后交叉韧带替代型骨水泥假体单侧膝关节置换：静脉注射与关节腔氨甲环酸并用可减少失血量及炎症反应

doi:10.3969/j.issn.2095-4344.1962

摘要/Abstract

摘要：

文章快速阅读：

文题释义：

膝关节置换围术期血液管理：该手术需要广泛松解软组织、截除关节面以及暴露髓腔，术后抗凝治疗、关节功能锻炼，往往伴随着大量失血，导致患者出现贫血。如果贫血状态得不到纠正会严重影响患者的预后，如增加感染风险、延缓术后康复、增加致残率和死亡率以及延长住院时间。因此在人工膝关节置换围手术期，做好血液管理显得尤为重要。

止血带：止血带的使用可以提供干燥清洁的手术区域，有助于改善术野、减少术中出血和缩短手术时间，但是止血带也可引起神经麻痹、肌肉萎缩、股四头肌无力等并发症，甚至止血带释放后局部纤溶系统的激活增加了术后出血量，如何减少全膝关节置换围手术期出血量和异体输血量是临床一直努力的方向。

摘要

背景：目前已有大量文献证实，全膝关节置换术中应用氨甲环酸可有效减少围术期出血，但哪种氨甲环酸使用方式最具优势尚无统一观点，而且给予氨甲环酸后血液中相关炎症因子的变化情况相关研究较少。

目的：探讨全膝关节置换术中不同氨甲环酸给药方法对围术期失血量及炎症反应的影响。

方法：选择2016年6月至2018年6月因膝关节骨性关节炎行初次单侧全膝关节置换的患者90例，利用信封抽签法随机分3组，每组30例，均进行后交叉韧带替代型骨水泥膝关节假体置换手术，A组术中静脉输注氨甲环酸止血，B组术中关节腔注射氨甲环酸止血，C组术中静脉输注与关节腔联合应用氨甲环酸止血。计算围术期患者总失血量及隐性失血量，并记录输血患者数和输血量；术前及术后1，3，7 d，检测纤维蛋白原水平、凝血酶原时间及活化部分凝血活酶时间；术前及术后1，3，7 d，测定炎性因子C-反应蛋白、白细胞介素6水平；术后1周检查是否有深静脉血栓形成，随访6个月观察下肢深静脉血栓及肺栓塞发生情况。研究方案经海南省第三人民医院伦理委员会批准。

结果与结论：①A、B组围术期总失血量高于C组(P < 0.05)；3组隐性失血量及输血率比较差异无显著性意义(P > 0.05)；②术前及术后1，3，7 d，3组间纤维蛋白原水平、凝血酶原时间及活化部分凝血活酶时间比较差异均无显著性意义(P > 0.05)；③术后1，3 d，各组C-反应蛋白及白细胞介素6水平均高于术前(P < 0.05)，3组间两指标比较差异无显著性意义(P > 0.05)；术后7 d，各组C-反应蛋白及白细胞介素6水平基本下降至术前水平，3组间两指标比较差异无显著性意义(P > 0.05)；④术后1周双下肢血管超声显示3组均无深静脉血栓形成；随访6个月，3组均未出现下肢深静脉血栓及肺栓塞病例；⑤结果表明与单独静脉注射及关节腔应用相比，二者联合应用氨甲环酸能明显降低全膝关节置换围术期的总出血量，并且不增加深静脉血栓形成的风险。不同氨甲环酸使用方式对炎症反应无明显影响。

ORCID: 0000-0001-5429-2481(吴兴源)

中国组织工程研究杂志出版内容重点：人工关节；骨植入物；脊柱；骨折；内固定；数字化骨科；组织工程

关键词: 全膝关节置换术, 氨甲环酸, 关节腔内注射, 静脉注射, 出血量, C-反应蛋白, 白细胞介素6, 深静脉血栓

Abstract:

BACKGROUND: A large number of literatures have confirmed that the use of tranexamic acid in total knee arthroplasty can effectively reduce perioperative bleeding, but there is no consensus on which tranexamic acid is most used. Little is reported on the changes of related inflammatory factors in blood after tranexamic acid is given.

OBJECTIVE: To investigate the effects of different tranexamic acid administration methods on perioperative blood loss and inflammatory response in total knee arthroplasty.

METHODS: Ninety patients who underwent unilateral total knee arthroplasty due to knee osteoarthritis from June 2016 to June 2018 were included in this study. They were randomly divided into three groups, 30 in each group using the envelope lottery method. All of them received cemented posterior cruciate ligament-retaining unilateral total knee arthroplasty. In group A, patients were treated by intravenous infusion of tranexamic acid. In group B, intraarticular injection of tranexamic acid was performed. In group C, both intravenous and intraarticular administration of tranexamic acid was used. Perioperative total blood loss and occult blood loss were calculated, and the number of patients receiving blood transfusion and the volume of blood transfused were recorded. Fibrinogen level, prothrombin time, activated partial thromboplastin time, and the levels of inflammatory factors C-reactive protein and interleukin-6 were measured before and 1, 3 and 7 days after surgery. Deep vein thrombosis was examined at 1 week after surgery. All patients were followed up for 6 months to determine the occurrence of deep vein thrombosis and pulmonary embolism. This study was approved by the Medical Ethics Committee of the Third People’s Hospital of Hainan Province, China.

RESULTS AND CONCLUSION: (1) Total perioperative blood loss in groups A and B was significantly higher than that in group C (P < 0.05). There were no significant differences in occult blood loss and blood transfusion rate among the three groups (P > 0.05). (2) There were no significant differences in fibrinogen level, prothrombin time and activated partial thromboplastin time among three groups before surgery and at 1, 3 and 7 days after surgery (P > 0.05). (3) In each group, C-reactive protein and interleukin-6 levels at 1 and 3 days after surgery were significantly higher than those before surgery (P < 0.05), and there were no significant differences in C-reactive protein and interleukin-6 levels among three groups (P > 0.05). (4) At 7 days after surgery, the levels of C-reactive protein and interleukin-6 in each group decreased to the levels before surgery, and there were no significant differences among three groups (P > 0.05). Vascular ultrasound examination of the both lower limbs showed no deep vein thrombosis at 1 week after surgery. After 6 months of follow-up, there were no cases of deep venous thrombosis and pulmonary embolism in the lower limbs. (5) The results suggest that compared with simple intravenous or intraarticular administration of tranexamic acid, combined intravenous and intraarticular administration of tranexamic acid can greatly reduce total perioperative blood loss and does not increase the risk of developing deep vein thrombosis after total knee arthroplasty. Different administration methods of tranexamic acid have no obvious effects on inflammatory response.

Key words: total knee arthroplasty, tranexamic acid, intraarticular injection, intravenous injection, amount of blood loss, C-reactive protein, interleukin-6, deep vein thrombosis

中图分类号:

R618|R453.9|R318

吴兴源，张国如，刘傥，周才盛. 后交叉韧带替代型骨水泥假体单侧膝关节置换：静脉注射与关节腔氨甲环酸并用可减少失血量及炎症反应[J]. 中国组织工程研究, 2019, 23(36): 5753-5759.

Wu Xingyuan, Zhang Guoru, Liu Tang, Zhou Caisheng. Intravenous and intraarticular tranexamic acid can reduce blood loss and inflammatory response during cemented posterior cruciate ligament-retaining unilateral total knee arthroplasty[J]. Chinese Journal of Tissue Engineering Research, 2019, 23(36): 5753-5759.

图/表（结果） 4

参考文献

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引言

材料方法

1.1 设计 随机对照试验。

1.2 时间及地点 试验于2016年6月至2018年6月在海南省第三人民医院骨关节外科完成。

1.3 对象 选择2016年6月至2018年6月因膝关节骨性关节炎行初次单侧全膝关节置换的患者90例，其中男38例，女52例。根据信封抽取法随机分为3组，每组30例，A组为氨甲环酸静脉输注组，B组为氨甲环酸关节腔应用组，C组为氨甲环酸静脉输注+关节腔应用组，3组均使用施乐辉公司的后交叉韧带替代型骨水泥人工膝关节假体。此次研究方案经海南省第三人民医院伦理委员会批准，患者对治疗知情同意并签署知情同意书。

纳入标准：①原发性膝关节骨性关节炎患者；②行初次单侧全膝关节置换患者；③术前血红蛋白含量及凝血功能均正常的患者；④患者对治疗知情同意并签署知情同意书。

排除标准：①类风湿性关节炎、创伤性关节炎患者；②凝血障碍或术前有抗凝药物服用史的患者；③有血管栓塞疾病史患者；④有下肢感染史患者；⑤贫血患者；⑥肝肾功能异常患者；⑦氨甲环酸过敏患者；⑧有高血栓形成风险患者；⑨癫痫患者。

1.4 假体 后交叉韧带替代型骨水泥人工膝关节假体理化性能，见表1。

1.5 方法

手术及分组给药方法：3组手术由同一组手术医师完成，术后引流管临时夹闭4 h。患者取仰卧位，全身麻醉，切皮前使用止血带。行膝关节正中切口，髌旁内侧入路，均不进行髌骨置换，仅修整髌骨面，行髌周去神经化处理，膝关节假体采用后交叉韧带替代型骨水泥假体。骨水泥固定后放置负压引流管，对切口进行逐层缝合，松止血带。A组将15 mg/kg氨甲环酸(山西普德药业有限公司，国药准字：14020886)溶于100 mL生理盐水，于松止血带时静脉输入；B组于关闭关节囊后关节腔内注入15 mg/kg氨甲环酸；C组同样将15 mg/kg氨甲环酸溶于100 mL生理盐水，于松止血带时静脉注射80 mL，在关闭关节囊后关节腔内注射20 mL。

术后处理：术后引流管夹闭2 h后开始引流，48 h后拔出引流管，之后即开始早期功能锻炼。术后12 h患者常规口服抗凝药物利伐沙班(拜耳，注册证号：H20140132) 10 mg，1次/d，使用15 d，预防下肢静脉血栓形成。分别于术后1，3，5 d常规复查血常规，当血红蛋白<80 g/L时予以输血治疗。

1.6 主要观察指标

1.6.1 围术期失血量及输血情况计算患者总失血量及隐性失血量，并记录患者身高、体质量、输血例数和输血量。总失血量=术前血容量×(红细胞压积_术前-红细胞压积_术后)；隐性失血量=总失血量+异体输血量-术中失血量-术后总引流量。其中术前血容量采用Nadler公式计算^[5]：血容量(L)=K₁×身高(m)+K₂×体质量(kg)+K₃，男性：K₁=0.366 9，K₂=0.032 19，K₃=0.604 1；女性：K₁=0.356 1，K₂=0.330 8，K₃=0.183 3。

1.6.2 凝血功能术前及术后1，3，7 d，采用德国BE血凝仪检测纤维蛋白原水平、凝血酶原时间、活化部分凝血活酶时间和D-二聚体水平。

1.6.3 炎性因子变化术前及术后1，3，7 d，采用ELISA法测定炎性因子C-反应蛋白及白细胞介素6水平(ELISA试剂盒购于江苏科晶生物科技有限公司)。

1.6.4 血栓发生情况术后1周进行双下肢血管超声检查观察是否有深静脉血栓形成。随访至6个月，观察下肢深静脉血栓及肺栓塞发生情况。

1.7 统计学分析 采用SPSS 21.0软件进行数据录入及统计学处理。3组间计量资料比较使用单因素方差分析，组间两两比较采用LSD法，计数资料比较采用卡方检验，P < 0.05为差异有显著性意义。