Ulinastatin treatment mitigates glycocalyx degradation and associated with lower postoperative delirium risk in patients undergoing cardiac surgery: a multicentre observational study

Ulinastatin (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. A 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. Both 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. UTI 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.