不同麻醉方式对膝关节置换后下肢静脉血栓形成的影响：Meta 分析

doi:10.3969/j.issn.2095-4344.2015.35.029

摘要/Abstract

摘要：

背景：虽然全膝关节置换治疗严重膝关节炎患者疗效可靠，但是，下肢静脉血栓形成仍会在很多患者中发生，因此下肢静脉血栓形成也成了目前接受全膝关节置换后突然死亡的最主要原因。
目的：比较不同麻醉方式下进行全膝关节置换后下肢静脉血栓形成的差异。
方法：利用“total knee arthroplasty” ， “TKA” ， “thrombosis” ，“DVT” ， “randomized controlled trial” ，“RCT”，“全膝关节置换”“血栓”“麻醉”等关键词在“PubMed” ，“Medline” ，“Elsevier” ，“Embase”，“Cochrane library” ，“万方”，“CNKI”等国内外主要数据库搜集了2000年1月到2015年3月期间发表的涉及到不同麻醉方式对膝关节置换后下肢深静脉血栓形成的影响方面的文献资料。通过双盲法进行数据提取，文献质量评估，并利用Revman5.3 统计软件对所提取的数据进行了meta分析。
结果与结论：最后总共有包含885例患者的8个文献被纳入此研究。通过分析发现在纳入的文献之间不存在显著异质性(I²=0, P=0.72)。数据合成后的OR是0.25(95% CI: 0.18, 1.35)，说明利用连续硬膜外麻醉方式进行全膝关节置换能显著降低术后深静脉血栓形成的可能。因为缺乏全身麻醉与硬膜外麻醉下的患者凝血因子变化情况等数据，硬膜外麻醉降低深静脉血栓发生率的机制尚需进一步研究。说明在接受下肢静脉血栓的患者中，利用连续硬膜外麻醉可显著降低下肢静脉血栓的形成可能。因此在下肢静脉血栓形成高危患者中应该优先使用硬膜外麻醉方式进行膝关节置换。

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, 膝关节置换, 下肢静脉血栓形成, 全身麻醉, 硬膜外麻醉, Meta分析

Abstract:

BACKGROUND: Although the therapeutic effect of total knee arthroplasty for severe gonarthritis is reliable, deep vein thrombosis also occurred in many patients. Therefore, deep vein thrombosis has been a major reason for unexpected death after total knee arthroplasty.
OBJECTIVE: To study the incidence of deep vein thrombosis after total knee arthroplasty with general and epidural anesthesia.
METHODS: We searched “PubMed”, “Medline”, “Elsevier”, “Embase”, Cochrane library, “Wanfang”, “China National Knowledge Infrastructure” for papers published from January 2000 to March 2015. The mesh words were “total knee arthroplasty”, “TKA”, “thrombosis”, “DVT”, “randomized controlled trial”, “RCT” for studies concerning deep vein thrombosis after total knee arthroplasty with different anesthetic methods. The double blind method was used for data extraction and assessment of literature quality. Revman5.3 software was utilized to analyze the extracted data using meta-analysis.
RESULTS AND CONCLUSION: There were 8 studies including 885 patients. The heterogeneity of the included studies was very low (I²=0, P=0.72). The combined OR was 0.25 (95% confidence interval: 0.18, 1.35), indicating that continuous epidural anesthesia in total knee arthroplasty could apparently reduce the possible formation of postoperative deep vein thrombosis. Because of lack of the changes in coagulation factors under general anesthesia and epidural anesthesia, the mechanism underlying epidural anesthesia to reduce the incidence of deep vein thrombosis deserves further investigations. Among patients with deep vein thrombosis, continuous epidural anesthesia could diminish the possible formation of deep vein thrombosis. Thus, epidural anesthesia should be used firstly for knee replacement in patients with high 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: Arthroplasty, Replacement, Knee, Venous Thrombosis, Anesthesia, Anesthesia, Epidural

中图分类号:

R318

艾克热木江•木合热木，黄筑忆，冯磊，马显志，刘庆. 不同麻醉方式对膝关节置换后下肢静脉血栓形成的影响：Meta 分析[J]. 中国组织工程研究, 2015, 19(35): 5735-5740.

Aikeremujiang•Muheremu, Huang Zhu-yi, Feng Lei, Ma Xian-zhi, Liu Qing. Effects of general and epidural anesthesia on the formation of deep vein thrombosis after total knee arthroplasty: a meta-analysis[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(35): 5735-5740.

图/表（结果） 5

参考文献

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[2] Huisman MV, Klok FA. Diagnostic management of acute deep vein thrombosis and pulmonary embolism. J Thromb Haemost. 2013;11(3):412-422.
[3] Carrier M, Righini M, Le Gal G. Symptomatic subsegmental pulmonary embolism: what is the next step? J Thromb Haemost. 2012;10(8):1486-1490.
[4] Fisher WD. Impact of venous thromboembolism on clinical management and therapy after hip and knee arthroplasty. Can J Surg. 2011;54(5):344-351.
[5] Furlan AD, Pennick V, Bombardier C, et al. 2009 updated method guidelines for systematic reviews in the Cochrane Back Review Group. Spine (Phila Pa 1976). 2009;34(18): 1929-1941.
[6] Chen XY. Risk factors of deep vein thrombosis formation after arthroplasty. Guangdong Yixue. 2009;30(8):1159-1161.
[7] Song WJ, Dong JL, Li X, etn al. Effect of different anesthetic methods on the blood coagulation after total knee arthroplasty. Zhongguo Laonian Xue Zazhi. 2010; 30(2):549-550.
[8] Chen H. Analysis of the incidence of deep venous thrombosis after total knee arthroplasty in different anaesthesia way. Urumqi: Xinjiang Medical University. 2012.
[9] Wu JM, Fan LH, Lingbing Zhang LB, et al. Study on the application of general anesthesia and epidural anesthesia during total knee arthroplasty. Zhongguo Xiangcun Yixue. 2013;22(22):42-43.
[10] Lu WB, Yang SZ, Shao XQ. Influence on perioperative blood conservation and deep vein thrombosis incidence in perioperative period of total knee arthroplasty on general anesthesia and continuous epidural anesthesia. Zhongguo Yiyao Daobao. 2013;10(35):109-111.
[11] Yan PY, Song CJ, Shenglong Miao SL, et al. The correlation analysis of the risk factors of lower limb deep vein thrombosis after total joint arthroplasty. Zhongguo Gu yu Guanjie Zazhi. 2013(3):159-162.
[12] Guo JB. Hematology detection of lower limb deep vein thrombosis and analyze of risk factors after total joint arthroplasty. Xi’an: The Forth Military Medical University. 2013.
[13] Zhu JG. Analysis of relative risk factors for lower limb deep venous thrombosis after prosthetic replacement for joint. Xinxueguan Kangfu Yixue Zazhi. 2014;23(6):626-630.
[14] Levy YD, Hardwick ME, Copp SN, et al. Thrombosis incidence in unilateral vs. simultaneous bilateral total knee arthroplasty with compression device prophylaxis. J Arthroplasty. 2013;28(3):474-478.
[15] Misaki T, Kitajima I, Kabata T, et al. Changes of the soluble fibrin monomer complex level during the perioperative period of hip replacement surgery. J Orthop Sci. 2008;13(5): 419-424.
[16] Goldhaber SZ. Venous thromboembolism: epidemiology and magnitude of the problem. Best Pract Res Clin Haematol. 2012;25(3):235-242.
[17] White RH. The epidemiology of venous thromboembolism. Circulation. 2003;107(23 Suppl 1):I4-8.
[18] Modig J, Borg T, Karlström G, et al. Thromboembolism after total hip replacement: role of epidural and general anesthesia. Anesth Analg. 1983;62(2):174-180.
[19] Davis FM, Laurenson VG, Gillespie WJ, et al. Deep vein thrombosis after total hip replacement. A comparison between spinal and general anaesthesia. J Bone Joint Surg Br. 1989; 71(2):181-185.
[20] Nielsen PT, Jørgensen LN, Albrecht-Beste E, et al. Lower thrombosis risk with epidural blockade in knee arthroplasty. Acta Orthop Scand. 1990;61(1):29-31.
[21] Modig J, Borg T, Bagge L, et al. Role of extradural and of general anaesthesia in fibrinolysis and coagulation after total hip replacement. Br J Anaesth. 1983;55(7):625-629.
[22] Sharma SK, Philip J. The effect of anesthetic techniques on blood coagulability in parturients as measured by thromboelastography. Anesth Analg. 1997;85(1):82-86.
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引言

The invention of total knee arthroplasty (TKA) is one of the most significant advancements in the 20th century medicine. This technique has effectively alleviated the pain of patients with late-stage osteoarthritis, enhanced their ability of mobility, and raised the quality of their life. With the economic development and the increase in the number of elderly population, TKA has already become one of the common surgical procedures in most regional center hospitals. However, patients who underwent TKA have high risks for developing deep vein thrombosis (DVT)^[1]. DVT, especially the pulmonary thromboembolism that can be caused by DVT, is a major reason of mortality in patients after the surgery^[2-4]. Considering the high mortality that can be caused by DVT after TKA, how to avoid it is one of the most important factors in reducing mortality rate after TKA.

Although many studies analyze the risk factors for the formation of DVT in patients who underwent TKA, there are no randomized controlled studies including large patient samples to reach a conclusion with high evidence level. General and epidural anesthesia are the most commonly used anesthetic methods while performing TKA. Since these two methods have significantly different working mechanisms, they have different effects on the hemodynamics and blood coagulation factors during and after the surgery. We assume that choosing general or epidural anesthesia should lead to different incidences of DVT. However, there are no studies with large sample or meta-analysis to find out if choosing general or epidural anesthesia affects the incidence of DVT after TKA. In the current study, we did a meta-analysis on current publications comparing the incidence of DVT after TKA under different anesthetic methods to come up with evidence of higher quality, and to guide clinical work in the future.

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

材料方法

Search strategy
Two independent reviewers underwent computerized search of databases as PubMed (2000-2015), Medline (2000-2015), Embase (2000-2015), Elsevier (2000-2014), Cochrane library (2008-2014), China National Knowledge Infrastructure (2000-2015) with the mesh words: “total knee arthroplasty”, “TKA”, “thrombosis”, “DVT”, “randomized controlled trial”, “RCT”. For the papers whose eligibility for the inclusion criteria failed to reach consensus between the two authors, the third author was invited to settle the disputes.

Inclusion criteria and exclusion criteria
Inclusion criteria: (1) Study design: randomized controlled trials, half randomized controlled studies, prospective and retrospective cohort studies; (2) objective: patients who needed TKA; (3) intervention methods: TKA under general and epidural anesthesia; (4) outcome indicators: formation of DVT observed by ultrasound examinations after the surgery.

Exclusion criteria: included patients with DVT before the surgery; included patients with conditions that may easily cause DVT; papers in languages other than English and Chinese; reviews, expert opinions, lectures.

Study quality assessment
Two authors independently assessed the quality of the included studies by the 12 criteria recommended by the Cochrane Back Review Group^[5]. Each study was scored by “+” (positive), “-” (negative) and “?” (unclear). In the case of disputes, the third author made the final decisions. Studies with less than six “+” were recognized as with low methodological quality and high risk of bias. The methodological quality of the included trials is outlined in Table 3.

Data extraction
Data in the included trails were extracted by two independent reviewers. Authors of each study, study design, patient size, patients’age, origin, time of follow up as well as intervention methods. Patient numbers with and without DVT in each study were extracted and recorded in specific tables. In the cases that the same patients were analyzed in more than one study, they were extracted and analyzed as one patient population.

Statistical analysis
Data were analyzed and processed in Review Manager 5.3 as supplied by the Cochrane Collaboration (Oxford, UK). Two authors checked the data input to make sure that no errors were made. Considering that there can be publication bias between the papers, the analyses were performed using random effect models. I²test was used to test the heterogeneity. Studies were considered to have significant heterogeneity if I² >50%. Subgroup or sensitivity analysis was used at the incidence of significant heterogeneity due to methodological quality of included trials. The differences in each study were defined by the odds ratio (OR) with 95% confidence intervals (95%CI) of the categorical outcome frequencies in the study groups and the control groups, respectively. OR of each individual trial was shown in a forest plot.

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

DVT is caused by the abnormal coagulation of blood in the deep vein. DVT often appears in lower extremities, and is one of the most serious complications after TKA. In most cases, DVT could cause swelling and pain of the lower extremities, and when the thrombus moves to lung and causes pulmonary embolism, it may end up with sudden death of the patient. With the application of anticoagulation drugs, the incidence of DVT has been dropped to 42% from the original 88% without any anticoagulants. Statistically, 0.2% of those patients developed pulmonary thromboembolism and resulted in sudden death^[14-15]. More than 300 thousand patients died of pulmonary thromboembolism each year^[16]. The prevention of thromboembolic disease is one of the most important points in preventing mortality after TKA.

Plenty of studies concern the risk factors of DVT after TKA. According to the current literature, the high risk factors of DVT formation after TKA include old age, female, overweight and application of bone cement during the surgery^[17]. In the current meta-analysis, patients with epidural anesthesia had significantly less DVT than patients who underwent TKA with general anesthesia. This result is in accordance with some other studies^[18-19].

A number of reasons could be the causes of this effect. Epidural anesthesia has less effect on the blood coagulation than general anesthesia, drives more volume flow to the lower limbs and reduces the surgical stress response in the patient^[20-21]. Epidural anesthesia can deactivate sympathetic nerves, dilate the blood vessels and increase the blood flow of the lower limb, decrease the secretion of catecholamine^[22-23]. Moreover, patients with epidural anesthesia can walk shortly after the surgery, and then lower the incidence of DVT.

Although there were no significant differences between the two groups concerning factors that could affect the incidence of DVT formation after the surgery, such as duration of the surgery, intraoperative blood loss, PT, PTA, FIB, APTT and TT, it is possibly the bias that was caused by the sample size included in those meta-analysis.
It can be concluded from the current study that, continuous epidural anesthesia can significantly reduce the incidence of DVT if it replaces general anesthesia during TKA. This alteration should be considered in patients with high risk of forming thromboembolism such as varicose veins, malignancy, smoking, old age and the use of oral oestrogens[19]. We believe it is also possible that the incidence of DVT can be significantly lowered if general anesthesia is replaced by epidural anesthesia in patients with severe fractures of the lower extremity.

To our knowledge, the current meta-analysis is so far the study with the largest sample size. Although most of the studies included were published in Chinese language, the quality of those studies was tested by the Dephli list and proved to be qualified enough to be included in the meta-analysis. Moreover, the results driven from these studies can still serve as high grade evidence that can guide future clinical practice.

Results of this meta-analysis reveal that the ratio of DVT formation can be significantly (P < 0.01) reduced if general anesthesia can be replaced by epidural anesthesia in patients undergoing TKA.

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