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      Efficacy and Safety of Orally and Intravenously Administration of Tranexamic Acid in Patients with Elderly Femoral Neck Fracture

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          Abstract

          Objective

          For elderly femoral neck fracture patients, anemia is one of the most common complications, increasing the risk of postoperative adverse events. Tranexamic acid (TXA) has been widely applied to the perioperative blood management. However, the optimal route of TXA administration in elderly femoral neck fracture remains unclear. The aim of this study is to evaluate the efficacy and safety of oral and intravenous (IV) application of TXA in elderly patients with femoral neck fracture undergoing total hip arthroplasty (THA) and hemiarthroplasty (HA).

          Methods

          All elderly patients aged over 65 years old diagnosed with femoral neck fracture admitted to the trauma orthopedics from August 1, 2020 to February 28, 2022 were enrolled in this prospective cohort study. Participants were divided into three groups: oral group: TXA 2g orally 2 h before incision; IV group: intravenous infusion of TXA 1g 15 min before incision; and control group: usual hemostatic method. The primary outcomes were total blood loss, allogeneic transfusion rate, and postoperative thromboembolic events. SPSS 23.0 (IBM, Armonk, NY, USA) was used for statistical analysis, and p ≤ 0.05 was considered statistically significant.

          Results

          A total of 100 patients were enrolled, including 32 cases in the oral group, 34 cases in the IV group and 34 cases in the control group. Compared with the control group, the total perioperative blood loss in the oral and IV groups was significantly decreased (763.92 ± 358.64 mL vs 744.62 ± 306.88 mL vs 1250.60 ± 563.37 mL, p = 0.048). No significant difference was identified between the oral and IV groups ( p = 0.970). The rate of allogeneic transfusion was lower in the oral and IV groups than in the control group, but the difference had no statistical significant (6 vs 5 vs 12, p = 0.108), However, subgroup analysis showed that the IV and oral groups in patients who underwent THA have significant lower transfusion rate compared with the control group (1 vs 3 vs 7, p = 0.02). During 6 months follow‐up, no thromboembolic events were identified. Two patients (one from the oral group and one from the control group) died of respiratory failure. The cost of blood management from the oral group was significantly lower than IV ( p < 0.001) and control groups ( p = 0.009).

          Conclusion

          Elderly patients with femoral neck fracture undergoing THA can benefit from both IV and oral administration of tranexamic acid. The results of these two administration routes are similar in safety and effectiveness. A similar tendency was observed in patients undergoing HA. Oral TXA is more cost–benefit compared with intravenous applications.

          Abstract

          Flow chart of the participants for this study.

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          Most cited references32

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          Prediction of blood volume in normal human adults.

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            Estimating allowable blood loss: corrected for dilution.

            J B Gross (1983)
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              Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial

              (2019)
              Summary Background Tranexamic acid reduces surgical bleeding and decreases mortality in patients with traumatic extracranial bleeding. Intracranial bleeding is common after traumatic brain injury (TBI) and can cause brain herniation and death. We aimed to assess the effects of tranexamic acid in patients with TBI. Methods This randomised, placebo-controlled trial was done in 175 hospitals in 29 countries. Adults with TBI who were within 3 h of injury, had a Glasgow Coma Scale (GCS) score of 12 or lower or any intracranial bleeding on CT scan, and no major extracranial bleeding were eligible. The time window for eligibility was originally 8 h but in 2016 the protocol was changed to limit recruitment to patients within 3 h of injury. This change was made blind to the trial data, in response to external evidence suggesting that delayed treatment is unlikely to be effective. We randomly assigned (1:1) patients to receive tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Patients were assigned by selecting a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was head injury-related death in hospital within 28 days of injury in patients treated within 3 h of injury. We prespecified a sensitivity analysis that excluded patients with a GCS score of 3 and those with bilateral unreactive pupils at baseline. All analyses were done by intention to treat. This trial was registered with ISRCTN (ISRCTN15088122), ClinicalTrials.gov (NCT01402882), EudraCT (2011-003669-14), and the Pan African Clinical Trial Registry (PACTR20121000441277). Results Between July 20, 2012, and Jan 31, 2019, we randomly allocated 12 737 patients with TBI to receive tranexamic acid (6406 [50·3%] or placebo [6331 [49·7%], of whom 9202 (72·2%) patients were treated within 3 h of injury. Among patients treated within 3 h of injury, the risk of head injury-related death was 18·5% in the tranexamic acid group versus 19·8% in the placebo group (855 vs 892 events; risk ratio [RR] 0·94 [95% CI 0·86–1·02]). In the prespecified sensitivity analysis that excluded patients with a GCS score of 3 or bilateral unreactive pupils at baseline, the risk of head injury-related death was 12·5% in the tranexamic acid group versus 14·0% in the placebo group (485 vs 525 events; RR 0·89 [95% CI 0·80–1·00]). The risk of head injury-related death reduced with tranexamic acid in patients with mild-to-moderate head injury (RR 0·78 [95% CI 0·64–0·95]) but not in patients with severe head injury (0·99 [95% CI 0·91–1·07]; p value for heterogeneity 0·030). Early treatment was more effective than was later treatment in patients with mild and moderate head injury (p=0·005) but time to treatment had no obvious effect in patients with severe head injury (p=0·73). The risk of vascular occlusive events was similar in the tranexamic acid and placebo groups (RR 0·98 (0·74–1·28). The risk of seizures was also similar between groups (1·09 [95% CI 0·90–1·33]). Interpretation Our results show that tranexamic acid is safe in patients with TBI and that treatment within 3 h of injury reduces head injury-related death. Patients should be treated as soon as possible after injury. Funding National Institute for Health Research Health Technology Assessment, JP Moulton Charitable Trust, Department of Health and Social Care, Department for International Development, Global Challenges Research Fund, Medical Research Council, and Wellcome Trust (Joint Global Health Trials scheme). Translations For the Arabic, Chinese, French, Hindi, Japanese, Spanish and Urdu translations of the abstract see Supplementary Material.
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                Author and article information

                Contributors
                ruiyunfeng@126.com
                Journal
                Orthop Surg
                Orthop Surg
                10.1111/(ISSN)1757-7861
                OS
                Orthopaedic Surgery
                John Wiley & Sons Australia, Ltd (Melbourne )
                1757-7853
                1757-7861
                20 May 2024
                July 2024
                : 16
                : 7 ( doiID: 10.1111/os.v16.7 )
                : 1581-1591
                Affiliations
                [ 1 ] Department of Orthopaedics, Zhongda Hospital, School of Medicine Southeast University Nanjing China
                [ 2 ] Orthopaedic Trauma Institute (OTI) Southeast University Nanjing China
                [ 3 ] Multidisciplinary Team (MDT) for elderly Hip Fracture Comprehensive Management, Zhongda Hospital, School of Medicine Southeast University Nanjing China
                [ 4 ] The Fourth Affiliated Hospital of Nanjing Medical University Nanjing China
                [ 5 ] Handan First Hospital Handan China
                Author notes
                [*] [* ] Address for correspondence Yun‐feng Rui. Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing 210009, Jiangsu Province, China. Email: ruiyunfeng@ 123456126.com

                Author information
                https://orcid.org/0000-0001-7338-2837
                Article
                OS14089
                10.1111/os.14089
                11216831
                38766813
                65bb41f7-a20a-477e-b05a-5cecae85e949
                © 2024 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 11 April 2024
                : 13 August 2023
                : 17 April 2024
                Page count
                Figures: 5, Tables: 5, Pages: 11, Words: 6600
                Funding
                Funded by: Winfast Charity Foundation Project
                Award ID: YL20220525
                Categories
                Clinical Article
                Clinical Articles
                Custom metadata
                2.0
                July 2024
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.4.5 mode:remove_FC converted:01.07.2024

                elderly,femoral neck fracture,hip arthroplasty,oral application,tranexamic acid

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