Journal Article

Systemic inflammation and delirium during critical illness

Ely, E. Wesley, Pandharipande, Pratik P, Bernard, Gordon R, Raman, Rameela, Ware, Lorraine B, Girard, Timothy D, Hughes, Christopher G, Thompson, Jennifer L, Brummel, Nathan E, Orun, Onur M, McNeil, J. Brennan, Harrison, Fiona E

2024

Overview

PurposeThe purpose of this study was to determine associations between markers of inflammation and endogenous anticoagulant activity with delirium and coma during critical illness.MethodsIn 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.ResultsAmong 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.ConclusionMarkers of inflammation and possibly endogenous anticoagulant activity are associated with delirium and coma during critical illness.

• Publisher: Springer Nature B.V
• Subject: Anticoagulants / Biomarkers / C-reactive protein / Coma / Corticosteroids / Delirium / Gelatinase B / IL-1β / Illnesses / Inflammation / Intensive care / Intensive care units / Interleukin 1 / Interleukin 10 / Interleukin 12 / Interleukin 6 / Interleukin 8 / Matrix metalloproteinase / Matrix metalloproteinases / Metalloproteinase / Protein C / Proteins / Sedatives / Sepsis / Tumor necrosis factor receptor 1 / Tumor necrosis factor receptors / Tumor necrosis factor-TNF / Tumor necrosis factor-α / γ-Interferon