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中华关节外科杂志(电子版) ›› 2025, Vol. 19 ›› Issue (04) : 427 -444. doi: 10.3877/cma.j.issn.1674-134X.2025.04.005

荟萃分析

氨甲环酸改善股骨粗隆间骨折内固定围术期失血的Meta分析
虞兵兵1,2, 王婷婷3, 方俊霖1,2, 罗莹莹1, 阳鹏2, 郭云2, 袁丁2, 沈忠园2,(), 黄英如1   
  1. 1400016 重庆医科大学中医药学院
    2402560 重庆医科大学附属铜梁区中医院骨伤科
    3400016 重庆医科大学护理学院
  • 收稿日期:2024-11-26 出版日期:2025-08-01
  • 通信作者: 沈忠园
  • 基金资助:
    国家自然科学基金面上项目(81674002); 国家中医药管理局全国基层名老中医传承工作室建设项目(国中医药人教发[2018]133号); 重庆市科卫联合中医药科研项目(2023MSXM184); 第四批全国中医(临床、基础)优秀人才研修项目(国中医药人教发[2017]24号)

Meta analysis on tranexamic acid reduces perioperative blood loss in internal fixation of intertrochanteric fractures

Bingbing Yu1,2, Tingting Wang3, Junlin Fang1,2, Yingying Luo1, Peng Yang2, Yun Guo2, Ding Yuan2, Zhongyuan Shen2,(), Yingru Huang1   

  1. 1Chongqing Medical University School of Traditional Chinese Medicine, Chongqing 400016, China
    2Department of Orthopedics at Affiliated Traditional Chinese Medicine Hospital of Chongqing Medical University in Tongliang District, Chongqing 402560, China
    3Chongqing Medical University School of Nursing, Chongqing 400016, China
  • Received:2024-11-26 Published:2025-08-01
  • Corresponding author: Zhongyuan Shen
引用本文:

虞兵兵, 王婷婷, 方俊霖, 罗莹莹, 阳鹏, 郭云, 袁丁, 沈忠园, 黄英如. 氨甲环酸改善股骨粗隆间骨折内固定围术期失血的Meta分析[J/OL]. 中华关节外科杂志(电子版), 2025, 19(04): 427-444.

Bingbing Yu, Tingting Wang, Junlin Fang, Yingying Luo, Peng Yang, Yun Guo, Ding Yuan, Zhongyuan Shen, Yingru Huang. Meta analysis on tranexamic acid reduces perioperative blood loss in internal fixation of intertrochanteric fractures[J/OL]. Chinese Journal of Joint Surgery(Electronic Edition), 2025, 19(04): 427-444.

目的

评估氨甲环酸(TXA)改善股骨粗隆间骨折(ITF)患者股骨近端防旋髓内钉(PFNA)内固定术围术期失血的有效性和安全性。

方法

通过中国知网、中国生物医学文献服务系统、维普资讯、万方数据、科学引文索引(WOS)、PubMed、荷兰医学文摘数据库(Excerpta Medica Database,Embase)以及Cochrane图书馆(Cochrane Library)等医学电子数据库检索TXA对改善ITF患者PFNA围术期出血的临床随机对照试验(RCTs)。检索时限设为自各数据库建立起至2024年10月31日。使用修改后Jadad量表和Cochrane随机对照试验偏倚风险评估工具2.0评估纳入研究的质量和偏倚风险。通过StataSE 15进行Meta分析、异质性分析、敏感性分析、亚组分析、发表偏倚分析、剪补法分析和试验序贯分析,并运用TSA 0.9.5进行试验序贯分析。

结果

本研究包括21项RCTs,共1 938例患者。Meta分析显示,与等量生理盐水或空白对照相比,TXA可显著降低总失血量[均值差(MD)=-225.42,95%置信区间(CI)(-281.49,-169.36),P<0.001]、隐性失血量[MD=-215.43,95%CI(-267.48,-163.38),P<0.001]、输血率[相对危险度(RR)=0.54,95%CI(0.48,0.62),P<0.001],并可降低显性失血量、术中出血量、术后24 h引流量、输血量并保持术后第3天血红蛋白浓度,而严重不良事件发生率不增加。亚组分析显示TXA降低股骨粗隆间患者PFNA围术期失血的效果不受干预措施类别、患者年龄、身体质量指数(BMI)、术前血红蛋白浓度以及TXA总剂量影响,均显著优于对照组。发表偏倚分析显示总失血量、隐形失血量、输血率等主要结局指标均未出现显著的发表偏倚。试验序贯分析进一步验证了主要结局指标结论的确凿性。

结论

TXA在减少ITF患者PFNA围术期失血方面有效且安全。但由于现有研究在设计和方法学上存在缺陷,需谨慎解读本结论。未来需开展更多设计严密和高质量的RCTs以进一步验证此结论。

Objective

To evaluate the efficacy and safety of tranexamic acid (TXA) in reducing perioperative blood loss in patients with intertrochanteric fractures (ITF) undergoing proximal femoral nail antirotation (PFNA) treatment.

Methods

Randomized controlled trials (RCTs) evaluating the effect of TXA on perioperative blood loss in ITF patients treated with PFNA were searched in medical electronic databases, including China National Knowledge Infrastructure, China Biology Medicine Database, VIP Journal Integration Platform, Wanfang Data Knowledge Service Platform, Web of Science, PubMed, Excerpta Medica Database (Embase), and Cochrane Library, from the establishment of each database up to October 31, 2024. The quality and risk of bias of the included studies were assessed using the modified Jadad scale and the Cochrane Risk of Bias Tool 2.0 for randomized controlled trials. Meta-analysis, heterogeneity analysis, sensitivity analysis, subgroup analysis, publication bias analysis, trim-and-fill analysis, and trial sequential analysis were performed using StataSE 15, with trial sequential analysis conducted using TSA 0.9.5.

Results

This study included 21 RCTs with a total of 1 938 patients. Meta-analysis indicated that compared to equivalent normal saline or placebo controls, TXA significantly reduced total blood loss [mean difference (MD)=-225.42, 95% confidence interval (CI) (-281.49, -169.36), P<0.001], hidden blood loss [MD=-215.43, 95% CI (-267.48, -163.38), P<0.001], and transfusion rate [relative risk (RR)= 0.54, 95% CI (0.48, 0.62), P<0.001]. It also reduced visible blood loss, intraoperative bleeding, postoperative 24h drainage volume, transfusion volume, and maintained hemoglobin concentration on the third postoperative day without significantly increasing the incidence of serious adverse events. Subgroup analysis demonstrated that the reduction in perioperative blood loss for patients with ITF treated with PFNA using TXA was not influenced by the type of intervention, average patient age, average body mass index (BMI), preoperative hemoglobin concentration, or total TXA dosage, all showing significant superiority over the control group. The publication bias analysis did not reveal significant publication bias for primary outcomes such as total blood loss, hidden blood loss, and transfusion rate. Trial sequential analysis further confirmed the robustness of the conclusions regarding the primary outcome measures.

Conclusions

TXA is effective and safe in reducing perioperative blood loss in ITF patients undergoing PFNA. However, due to methodological and design limitations in existing studies, these conclusions should be interpreted with caution. More rigorously designed and high-quality RCTs are needed in the future to further validate these findings.

图1 检索流程图
Figure 1 Retrieval flowchart
表1 纳入文献基本特征
Table 1 General characteristics of included studies
文献Literatures 样本量Sample size 性别Gender 年龄(岁) Age 手术时间(min)Operation time BMI(kg/m2
T/C T C T C T C T C
Wang 2023[23] 33/33 14/19 11/22 64.1±8.3 65.1±7.4 - - 21.1±4.1 19.8±2.7
Zhang 2022[34] 61/61 28/33 34/27 79.1±11.9 76.1±16.6 80.1±18.9 81.4±23.4 21.6±3.2 21.8±3.2
Zhou 2019[30] 50/50 15/35 28/22 75.1±8.3 77.8±6.4 75.5±24.9 79.9±21.5 21.9±6.6 22.9±5.3
Tian 2018[33] 50/50 19/31 14/36 77.7±6.5 79.3±6.5 101.2±30.5 99.5±26.8 24.2±4.1 22.9±3.8
Lei 2017[29] 37/40 5/32 7/33 77.8±9.7 79.2±6.5 - - 23.8±2.2 23.3±2.9
Luo 2024[22] 75/73 20/55 26/47 79.7±8.0 78.5±7.7 80.0(70.0, 92.0) 80.0(70.0, 100.0) - -
王皓2021(A)[20] 33/32 10/23 10/22 75.1±9.4 72.3±7.7 98.9±23.54 88.1±25.8 25.8±3.0 24.7±2.9
王皓2021(B)[20] 35/32 9/26 10/22 74.3±7.1 72.3±7.7 92.5±22.8 88.1±25.8 24.9±2.7 24.7±2.9
史庆轩2018[25] 24/24 - - 88.1±6.2 89.2±7.1 - - 23.1±4.0 22.7±4.7
林锦秀2016[28] 57/56 14/43 15/41 76.5±6.2 77.4±5.6 52.3±5.6 53.0±4.8 21.0±1.5 21.2±2.1
周述清2022[26] 51/51 17/34 19/32 78.2±6.1 77.6±5.4 56.6±8.0 53.5±10.8 21.9±0.6 22.0±0.5
崔树北2022(A)[19] 48/49 26/22 28/21 46.1±9.1 46.0±9.0 93.6±20.1 93.2±20.1 - -
崔树北2022(B)[19] 48/49 29/19 28/21 46.1±9.1 46.0±9.0 92.8±19.0 93.2±20.1 - -
张辉2020[31] 40/40 11/29 13/27 76.1±7.5 76.3±7.6 78.3±28.1 79.4±28.2 - -
王志猛2020(A)[21] 50/50 27/23 22/28 79.3±6.5 77.7±6.5 - - - -
王志猛2020(B)[21] 50/50 19/31 22/28 74.3±6.0 77.7±6.5 - - - -
王志猛2020(C)[21] 50/50 24/26 22/28 76.6±6.2 77.7±6.5 - - - -
张忠岩2018[27] 30/30 16/14 18/12 63.6±11.3 64.5±10.6 - - 24.2±3.6 25.1±2.8
刘敏2018[24] 50/50 27/23 26/24 72.6±5.4 73.5±6.1 - - - -
王小军2017[32] 35/35 7/28 8/27 73.8±5.4 74.1±6.2 57.8±7.3 55.2±6.9 21.7±1.6 21.4±1.5
程辉光2017[35] 64/62 18/46 17/45 78.5±6.4 77.9±7.1 46.7±14.6 44.8±13.2 24.7±6.7 23.3±7.9
文献Literatures 术前血红蛋白浓度(g/L)Preoperative hemoglobin concentration 干预措施Intervention 结局指标Outcome measures
T C T C
Wang 2023[23] 137.7±15.4 132.2±15.4 骨折断端局部注射TXA 0.5 g 等量生理盐水 ①④⑤⑥⑦⑩
Zhang 2022[34] 100.1±13.7 97.3±14.4 术前、术后3 h静脉滴注TXA 1.0 g 等量生理盐水 ①③④⑤⑥⑧
Zhou 2019[30] 101.6±20.2 107.9±18.7 术前静脉滴注TXA 1.0 g 空白对照 ①③④⑤⑥⑦⑧⑨⑩
Tian 2018[33] - - 术前、术后5 h静脉滴注TXA 10.0 mg/kg 空白对照 ①②③④⑤⑥⑦⑧⑨
Lei 2017[29] 109.5±15.1 112.1±13.3 术前静脉滴注TXA 1.0 g 等量生理盐水 ①②③④⑤⑥⑦⑧⑨⑩
Luo 2024[22] 103.9±17.7 103.9±17.4 髓腔局部注射TXA 1.0 g 等量生理盐水 ①③④⑤⑥⑧⑨⑩
王皓2021(A)[20] 109.4±13.7 107.6±10.1 术前静脉滴注TXA 1.0 g 等量生理盐水 ①③④⑤⑥⑧
王皓2021(B)[20] 113.3±12.2 107.6±10.1 术前、术后3 h、术后6 h静脉滴注TXA 1.0 g 等量生理盐水 ①③④⑤⑥⑧
史庆轩2018[25] 129.0±12.7 128.5±11.9 髓腔局部注射TXA 2.0 g 等量生理盐水 ①③⑤⑦⑨⑩
林锦秀2016[28] 108.0±7.0 110.0±10.0 髓腔局部注射TXA 2.0 g 等量生理盐水 ①②③④⑤⑧
周述清2022[26] 102.5±6.6 99.8±7.1 髓腔、骨折断端局部注射TXA 2.0 g 空白对照 ①②③④⑤⑧⑨
崔树北2022(A)[19] - - 术前静脉滴注TXA 1.0 g 等量生理盐水 ①②③④⑤⑥⑦⑧⑩
崔树北2022(B)[19] - - 术前、术后7 h、术后14 h静脉滴注TXA 1.0 g 等量生理盐水 ①②③④⑤⑥⑦⑧⑩
张辉2020[31] - - 术前静脉滴注TXA 1.0 g 等量生理盐水 ①②③④⑤⑧
王志猛2020(A)[21] 127.8±22.3 118.2±23.0 术前静脉滴注TXA 1.0 g 等量生理盐水 ①③④⑤⑩
王志猛2020(B)[21] 126.7±21.1 118.2±23.0 骨折断端局部注射TXA 1.0 g 等量生理盐水 ①③④⑤⑩
王志猛2020(C)[21] 122.5±21.7 118.2±23.0 术前静脉滴注TXA 1.0 g、骨折断端局部注射TXA 1.0 g 等量生理盐水 ①③④⑤⑩
张忠岩2018[27] - - 髓腔局部注射TXA 2.0 g 空白对照 ①②③④⑤⑦⑩
刘敏2018[24] 142.4±12.3 143.1±10.8 髓腔局部注射TXA 2.0 g 等量生理盐水 ①②③⑤⑨⑩
王小军2017[32] 129.8±18.7 130.2±17.6 术前静脉滴注TXA 1.0 g 等量生理盐水 ①③④⑤⑥⑦⑧⑨⑩
程辉光2017[35] 101.5±13.6 102.9±14.7 术前静脉滴注TXA 1.0 g、术后24 h静脉滴注TXA 3.0 g 等量生理盐水 ①④⑤⑧⑨⑩
图2 偏倚风险评价图
Figure 2 Risk of bias assessment graph
图3 总失血量的敏感性分析
Figure 3 Sensitivity analysis of total blood loss
图4 总失血量的Meta分析
Figure 4 Meta-analysis of total blood loss
表2 主要结局指标的亚组分析
Table 2 Subgroup analysis of primary outcomes
亚组Subgroups 研究数量Number of studies 样本量Sample size 异质性分析Heterogeneity analysis 荟萃分析Meta-analysis 效应模型Effect model
T C I2值(%) P MD/RR(95% CI P
总失血量影响因素Influences on total blood loss           MD(95% CI    
治疗组干预措施Treatment group interventions                
单剂量静脉滴注Single dose intravenous drip 7 293 296 63 0.01 -218.55(-274.00,-163.11) <0.001 随机
局部注射Local injection 8 370 367 94 <0.001 -155.06(-211.20,-88.92) <0.001 随机
重复静脉滴注Repeated intravenous drip 5 258 254 69 0.01 -342.49(-422.98,-262.00) <0.001 随机
对照组干预措施Control group interventions                
等量生理盐水Saline 17 790 786 93 <0.001 -238.52(-295.19,-181.85) <0.001 随机
空白对照Blank control 4 181 181 93 <0.001 -167.80(-277.55,-58.05) 0.003 随机
年龄Age                
≥65岁 17 812 806 89 <0.001 -209.45(-261.25,-157.64) <0.001 随机
<65岁 4 159 161 96 <0.001 -263.66(-364.25,-163.07) <0.001 随机
BMI                
≤23.9 kg/m2 7 324 326 96 <0.001 -210.11(-305.22,-115.00) <0.001 随机
>23.9 kg/m2 5 212 206 77 0.002 -242.52(-337.79,-147.25) <0.001 随机
术前血红蛋白浓度Preoperative hemoglobin concentration                
≥110 g/L 9 364 364 84 <0.001 -230.82(-296.19,-165.45) <0.001 随机
<110 g/L 7 391 385 89 <0.001 -178.27(-248.76,-107.78) <0.001 随机
TXA                
1 g 9 418 419 55 0.02 -204.06(-248.92,-159.21) <0.001 随机
2 g 7 323 322 92 <0.001 -171.43(-232.48,-110.37) <0.001 随机
3 g 2 83 81 0 0.69 -376.69(-405.85,-347.53) <0.001 固定
手术时间Operation time                
>60 min 9 440 436 92 <0.001 -257.83(-335.85,-179.82) <0.001 随机
≤60 min 4 207 204 88 <0.001 -123.80(-206.07,-41.52) 0.003 随机
                 
隐性失血量影响因素Influences on hidden blood loss           MD(95% CI    
治疗组干预措施Treatment group interventions                
单剂量静脉滴注Single dose intravenous drip 7 293 296 88 <0.001 -213.25(-279.02,-147.48) <0.001 随机
局部注射Local injection 7 337 334 94 <0.001 -143.11(-199.27,-86.95) <0.001 随机
重复静脉滴注Repeated intravenous drip 4 194 192 85 <0.001 -319.50(-425.11,-213.89) <0.001 随机
对照组干预措施Control group interventions                
等量生理盐水Saline 15 693 691 95 <0.001 -238.73(-293.82,-183.65) <0.001 随机
空白对照Blank control 4 181 181 97 <0.001 -133.15(-230.48,-35.82) 0.007 随机
年龄Age                
≥65岁 16 748 744 93 <0.001 -211.49(-268.07,-154.91) <0.001 随机
<65岁 3 126 128 99 <0.001 -232.38(-345.59,-119.17) <0.001 随机
BMI                
≤23.9 kg/m2 6 291 293 90 <0.001 -173.58(-251.79,-95.38) <0.001 随机
>23.9 kg/m2 4 148 144 76 0.007 -214.49(-295.57,-133.42) <0.001 随机
术前血红蛋白浓度Preoperative hemoglobin concentration                
≥110 g/L 8 331 331 82 <0.001 -239.46(-304.47,-174.44) <0.001 随机
<110 g/L 5 216 218 98 <0.001 -227.26(-310.15,-144.38) <0.001 随机
TXA                
1 g 9 418 419 84 <0.001 -198.38(-254.18,-142.59) <0.001 随机
2 g 7 323 322 96 <0.001 -203.14(-270.92,-135.36) <0.001 随机
3 g 2 83 81 0 0.71 -341.62(-359.48,-323.76) <0.001 固定
手术时间Operation time                
>60 min 9 440 436 96 <0.001 -243.59(-317.94,-169.24) <0.001 随机
≤60 min 3 143 142 89 <0.001 -106.66(-183.82,-29.50) 0.007 随机
                 
输血率影响因素Influences on transfusion rate           RR(95% CI    
治疗组干预措施Treatment group interventions                
单剂量静脉滴注Single dose intravenous drip 7 293 297 15 0.32 0.41(0.30,0.55) <0.001 固定
局部注射Local injection 6 296 293 0 0.56 0.57(0.45,0.72) <0.001 固定
重复静脉滴注Repeated intravenous drip 5 258 254 66 0.02 0.62(0.52,0.74) <0.001 随机
对照组干预措施Control group interventions                
等量生理盐水Saline 14 716 713 26 0.17 0.58(0.50,0.67) <0.001 固定
空白对照Blank control 5 181 181 75 0.008 0.39(0.20,0.78) 0.007 随机
年龄Age                
≥65岁 15 738 733 40 0.06 0.57(0.50,0.65) <0.001 固定
<65岁 4 159 161 39 0.18 0.34(0.21,0.57) <0.001 固定
BMI                
≤23.9 kg/m2 7 324 327 25 0.24 0.51(0.41,0.62) <0.001 固定
>23.9 kg/m2 5 212 206 54 0.07 0.62(0.43,0.89) 0.01 随机
术前血红蛋白浓度Preoperative hemoglobin concentration                
≥110 g/L 7 290 291 0 0.90 0.52(0.38,0.72) <0.001 固定
<110 g/L 7 391 385 66 0.007 0.56(0.41,0.76) <0.001 随机
TXA                
1 g 9 418 420 13 0.33 0.46(0.36,0.59) <0.001 固定
2 g 5 249 248 0 0.41 0.51(0.39,0.66) <0.001 固定
3 g 2 83 81 0 0.51 0.18(0.05,0.60) 0.005 固定
手术时间Operation time                
>60 min 9 440 436 49 0.05 0.47(0.38,0.58) <0.001 固定
≤60 min 4 207 204 10 0.34 0.68(0.57,0.81) <0.001 固定
图5 隐性失血量的敏感性分析
Figure 5 Sensitivity analysis of hidden blood loss
图6 隐性失血量的Meta分析
Figure 6 Meta-analysis of hidden blood loss
图7 输血率的Meta分析
Figure 7 Meta-analysis of transfusion rate
图8 显性失血量的敏感性分析
Figure 8 Sensitivity analysis of visible blood loss
图9 显性失血量的Meta分析
Figure 9 Meta-analysis of visible blood loss
图10 术中出血量的敏感性分析
Figure 10 Sensitivity analysis of intraoperative blood loss
图11 术中出血量的Meta分析
Figure 11 Meta-analysis of intraoperative blood loss
图12 输血量的敏感性分析
Figure 12 Sensitivity analysis of transfusion volume
图13 输血量的Meta分析
Figure 13 Meta-analysis of transfusion volume
图14 血红蛋白浓度的敏感性分析
Figure 14 Sensitivity analysis of hemoglobin concentration
图15 血红蛋白浓度的Meta分析
Figure 15 Meta-analysis of hemoglobin concentration
图16 24 h引流量敏感性分析
Figure 16 Sensitivity analysis of 24 h drainage volume
图17 24 h引流量森林图
Figure 17 Forest plot of meta-analysis for 24 h drainage volume
图18 深静脉血栓发生率的敏感性分析
Figure 18 Sensitivity analysis of deep vein thrombosis incidence rate
图19 肺栓塞发生率的Meta分析
Figure 19 Meta-analysis of pulmonary embolism incidence rate
图20 死亡率的Meta分析
Figure 20 Meta-analysis of mortality rate
图21 总失血量(A)、隐性失血量(B)、输血率(C)的发表偏倚漏斗图
Figure 21 Funnel plots for publication bias: total blood loss (A), hidden blood loss (B), and transfusion rate (C)
表3 纳入研究的修改后Jadad量表评估结果
Table 3 Modified Jadad scale assessment results of included studies
图22 总失血量(左上)、隐性失血量(右上)、输血率(下)的序贯分析图
Figure 22 Trial sequential analysis plots: total blood loss (top-left), hidden blood loss (top-right), and transfusion rate (bottom)
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