Christina J Hayhurst1, Mayur B Patel2, J Brennan McNeil3, Timothy D Girard4, Nathan E Brummel3, Jennifer L Thompson5, Rameela Chandrasekhar6, Lorraine B Ware7, Pratik P Pandharipande8, E Wesley Ely9, Christopher G Hughes10. 1. Department of Anesthesiology, Division of Anesthesiology Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, United States. Electronic address: Christina.j.hayhurst@vumc.org. 2. Section of Surgical Sciences, Departments of Surgery, Neurosurgery, and Hearing & Speech Sciences, Division of Trauma and Surgical Critical Care, Vanderbilt Brain Institute, Center for Health Services Research, Vanderbilt University Medical Center, Nashville Veterans Affairs Medical Center, Tennessee Valley Healthcare System, United States. 3. Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, United States. 4. Department of Critical Care Medicine and Clinical Research, Investigation, and Systems Modeling of Acute Illnesses Center, University of Pittsburgh, Pittsburgh, PA, United States. 5. Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN, United States. 6. Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, United States. 7. Departments of Medicine and Pathology, Microbiology and Immunology, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, United States. 8. Departments of Anesthesiology and Surgery, Division of Anesthesiology Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, United States. 9. Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Center for Health Services Research, Vanderbilt University Medical Center, Geriatric Research, Education and Clinical Center Service, Nashville Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN, United States. 10. Department of Anesthesiology, Division of Anesthesiology Critical Care Medicine, Center for Health Services Research, Vanderbilt University Medical Center, Nashville, TN, United States.
Abstract
PURPOSE: Delirium is prevalent but with unclear pathogenesis. Neuronal injury repair pathways may be protective. We hypothesized that higher concentrations of neuronal repair biomarkers would be associated with decreased delirium in critically ill patients. MATERIALS AND METHODS: We performed a nested study of hospital survivors within a prospective cohort that enrolled patients within 72 h of respiratory failure or shock. We measured plasma concentrations of ubiquitin carboxyl-terminal-esterase-L1 (UCHL1) and brain-derived neurotrophic factor (BDNF) from blood collected at enrollment. Delirium was assessed twice daily using the CAM-ICU. Multivariable regression was used to examine the associations between biomarkers and delirium prevalence/duration, adjusting for covariates and interactions with age and IL-6 plasma concentration. RESULTS: We included 427 patients with a median age of 59 years (IQR 48-69) and APACHE II score of 25 (IQR 19-30). Higher plasma concentration of UCHL1 on admission was independently associated with lower prevalence of delirium (p = .04) but not associated with duration of delirium (p = .06). BDNF plasma concentration was not associated with prevalence (p = .26) or duration of delirium (p = .36). CONCLUSIONS: During critical illness, higher UCHL1 plasma concentration is associated with lower prevalence of delirium; BDNF plasma concentration is not associated with delirium. Clinical trial number: NCT00392795; https://clinicaltrials.gov/ct2/show/NCT00392795.
PURPOSE:Delirium is prevalent but with unclear pathogenesis. Neuronal injury repair pathways may be protective. We hypothesized that higher concentrations of neuronal repair biomarkers would be associated with decreased delirium in critically illpatients. MATERIALS AND METHODS: We performed a nested study of hospital survivors within a prospective cohort that enrolled patients within 72 h of respiratory failure or shock. We measured plasma concentrations of ubiquitin carboxyl-terminal-esterase-L1 (UCHL1) and brain-derived neurotrophic factor (BDNF) from blood collected at enrollment. Delirium was assessed twice daily using the CAM-ICU. Multivariable regression was used to examine the associations between biomarkers and delirium prevalence/duration, adjusting for covariates and interactions with age and IL-6 plasma concentration. RESULTS: We included 427 patients with a median age of 59 years (IQR 48-69) and APACHE II score of 25 (IQR 19-30). Higher plasma concentration of UCHL1 on admission was independently associated with lower prevalence of delirium (p = .04) but not associated with duration of delirium (p = .06). BDNF plasma concentration was not associated with prevalence (p = .26) or duration of delirium (p = .36). CONCLUSIONS: During critical illness, higher UCHL1 plasma concentration is associated with lower prevalence of delirium; BDNF plasma concentration is not associated with delirium. Clinical trial number: NCT00392795; https://clinicaltrials.gov/ct2/show/NCT00392795.
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