋白,Syndecan-1,E-Selectin,VCAM-1,ICAM-1,CXCL5,NSE,和uPAR)。在手术后的前五天评估POD的发展,使用ICU混淆评估方法(CAM-ICU),CAM,4-\'A\'s测试(4AT),和谵妄观察量表(DOS)。如果通过任何应用的方法在探视期间至少检测到POD一次,则认为患者为阳性。非参数测试,以及倾向评分匹配用于统计分析.
结果:共有118例患者被纳入最终分析;69%接受了非心脏手术,患者年龄中位数为71岁,59%的患者为男性。在整个队列中,POD发生率为28%。男性性别与POD的发展显著相关(p=0.0004),以及较高的ASA状态III(p=0.04)。此外,心脏手术患者POD的发生率显着增加(p=0.002)。手术引起除uPAR外的几乎所有生物标志物的血清水平的高度显著变化。在术前血清样本中,在随后的POD患者中,分析的参数均未发生显着改变。在术后样本中,在POD患者中CCL2显著增加1.75倍(p=0.03),与无POD队列相比。在倾向得分匹配之后,CCL2仍然是唯一显示术后值显著差异的生物标志物(p=0.01)。在心脏手术患者中,术后血清CCL2水平比非心脏手术后高3.5倍以上(p<0.0001).此外,心脏手术后,POD患者血清Syndecan-1水平显著升高,与非POD心脏手术患者相比(p=0.04)。
结论:在非心脏手术和心脏手术患者的混合队列中,术前血清生物标志物分析对血管功能障碍和全身性炎症具有特异性,并不预示随后发生POD.手术诱导的全身性炎症-如CCL2释放的显着增加所证明-与POD相关,特别是在心脏手术之后.在这些患者中,术后糖萼损伤可能进一步促进POD的发展。
BACKGROUND: Postoperative delirium (POD) ranks among the most common complications in surgical patients. Blood-based biomarkers might help identify the patient at risk. This
study aimed to assess how serum biomarkers with specificity for vascular and endothelial function and for inflammation are altered, prior to or following surgery in patients who subsequently develop POD.
METHODS: This was a
study on a subcohort of consecutively recruited elective non-cardiac as well as cardiac surgery patients (age > 60 years) of the single-center PROPDESC
trial at a German tertiary care hospital. Serum was sampled prior to and following surgery, and the samples were subjected to bead-based multiplex analysis of 17 serum proteins (IL-3, IL-8, IL-10, Cripto, CCL2, RAGE, Resistin, ANGPT2, TIE2, Thrombomodulin, Syndecan-1, E-Selectin, VCAM-1, ICAM-1, CXCL5, NSE, and uPAR). Development of POD was assessed during the first five days after surgery, using the Confusion Assessment Method for ICU (CAM-ICU), the CAM, the 4-\'A\'s test (4AT), and the Delirium Observation Scale (DOS). Patients were considered positive if POD was detected at least once during the visitation period by any of the applied methods. Non-parametric testing, as well as propensity score matching were used for statistical analysis.
RESULTS: A total of 118 patients were included in the final analysis; 69% underwent non-cardiac surgery, median overall patient age was 71 years, and 59% of patients were male. In the whole cohort, incidence of POD was 28%. The male gender was significantly associated with the development of POD (p = 0.0004), as well as a higher ASA status III (p = 0.04). Incidence of POD was furthermore significantly increased in cardiac surgery patients (p = 0.002). Surgery induced highly significant changes in serum levels of almost all biomarkers except uPAR. In preoperative serum samples, none of the analyzed parameters was significantly altered in subsequent POD patients. In postoperative samples, CCL2 was significantly increased by a factor of 1.75 in POD patients (p = 0.03), as compared to the no-POD cohort. Following propensity score matching, CCL2 remained the only biomarker that showed significant differences in postoperative values (p = 0.01). In cardiac surgery patients, postoperative CCL2 serum levels were more than 3.5 times higher than those following non-cardiac surgery (p < 0.0001). Moreover, after cardiac surgery, Syndecan-1 serum levels were significantly increased in POD patients, as compared to no-POD cardiac surgery patients (p = 0.04).
CONCLUSIONS: In a mixed cohort of elective non-cardiac as well as cardiac surgery patients, preoperative serum biomarker profiling with specificity for vascular dysfunction and for systemic inflammation was not indicative of subsequent POD development. Surgery-induced systemic inflammation-as evidenced by the significant increase in CCL2 release-was associated with POD, particularly following cardiac surgery. In those patients, postoperative glycocalyx injury might furthermore contribute to POD development.