Smith Ryan J, Lachner Christian, Singh Vijay P, Trivedi Shubham, Khatua Biswajit, Cartin-Ceba Rodrigo
Mayo Clinic School of Graduate Medical Education, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
Division of Psychiatry, Department of Neurology, Mayo Clinic Florida, Jacksonville, FL, USA.
Acute Crit Care. 2022 Aug;37(3):415-428. doi: 10.4266/acc.2021.01508. Epub 2022 Jun 20.
Neuroinflammation causing disruption of the blood-brain barrier and immune cell extravasation into the brain parenchyma may cause delirium; however, knowledge of the exact pathophysiologic mechanism remains incomplete. The purpose of our study was to determine whether cytokine profiles differ depending on whether delirium occurs in the setting of sepsis, coronavirus disease 2019 (COVID-19), or recent surgery.
This prospective observational cohort study involved 119 critically ill patients admitted to a multidisciplinary intensive care unit (ICU) during 2019 and 2020. Delirium was identified using the validated confusion assessment method for the ICU. Multiple delirium risk factors were collected daily including clinical characteristics, hospital course, lab values, vital signs, surgical exposure, drug exposure, and COVID-19 characteristics. Serums samples were collected within 12 hours of ICU admission and cytokine levels were measured.
The following proinflammatory cytokines were elevated in our delirium population: tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-18, C-C motif ligand (CCL) 2, CCL3, C-X-C motif chemokine ligand (CXCL)1, CXCL10, IL-8, IL-1 receptor antagonist, and IL-10. Analysis of relative cytokine levels in those patients that developed delirium in the setting of sepsis, COVID-19, and recent surgery showed elevations of CCL2, CXCL10, and TNF-α in both the sepsis and COVID-19 group in comparison to the postsurgical population. In the postsurgical group, granulocyte colony-stimulating factor was elevated and CXCL10 was decreased relative to the opposing groups.
We identify several cytokines and precipitating factors known to be associated with delirium. However, our study suggests that the cytokine profile associated with delirium is variable and contingent upon delirium precipitating factors.
神经炎症导致血脑屏障破坏以及免疫细胞渗入脑实质可能会引起谵妄;然而,确切的病理生理机制仍不完全清楚。我们研究的目的是确定细胞因子谱是否因谵妄发生于脓毒症、2019冠状病毒病(COVID-19)或近期手术背景下而有所不同。
这项前瞻性观察性队列研究纳入了2019年至2020年期间入住多学科重症监护病房(ICU)的119例危重症患者。使用经过验证的ICU意识模糊评估方法来识别谵妄。每天收集多种谵妄危险因素,包括临床特征、住院病程、实验室检查值、生命体征、手术暴露情况、药物暴露情况以及COVID-19特征。在入住ICU后12小时内采集血清样本并检测细胞因子水平。
在我们的谵妄患者群体中,以下促炎细胞因子水平升高:肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、IL-18、C-C基序配体(CCL)2、CCL3、C-X-C基序趋化因子配体(CXCL)1、CXCL10、IL-8、IL-1受体拮抗剂和IL-10。对在脓毒症、COVID-19和近期手术背景下发生谵妄的患者的相对细胞因子水平分析显示,与术后人群相比,脓毒症组和COVID-19组的CCL2、CXCL10和TNF-α均升高。在术后组中,与其他组相比,粒细胞集落刺激因子升高而CXCL10降低。
我们识别出了几种已知与谵妄相关的细胞因子和诱发因素。然而,我们的研究表明,与谵妄相关的细胞因子谱是可变的,且取决于谵妄的诱发因素。