Hindman Bradley J, Olinger Catherine R, Woodroffe Royce W, Zanaty Mario, Streese Carolina Deifelt, Zacharias Zeb R, Houtman Jon C D, Wendt Linder H, Eyck Patrick P Ten, O'Connell-Moore Debra J, Ray Emanuel J, Lee Sarah J, Waldschmidt Daniel F, Havertape Lauren G, Nguyen Lanchi B, Chen Pei-Fu, Banks Matthew I, Sanders Robert D, Howard Matthew A
Department of Anesthesia, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
Department of Orthopedics and Rehabilitation, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
medRxiv. 2024 Oct 17:2024.10.16.24315638. doi: 10.1101/2024.10.16.24315638.
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.
Adults undergoing elective posterior lumbar fusion randomly received intraoperative intravenous TXA (n=43: 10 mg kg loading dose, 2 mg kg h 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.
Delirium incidence in the TXA group (7/32=22%) was not significantly less than in the Placebo group (11/33=33%); =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 (=0.001) and with postoperative interleukin -8 and -10 concentrations (=0.00008 and =0.005, respectively) and these associations were not significantly modified by TXA. In the Placebo group, delirium severity was associated with S100B concentration (=0.0009) and the strength of the association was decreased by TXA (=0.002).
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.
术后谵妄可能由围手术期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）可能会降低术后谵妄的发生率。为了探究这一假设，我们修改了一项正在进行的TXA随机试验，增加了术后谵妄、认知功能、全身细胞因子和星形胶质细胞活化的测量指标。
接受择期后路腰椎融合术的成年人被随机分为术中静脉注射TXA组（n = 43：负荷剂量10 mg/kg，输注速度2 mg·kg⁻¹·h⁻¹）或安慰剂组（n = 40）。在术前和术后24小时采集血液（n = 32），用于检测全身炎症生物标志物（细胞因子）和星形胶质细胞活化标志物（S100B）。使用3分钟诊断性访谈的谵妄评估方法，对参与者进行每日两次的谵妄评估（n = 65）。参与者在术前和出院后随访期间接受4项认知功能测量。
TXA组的谵妄发生率（7/32 = 22%）并不显著低于安慰剂组（11/33 = 33%）；P = 0.408，绝对差异 = 11%，相对差异 = 33%，效应量 = -0.258（95% CI -0.744至0.229）。在安慰剂组（n = 16）中，谵妄严重程度与固定椎体节段数有关（P = 0.001），与术后白细胞介素-8和-10浓度有关（分别为P = 0.00008和P = 0.005），且这些关联未被TXA显著改变。在安慰剂组中，谵妄严重程度与S100B浓度有关（P = 0.0009），且这种关联强度被TXA降低（P = 0.002）。
术后谵妄发生率相对降低33%的可能性证明有必要进行一项有足够效力的临床试验，以确定术中TXA是否能降低接受腰椎融合术成年人的谵妄发生率。
