Journal of Orthopaedic Science 21 (2016) 44e47
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Comparison between topical and intravenous administration of tranexamic acid in primary total hip arthroplasty Masaya Ueno a, *, Motoki Sonohata a, Norio Fukumori b, Shunsuke Kawano a, Masaru Kitajima a, Masaaki Mawatari a a b
Department of Orthopaedic Surgery, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan Department of Community Medical Support Institute, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan
a r t i c l e i n f o
a b s t r a c t
Article history: Received 23 March 2015 Received in revised form 25 September 2015 Accepted 30 September 2015 Available online 18 November 2015
Background: Tranexamic acid has been reported to be safer with topical administration than with intravenous administration in total knee arthroplasty. However, the most effective administration route of tranexamic acid in total hip arthroplasty remains controversial. This study compared the effectiveness of topical tranexamic acid administration with that of intravenous tranexamic acid administration in total hip arthroplasty. Methods: We retrospectively examined the medical records of 886 patients with osteoarthritis of the hip joint, who had undergone unilateral primary total hip arthroplasty. The patients were divided into a control group (n ¼ 302; did not receive tranexamic acid), topical group (n ¼ 265; topically administered 2 g tranexamic acid in 30 mL normal saline via drain tubes placed in the joint before wound closure along with posterior soft tissue repair), and intravenous group (n ¼ 319; intravenously administered 1 g tranexamic acid before skin incision along with posterior soft tissue repair). Data on blood loss, hemoglobin levels, transfusion rates, and occurrence of deep vein thrombosis and pulmonary embolization were collected. Results: The mean operation times were approximately 40 min in all of the groups. The operation time and intra-operative blood loss were signiﬁcantly lower in the control group than in the topical and intravenous groups. However, the post-operative blood loss, total blood loss, and decrease in the hemoglobin level were signiﬁcantly higher in the control group than in the topical and intravenous groups. There were no signiﬁcant differences in terms of blood loss and systemic complications between the tranexamic acid administration methods. Conclusions: Tranexamic acid reduces both post-operative and total blood loss in total hip arthroplasty. Moreover, a lower amount of tranexamic acid can be used to reduce blood loss in total hip arthroplasty with intravenous tranexamic acid administration than with topical tranexamic acid administration. Therefore, we suggest that tranexamic acid should be intravenously administered pre-operatively and the posterior soft tissue should be repaired to decrease total hip arthroplasty-related complications. © 2015 The Authors. Published by Elsevier B.V. on behalf of The Japanese Orthopaedic Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
1. Introduction Total hip arthroplasty (THA) is one of the most common orthopedic operations for osteoarthritis. However, THA often results in severe peri-operative blood loss that requires blood transfusion [1,2], which increases the risk of joint infection  and viral transmission [4,5].
* Corresponding author. Tel.: þ81 852 34 2343; fax: þ81 952 34 2059. E-mail address: [email protected]
Skillful procedure will help to avoid these risks. Additionally, many different blood-conserving techniques, including autologous blood transfusion  and use of autologous ﬁbrin tissue , have been developed to reduce blood loss and post-operative blood transfusion rates . Tranexamic acid (TXA) is a synthetic antiﬁbrinolytic agent that has been successfully used to control bleeding in several surgical ﬁelds. Studies have shown that it reduces blood loss and prevents a decrease in hemoglobin levels without increasing the risk of deep vein thrombosis (DVT) in THA [9,10]. TXA can be administered through different routes, including intramuscular (IM), oral, intravenous (IV), and topical, and each
http://dx.doi.org/10.1016/j.jos.2015.10.011 0949-2658/© 2015 The Authors. Published by Elsevier B.V. on behalf of The Japanese Orthopaedic Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
M. Ueno et al. / Journal of Orthopaedic Science 21 (2016) 44e47
route has a different time to reach maximum plasma TXA levels (5e15 min for IV injection, 30 min for IM injection, and 2 h for oral administration ). TXA has been reported to be safer with topical administration than with IV administration in total knee arthroplasty (TKA) . Many recent studies have reported that IV TXA administration reduces blood loss in THA [8,10,13e17], and the efﬁcacy of topical TXA administration in THA was also investigated [18e21]. However, the most effective administration route of TXA in THA remains controversial. The aim of the present study was to compare the effectiveness of topical TXA administration with that of IV TXA administration in THA. 2. Materials and methods In this case series, we retrospectively examined the medical records of 886 patients with osteoarthritis of the hip joint, who had undergone unilateral primary THA performed by 6 senior surgeons between August 2009 and March 2013. Patients who had been administered anticoagulants and antiplatelet drugs pre-operatively and those with ischemic heart disease, chronic renal failure, a history of hip surgery, thromboembolic episodes, rheumatoid arthritis, idiopathic osteonecrosis of the femoral head, or a preoperative hemoglobin level below 8 g/dL were excluded. All surgeons used the same surgical instruments and standardized operative method. All THA procedures were performed under spinal anesthesia, using a posterior approach. Cementless stems and cups (Kyocera PerFix Total Hip System 910 Series; Kyocera, Osaka, Japan) and a suction drain were used in all cases. The suction drain was removed 2 days after the operation. All patients followed the same clinical pathway, including standard post-operative care and antithrombotic therapy. Based on the guidelines for blood transfusion, red blood cells were transfused for symptoms of anemia, including vertigo, hypotension, and bradycardia. Laboratory data were obtained 1e2 days before and 1 and 7 days after the operation. Blood loss (intra-operative, post-operative, and total), decrease in the hemoglobin level, and transfusion rates were recorded. Intra-operative blood loss was determined based on the contents of the suction bottle and the change in the weight of the used surgical sponges, while post-operative blood loss was determined based on the contents of the drain. The primary outcomes were operation time, blood loss (intraoperative, post-operative, and total), and decrease in the hemoglobin level at 1 and 7 days after the operation. The secondary outcomes were the transfusion rate, DVT, and occurrence of pulmonary embolization (PE) events. The patients were divided into the following 3 groups: the control group (patients who did not receive TXA between August 2009 and September 2010; n ¼ 302), topical group (patients who received topical TXA administration [2 g] before wound closure between October 2010 and December 2011; n ¼ 265), and IV group (patients who received IV TXA administration [1 g] before skin
incision between January 2012 and March 2013; n ¼ 319). In the topical group, TXA was administered with 30 mL normal saline via the drain tubes. Patients in the topical and IV groups underwent repair of the capsule of the hip joint and short rotator muscles. Because the Ministry of Health, Labour and Welfare in Japan limits IV TXA administration to a maximum of 1 g in a single dose, we used 2 different doses for IV (1 g) and topical (2 g) administration. The groups were compared using the KruskaleWallis test and chisquare test. All statistical analyses were performed using SPSS Version 21 for Windows (IBM Corp, Armonk, NY). A p-value <0.05 was considered signiﬁcant. The institutional review board approved this study, and the requirement for informed consent was waived owing to the retrospective nature of the study. 3. Results The control, topical, and IV groups included 302, 265, and 319 patients, respectively. Regarding the patient characteristics, no statistically signiﬁcant differences were noted in height, weight, body mass index, and pre-operative hemoglobin level between the groups. However, the age of the patients was lower in the control group than in the IV group (Table 1). The mean operation times were approximately 40 min in all of the groups. The operation time and intra-operative blood loss were signiﬁcantly lower in the control group than the topical and IV groups (Table 2). However, the post-operative blood loss, total blood loss, and decrease in the hemoglobin level were signiﬁcantly higher in the control group than in the topical and IV groups. There were no signiﬁcant differences in blood loss (intra-operative, postoperative, and total) and hemoglobin levels between the topical and IV groups. Because the age of the patients was low in the control group, linear regression analyses were performed to determine the potential relationships of the variables with age. We found that the relationship between age and operation time, blood loss, or change in the hemoglobin level was not signiﬁcant. There were no statistically signiﬁcant differences in transfusion rates between the groups (Table 3). One case of asymptomatic DVT was noted in the IV group; however, a symptomatic PE event did not occur in any of the groups. 4. Discussion The present study found that TXA reduced both post-operative and total blood loss in THA. Additionally, no signiﬁcant differences were noted between the TXA administration methods in terms of blood loss (intra-operative, post-operative, or total), hemoglobin levels, transfusion rates, and systemic complications, despite a difference in the amount of TXA administered between the topical and IV groups. The mean operation times were approximately 40 min in all of the groups, which are remarkably lower than the operation times
Table 1 Characteristics of patients who had undergone total hip arthroscopy with or without tranexamic acid administration.
Age (years) Gender (M:F) Body weight (kg) Body mass index (kg/m2) Preoperative hemoglobin level (g/dL)
Control group (n ¼ 302)
Topical group (n ¼ 265)
Intravenous group (n ¼ 319)
63.6 ± 9.7 26:276 56.7 ± 10.2 24.5 ± 4.0 13.0 ± 1.3
64.9 ± 10.5 33:232 57.5 ± 20.6 24.6 ± 3.7 13.0 ± 1.2
65.8 ± 9.4a 46:273 57.2 ± 11.3 24.4 ± 4.2 13.0 ± 1.3
Data are reported as mean ± SD or as the total number. a Denotes signiﬁcant differences between the control and intravenous groups based on a KruskaleWallis test.
M. Ueno et al. / Journal of Orthopaedic Science 21 (2016) 44e47
Table 2 Perioperative outcomes of patients who had undergone total hip arthroscopy with or without tranexamic acid administration. Control group (n ¼ 302) Operation time (min) 39.2 Decrease in hemoglobin levels (g/dL) Day 1 3.2 Day 7 3.6 Blood loss (g) Intra-operative 241.1 Post-operative 372.2 Total 613.3
Topical group (n ¼ 265)
Intravenous group (n ¼ 319)
42.2 ± 8.0a
43.5 ± 9.0a
± 1.1 ± 1.4
1.9 ± 0.8a 2.1 ± 0.9a
1.9 ± 0.9a 2.2 ± 0.9a
278.7 ± 113.0a 240.7 ± 127.1a 519.4 ± 184.6a
290.3 ± 124.1a 252.9 ± 127.8a 560.0 ± 194.7a
0.542 0.982 0.439
± 97.0 ± 172.7 ± 199.5
Data are reported as mean ± SD. The p-value reﬂects the comparison between the topical and intravenous groups. a Denotes signiﬁcant differences between the control group and intravenous group or topical group based on KruskaleWallis tests.
Table 3 Rates of blood transfusion and incidence of thromboembolic events in patients who had undergone total hip arthroscopy with or without tranexamic acid administration.
Blood transfusion Deep vein thrombosis Pulmonary embolism
Control group (n ¼ 292)
Topical group (n ¼ 260)
Intravenous group (n ¼ 312)
10 (3.3%) 0 0
5 (1.9%) 0 0
7 (2.2%) 1 (0.5%) 0
Data are presented as number (percentage).
reported previously [14,21]. To minimize the occurrence of complications and side effects after THA, we standardized the operative method and shortened the operation time. All surgeons in our hospital use the same surgical instruments and standardized operative method. Therefore, we succeeded in improving the THA technique and the skill of the surgical staff, resulting in reduced operation durations and lower blood loss in our hospital compared to those reported in previous studies. To reduce blood loss and the occurrence of complications even further, we started administering TXA and repairing the posterior soft tissue to maintain the TXA close to the surgical site. We found that these modiﬁcations increased the operation time and the intra-operative blood loss with both topical and IV administration of TXA. However, repair of the posterior soft tissue can decrease the risk of dislocation. We believe that TXA administration and repair of the posterior soft tissue decreased the occurrence of THA-related complications, despite the disadvantage of a long operation time. A previous study reported that TXA is safer with topical administration than with IV administration in TKA because topical TXA administration minimizes the occurrence of systemic complications . Furthermore, topical TXA injection has the advantage of inducing partial microvascular hemostasis by inhibiting the dissolution of ﬁbrin clots in the affected area . However, it is difﬁcult to compare TKA with THA because TKA is usually performed with a tourniquet, and TXA administered intravenously does not reach the surgical site. Although a direct relationship has been reported between the total amount of TXA administered and post-operative blood loss , in the present study, there were no signiﬁcant differences between topical TXA administration (2 g) and IV TXA administration (1 g) in terms of blood loss (intra-operative, post-operative, and total), despite differences in the amount of TXA administered. Therefore, a lower amount of TXA can be used to achieve appropriate outcomes in THA with IV TXA administration than with topical TXA administration. In the present study, ﬁbrinolysis would not have been completely activated at the end of the operation in the IV group because the operation time was remarkably shorter in the IV group than in groups presented in previous study . TXA binds reversibly to plasminogen and blocks the binding of plasminogen to ﬁbrin, which activates and transforms plasminogen to plasmin
; TXA requires the time for plasminogen to be activated. Dahl et al. reported that the ﬁbrinolytic response occurs in the early phases of operative procedures , and Imai et al. reported that TXA reduces intra-operative blood loss . However, because of the short operation times in the present study, pre-operative TXA administration could not reduce intra-operative blood loss. Therefore, if the operation times were long, intra-operative blood loss would be low with pre-operative TXA administration. IV TXA administration at the end of the operation has been shown not to reduce post-operative blood loss in hip arthroplasty . Therefore, IV TXA administration should be performed pre-operatively. TXA reduced both post-operative and total blood loss in THA. Additionally, we found no signiﬁcant differences in blood loss and systemic complications between the TXA administration methods. Moreover, a lower amount of TXA can be used to reduce blood loss in THA with IV TXA administration than with topical TXA administration. Therefore, we suggest that TXA should be intravenously administered pre-operatively and the posterior soft tissue should be repaired to decrease THA-related complications.
Conﬂict of interest The authors have no conﬂicts of interest and certify that they have no afﬁliation with or ﬁnancial involvement in any organization or entity with a direct ﬁnancial interest in the subject matter or materials discussed in this manuscript.
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