EHR-derived modified cardiovascular-kidney-metabolic syndrome stage and risk of delirium in sepsis: A study in two...

Cardiovascular-kidney-metabolic (CKM) syndrome staging may summarize chronic multisystem vulnerability, but its relevance to sepsis-associated delirium is unclear.

To evaluate the association between EHR-derived modified CKM stage and incident chart-documented delirium among adults with sepsis.

We performed a retrospective cohort study using two U.S. intensive care unit (ICU) electronic health record databases, Medical Information Mart for Intensive Care (MIMIC)-IV and eICU Collaborative Research Database (eICU). Adults with sepsis were included after excluding ICU stays shorter than 24 h, delirium within the first 24 h, and missing CKM stage. The analytic time zero was defined as 24 h after ICU admission. The primary outcome was incident delirium; in-hospital mortality was secondary. Cohort-specific Cox and Fine-Gray models were considered the primary evidence. Pooled individual-patient-data and inverse-variance meta-analytic estimates were interpreted as secondary cross-database summaries.

We included 24,142 MIMIC-IV and 13,198 eICU patients. In fully adjusted Fine-Gray analyses, modified CKM stage was associated with incident delirium in MIMIC-IV and showed directionally consistent but less precise estimates in eICU. Fixed-effect synthesis yielded subdistribution hazard ratios of 1.31 (95% CI, 1.10-1.57) for stage 0, 1.23 (1.09-1.38) for stage 2, 1.51 (1.34-1.72) for stage 3, and 1.31 (1.16-1.47) for stage 4 versus stage 1. Mortality associations were highly heterogeneous between databases.

EHR-derived modified CKM stage was associated with incident delirium in adults with sepsis, although pooled and stage-specific estimates require cautious interpretation. Mortality associations were heterogeneous and did not support a robust pooled conclusion.