Delirium Subphenotypes in the ICU: Comparing Effects on Cognition and Mortality

Abstract

Introduction Delirium is a common and serious complication in intensive care unit (ICU) patients, associated with neuropsychiatric morbidity and mortality. Traditionally, delirium subtyping was based on observable psychomotor symptoms, which may not fully capture underlying biological mechanisms, limiting targeted interventions. This retrospective cohort study investigated the relationship between clinically defined delirium subphenotypes, long-term cognitive outcomes and mortality in adult ICU patients.

Methods Patients were categorized into six delirium subphenotypes based on clinical criteria: Respiratory, Circulatory, Pain, Infectious, Metabolic and Sedative. The duration of individual subphenotypes, allowing for co-occurrence, was analysed. 2289 ICU admissions (2007-2023) were analysed. Cognitive function was assessed using the Cognitive Failure Questionnaire-14 (CFQ-14) one year after discharge. Additionally, one-year mortality was determined.

Results Delirium was highly prevalent (88.6%). Circulatory (73.7%) and respiratory (79.7%) subphenotypes were most common and frequently co-occurred. Multivariable linear regression showed no significant association between individual subphenotype duration and CFQ-14 at one-year follow-up. Similarly, logistic regression found no association between subphenotype duration and one-year mortality. However, time-dependent Cox regression showed that delirium duration increased the hazard of death over time (HR = 1.009 [95% CI: 1.002-1.016]).

Discussion Our study found no differences in association between delirium subphenotypes and long-term cognitive impairment or mortality, potentially supporting a final common pathway for delirium. Discrepancies with previous studies may be explained by differences in follow-up response rates or the protective effect of delirium monitoring. Further research with objective measures or prospectively collected data is needed to investigate the role of delirium subphenotyping in patient care.