title: Combined Intra-Articular and Intravenous Tranexamic Acid Reduces Blood Loss in Total Knee Arthroplasty: A Randomized, Double-Blind, Placebo-Controlled Trial.
abstract: BACKGROUND
  In total knee arthroplasty, both intravenous (IV) and intra-articular (IA) administration of tranexamic acid (TXA) have been shown to reduce blood loss in several randomized controlled trials, although routine use of systemic TXA is considerably more common. However, to our knowledge, the additional benefit of IA administration of TXA when combined with IV administration, without the use of a tourniquet, has not been previously investigated. Thus, the aim of this study was to evaluate whether combined IV and IA administration of TXA reduced total blood loss compared with IV-only administration of TXA.
  
  
  METHODS
  In this randomized, double-blind, placebo-controlled trial, 60 patients scheduled for total knee arthroplasty were randomized to one of two interventions. The TXA IV and IA group received combined administration of TXA consisting of 1 g administered intravenously preoperatively and 3 g diluted in 100 mL of saline solution administered intra-articularly after closure of the capsule. The TXA IV and placebo group received 1 g of TXA administered intravenously only and 100 mL of saline solution administered intra-articularly. IA TXA was administrated through a needle. The primary outcome was the 24-hour calculated blood loss. Secondary outcomes were blood loss on postoperative day 2, thromboembolic complications, and transfusion rate. Blood loss was calculated by hemoglobin differences using the Gross formula.
  
  
  RESULTS
  Data on the primary outcome were available for all 60 included patients. Baseline characteristics were comparable between the allocation groups. The mean 24-hour blood loss (and standard deviation) was 466 ± 313 mL in the TXA IV and IA group compared with 743 ± 358 mL in the TXA IV and placebo group; treatment effect (difference), 277 mL (95% confidence interval [CI], 103 to 451 mL) (p = 0.002). Second-day blood loss was 644 ± 382 mL in the TXA IV and IA group compared with 1017 ± 519 mL in the TXA IV and placebo group; treatment effect, 373 mL (95% CI, 132 to 614 mL) (p = 0.003). No thromboembolic complications were observed within 90 days postoperatively.
  
  
  CONCLUSIONS
  The combined administration of IV and IA TXA resulted in a clinically relevant reduction in blood loss of 37% compared with IV TXA alone both at 24 hours postoperatively and on postoperative day 2. No thromboembolic complications were observed.
  
  
  METHODS
  Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
authors.affiliation: Department of Orthopaedic Surgery (C.S.N., T.Ø., A.T., and H.H.) and Department of Anesthesia (N.B.F.), Copenhagen University Hospital Hvidovre, Copenhagen, Denmark Harris Orthopaedic Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, Massachusetts christianskovgaard@dadlnet.dk.
authors.forename: Christian Skovgaard
authors.initials: CS
authors.lastname: Nielsen
authors.affiliation: Section of Surgical Pathophysiology, Rigshospitalet, Copenhagen, Denmark Lundbeck Foundation Centre for Fast-Track Hip and Knee Arthroplasty, Denmark oeivind.jans@rh.regionh.dk.
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Jans
authors.affiliation: Department of Orthopaedic Surgery (C.S.N., T.Ø., A.T., and H.H.) and Department of Anesthesia (N.B.F.), Copenhagen University Hospital Hvidovre, Copenhagen, Denmark Thue.Oersnes@regionh.dk.
authors.forename: Thue
authors.initials: T
authors.lastname: Ørsnes
authors.affiliation: Department of Orthopaedic Surgery (C.S.N., T.Ø., A.T., and H.H.) and Department of Anesthesia (N.B.F.), Copenhagen University Hospital Hvidovre, Copenhagen, Denmark nicolai.bang.foss@regionh.dk.
authors.forename: Nicolai Bang
authors.initials: NB
authors.lastname: Foss
authors.affiliation: Department of Orthopaedic Surgery (C.S.N., T.Ø., A.T., and H.H.) and Department of Anesthesia (N.B.F.), Copenhagen University Hospital Hvidovre, Copenhagen, Denmark Lundbeck Foundation Centre for Fast-Track Hip and Knee Arthroplasty, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Troelsen
authors.affiliation: Department of Orthopaedic Surgery (C.S.N., T.Ø., A.T., and H.H.) and Department of Anesthesia (N.B.F.), Copenhagen University Hospital Hvidovre, Copenhagen, Denmark Lundbeck Foundation Centre for Fast-Track Hip and Knee Arthroplasty, Denmark henrikhusted@dadlnet.dk.
authors.forename: Henrik
authors.initials: H
authors.lastname: Husted
mesh_terms: D000368:Aged; D000933:Antifibrinolytic Agents / Q000008:administration & dosage*; D019645:Arthroplasty, Replacement, Knee; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D001803:Blood Transfusion; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007270:Injections, Intra-Articular; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000601:surgery*; D019106:Postoperative Hemorrhage / Q000209:etiology / Q000517:prevention & control*; D013923:Thromboembolism / Q000209:etiology; D014148:Tranexamic Acid / Q000008:administration & dosage*
chemical_list: D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid