Background: Postoperative delirium may be mediated by perioperative systemic- and neuro-inflammation. By inhibiting the pro-inflammatory actions of plasmin, tranexamic acid (TXA) may decrease postoperative delirium. To explore this hypothesis, we modified an ongoing randomised trial of TXA, adding measures of postoperative delirium, cognitive function, systemic cytokines, and astrocyte activation. Methods: Adults undergoing elective posterior lumbar fusion randomly received intraoperative intravenous TXA (n=43: 10 mg kg-1 loading dose, 2 mg kg-1 h-1 infusion) or Placebo (n=40). Blood was collected pre- and at 24 h post-operatively (n=32) for biomarkers of systemic inflammation (cytokines) and astrocyte activation (S100B). Participants had twice daily delirium assessments using the 3-minute diagnostic interview for Confusion Assessment Method (n=65). Participants underwent 4 measures of cognitive function preoperatively and during post-discharge follow-up. Results: Delirium incidence in the TXA group (7/32=22%) was not significantly less than in the Placebo group (11/33=33%); P=0.408, absolute difference=11%, relative difference=33%, effect size = -0.258 (95% CI -0.744 to 0.229). In the Placebo group (n=16), delirium severity was associated with the number of instrumented vertebral levels (P=0.001) and with postoperative interleukin -8 and -10 concentrations (P=0.00008 and P=0.005, respectively) and these associations were not significantly modified by TXA. In the Placebo group, delirium severity was associated with S100B concentration (P=0.0009) and the strength of the association was decreased by TXA (P=0.002). 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.

The authors have declared no competing interest.

NCT04272606

This work was supported by the National Center For Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR004403. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA086862. Other financial support was provided by The University of Iowa Roy J. and Lucille A. Carver College of Medicine Department of Neurosurgery.

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