白细胞介素8与术后谵妄——两项研究的初步结果
Interleukin 8 in postoperative delirium - Preliminary findings from two studies.
作者信息
Lammers-Lietz Florian, Akyuz Levent, Feinkohl Insa, Lachmann Cornelia, Pischon Tobias, Volk Hans-Dieter, von Häfen Clarissa, Yürek Fatima, Winterer Georg, Spies Claudia D
机构信息
Department of Anaesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, Berlin, Germany.
BIH Center for Regenerative Therapies (BCRT) and Institute for Medical Immunology, Charité - Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, Germany.
出版信息
Brain Behav Immun Health. 2022 Jan 21;20:100419. doi: 10.1016/j.bbih.2022.100419. eCollection 2022 Mar.
OBJECTIVE
Studies have suggested that inflammation contributes to the pathogenesis of postoperative delirium, but previous results on the proinflammatory cytokine IL-8 in plasma are contradictory. Additionally, a significant fraction of IL-8 is bound to erythrocytes, but the relevance of whole blood IL-8 in delirium has not been studied. In this work, we analyzed the association of postoperative delirium with levels of unbound IL-8 in plasma and levels of IL-8 in whole blood in patients from two studies which were conducted in our department and have not been presented previously. We assessed the prognostic value of whole blood IL-8.
METHODS
Plasma/whole blood IL-8 was measured at least once in N = 504 patients preoperatively, on day one (d1) and/or three months after surgery in the BioCog observational study. Whole blood IL-8 was measured in N = 64 patients from the PHYDELIO trial preoperatively, on d1 and d7 after surgery. For the determination of whole blood IL-8, EDTA-preserved blood samples underwent lysis by adding Triton-X100 surfactant. Plasma and whole blood IL-8 levels were assessed with two different immunoassay kits. Delirium was appraised systematically for seven postoperative days according to DSM criteria using two comparable protocols consisting of validated screening tools.
RESULTS
Delirium occurred in 25% of BioCog and 14% of PHYDELIO patients. In BioCog, IL-8 was elevated on d1 and in delirious patients. A steeper postoperative increase in delirium was confounded by surgery-related factors. A crescendo-decrescendo pattern of whole blood IL-8 levels was observed in non-delirious patients with a peak on d1. This pattern was more distinct in delirious BioCog patients, but inverted in delirious PHYDELIO patients. Preoperative whole blood IL-8>318.4 pg/mL (reference <150 pg/mL) had adequate sensitivity (0.79/0.78) and specificity (0.53/0.67) for delirium in both samples.
CONCLUSION
Our results contribute to an inflammatory hypothesis of postoperative delirium.
目的
研究表明炎症与术后谵妄的发病机制有关，但先前关于血浆中促炎细胞因子白细胞介素-8（IL-8）的研究结果相互矛盾。此外，相当一部分IL-8与红细胞结合，但全血IL-8在谵妄中的相关性尚未得到研究。在本研究中，我们分析了在我们科室进行的两项尚未发表的研究中患者术后谵妄与血浆中游离IL-8水平和全血中IL-8水平之间的关联。我们评估了全血IL-8的预后价值。
方法
在BioCog观察性研究中，对N = 504例患者在术前、术后第1天（d1）和/或术后3个月至少测量一次血浆/全血IL-8。在PHYDELIO试验中，对N = 64例患者在术前、术后d1和d7测量全血IL-8。为了测定全血IL-8，用添加Triton-X100表面活性剂的方法对乙二胺四乙酸（EDTA）保存的血样进行裂解。血浆和全血IL-8水平用两种不同的免疫分析试剂盒进行评估。根据《精神疾病诊断与统计手册》（DSM）标准，使用由经过验证的筛查工具组成的两个可比方案，对术后7天的谵妄进行系统评估。
结果
BioCog研究中25%的患者和PHYDELIO研究中14%的患者发生了谵妄。在BioCog研究中，d1时以及谵妄患者中IL-8水平升高。术后谵妄更急剧的增加与手术相关因素混淆。在未发生谵妄的患者中观察到全血IL-8水平呈峰谷模式，在d1时达到峰值。这种模式在BioCog研究的谵妄患者中更明显，但在PHYDELIO研究的谵妄患者中则相反。术前全血IL-8>318.4 pg/mL（参考值<150 pg/mL）在两个样本中对谵妄都有足够的敏感性（0.79/0.78）和特异性（0.53/0.67）。
结论
我们的结果支持术后谵妄的炎症假说。
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