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白波, 周璞, 陈国栋, 牛增广. 髋膝关节置换术后预防下肢深静脉血栓形成的方法及其效果与安全性[J]. 武警医学, 2017,28(10): 1031-1034
BAI Bo, ZHOU Pu, CHEN Guodong, NIU Zengguang. Effectiveness of Low-molecular-weight heparin in combination with intermittent pneumatic compression against deep venous thrombosis following arthroplasty[J]. Medical Journal of the Chinese People's Armed Police Forces, 2017,28(10): 1031-1034  
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髋膝关节置换术后预防下肢深静脉血栓形成的方法及其效果与安全性
白波1, 周璞2, 陈国栋1, 牛增广1
1.066000,秦皇岛市第一医院骨一科
2.255000,淄博职业学院电子电气工程学院
通信作者: 陈国栋,E-mail:chenguodongspine@163.com

作者简介:白 波,硕士,主治医师。

收稿日期: 2017-05-05
摘要

目的 探讨间歇充气加压装置(intermittent pneumatic compression,IPC)联合低分子肝素(Low molecular weight heparin,LMWH)抗凝治疗预防膝、髋关节置换术后下肢深静脉血栓(deep venous thrombosis,DVT)的效果和安全性。方法 选取2015-01至2016-01于我科收治的膝髋关节置换患者80例,随机分为两组,一组单独使用LMWH抗凝治疗,另一组采用LMWH联合IPC预防下肢深静脉血栓形成。定期复查下肢静脉超声,可疑肺栓塞( pulmonary embolism,PE)患者行CT肺血管造影检查(computer tomography pulmonary angiography, CTPA)以明确诊断,监测血小板计数和凝血指标。所有患者出院后3个月内均进行随访,统计DVT发生率。结果 LMWH联合IPC抗凝组术后DVT发生率明显低于单独使用LMWH组( P<0.05),术后随访所有患者均未出现PE。所有患者INR均在2.5以内,血小板计数未减少。结论 IPC联合LMWH抗凝治疗与单纯应用LMWH抗凝治疗相比能够明显降低膝、髋置换术后早期下肢DVT的发生率,且具有良好的安全性。

关键词: 关节成形术; 置换; 静脉血栓形成; 肝素; 低分子量; 间歇充气加压装置
中图分类号:R687.4
Effectiveness of Low-molecular-weight heparin in combination with intermittent pneumatic compression against deep venous thrombosis following arthroplasty
BAI Bo1, ZHOU Pu2, CHEN Guodong1, NIU Zengguang1
1.Department of Orthopedics, The First Hospital of Qinhuangdao Qinhuangdao 066000, China
2.Zibo Vocational Institute Electric And Electronic Engineering,Zibo 255000,China
Abstract

Objective To investigate the effectiveness of intermittent pneumatic compression (IPC) device combined with low molecular weight heparin (LMWH) for the prevention of deep venous thrombosis(DVT) after joint replacement surgery. Methods 80 cases with hip or knee joint peripheral fractures and artificial joint replacements who were admitted to our hospital between January 2015 and January 2016 were randomly divided into two groups. The observation group was treated with low molecular heparin by subcutaneous injection and intermittent pneumatic compression to both lower limbs alternately, while the control group was treated with low molecular heparin alone after operation. The clinical symptoms of venous thromboembolism were observeded, deep venous thrombosis of both lower limbs examined by colour duplex ultrasonography ,and platelet count and blood coagulation were monitored after operation to check the presence of DVT. Results The incidence rates of venous thromboembolism in lower limbs after operation were significantly lower in the observation group than in the control group,so was the amount of bleeding. Pulmonary embolism did not occur in any of the cases. International normalized ratio( INR) did not exceed 2.5 and platelet count did not decrease. Conclusions LMWH in combination with IPC can significantly reduce the incidence of VTE after hip or knee surgery, and is quite safe.

Keyword: arthroplasty; replacement; venous thrombosis; heparin; low-molecular-weight; intermittent pneumatic compression

深静脉血栓形成是人工髋膝关节置换术后的主要并发症之一。致死性肺血栓栓塞症是深静脉血栓形成最严重的后果[1, 2], 也是人工关节置换术后最主要的致死原因, 人工关节置换术后的死亡有68%归因于肺血栓栓塞症[3]。引起肺血栓栓塞症主要来源于深静脉血栓形成, 尤其是下肢近端深静脉血栓(deep venous thrombosis, DVT)。肺栓塞(pulmonary embolism, PE)是DVT常见和严重的并发症, 也是导致死亡的主要原因[4, 5, 6]。

目前, 对于下肢深静脉血栓形成的干预措施主要分为两大类, 分别为药物干预和物理干预, 药物干预目前应用较多的是低分子肝素(Low molecular weight heparin, LMWH)[7], 物理干预措施包括间歇充气加压装置(intermittent pneumatic compression, IPC), 原理为通过加压加速下肢血流运动, 改变原有流速, 其临床作用已得到证实[8, 9]。随着人口老龄化, 人工关节置换手术数量必将呈上升趋势, 因此, 降低术后DVT的发生率, 已成为摆在关节外科医师面前的首要问题。本研究旨在通过随机对照研究, 探讨能否通过联合应用药物和物理干预措施来降低人工关节置换术后下肢深静脉血栓的发生率, 并对其安全性进行研究。

1 对象与方法
1.1 对象

选取自2015-01至2016-01于我科初次行人工全膝、全髋关节置换患者80例, 男32例, 女48例, 27~91岁, 平均(55.6± 3.2)岁; 体重55.0~85.0 kg, 平均(62.3± 5.2)kg。所有入选患者知晓试验方法和过程, 并通过院伦理委员会备案审核, 均签署知情同意书。排除标准:严重心功能衰竭、肾功能不全, 肝素过敏史、近期活动性出血史、确诊血栓形成者。将80例随机分为两组, 仅使用低分子肝素(low molecular weight heparin, LMWH)组(以下简称药物组)40例, 男18例, 女22例, 年龄30~91岁, 平均(52.6± 5.2)岁; 体重52.0~86.0 kg, 平均(63.4± 7.9)kg; 联合应用LMWH和IPC组(以下简称联合组)40例, 男14例, 女26例, 年龄27~86岁, 平均(53.4± 6.9)岁; 体重52.0~81.0 kg, 平均(65.5± 6.7)kg。两组患者性别、年龄、体重等指标均无统计学差异(P> 0.05)。

1.2 仪器与试剂

1.2.1 低分子量肝素钙注射液(万脉舒) 4100AXaIU, 河北常山生化药业股份有限公司。

1.2.2 间歇充气加压装置 Lympha-Tron(DL-1200K), 韩国( 株) 大星产业。

1.3 手术操作及术后处理

所有手术均由我科同一组高年资医师完成。人工全膝关节置换术采用膝前正中切口髌旁入路显露膝关节, 充分松解, 清除骨赘, 胫骨近端采用髓外定位截骨, 股骨远端采用髓内定位截骨, 选择合适型号假体及垫片, 所有患者未置换髌骨, 均用电刀灼烧髌骨周缘以去神经化。术后检查膝关节活动度及髌骨轨迹是否满意。人工全髋关节置换术采用髋关节后外侧入路, 显露臀大肌后, 将其钝性分离并轻度内旋髋关节, 切断外旋肌群, 进入关节囊后, 将髋关节脱位, 以小粗隆上方1.5 cm 左右作为截骨参考, 按照前倾10° ~15° , 外展约45° 安装髋臼假体, 股骨扩髓后选取适当股骨柄假体打入股骨髓腔。对髋关节进行复位, 并活动检查假体位置是否满意。48 h后拔除引流管, 术后14 d拆线。药物组术后8 h开始皮下注射低分子量肝素钙注射液(4100 IU), 1/d。联合组在皮下注射低分子量肝素钙注射液同时, 术后即开始使用间歇充气加压装置8 h, 从第2日至伤口拆线, 每天使用两次间歇充气加压装置, 每次持续1 h。

1.4 记录指标

动态监测凝血指标, 记录手术前后血小板计数和国际标准化比值(International normalized ration, INR) , 并观察双下肢肿胀情况, 其中包括皮温增高、下肢胀痛、皮肤暗红等DVT体征, 如有发现, 则立即行彩超检查。术后3、5、7和14 d复查双下肢静脉超声, 可疑PE患者, 立即行CT肺血管造影检查(computer tomography pulmonary angiography, CTPA)。术后随访至12周。

1.5 统计学处理

采用SPSS17.0进行统计学分析。计量资料以 x̅± s表示, 组间比较采用t检验; 计数资料以率(%)表示, 组间比较采用χ 2检验。P< 0.05为差异有统计学意义。

2 结 果

所有患者均随访至术后3个月, 药物组发生下肢深静脉血栓6例, 其中人工全膝关节置换2例, 人工全髋关节置换4例; 院内3例, 随访期间3例, 血栓发生率为15%; 联合组共发现下肢血栓1例, 为人工全髋关节置换术后患者, 术后8周随访时发现, 血栓发生率为2.5%。联合组术后DVT发生率明显低于药物组(χ 2=4.780, P=0.028), 差异有统计学意义(P< 0.05)。联合组术后DVT发生率明显低于药物组。所有确诊DVT患者, 立即停止使用IPC, 嘱患者卧床制动, 避免揉捏患肢。所有患者手术前后血小板计数, 未见减少, INR值均在2.5以内。

本次试验未发现PE患者。

3 讨 论

随着关节外科手术技术的不断进步与创新, 外科医师面临的不仅是技术难题, DVT和PE也同样摆在面前[10, 11, 12]。静脉血栓的形成因素大概可分为三类:血流瘀滞、血管壁受损及血液的高凝状态[13, 14, 15, 16]。膝髋关节置换术后患者, 术后卧床制动、运动量减少, 都可以造成静脉血流缓慢, 导致血栓形成。关节置换术中, 暴露牵拉、术中调整体位屈曲旋转下肢的同时, 可能造成血管壁受损, 导致血液瘀滞, 进一步形成血栓[17]。关节置换属于骨科大手术, 血小板应激状态下, 粘附性增大, 血液处于高凝状态[18, 19, 20]。据报道, 髋膝关节置换术患者都属于高危病例组, 其中近端DVT发生率10%~20%, 出现致命性PE 1%~5%[21], DVT常发生在术后7 d内[22], 因此从手术开始就应该从改善静脉瘀滞和控制高凝状态入手预防。

荟萃分析显示, LMWH作为预防骨科大手术后下肢DVT的临床措施, 术后6~9 h使用效果最佳, 并且无出血风险, 不会增加并发症[23], 这也是本试验中在术后8 h开始使用LMWH的原因, 结果也与文献报道一致, 术后使用LMWH效果确实, 未发现严重出血并发症。

作为物理预防措施, IPC可对患肢进行序贯加压, 从而增加静脉回流, 减少血液滞留, 以降低DVT的发生。同时, IPC治疗还可增加血浆纤维蛋白溶解作用。资料显示, IPC具有良好的预防DVT效果, 能使膝关节置换术后DVT发生率从35%~45%下降到10%~15%, 髋关节置换术后DVT发生率从45%~50%下降到10%~20%[24]。另有文献报道, IPC相对于逐级加压弹力袜, 具有更好的预防下肢DVT的效果, 术后早期使用, IPC可以替代下肢肌肉“ 静脉泵” 功能, 刺激下肢静脉回流, 促进血液循环[25]。因此, 我们采用IPC进行研究, 也是基于上述因素考虑, 没有采用逐级加压弹力袜。

单纯应用物理措施对于预防骨科大手术后下肢DVT效果差于药物预防, 但可以避免单纯使用药物抗凝的一些并发症, 比如出血倾向等, 可以单独应用于有高危出血风险的患者[26]; 传统药物抗凝的效果显著, 但是存在增加出血风险和一些并发症。多位学者研究结果表明, 不推荐单独使用物理预防措施, 可联合药物应用来提高预防效果。联合应用可避免单纯药物抗凝的并发症, 并提高疗效[27, 28]。膝髋关节置换术后属于高出血风险, 当高出血风险下降时, 推荐药物联合物理措施来预防DVT的形成。以此为依据, 作为设计本试验的理论基础, 联合多种模式可以发挥最大抗凝效果的同时, 避免不良并发症。本研究结果显示, 药物组DVT发生率为15%明显高于联合组的2.5%。LMWH联合IPC在人工关节置换术后预防下肢DVT的效果更为显著, 能够明显降低膝、髋置换术后早期下肢DVT的发生率, 具有统计学意义。所有患者手术前后血小板计数未见减少, INR值均在2.5以内, 未发现PE患者, 未发现出血并发症。试验结果表明, 联合应用IPC和LMWH是具有临床安全性的。

IPC和LMWH在临床中的选择, 需要根据患者病情制定进一步诊疗方案。如果术前已形成DVT, 术后IPC治疗可能引起血栓脱落, 导致PE, 危及生命。另外, 如患者存在凝血机制异常、有出血倾向及近期有颅内或消化道出血史, 则不建议使用LMWH, 而此时IPC可作为预防措施应用。因此, 根据患者情况, 合理使用药物及物理预防措施来控制血栓形成, 值得临床推广应用。本试验入选患者仅80例, 因此, 建立更大样本量、多中心、随机对照研究更具临床价值。

综上所述, IPC联合LMWH抗凝治疗与单纯应用LMWH抗凝治疗相比能够明显降低膝、髋置换术后早期下肢DVT的发生率, 且具有良好的安全性。

责任编辑 梁秋野

The authors have declared that no competing interests exist.

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