Christopher G Hughes1,2, Mayur B Patel3,4, Nathan E Brummel5, Jennifer L Thompson6, J Brennan McNeil5, Pratik P Pandharipande7,4, James C Jackson8,9, Rameela Chandrasekhar6, Lorraine B Ware10, E Wesley Ely8,11, Timothy D Girard12. 1. Department of Anesthesiology, Division of Anesthesiology Critical Care Medicine and Center for Health Services Research, Vanderbilt University Medical Center, Nashville, USA. christopher.hughes@vanderbilt.edu. 2. Nashville Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, USA. christopher.hughes@vanderbilt.edu. 3. Section of Surgical Sciences, Departments of Surgery, Neurosurgery and Hearing and Speech Sciences, Division of Trauma and Surgical Critical Care, Vanderbilt Brain Institute, Center for Health Services Research, Vanderbilt University Medical Center, Nashville, USA. 4. Nashville Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, USA. 5. Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, USA. 6. Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, USA. 7. Departments of Anesthesiology and Surgery, Division of Anesthesiology Critical Care Medicine, Vanderbilt University Medical Center, Nashville, USA. 8. Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine and Center for Health Services Research, Vanderbilt University Medical Center, Nashville, USA. 9. Research Service, Nashville Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, USA. 10. Departments of Medicine and Pathology, Microbiology and Immunology, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, USA. 11. Geriatric Research, Education and Clinical Center Service, Nashville Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, USA. 12. Department of Critical Care Medicine and Clinical Research, Investigation and Systems Modeling of Acute Illnesses Center, University of Pittsburgh, Pittsburgh, USA.
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.
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.
Authors: Christopher G Hughes; Mayur B Patel; James C Jackson; Timothy D Girard; Sunil K Geevarghese; Brett C Norman; Jennifer L Thompson; Rameela Chandrasekhar; Nathan E Brummel; Addison K May; Mark R Elstad; Mitzi L Wasserstein; Richard B Goodman; Karel G Moons; Robert S Dittus; E Wesley Ely; Pratik P Pandharipande Journal: Ann Surg Date: 2017-06 Impact factor: 12.969
Authors: Christopher G Hughes; Pratik P Pandharipande; Jennifer L Thompson; Rameela Chandrasekhar; Lorraine B Ware; E Wesley Ely; Timothy D Girard Journal: Crit Care Med Date: 2016-09 Impact factor: 7.598
Authors: Barbara C van Munster; Johanna C Korevaar; Catharina M Korse; Johannes M Bonfrer; Aeilko H Zwinderman; Sophia E de Rooij Journal: Int J Geriatr Psychiatry Date: 2010-03 Impact factor: 3.485
Authors: Marcos G Lopez; Christopher G Hughes; Anthony DeMatteo; Jason B O'Neal; J Brennan McNeil; Matthew S Shotwell; Jennifer Morse; Michael R Petracek; Ashish S Shah; Nancy J Brown; Frederic T Billings Journal: Anesthesiology Date: 2020-03 Impact factor: 7.892
Authors: J Brennan McNeil; Christopher G Hughes; Timothy Girard; Lorraine B Ware; E Wesley Ely; Rameela Chandrasekhar; Jin H Han Journal: PLoS One Date: 2019-12-19 Impact factor: 3.240
Authors: Mohamed D Hashem; Ramona O Hopkins; Elizabeth Colantuoni; Victor D Dinglas; Pratik Sinha; Lisa Aronson Friedman; Peter E Morris; James C Jackson; Catherine L Hough; Carolyn S Calfee; Dale M Needham Journal: Thorax Date: 2021-06-10 Impact factor: 9.139