• Xiao Ran, Tingting Xu, Jieqiong Liu, Shaobing Yang, Fang Luo, Rongxue Wu, Juan Tan, Hang Ruan, and Qin Zhang.
• Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, China.
• Crit Care. 2025 Jan 29; 29 (1): 5252.

BackgroundUlinastatin (UTI), recognized for its anti-inflammatory properties, holds promise for patients undergoing cardiac surgery. This study aimed to investigate the relationship between intraoperative UTI administration and the incidence of delirium following cardiac surgery.MethodsA retrospective analysis was performed on a retrospective cohort of 6,522 adult cardiac surgery patients to evaluate the relationship between UTI treatment and the incident of postoperative delirium (POD) in patients ongoing cardiac surgery. This was followed by a prospective observational cohort study of 241 patients and an in vitro study to explore the findings and the potential role of UTI in preventing cardiac ischemia-reperfusion induced glycocalyx degradation.ResultsBoth univariate and multivariate logistic regression analyses in retrospective cohort indicated that intraoperative administration of UTI was associated with a significant lower risk of POD among cardiac surgery patients, a finding confirmed through employing propensity score matching. The subsequent prospective observational cohort further supported these findings (adjusted Odds Ratio = 0.392, 95% CI: 0.157-0.977, P = 0.044). Furthermore, UTI mitigated glycocalyx degradation, as demonstrated by in vitro study.ConclusionsUTI administration may mitigate glycocalyx degradation, potentially lowering the risk of POD in cardiac surgery patients, offering valuable insights for future interventions to prevent POD and enhance patient outcomes. Trial registration number ClinicalTrials.gov (No. NCT06268249). Retrospectively registered 4 February 2024.© 2025. The Author(s).

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