Efficacy and safety of tranexamic acid application in total hip arthroplasty: a meta-analysis

doi:10.3969/j.issn.2095-4344.2014.35.022

Abstract

Abstract:

BACKGROUND: Whether tranexamic acid can effectively and safely reduce blood loss and allogeneic transfusion rate in total hip arthroplasty remains controversial at present.
OBJECTIVE: To assess the efficacy and safety of tranexamic acid administration in total hip arthroplasty using meta-analysis.
METHODS: Clinical randomized controlled trials concerning tranexamic acid application in total hip arthroplasty published from January 1969 to December 2013 were retrieved from the PubMed, Ovid, Elsevier, Cochrane library, China National Knowledge Infrastructure and Wanfang database. Intraoperative blood loss, postoperative blood loss, total blood loss, allogeneic transfusion rate and incidence of venous thromboembolism were compared using meta-analysis between the tranexamic acid and control groups. Detection and literature references were used as supplementary data. RevMan 5.0 software provided by Cochrane collaboration was used for meta-analyses. Conclusion was obtained according to analysis. The analysis checked the heterogeneity of data.
RESULTS AND CONCLUSION: After comprehensive and rigorous screening, 19 high-quality (Jadad score not less than 3) randomized controlled studies were included. Meta-analysis results demonstrated that compared with the control group, tranexamic acid decreased the total blood loss [weighted mean difference (WMD)=-341.04, 95% confidence interval (CI) (-508.10, -173.97), P < 0.001], intraoperative blood loss
[WMD=-63.26, 95%CI (-111.33, -15.18), P=0.01] and postoperative blood loss [WMD=-229.53, 95%CI (-338.11, -120.94), P < 0.000 1], and diminished allogeneic transfusion rate [relative risk=0.45, 95%CI (0.35, 0.57),P < 0.000 1] in patients undergoing total hip arthroplasty. No significant difference in incidence of venous thromboembolism was detectable. These data suggested that tranexamic acid could reduce blood loss and transfusion rate in patients undergoing total hip arthroplasty without increasing the risk of incidence of venous thromboembolism.

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

全文链接：

Key words: arthroplasty, replacement, hip, tranexamic acid, blood loss, surgical, meta-analysis

CLC Number:

R318

Liu Bing-gen, Pang Qing-jiang . Efficacy and safety of tranexamic acid application in total hip arthroplasty: a meta-analysis[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(35): 5699-5706.

Figures/Tables 6

2.1 检索结果及纳入文献的质量评价图1显示了本次研究是如何依据文献纳入和排除标准来检索相关文献。通过检索前文提到的这些数据库，一共检索出了604篇可能符合纳入标准的文献。经过筛选，最后剩余19篇文献进入最终研究[9-27]。19篇文献多为38-100例的小样本量研究，共960例。纳入的19项随机对照试验研究中，18项研究为英文，1项研究为中文。 19项随机对照试验按照改良Jadad量表的质量评价标准进行严格的方法学质量评价，结果17项为Jadad评分大于3分，另2项Jadad评分为3分。其中14篇报道了相应方法，包括随机选择信封、随机数字表和计算机生成随机数字法等。13篇使用了双盲法，3篇使用了单盲法，16准确描述退出与失访状况的文献。所有患者960例，其中氨甲环酸组482例，对照组478例，所有患者均接受初次全髋关节置换，置换前诊断髋关节骨关节炎为主要的病因，其他的一些病因还包括了类风湿性关节炎及股骨头缺血坏死等，每篇文献均做了患者特点的基线对比，包括年龄、性别、体质量指数、术前血红蛋白水平等。 13项研究用生理盐水作为安慰剂[9-12，14-16，18-20，23，26-27]， 6项采用空白对照[13，17，21-22，24-25]，所有纳入研究的氨甲环酸均为静脉使用，无口服及肌肉注射氨甲环酸的研究，静脉给予氨甲环酸剂量和给药方式有多种，剂量有10-20 mg/kg，1 g，1 mg/(kg•h)泵入。给药时间也有多种，包括术前给药、手术结束时给药、持续静脉泵入给药及术后追加第二剂等方式。 6项研究采用全身+硬膜外麻醉[17-19，21-22，26]，1项腰麻[13]，2项硬膜外麻醉[15，25]，1项未提及麻醉方法[27]，其余均采用椎管内麻醉。 7项研究使用骨水泥型假体[10，12，14，18-20，22]，3项使用非骨水泥型假体[13，15，17，23，25-27]，1项使用混合型假体[16]，2项为非骨水泥或骨水泥型[9，24]，2项为非骨水泥或骨水泥型或混合型假体[11，21]。 2项研究单纯使用物理方法预防深静脉血栓形成外[10，13]，8项使用低分子肝素预防[9，14-17，19-20]，4项用低分子肝素和物理方法预防[10-12，18]，2项用其他的方法预防，2项未提及预防方法[26-27]。 8项研究采用静脉超声、造影或全身增强CT常规检测深静脉血栓形成[10-11，16-17，19-20，22，26]，余11项根据临床表现对可疑病例进行辅助检查。 8项研究平均手术时间< 90 min [9，13-14，17-18，21，23，25]，院6项平均手术时间≥90 min[11-12，15-16，18，26]，5项未提及[19，20，22，24，27]。纳入研究的一般资料见表1，2。"

2.2 Meta分析结果 2.2.1 术中失血量 10篇文献报道了全髋关节置换中失血量[11，13-16，20-21，24-26]。各研究间有统计学异质性(I2=64%，P=0.003)，故采用随机效应模型，结果显示氨甲环酸组术中失血量显著低于对照组[WMD=-63.26，95%CI (-111.33，-15.18)，P=0.01，表3]。对纳入的每项研究剔除1次，剩余研究做合并分析，此敏感性分析显示单项研究对结果影响较小，WMD的范围为-86.71[95%CI(-147.39，-26.04)]到-44.90[95%CI(-87.36，-2.45)]。以上分析说明Meta分析结果的稳定性较好。 2.2.2 术后失血量 8篇文献报道了全髋关节置换后失血量[10-11，13-14，16，20，25-26]。各研究间有统计学异质性(I2=90%， P < 0.000 1)，故采用随机效应模型，结果显示氨甲环酸组术后失血量显著低于对照组[WMD=-229.53，95%CI (-338.11，-120.94)，P < 0.0001，表3]。对纳入的每项研究剔除1次，剩余研究做合并分析，此敏感性分析显示单项研究对结果影响较小，WMD的范围为-269.38 [95%CI(-381.03，-157.72)]到-166.20[95%CI (-230.36，-102.04)]。以上分析说明Meta分析结果的稳定性较好。 2.2.3 总失血量共有8篇文献报道了全髋关节置换总失血量[10-11，13-14，16，20-21，26]。各研究间有统计学异质性(I2=77%， P ，故采用随机效应模型，结果显示氨甲环酸组总失血量显著低于对照组[WMD=-341.04，95%CI(-508.10，-173. 97)，P < 0.001，表3]。< 0.001) 对纳入的每项研究剔除1次，剩余研究做合并分析，此敏感性分析显示单项研究对结果影响较小，WMD的范围为-387.13[95%CI(-546.43，-227.84)]到-289.42[95%CI (-421.66，-157.17)]。以上分析说明Meta分析结果的稳定性较好。 2.2.4 隐性失血量 2篇文献报道了全髋关节置换隐性失血量[14，27]。各研究间无统计学异质性(I2=0，P=0.95)，故采用固定效应模型，结果显示氨甲环酸组隐性失血量显著低于对照组[WMD=-52.70，95%CI(-187.98，-117.42)，P < 0.001，表3]。 2.2.5 异体输血率 18篇文献提供了患者的异体输血率，其中14篇数据可用[9-12，14，16，18-21，23-26]，无统计学异质性(I2=42%，P=0.04)，采用固定效应模型。氨甲环酸组异体输血率显著低于对照组[RR=0.45，95%CI(0.35，0.57)， P < 0.000 1，表3]。对纳入的每项研究剔除1次，剩余研究做合并分析，此敏感性分析显示单项研究对结果影响较小，WMD的范围为0.47[95%CI(0.37，0.60)]到0.38 [95%CI (0.29，0.49)]。以上分析说明Meta分析结果的稳定性较好。 2.2.6 静脉血栓栓塞发生率 17篇文献提供了静脉血栓栓塞的发生率，其中7篇数据可用[10，16-21]，对静脉血栓栓塞的各研究间无统计学异质性(I2=0，P=0.88)，采用固定效应模型，氨甲环酸组与安慰剂组静脉血栓的发生率差异无显著性意义[RR=1.30，95%CI(0.62，2.73)，P=0.48，表3]。对纳入的每项研究剔除1次，剩余研究做合并分析，此敏感性分析显示单项研究对结果影响较小，WMD的范围为1.47[95%CI(0.67，3.24)]到1.04[95%CI(0.47，2.30)]。以上分析说明Meta分析结果的稳定性较好。"

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