Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University College of Medicine, Columbus, OH, USA.
Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Intensive Care Med. 2024 May;50(5):687-696. doi: 10.1007/s00134-024-07388-6. Epub 2024 Apr 22.
The purpose of this study was to determine associations between markers of inflammation and endogenous anticoagulant activity with delirium and coma during critical illness.
In this prospective cohort study, we enrolled adults with respiratory failure and/or shock treated in medical or surgical intensive care units (ICUs) at 5 centers. Twice per day in the ICU, and daily thereafter, we assessed mental status using the Richmond Agitation Sedation Scale (RASS) and the Confusion Assessment Method-Intensive Care Unit (CAM-ICU). We collected blood samples on study days 1, 3, and 5, measuring levels of C-reactive protein (CRP), interferon gamma (IFN-γ), interleukin (IL)-1 beta (IL-1β), IL-6, IL-8, IL-10, IL-12, matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-alpha (TNF-α), tumor necrosis factor receptor 1 (TNFR1), and protein C using validated protocols. We used multinomial logistic regression to analyze associations between biomarkers and the odds of delirium or coma versus normal mental status the following day, adjusting for age, sepsis, Sequential Organ Failure Assessment (SOFA), study day, corticosteroids, and sedatives.
Among 991 participants with a median age (interquartile range, IQR) of 62 [53-72] years and enrollment SOFA of 9 [7-11], higher concentrations of IL-6 (odds ratio [OR] [95% CI]: 1.8 [1.4-2.3]), IL-8 (1.3 [1.1-1.5]), IL-10 (1.5 [1.2-1.8]), TNF-α (1.2 [1.0-1.4]), and TNFR1 (1.3 [1.1-1.6]) and lower concentrations of protein C (0.7 [0.6-0.8])) were associated with delirium the following day. Higher concentrations of CRP (1.4 [1.1-1.7]), IFN-γ (1.3 [1.1-1.5]), IL-6 (2.3 [1.8-3.0]), IL-8 (1.8 [1.4-2.3]), and IL-10 (1.5 [1.2-2.0]) and lower concentrations of protein C (0.6 [0.5-0.8]) were associated with coma the following day. IL-1β, IL-12, and MMP-9 were not associated with mental status.
Markers of inflammation and possibly endogenous anticoagulant activity are associated with delirium and coma during critical illness.
本研究旨在确定炎症标志物和内源性抗凝活性与危重病期间谵妄和昏迷之间的关系。
在这项前瞻性队列研究中，我们招募了在 5 个中心的内科或外科重症监护病房（ICU）中患有呼吸衰竭和/或休克的成年人。每天在 ICU 中进行两次，之后每天使用 Richmond 激动镇静量表（RASS）和 ICU 意识混乱评估方法（CAM-ICU）评估精神状态。在研究第 1、3 和 5 天采集血样，使用验证过的方案测量 C 反应蛋白（CRP）、干扰素 γ（IFN-γ）、白细胞介素（IL）-1β（IL-1β）、IL-6、IL-8、IL-10、IL-12、基质金属蛋白酶-9（MMP-9）、肿瘤坏死因子-α（TNF-α）、肿瘤坏死因子受体 1（TNFR1）和蛋白 C 的水平。我们使用多项逻辑回归分析炎症标志物与谵妄或昏迷与次日正常精神状态之间的关联，调整因素包括年龄、败血症、序贯器官衰竭评估（SOFA）、研究日、皮质类固醇和镇静剂。
在 991 名中位年龄（四分位距，IQR）为 62[53-72]岁、入组 SOFA 为 9[7-11]的参与者中，更高浓度的 IL-6（比值比[OR] [95%CI]：1.8[1.4-2.3]）、IL-8（1.3[1.1-1.5]）、IL-10（1.5[1.2-1.8]）、TNF-α（1.2[1.0-1.4]）和 TNFR1（1.3[1.1-1.6]）以及更低浓度的蛋白 C（0.7[0.6-0.8]））与次日的谵妄有关。更高浓度的 CRP（1.4[1.1-1.7]）、IFN-γ（1.3[1.1-1.5]）、IL-6（2.3[1.8-3.0]）、IL-8（1.8[1.4-2.3]）和 IL-10（1.5[1.2-2.0]）以及更低浓度的蛋白 C（0.6[0.5-0.8]）与次日的昏迷有关。IL-1β、IL-12 和 MMP-9 与精神状态无关。
炎症标志物和可能的内源性抗凝活性与危重病期间的谵妄和昏迷有关。
