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

J Crit Care. 2020 Apr:56:94-99. doi: 10.1016/j.jcrc.2019.12.010. Epub 2019 Dec 16.

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.

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

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood*
  • Brain-Derived Neurotrophic Factor / blood
  • Critical Illness*
  • Delirium / etiology*
  • Female
  • Humans
  • Inflammation / physiopathology*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Patient Discharge
  • Prevalence
  • Prospective Studies
  • Respiratory Insufficiency / complications
  • Shock / complications
  • Survivors
  • Treatment Outcome
  • Ubiquitin Thiolesterase / blood

Substances

  • Biomarkers
  • Brain-Derived Neurotrophic Factor
  • UCHL1 protein, human
  • BDNF protein, human
  • Ubiquitin Thiolesterase

Associated data

  • ClinicalTrials.gov/NCT00392795