Association of neuronal repair biomarkers with delirium among survivors of critical illness

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://ichgcp.net/clinical-trials-registry/NCT00392795.

Keywords: Brain-derived neurotrophic factor; Cognitive dysfunction; Critical illness.

Conflict of interest statement

Declaration of Competing Interest The authors declare no competing interests in the past 36 months.

Copyright © 2019 Elsevier Inc. All rights reserved.

Figures

Figure 1:. UCHL1 Plasma Concentration versus Delirium Prevalence

Higher UCHL1 plasma concentration was associated with decreased prevalence of delirium (p=0.04) after adjusting for age, Sequential Organ Failure Assessment score,[25] Acute Physiology and Chronic Health Evaluation II acute physiology component,[26] Informant Questionnaire on Cognitive Decline in the Elderly Short Form score,[27] Charlson comorbidity index,[28] Framingham stroke risk profile,[29] presence of severe sepsis, and interleukin-6 plasma concentration. The solid line demonstrates the point estimate of the association between UCHL1 plasma concentration versus delirium prevalence, with the ribbon indicating the 95% confidence intervals.

Figure 2.. UCHL1 Plasma Concentration versus Delirium Duration

Higher UCHL1 plasma concentration was not associated with fewer days of delirium (p=0.06) after adjusting for age, Sequential Organ Failure Assessment score,[25] Acute Physiology and Chronic Health Evaluation II acute physiology component,[26] Informant Questionnaire on Cognitive Decline in the Elderly Short Form score,[27] Charlson comorbidity index,[28] Framingham stroke risk profile,[29] presence of severe sepsis, and interleukin-6 plasma concentration. The solid line demonstrates the point estimate of the association between UCHL1 plasma concentration versus delirium duration, with the ribbon indicating the 95% confidence intervals.