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

BJA open Pub Date : 2025-04-14 DOI:10.1016/j.bjao.2025.100403

Bradley J. Hindman , Catherine R. Olinger , Royce W. Woodroffe , Mario Zanaty , Carolina Deifelt Streese , Zeb R. Zacharias , Jon C.D. Houtman , Linder H. Wendt , Patrick P. Ten Eyck , Debra J. O'Connell-Moore , Emanuel J. Ray , Sarah J. Lee , Daniel F. Waldschmidt , Lauren G. Havertape , Lanchi B. Nguyen , Pei-fu Chen , Matthew I. Banks , Robert D. Sanders , Matthew A. Howard III

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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.

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氨甲环酸减少成人腰椎融合术术后谵妄的探索性随机试验-一项试验提前停止

背景术后谵妄可能由全身炎症和神经炎症介导。通过抑制纤溶酶的促炎作用，氨甲环酸（TXA）可减少术后谵妄。为了探索这一假设，我们修改了一项正在进行的TXA对失血的随机试验，增加了谵妄、认知、全身炎症和星形胶质细胞激活的测量。方法接受择期腰椎后路融合术的成年人随机接受术中静脉注射TXA （n=43: 10 mg kg−1负荷剂量，2 mg kg−1 h−1输注）或安慰剂（n=40）。术前和术后24 h采血（n=32）检测生物标志物（细胞因子和S100B）。参与者每天进行两次谵妄评估（n=65）。参与者在手术前和出院后随访期间接受了四项认知功能测量。结果与安慰剂组相比，TXA组术后出血量减少约38%，中位数分别为128和207 ml， P=0.013。TXA组和安慰剂组的总失血量无差异，中位数分别为305和333 ml， P=0.472。TXA组谵妄发生率（7/32=22%）不显著低于安慰剂组（11/33=33%）；P=0.408，效应值= -0.258（95%置信区间为-0.744 ~ 0.229）。结论：术后谵妄发生率相对降低33%的可能性证明了一项足够有力的临床试验，以确定术中TXA是否能减少腰椎融合术中成人谵妄的发生率。临床试验注册号nct04272606。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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