Plasma neurofilament light chain protein as a predictor of days in delirium and deep sedation, mortality and length of stay in critically ill patients

Page, Valerie J., Watne, Leiv Otto, Heslegrave, Amanda, Clark, Allan ORCID:, McAuley, Daniel F., Sanders, Robert D. and Zetterberg, Henrik (2022) Plasma neurofilament light chain protein as a predictor of days in delirium and deep sedation, mortality and length of stay in critically ill patients. EBioMedicine, 80. ISSN 2352-3964

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Background: Delirium predicts poor outcomes, however identifying patients with the worst outcomes is challenging. Plasma neurofilament light protein (NfL) is a sensitive indicator of neuronal damage. We undertook an exploratory observational study to determine the association between plasma NfL and delirium in the critically ill. Methods: MoDUS was a randomised placebo-controlled delirium trial of simvastatin done in an UK adult general ICU. We measured NfL levels in plasma samples using a Single molecule array (Simoa) platform. We explored associations between patient's plasma NfL levels and number of delirium days, and clinical outcomes. The control group for baseline NfL were preoperative patients undergoing major surgery. Findings: The majority of critically ill patients already had a high NfL level on admission. Patients with higher plasma NfL levels at days one and three spent more days in delirium or deep sedation. Patients with zero or one day in delirium or deep sedation had day one mean concentrations of 37.8 pg/ml (SD 32.6) compared with 96.5 pg/ml (SD 106.1)) for patients with two days or more, p-value 0.002 linear mixed effects model. Survivors discharged before 14 days had lower mean plasma NfL concentrations compared to those with longer hospital stays and/or who died within six months. The area under ROC curve for predicting death within six months using day one NfL was 0.81 (0.7,0.9). Interpretation: Measurement of plasma NfL within three days of admission may be useful to identify those patients with worse clinical outcomes, and as an enrichment strategy for future delirium interventional trials in the critically ill.

Item Type: Article
Additional Information: Data sharing statement: Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices) will be shared beginning three months and ending 36 months following article publication, to researchers who provide a methodologically sound proposal. Proposals should be directed to and to gain access, data requestors will need to sign a data access agreement. Acknowledgments: Funding for this project was provided by Alzheimer's Society UK and UK Dementia Research Institute.
Uncontrolled Keywords: biomarker,critical care,delirium,intensive care,neurofilament light protein,biochemistry, genetics and molecular biology(all) ,/dk/atira/pure/subjectarea/asjc/1300
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 11 May 2022 11:31
Last Modified: 22 Oct 2022 18:31
DOI: 10.1016/j.ebiom.2022.104043

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