Circulating Endothelial Signature: A Biomarker of Delirium Risk and Severity in Postoperative Patients
Rosa Dolores Prieto-Utrera1, Adrián García-Concejo2, Esther Gómez-Sánchez3
1Group for Biomedical Research in Critical Care (BioCritic), Valladolid, Spain; Institute of Health Sciences of Castile and Leon, Soria, Spain; Research Unit, University Clinical Hospital of Valladolid, Valladolid, Spain; Biomedical Research Institute of Valladolid.
Background:
Delirium is a frequent complication in critically ill and septic patients and has been linked to endothelial dysfunction, microvascular injury, and blood-brain barrier disruption. Circulating endothelial cells may reflect endothelial phenotypic alterations beyond soluble markers. The authors investigated the association between endothelial subsets and postoperative sepsis-related delirium in intensive care unit (ICU) patients. This study aimed to investigate the role of circulating endothelial subsets in the development of delirium in postsurgical sepsis patients and their relationship with hypoperfusion and clinical outcomes, to identify potential prognostic biomarkers and mechanistic insights.
Methods:
In this prospective cohort study, 214 postoperative ICU patients were enrolled at the time of surgery or sepsis diagnosis and classified as nonseptic ICU (n = 77), sepsis (n = 61), or septic shock (n = 76) according to Sepsis-3 criteria. Blood samples were obtained within 24 h of critical illness onset. Circulating endothelial subsets were characterized using high-dimensional flow cytometry with unsupervised clustering. Delirium was assessed daily using the Confusion Assessment Method for the ICU. Cox regression, receiver operating characteristic analysis, and causal mediation models were applied to evaluate associations with 28-day delirium and organ dysfunction-related clinical events occurring after sampling.
Results:
Among 13 endothelial subpopulations identified, the CD32b + subset was independently associated with 28-day delirium (hazard ratio [HR], 2.41; 95% CI, 1.32 to 4.40; P = 0.004). The CD32b + subset demonstrated discriminative performance for delirium (area under the receiver operating characteristics curve [AUC], 0.79; 95% CI, 0.60 to 0.98), which improved after adjustment for age and sex (AUC, 0.89; 95% CI, 0.82 to 0.98). Models based solely on organ dysfunction-related clinical events showed lower performance (AUC, 0.69; 95% CI, 0.52 to 0.86). Mediation analysis indicated that approximately 20% of the total effect was mediated through organ dysfunction-related events, suggesting partial mediation, while the remaining 80% may involve alternative endothelial and microvascular mechanisms not captured by conventional measures.
Conclusions:
The elevated CD32b + subset is associated with postoperative delirium and organ dysfunction-related clinical events in critically ill patients, supporting an association between endothelial phenotypic alterations and vulnerability to brain dysfunction.
