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

Abstract：

PURPOSE: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. METHODS: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 markers within 72 h of ICU admission. At 3 and 12 months 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. RESULTS:Our study included 419 survivors of critical illness with median age 59 years and APACHE II score 25. Higher S100B was associated with worse global cognition at 3 and 12 months (P = 0.008; P = 0.01). UCHL1 was nonlinearly associated with global cognition at 3 months (P = 0.02). Higher E-selectin was associated with worse global cognition (P = 0.006 at 3 months; P = 0.06 at 12 months). 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 3 months. CONCLUSIONS: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.

journal_name

Intensive Care Med

journal_title

Intensive care medicine

authors

Hughes CG,Patel MB,Brummel NE,Thompson JL,McNeil JB,Pandharipande PP,Jackson JC,Chandrasekhar R,Ware LB,Ely EW,Girard TD

doi

10.1007/s00134-018-5120-1

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

345-355

issue

eissn

0342-4642

issn

1432-1238

pii

10.1007/s00134-018-5120-1

journal_volume

pub_type

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