Relationships between markers of neurologic and endothelial injury during critical illness and long-term cognitive impairment and disability.

Abstract

Neurologic and endothelial injury biomarkers are associated with prolonged delirium during critical illness and may reflect injury pathways that lead to poor long-term outcomes. We hypothesized that blood-brain barrier (BBB), neuronal, and endothelial injury biomarkers measured during critical illness are associated with cognitive impairment and disability after discharge. We enrolled adults with respiratory failure and/or shock and measured plasma concentrations of BBB (S100B), neuronal (UCHL1, BDNF), and endothelial (E-selectin, PAI-1) injury markerswithin 72h of ICU admission. At 3 and 12months post-discharge, we assessed participants' global cognition, executive function, and activities of daily living (ADL). We used multivariable regression to determine whether biomarkers were associated with outcomes after adjusting for relevant demographic and acute illness covariates. Our study included 419 survivors of critical illness with median age 59years and APACHE II score 25. Higher S100B was associated with worse global cognition at 3 and 12months (P = 0.008; P = 0.01). UCHL1 was nonlinearly associated with global cognition at 3months (P = 0.02). Higher E-selectin was associated with worse global cognition (P = 0.006 at 3months; P = 0.06 at 12months). BDNF and PAI-1 were not associated with global cognition. No biomarkers were associated with executive function. Higher S100B (P = 0.05) and E-selectin (P = 0.02) were associated with increased disability in ADLs at 3months. S100B, a marker of BBB and/or astrocyte injury, and E-selectin, an adhesion molecule and marker of endothelial injury, are associated with long-term cognitive impairment after critical illness, findings that may reflect mechanisms of critical illness brain injury.