The Effect of  Graduated Compression Stocking Alone or Combined with Intermittent Pneumatic Compression for Preventing Deep Vein Thrombosis in Major Surgery <?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

袁训芝*  吴新民*
宋琳琳*  袁家颖#
＊北京大学第一医院麻醉科，北京 100034
＃北京大学第一医院检验科，北京 100034

Xun-zhi Yuan*, Xin-min Wu*, Lin-Lin Song* , Jia-ying Yuan#

*Department of Anesthesiology, Peking  University First Hospital, Beijing 100034, China
#Department of Laboratory Medicine, Peking  University First Hospital, Beijing 100034, China

ABSTRACT

Objective：This prospective study was to evaluate the efficacy and safety of graduated compression stocking (GCS) alone or combined with intermittent pneumatic compression (IPC) for preventing deep venous thrombosis (DVT) in patients performing major surgery with malignancy. Changes of hemostatic substrate were observed perioperatively.

Methods：Consecutive 240 cases of patients with malignant tumor from department of thoracic surgery, urology and hepatobilliary surgery were allocated into control or one of and three test groups (GCS alone, GCS + full-time IPC and GCS + postoperative IPC). GCS was taken before surgery and continued postoperatively until recovery to normal mobility.IPC was initiated before surgery in group of GCS+full-time IPC and immediately after surgery in group of GCS+postoperative IPC until next morning, then intermittent 2h use with 2h interval until off-bed mobility. Deep venous ultrasound imaging were performed in all patients 3~8d postoperatively for thrombosis screening and blood velocity determination. Blood was sampled in 15 cases of GCS+full-time IPC and 15 cases of controls immediately before surgery, 2h after skin incision and 24h after surgery for the determination of plasma D-Dimer (D-D), tissue-type plasminogen activator antigen (tPA-Ag), plasminogen activator inhibitor antigen (PAI-Ag), von Willebrand factor (vWF), activated partial thromboplastin time (APTT) and prothrombin time (PT). No thrombo-embolic history were found in all patients. The risk for thromboembolism were assessed before surgery.
　　Results：DVT were found in 9/60 (15%), 14/60 (23.3%), 18/60 (30%) in group GCS+full-time IPC, GCS+postoperative IPC and GCS alone respectively, compared with 29/60 (48.3%) in control group with no prophylaxis, P<0.05. Proximal thrombosis was fond in only one case. Hemostatic parameter: D-D increased significantly 24h postoperatively in test group but not in controls. tPA-Ag level was lower in test group compared with controls 2h after surgery, in contrast, vWF was higher in test group, no significant changes were fond for PAI. The higher the age, body weight and risk factor, the more the DVT incidence.
　　Conclusions：In high risk patients with major surgery and malignant tumor, prophylaxis with GCS+full-time IPC and GCS+postoperative IPC can prevent DVT effectively. GCS alone may only apply to mild to intermediate risk of patients thrombosis prevention. Hemostatic changes after surgery in group of GCS+full-time IPC showed that mechanic measures may contribute to decreased thrombosis by increasing fibrinolytic activity.
　　Key Words：Deep venous thrombosis; Major surgery; Malignancy; Risk factor; Coagulation; Fibrinolysis
　　Corresponding author：Xin-min Wu; E-mail: xmwu2784@hotmail.com

静脉血栓栓塞包括深静脉血栓形成(DVT)和肺栓塞，过去大多数人一直认为亚洲患者此类并发症少见，但国内外研究证实大手术术后静脉血栓栓塞不但发生率高，还是致死和致残的主要原因^[1,2,3]。随着外科手术技术的发展，手术相关的并发症下降，预防大手术术后DVT和肺栓塞更显重要。本研究连续对胸科、泌尿外科、肝胆外科恶性肿瘤根治手术患者，使用物理方法进行术后DVT的预防，并对压力梯度长袜(GCS)联合间歇气压装置(IPC)全程组患者血栓相关的分子标志物进行动态观察，现报告如下。<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

一、临床资料与方法
　　入选标准: 所有胸外科(肺癌、食管癌等)、泌尿外科(包括肾癌、输尿管癌、前列腺癌、膀胱癌等)及肝胆外科(肝癌、胆囊癌、胰腺癌及胆管探查等)等患者。
　　排除标准: 术前正在应用肝素或口服华法令抗凝治疗患者，年龄小于40岁。
　　记录伴随危险因素: 高龄(>60岁)、高血压、高脂血症、糖尿病、吸烟、长时间制动、瘫痪、静脉血栓栓塞病史、血栓栓塞的家族史、肿瘤、肥胖、静脉曲张、心肌梗死、充血性心衰、缺血性脑卒中、短暂脑缺血发作、肝素诱发的血小板减少症、癌症化疗、肾病综合征、炎症性肠病(溃疡性结肠炎等)、口服避孕药及雌激素应用。
　　麻醉方法及监测: 患者入室后常规开放静脉，给咪唑安定1～2mg。动脉直接测压，行脉搏血氧饱和度(SPO₂)、呼气末二氧化碳(ETCO₂)及心电图(ECG)等监测。硬膜外穿刺置管用于术中麻醉和术后止痛。麻醉诱导采用丙泊酚1～2mg /kg或依托咪酯0.2～0.3mg/kg、芬太尼0.1～0.2mg 、维库溴铵0.06～0.1mg/kg 或罗库溴铵0.6mg/kg快速诱导，行气管插管。术中异氟烷、氧化亚氮、硬膜外麻醉和肌松剂维持。所有患者术后三天内硬膜外自控镇痛(PCEA)或静脉自控镇痛(PCA)。
　　物理方法预防下肢DVT: 连续入选符合条件患者40例，分为4组，即对照组(C)和三个实验组，实验组包括GCS组、GCS+IPC全程应用组(术前开始)、GCS+IPC术后应用组。逐步加压长袜和间歇气压装置均由美国泰科医疗提供，名称为TCD梯度压力抗栓袜和SCD RESPONSE压力抗栓泵。GCS组: 患者入室后，测量大腿根部周径(A)，如A≤63.5cm选腿长型弹力袜；然后测量小腿最粗部分周径(B)，B≤30.5cm选小号，30.5cm<B≤38.1cm选中号，38.1cm<B≤44.51cm选大号，嘱患者出院后活动接近正常后脱掉；GCS+IPC全程组：按GCS组选好合适袜子，将合适型号压力腿套(型号与袜子一致)固定在袜子外面，连接IPC，手术切皮前即刻开始应用，持续应用至次日晨，然后每隔h应用h，一直应用到患者下床活动；GCS+IPC术后组：手术结束回病房或ICU即刻开始应用，持续至次日晨，然后每隔2h应用2h，一直应用到患者下床活动。
　　下肢血管超声检查: 所有患者于术后3～8d使用美国百胜Du3型高分辨率床旁彩色多普勒超声，行双下肢深静脉血管超声检查。加压超声纵切和横切血管不可压迫，血流及声音消失为超声诊断静脉血栓形成的标准^[1]，记录双下肢血栓发生的部位。如果发生在?静脉(包括?静脉)以上为近端DVT，如果发生在?静脉(不含?静脉)以下为远端DVT。

综合上述，无论是单纯采用GCS 或与IPC联合应用预防恶性肿瘤根治手术患者预防围术期发生DVT是一个综合过程，要取得最佳效果，除了提高手术技术外，还应注意:
　　(1)依从性差是GCS或IPC应用中主要问题，因此术前做好患者和家属预防DVT教育，取得配合;
　　(2)积极、早期(在手术室内)应用预防血栓的措施，血栓高危或极高危患者应GCS和IPC联合、持续应用，尤其在手术的第一个24小时内持续应用;
　　(3)合并多种血栓高危因素的患者，如高龄、肥胖和心脑血管合并症等患者，GCS或 ICP需联合药物抗凝，如低分子肝素等;
　　(4)GCS应首选膝以上长袜、要正确测量患者下肢周径、选择合适尺寸、保证足趾活动正常、每日脱下时间不应大于30分钟等;
　　(5)完善的术后镇痛，通过应用术后自控镇痛泵，鼓励患者尽早床上或下床活动，包括踝关节主动或被动运动，旋转大于20次/小时，尽量减少手术后制动时间;
　　(6)避免围术期行下肢外周静脉输液，避免下肢静脉炎发生和影响下肢活动，抬高下肢，超过心脏水平，以促进腿部静脉回流、排空。
　　总之，外科大手术后患者预后不但取决于手术是否成功，还与是否积极采取预防DVT的措施直接相关，手术后不明原因呼吸困难或猝死几乎都与深静脉血栓和肺栓塞有关^[1，3]。GCS与IPC联合、全程、持续应用能有效降低下肢DVT发生率，但如何更有效预防血栓高危或极高危手术患者下肢DVT和致命性肺栓塞，还需更大规模的临床研究。<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

参考文献
1. 许俊堂, 胡大一, 丛玉隆, 主编. 心血管血栓的溶栓与抗栓疗法. 北京: 人民卫生出版社, 2000;1-81.
2. 袁训芝,吴新民,陈铭, 等.开胸患者术后DVT与血液凝血活性的变化.北京大学  医学版,2004; 36:529-532.
3. William HG,Graham FP,John AH, et al.The Seventh (2004) ACCP conference on Antithrombotic and thrombolytic Therapy .Chest, 2004; 126: 338S-400S.
4. Enc F,Silvia B, Msc R, et al.Blood-flow augmentation of intermittent pneumatic compression systems used for the prevention of deep vein thrombosis prior to surgery. American Journal of Surgery, 1996; 171:312-315.
5. Comerota, Anthony J. Chouhan, The fibrinolytic effects of Intermittent Pneu matic Compression: Mechanism of enhanced fibrinolysis Annals of Surgery, September 1997;226(3):306-314.
6. 袁训芝, 金国光, 朱佐民,等. 剖腹产患者凝血纤溶活性变化的研究. 中华麻醉学杂志, 1997;17: 316.
7. 陈小云, 吴新民. 硬膜外腔阻滞对胸科手术凝血及血液流变学影响. 中华麻醉学杂志, 2004; 24: 393-395.
8. 汤文浩, 李国强, 王凤臣,等. 食管癌组织中纤溶成份的表达及其意义. 中华消  化杂志, 2000; 20: 85~88.
9. kwaan HC, Parmar S, Wang J. Pathogenesis of increased risk of thrombosis in cancer. Seminars in Thrombosis and Hemostasis, 2003;29: 283-290。