氨甲环酸用于全膝关节置换降低失血量的有效性及安全性

doi:10.3969/j.issn.2095-4344.2015.31.005

摘要/Abstract

摘要：

背景：氨甲环酸是一种人工合成的抗纤维蛋白溶解的药物，可以经静脉有效的控制全膝关节置换后失血。
目的：观察氨甲环酸对初次行单侧全膝关节置换患者置换后失血的有效性及安全性。
方法：选取2014至2015年在四川省骨科医院下肢科行单侧全膝关节置换的100例患者。以使用氨甲环酸与否分为试验组和对照组，各50例。试验组患者在全膝关节置换前10 min静脉注射氨甲环酸1 g，而对照组不给予氨甲环酸。
结果与结论：试验组患者置换后围手术期总失血量、置换后24 h引流量、输血量明显少于对照组(P < 0.05)；试验组与对照组术中出血量、输血人数差异无显著性意义。两组患者患者置换前血红蛋白水平差异无显著性意义，而置换后血红蛋白水平均下降，且试验组患者置换后血红蛋白水平均明显高于对照组。置换后24 h，两组患者凝血功能差异无显著性意义。置换后6 d，2组患者双下肢静脉彩色多普勒超声检查均未见深静脉血栓。提示初次单侧全膝关节置换前静脉给予氨甲环酸能明显减少围手术期失血量及输血量，降低输血风险及输血费用，利于术后功能恢复，且不增加下肢深静脉血栓的风险。

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: 植入物, 人工假体, 氨甲环酸, 全膝关节置换, 失血量, 深静脉血栓, 输血

Abstract:

BACKGROUND: Tranexamic acid is a synthetic anti-fibrinolytic drug, and can effectively control blood loss after total knee arthroplasty through vein.
OBJECTIVE: To evaluate the effectiveness and safety of tranexamic acid in reducing blood loss after primary unilateral total knee arthroplasty.
METHODS: From 2014 to 2015, 100 patients from the Department of Lower Limb, Sichuan Orthopaedic Hospital underwent primary unilateral total knee arthroplasty, and randomly divided into test group which used tranexamic acid and control group which used tranexamic acid, with 50 cases in each group. 1 g tranexamic acid was infused into the vein at 10 minutes before total knee arthroplasty in the test group, but tranexamic acid was not given in the control group.
RESULTS AND CONCLUSION: The amount of total blood loss, postoperative wound drainage in 24 hours, and the amount of blood transfusion were significantly less in the test group than in the control group (P < 0.05). No significant differences in intraoperative blood loss and the number of patients receiving blood transfusion were found between the test and control groups. No significant difference in preoperative hemoglobin levels was detected before surgery, but hemoglobin levels were decreased after surgery between the two groups. Postoperative hemoglobin levels were apparently higher in the test group than in the control group after surgery. At 24 hours after surgery, no significant difference in coagulation was detectable between the two groups. At 6 days, double lower limb vein color Doppler ultrasound examination did not reveal deep vein thrombosis in both groups. These findings verify that treatment with tranexamic acid in the vein before primary unilateral total knee arthroplasty can evidently diminish the amount of perioperative blood loss and blood transfusion, reduce the risk and cost of blood transfusion, which is good for rehabilitation and does not increase the risk of deep vein thrombosis.

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

Key words: Tranexamic Acid, Arthroplasty, Replacement, Knee, Venous Thrombosis, Blood Transfusion

中图分类号:

R318

曹万军，朱绍灵，刘显东，唐承杰，郑金文，陈星宇，刘颖，肖鹏. 氨甲环酸用于全膝关节置换降低失血量的有效性及安全性[J]. 中国组织工程研究, 2015, 19(31): 4944-4948.

Cao Wan-jun, Zhu Shao-ling, Liu Xian-dong, Tang Cheng-jie, Zheng Jin-wen, Chen Xing-yu, Liu Ying, Xiao Peng. Tranexamic acid reduces blood loss in total knee arthroplasty: effectiveness and safety[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(31): 4944-4948.

图/表（结果） 5

参考文献

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引言

材料方法

设计：同期非随机对比观察。
时间及地点：试验于2014至2015年在四川省骨科医院下肢科完成。
对象：选择2014至2015年在四川省骨科医院下肢科行单侧全膝关节置换的患者。
纳入标准：①首次行单侧全膝关节置换且年龄位于60-90岁的骨关节炎和类风湿性关节炎患者。②置换前实验室检查及双下肢静脉彩超均正常。③无膝关节开放手术史。
排除标准：①使用氨甲环酸禁忌者：包括血栓形成倾向的房颤患者、支架植入者。②氨甲环酸过敏者。③凝血功能异常者。④既往发生过深静脉血栓者。⑤严重心、肺、肝、肾功能不全者。
通过纳入标准及排除标准筛选出100例患者。以使用氨甲环酸与否进行分组：静脉注射氨甲环酸者为试验组(n=50)，不注射的患者为对照组(n=50)。两组患者基本资料在年龄、性别、体质量指数、病种差异均无显著性意义(P > 0.05)。
材料：假体为后叉韧带替代型骨水泥固定人工膝关节，购自英国Smith & Nephew公司。
方法：
全膝关节置换：所有手术均由同一高年资医师完成，全身麻醉下采用髌旁内侧入路，所有手术均在止血带控制下完成，并于切皮前进行止血带充气，止血带压力为 240-280 mm Hg(1 mm Hg=0.133 kPa)，伤口包扎完成后释放。其余所有患者的血液管理方法两组均相同，均未予术中自体血回输。所有患者均未进行置换前自体血储存或接受促红细胞生成素治疗。两组患者均使用弹力绷带加压包扎，置换后24 h拔出引流管，置换后两组患者进行标准补液和多模式镇痛。对于血红蛋白小于75 g/L的患者予输血治疗，大于75 g/L而小于100 g/L根据患者具体一般情况酌情输血治疗。所有患者均按照《中国预防骨科大手术深静脉血栓形成指南》进行正规抗凝治疗[2]。置换后2周切口拆线出院。
氨甲环酸治疗：试验组患者在全膝关节置换前10 min将氨甲环酸1 g稀释于100 mL生理盐水后静脉注射，而对照组不给予氨甲环酸。
手术指标观察：比较2组患者术中出血量、围手术期总失血量、置换后24 h总引流量、输血量、输血率。围手术期总失血量根据Nadler[3]、Gross等[4]关于失血量计算方法进行计算。
血液指标分析：置换后6 h，1 d，2 d，3 d时血红蛋白水平以及置换后24 h凝血酶原时间、活化部分凝血酶原时间、纤维蛋白原、深静脉血栓发生率及并发症情况^[5]。
主要观察指标：2组患者的手术指标和深静脉血栓发生情况。
统计学分析：数据采用SPSS 19.0软件包进行统计分析。计量资料数据以x(_)±s表示。两组计量资料比较采用独立样本t 检验；不同时期计量资料之间比较采用重复测量资料的方差分析；计数资料之间比较采用卡方检验，P < 0.05为差异有显著性意义。

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

讨论

全膝关节置换的失血量通常较大，而置换后失血相关并发症也更为严重。通常认为膝关节周围软组织内出血会加重疼痛、关节僵硬并使术后恢复时间延长。此外，关节腔内积血会导致膝关节肿胀、伤口延迟愈合并增加感染的风险。而目前与之相关的血液方案包括术前自体血储存、围手术期使用促红细胞生成素^[6]、术中血液稀释、切口中局部使用促凝血药物等，花费较高且可能导致相关并发症发生。同种异体输血不仅价格昂贵，并且有传播血源性疾病的风险^[7-8]。输血还可能导致各种免疫调节反应，更重要的是目前已经公认其有导致关节假体周围感染的风险^[9]。

由于全膝关节置换后的出血主要是由于纤溶亢进所致^[10-11]，因此越来越多的关节外科医师开始关注抗纤溶药物在全膝关节置换中的应用。氨甲环酸作为一种合成的抗纤溶药物，其不良反应相对较少，最早1995年Royston^[12]在胸外科手术中使用，目前已广泛应用于心脏外科、肝脏移植及妇科等手术中^[1，13-15]，并且获得了满意的止血效果。Hiippala等^[16]对75例接受全膝关节置换的患者进行随机对照研究，发现使用氨甲环酸者围手术期的失血量和平均输血量均明显减少。近年来已有相关文献报道氨甲环酸应用于脊柱外科及关节外科，其止血效果满意。最近的Meta分析报道氨甲环酸可以有效降低全膝关节置换后的失血量^[16]。

与此同时，对于氨甲环酸的使用方案也并未形成统一的意见，使用方法包括静脉滴注、肌内注射、关节腔内局部使用和口服。静脉使用氨甲环酸后血浆浓度达到峰值的时间为5-15 min，明显短于肌注和口服，因此静脉使用被认为是最有效的方法。Maniar等^[17]发现手术前后不同时间点使用氨甲环酸者的出血量均比未使用者下降，而术前使用的效果要优于松止血带时使用的效果，并由此推断出在纤溶亢进的开始阶段使用的效果优于纤溶达顶峰时使用的效果。本试验中氨甲环酸的使用方法仅在切皮前静脉滴注1 g剂量的氨甲环酸。与MacGillavray等^[18]的结果不同，本试验中患者对异体输血的需求较低，对照组患者置换后对异体输血的需求是试验组的3倍，结果体现了应用氨甲环酸的益处。

由于氨甲环酸具有抗纤维蛋白溶解效应，因此在理论上存在发生深静脉血栓事件的风险^{[1，14，16，18-39]}，而关节置换患者本身就存在较高的静脉血栓栓塞事件风险，因此在这些患者使用氨甲环酸仍存在一定的顾虑。本试验于置换后6 d常规进行多普勒超声检查监测下肢深静脉血栓形成情况，发现2组患者均未出现静脉血栓栓塞体征或症状。这进一步证实了meta分析关于氨甲环酸并不会增加全关节置换病例深静脉血栓事件发生率的结论^[40-42]。

本试验的主要不足之处在于回顾性研究具有一定局限性，一些未检测到的混杂变量可能会影响到研究结果的准确性。然而，本试验是对在一较短时期内(12个月)接受单侧全膝关节置换的连续病例进行的评估，全部手术均由同一名医师采用标准临床路径完成，且研究期间无任何可能影响术后失血量的医疗护理方案的更改。此外，未发现2组患者置换前特征有差异。本试验的优势在于研究设计上具有很高的均质性(单一术者、完全相同的假体和手术技术)、无混杂变量(无术前自体血储存、未采用其他血液保护方法且未放置引流)以及病例样本量较大。

综上所述，本试验发现在单侧全膝关节置换切皮前注射单次剂量氨甲环酸(1 g)可以显著降低围手术期失血量及输血率，避免为输血而额外付费，同时避免了输血相关并发症的风险，该使用方案有效并且安全。下一步将通过对比氨甲环酸不同的使用方法，寻找到最佳的用药方案。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