Tranexamic acid use and the risk of postoperative delirium after spine surgery: a retrospective cohort study

Postoperative delirium (POD) is a common complication after major surgery and has been linked to perioperative neuroinflammation. Tranexamic acid (TXA), an antifibrinolytic agent, may influence inflammatory pathways, but its effect on POD remains unclear. This post hoc analysis investigated the association between intraoperative TXA administration, POD, and perioperative biomarkers of inflammation and neuronal injury.

This post hoc analysis of the prospective CONFESS cohort included patients aged ≥ 60 years undergoing elective spine surgery. POD was assessed using the Nursing Delirium Screening Scale and DSM-5 criteria. Multivariable logistic regression evaluated the association between TXA and POD. Perioperative changes in IL-6, S100β, sTREM2, and Gasdermin D were analyzed using repeated-measures ANOVA. False discovery rate correction was applied for multiple testing.

Among 93 enrolled patients, POD screening was available for 89, of whom 42 (47.2%) received intraoperative TXA. Overall, 17 patients (18.7%) developed POD, including 12 (70.6%) who had received TXA. In univariate analysis, TXA administration was associated with POD (OR 3.36, 95% CI 1.07-10.54; p = 0.035), but this association was not maintained after multivariable adjustment and false discovery rate correction. Gasdermin D was the only biomarker independently associated with POD (OR = 0.212 [0.046-0.974], p = 0.046). Significant perioperative biomarker changes were observed, with a significant time × treatment interaction only for IL-6 (p = 0.028). In exploratory subgroup analyses, TXA exposure was associated with a higher incidence of POD among patients aged ≥ 75 years, whereas no association was observed in younger patients.

In this exploratory post hoc analysis, intraoperative TXA administration was not independently associated with postoperative delirium after adjustment for relevant confounders. Although perioperative biomarker dynamics reflected the expected inflammatory response to surgery, only IL-6 demonstrated differential temporal changes according to TXA exposure, while Gasdermin D emerged as a potential biomarker associated with POD. Given the observational design, limited sample size, and small number of delirium events, these findings should be regarded as hypothesis-generating. Larger randomized studies using standardized TXA protocols are warranted to clarify the relationship between TXA, perioperative neuroinflammation, and postoperative delirium.