Temporal biomarker profiles and their association with ICU acquired delirium: a cohort study.

BACKGROUND: Neuroinflammation is thought to play an important role in the pathogenesis of ICU-acquired delirium, but the association between inflammatory and brain-specific proteins and ICU delirium is poor. We investigated whether or not serial determinations of markers may improve this association. METHODS: Critically ill patients with a high risk of ICU delirium and with an ICU length of stay of at least 6 days were included in the study. Blood was drawn on days 1, 2, 4 and 6 after ICU admission and analyzed for different markers of inflammation and several brain proteins. Differences in courses over time prior to and following the onset of delirium and absolute differences over time were analyzed in patients with and without delirium using repeated measurement analysis of variance. In addition, a cross-sectional analysis of levels of these markers before the first onset of delirium was performed. RESULTS: Fifty patients were included in this study. In the longitudinal analysis, there were no differences in the levels of any of the markers immediately prior to and following the onset of delirium, but overall, median levels of adiponectin (9019 (IQR 5776-15,442) vs. 6148 (IQR 4447-8742) ng/ml, p = 0.05) were significantly higher in patients with delirium compared to patients without delirium. In the cross-sectional analysis, median levels of the brain protein Tau (90 (IQR 46-224) vs. 31 (IQR 31-52) pg/ml, p = 0.009) and the ratio Tau/amyloid ß1-42 (1.42 ((IQR 0.9-2.57) vs. 0.68 (IQR 0.54-0.96), p = 0.003) were significantly higher in patients with hypoactive delirium compared to patients without. Levels of neopterin (111 (IQR 37-111) vs. 29 (IQR 16-64) mmol/l, p = 0.004) and IL-10 (28 (IQR 12-39) vs. 9 (IQR 4-12) pg/ml, p = 0.001) were significantly higher in patients with hypoactive delirium compared to patients with mixed-type delirium. CONCLUSIONS: While there are differences in markers (adiponectin and several brain proteins) between patients with and without delirium, the development of delirium is not preceded by a change in the biomarker profile of inflammatory markers or brain proteins. Patients with hypoactive delirium account for the observed differences in biomarkers. TRIAL REGISTRATION: ClinicalTrials.gov, NCT 01274819 . Registered on 12 January 2011.