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Tranexamic Acid Administration in Arthroscopic Surgery Is a Safe Adjunct to Decrease Postoperative Pain and Swelling: A Systematic Review and Meta-analysis

Published:October 13, 2021DOI:https://doi.org/10.1016/j.arthro.2021.10.001

      Purpose

      To systematically screen the literature in an effort to critically examine the effect of tranexamic acid (TXA) in patients undergoing arthroscopic surgery, specifically pertaining to pain, blood loss, length of surgery, and both major and minor complications.

      Methods

      In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) guidelines, 3 databases (MEDLINE, EMBASE, and Cochrane) were searched April 2020 and screened in duplicate using inclusion and exclusion criteria for studies on the given subject. Study findings were reviewed, and meta-analysis was then performed on sufficiently congruent data using a random-effects model.

      Results

      There were 7 eligible randomized controlled trials, with 724 total patients, undergoing anterior cruciate ligament reconstruction (4 studies, 537 patients), meniscectomy (1 study, 45 patients), femoroacetabular impingement (1 study, 70 patients), or rotator cuff repair (1 study, 72 patients). The mean age throughout the included studies was 33.9 years, with a mean of 27.7% female patients. There was a 1% drop out rate at 3 months postoperatively. There were significantly lower visual analog scale scores at 2 weeks postoperatively in the TXA groups (mean difference: –1.65, 95% confidence interval [CI] –3.41 to 0.10, P = .06, I2 = 97%). Furthermore, there was a significant decrease in the number of patients requiring joint aspiration in the TXA groups (risk ratio 0.27, 95% CI 0.12-0.56, I2 = 0%, P = .0006). The drainage output in TXA groups was also significantly decreased (mean difference: –61.14 mL, 95% CI –104.43 to –17.85, I2 = 94%, P = .006). Furthermore, there was a statistically significant decrease in hemarthrosis grade (Coupens & Yates) at 2 weeks postoperatively (Mean difference: –0.76, 95% CI –0.97 to –0.54, I2 = 0%, P < .0001). Finally, there was no significant difference in operating time, across all studies (Mean difference: 0.53, 95% CI –3.43 to 4.50, I2 = 57%, P < .79). The use of TXA showed no increased incidence of deep vein thrombosis, infection, arthrofibrosis, or other major complications or adverse reactions between the TXA and control groups.

      Conclusions

      This systematic review and meta-analysis of randomized controlled trialss found that the use of TXA significantly improves pain scores up to 6 weeks postoperatively, decreases drainage output, decreases the need for joint aspirations, decreases incidence of hemarthrosis, increases visual clarity and technical ease, and has no increased incidence of other complications, at no loss to operative time. These findings indicate that TXA may be a useful adjunct in arthroscopic knee and shoulder surgery.

      Level of Evidence

      II.
      Tranexamic acid (TXA) was synthesized using research on an isomer of 4-aminomethyl-cyclohexane-1-carboxylic acid.
      • Okamoto S.
      • Sato S.
      • Takada Y.
      • Okamoto U.
      An active stereo-isomer (trans-form) of amcha and its antifibrinolytic (anti-plasminic) action in vitro and in vivo.
      It was discovered in the early 1960s in Japan, by Utako and Shosuke Okamoto, and was used infrequently up until the late 1990s.
      • Coats T.J.
      Tranexamic acid: There’s new life in the old drug.
      Historically, TXA was used in female patients with heavy menstrual blood loss and patients with hereditary bleeding disorders.
      • Tengborn L.
      • Blombäck M.
      • Berntorp E.
      Tranexamic acid—An old drug still going strong and making a revival.
      Due to its success and larger subsequent trials, TXA was quickly adopted in elective surgery
      • Tengborn L.
      • Blombäck M.
      • Berntorp E.
      Tranexamic acid—An old drug still going strong and making a revival.
      and has since shown strong evidence supporting its use in a variety of areas, such as cardiac surgery, elective cesarean delivery, total knee arthroplasty, and spinal surgery, among others. Most notable are its uses in trauma patients, as well as with postpartum hemorrhage, where, in both cases, TXA was shown to reduce mortality.
      • Chauncey J.M.
      • Wieters J.S.
      Tranexamic Acid-StatPearls-NCBI Bookshelf. StatsPearls Publishing.
      Ultimately, TXA has been widely used in a variety of surgical specialties and has been found effective in reducing blood loss, the need for transfusion, and the need for reoperation due to significant or recurrent bleeding. TXA also appears to be free of any serious adverse effects
      • Henry D.A.
      • Carless P.A.
      • Moxey A.J.
      • et al.
      Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion.
      ; specifically, there has been no reproducible evidence of significant increase in risk of thrombotic events.
      • Shakur H.
      • Elbourne D.
      • Gülmezoglu M.
      • et al.
      The WOMAN Trial (World Maternal Antifibrinolytic Trial): Tranexamic acid for the treatment of postpartum haemorrhage: An international randomised, double blind placebo controlled trial.
      Despite its favorable safety profile, TXA is contraindicated in patients with a history of thromboembolic events, those with defective color vision, and those with intracranial bleeding,
      • Chauncey J.M.
      • Wieters J.S.
      Tranexamic Acid-StatPearls-NCBI Bookshelf. StatsPearls Publishing.
      whereas dosage may need to be adjusted in patients with renal insufficiency.
      • Dunn C.J.
      • Goa K.L.
      Tranexamic acid: A review of its use in surgery and other indications.
      TXA is an extremely potent synthetic lysine-analogue
      • McCormack P.L.
      Tranexamic acid: A review of its use in the treatment of hyperfibrinolysis.
      that functions as an antifibrinolytic by inhibiting, directly and indirectly, both plasminogen activation and plasmin activity. By attaching to the lysine-binding sites on plasminogen, it prevents plasminogen’s ability to bind to lysine residues on fibrin. This mechanism results in reduced plasminogen activation into plasmin, preventing clot breakdown. In terms of direct effects on plasmin, the lysine-binding site blockade on circulating plasmin prevents its ability to bind to fibrin, which prevents subsequent clot breakdown.
      • Chang R.
      • Holcomb J.B.
      • Leibner E.
      • Pommerening M.
      • Kozar R.A.
      Hemostasis, Surgical Bleeding, and Transfusion.
      ,
      • Zehnder J.L.
      Drugs Used in Disorders of Coagulation.
      At therapeutic levels, it has shown strong safety parameters and does not significantly affect platelets or coagulation values.
      • Chang R.
      • Holcomb J.B.
      • Leibner E.
      • Pommerening M.
      • Kozar R.A.
      Hemostasis, Surgical Bleeding, and Transfusion.
      Greater than 95% of the total TXA is excreted unchanged by the kidneys, and only very small amounts are metabolized in the body. The half-life is approximately two hours when administered intravenously.
      • Mielke R.T.
      • Obermeyer S.
      The use of tranexamic acid to prevent postpartum hemorrhage.
      As mentioned, TXA has been used in several surgical fields, with excellent outcomes.
      • Chang R.
      • Holcomb J.B.
      • Leibner E.
      • Pommerening M.
      • Kozar R.A.
      Hemostasis, Surgical Bleeding, and Transfusion.
      Although TXA has been studied extensively within certain areas of orthopaedics, and in particular open surgery, there is also growing interest in its application to arthroscopic procedures. Hemarthrosis is a relatively common complication that accounts for 60.1% of all complications in arthroscopic surgeries.
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      Hemarthrosis may lead to increased postoperative pain and swelling, decreased range of motion, and may affect a patient's evaluation of the success of the operation.
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      With the success in decreasing blood loss during open surgeries, and as hemarthrosis can lead to long term impairments, some arthroscopists have incorporated TXA into their practice. These experiences have largely been only anecdotally reported.
      In addition, we must consider the significant impacts the opioid epidemic has had on the population as a whole, as well as the world of orthopaedics. Current noncancer pain guidelines in Canada recommend that opioid medications be avoided as much as possible, and that treatment rely mostly on nonopiate or nonpharmacologic treatments.
      • Busse J.W.
      • Craigie S.
      • Juurlink D.N.
      • et al.
      Guideline for opioid therapy and chronic noncancer pain.
      Studies have shown that surgical patients with greater decreases in baseline pain up to 6 months postoperatively resulted in decreased usage of opioids at 6 months.
      • Goesling J.
      • Moser S.E.
      • Zaidi B.
      • et al.
      Trends and predictors of opioid use after total knee and total hip arthroplasty.
      TXA has shown promise as an adjunct to optimize patient outcomes, including pain outcomes.
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      Ultimately, there is not a well-established consensus regarding the use of TXA in arthroscopic surgery. The purpose of this systematic review is to systematically screen the literature in an effort to critically examine the effect of TXA in patients undergoing arthroscopic surgery, specifically pertaining to pain, blood loss, length of surgery, and both major and minor complications. It is hypothesized that the use of TXA in arthroscopic surgeries will decrease blood loss and in turn lead to decreased complications of arthroscopic surgery, as well as improve overall postoperative function and positive outcomes.

      Methods

      The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines
      Institute of Medicine
      Finding What Works in Health Care: Standards for Systematic Reviews. 2011.
      and Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) guidelines
      • Kung J.
      From systematic reviews to clinical recommendations for evidence-based health care: Validation of Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) for Grading of Clinical Relevance.
      were used in this review. These guidelines include elements such as a priori study design, duplicate study selection and data extraction, comprehensive literature search, scientific quality assessment of included studies, and assessment of the likelihood of publication bias.
      • Kung J.
      From systematic reviews to clinical recommendations for evidence-based health care: Validation of Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) for Grading of Clinical Relevance.

      Search Strategy

      Three databases (PubMed, EMBASE, Cochrane) were searched for literature evaluating TXA use in arthroscopic surgery; the references of the included studies were reviewed for additional articles for inclusion. The search was conducted on April 24, 2020, and retrieved data from database inception to the search date. The search included the MeSH terms, “Tranexamic Acid,” “Antifibrinolytic Agents,” and “Arthroscopy” and the key words “tranexamic acid” and “arthroscop∗.” Figure 1 outlines the search strategy. The research questions and individual study inclusion and exclusion criteria were established a priori. The inclusion criteria were (1) original research articles, (2) articles with Level of Evidence I or II, (3) articles in the English language, (4) articles published on or after January 1, 2000, (5) human trials, (6) any populations, (7) arthroscopic procedures of any kind, and (8) use of TXA. The exclusion criteria were (1) non-original articles, (2) articles not published in the English language, (3) articles published before January 1, 2000, (4) articles without available full text, (5) non-human trials, and (6) studies focusing on open procedures.
      Figure thumbnail gr1
      Fig 1Preferred Reporting Items for Systematic Reviews and Meta-Analyses chart.

      Study Screening

      Two reviewers independently reviewed the title, abstract, and full text of all studies retrieved. Any discrepancies between reviewers were carried to the next stage of screening for thoroughness. There were no disagreements between reviewers at the full text stage.

      Quality Assessment of Included Studies

      A quality assessment of included studies was performed using the Cochrane Handbook for Systematic Reviews of Interventions, and version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2).
      • Higgins J.
      Chapter 8: Assessing risk of bias in a randomized trial | Cochrane Training.
      Each of the 5 items in the risk of bias summary were separated between low risk of bias (green), unclear risk of bias (yellow), and high risk of bias (red), giving an overall value of the potential bias involved with each study (Figure 2; Appendix Table 1, available at www.arthroscopyjournal.org).
      For studies without predetermined level of evidence, evaluation was performed using established literature (Appendix Table 2, available at www.arthroscopyjournal.org). Two articles with similar criteria were used to ensure consistency in evaluation. The first, by Poehling and Jenkins,
      • Poehling G.
      • Jenkins C.
      Levels of evidence and your therapeutic study: What’s the difference with cohorts, controls, and cases?.
      outlines that a level of evidence I RCT “shows a significant difference between treatment groups or achieves narrow confidence intervals,” and states that a Level of Evidence II RCT has “less than 80% follow-up.
      • Poehling G.
      • Jenkins C.
      Levels of evidence and your therapeutic study: What’s the difference with cohorts, controls, and cases?.
      The second article, by Wright, describes a Level of Evidence I study as a “high quality randomized trial with statistically significant difference or no statistically significant difference but narrow confidence intervals,”

      Wright J. Levels of evidence and grades of recommendations: An evaluation of literature. American Academy of Orthopaedic Surgeons, 2005.

      and describes a Level II RCT as a “lesser quality RCT (e.g., <80% follow-up, no blinding, or improper randomization).”

      Wright J. Levels of evidence and grades of recommendations: An evaluation of literature. American Academy of Orthopaedic Surgeons, 2005.

      Data Abstraction

      Relevant data were abstracted from all included articles, including demographic information. Clinical data included surgical procedure, route of TXA administration, blood loss and hemarthrosis grade, visual analog scale (VAS) pain scores, analgesia use as measured by morphine milligram equivalent, functional assessment scores, degree of swelling, visual clarity, and any complications of surgery.

      Statistical Analysis

      An unweighted kappa (k) statistic was calculated for each stage of article screening to evaluate inter-reviewer agreement. Agreement was categorized a priori as: k < 0.01 to indicate less than chance agreement, 0.01 < k < 0.20 to indicate slight agreement, 0.21 < k < 0.40 to indicate moderate agreement, 0.41 < k < 0.60 to indicate moderate agreement, 0.61 < k < 0.80 to indicate substantial agreement, 0.81 < k < 0.99 to indicate almost perfect agreement, and k = 1 to indicate perfect agreement.
      • McHugh M.L.
      Interrater reliability: The kappa statistic.
      After the full-text screening had been performed, the only studies that met inclusion criteria were RCTs. A priori it was decided that outcome measures reported uniformly with a minimum of three studies would be pooled. Data were pooled for outcome measures including VAS pain scores, drainage output, hemarthrosis grade, postoperative function and swelling, and operative time via mean differences. The aforementioned continuous outcomes were combined using a random effects model given the anticipated heterogeneity with respect to rehabilitation protocols. Aspiration of the joint (a dichotomous outcome) was pooled using risk ratios with a random effects model, given anticipated heterogeneity with respect to procedures and joints assessed. It is important to note that one study
      • Karaaslan F.
      • Seijas R.
      • Sallent A.
      • et al.
      Tranexamic acid in bolus alone vs bolus and continuous infusion in hip arthroscopy.
      compared the use of TXA given solely as a bolus against the use of a bolus as well as continuous infusion throughout the procedure. Since there was no outright control group, this study was excluded from the meta-analysis. Pooled analyses were performed using the Review Manager software (RevMan) 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, 2012). The pooled mean values are all presented with 95% confidence intervals (CIs). P values < .05 were considered the threshold for statistical significance. The I2 test was used to assess the statistical between-study heterogeneity for each pooled outcome, determining the proportion of the variability not related to chance, with I2 < 30% considered as low statistical heterogeneity.
      • Mantel N.
      • Haenszel W.
      Statistical aspects of the analysis of data from retrospective studies of disease.
      For other variables, where results were presented in a non-uniform nature across studies, the results are presented in narrative summary fashion. When studies reported means with standard deviations or ranges, data were reported as means along with ranges from studies that reported range values. Descriptive statistics were used including means, ranges, counts, and percentages.

      Results

      Search Results and Study Quality

      The literature search returned 71 unique articles, 7 of which satisfied the inclusion criteria. Between reviewers, there was substantial agreement at the title screening stage (k = 0.797; 95% CI 0.655-0.940) and abstract screening stage (k = 0.716; 95% CI 0.410-1), and perfect agreement at the full-text screening stage (k = 1; 95% CI 1-1). A review of the references of included studies provided no additional studies. All included articles were RCTs; risk of bias was evaluated in tandem using the RoB 2 tool from Cochrane.
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      ,
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      ,
      • Karaaslan F.
      • Seijas R.
      • Sallent A.
      • et al.
      Tranexamic acid in bolus alone vs bolus and continuous infusion in hip arthroscopy.
      ,
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      • Liu Y.F.
      • Hong C.K.
      • Hsu K.L.
      • et al.
      Intravenous administration of tranexamic acid significantly improved clarity of the visual field in arthroscopic shoulder surgery. A prospective, double-blind, and randomized controlled trial.
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      All articles were Level of Evidence I or II. Evaluation of Level of Evidence was completed for 2 articles,
      • McHugh M.L.
      Interrater reliability: The kappa statistic.
      ,
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      using established literature as described previously. One study
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      was determined to have low risk of bias
      • Kung J.
      From systematic reviews to clinical recommendations for evidence-based health care: Validation of Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) for Grading of Clinical Relevance.
      and had statistically significant difference between intervention groups and control groups in multiple outcomes but had a low sample size of 48 patients. Although a high-quality randomized trial, this low power prevents the study from fulfilling Level of Evidence I criteria as stated by Poehling and Jenkins.
      • Poehling G.
      • Jenkins C.
      Levels of evidence and your therapeutic study: What’s the difference with cohorts, controls, and cases?.
      However, no patients were lost to follow-up,
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      and therefore the study does fulfill Level of Evidence II criteria as outlined by both Poehling and Jenkins
      • Poehling G.
      • Jenkins C.
      Levels of evidence and your therapeutic study: What’s the difference with cohorts, controls, and cases?.
      and Wright.

      Wright J. Levels of evidence and grades of recommendations: An evaluation of literature. American Academy of Orthopaedic Surgeons, 2005.

      The other study
      • McHugh M.L.
      Interrater reliability: The kappa statistic.
      that required level of evidence determination had high risk of bias due to a lack of comment on surgeon blinding,
      • Kung J.
      From systematic reviews to clinical recommendations for evidence-based health care: Validation of Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) for Grading of Clinical Relevance.
      although this was determined to be unlikely to have any clinical effects on outcome. There were no concerns regarding the quality of the study, including randomization and follow-up. The study again had a low sample size of 70 patients,
      • McHugh M.L.
      Interrater reliability: The kappa statistic.
      and this low power once again prevented the article from fulfilling Poehling and Jenkins’ Level of Evidence I criteria.
      • Poehling G.
      • Jenkins C.
      Levels of evidence and your therapeutic study: What’s the difference with cohorts, controls, and cases?.
      ,

      Wright J. Levels of evidence and grades of recommendations: An evaluation of literature. American Academy of Orthopaedic Surgeons, 2005.

      The study does fulfill criteria for Level of Evidence II as described by Poehling and Jenkins and Wright.
      • Poehling G.
      • Jenkins C.
      Levels of evidence and your therapeutic study: What’s the difference with cohorts, controls, and cases?.

      Wright J. Levels of evidence and grades of recommendations: An evaluation of literature. American Academy of Orthopaedic Surgeons, 2005.

      • McHugh M.L.
      Interrater reliability: The kappa statistic.
      Thus, all articles included in this systematic review and meta-analysis were Level of Evidence I or II.

      Study Characteristics

      The 7 studies collectively covered 4 arthroscopic procedures including anterior cruciate ligament reconstruction (ACLR) (4 studies, 537 patients), meniscectomy (1 study, 45 patients), femoroacetabular impingement (1 study, 70 patients), and rotator cuff repair (1 study, 72 patients). There were 724 total patients with ages ranging from at least 22 to 79 years. Of the patients included in the studies, 396 (54.7% of patients) received TXA, whereas 328 (45.3%) were members of a non-TXA control group. Of the patients given TXA, 152 (38.3% of patients receiving TXA) received a 10-mL intra-articular bolus immediately postoperatively; 116 (29.3%) received only an intravenous (IV) bolus of doses ranging from 0.5 to 2 g of TXA administered at times ranging from 30 minutes preoperatively to immediately before tourniquet inflation; 40 (10.1%) received IV infusion of TXA 15 mg/kg 20 minutes before tourniquet release; 53 (13.4%) received TXA via 15 mg/kg IV bolus 10 minutes before tourniquet inflation and IV infusion of 10 mg/kg each hour for 3 hours postoperatively; and 35 (8.8%) received a 2-g IV bolus 30 minutes before surgery and IV infusion of 10 mg/kg each hour during surgery. Patients were followed from immediately postoperatively to upwards of 3 months postoperatively (Appendix Table 3, available at www.arthroscopyjournal.org).

      Pain

      Pain was reported using VAS pain scores. Three studies (443 patients)
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      ,
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      ,
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      reported VAS pain scores 3 days postoperatively. Of these, 2 studies
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      ,
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      reported statistically significant reductions in pain in the TXA group compared with the non-TXA control group. Overall, there was no significant difference in VAS scores at 3 days postoperatively between the TXA groups (N = 222) and non-TXA groups (N = 221) (mean difference –1.65, 95% CI –3.41 to 0.10, P = .06, I2 = 97%).
      Three studies (190 patients)
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      ,
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      ,
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      reported VAS pain scores 2 weeks postoperatively. Of these studies, two
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      ,
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      reported statistically significantly lower scores in the TXA group compared to the non-TXA control group. Overall, there were significantly lower VAS scores at 2 weeks postoperatively in the TXA groups (N = 93) compared with the non-TXA groups (N = 97) (mean difference –1.66, 95% CI –2.33 to –1.00, P < .0001, I2 = 79%) (Fig 3).
      Figure thumbnail gr3
      Fig 3Forest plots depicting the mean difference (SD) in visual analog scale pain scores between tranexamic acid (TXA) groups and control groups at 3 days’ and 2 weeks’ postoperative time. (CI, confidence interval; IV, independent variable; SD, standard deviation.)
      Five studies
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      ,
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      ,
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      • Liu Y.F.
      • Hong C.K.
      • Hsu K.L.
      • et al.
      Intravenous administration of tranexamic acid significantly improved clarity of the visual field in arthroscopic shoulder surgery. A prospective, double-blind, and randomized controlled trial.
      (563 patients) reported VAS scores as short-term results (2 weeks postoperative or shorter). Four of these studies
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      ,
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      • Liu Y.F.
      • Hong C.K.
      • Hsu K.L.
      • et al.
      Intravenous administration of tranexamic acid significantly improved clarity of the visual field in arthroscopic shoulder surgery. A prospective, double-blind, and randomized controlled trial.
      indicated significantly lower pain scores in the TXA groups compared with the non-TXA groups, whereas one study
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      reported no significant difference. Four studies
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      ,
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      ,
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      ,
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      (487 patients) reported mid-term results (longer than 2 weeks but shorter than 6 weeks postoperative). Three
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      ,
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      ,
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      of 4 studies reported significantly lower mid-term VAS scores in TXA groups and one
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      reported no significant difference between groups. One study
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      (48 patients) reported long-term VAS scores (6 weeks postoperative or longer) and found significantly lower pain scores at 6 weeks postoperatively in the TXA group, but no significant differences by 12 weeks.
      Two studies
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      ,
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      (104 patients) reported the change in VAS pain scores from preoperative measures. One study
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      found significantly improved short-term pain in the TXA group compared with the non-TXA group, whereas one
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      found no statistically significant differences. Neither study reported significant differences in VAS scores between groups in mid- or long-term measurements.
      Each study used a standardized analgesia routine between groups. One study
      • Liu Y.F.
      • Hong C.K.
      • Hsu K.L.
      • et al.
      Intravenous administration of tranexamic acid significantly improved clarity of the visual field in arthroscopic shoulder surgery. A prospective, double-blind, and randomized controlled trial.
      (72 patients) also reported the need for additional pain medication, administered as required in each group. It found a statistically significant reduction in the use of opioid medication morphine equivalents for pain control, measured in morphine milligram equivalents, in the TXA group compared to the non-TXA control group (9.6 ± 9.7 vs 14.7 ± 13.4, P = .037) (Appendix Table 4, available at www.arthroscopyjournal.org).

      Blood Loss

      Four studies (533 patients)
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      ,
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      ,
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      ,
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      reported the number of patients requiring joint aspiration after surgery. Two of these studies
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      ,
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      showed statistically significantly fewer patients requiring aspiration in the TXA groups. Pooled data showed a significant decrease in the number of patients requiring joint aspiration in the TXA groups (N = 268) compared with the non-TXA groups (N = 265) (risk ratio 0.27, 95% CI 0.12-0.56, I2 = 0%, P = .0006) (Fig 4).
      Figure thumbnail gr4
      Fig 4Forest plot of the aspiration rates (number of patients requiring aspiration) and risk ratios reported across studies for the tranexamic acid (TXA) and control groups. (CI, confidence interval; M-H, Mantel–Haenszel; SD, standard deviation.)
      Drainage output 24 hours postoperatively was reported in 3 studies (485 patients).
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      ,
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      ,
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      Each of these studies reported significantly lower output in TXA groups. Overall, the decrease in drainage output of the TXA groups (N = 244) compared with the non-TXA groups (N = 241) was statistically significant (mean difference –61.14 mL, 95% CI –104.43 to –17.85, I2 = 94%, P = .006) (Fig 5).
      Figure thumbnail gr5
      Fig 5Forest plot of the mean drainage output 24 hours postoperative (mL) reported across studies for the tranexamic acid (TXA) and control groups. (CI, confidence interval; IV, independent variable; SD, standard deviation.)
      Hemarthrosis was measured using Coupens and Yates hemarthrosis grading (Appendix Table 8, available at www.arthroscopyjournal.org).
      • Coupens S.D.
      • Yates C.K.
      The effect of tourniquet use and hemovac drainage on postoperative hemarthrosis.
      Three studies (233 patients)
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      ,
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      ,
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      measured the hemarthrosis grade at 2 weeks, all of which reported significantly lower hemarthrosis grades in the TXA groups (N = 117) compared with non-TXA control groups (N = 116) (mean difference –0.76, 95% CI –0.97 to –0.54, I2 = 0%, P < .0001) (Fig 6).
      Figure thumbnail gr6
      Fig 6Forest plot of the mean hemarthrosis Grade 2 weeks postoperatively (Coupens and Yates) reported across studies for the tranexamic acid (TXA) and control groups. (CI, confidence interval; IV, independent variable; SD, standard deviation.)
      Four studies
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      ,
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      ,
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      ,
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      (533 patients) reported short-term hemarthrosis grades, and all 4 found significant short-term reductions in TXA groups. Two studies
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      ,
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      (380 patients) reported mid-term hemarthrosis grades, and neither found significant differences between TXA and non-TXA groups. Two studies
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      ,
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      (128 patients) reported long-term results, where one study found significantly lower hemarthrosis grades in the TXA group and one study reported no significant difference between groups.
      Two studies
      • Liu Y.F.
      • Hong C.K.
      • Hsu K.L.
      • et al.
      Intravenous administration of tranexamic acid significantly improved clarity of the visual field in arthroscopic shoulder surgery. A prospective, double-blind, and randomized controlled trial.
      ,
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      (152 patients) measured hemoglobin level in TXA and non-TXA groups. Neither study found significant differences between groups immediately postoperatively or 1 day postoperatively. One study
      • Karaaslan F.
      • Seijas R.
      • Sallent A.
      • et al.
      Tranexamic acid in bolus alone vs bolus and continuous infusion in hip arthroscopy.
      (70 patients) measured hemoglobin level in 2 groups receiving TXA. Group 1 received TXA via both preoperative IV bolus and intraoperative infusion, whereas Group 2 received TXA via preoperative IV bolus alone. This study found significantly greater hemoglobin levels in Group 1 postoperatively, as well as a significantly smaller decrease in hemoglobin level from preoperative measures in the same group.
      Two studies
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      ,
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      (185 patients) measured hematocrit level in TXA and non-TXA groups. One study reported no significant difference in hematocrit levels between groups at 1 day postoperatively.
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      While the other study did report significantly greater hematocrit in the TXA group 1 day postoperatively, it also reported significantly greater preoperative levels in the TXA group, so this variable may be confounded.
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      This confounding variable is further supported by the same study reporting no significant difference in the change in hematocrit between preoperative and 1 day postoperative levels. One study
      • Karaaslan F.
      • Seijas R.
      • Sallent A.
      • et al.
      Tranexamic acid in bolus alone vs bolus and continuous infusion in hip arthroscopy.
      (70 patients) measured hematocrit levels in a group receiving TXA via IV bolus and intraoperative infusion (Group 1) and a group receiving TXA via only IV bolus (Group 2). Group 1 was found to have significantly greater hematocrit levels postoperatively than Group 2, as well as a significantly smaller decrease in hematocrit levels (Appendix Table 5, available at www.arthroscopyjournal.org).

      Function and Swelling

      For ACLR and meniscectomies, function was reported through various outcome measures including range of motion, quadriceps strength, International Knee Documentation Committee (IKDC) scores, Lysholm scores, and Tegner scores.
      • Collins N.J.
      • Misra D.
      • Felson D.T.
      • Crossley K.M.
      • Roos E.M.
      Measures of knee function: International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form, Knee Injury and Osteoarthritis Outcome Score (KOOS), Knee Injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS), Knee O.
      Postoperative swelling after different procedures was measured using IKDC effusion scores, patellar circumference, suprapatellar girth or thigh circumference, and calf girth for ACLR and meniscectomies and change in deltoid and axillary size for rotator cuff repair.
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      ,
      • Liu Y.F.
      • Hong C.K.
      • Hsu K.L.
      • et al.
      Intravenous administration of tranexamic acid significantly improved clarity of the visual field in arthroscopic shoulder surgery. A prospective, double-blind, and randomized controlled trial.
      ,
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      Three studies
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      ,
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      ,
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      (243 patients) reported range of motion of the knee as a short-term outcome. All three studies found a significantly greater range of motion in TXA groups than non-TXA groups. Two studies
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      ,
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      (380 patients) measured range of motion of the knee as a mid-term outcome. Neither study found significant differences between TXA and non-TXA groups. Similarly, 2 studies
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      ,
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      (128 patients) reported range of motion of the knee as a long term-outcome, neither of which found significant differences between groups. One study
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      (34 patients) reported the change of range of motion of the knee from preoperative measures, and did not report any significant differences between TXA and non-TXA groups at any time.
      One study
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      (300 patients) reported IKDC function score as a mid-term outcome. The study reported no significant differences between the TXA and non-TXA groups. A separate study
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      (80 patients) measured passive motion deficit IKDC score and did not report any significant differences between TXA and non-TXA groups. The same study reported the ligament examination IKDC score and did not find any significant differences between groups. This study also measured the subjective IKDC score, and once again found no significant differences.
      One study
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      (80 patients) reported quadriceps strength as a functional outcome. While short-term measurements showed significantly greater strength in the TXA group than non-TXA group, mid-term and long-term measurements showed no significant differences.
      Lysholm score was reported as a short-term outcome in 3 studies
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      ,
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      ,
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      (190 patients). Two studies
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      ,
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      found significantly greater scores in TXA groups than non-TXA groups, whereas one study
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      reported no significant differences. Three studies
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      ,
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      ,
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      (219 patients) reported mid-term Lysholm scores. While one of these studies
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      reported significantly greater scores in the TXA group, the other two
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      ,
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      reported no significant differences between TXA and non-TXA groups. Two studies
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      ,
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      (128 patients) measured Lysholm scores as long-term outcomes. One study
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      reported significantly greater scores in the TXA group compared with the non-TXA group, whereas a different study
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      found no significant differences.
      Tegner scores were reported in one study
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      (34 patients). Significantly greater scores were found in the TXA group at 3 days postoperatively, but no differences were found at 14 or 30 days. In addition, the study measured the change in Tegner scores from preoperative measures. It found no significant differences between groups at any time.
      Swelling was measured using IKDC effusion scores in one study
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      (80 patients). No significant differences between TXA and non-TXA groups were reported at any time. The same study
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      measured the difference in patellar circumference between the affected and contralateral sides. While patellar circumference was significantly less in the TXA group in short-term measurements, there were no reported differences between groups in mid- or long-term measurements. One study
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      (34 patients) reported swelling as the changes in suprapatellar girth and calf girth from preoperative measurements. There were no significant differences between TXA and non-TXA groups reported at any time. Shoulder swelling was reported in one study
      • Liu Y.F.
      • Hong C.K.
      • Hsu K.L.
      • et al.
      Intravenous administration of tranexamic acid significantly improved clarity of the visual field in arthroscopic shoulder surgery. A prospective, double-blind, and randomized controlled trial.
      (72 patients) using change in shoulder size from preoperative measurements. Both deltoid and axillary measurements were reported, and neither showed significant differences between the TXA and non-TXA groups at any time (Appendix Table 6, available at www.arthroscopyjournal.org).

      Technical Ease and Complications

      Operative time was reported in 6 studies (676 patients).
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      ,

      Wright J. Levels of evidence and grades of recommendations: An evaluation of literature. American Academy of Orthopaedic Surgeons, 2005.

      ,
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      • Liu Y.F.
      • Hong C.K.
      • Hsu K.L.
      • et al.
      Intravenous administration of tranexamic acid significantly improved clarity of the visual field in arthroscopic shoulder surgery. A prospective, double-blind, and randomized controlled trial.
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      Five of these studies
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      ,
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      • Liu Y.F.
      • Hong C.K.
      • Hsu K.L.
      • et al.
      Intravenous administration of tranexamic acid significantly improved clarity of the visual field in arthroscopic shoulder surgery. A prospective, double-blind, and randomized controlled trial.
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      (606 patients) compared TXA and a non-TXA control group. None of the individual 5 studies reported significant differences in operative time between groups. Pooled data similarly showed no significant differences between TXA groups (N = 302) and non-TXA groups (N = 304) (P = .79) (Fig 7). The remaining study
      • Karaaslan F.
      • Seijas R.
      • Sallent A.
      • et al.
      Tranexamic acid in bolus alone vs bolus and continuous infusion in hip arthroscopy.
      (70 patients) of the 6 compared a group receiving TXA through IV bolus alone and a group receiving TXA through both IV bolus and intraoperative infusion. This study did not report significant differences in operative time between groups.
      Figure thumbnail gr7
      Fig 7Forest plot of the mean operative time (minutes) reported across studies in the tranexamic acid (TXA) and control groups. (CI, confidence interval; IV, independent variable; SD, standard deviation.)
      Visual clarity during surgery was reported in one study (72 patients).
      • Liu Y.F.
      • Hong C.K.
      • Hsu K.L.
      • et al.
      Intravenous administration of tranexamic acid significantly improved clarity of the visual field in arthroscopic shoulder surgery. A prospective, double-blind, and randomized controlled trial.
      Clarity was measured every 15 minutes intraoperatively on a 3-point scale, where 1 indicated “poor visibility,” 2 indicated “fair visibility,” and 3 indicated “good visibility.” The TXA group showed significantly fewer “poor visibility” scores and a significantly greater number of “good visibility” scores than the non-TXA group. There was no reported difference between groups in the number of “fair visibility” scores. In addition, the average score was significantly higher in the TXA group than the non-TXA group (Appendix Table 7, available at www.arthroscopyjournal.org).
      Other complications explicitly reported included deep vein thrombosis (DVT), infection, and arthrofibrosis. Five studies
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      ,
      • Karaaslan F.
      • Seijas R.
      • Sallent A.
      • et al.
      Tranexamic acid in bolus alone vs bolus and continuous infusion in hip arthroscopy.
      ,
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      ,
      • Liu Y.F.
      • Hong C.K.
      • Hsu K.L.
      • et al.
      Intravenous administration of tranexamic acid significantly improved clarity of the visual field in arthroscopic shoulder surgery. A prospective, double-blind, and randomized controlled trial.
      ,
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      (375 patients) reported the number of DVT in each group, four studies
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      • Liu Y.F.
      • Hong C.K.
      • Hsu K.L.
      • et al.
      Intravenous administration of tranexamic acid significantly improved clarity of the visual field in arthroscopic shoulder surgery. A prospective, double-blind, and randomized controlled trial.
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      (557 patients) reported infection rates between groups, and one study
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      (300 patients) reported patients in each group with arthrofibrosis. No patients in either group in any study experienced DVT, infection, or arthrofibrosis, and thus there were no significant differences between groups in any of these measures. It should be noted that one study
      • Karaaslan F.
      • Seijas R.
      • Sallent A.
      • et al.
      Tranexamic acid in bolus alone vs bolus and continuous infusion in hip arthroscopy.
      measuring DVT compared groups receiving TXA via IV bolus and TXA via both IV bolus and intraoperative infusion rather than comparing a TXA group and non-TXA group. No other complications were consistently and clearly reported across studies, although all studies reported a lack of complications apart from those previously mentioned.
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      ,
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      ,
      • Karaaslan F.
      • Seijas R.
      • Sallent A.
      • et al.
      Tranexamic acid in bolus alone vs bolus and continuous infusion in hip arthroscopy.
      ,
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      • Liu Y.F.
      • Hong C.K.
      • Hsu K.L.
      • et al.
      Intravenous administration of tranexamic acid significantly improved clarity of the visual field in arthroscopic shoulder surgery. A prospective, double-blind, and randomized controlled trial.

      Discussion

      The primary findings from this review demonstrated that patients experienced significantly improved postoperative pain scores up to 6 weeks postoperatively, reduced hemarthrosis, and decreased perioperative blood loss as measured by VAS pain scores and analgesic use, Coupons and Yates hemarthrosis grade, and surgical drainage output, respectively. Moreover, there were no reported complications such as infection, venous thromboembolism, and arthrofibrosis associated with TXA use.
      While TXA use in arthroscopy does not present the same advantage of reduction in blood transfusion as it does following open procedures, the benefits of reducing hemarthrosis and blood loss should not be underestimated. Hemarthrosis is one of the most common complications following arthroscopic surgery.
      • Small N.C.
      Complications in arthroscopic surgery performed by experienced arthroscopists.
      Hemarthrosis is associated with increased postoperative pain scores, delayed motion, and increases the joints’ susceptibility to septic arthritis.
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      In addition to greater pain scores, hemarthrosis can lead to synovitis, scar tissue formation and resultant arthrofibrosis.
      • Bahl V.
      • Goyal A.
      • Jain V.
      • Joshi D.
      • Chaudhary D.
      Effect of haemarthrosis on the rehabilitation of anterior cruciate ligament reconstruction-single bundle versus double bundle.
      Moreover, the mere presence of knee joint effusion and quadriceps inhibition has also been well documented.
      • Spencer J.D.
      • Hayes K.C.
      • Alexander I.J.
      Knee joint effusion and quadriceps reflex inhibition in man.
      Delayed rehabilitation can have profound socioeconomic impacts by way of impeding return to work and sports, and it may potentially result in return to the operating room for procedures such as manipulation of the joint under anesthesia and surgical releases. It should be noted that, although the differences in hemarthrosis grade between TXA and control groups were found to be statistically significant, no established literature could be found discussing minimum clinically important difference. In association with hemarthrosis, and intraoperative blood loss, we see acute decreases in hemoglobin. Despite its low clinical impact, blood loss in arthroscopic surgery should remain an important clinical consideration, especially if the patient has cardiovascular disease, a blood disorder, or is at risk for anemia.
      • Seijas R.
      • Espinosa W.
      • Sallent A.
      • Cuscó X.
      • Cugat R.
      • Ares O.
      Comparison of pre- and postoperative hemoglobin and hematocrit levels in hip arthroscopy.
      Although TXA did not show any benefit to postoperative hemoglobin and hematocrit levels when compared with control groups, the route of administration may have some effect.
      • Karaaslan F.
      • Seijas R.
      • Sallent A.
      • et al.
      Tranexamic acid in bolus alone vs bolus and continuous infusion in hip arthroscopy.
      ,
      • Liu Y.F.
      • Hong C.K.
      • Hsu K.L.
      • et al.
      Intravenous administration of tranexamic acid significantly improved clarity of the visual field in arthroscopic shoulder surgery. A prospective, double-blind, and randomized controlled trial.
      ,
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      Administering TXA via preoperative IV bolus with additional intraoperative infusion resulted in statistically significantly greater postoperative hemoglobin and hematocrit levels than administering via preoperative IV bolus alone.
      • Karaaslan F.
      • Seijas R.
      • Sallent A.
      • et al.
      Tranexamic acid in bolus alone vs bolus and continuous infusion in hip arthroscopy.
      The former route of administration may therefore be beneficial, although there is a small sample size for comparison, few data reported on other differences between the 2 routes, and an increased cost with the additional intraoperative infusion. It also should be noted that no patients in either the bolus or infusion group required transfusion due to low hemoglobin concentrations, and therefore dosing method does not appear to have clinical significance for hemoglobin. Further research may be advantageous to determining benefits of different dosing methods in regards to other outcomes.
      Optimal pain control improves patient satisfaction and outcomes after surgery, decreases opioid consumption, and facilitates early rehabilitation.
      • Shin J.J.
      • McCrum C.L.
      • Mauro C.S.
      • Vyas D.
      Pain management after hip arthroscopy: Systematic review of randomized controlled trials and cohort studies.
      While improvement in function scores is unlikely attributable to TXA itself, they are likely correlated with decreased pain scores leading to earlier mobility and stricter adherence to rehabilitation regimens. Studies have shown that the minimal clinically important difference does not vary when using VAS throughout different sexes, mechanism of injury, or severity of pain. Ultimately, based on 2 separate studies, a change of 9 mm or 13 mm (0.9 and 1.3 cm, respectively, when used on a 10 cm scale) of the VAS is clinically significant.
      • Kelly A.
      The minimum clinically significant difference in visual analogue scale pain score does not differ with severity of pain.
      Studies suggest that absolute values of VAS are more clinically relevant than change in VAS scores.
      • Bodian C.A.
      • Freedman G.
      • Hossain S.
      • Eisenkraft J.B.
      • Beilin Y.
      The visual analog scale for pain: Clinical significance in postoperative patients.
      Using 1.3 as the minimal clinically important difference in VAS scores, the statistical difference between TXA and control groups is also found to be clinically significant in 4 of 5 studies up to 3 days postoperatively.
      Furthermore, in North America, arthroscopic surgeries are most frequently performed as a day surgery, often in ambulatory surgical centers. Inadequate pain control can delay discharge and with escalating awareness of the opioid epidemic, there has been increasing attention to multimodal analgesia. TXA has a role in decreasing opioid use by way of preventing hemarthrosis and decreasing VAS pain scores in early weeks after surgery. In addition to the decreased exposure to opioids, TXA may increase the cost-effectiveness of arthroscopic surgeries. According to McKesson Canada, TXA costs less than CA$40.00/g.

      McKesson Canada. https://www.mckesson.ca/. Accessed July 24, 2020.

      Although this price may still exceed the savings associated with decreased analgesia usage, TXA may be cost-effective if the cost of complications and readmissions are considered. One study
      • Bohensky M.A.
      • Ademi Z.
      • deSteiger R.
      • et al.
      Quantifying the excess cost and resource utilisation for patients with complications associated with elective knee arthroscopy: A retrospective cohort study.
      reported the mean excess cost for the most common complications following elective knee arthroscopy. The study reported excess 30-day cost for venous thromboembolism, joint complications, and infections as US$3227, US$2247, and US$4363, respectively.
      • Bohensky M.A.
      • Ademi Z.
      • deSteiger R.
      • et al.
      Quantifying the excess cost and resource utilisation for patients with complications associated with elective knee arthroscopy: A retrospective cohort study.
      TXA was noted to reduce short-term hemarthrosis grading, as well as possible decreases in patients requiring joint aspiration, which may reduce costs associated with readmission for joint complications. Further research may be required to determine the overall cost-effectiveness of TXA.
      TXA also appears to improve the technical ease of the surgery. Without contributing to significant increases in operative time, TXA improves intraoperative visual clarity, as reported by one study.
      • Liu Y.F.
      • Hong C.K.
      • Hsu K.L.
      • et al.
      Intravenous administration of tranexamic acid significantly improved clarity of the visual field in arthroscopic shoulder surgery. A prospective, double-blind, and randomized controlled trial.
      This leads to safer, more effective procedures in addition to the aforementioned benefits to pain scores, function, and hemarthrosis. TXA has also been shown to be safe, and does not show any signs of increasing mortality, or any significant morbidity, specifically without an increase in complications such as DVT.
      TXA is included on the World Health Organization Model List of Essential Medicines,
      World Health Organziation Model List of Essential Medicines 21st List.
      but its only applications approved by Health Canada are for treatment of hereditary angioneurotic edema and in diagnoses that indicate hyperfibrinolysis.
      These approved uses are similar throughout other countries.
      • Chauncey J.M.
      • Wieters J.S.
      Tranexamic Acid-StatPearls-NCBI Bookshelf. StatsPearls Publishing.
      All other applications, including severe traumatic bleeding and in certain surgeries, are therefore off-label and thus TXA usage is not widespread.
      • Chauncey J.M.
      • Wieters J.S.
      Tranexamic Acid-StatPearls-NCBI Bookshelf. StatsPearls Publishing.
      Although the administration of TXA has gained popularity because of its efficacy and cost effectiveness in arthroplasty, ongoing studies are necessary to determine the potential side effects of TXA in the arthroscopic setting. Some in vitro studies have demonstrated an increase in cell apoptosis among chondrocytes exposed to 1 hour of TXA at 100 mg/mL,
      • McLean M.
      • McCall K.
      • Smith I.D.M.
      • et al.
      Tranexamic acid toxicity in human periarticular tissues.
      whereas other studies have reported chondrotoxic effects at concentrations exceeding 25 mg/mL.
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      One subsequent study
      • Goderecci R.
      • Giusti I.
      • Necozione S.
      • et al.
      Short exposure to tranexamic acid does not affect, in vitro, the viability of human chondrocytes.
      did not observe significant effect on cell viability when TXA was limited to 10 minutes followed by thorough washes. Finally, studies using doses of TXA approximating current clinical protocols (≤4 mg/mL) for topical use have not exhibited chondrotoxic effects even after 6 hours of exposure.
      • Ambra L.F.
      • de Girolamo L.
      • Niu W.
      • Phan A.
      • Spector M.
      • Gomoll A.H.
      No effect of topical application of tranexamic acid on articular cartilage.
      Clinicians should be mindful of TXA’s potentially chondrotoxic effects, especially during topical intra-articular administration, as high doses of prolonged exposure to relatively benign substances can have devastating outcomes.
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      ,
      • Buchko J.Z.
      • Gurney-Dunlop T.
      • Shin J.J.
      Knee chondrolysis by infusion of bupivacaine with epinephrine through an intra-articular pain pump catheter after arthroscopic ACL reconstruction.
      The studies included in this review used TXA as an addition to current guidelines on surgical technique. This includes the use of tourniquet and intra-articular drains for arthroscopic knee procedures, as well as structured postoperative analgesic and rehabilitation regimens. Although both tourniquets and drains may be used with a goal to decrease hemarthrosis risk, evidence for their use in reducing hemarthrosis, pain, and swelling is conflicting.
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      ,
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      ,
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      ,
      • Coupens S.D.
      • Yates C.K.
      The effect of tourniquet use and hemovac drainage on postoperative hemarthrosis.
      TXA has shown benefits in all three of these measures. Cryotherapy also has been used to reduce pain up to 48 hours after arthroscopic procedures, but evidence is unclear on benefits for other measures including function, swelling, blood loss, and analgesic medication usage.
      • Martimbianco A.L.C.
      • Gomes da Silva B.N.
      • de Carvalho A.P.V.
      • Silva V.
      • Torloni M.R.
      • Peccin M.S.
      Effectiveness and safety of cryotherapy after arthroscopic anterior cruciate ligament reconstruction. A systematic review of the literature.
      Although there is a lack of research comparing TXA and cryotherapy, TXA appears to have additional advantages that cryotherapy does not. Further studies could include direct comparisons between TXA and alternative methods of promoting hemostasis, pain relief, and other factors. These methods include intra-articular drains, tourniquets, electrocautery, and cryotherapy.
      One study in this review assessed visual clarity with TXA compared to saline, where significant positive results for TXA were noted.
      • Liu Y.F.
      • Hong C.K.
      • Hsu K.L.
      • et al.
      Intravenous administration of tranexamic acid significantly improved clarity of the visual field in arthroscopic shoulder surgery. A prospective, double-blind, and randomized controlled trial.
      Other studies have examined visual clarity and technical ease in arthroscopic surgery using other methods. For example, one systematic review of 3 articles found significant improvements in visual clarity using epinephrine in the irrigation fluid.
      • Kuo L.T.
      • Chen C.L.
      • Yu P.A.
      • Hsu W.H.
      • Chi C.C.
      • Yoo J.C.
      Epinephrine in irrigation fluid for visual clarity in arthroscopic shoulder surgery: A systematic review and meta-analysis.
      • Van Montfoort D.O.
      • Van Kampen P.M.
      • Huijsmans P.E.
      Epinephrine diluted saline-irrigation fluid in arthroscopic shoulder surgery: A significant improvement of clarity of visual field and shortening of total operation time. a randomized controlled trial.

      Avery DM, Gibson BW, Carolan GF. Surgeon-rated visualization in shoulder arthroscopy: A randomized blinded controlled trial comparing irrigation fluid with and without epinephrine. Arthroscopy 22015;31:12-18.

      • Jensen K.H.
      • Werther K.
      • Stryger V.
      • Schultz K.
      • Falkenberg B.
      Arthroscopic shoulder surgery with epinephrine saline irrigation.
      Although different scales were used in these studies compared with the study using TXA, which adds uncertainty to comparisons between TXA and epinephrine’s impact on visual clarity, it does appear that epinephrine increased visual clarity to a greater extent than TXA.
      • Liu Y.F.
      • Hong C.K.
      • Hsu K.L.
      • et al.
      Intravenous administration of tranexamic acid significantly improved clarity of the visual field in arthroscopic shoulder surgery. A prospective, double-blind, and randomized controlled trial.
      ,
      • Kuo L.T.
      • Chen C.L.
      • Yu P.A.
      • Hsu W.H.
      • Chi C.C.
      • Yoo J.C.
      Epinephrine in irrigation fluid for visual clarity in arthroscopic shoulder surgery: A systematic review and meta-analysis.
      • Van Montfoort D.O.
      • Van Kampen P.M.
      • Huijsmans P.E.
      Epinephrine diluted saline-irrigation fluid in arthroscopic shoulder surgery: A significant improvement of clarity of visual field and shortening of total operation time. a randomized controlled trial.

      Avery DM, Gibson BW, Carolan GF. Surgeon-rated visualization in shoulder arthroscopy: A randomized blinded controlled trial comparing irrigation fluid with and without epinephrine. Arthroscopy 22015;31:12-18.

      • Jensen K.H.
      • Werther K.
      • Stryger V.
      • Schultz K.
      • Falkenberg B.
      Arthroscopic shoulder surgery with epinephrine saline irrigation.
      Further research would be needed to draw definitive conclusions. It should be noted that the TXA study and the epinephrine studies employed the use of a pressure-controlled pump, and thus both chemicals can be considered to have additional benefits to a pump without either intervention.
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      ,
      • Kuo L.T.
      • Chen C.L.
      • Yu P.A.
      • Hsu W.H.
      • Chi C.C.
      • Yoo J.C.
      Epinephrine in irrigation fluid for visual clarity in arthroscopic shoulder surgery: A systematic review and meta-analysis.
      • Van Montfoort D.O.
      • Van Kampen P.M.
      • Huijsmans P.E.
      Epinephrine diluted saline-irrigation fluid in arthroscopic shoulder surgery: A significant improvement of clarity of visual field and shortening of total operation time. a randomized controlled trial.

      Avery DM, Gibson BW, Carolan GF. Surgeon-rated visualization in shoulder arthroscopy: A randomized blinded controlled trial comparing irrigation fluid with and without epinephrine. Arthroscopy 22015;31:12-18.

      • Jensen K.H.
      • Werther K.
      • Stryger V.
      • Schultz K.
      • Falkenberg B.
      Arthroscopic shoulder surgery with epinephrine saline irrigation.
      Because TXA does not provide joint distension or irrigation, it should only be utilized in addition to an irrigation pump.

      Strengths

      All studies involved in this systematic review had a Level of Evidence of I or II. Due to their high level of evidence and the sufficient power of these studies we were able to complete a meta-analysis that showed statistically and clinically significant findings. This gives us strong supporting evidence for our findings and enables the results to generate discussion surrounding the true benefits of TXA in arthroscopic surgeries of the knee and hip, as well as to extrapolate to other joints within appropriate limits.
      A narrative has been created that focuses on the results of each individual study, when grouped together, that provides positive findings to support the hypothesis that TXA decreases blood loss and increases positive outcomes of arthroscopic surgery. The topic was approached without bias, and a fair review of the current literature of how TXA may be used in arthroscopic surgeries of the knee, shoulder, and possibly other joints. This review will enable clinical practitioners to focus on how this may be applied to their clinical practice.
      It is important to acknowledge that another study has recently been published on this topic in Arthroscopy: The Journal of Arthroscopic and Related Surgery in December 2020.
      • Belk J.W.
      • McCarty E.C.
      • Houck D.A.
      • Dragoo J.L.
      • Savoie F.H.
      • Thon S.G.
      Tranexamic acid use in knee and shoulder arthroscopy leads to improved outcomes and fewer hemarthrosis-related complications: A systematic review of level I and II studies.
      Although the topic and some of the articles were identical, a search of the literature had returned 2 additional studies which were both RCTs with Level of Evidence II. These were not included in the previous study, and this additional data allowed a meta-analysis to be performed. This added to the overall impact of the study and provides important support to the statistically and clinically significant findings. The findings are ultimately similar, which demonstrates clear support for the likely positive effects and benefits of TXA in arthroscopic surgery of the shoulder and knee.

      Limitations

      This review was composed entirely of RCTs, and the risk of bias was appropriately evaluated and taken into consideration. With that in mind, there are some limitations that are important to mention. First, and most importantly, the number of enrolled participants was relatively low. It is important to note that the studies that were included in this review focused mainly on knee arthroscopy, with one study covering the shoulder and another the hip. Although some generalizations can be made, we should be careful not to extrapolate the data to make confident conclusions in regard to the other joints. With respect to study quality, both Level of Evidence I and II RCTs were included, and some studies required level of evidence determination. Although high-quality RCTs, the Level of Evidence II studies generally had low sample sizes, and although the studies without predetermined level of evidence were evaluated using established and recognized literature, this may be a potential limitation. There were also a number of studies that used subjective measurements regarding some of their outcomes (i.e., visual clarity), which increases the risk of biases. In addition, certain measured outcomes reported in the systematic review were not reported in enough studies to meet the inclusion criteria for a meta-analysis; specifically, the lack of analysis of pain control medication and morphine equivalents could have been clinically relevant, as discussed in one study.
      • Liu Y.F.
      • Hong C.K.
      • Hsu K.L.
      • et al.
      Intravenous administration of tranexamic acid significantly improved clarity of the visual field in arthroscopic shoulder surgery. A prospective, double-blind, and randomized controlled trial.
      These variables were therefore not reported in the meta-analysis, despite probable clinical importance.

      Conclusions

      This systematic review and meta-analysis of RCTs found that the use of TXA significantly improves pain scores up to 6 weeks postoperatively, decreases drainage output, decreases the need for joint aspirations, decreases incidence of hemarthrosis, increases visual clarity and technical ease, and has no increased incidence of other complications, at no loss to operative time. These findings indicate that TXA may be a useful adjunct in arthroscopic knee and shoulder surgery.

      Supplementary Data

      Appendix

      Appendix Table 2Level of Evidence Determination
      • Poehling G.
      • Jenkins C.
      Levels of evidence and your therapeutic study: What’s the difference with cohorts, controls, and cases?.
      ,

      Wright J. Levels of evidence and grades of recommendations: An evaluation of literature. American Academy of Orthopaedic Surgeons, 2005.

      StudyLevel of EvidenceDescription
      Poehling and Jenkins
      • Poehling G.
      • Jenkins C.
      Levels of evidence and your therapeutic study: What’s the difference with cohorts, controls, and cases?.
      IRCT that shows a significant difference between treatment groups or achieves narrow confidence intervals
      IIRandomized controlled trial with less than 80% follow-up
      Prospective cohort study
      IIIRetrospective cohort study
      Case–control study
      IVCase series study
      Wright

      Wright J. Levels of evidence and grades of recommendations: An evaluation of literature. American Academy of Orthopaedic Surgeons, 2005.

      IHigh-quality RCT with statistically significant difference or no statistically significant difference but narrow confidence intervals
      IILesser quality RCT (e.g., <80% follow-up, no blinding, or improper randomization)
      RCT, randomized clinical trial.
      Appendix Table 3Characteristics of Included Studies


      Study
      Study DesignLOESample SizeAge
      Data reported as mean ± standard deviation or mean (range).
      Sex (Male/Female)
      A represents TXA group, B represents non-TXA control group, except Karaaslan et al. 2017,22 where A represents TXA bolus group, B represents TXA bolus and infusion group.
      Arthroscopic SurgeryDosage/Route of TXA AdministrationFollow-UpNumber Followed up
      Chiang et al., 2019
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      Prospective comparativeII304A: 25.7 ± 8.4; B: 27.6 ± 6.9A: 125/26; B: 119/30ACLR10-mL intra-articular injection after surgery24 hours; 3 days; 4 weeks300
      Felli et al., 2019
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      Randomized controlledI80A: 30.7 ± 11.0; B: 32.0 ± 10.5A: 27/13; B: 36/4ACLR15 mg/kg IV infusion 20 minutes before tourniquet inflation24 hours; 7 days; 15 days; 1 month; 3 months80
      Karaaslan et al., 2015
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      Prospective, randomized, controlledI105A: 28.23 ± 6.59; B: 28.31 ± 9.01A: 51/2; B: 49/3ACLR15 mg/kg IV bolus 10 minutes before tourniquet inflation and 10 mg/kg/h infusion for 3-hours postoperatively24 hours; 2 days; 3 days; 7 days; 2 weeks; 3 weeks; 4 weeks105
      Pande et al., 2019
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      Prospective interventionalNot reported48A: 29.75; B: 29.33Not reportedACLR10 mL IV bolus before tourniquet inflation1 day; 3 days; 2 weeks; 6 weeks; 12 weeksNot reported
      Nugent et al. 2019
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      Double-blind randomized controlledII45Total: 53 (22-79); A: 48 (25-70); B: 53 (22-79)A: 12/6; B: 18/5Meniscectomy1 g IV bolus before tourniquet inflation3 days; 14 days; 30 days38, 37, 34
      Data reported as patients at 3 days, patients at 14 days, and patients at 30 days.
      Karaaslan et al., 2017
      • Karaaslan F.
      • Seijas R.
      • Sallent A.
      • et al.
      Tranexamic acid in bolus alone vs bolus and continuous infusion in hip arthroscopy.
      ProspectiveNot reported70A: 43.10 ± 13.35; B: 42.50 ± 13/91A: 18/17; B: 19/16Femoroacetabular impingementA: 2-g IV bolus 30 minutes before and 10 mg/kg/h infusion during surgery; B: 2-g IV bolus 30 minutes before surgeryImmediately70
      Liu et al., 2020
      • Liu Y.F.
      • Hong C.K.
      • Hsu K.L.
      • et al.
      Intravenous administration of tranexamic acid significantly improved clarity of the visual field in arthroscopic shoulder surgery. A prospective, double-blind, and randomized controlled trial.
      Prospective double-blind randomized controlledII72A: 58.9 ± 6.8; B: 60.2 ± 8A: 19/18; B: 17/18Rotator cuff repair1000 mg IV bolus 10 minutes before surgery1 day72
      ACLR, anterior cruciate ligament reconstruction; IV, intravenous; LOE, Level of Evidence; TXA, tranexamic acid.
      Data reported as mean ± standard deviation or mean (range).
      A represents TXA group, B represents non-TXA control group, except Karaaslan et al. 2017,
      • Karaaslan F.
      • Seijas R.
      • Sallent A.
      • et al.
      Tranexamic acid in bolus alone vs bolus and continuous infusion in hip arthroscopy.
      where A represents TXA bolus group, B represents TXA bolus and infusion group.
      Data reported as patients at 3 days, patients at 14 days, and patients at 30 days.
      Appendix Table 4Measurements of Pain
      Pain
      Data reported as mean ± standard deviation, mean (95% confidence interval), or median [range].
      StudyGroupPreoperative1 Day3 Days7 Days2 Weeks3 Weeks1 Month6 Weeks3 MonthsSignificant Dates
      Statistical significance defined as P < .05.
      VAS
      Chiang et al.
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      TXA3.2 ± 1.01.7 ± 0.63 days; 1 month
      Control6.7 ± 2.52.0 ± 1.1
      Karaaslan et al., 2015
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      TXA1.4 [1-5]2 [1-4]2 [1-4]3 days; 2 weeks; 3 weeks
      Control2.9 [2-5]4 [2-5]3 [1-4]
      Pande et al.
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      TXAMedian of 2.5-2 [1-4]1 [0-2][0-1]2 weeks; 6 weeks
      ControlMedian of 54 [2-5]2 [1-3][0-1]
      Nugent et al.
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      TXA3.9 (2.8-5.0)2.8 (1.5-4.1)2 (0.8-3.2)1.5 (0.7-2.4)None
      Control4.2 (3.3-5.2)2.2 (1.1-3.4)1.6 (0.6-2.5)1.9 (0.8-3.9)
      Liu et al.
      • Liu Y.F.
      • Hong C.K.
      • Hsu K.L.
      • et al.
      Intravenous administration of tranexamic acid significantly improved clarity of the visual field in arthroscopic shoulder surgery. A prospective, double-blind, and randomized controlled trial.
      TXA3.0 ± 1.51 day
      Control4.3 ± 2.0
      VAS Change from PreoperativeStudyGroupPreoperative1 Day3 Days7 Days2 Weeks3 Weeks1 Month6 Weeks3 MonthsSignificant Days
      Statistical significance defined as P < .05.
      Felli et al.
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      TXA2.0 ± 2.70.4 ± 2.2 (–0.3 to 1.1)–1.7 ± 2.1 (–2.4 to 1.0)–1.6 ± 2.7 (–2.5 to –0.7)–2.5 ± 3.1 (–3.5 to –1.5)7 days; 15 days
      Control1.8 ± 2.41.1 ± 3.1 (0.1-2.1)–0.1 ± 2.9 (–1.0 to 0.8)–1.1 ± 2.6 (–1.9 to –0.3)–2.4 ± 2.5 (–3.2 to –1.6)
      Pande et al.
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      TXAMedian of 3None
      ControlMedian of 6
      Nugent et al.
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      TXA3.9 (2.8-5.0)–1.1 (–2.0 to –0.1)–1.8 (–2.6 to –0.9)–2.3 (–3.2 to –1.4)None
      Control4.2 (3.3-5.2)–1.9 (–3.1 to –0.7)–2.7 (–3.7 to –1.7)–2.4 (–3.5 to –1.2)
      Analgesic drug use, mgStudyGroup[MME]Significance
      Statistical significance defined as P < .05.
      Liu et al.
      • Liu Y.F.
      • Hong C.K.
      • Hsu K.L.
      • et al.
      Intravenous administration of tranexamic acid significantly improved clarity of the visual field in arthroscopic shoulder surgery. A prospective, double-blind, and randomized controlled trial.
      TXA9.6 ± 9.7Yes
      Control14.7 ± 13.4
      MME, morphine milligram equivalent; TXA, tranexamic acid; VAS, visual analog scale.
      Data reported as mean ± standard deviation, mean (95% confidence interval), or median [range].
      Statistical significance defined as P < .05.
      Appendix Table 5Measurements of Blood Loss
      Blood Loss
      Data reported as number of patients, mean ± standard deviation, mean (95% confidence interval), mean ± standard deviation (95% confidence interval), or median [range].
      StudyGroupPatients Requiring AspirationSignificance
      Statistical significance defined as P < .05.
      Aspiration (number of patients)
      Chiang et al.
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      TXA0No
      Control0
      Felli et al.
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      TXA0No
      Control3
      Karaaslan et al.
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      TXA3 once; 1 twiceYes
      Control18 once; 1 twice
      Pande et al.
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      TXA3Yes
      Control7
      Drainage Output, mLStudyGroup24 hours PostoperativeSignificance
      Statistical significance defined as P < .05.
      Chiang et al.
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      TXA56.1 ± 34.1 (50.7-68.4)Yes
      Control80.1 ± 48 (72.4-92.3)
      Felli et al.
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      TXA59.3 ± 29.5 (49.9-68.7)Yes
      Control133.3 ± 56.1 (115.4-151.3)
      Karaaslan et al.
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      TXA60 [20-150]Yes
      Control150 [75-500]
      Hemarthrosis GradeStudyGroupPreoperative1 Day3 Days7 Days2 Weeks15 Days4 Weeks1 Month6 Weeks3 MonthsSignificant Dates
      Statistical significance defined as P < .05.
      Coupens and Yates
      Data reported as number grade 1/number grade 2/number grade 3/number grade 4/number grade 5, mean ± standard deviation, or mean ± standard deviation (95% confidence interval).
      Chiang et al.
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      TXA20/63/35/26/758/77/10/6/03 days
      Control3/22/49/45/3060/61/17/11/0
      Felli et al.
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      TXA0.6 ± 0.5 (0.4-0.8)1.6 ± 0.9 (1.3-1.9)2.1 ± 1.2 (1.7-2.4)1.5 ± 0.9 (1.2-2.8)0.8 ± 0.9 (0.5-1.1)0.3 ± 0.5 (0.1-0.5)1 day; 7 days; 15 days
      Control0.7 ± 0.6 (0.5-0.9)2.1 ± 0.9 (1.8-2.4)2.8 ± 1.2 (2.4-3.2)2.3 ± 1.1 (1.9-2.6)1.0 ± 0.9 (0.7-1.3)0.2 ± 0.4 (0.7-0.3)
      Karaaslan et al.
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      TXA15/24/8/5/120/29/3/1/07 days; 2 weeks
      Control0/6/12/16/183/24/19/6/0
      Pande et al.
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      TXA1.6 ± 0.70.37 ± 0.492 weeks; 6 weeks; 3 months
      Control2.1± 1.010.75 ± 0.0600.16 ± 0.38
      Hemoglobin level, G/dLStudyGroupPreoperativePostoperativePre- to Postoperative Change1 DayPreoperative to 1 Day ChangeSignificant Dates
      Statistical significance defined as P < .05.
      Felli et al.
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      TXA13.4 ± 7.6 (13.0 – 13.7)None
      Control13.9 ± 8.9 (13.6-14.2)
      Liu et al.
      • Liu Y.F.
      • Hong C.K.
      • Hsu K.L.
      • et al.
      Intravenous administration of tranexamic acid significantly improved clarity of the visual field in arthroscopic shoulder surgery. A prospective, double-blind, and randomized controlled trial.
      TXA1.0 ± 0.6None
      Control1.1 ± 0.7
      Karaaslan et al.
      • Karaaslan F.
      • Seijas R.
      • Sallent A.
      • et al.
      Tranexamic acid in bolus alone vs bolus and continuous infusion in hip arthroscopy.
      TXA Bolus and Infusion14.52 ± 1.2413.34 ± 1.45–1.18 ± 0.99Postoperative; pre- to postoperative change
      TXA Bolus14.30 ± 1.6512.46 ± 1.73–1.84 ± 0.78
      Hematocrit level, %StudyGroupPreoperativePostoperativePre- to Postoperative Change1 DayPreoperative to 1 Day ChangeSignificant Dates
      Statistical significance defined as P < .05.
      Felli et al.
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      TXA39.7 ± 3.2 (38.7-40.7)None
      Control39.7 ± 4.2 (38.3-41.1)
      Karaaslan et al.
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      TXA46.65 ± 3.3046.42 ± 3.37-0.23 ± 0.40Preoperative; 1 day
      Control45.22 ± 2.8744.89 ± 2.89-0.33 ± 0.44
      Karaaslan et al.
      • Karaaslan F.
      • Seijas R.
      • Sallent A.
      • et al.
      Tranexamic acid in bolus alone vs bolus and continuous infusion in hip arthroscopy.
      TXA Bolus and Infusion43.01 ± 1.2739.49 ± 3.45–3.52 ± 3.37Postoperative; pre- to postoperative change
      TXA bolus42.26 ± 4.5737.18 ± 4.60–5.08 ± 2.45
      TXA, tranexamic acid.
      Data reported as number of patients, mean ± standard deviation, mean (95% confidence interval), mean ± standard deviation (95% confidence interval), or median [range].
      Statistical significance defined as P < .05.
      Data reported as number grade 1/number grade 2/number grade 3/number grade 4/number grade 5, mean ± standard deviation, or mean ± standard deviation (95% confidence interval).
      Appendix Table 6Measurements of Function and Swelling
      Function and Swelling
      Data reported as mean ± standard deviation, mean (95% confidence interval), mean ± standard deviation (95% confidence interval), or median [range].
      StudyGroupPreoperative1 Day2 Days3 Days7 Days2 Weeks1 Month6 Weeks3 MonthsSignificant Dates
      Statistical significance defined as P < .05.
      Range of motion of knee (°)
      Chiang et al.
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      TXA118.5 ± 30.5None
      Control116 ± 33.9
      Felli et al.
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      TXA118.6 ± 14.6 (113.9-123.3)54.6 ± 24.9 (46.6-62.6)86.1 ± 11.9 (82.3-89.9)97.5 ± 12.5 (93.5-101.5)113.2 ± 12.8 (109.1-117.3)133.1 ± 2.5 (132.3-133.9)7 Days
      Control111.5 ± 21.9 (104.5-118.5)51.9 ± 34.1 (41.0-62.8)69.2 ± 27.1 (60.5-77.9)95.0 ± 13.3 (90.7-99.2)111.2 ± 10.7 (107.8-114.6)133.1 ± 2.1 (132.4-133.8)
      Karaaslan et al.
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      TXA99.43 ± 9.08107.36 ± 8.362 Days
      Control96.54 ± 7.11103.65 ± 7.68
      Pande et al.
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      TXA95.25 ± 5.5120.26 ± 7.82 Weeks
      Control84.21 ± 2.5116.45 ± 7.8
      Range of Motion of KneeStudyGroupPreoperative1 Day2 Days3 Days7 Days2 Weeks1 Month6 Weeks3 MonthsSignificant Dates
      Statistical significance defined as P < .05.
      Change from preoperative (°)Nugent et al.
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      TXA117.44 (109.54-125.34)–35.83 (–46.25 to –25.41)–2.93 (–11.62 to 5.75)5.2 (–2.03 to 12.43)None
      Control121.48 (113.43-129.53)–34.57 (–46.33 to –22.81)–16.18 (–27.32 to –5.04)0.47 (–8.70 to 9.65)
      IKDC Function ScoreStudyGroupPreoperative1 MonthSignificant Dates
      Statistical significance defined as P < .05.
      Chiang et al.
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      TXA4.7 ± 2.17.8 ± 1.5None
      Control4.4 ± 2.67.6 ± 1.0
      IKDC Passive Motion DeficitStudyGroupPreoperative1 Month3 MonthsSignificant Dates
      Statistical significance defined as P < .05.
      Felli et al.
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      TXA2.1 ± 0.8 (1.8-2.4)2.5 ± 0.8 (2.2-2.8)1.0 ± 0.3 (0.9-1.1)None
      Control2.2 ± 1.2 (1.8-2.6)2.5 ± 0.9 (2.2-2.8)1.0 ± 0.2 (0.9-1.1)
      IKDC Ligament ExaminationStudyGroupPreoperative1 Month3 MonthsSignificant dates
      Statistical significance defined as P < .05.
      Felli et al.
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      TXA3.2 ± 0.4 (3.1-3.3)1.1 ± 0.4 (1.0-1.2)1.1 ± 0.3 (1.0-1.2)None
      Control3.1 ± 0.5 (2.9-3.3)1.1 ± 0.3 (1.0-1.2)1.1 ± 0.2 (1.0-1.2)
      Subjective IKDC ScoreStudyGroupPreoperative1 Month3 MonthsSignificant dates
      Statistical significance defined as P < .05.
      Felli et al.
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      TXA53.9 ± 15.8 (48.9-58.9)62.4 ± 12.4 (58.4-66.4)80.8 ± 7.8 (78.3-83.3)None
      Control54.4 ± 16.3 (49.2-59.6)61.6 ± 8.8 (58.8-64.4)80.3 ± 4.9 (78.7-81.9)
      Quadriceps Strength (0-5)StudyGroupPreoperative1 Day7 Days2 Weeks1 Month3 MonthsSignificant dates
      Statistical significance defined as P < .05.
      Felli et al.
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      TXA4.1 ± 0.5 (3.9-4.3)2.6 ± 0.5 (2.4-2.8)3.1 ± 0.4 (3.0-3.2)3.9 ± 0.5 (3.7-4.1)4.2 ± 0.3 (4.1-4.3)4.7 ± 0.5 (4.5-4.9)7 days; 2 weeks
      Control4.1 ± 0.6 (3.9-4.3)2.4 ± 0.6 (2.2-2.6)2.7 ± 0.8 (2.4-3.0)3.4 ± 0.9 (3.1-3.7)4.2 ± 0.4 (4.1-4.3)4.8 ± 0.4 (4.6-5.0)
      Lysholm ScoreStudyGroupPreoperative3 Days2 Weeks1 Month6 Weeks3 MonthsSignificant Dates
      Statistical significance defined as P < .05.
      Felli et al.
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      TXA60.2 ± 21.3 (53.4-67.0)83.9 ± 11.9 (80.1-87.7)98.5 ± 2.1 (97.8-99.2)None
      Control61.8 ± 14/8 (57.1-66.5)80.2 ± 11.2 (76.6-83.8)98.0 ± 2.2 (97.3-98.7)
      Karaaslan et al.
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      TXA75 [50-90]80 [70-85]2 weeks; 1 months
      Control70 [40-85]75[50-85]
      Pande et al.
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      TXA53.83 ± 10.6370.70 ± 6.0783.70 ± 5.322 weeks; 6 weeks; 3 months
      Control41.58 ± 5.0558.54 ± 7.1371.83 ± 4.25
      Nugent et al.
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      TXA61.0 (50.4-70.6)66.8 (56.8-76.8)82.6 (74.5-90.8)88.3 (83.8-92.9)None
      Control58.7 (50.8-66.7)75.1 (68.1-82.1)83.0 (75.8-90.1)88.9 (84.5-93.4)
      Tegner ScoreStudyGroupPreoperative3 Days2 Weeks1 MonthSignificant Dates
      Statistical significance defined as P < .05.
      Nugent et al.
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      TXA4.8 (3.8-5.8)2.7 (2.2-3.1)3.6 (3.1-4.0)4.6 (4.0-5.2)3 Days
      Control4.4 (3.5-5.4)1.7 (1.2-2.3)3.1 (2.6-3.7)4.3 (3.6-4.9)
      Tegner Score Change from PreoperativeStudyGroupPreoperative3 Days2 Weeks1 MonthSignificant Dates
      Statistical significance defined as P < .05.
      Nugent et al.
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      TXA4.8 (3.8-5.8)2.1 (1.2-3.0)1.2 (0.2-2.2)0.9 (-0.8-1.0)None
      Control4.4 (3.5-5.4)2.6 (1.3-3.8)1.4 (0.1-2.7)0.2 (-0.9-1.4)
      Effusion IKDC ScoreStudyGroupPreoperative1 Month3 MonthsSignificant Dates
      Statistical significance defined as P < .05.
      Felli et al.
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      TXA1.4 ± 0.5 (1.2-1.6)1.6 ± 0.7 (1.4-1.8)1.2 ± 0.4 (1.1-1.3)None
      Control1.5 ± 0.6 (1.3-1.7)1.6 ± 0.6 (1.4-1.8)1.2 ± 0.4 (1.1-1.3)
      Patellar circumference, cmStudyGroupPreoperativeChange Preoperative vs 1 Day1 Day3 Days7 Days14 Days1 Month3 MonthsSignificant Dates
      Statistical significance defined as P < .05.
      Difference b/w affected and contralateralFelli et al.
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      TXA1.4 ± 3.5 (0.3-2.5)14.6 ± 11.6 (10.9-18.3)19.6 ± 17.1 (14.1-25.1)10.4 ± 12.5 (6.4-14.4)8.6 ± 13.1 (4.4-12.8)2.4 ± 4.5 (1.0-3.8)7 days; 15 days
      Control3.8 ± 7.5 (1.4-6.2)14.2 ± 11.5 (10.5-17.9)26.2 ± 14.6 (21.5-30.9)16.2 ± 12.3 (12.3-20.1)9.6 ± 11.6 (5.9-13.3)1.0 ± 2.9 (0.1-1.9)
      Suprapatellar Girth, cmStudyGroupPreoperativeChange Preoperative vs 1 Day1 Day3 Days7 Days14 Days1 Month3 MonthsSignificant Dates
      Statistical significance defined as P < .05.
      Change from preoperativeNugent et al.
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      TXA1.23 (0.75-1.71)0.59 (–0.03 to 1.22)0.07 (–0.68 to 0.81)None
      Control1.62 (0.67-2.56)0.99 (0.28-1.70)0.52 (–0.18 to 1.21)
      Calf Girth, cmStudyGroupPreoperativeChange Preoperative vs 1 Day1 Day3 Days7 Days14 Days1 Month3 MonthsSignificant Dates
      Statistical significance defined as P < .05.
      Change from preoperativeNugent et al.
      • Nugent M.
      • May J.H.
      • Parker J.D.
      • et al.
      Does tranexamic acid reduce knee swelling and improve early function following arthroscopic meniscectomy? a double-blind randomized controlled trial.
      TXA0.41 (–0.13 to 0.95)–0.01 (–0.59 to 0.57)–0.28 (–0.93 to 0.37)None
      Control0.54 (0.09-1.00)–0.21 (–0.79 to 0.36)0.10 (–0.69 to 0.89)
      Shoulder Size (Deltoid)StudyGroupPreoperativeChange Preoperative vs 1 Day1 Day3 Days7 Days14 Days1 Month3 MonthsSignificant Dates
      Statistical significance defined as P < .05.
      Change from preoperativeLiu et al.
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      TXA1.7 ± 1.2None
      Control1.9 ± 1.1
      Shoulder Size (Axillary)StudyGroupPreoperativeChange Preoperative vs 1 Day1 Day3 Days7 Days14 Days1 Month3 MonthsSignificant Dates
      Statistical significance defined as P < .05.
      Change from preoperativeLiu et al.
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      TXA3.0 ± 2.4None
      Control3.0 ± 1.7
      IKDC, International Knee Documentation Committee; TXA, tranexamic acid.
      Data reported as mean ± standard deviation, mean (95% confidence interval), mean ± standard deviation (95% confidence interval), or median [range].
      Statistical significance defined as P < .05.
      Appendix Table 7Measurements of Technical Ease
      Technical Ease
      Data reported as mean ± standard deviation or mean ± standard deviation (95% confidence interval).
      StudyGroupTimeSignificance
      Statistical significance defined as P < .05.
      Operative time, min
      Chiang et al.
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      TXA54.5 ± 17.2Not reported
      Control50.3 ± 19.3
      Felli et al.
      • Felli L.
      • Revello S.
      • Burastero G.
      • et al.
      Single Intravenous administration of tranexamic acid in anterior cruciate ligament reconstruction to reduce postoperative hemarthrosis and increase functional outcomes in the early phase of postoperative rehabilitation: A randomized controlled trial.
      TXA45.0 ± 6.6 (42.9-47.1)No
      Control40.8 ± 12.8 (36.7-44.9)
      Karaaslan et al.
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      TXA40 ± 18Not reported
      Control45 ± 15
      Pande et al.
      • Pande A.
      • Bhaskarwar A.P.
      Assessing the effect of per operative intravenous injection of tranexamic acid in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
      TXA43 ± 8Not reported
      Control45 ± 10
      Liu et al.
      • Liu Y.F.
      • Hong C.K.
      • Hsu K.L.
      • et al.
      Intravenous administration of tranexamic acid significantly improved clarity of the visual field in arthroscopic shoulder surgery. A prospective, double-blind, and randomized controlled trial.
      TXA115.2 ± 31.8No
      Control119.7 ± 35.1
      Karaaslan et al.
      • Karaaslan F.
      • Seijas R.
      • Sallent A.
      • et al.
      Tranexamic acid in bolus alone vs bolus and continuous infusion in hip arthroscopy.
      TXA bolus146.14 ± 36.80Not reported
      TXA bolus and infusion140.34 ± 35.67
      Visual Clarity (1-3)StudyGroupAverageGrade 1 (%)Grade 2 (%)Grade 3 (%)Significance
      Statistical significance defined as P < .05.
      Liu et al.
      • Liu Y.F.
      • Hong C.K.
      • Hsu K.L.
      • et al.
      Intravenous administration of tranexamic acid significantly improved clarity of the visual field in arthroscopic shoulder surgery. A prospective, double-blind, and randomized controlled trial.
      TXA2.5 ± 0.24.2 ± 9.142.3 ± 19.753.7 ± 18.9Average; grade 1; grade 3
      Control2.3 ± 0.39.2 ± 13.249.5 ± 21.940.5 ± 22.1
      TXA, tranexamic acid.
      Data reported as mean ± standard deviation or mean ± standard deviation (95% confidence interval).
      Statistical significance defined as P < .05.
      Appendix Table 8Coupens and Yates Hemarthrosis Grading
      • Coupens S.D.
      • Yates C.K.
      The effect of tourniquet use and hemovac drainage on postoperative hemarthrosis.
      GradeDescription
      0No detectable fluid
      1Fluid present with fluid wave
      2Palpable fluid in suprapatellar space
      3Ballotable patella
      4Tense hemarthrosis
      Appendix Table 1Risk of Bias Concerns
      Chiang
      • Chiang E.R.
      • Chen K.H.
      • Wang S.T.
      • et al.
      Intra-articular injection of tranexamic acid reduced postoperative hemarthrosis in arthroscopic anterior cruciate ligament reconstruction: A prospective randomized study.
      • No proposed method of evaluation prior to randomization
      Karaaslan et al.
      • Karaaslan F.
      • Karaoʇlu S.
      • Yurdakul E.
      Reducing intra-articular hemarthrosis after arthroscopic anterior cruciate ligament reconstruction by the administration of intravenous tranexamic acid.
      • Unable to find selection method of reported results
      Nugent
      • Dunn C.J.
      • Goa K.L.
      Tranexamic acid: A review of its use in surgery and other indications.
      • 3 observers, no comment on if they were blinded
      • Results were mainly subjective, not deemed high risk
      Karaaslan et al.
      • Karaaslan F.
      • Seijas R.
      • Sallent A.
      • et al.
      Tranexamic acid in bolus alone vs bolus and continuous infusion in hip arthroscopy.
      • No comment on whether surgeon was blinded to transfusion method; no effort in concealing method with placebo arm for infusion

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