Exploratory randomised trial of tranexamic acid to decrease postoperative delirium in adults undergoing lumbar fusion—a trial stopped early

Abstract

Background: Postoperative delirium may be mediated by systemic inflammation and neuroinflammation. By inhibiting the proinflammatory actions of plasmin, tranexamic acid (TXA) may decrease postoperative delirium. To explore this hypothesis, we modified an ongoing randomised trial of TXA on blood loss, adding measures of delirium, cognition, systemic inflammation, and astrocyte activation. Methods: Adults undergoing elective posterior lumbar fusion randomly received intraoperative i.v. TXA (n=43: 10 mg kg−1 loading dose, 2 mg kg−1 h−1 infusion) or placebo (n=40). Blood was collected before surgery and 24 h after surgery (n=32) for biomarkers (cytokines and S100B). Participants had twice daily delirium assessments (n=65). Participants underwent four measures of cognitive function before surgery and during post-discharge follow-up. Results: Postoperative blood loss was ∼38% less in the TXA group compared with the placebo group with medians of 128 and 207 ml level−1, respectively, P=0.013. Total blood loss in the TXA and placebo groups did not differ with medians of 305 and 333 ml level−1, respectively, P=0.472. Delirium incidence in the TXA group (7/32=22%) was not significantly less than in the placebo group (11/33=33%); P=0.408, effect size =–0.258 (95% confidence interval –0.744 to 0.229). Conclusions: A potential 33% relative decrease in postoperative delirium incidence justifies an adequately powered clinical trial to determine if intraoperative TXA decreases delirium in adults undergoing lumbar fusion. Clinical trial registration: NCT04272606.