静脉应用不同剂量氨甲环酸对微创小切口经椎间孔腰椎椎间融合术围术期失血量影响的前瞻性随机对照研究

Prospective randomized controlled trial on the effectiveness of low-dose and high-dose intravenous tranexamic acid in reducing perioperative blood loss in single-level minimally invasive transforaminal lumbar interbody fusion

目的 采用前瞻性随机对照研究静脉应用不同剂量氨甲环酸(tranexamic acid,TXA)在单节段单侧微创小切口经椎间孔腰椎椎间融合术(minimally invasive transforaminal lumbar interbody fusion,MIS-TLIF)中应用的有效性及安全性。方法 纳入2019年9月-2020年10月符合选择标准的116例行单节段单侧MIS-TLIF手术患者,按随机数字表法分为低剂量(low-dose,LD)组(39例)、高剂量(high-dose,HD)组(39例)、安慰剂对照(placebo-controlled,PC)组(38例)。其中LD、HD组分别于全身麻醉后切皮前30 min给予患者静脉滴注TXA20 mg/kg和50 mg/kg,PC组则予以等量生理盐水。3组患者年龄、性别、身体质量指数、手术节段及术前血液学检查指标[红细胞压积(hematocrit,HCT)、血红蛋白(hemoglobin,HGB)、凝血酶原时间(prothrombin time,PT)、国际标准化比值(international normalized ratio,INR)、D-二聚体(D-dimer)、纤维蛋白(原)降解产物(fibrin degradation products,FDP)、活化部分凝血活酶时间(activated partial prothromboplastin time,APTT)、谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)、肌酐(creatinine,Cr)、尿素)]比较,差异均无统计学意义(P>0.05)。比较3组术中失血量(introperative blood loss,IBL)、术后引流量、手术时间,术后第1天总失血量(total blood loss,TBL)、隐性失血量(hidden blood loss,HBL)、输血情况,术后第1天血液学检查指标,术后1个月内并发症发生情况。结果 LD、HD、PC组分别有3、2、4例患者行自体血回输,3组均无同种异体血输血患者。3组间IBL、术后引流量和手术时间比较差异无统计学意义(P>0.05)。LD、HD组TBL、HBL和HGB下降值均明显低于PC组,HD组TBL、HBL明显低于LD组,差异均有统计学意义(P<0.05);LD组和HD组间HGB下降值比较差异无统计学意义(P>0.05)。术后第1天LD、HD组D-dimer显著低于PC组,差异有统计学意义(P<0.05);LD组和HD组间差异无统计学意义(P>0.05)。3组间其余血液学指标比较差异均无统计学意义(P>0.05)。所有患者均获1个月随访,3组均无下肢深静脉血栓形成、肺栓塞、癫痫等TXA相关并发症发生。结论 在单节段单侧MIS-TLIF术中静脉应用TXA,能明显减少术后1 d内的TBL及HBL,且呈剂量依赖性;同时可降低术后纤溶指标,且不增加下肢深静脉血栓形成及肺栓塞等并发症发生风险。

Objective A prospective randomized controlled trial was conducted to study the effectiveness and safety of intravenous different doses tranexamic acid(TXA) in single-level unilateral minimally invasive transforaminal lumbar interbody fusion(MIS-TLIF). Methods The patients treated with single-level unilateral MIS-TLIF between September 2019 and October 2020 were enrolled and randomly classified into low-dose TXA(LD) group(n=39), highdose TXA(HD) group(n=39), and placebo-controlled(PC) group(n=38). The LD, HD, and PC groups received intravenous TXA 20 mg/kg, TXA 50 mg/kg, the same volume of normal saline at 30 minute before skin incision after general anesthesia, respectively. There was no significant difference on baseline characteristics and preoperative laboratory results among 3 groups(P>0.05), including age, gender, body mass index, surgical segments, hematocrit(HCT),hemoglobin(HGB), prothrombin time(PT), international normalized ratio(INR), D-dimer, fibrin degradation products(FDP), activated partial prothromboplastin time(APTT), alanine aminotransferase(ALT), aspartate aminotransferase(AST), creatinine(Cr), urea. The intraoperative blood loss(IBL), postoperative drainage volume, operation time, total blood loss(TBL), hidden blood loss(HBL), blood transfusion, hematological examination indexes on the first day after operation, and the incidence of complications within 1 month were compared among the 3 groups. Results There were3, 2, and 4 patients in the LD, HD, and PC groups who underwent autologous blood transfusion, respectively, and there was no allogeneic blood transfusion patients in the 3 groups. There was no significant difference in IBL, postoperative drainage volume, and operation time between groups(P>0.05). The TBL, HBL, and the decreased value of HGB in LD and HD groups were significantly lower than those in PC group(P<0.05), and TBL and HBL in HD group were significantly lower than those in LD group(P<0.05);the decreased value of HGB between LD group and HD group showed no significant difference(P>0.05). On the first day after operation, D-dimer in LD and HD groups were significantly lower than that in PC group(P<0.05);there was no significant difference between LD and HD groups(P>0.05). There was no significant difference in other hematological indexes between groups(P>0.05). All patients were followed up 1 month, and there was no TXA-related complication such as deep venous thrombosis of lower extremity, pulmonary embolism, and epilepsy in the 3 groups. Conclusion Intravenous administration of TXA in single-level unilateral MIS-TLIF is effective and safe in reducing postoperative TBL and HBL within 1 day in a dose-dependent manner. Also, TXA can reduce postoperative fibrinolysis markers and do not increase the risk of thrombotic events, including deep venous thrombosis and pulmonary embolism.