Is combined topical with intravenous tranexamic acid superior than topical, intravenous tranexamic acid alone and control groups for blood loss controlling after total knee arthroplasty: A meta-analysis

Chunmei Lin, Yingmei Qi, Li Jie, Hong-Biao Li, Xi-Cheng Zhao, Lei Qin, Xin-Qiang Jiang, Zhen-Hua Zhang, Liping Ma, Chunmei Lin, Yingmei Qi, Li Jie, Hong-Biao Li, Xi-Cheng Zhao, Lei Qin, Xin-Qiang Jiang, Zhen-Hua Zhang, Liping Ma

Abstract

Background: The purpose of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to evaluate the efficacy and safety of combined topical with intravenous tranexamic acid (TXA) versus topical, intravenous TXA alone or control for reducing blood loss after a total knee arthroplasty (TKA).

Methods: In May 2016, a systematic computer-based search was conducted in the PubMed, Embase, Cochrane Library, Web of Science, and Chinese Wanfang database. This systematic review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement criteria. Only patients prepared for primary TKA that administration combined topical with intravenous TXA with topical TXA, intravenous (IV) TXA, or control group for reducing blood loss were included. Eligible criteria were published RCTs about combined topical with intravenous TXA with topical alone or intravenous alone. The primary endpoint was the total blood loss and need for transfusion. The complications of deep venous thrombosis (DVT) were also compiled to assess the safety of combined topical TXA with intravenous TXA. Relative risks (RRs) with 95% CIs were estimated for dichotomous outcomes, and mean differences (MDs) with 95% CIs for continuous outcomes. The Cochrane risk of bias tool was used to appraise a risk of bias. Stata 12.0 software was used for meta-analysis.

Results: Fifteen studies involving 1495 patients met the inclusion criteria. The pooled meta-analysis indicated that combined topical TXA with intravenous TXA can reduce the total blood loss compared with placebo with a mean of 458.66 mL and the difference is statistically significant (MD = -458.66, 95% CI: -655.40 to 261.91, P < 0.001). Compared with intravenous TXA, combined administrated TXA can decrease the total blood loss, and the difference is statistically significant (MD = -554.03, 95% CI: -1066.21 to -41.85, P = 0.034). Compared with the topical administration TXA, the pooled meta-analysis indicated that combined TXA can decrease the amount of total blood loss with mean 107.65 mL with statistically significant(MD = -107.65, 95% CI: -525.55 to -239.9141.85, P = 0.001). The pooled results indicated that combined topical with intravenous TXA can decrease the need for transfusion (RR = 0.34, 95% CI: 0.23-0.50, P < 0.001). There is no significant difference between combined topical with intravenous TXA with topical or intravenous TXA (P > 0.05) in terms of need for transfusion and the occurrence of DVT.

Conclusion: Compared with topical, intravenous TXA alone or control group, combined topical with TXA, can decrease the total blood loss and subsequent need for transfusion without increasing the occurrence of DVT. The dose and timing to administration TXA is different, and more randomized controlled trials are warranted to clarify the optimal dosing and time to administration TXA.

Conflict of interest statement

The authors have no funding and conflicts of interest to disclose.

Figures

Figure 1
Figure 1
The risk of bias summary of the included studies.
Figure 2
Figure 2
The risk of bias of each included studies.
Figure 3
Figure 3
Forest plot of the combined TXA with topical or intravenous or topical for total blood loss. TXA = tranexamic acid.
Figure 4
Figure 4
Sensitivity analysis for the total blood loss.
Figure 5
Figure 5
Funnel plot of the total blood loss for the test for the publication bias.
Figure 6
Figure 6
Begg's test for the publication bias.
Figure 7
Figure 7
Forest plot comparing the combined TXA for need for transfusion with topical or intravenous or control group. TXA = tranexamic acid.
Figure 8
Figure 8
Forest plot comparing the occurrence of DVT of combined TXA with topical or intravenous or control group. DVT = deep venous thrombosis, TXA = tranexamic acid.

References

    1. Kurtz S, Ong K, Lau E, et al. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am 2007;89:780–5.
    1. Kapadia BH, Banerjee S, Issa K, et al. Preoperative blood management strategies for total knee arthroplasty. J Knee Surg 2013;26:373–7.
    1. Good L, Peterson E, Lisander B. Tranexamic acid decreases external blood loss but not hidden blood loss in total knee replacement. Brit J Anaesth 2003;90:596–9.
    1. Hiippala ST, Strid LJ, Wennerstrand MI, et al. Tranexamic acid radically decreases blood loss and transfusions associated with total knee arthroplasty. Anesth Analg 1997;84:839–44.
    1. Charoencholvanich K, Siriwattanasakul P. Tranexamic acid reduces blood loss and blood transfusion after TKA: a prospective randomized controlled trial. Clin Orthop Relat Res 2011;469:2874–80.
    1. Oei W, Neslo R, Janssen MP. A consensus-based tool for ranking the risk of blood-transmissible infections. Transfusion 2016;56:2108–14.
    1. Douros A, Jobski K, Kollhorst B, et al. Risk of venous thromboembolism in cancer patients treated with epoetins or blood transfusions. Brit J Clin Pharmacol 2016;82:839–48.
    1. Antinolfi P, Innocenti B, Caraffa A, et al. Post-operative blood loss in total knee arthroplasty: knee flexion versus pharmacological techniques. Knee Surg Sports Traumatol Arthrosc 2014;22:2756–62.
    1. Aguilera X, Martinez-Zapata MJ, Hinarejos P, et al. Topical and intravenous tranexamic acid reduce blood loss compared to routine hemostasis in total knee arthroplasty: a multicenter, randomized, controlled trial. Arch Orthop Trauma Surg 2015;135:1017–25.
    1. Lin ZX, Woolf SK. Safety efficacy and cost-effectiveness of tranexamic acid in orthopedic surgery. Orthopedics 2016;39:119–30.
    1. Aggarwal AK, Singh N, Sudesh P. Topical vs intravenous tranexamic acid in reducing blood loss after bilateral total knee arthroplasty: a prospective study. J Arthroplasty 2015;31:1442–8.
    1. Pinsornsak P, Rojanavijitkul S, Chumchuen S. Peri-articular tranexamic acid injection in total knee arthroplasty: a randomized controlled trial. BMC Musculoskelet Disord 2016;17:313.
    1. Benoni G, Björkman S, Fredin H. Application of pharmacokinetic data from healthy volunteers for the prediction of plasma concentrations of tranexamic acid in surgical patients. Clin Drug Invest 1995;10:280–7.
    1. Sano M, Hakusui H, Kojima C, et al. Absorption and excretion of tranexamic acid following intravenous, intramuscular and oral administrations in healthy volunteers. Jpn J Clin Pharmacol Therapeutics 1976;7:375–82.
    1. Wang H, Shen B, Zeng Y. Comparison of topical versus intravenous tranexamic acid in primary total knee arthroplasty: a meta-analysis of randomized controlled and prospective cohort trials. Knee 2014;21:987–93.
    1. Wu Q, Zhang HA, Liu SL, et al. Is tranexamic acid clinically effective and safe to prevent blood loss in total knee arthroplasty? A meta-analysis of 34 randomized controlled trials. Eur J Orthop Surg Traumatol 2015;25:525–41.
    1. Alshryda S, Sukeik M, Sarda P, et al. A systematic review and meta-analysis of the topical administration of tranexamic acid in total hip and knee replacement. Bone Joint J 2014;96-b:1005–15.
    1. Zhao G-H, Ma J-B, Duan H-H, et al. The safety and efficacy of combined administration of tranexamic acid to reduce blood loss on total knee arthroplasty. J Pract Orthop 2015;21:691–4.
    1. Huang Z, Ma J, Shen B, et al. Combination of intravenous and topical application of tranexamic acid in primary total knee arthroplasty: a prospective randomized controlled trial. J Arthroplasty 2014;29:2342–6.
    1. Jain NP, Nisthane PP, Shah NA. Combined administration of systemic and topical tranexamic acid for total knee arthroplasty: can it be a better regimen and yet safe? a randomized controlled trial. J Arthroplasty 2015;31:542–7.
    1. Zhang J, Zhao M, Kan Z-K. A clinical study of the effect using locally implemented combined with intravenous tranexamic acid on the blood loss after total knee arthroplasty. Ningxia Med J 2016;38:130–2.
    1. Karaaslan F, Karaoğlu S, Mermerkaya MU, et al. Reducing blood loss in simultaneous bilateral total knee arthroplasty: Combined intravenous–intra-articular tranexamic acid administration. A prospective randomized controlled trial. Knee 2015;22:131–5.
    1. Zhao Liang-Hu, Liu Dian-Feng, Huang Jin, et al. Effect of intravenous and topical application of tranexamic acid on bleeding amount in the perioperative period of unilateral total knee replacement and its safety evaluation. Rheum Arthritis 2015;4:14–6.
    1. Liu Lin, Yang Zhi, Yao Jian-Feng, et al. Effect of local injections combined intravenous drip tranexamic acid on blood loss in total knee arthroplasty. J North Sichuan Med Coll 2015;30:611–4.
    1. Lin S-Y, Chen C-H, Fu Y-C, et al. The efficacy of combined use of intraarticular and intravenous tranexamic acid on reducing blood loss and transfusion rate in total knee arthroplasty. J Arthroplasty 2015;30:776–80.
    1. Nielsen CS, Jans O, Orsnes T, et al. Combined intra-articular and intravenous tranexamic acid reduces blood loss in total knee arthroplasty: a randomized, double-blind, placebo-controlled trial. J Bone Joint Surg Am 2016;98:835–41.
    1. Tu S-L, Xu Huo R, Guo H-M. The effect of blood loss control of combined intravenous with intra-articular tranexamic acid for total knee arthroplasty. Chin J Clin Basic Orthop Res 2015;7:44–7.
    1. Cui X-H, Wu H-B. The nursing effect of combined intravenous with topical administration tranxemic acid for blood loss after total knee arthroplasty. J North Pharm 2015;12:195–6.
    1. Ying-Ming W, Rong K, De Wan S, et al. Effects of intravenous and intra-articular tranexamic acid on postoperative blood loss of primary total knee arthroplasty. Anhui Med J 2015;36:1350–2.
    1. Zhao Z, Tao H, Tan J-X, et al. Efficacy and safety of intravenous and intra-articular sequential application of tranexamic acid during total knee arthroplasty. J Chongqing Med Univ 2015;41:142–6.
    1. Callaghan JJ, O’Rourke MR, Liu SS. Blood management: issues and options. J Arthroplasty 2005;20(4 suppl 2):51–4.
    1. Jiang FZ, Zhong HM, Hong YC, et al. Use of a tourniquet in total knee arthroplasty: a systematic review and meta-analysis of randomized controlled trials. J Orthop Sci 2015;20:110–23.
    1. Astedt B, Liedholm P, Wingerup L. The effect of tranexamic acid on the fibrinolytic activity of vein walls. Ann Chirurgiae Gynaecol 1978;67:203–5.

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