{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:51:31Z","timestamp":1792788691221,"version":"4.5.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Beijing Municipality","award":["L232006"],"award-info":[{"award-number":["L232006"]}]},{"name":"National High Level Hospital Clinical Research Funding","award":["2025-PUMCH-A-051"],"award-info":[{"award-number":["2025-PUMCH-A-051"]}]},{"name":"Peking Union Medical College Hospital Talent Development Program Funding","award":["UGG10119"],"award-info":[{"award-number":["UGG10119"]}],"id":[{"id":"https:\/\/ror.org\/04jztag35","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>This study compared femoral-canal administration of tranexamic acid (TXA), which is a modified intraosseous regional administration (IORA) technique, with intravenous (IV) TXA and combined IORA+IV-TXA across prosthesis designs in tourniquet-assisted, manual total knee arthroplasty (TKA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>This single-center study comprised 2 consecutive prospective, randomized, placebo-controlled, triple-blind cohorts: a previously reported cruciate-retaining (CR) cohort followed by a posterior-stabilized (PS) cohort. Within each cohort, patients undergoing primary, unilateral, manual TKA were randomized to IORA-TXA, IV-TXA, or IORA+IV-TXA. The primary outcome was total blood loss (TBL). Secondary outcomes included transfusion, inflammatory and coagulation markers, pain, knee function, and complications. Pooled and prosthesis-stratified analyses were performed, including treatment-by-prosthesis interaction testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Among 202 randomized participants (mean age, 69.1 years [SD, 6.5]; 162 women [80%]; CR, 97; PS, 105), TBL differed significantly among groups. Compared with IV-TXA (578.7 \u00b1 \u00b1277.4 mL), TBL was lower with IORA-TXA (429.2 \u00b1 293.9 mL, p = 0.010) and IORA+IV-TXA (354.3 \u00b1 252.1 mL, p &lt; 0.001). The treatment-by-prosthesis interaction for TBL was not significant (p = 0.289). Transfusion occurred in 1 participant in the IV-TXA group and none in the IORA-TXA or IORA+IV groups. Statistically significant differences were observed in the selected early inflammatory and clinical outcomes, primarily involving the combined regimen; however, these differences did not translate into clinically meaningful differences in pain scores, range of motion, or KOOS-JR scores by 90 days. No statistically detectable differences in complications were observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>In tourniquet-assisted manual TKA, femoral-canal IORA-TXA reduced TBL compared with IV-TXA, and IORA+IV-TXA showed the lowest mean TBL. These findings should be interpreted within the pre\u2013tourniquet-release IV-TXA protocol; evidence was insufficient to establish corresponding reductions in transfusion or clinically meaningful functional benefits by 90 days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Level of Evidence:<\/jats:title>\n                    <jats:p>\n                      Therapeutic\n                      <jats:underline>Level II<\/jats:underline>\n                      . See Instructions for Authors for a complete description of levels of evidence.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.2106\/jbjs.oa.26.00161","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:00:55Z","timestamp":1792087255000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Femoral-Canal Administration of Tranexamic Acid in Tourniquet-Assisted Total Knee Arthroplasty"],"prefix":"10.2106","volume":"11","author":[{"given":"Muyang","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Orthopedics Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingwei","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Te","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4067-1373","authenticated-orcid":false,"given":"Yiming","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingdong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiming","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xisheng","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0898-8028","authenticated-orcid":false,"given":"Bin","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,10]]},"reference":[{"issue":"2","key":"R1-20261015","doi-asserted-by":"crossref","first-page":"89","DOI":"10.2106\/JBJS.22.01030","article-title":"What's new in adult reconstructive knee surgery","volume":"105","author":"Villa","year":"2023","journal-title":"J Bone Jt Surg."},{"issue":"7","key":"R2-20261015","first-page":"e65386","article-title":"The impact of tranexamic acid on blood loss management in primary total knee arthroplasty: a comprehensive review","volume":"16","author":"Sawant","year":"2024","journal-title":"Cureus"},{"issue":"3","key":"R3-20261015","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1007\/s00264-023-05983-8","article-title":"Intra-articular injection of tranexamic acid in patients with haemophilia arthritis: retrospective controlled study in total knee arthroplasty","volume":"48","author":"Xiang","journal-title":"Int Orthop"},{"issue":"may17 1","key":"R4-20261015","doi-asserted-by":"crossref","first-page":"e3054","DOI":"10.1136\/bmj.e3054","article-title":"Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis","volume":"344","author":"Ker","year":"2012","journal-title":"BMJ"},{"issue":"13","key":"R5-20261015","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.2106\/JBJS.K.00873","article-title":"Effectiveness and safety of tranexamic acid in reducing blood loss in total knee arthroplasty: a meta-analysis","volume":"94","author":"Yang","year":"2012","journal-title":"J Bone Jt Surg."},{"issue":"9","key":"R6-20261015","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1007\/s00167-011-1754-z","article-title":"The effect of tranexamic acid on blood loss and use of blood products in total knee arthroplasty: a meta-analysis","volume":"20","author":"Zhang","year":"2012","journal-title":"Knee Surg Sports Traumatol Arthrosc."},{"issue":"12","key":"R7-20261015","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1302\/0301-620X.93B12.26989","article-title":"Tranexamic acid in total knee replacement","volume":"93-B","author":"Alshryda","year":"2011","journal-title":"J Bone Jt Surg Br"},{"issue":"8","key":"R8-20261015","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1111\/j.1537-2995.2005.00204.x","article-title":"Tranexamic acid reduces allogeneic red cell transfusions in patients undergoing total knee arthroplasty: results of a meta-analysis of randomized controlled trials","volume":"45","author":"Cid","year":"2005","journal-title":"Transfusion"},{"issue":"10","key":"R9-20261015","doi-asserted-by":"crossref","first-page":"3090","DOI":"10.1016\/j.arth.2018.04.043","article-title":"The efficacy of tranexamic acid in total knee arthroplasty: a network meta-analysis","volume":"33","author":"Fillingham","journal-title":"J Arthroplasty"},{"issue":"4","key":"R10-20261015","doi-asserted-by":"crossref","first-page":"e20.00001","DOI":"10.2106\/JBJS.ST.20.00001","article-title":"Intraosseous regional administration of antibiotic prophylaxis in total knee arthroplasty","volume":"10","author":"Arthur","year":"2020","journal-title":"JBJS Essent Surg Tech"},{"issue":"4","key":"R11-20261015","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.arth.2022.10.023","article-title":"Intraosseous regional administration of antibiotic prophylaxis for total knee arthroplasty: a systematic review","volume":"38","author":"Miltenberg","journal-title":"J Arthroplasty"},{"issue":"11","key":"R12-20261015","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1302\/0301-620X.105B11.BJJ-2023-0708","article-title":"Intraosseous regional prophylaxis in total knee arthroplasty","volume":"105-B","author":"Young","year":"2023","journal-title":"Bone Jt J."},{"issue":"5","key":"R13-20261015","doi-asserted-by":"crossref","first-page":"634","DOI":"10.3390\/antibiotics11050634","article-title":"Intraosseous regional administration of prophylactic antibiotics in total knee arthroplasty","volume":"11","author":"Wells","year":"2022","journal-title":"Antibiotics"},{"issue":"6","key":"R14-20261015","doi-asserted-by":"crossref","first-page":"S139","DOI":"10.1016\/j.arth.2021.10.009","article-title":"Intraosseous morphine decreases postoperative pain and pain medication use in total knee arthroplasty: a double-blind, randomized controlled trial","volume":"37","author":"Brozovich","year":"2022","journal-title":"J Arthroplasty"},{"key":"R15-20261015","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.knee.2023.06.002","article-title":"A multimodal intraosseous infusion of morphine and ketorolac decreases early postoperative pain and opioid consumption following total knee arthroplasty","volume":"43","author":"McNamara","year":"2023","journal-title":"Knee"},{"issue":"2","key":"R16-20261015","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1213\/ANE.0b013e3181c03c7f","article-title":"Intraosseous infusions: a review for the anesthesiologist with a focus on pediatric use","volume":"110","author":"Tobias","year":"2010","journal-title":"Anesth Analgesia"},{"issue":"2","key":"R17-20261015","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1097\/00130478-200104000-00016","article-title":"Pulmonary fat embolism and intraosseous infusion","volume":"2","author":"Byrick","year":"2001","journal-title":"Pediatr Crit Care Med"},{"key":"R18-20261015","article-title":"Effectiveness and safety of intraosseous regional administration versus intravenous tranexamic acid in primary total knee arthroplasty: a randomized, triple-blind, placebo-controlled trial","volume":"Dec 10","author":"Yu","year":"2025","journal-title":"Int J Surg"},{"issue":"2","key":"R19-20261015","doi-asserted-by":"crossref","first-page":"e077393","DOI":"10.1136\/bmjopen-2023-077393","article-title":"Impact of intraosseous regional administration of tranexamic acid in total knee arthroplasty on perioperative blood loss: a protocol for a randomised controlled trial","volume":"14","author":"Wei","year":"2024","journal-title":"BMJ Open"},{"issue":"2","key":"R20-20261015","first-page":"65","article-title":"Guidelines for prevention of venous thromboembolism in major orthopedic operations in China","volume":"36","year":"2016","journal-title":"Chin J Orthop"},{"issue":"2","key":"R22-20261015","first-page":"224","article-title":"Prediction of blood volume in normal human adults","volume":"51","author":"Nadler","year":"1962","journal-title":"Surgery"},{"issue":"3","key":"R23-20261015","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1097\/00000542-198303000-00016","article-title":"Estimating allowable blood loss: corrected for dilution","volume":"58","author":"Gross","year":"1983","journal-title":"Anesthesiology"},{"issue":"1","key":"R24-20261015","doi-asserted-by":"crossref","first-page":"75","DOI":"10.4103\/0366-6999.147817","article-title":"Changes of hemoglobin and hematocrit in elderly patients receiving lower joint arthroplasty without allogeneic blood transfusion","volume":"128","author":"Zhou","year":"2015","journal-title":"Chin Med J"},{"issue":"10","key":"R25-20261015","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1007\/s00264-017-3519-x","article-title":"The efficacy and safety of multiple-dose intravenous tranexamic acid on blood loss following total knee arthroplasty: a randomized controlled trial","volume":"41","author":"Lei","year":"2017","journal-title":"Int Orthop"},{"key":"R26-20261015","doi-asserted-by":"crossref","first-page":"12769","DOI":"10.2147\/JIR.S532632","article-title":"Study on the effects of tranexamic acid on perioperative inflammation, long-term functional recovery, and satisfaction in total knee arthroplasty: a Follow-up study","volume":"18","author":"Lin","year":"2025","journal-title":"J Inflamm Res."},{"issue":"7","key":"R27-20261015","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.3390\/medicina60071183","article-title":"The effect of intravenous tranexamic acid on perioperative blood loss, transfusion requirements, verticalization, and ambulation in total knee arthroplasty: a randomized double-blind study","volume":"60","author":"Jovanovic","year":"2024","journal-title":"Medicina"},{"issue":"1","key":"R28-20261015","doi-asserted-by":"crossref","first-page":"e024350","DOI":"10.1136\/bmjopen-2018-024350","article-title":"Comparison of intravenous, topical or combined routes of tranexamic acid administration in patients undergoing total knee and hip arthroplasty: a meta-analysis of randomised controlled trials","volume":"9","author":"Sun","year":"2019","journal-title":"BMJ Open"},{"issue":"1","key":"R29-20261015","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1186\/s12891-023-07036-y","article-title":"Blood-conserving and therapeutic efficacy of intravenous tranexamic acid at different time points after primary total knee arthroplasty with tourniquet application: a randomised controlled trial","volume":"24","author":"Wang","year":"2023","journal-title":"BMC Musculoskelet Disord"},{"issue":"5","key":"R30-20261015","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1302\/0301-620X.83B5.0830702","article-title":"Timing of the administration of tranexamic acid for maximum reduction in blood loss in arthroplasty of the knee","volume":"83-B","author":"Tanaka","year":"2001","journal-title":"J Bone Jt Surg Br"},{"issue":"5","key":"R31-20261015","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1093\/bja\/aeg111","article-title":"Tranexamic acid decreases external blood loss but not hidden blood loss in total knee replacement","volume":"90","author":"Good","year":"2003","journal-title":"Br J Anaesth"},{"issue":"1","key":"R32-20261015","doi-asserted-by":"crossref","first-page":"e6","DOI":"10.1016\/j.thromres.2012.11.006","article-title":"Duration of postoperative fibrinolysis after total hip or knee replacement: a laboratory follow-up study","volume":"131","author":"Blanie","year":"2013","journal-title":"Thromb Res."},{"issue":"19","key":"R33-20261015","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1182\/blood-2015-03-635524","article-title":"IL-1\u03b2, in contrast to TNF\u03b1, is pivotal in blood-induced cartilage damage and is a potential target for therapy","volume":"126","author":"van Vulpen","year":"2015","journal-title":"Blood"},{"issue":"11","key":"R34-20261015","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1016\/j.joca.2012.07.021","article-title":"Cartilage and bone markers and inflammatory cytokines are increased in synovial fluid in the acute phase of knee injury (hemarthrosis) -a cross-sectional analysis","volume":"20","author":"Sw\u00e4rd","year":"2012","journal-title":"Osteoarthritis Cartilage"},{"issue":"5","key":"R35-20261015","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/j.bja.2021.01.021","article-title":"Minimal clinically important differences in randomised clinical trials on pain management after total hip and knee arthroplasty: a systematic review","volume":"126","author":"Laigaard","year":"2021","journal-title":"Br J Anaesth."},{"issue":"7","key":"R36-20261015","doi-asserted-by":"crossref","first-page":"S71","DOI":"10.1016\/j.arth.2018.02.029","article-title":"How much pain is significant? Defining the minimal clinically important difference for the visual analog scale for pain after total joint arthroplasty","volume":"33","author":"Danoff","year":"2018","journal-title":"J Arthroplasty"},{"issue":"1","key":"R37-20261015","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s40634-023-00628-6","article-title":"Robotic-assisted total knee arthroplasty is not associated with increased risk of postoperative deep vein thrombosis","volume":"10","author":"Itou","year":"2023","journal-title":"J Exp Orthop."},{"issue":"2","key":"R38-20261015","doi-asserted-by":"crossref","first-page":"2309499020926790","DOI":"10.1177\/2309499020926790","article-title":"Multimodal thromboprophylaxis in low-risk patients undergoing lower limb arthroplasty: a retrospective observational cohort analysis of 1400 patients with ultrasound screening","volume":"28","author":"Harrison-Brown","year":"2020","journal-title":"J Orthop Surg (Hong Kong)"},{"issue":"331","key":"R39-20261015","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1097\/00003086-199610000-00027","article-title":"Transesophageal echocardiographic monitored events during total knee arthroplasty","volume":"331","author":"Morawa","year":"1996","journal-title":"Clin Orthop Relat Res."},{"issue":"6","key":"R40-20261015","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.jen.2010.09.001","article-title":"Recommendations for the use of intraosseous vascular access for emergent and nonemergent situations in various healthcare settings: a consensus paper","volume":"36","author":"Phillips","year":"2010","journal-title":"J Emerg Nurs"},{"issue":"2","key":"R41-20261015","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.21037\/apm-20-1857","article-title":"What is the ideal route of administration of tranexamic acid in total knee arthroplasty? A meta-analysis based on randomized controlled trials","volume":"10","author":"Lu","year":"2021","journal-title":"Ann Palliat Med."},{"issue":"1","key":"R42-20261015","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1186\/s12891-018-2181-9","article-title":"The efficacy and safety of combined administration of intravenous and topical tranexamic acid in primary total knee arthroplasty: a meta-analysis of randomized controlled trials","volume":"19","author":"Xiong","year":"2018","journal-title":"BMC Musculoskelet Disord"}],"container-title":["JBJS Open Access"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.2106\/JBJS.OA.26.00161","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:01:03Z","timestamp":1792087263000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.2106\/JBJS.OA.26.00161"}},"subtitle":["A Prospective Randomized Trial"],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":41,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.2106\/jbjs.oa.26.00161","relation":{},"ISSN":["2472-7245","2472-7245"],"issn-type":[{"value":"2472-7245","type":"electronic"},{"value":"2472-7245","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]}}}