Formula used to assess the primary outcome, calculated ...



Supplemental Digital ContentTable of Contents TOC \o "1-3" \h \z \u Formula used to assess the primary outcome, calculated perioperative blood loss PAGEREF _Toc482278809 \h 2Assumptions for sample size calculation PAGEREF _Toc482278810 \h 3Studies selected as a basis for blood loss assumptions PAGEREF _Toc482278811 \h 3Estimated blood loss reduction with tranexamic acid PAGEREF _Toc482278812 \h 4Sample size calculation PAGEREF _Toc482278813 \h 4Report of the methods used for the meta-analysis following the PRISMA guideline PAGEREF _Toc482278814 \h 5Flow chart of the study selection process PAGEREF _Toc482278815 \h 10Summarized results of individual studies included in the meta-analysis PAGEREF _Toc482278816 \h 11Meta-analysis forest plot for red blood cell transfusion PAGEREF _Toc482278817 \h 12References PAGEREF _Toc482278818 \h 13Formula used to assess the primary outcome, calculated perioperative blood lossThe method used to calculate perioperative blood loss was based on Hb balance as described previously byJohansson and colleagues. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"DUco9ez2","properties":{"formattedCitation":"{\\rtf \\super 1\\nosupersub{}}","plainCitation":"1"},"citationItems":[{"id":629,"uris":[""],"uri":[""],"itemData":{"id":629,"type":"article-journal","title":"Tranexamic acid in total hip arthroplasty saves blood and money: a randomized, double-blind study in 100 patients","container-title":"Acta Orthopaedica","page":"314-319","volume":"76","issue":"3","source":"PubMed","abstract":"BACKGROUND: A blood transfusion is a costly transplantation of tissue that may endanger the health for the recipient. Blood transfusions are common after total hip arthroplasty. The total saving potential is substantial if the blood loss could be reduced. Studies on the use of tranexamic acid have shown interesting results, but its benefits in total hip arthroplasty have not yet been resolved.\nPATIENTS AND METHODS: 100 patients receiving a total hip arthroplasty (THA) got a single injection of tranexamic acid (15 mg/kg) or placebo intravenously before the start of the operation. The study was double-blind and randomized. Total blood loss was calculated from the hemoglobin (Hb) balance. Volume and Hb concentration of the drainage was measured 24 h after the operation. Intraoperative blood loss was estimated volumetrically and visually.\nRESULTS: The patients who received tranexamic acid (TA) bled less. The total blood loss was on average 0.97 L in the TA group and 1.3 L in the placebo group (p < 0.001). 8/47 (0.2) in the TA group were given blood transfusion versus 23/53 (0.4) in the placebo group (p = 0.009). Drainage volume and drainage Hb concentration were less in the TA group (p < 0.001 and p = 0.001). No thromboembolic complications occurred.\nINTERPRETATION: Considering the cost of blood and tranexamic acid only, use of the drug would save EUR 47 Euro per patient. We recommend a preoperative single dose of tranexamic acid for standard use in THA.","ISSN":"1745-3674","note":"PMID: 16156456","shortTitle":"Tranexamic acid in total hip arthroplasty saves blood and money","journalAbbreviation":"Acta Orthop","language":"eng","author":[{"family":"Johansson","given":"Torsten"},{"family":"Pettersson","given":"Lars-G?ran"},{"family":"Lisander","given":"Bj?rn"}],"issued":{"date-parts":[["2005",6]]}}}],"schema":""} 1 The following formulas were used:Hb loss = (Hbpre – Hbe ) × BV + HbtWhere Hbpre is the initial preoperative Hb concentration (g/l), Hbe is the Hb concentration (g/l) on the fifth postoperative day, and Hbt is the total amount of allogeneic transfused Hb (g). 1 unit of red blood cells was considered to contain 52 g of Hb (personal communication from Etablissement Fran?ais du Sang, Saint Priest en Jarez, France).We assumed that the blood volume (BV, ml) was normalized on the fifth postoperative day.BV was estimated as described previously by Rosencher and colleagues ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2Ku0Lclq","properties":{"formattedCitation":"{\\rtf \\super 2\\nosupersub{}}","plainCitation":"2"},"citationItems":[{"id":1627,"uris":[""],"uri":[""],"itemData":{"id":1627,"type":"article-journal","title":"Orthopedic Surgery Transfusion Hemoglobin European Overview (OSTHEO) study: blood management in elective knee and hip arthroplasty in Europe","container-title":"Transfusion","page":"459-469","volume":"43","issue":"4","source":"PubMed","abstract":"BACKGROUND: The purpose of this study was to assess current practices in blood management in elective orthopedic surgery in Europe.\nSTUDY DESIGN AND METHODS: For this 225-center prospective survey, data were collected on 3996 patients. Actual perioperative blood loss was compared to preoperative estimates. Differences in Hb levels and other outcome variables for patients receiving allogeneic versus autologous transfusions were evaluated. The probability of allogeneic transfusion based on selected predictor variables was estimated.\nRESULTS: A total of 2640 (67%) hip and 1305 (33%) knee arthroplasty patients were evaluated. Estimated blood loss (median, 750 mL) was significantly lower than computed blood loss (median, 1944 mL). A total of 2762 (69%) patients received transfusions, including 1393 (35%) autologous-only and 1024 (25%) allogeneic-only. The probability of allogeneic transfusion decreased with increasing baseline Hb, but differentially so for men and women. Transfusion triggers were Hb levels of 8.93 +/- 1.83 g per dL for allogeneic transfusions, and 21 percent of these occurred when the Hb level was greater than 10 g per dL. Autologous blood transfusion was associated with a significantly lower rate (1%) of wound infections than allogeneic blood transfusion (4.2%).\nCONCLUSION: Accurate assessment of preoperative Hb levels, better estimation of perioperative blood loss, efficient use of autologous blood, adherence to transfusion guidelines, and pharmacologic alternatives contribute to effective and comprehensive blood and anemia management.","ISSN":"0041-1132","note":"PMID: 12662278","shortTitle":"Orthopedic Surgery Transfusion Hemoglobin European Overview (OSTHEO) study","journalAbbreviation":"Transfusion","language":"eng","author":[{"family":"Rosencher","given":"Nadia"},{"family":"Kerkkamp","given":"Hans E. M."},{"family":"Macheras","given":"G."},{"literal":"L. M. Munuera"},{"family":"Menichella","given":"G."},{"family":"Barton","given":"David M."},{"family":"Cremers","given":"Saskia"},{"family":"Abraham","given":"Ivo L."},{"literal":"OSTHEO Investigation"}],"issued":{"date-parts":[["2003",4]]}}}],"schema":""} 2:BV (ml) = body surface area (m2) x 2530 (in men) Or body surface area (m2) x 2430 (in women)body surface area (m2) = 0.0235 x height (cm) 0.42246 x weight (kg) 0.51456Blood loss (ml) was calculated in relation to the patient’s preoperative Hb value:blood loss (m) = 1000 × Hb loss / HbpreHemoglobin measurements?were obtained as?part?of a?complete blood count by a Coulter counter analyzer.Assumptions for sample size calculationStudies selected as a basis for blood loss assumptions ReferenceYearTranexamic acidregimenDesign Patients randomizedPerioperative blood loss, mlMean +/- SDTranexamic acidControlTranexamic acidControlRandomized trials assessing a single preoperative bolus of tranexamic acid versus placebo or no treatmentDuquenne P ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"ji8k9ondv","properties":{"formattedCitation":"{\\rtf \\super 3\\nosupersub{}}","plainCitation":"3"},"citationItems":[{"id":1630,"uris":[""],"uri":[""],"itemData":{"id":1630,"type":"article-journal","title":"Tranexamic acid reduces postoperative blood losses associated with elective total hip replacement","collection-title":"J Bone Joint Surg Br","page":"233","volume":"81(suppl 2)","journalAbbreviation":"J Bone Joint Surg Br","author":[{"family":"Duquenne","given":"P"},{"family":"Lhoehst","given":"L"},{"family":"Henkes","given":"W"},{"family":"De Sart","given":"F"}],"issued":{"date-parts":[["1999"]]}}}],"schema":""} 3199915 mg/kg before surgerydouble- blind3535803 +/- 312907 +/- 438Benoni G ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"Pa326dws","properties":{"formattedCitation":"{\\rtf \\super 4\\nosupersub{}}","plainCitation":"4"},"citationItems":[{"id":365,"uris":[""],"uri":[""],"itemData":{"id":365,"type":"article-journal","title":"Blood conservation with tranexamic acid in total hip arthroplasty: a randomized, double-blind study in 40 primary operations","container-title":"Acta Orthopaedica Scandinavica","page":"442-448","volume":"72","issue":"5","source":"PubMed","abstract":"We performed a randomized, double-blind study on the effect of tranexamic acid on blood loss and blood transfusions in 40 primary total hip arthroplasties. Tranexamic acid, 10 mg/kg body weight, or placebo, was given intravenously just before the operation. Blood loss during the operation and postoperatively into the drains was recorded, as also were blood hemoglobin concentrations. Ultrasound examination 1 week postoperatively was done to estimate the blood loss due to remaining hematomas. Total (operation + drain) blood loss was 0.76 (95 CI 0.63-0.89) L in the tranexamic acid group as compared to 1.0 (CI 0.81-1.2) L in the placebo group (p = 0.03). The number of blood transfusions during the day of operation was 2 vs. 10 (p = 0.07) and the total number during the hospital stay was 5 vs. 13 (p = 0.2). 1 patient in each group had a pulmonary embolism.","DOI":"10.1080/000164701753532754","ISSN":"0001-6470","note":"PMID: 11728069","shortTitle":"Blood conservation with tranexamic acid in total hip arthroplasty","journalAbbreviation":"Acta Orthop Scand","language":"eng","author":[{"family":"Benoni","given":"G."},{"family":"Fredin","given":"H."},{"family":"Knebel","given":"R."},{"family":"Nilsson","given":"P."}],"issued":{"date-parts":[["2001",10]]}}}],"schema":""} 4200110 mg/kg before surgerydouble- blind18201028 +/- 3331382 +/- 455Yamasaki S ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"0hs6am3E","properties":{"formattedCitation":"{\\rtf \\super 5\\nosupersub{}}","plainCitation":"5"},"citationItems":[{"id":139,"uris":[""],"uri":[""],"itemData":{"id":139,"type":"article-journal","title":"Tranexamic acid reduces blood loss after cementless total hip arthroplasty-prospective randomized study in 40 cases","container-title":"International Orthopaedics","page":"69-73","volume":"28","issue":"2","source":"PubMed","abstract":"We investigated the effects of tranexamic acid in 40 patients who had received cementless total hip arthroplasty (THA) in a prospective, randomized study. In 20 patients, 1000 mg of whole-body tranexamic acid was administered intravenously 5 min before the operation started. The other 20 patients served as a control group and were operated on without tranexamic acid. Perioperative blood loss was similar in the tranexamic acid group and in the control group. Postoperative blood loss of the tranexamic acid group was significantly less than that of the control group at 2, 4, 6, 8, 10, and 12 h. Regarding time-related changes of postoperative blood loss, significant reduction was observed during the first 2 h after surgery in the tranexamic acid group ( P<0.001). After the first 2 h, there was no significant difference between the tranexamic acid group and the control group. Preoperative administration of tranexamic acid decreased postoperative blood loss until 12 h and total bleeding in cementless THA by reduction of blood loss during the first 2 h after surgery.","DOI":"10.1007/s00264-003-0511-4","ISSN":"0341-2695","note":"PMID: 15224162\nPMCID: PMC3474476","journalAbbreviation":"Int Orthop","language":"eng","author":[{"family":"Yamasaki","given":"Satoshi"},{"family":"Masuhara","given":"Kensaku"},{"family":"Fuji","given":"Takeshi"}],"issued":{"date-parts":[["2004",4]]}}}],"schema":""} 520031 g before surgeryopen20201350 +/- 4771667 +/- 401Johansson T ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"z0ucEiOD","properties":{"formattedCitation":"{\\rtf \\super 1\\nosupersub{}}","plainCitation":"1"},"citationItems":[{"id":629,"uris":[""],"uri":[""],"itemData":{"id":629,"type":"article-journal","title":"Tranexamic acid in total hip arthroplasty saves blood and money: a randomized, double-blind study in 100 patients","container-title":"Acta Orthopaedica","page":"314-319","volume":"76","issue":"3","source":"PubMed","abstract":"BACKGROUND: A blood transfusion is a costly transplantation of tissue that may endanger the health for the recipient. Blood transfusions are common after total hip arthroplasty. The total saving potential is substantial if the blood loss could be reduced. Studies on the use of tranexamic acid have shown interesting results, but its benefits in total hip arthroplasty have not yet been resolved.\nPATIENTS AND METHODS: 100 patients receiving a total hip arthroplasty (THA) got a single injection of tranexamic acid (15 mg/kg) or placebo intravenously before the start of the operation. The study was double-blind and randomized. Total blood loss was calculated from the hemoglobin (Hb) balance. Volume and Hb concentration of the drainage was measured 24 h after the operation. Intraoperative blood loss was estimated volumetrically and visually.\nRESULTS: The patients who received tranexamic acid (TA) bled less. The total blood loss was on average 0.97 L in the TA group and 1.3 L in the placebo group (p < 0.001). 8/47 (0.2) in the TA group were given blood transfusion versus 23/53 (0.4) in the placebo group (p = 0.009). Drainage volume and drainage Hb concentration were less in the TA group (p < 0.001 and p = 0.001). No thromboembolic complications occurred.\nINTERPRETATION: Considering the cost of blood and tranexamic acid only, use of the drug would save EUR 47 Euro per patient. We recommend a preoperative single dose of tranexamic acid for standard use in THA.","ISSN":"1745-3674","note":"PMID: 16156456","shortTitle":"Tranexamic acid in total hip arthroplasty saves blood and money","journalAbbreviation":"Acta Orthop","language":"eng","author":[{"family":"Johansson","given":"Torsten"},{"family":"Pettersson","given":"Lars-G?ran"},{"family":"Lisander","given":"Bj?rn"}],"issued":{"date-parts":[["2005",6]]}}}],"schema":""} 1200415 mg/kg before surgerydouble- blind4753969 +/- 4341324 +/- 577Lemay E ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"bq90b9eO","properties":{"formattedCitation":"{\\rtf \\super 6\\nosupersub{}}","plainCitation":"6"},"citationItems":[{"id":1631,"uris":[""],"uri":[""],"itemData":{"id":1631,"type":"article-journal","title":"Tranexamic acid reduces the need for allogenic red blood cell transfusions in patients undergoing total hip replacement","container-title":"Canadian Journal of Anaesthesia","page":"31-37","volume":"51","issue":"1","source":"PubMed","abstract":"PURPOSE: This prospective randomized double-blind trial evaluates the efficacy of tranexamic acid (TA) to decrease blood losses and red blood cell transfusions in patients undergoing primary unilateral total hip replacement (THR).\nMETHODS: Forty ASA class I to III patients received either iv TA 10 mg.kg(-1) bolus before surgery plus a 1 mg.kg(-1).hr(-1) infusion until wound closure (Group TA) or a placebo (Group P). Red blood cell transfusions were administered according to a standardized protocol.\nRESULTS: One patient of Group P was excluded because of an erroneous diagnosis at enrollment. Total measured blood losses (Group TA: 1308 +/- 462 mL vs Group P: 1469 +/- 405 mL), preoperative hemoglobin levels (Group TA: 130.4 +/- 12.5 g.L(-1) vs Group P: 131.4 +/- 12.8 vs g.L(-1)), and seven-day postoperative hemoglobin values (Group TA: 97.8 +/- 11.8 g.L(-1) vs Group P: 102.9 +/- 12.2 g.L(-1)) were similar. Autologous whole blood was available in five patients of Group P and seven patients of Group TA. Fewer patients in Group TA required red blood cells (Group TA: 6/20 vs Group P: 13/19; P = 0.026) and allogenic red blood cell transfusions (Group TA: 0/20 vs Group P: 8/19; P = 0.0012). The median number of transfused unit per patient was also significantly less in patients of Group TA (0 unit) than in Group P (2 units; P = 0.03).\nCONCLUSION: TA did not change measured blood losses but reduced red blood cell transfusion requirements in patients undergoing primary unilateral THR.","DOI":"10.1007/BF03018543","ISSN":"0832-610X","note":"PMID: 14709457","journalAbbreviation":"Can J Anaesth","language":"eng","author":[{"family":"Lemay","given":"Erik"},{"family":"Guay","given":"Joanne"},{"family":"C?té","given":"Christiane"},{"family":"Roy","given":"Alain"}],"issued":{"date-parts":[["2004",1]]}}}],"schema":""} 6200410 mg/kg before surgery + 1 mg/kg/h during surgerydouble- blind20191308 +/- 4621469 +/- 405Garneti N ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"00czUNxU","properties":{"formattedCitation":"{\\rtf \\super 7\\nosupersub{}}","plainCitation":"7"},"citationItems":[{"id":1633,"uris":[""],"uri":[""],"itemData":{"id":1633,"type":"article-journal","title":"Bone bleeding during total hip arthroplasty after administration of tranexamic acid","container-title":"The Journal of Arthroplasty","page":"488-492","volume":"19","issue":"4","source":"PubMed","abstract":"Numerous methods of controlling bleeding during total hip arthroplasty have been used. Thromboplastic agents have been used with some success, but the resultant fibrin layer interposed between the bone and cement weakens the interface. Topical freezing saline and hypotensive anesthesia have proved to be the most effective to date. The goal of this randomized, double blind, controlled study is to determine the effect of a single bolus dose of tranexamic acid, administered at the time of anesthesia, on bleeding during primary total hip arthroplasty. Fifty patients were randomized to receive either 10 mg/kg of tranexamic acid or a similar volume of normal saline as a preoperative bolus. Patients were not given pharmacologic thrombotic prophylaxis until 48 hours after surgery. The goal was to measure blood loss from the femoral canal at the time of surgery. An estimate of the internal and external blood loss during and after surgery was performed, and the transfusion requirement was recorded. No significant difference was found between the groups in terms of blood loss from the femoral canal, the perioperative bleeding, and postoperative hemoglobin. In the group that received tranexamic acid, a greater number of patients required transfusion than in the placebo group. The results of this study do not support the routine use of tranexamic acid in primary total hip arthroplasty.","ISSN":"0883-5403","note":"PMID: 15188109","journalAbbreviation":"J Arthroplasty","language":"eng","author":[{"family":"Garneti","given":"Narendra"},{"family":"Field","given":"Jeremy"}],"issued":{"date-parts":[["2004",6]]}}}],"schema":""} 7200410 mg/kg before surgerydouble- blind25251443 +/- 8091340 +/- 665Claeys MA ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"QiZOXaTo","properties":{"unsorted":true,"formattedCitation":"{\\rtf \\super 8\\nosupersub{}}","plainCitation":"8"},"citationItems":[{"id":232,"uris":[""],"uri":[""],"itemData":{"id":232,"type":"article-journal","title":"Reduction of blood loss with tranexamic acid in primary total hip replacement surgery","container-title":"Acta Chirurgica Belgica","page":"397-401","volume":"107","issue":"4","source":"PubMed","abstract":"BACKGROUND: In this prospective, placebo-controlled, double-blind, randomized clinical trial, we investigated the effect of a single preoperative bolus dose of tranexamic acid (15 mg/kg) on perioperative blood losses and packed cell transfusion requirements in patients scheduled for primary unilateral total hip replacement surgery for degenerative osteoarthrosis.\nPATIENTS AND METHODS: 40 patients were randomized to receive either 15 mg/kg tranexamic acid (TA group) or an equal volume of saline (placebo group) given as a single slow intravenous bolus injection 15 minutes before incision. We recorded per- and postoperative blood losses and transfusion requirements up to 24 hours postoperatively. The patients were screened for deep venous thrombosis with bilateral compression ultrasonography using colour Doppler imaging on the tenth postoperative day.\nRESULTS: Peroperative blood loss was not significantly different between the two treatment groups (TA group : 423 ml, placebo group 516 ml ; p = 0.093). Postoperative blood loss up to 24 hrs, and total blood loss were significantly less in the TA group : 352 vs 524 ml (p = 0.013), and 801 vs 1038 ml (p = 0.013), respectively. Packed red blood cell transfusion requirements were significantly lower in the TA group (1/20 patients, total 2 units) compared to the placebo group (6/20 patients, total 13 units). Compression ultrasonography on the 10th postoperative day was positive for deep venous thrombosis in 3 patients in the TA group (17 patients screened) and negative in all patients of the placebo group (18 patients screened).\nCONCLUSION: Tranexamic acid 15 mg/kg given as a single preoperative bolus dose reduces postoperative and total blood loss, and packed cell transfusion requirements in primary total hip replacement surgery.","ISSN":"0001-5458","note":"PMID: 17966532","journalAbbreviation":"Acta Chir. Belg.","language":"eng","author":[{"family":"Claeys","given":"M. A."},{"family":"Vermeersch","given":"N."},{"family":"Haentjens","given":"P."}],"issued":{"date-parts":[["2007",8]]}}}],"schema":""} 8200715 mg/kg before surgerydouble- blind2020801 +/- 2441038 +/- 289Rajesparan K ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"fLyftXvg","properties":{"formattedCitation":"{\\rtf \\super 9\\nosupersub{}}","plainCitation":"9"},"citationItems":[{"id":22,"uris":[""],"uri":[""],"itemData":{"id":22,"type":"article-journal","title":"The effect of an intravenous bolus of tranexamic acid on blood loss in total hip replacement","container-title":"The Journal of Bone and Joint Surgery. British Volume","page":"776-783","volume":"91","issue":"6","source":"PubMed","abstract":"Tranexamic acid is a fibrinolytic inhibitor which reduces blood loss in total knee replacement. We examined the effect on blood loss of a standardised intravenous bolus dose of 1 g of tranexamic acid, given at the induction of anaesthesia in patients undergoing total hip replacement and tested the potential prothrombotic effect by undertaking routine venography. In all, 36 patients received 1 g of tranexamic acid, and 37 no tranexamic acid. Blood loss was measured directly per-operatively and indirectly post-operatively. Tranexamic acid reduced the early post-operative blood loss and total blood loss (p = 0.03 and p = 0.008, respectively) but not the intraoperative blood loss. The tranexamic acid group required fewer transfusions (p = 0.03) and had no increased incidence of deep-vein thrombosis. The reduction in early post-operative blood loss was more marked in women (p = 0.05), in whom this effect was dose-related (r = -0.793). Our study showed that the administration of a standardised pre-operative bolus of 1 g of tranexamic acid was cost-effective in reducing the blood loss and transfusion requirements after total hip replacement, especially in women.","DOI":"10.1302/0301-620X.91B6.22393","ISSN":"0301-620X","note":"PMID: 19483232","journalAbbreviation":"J Bone Joint Surg Br","language":"eng","author":[{"family":"Rajesparan","given":"K."},{"family":"Biant","given":"L. C."},{"family":"Ahmad","given":"M."},{"family":"Field","given":"R. E."}],"issued":{"date-parts":[["2009",6]]}}}],"schema":""} 920091 g before surgeryopen36371372+/-4361683+/-705Kazemi SM ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"aMrUhzNk","properties":{"formattedCitation":"{\\rtf \\super 10\\nosupersub{}}","plainCitation":"10"},"citationItems":[{"id":1635,"uris":[""],"uri":[""],"itemData":{"id":1635,"type":"article-journal","title":"The effect of tranexamic acid on reducing blood loss in cementless total hip arthroplasty under epidural anesthesia","container-title":"Orthopedics","page":"17","volume":"33","issue":"1","source":"PubMed","abstract":"Total hip arthroplasty (THA) is associated with high intraoperative and postoperative blood loss. Antifibrinolytic drugs have been used to minimize the potential risks of bleeding and blood transfusion. Studies on the effect of tranexamic acid on decreasing blood loss in THA have revealed interesting results, but most have focused on cemented THA. Yet its benefits in THA, especially in cementless THA, have not been proved. We conducted a prospective double-blind randomized controlled study on 64 patients who were candidates for cementless THA under epidural anesthesia between 2006 and 2008. Patients were randomly assigned into study and control groups. Patients in both groups were well matched regarding preoperative characteristics. Five minutes preoperatively 32 patients of the study and control groups received 15 mg/kg tranexamic acid or normal saline intravenously respectively. Our findings showed a significantly smaller decrease in 6- and 24-hour postoperative hemoglobin levels, less intraoperative and postoperative bleeding, and less need for allogenic blood transfusion in the tranexamic acid group. Our results also revealed a higher mean of 6- and 24-hour hematocrit level and shorter hospital stay in the tranexamic acid group compared to the control group, which were not statistically meaningful. In our study no thromboembolic event was seen; except 1 patient in the control group. Our study showed that administering tranexamic acid before the start of cementless THA under epidural anesthesia can reduce intraoperative and postoperative bleeding as well as need for blood transfusion.","DOI":"10.3928/01477447-20091124-30","ISSN":"1938-2367","note":"PMID: 20055345","journalAbbreviation":"Orthopedics","language":"eng","author":[{"family":"Kazemi","given":"Seyyed Morteza"},{"family":"Mosaffa","given":"Faramarz"},{"family":"Eajazi","given":"Alireza"},{"family":"Kaffashi","given":"Mohammad"},{"family":"Daftari Besheli","given":"Laleh"},{"family":"Bigdeli","given":"Mohammad Reza"},{"family":"Zanganeh","given":"Ramin Farhang"}],"issued":{"date-parts":[["2010",1]]}}}],"schema":""} 10201015 mg/kg before surgerydouble- blind3232n.a.n.a.McConnell JS ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"IC4jV6BO","properties":{"formattedCitation":"{\\rtf \\super 11\\nosupersub{}}","plainCitation":"11"},"citationItems":[{"id":451,"uris":[""],"uri":[""],"itemData":{"id":451,"type":"article-journal","title":"Reduction of blood loss in primary hip arthroplasty with tranexamic acid or fibrin spray","container-title":"Acta Orthopaedica","page":"660-663","volume":"82","issue":"6","source":"PubMed","abstract":"BACKGROUND AND PURPOSE: Previous studies have shown that either fibrin spray or tranexamic acid can reduce blood loss at total hip replacement, but the 2 treatments have not been directly compared. We therefore conducted a randomized, controlled trial.\nPATIENTS AND METHODS: In this randomized controlled trial we compared the effect of tranexamic acid and fibrin spray on blood loss in cemented total hip arthroplasty. 66 patients were randomized to 1 of 3 parallel groups receiving (1) a 10 mg/kg bolus of tranexamic acid prior to surgery, (2) 10 mL of fibrin spray during surgery, or (3) neither. All participants except the surgeon were blinded as to treatment group until data analysis was complete. Blood loss was calculated from preoperative and postoperative hematocrit.\nRESULTS: Neither active treatment was found to be superior to the other in terms of overall blood loss. Losses were lower than those in the control group, when using either tranexamic acid (22% lower, p = 0.02) or fibrin spray (32% lower, p = 0.02).\nINTERPRETATION: We found that the use of tranexamic acid at induction, or topical fibrin spray intraoperatively, reduced blood loss compared to the control group. Blood loss was similar in the fibrin spray group and in the tranexamic acid group. identifier: NCT00378872. EudraCT identifier: 2006-001299-19. Regional Ethics Committee approval: 06/S0703/55, granted June 6, 2006.","DOI":"10.3109/17453674.2011.623568","ISSN":"1745-3682","note":"PMID: 21999623\nPMCID: PMC3247881","journalAbbreviation":"Acta Orthop","language":"eng","author":[{"family":"McConnell","given":"Jamie S."},{"family":"Shewale","given":"Sandeep"},{"family":"Munro","given":"Niall A."},{"family":"Shah","given":"Kalpesh"},{"family":"Deakin","given":"Angela H."},{"family":"Kinninmonth","given":"Andrew W. G."}],"issued":{"date-parts":[["2011",12]]}}}],"schema":""} 11 201110 mg/kg before surgeryopen2222895+/-991110 +/- 139Randomized trials assessing a preoperative bolus and additional perioperative administration of tranexamic acid versus placebo or no treatmentEkb?ck G ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"9np8BmWd","properties":{"formattedCitation":"{\\rtf \\super 12\\nosupersub{}}","plainCitation":"12"},"citationItems":[{"id":30,"uris":[""],"uri":[""],"itemData":{"id":30,"type":"article-journal","title":"Tranexamic acid reduces blood loss in total hip replacement surgery","container-title":"Anesthesia and Analgesia","page":"1124-1130","volume":"91","issue":"5","source":"PubMed","abstract":"Intraoperatively administered, tranexamic acid (TA) does not reduce bleeding in total hip replacement (THR). Therefore, its prophylactic use was attempted in the present study because this has been shown to be more effective in cardiac surgery. We investigated 40 patients undergoing THR in a prospective, randomized, double-blinded study. Twenty patients received TA given in two bolus doses of 10 mg/kg each, the first just before surgical incision and the second 3 h later. In addition, a continuous infusion of TA, 1.0 mg. kg(-1). h(-1) for 10 h, was given after the first bolus dose. The remaining 20 patients formed a control group. Both groups used preoperative autologous blood donation and intraoperative autotransfusion. Intraoperative bleeding was significantly less (P: = 0.001) in the TA group compared with the control group (630 +/- 220 mL vs 850 +/- 260 mL). Postoperative drainage bleeding was correspondingly less (P: = 0.001) (520 +/- 280 vs 920 +/- 410 mL). Up to 10 h postoperatively, plasma D-dimer concentration was halved in the TA group compared with the control group. One patient in each group had an ultrasound-verified late deep vein thrombosis. In conclusion, we found TA, administrated before surgical incision, to be efficient in reducing bleeding during THR.\nIMPLICATIONS: In a prospective, double-blinded study of 40 patients undergoing total hip replacement, the preoperative administration of tranexamic acid reduced bleeding by 35%, probably by decreasing induced fibrinolysis. Whether tranexamic acid therapy can replace predonation of autologous blood or intraoperative autotransfusion requires further study.","ISSN":"0003-2999","note":"PMID: 11049894","journalAbbreviation":"Anesth. Analg.","language":"eng","author":[{"family":"Ekb?ck","given":"G."},{"family":"Axelsson","given":"K."},{"family":"Ryttberg","given":"L."},{"family":"Edlund","given":"B."},{"family":"Kjellberg","given":"J."},{"family":"Weckstr?m","given":"J."},{"family":"Carlsson","given":"O."},{"family":"Sch?tt","given":"U."}],"issued":{"date-parts":[["2000",11]]}}}],"schema":""} 12200010 mg/kg before surgery + 1 mg/kg/h over 10h + 10 mg/kg 3h after 1st bolusdouble- blind20201130 +/- 4001770 +/- 523Husted H ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"fawI3Eoq","properties":{"formattedCitation":"{\\rtf \\super 13\\nosupersub{}}","plainCitation":"13"},"citationItems":[{"id":78,"uris":[""],"uri":[""],"itemData":{"id":78,"type":"article-journal","title":"Tranexamic acid reduces blood loss and blood transfusions in primary total hip arthroplasty: a prospective randomized double-blind study in 40 patients","container-title":"Acta Orthopaedica Scandinavica","page":"665-669","volume":"74","issue":"6","source":"PubMed","abstract":"INTRODUCTION: We performed a prospective, randomized, double-blind study on 40 patients scheduled for primary total hip arthroplasty due to arthrosis or osteonecrosis to determine the effect of tranexamic acid on per- and postoperative blood losses and on the number of blood transfusions needed.\nPATIENTS AND METHODS: 40 patients were randomized to tranexamic acid (10 mg/kg given as a bolus intravenous injection, followed by a continuous infusion of 1 mg/kg/hour for 10 hours) or placebo (20 mL saline given intravenously) 15 minutes before the incision. We recorded the peroperative and postoperative blood losses at removal of the drain 24 hours after the operation and the number of blood transfusions.\nRESULTS: Patients receiving tranexamic acid had a mean peroperative blood loss of 480 mL versus 622 mL in patients receiving placebo (p = 0.3), a postoperative blood loss of 334 mL versus 609 mL (p = 0.001), a total blood loss of 814 mL versus 1231 mL (p = 0.001) and a total need for 4 blood transfusions versus 25 (p = 0.04). No patient in either group had symptoms of deep venous thrombosis, pulmonary embolism or prolonged wound drainage.\nINTERPRETATION: Transemic acid is effective in reducing the postoperative blood loss, the total blood loss and the need for blood transfusion in primary total hip arthroplasty.","DOI":"10.1080/00016470310018171","ISSN":"0001-6470","note":"PMID: 14763696","shortTitle":"Tranexamic acid reduces blood loss and blood transfusions in primary total hip arthroplasty","journalAbbreviation":"Acta Orthop Scand","language":"eng","author":[{"family":"Husted","given":"Henrik"},{"family":"Bl?nd","given":"Lars"},{"family":"Sonne-Holm","given":"Stig"},{"family":"Holm","given":"Gitte"},{"family":"Jacobsen","given":"Tine W."},{"family":"Gebuhr","given":"Peter"}],"issued":{"date-parts":[["2003",12]]}}}],"schema":""} 13200310 mg/kg before surgery + 1 mg/kg/h over 10 hdouble- blind2020814 +/- 12651231 +/- 1639Ido K ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"lFQlaEFR","properties":{"formattedCitation":"{\\rtf \\super 14\\nosupersub{}}","plainCitation":"14"},"citationItems":[{"id":1637,"uris":[""],"uri":[""],"itemData":{"id":1637,"type":"article-journal","title":"Reduction of blood loss using tranexamic acid in total knee and hip arthroplasties","container-title":"Archives of Orthopaedic and Trauma Surgery","page":"518-520","volume":"120","issue":"9","source":"PubMed","abstract":"There have been several attempts to reduce postoperative blood loss in patients undergoing total arthroplasty. Benoni et al. reported the usefulness of tranexamic acid in total knee arthroplasty (TKA). We investigated its effect in TKA and total hip arthroplasty (THA). Blood loss was significantly reduced in patients given tranexamic acid in both the TKA and THA groups, and no severe complications, such as venous or pulmonary thrombosis, were noted in any of the patients who received the agent. Administration of tranexamic acid seems to be useful for reducing postoperative blood loss in TKA and THA.","ISSN":"0936-8051","note":"PMID: 11011672","journalAbbreviation":"Arch Orthop Trauma Surg","language":"eng","author":[{"family":"Ido","given":"K."},{"family":"Neo","given":"M."},{"family":"Asada","given":"Y."},{"family":"Kondo","given":"K."},{"family":"Morita","given":"T."},{"family":"Sakamoto","given":"T."},{"family":"Hayashi","given":"R."},{"family":"Kuriyama","given":"S."}],"issued":{"date-parts":[["2000"]]}}}],"schema":""} 1420001 g before surgery + 1 g 3h after surgeryopen2020n.a.n.a.Niskanen R ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"SXqa7nq2","properties":{"formattedCitation":"{\\rtf \\super 15\\nosupersub{}}","plainCitation":"15"},"citationItems":[{"id":1639,"uris":[""],"uri":[""],"itemData":{"id":1639,"type":"article-journal","title":"Tranexamic acid reduces blood loss in cemented hip arthroplasty: a randomized, double-blind study of 39 patients with osteoarthritis","container-title":"Acta Orthopaedica","page":"829-832","volume":"76","issue":"6","source":"PubMed","abstract":"BACKGROUND: Tranexamic acid has been found to reduce blood loss and the need for blood transfusions in knee arthroplasty. In hip arthroplasty, the benefit of tranexamic acid is not as clear.\nPATIENTS AND METHODS: In a randomized, double-blind study, 39 patients with primary cemented hip arthroplasty for osteoarthritis were divided into two groups; one receiving tranexamic acid and the other not receiving it. Tranexamic acid was given in a dose of 10 mg/kg before the operation and twice thereafter, at 8-hour intervals.\nRESULTS AND INTERPRETATION: Total blood loss was smaller in the tranexamic acid group than in the control group. No thromboembolic complications were noticed. Tranexamic acid appears to be an effective and economic drug for reduction of blood loss in cemented primary hip arthroplasty for osteoarthritis.","DOI":"10.1080/17453670510045444","ISSN":"1745-3674","note":"PMID: 16470437","shortTitle":"Tranexamic acid reduces blood loss in cemented hip arthroplasty","journalAbbreviation":"Acta Orthop","language":"eng","author":[{"family":"Niskanen","given":"Raimo O."},{"family":"Korkala","given":"Olli L."}],"issued":{"date-parts":[["2005",12]]}}}],"schema":""} 15200510 mg/kg before surgery + 10 mg/kg 8h after + 10 mg/kg 16h afterdouble- blind1920792 +/- 3491102 +/- 464Local retrospective study on the use of a preoperative bolus and additional postoperative administration of tranexamic acid vs no treatment (unpublished)Farissier F201215 mg/kg before surgery + 15 mg/kg 3h after 1st bolus5417Blood loss difference 600 +/- 650Estimated blood loss reduction with tranexamic acidIn studies assessing a single preoperative bolus of tranexamic acid versus placebo or no treatment, the mean blood loss reductions ranged from 0 to 350 ml (SD 300-500). The overall mean blood loss reduction was approximately 250 ml (a).In studies assessing a preoperative bolus of tranexamic acid and additional perioperative administration versus placebo or no treatment, the mean blood loss reduction ranged from 300 to 640 ml (SD 350-1400). The overall mean blood loss reduction was approximately 500 ml (b). Indirect comparison favors the administration of an additional perioperative administration of tranexamic acid. The expected gain in blood loss was therefore assumed to be 500 - 250 ml (b-a), which is 250 ml.Sample size calculationAssuming a difference in perioperative blood loss of 250 ml with a standard deviation (SD) of 500 ml,?we calculated that a sample size of 84 patients per group would be required to achieve a power of 90% with a two-sided α risk of 0.05.Report of the methods used for the meta-analysis following the PRISMA guideline A meta-analysis of randomized trials was performed to assess the external validity of the PORTO study. The decision to perform this meta-analysis was taken after completion of the PORTO study. We report here the methods of this meta-analysis as recommended by the PRISMA guidelines for the reporting of systematic reviews.Protocol and registration: There was no review protocol. However, the methods of the analysis and the inclusion criteria were specified in advance.Eligibility criteria: Type of studies: Randomized clinical trials comparing a single preoperative tranexamic acid bolus with preoperative administration of tranexamic acid followed by perioperative tranexamic acid administration as a bolus or a continuous infusion. No language, publication date, or publication status restrictions were imposed.Types of participants: Studies had to be performed in adults in primary hip arthroplastyType of intervention: Tranexamic acid had to be administered exclusively intravenouslyTypes of outcome measures: The primary outcome was perioperative blood loss defined as the sum of intraoperative and postoperative blood loss. Perioperative blood loss could be measured or calculated. The secondary outcome was the percentage of patients requiring transfusion of at least 1 unit of allogeneic red blood cells during the perioperative period. There was no restriction for the length of follow rmation sources: Relevant trials were identified by a computerized search up to June 2016 in MEDLINE (PubMed) and the Cochrane Central Registry of Controlled Trials (Central). In addition, we checked the reference lists of the trials selected. Foreign papers were translated. The authors of the selected trials were contacted to supply missing information or clarifications. If a selected trial was published as an abstract, the author was asked if a full paper of the selected study had been published. Meeting abstracts were nott searched. One reviewer (PJZ) developed and conducted the search. Search: The search strategy in PubMed and Central included the key words “tranexamic acid” and “hip”. In PubMed, the search was limited to randomized controlled trials with use of the article type search filter. In Central, the search was limited to trials with use of the search filter. The search detail in PubMed was:("tranexamic acid"[MeSH Terms] OR ("tranexamic"[All Fields] AND "acid"[All Fields]) OR "tranexamic acid"[All Fields]) AND ("hip"[MeSH Terms] OR "hip"[All Fields]) AND Randomized Controlled Trial[ptyp]Study selection: Studies were first screened on the basis of title and/or abstract by one reviewer (PJZ). Assessment for study eligibility and inclusion was performed by two reviewers (CC, PJZ). The study selection process is presented below using the PRISMA flow chart.Data collection process: Data were extracted using a data extraction sheet designed for this review in Excel (Microsoft). One review author (PJZ) extracted the data from the studies included and a second author (CC) checked the extracted data. In the event of a discrepancy with regard to either study selection or data extraction, the decision of a third author (SM) was final. We contacted all authors for further information in July 2016. A reminder was sent in August 2016. All but one author answered. One author provided numerical data on the primary outcome that had only been presented graphically in the published paper. One study had also analyzed the data concering the per-protocol population. The author provided numerical data on the primary and secondary outcome for all the available patients. One study had been published in Russian and translated. The author was contacted to provide additional data on study characteristics and methodology. This author provided another Russian article that had not been identified by the electronic search. The analysis in the latter study had been performed on the per-protocol population. The author provided the results of the analysis on the intention-to-treat population and confirmed the accuracy of the information included in the review. This author is also an author of this manuscript (DB).Data items: “Information was extracted from each trial included with respect to: (1) the characteristics of trial participants (including age, weight, type of anesthesia, surgery and thromboprophylaxis implemented); (2) regimen of tranexamic acid used (dose, type of administration (bolus or infusion), duration or number of administrations); (3) type of outcome measure (including perioperative blood loss and the method used to measure this outcome, and the proportion of patients transfused with allogeneic red blood cells); (4) the number of patients randomized and the number of patients available for analyses. Risk of bias in individual studies: Studies were classified by consensual agreement of two authors (CC and PZ) as having a low risk of bias, an unclear risk of bias, or a high risk of bias, based on the Cochrane tool. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2vzlC8fW","properties":{"formattedCitation":"{\\rtf \\super 16\\nosupersub{}}","plainCitation":"16"},"citationItems":[{"id":1771,"uris":[""],"uri":[""],"itemData":{"id":1771,"type":"article-journal","title":"The Cochrane Collaboration's tool for assessing risk of bias in randomised trials","container-title":"BMJ (Clinical research ed.)","page":"d5928","volume":"343","source":"PubMed","ISSN":"1756-1833","note":"PMID: 22008217\nPMCID: PMC3196245","journalAbbreviation":"BMJ","language":"eng","author":[{"family":"Higgins","given":"Julian P. T."},{"family":"Altman","given":"Douglas G."},{"family":"G?tzsche","given":"Peter C."},{"family":"Jüni","given":"Peter"},{"family":"Moher","given":"David"},{"family":"Oxman","given":"Andrew D."},{"family":"Savovic","given":"Jelena"},{"family":"Schulz","given":"Kenneth F."},{"family":"Weeks","given":"Laura"},{"family":"Sterne","given":"Jonathan A. C."},{"literal":"Cochrane Bias Methods Group"},{"literal":"Cochrane Statistical Methods Group"}],"issued":{"date-parts":[["2011",10,18]]}}}],"schema":""} 16 The Cochrane tool takes into account random sequence generation, concealment of the allocation sequence, blinding of participants and study personnel, blinding of outcome assessment, incomplete outcome data, and selective reporting. Summary measures: Data concerning the primary continuous outcome, perioperative blood loss, were pooled using the ratio of the means method. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1MoRSYtx","properties":{"formattedCitation":"{\\rtf \\super 17\\nosupersub{}}","plainCitation":"17"},"citationItems":[{"id":356,"uris":[""],"uri":[""],"itemData":{"id":356,"type":"article-journal","title":"The ratio of means method as an alternative to mean differences for analyzing continuous outcome variables in meta-analysis: a simulation study","container-title":"BMC medical research methodology","page":"32","volume":"8","source":"PubMed","abstract":"BACKGROUND: Meta-analysis of continuous outcomes traditionally uses mean difference (MD) or standardized mean difference (SMD; mean difference in pooled standard deviation (SD) units). We recently used an alternative ratio of mean values (RoM) method, calculating RoM for each study and estimating its variance by the delta method. SMD and RoM allow pooling of outcomes expressed in different units and comparisons of effect sizes across interventions, but RoM interpretation does not require knowledge of the pooled SD, a quantity generally unknown to clinicians.\nOBJECTIVES AND METHODS: To evaluate performance characteristics of MD, SMD and RoM using simulated data sets and representative parameters.\nRESULTS: MD was relatively bias-free. SMD exhibited bias (~5%) towards no effect in scenarios with few patients per trial (n = 10). RoM was bias-free except for some scenarios with broad distributions (SD 70% of mean value) and medium-to-large effect sizes (0.5-0.8 pooled SD units), for which bias ranged from -4 to 2% (negative sign denotes bias towards no effect). Coverage was as expected for all effect measures in all scenarios with minimal bias. RoM scenarios with bias towards no effect exceeding 1.5% demonstrated lower coverage of the 95% confidence interval than MD (89-92% vs. 92-94%). Statistical power was similar. Compared to MD, simulated heterogeneity estimates for SMD and RoM were lower in scenarios with bias because of decreased weighting of extreme values. Otherwise, heterogeneity was similar among methods.\nCONCLUSION: Simulation suggests that RoM exhibits comparable performance characteristics to MD and SMD. Favourable statistical properties and potentially simplified clinical interpretation justify the ratio of means method as an option for pooling continuous outcomes.","DOI":"10.1186/1471-2288-8-32","ISSN":"1471-2288","note":"PMID: 18492289\nPMCID: PMC2430201","shortTitle":"The ratio of means method as an alternative to mean differences for analyzing continuous outcome variables in meta-analysis","journalAbbreviation":"BMC Med Res Methodol","language":"eng","author":[{"family":"Friedrich","given":"Jan O."},{"family":"Adhikari","given":"Neill K. J."},{"family":"Beyene","given":"Joseph"}],"issued":{"date-parts":[["2008"]]}}}],"schema":""} 17 Data concerning the binary outcome, transfusion of at least 1 unit of allogeneic red blood cells, were pooled using the Mantel-Haenszel odds ratio method without corrections. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"C3RzM69a","properties":{"formattedCitation":"{\\rtf \\super 18\\nosupersub{}}","plainCitation":"18"},"citationItems":[{"id":446,"uris":[""],"uri":[""],"itemData":{"id":446,"type":"article-journal","title":"Much ado about nothing: a comparison of the performance of meta-analytical methods with rare events","container-title":"Statistics in Medicine","page":"53-77","volume":"26","issue":"1","source":"PubMed","abstract":"For rare outcomes, meta-analysis of randomized trials may be the only way to obtain reliable evidence of the effects of healthcare interventions. However, many methods of meta-analysis are based on large sample approximations, and may be unsuitable when events are rare. Through simulation, we evaluated the performance of 12 methods for pooling rare events, considering estimability, bias, coverage and statistical power. Simulations were based on data sets from three case studies with between five and 19 trials, using baseline event rates between 0.1 and 10 per cent and risk ratios of 1, 0.75, 0.5 and 0.2. We found that most of the commonly used meta-analytical methods were biased when data were sparse. The bias was greatest in inverse variance and DerSimonian and Laird odds ratio and risk difference methods, and the Mantel-Haenszel (MH) odds ratio method using a 0.5 zero-cell correction. Risk difference meta-analytical methods tended to show conservative confidence interval coverage and low statistical power at low event rates. At event rates below 1 per cent the Peto one-step odds ratio method was the least biased and most powerful method, and provided the best confidence interval coverage, provided there was no substantial imbalance between treatment and control group sizes within trials, and treatment effects were not exceptionally large. In other circumstances the MH OR without zero-cell corrections, logistic regression and the exact method performed similarly to each other, and were less biased than the Peto method.","DOI":"10.1002/sim.2528","ISSN":"0277-6715","note":"PMID: 16596572","shortTitle":"Much ado about nothing","journalAbbreviation":"Stat Med","language":"eng","author":[{"family":"Bradburn","given":"Michael J."},{"family":"Deeks","given":"Jonathan J."},{"family":"Berlin","given":"Jesse A."},{"family":"Russell Localio","given":"A."}],"issued":{"date-parts":[["2007",1,15]]}}}],"schema":""} 18 Planned methods of analysis: In trials with more than two intervention groups, it was planned to combine results for groups that received similar but non-identical interventions (as long as the group fulfilled the criteria for eligibility, as defined above) and it was planned not to include an intervention group if it did not match our inclusion criteria. Heterogeneity was explored by visual inspection of the forest plot, calculation of the Cochran Q heterogeneity statistic and calculation of the I2 statistic. A fixed-effect model was planned in the absence of heterogeneity, defined by a p value > 0.10 for the Cochran Q heterogeneity statistic and an I2 value < 25%. The random-effects model approach is also presented.Risk of bias across studies: The risk of publication bias was checked using the funnel plot technique for the primary outcome.Additional analyses: A sensitivity analysis was performed by restricting the meta-analysis to studies considered at low risk of bias (data not shown).Software: The meta-analysis was performed using R software (meta package, version 2.15.1; downloaded from r-). Computation was performed by one review author (CC). Flow chart of the study selection process-14696412166600 Five studies were included in addition to the current trial. Two were identified in CENTRAL, ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"VZmnnqUd","properties":{"formattedCitation":"{\\rtf \\super 19\\nosupersub{}}","plainCitation":"19"},"citationItems":[{"id":405,"uris":[""],"uri":[""],"itemData":{"id":405,"type":"article-journal","title":"Reduction of perioperative blood loss during endoprosthetic replacement of large joints","container-title":"General Reanimatology","page":"34-37","volume":"7","issue":"4","archive_location":"CN-01034749","abstract":"to define the optimal tranexamic acid\n dosage\n regimen to reduce perioperative blood\n loss\n during total endo-\nprosthetic hip joint replacement\n (TEHJR).\n Subjects\n and\n methods.\n A randomized controlled trial enrolled 90 patients\nadmitted for\n elective\n primary cementless TEHJR. Prior to\n surgery,\n all the patients\n were\n given\n an intravenous bolus\ninjection of tranexamic acid in a dose of 1 g. A day before\n surgery,\n the patients\n were\n divided\n into 3 groups of 30 sub-\njects\n each. In Group 1, tranexamic acid was administered only before incision of the\n skin.\n In Group 2, a second bolus\nof tranexamic acid 1 g was injected 3 hours after start of\n surgery.\n In Group 3, 1 g of tranexamic acid was readminis-\ntered 6 hours\n following\n surgery\n if drainage blood\n loss\n volume exceeded 200 ml.\n Results.\n No\n statistically\n significant\n dif-\nferences\n were\n found between the study patient groups in terms of the amount of blood\n loss,\n the blood\n levels\n of hemo-\nglobin,\n needs for hemotransfusion therapy, and the frequency of postoperative complications.\n Conclusion.\n A second\nbolus of tranexamic acid 1 g does not reduce the amount of blood\n loss\n as compared to a\n single\n preoperative bolus dose\nof tranexamic acid 1 g during\n elective\n primary cementless\n TEHJP.\n Key\n words:\n tranexamic acid, endoprosthetic hip\njoint replacement, blood\n loss.","DOI":"","author":[{"family":"Borisov","given":"D.B."},{"family":"Yudin","given":"S.V."},{"family":"Krylov","given":"O.V."},{"family":"Markov","given":"B.B."},{"family":"Istomina","given":"N.A."}],"issued":{"date-parts":[["2011"]]}}}],"schema":""} 19, ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"c5h8qEOE","properties":{"formattedCitation":"{\\rtf \\super 20\\nosupersub{}}","plainCitation":"20"},"citationItems":[{"id":1767,"uris":[""],"uri":[""],"itemData":{"id":1767,"type":"article-journal","title":"Tranexamic acid for reduction of blood loss during total hip arthroplasty","container-title":"The Journal of Arthroplasty","page":"1838-1843","volume":"27","issue":"10","source":"PubMed","abstract":"In this study, we evaluated the hemostatic effects of tranexamic acid (TNA), an antifibrinolytic drug, by examining the timing of its administration during total hip arthroplasty. One hundred seven patients being treated for osteoarthritis of the hip joint were randomly divided into 5 groups based on the timing of TNA administration. The intraoperative blood loss, postoperative blood loss, and hemoglobin of these patients who received TNA at different times during the procedure were monitored. We found that the intraoperative blood loss in the preoperative TNA administration groups was significantly lower than both control and postoperative TNA administration groups. Furthermore, 1 g TNA 10 minutes before surgery and 6 hours after the first administration was most effective for the reduction of blood loss during total hip arthroplasty.","DOI":"10.1016/j.arth.2012.04.024","ISSN":"1532-8406","note":"PMID: 22704229","journalAbbreviation":"J Arthroplasty","language":"eng","author":[{"family":"Imai","given":"Norio"},{"family":"Dohmae","given":"Yoichiro"},{"family":"Suda","given":"Ken"},{"family":"Miyasaka","given":"Dai"},{"family":"Ito","given":"Tomoyuki"},{"family":"Endo","given":"Naoto"}],"issued":{"date-parts":[["2012",12]]}}}],"schema":""} 20 one in MEDLINE, ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"AuQqkkp3","properties":{"formattedCitation":"{\\rtf \\super 21\\nosupersub{}}","plainCitation":"21"},"citationItems":[{"id":157,"uris":[""],"uri":[""],"itemData":{"id":157,"type":"article-journal","title":"Tranexamic acid compared with placebo for reducing total blood loss in hip replacement surgery: a randomized clinical trial","container-title":"Anesthesia & Analgesia","page":"986-995","volume":"122","issue":"4","source":"CrossRef","DOI":"10.1213/ANE.0000000000001159","ISSN":"0003-2999","shortTitle":"Tranexamic Acid Compared with Placebo for Reducing Total Blood Loss in Hip Replacement Surgery","language":"en","author":[{"family":"Barrachina","given":"Borja"},{"family":"Lopez-Picado","given":"Amanda"},{"family":"Remon","given":"Maria"},{"family":"Fondarella","given":"Ana"},{"family":"Iriarte","given":"Ibai"},{"family":"Bastida","given":"Rebeca"},{"family":"Rodríguez-Gascón","given":"Alicia"},{"family":"Achaerandio","given":"Maria Aranzazu"},{"family":"Iturricastillo","given":"Maria Carmen"},{"family":"Aizpuru","given":"Felipe"},{"family":"Valero","given":"Cesar Augusto"},{"family":"Tobalina","given":"Ricardo"},{"family":"Hernanz","given":"Roberto"}],"issued":{"date-parts":[["2016",4]]}}}],"schema":""} 21 one in MEDLINE and CENTRAL ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"5NsJkEt5","properties":{"formattedCitation":"{\\rtf \\super 22\\nosupersub{}}","plainCitation":"22"},"citationItems":[{"id":429,"uris":[""],"uri":[""],"itemData":{"id":429,"type":"article-journal","title":"Single tranexamic acid dose to reduce perioperative morbidity in primary total hip replacement: a randomised clinical trial","container-title":"Hip Int","page":"63-68","volume":"24","issue":"1","source":"PubMed","abstract":"INTRODUCTION: Although prophylactic tranexamic acid (TXA) is a safe, low-cost option to reduce bleeding in patients undergoing total hip replacement (THR), its optimal dose and duration is unknown. We compared the safety and effectiveness of TXA given as either a single injection or continuous infusion in THR patients, hypothesising that a second TXA dose would not offer any clinical advantages over the single injection.\nMATERIALS AND METHODS: One hundred and sixty-four patients undergoing unilateral THR were randomised. Exclusion criteria were history of thromboembolic events (TE), epilepsy, thrombophilia, and severe chronic renal failure. Patients received either a single dose of 30 mg/kg TXA on induction of surgery (one shot [OS] group), or a loading dose of 10 mg/kg TXA followed two hours later by a continuous infusion of 2 mg/kg per hour for 20 hours (one day [OD] group). The primary outcome was blood loss (BL) calculated from haematocrit levels. Secondary outcomes were mortality and TE events within 90 days postoperatively.\nRESULTS: All patients completed treatment, with none lost to follow-up. Mean BL was 1107 ± 508 ml in Group OS and 1047 ± 442 ml in Group OD (p = 0.43). No patients were transfused prior to Day 10 postoperatively. At final follow-up, no patients had died, and there were no occurrences of major TE.\nCONCLUSION: The 30 mg/kg TXA single shot was as safe as continuous infusion. As it is also less cumbersome, we recommend it as part of routine care in THR patients.","DOI":"10.5301/hipint.5000090","ISSN":"1724-6067","note":"PMID: 24062227","shortTitle":"Single tranexamic acid dose to reduce perioperative morbidity in primary total hip replacement","journalAbbreviation":"Hip Int","language":"eng","author":[{"family":"Hourlier","given":"Hervé"},{"family":"Fennema","given":"Peter"}],"issued":{"date-parts":[["2014",2]]}}}],"schema":""} 22 and one was provided by a study investigator. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"GH9WFJkG","properties":{"formattedCitation":"{\\rtf \\super 23\\nosupersub{}}","plainCitation":"23"},"citationItems":[{"id":401,"uris":[""],"uri":[""],"itemData":{"id":401,"type":"article-journal","title":"Choice of a tranexamic acid dose regimen during endoprosthetic replacement of joints","container-title":"Messenger of Anesthesiology and Resuscitation","page":"41-44","volume":"8","issue":"5","abstract":"A randomized controlled study has established that during primary uncemented total hip replacement, continuous maintenance infusion of tranexamic acid after preoperative bolus injection of the agent allows a reduction in drainage blood loss as compared to a single injection of tranexamic acid prior to skin incision","ISSN":"ISSN 2078-5658","author":[{"family":"Borisov","given":"D.B."},{"family":"Yudin","given":"S.V."},{"family":"Lebedev","given":"L.A."},{"family":"Vardanashvili","given":"V.K."},{"family":"Istomina","given":"N.A."}],"issued":{"date-parts":[["2011"]]}}}],"schema":""} 23Summarized results of individual studies included in the meta-analysis *One patient did not undergo surgery; %one patient withdrew his consent and refused participation.ReferenceYearNumber of patients available for analysis/ Number of patients randomizedPerioperativeblood loss (ml)Mean (SD)Number of patients transfused with allogeneic red blood cellPerioperative groupPreoperative groupPerioperative groupPreoperative groupPerioperative groupPreoperative groupBorisov ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"pCXJHcRu","properties":{"formattedCitation":"{\\rtf \\super 19\\nosupersub{}}","plainCitation":"19"},"citationItems":[{"id":405,"uris":[""],"uri":[""],"itemData":{"id":405,"type":"article-journal","title":"Reduction of perioperative blood loss during endoprosthetic replacement of large joints","container-title":"General Reanimatology","page":"34-37","volume":"7","issue":"4","archive_location":"CN-01034749","abstract":"to define the optimal tranexamic acid\n dosage\n regimen to reduce perioperative blood\n loss\n during total endo-\nprosthetic hip joint replacement\n (TEHJR).\n Subjects\n and\n methods.\n A randomized controlled trial enrolled 90 patients\nadmitted for\n elective\n primary cementless TEHJR. Prior to\n surgery,\n all the patients\n were\n given\n an intravenous bolus\ninjection of tranexamic acid in a dose of 1 g. A day before\n surgery,\n the patients\n were\n divided\n into 3 groups of 30 sub-\njects\n each. In Group 1, tranexamic acid was administered only before incision of the\n skin.\n In Group 2, a second bolus\nof tranexamic acid 1 g was injected 3 hours after start of\n surgery.\n In Group 3, 1 g of tranexamic acid was readminis-\ntered 6 hours\n following\n surgery\n if drainage blood\n loss\n volume exceeded 200 ml.\n Results.\n No\n statistically\n significant\n dif-\nferences\n were\n found between the study patient groups in terms of the amount of blood\n loss,\n the blood\n levels\n of hemo-\nglobin,\n needs for hemotransfusion therapy, and the frequency of postoperative complications.\n Conclusion.\n A second\nbolus of tranexamic acid 1 g does not reduce the amount of blood\n loss\n as compared to a\n single\n preoperative bolus dose\nof tranexamic acid 1 g during\n elective\n primary cementless\n TEHJP.\n Key\n words:\n tranexamic acid, endoprosthetic hip\njoint replacement, blood\n loss.","DOI":"","author":[{"family":"Borisov","given":"D.B."},{"family":"Yudin","given":"S.V."},{"family":"Krylov","given":"O.V."},{"family":"Markov","given":"B.B."},{"family":"Istomina","given":"N.A."}],"issued":{"date-parts":[["2011"]]}}}],"schema":""} 19 201130/3030/301235 (605)994 (318)10Borisov ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"qE3fJj7e","properties":{"formattedCitation":"{\\rtf \\super 23\\nosupersub{}}","plainCitation":"23"},"citationItems":[{"id":401,"uris":[""],"uri":[""],"itemData":{"id":401,"type":"article-journal","title":"Choice of a tranexamic acid dose regimen during endoprosthetic replacement of joints","container-title":"Messenger of Anesthesiology and Resuscitation","page":"41-44","volume":"8","issue":"5","abstract":"A randomized controlled study has established that during primary uncemented total hip replacement, continuous maintenance infusion of tranexamic acid after preoperative bolus injection of the agent allows a reduction in drainage blood loss as compared to a single injection of tranexamic acid prior to skin incision","ISSN":"ISSN 2078-5658","author":[{"family":"Borisov","given":"D.B."},{"family":"Yudin","given":"S.V."},{"family":"Lebedev","given":"L.A."},{"family":"Vardanashvili","given":"V.K."},{"family":"Istomina","given":"N.A."}],"issued":{"date-parts":[["2011"]]}}}],"schema":""} 23 201135/3535/351035 (332)1034 (320)00Imai ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"dcX9PzNs","properties":{"formattedCitation":"{\\rtf \\super 20\\nosupersub{}}","plainCitation":"20"},"citationItems":[{"id":1767,"uris":[""],"uri":[""],"itemData":{"id":1767,"type":"article-journal","title":"Tranexamic acid for reduction of blood loss during total hip arthroplasty","container-title":"The Journal of Arthroplasty","page":"1838-1843","volume":"27","issue":"10","source":"PubMed","abstract":"In this study, we evaluated the hemostatic effects of tranexamic acid (TNA), an antifibrinolytic drug, by examining the timing of its administration during total hip arthroplasty. One hundred seven patients being treated for osteoarthritis of the hip joint were randomly divided into 5 groups based on the timing of TNA administration. The intraoperative blood loss, postoperative blood loss, and hemoglobin of these patients who received TNA at different times during the procedure were monitored. We found that the intraoperative blood loss in the preoperative TNA administration groups was significantly lower than both control and postoperative TNA administration groups. Furthermore, 1 g TNA 10 minutes before surgery and 6 hours after the first administration was most effective for the reduction of blood loss during total hip arthroplasty.","DOI":"10.1016/j.arth.2012.04.024","ISSN":"1532-8406","note":"PMID: 22704229","journalAbbreviation":"J Arthroplasty","language":"eng","author":[{"family":"Imai","given":"Norio"},{"family":"Dohmae","given":"Yoichiro"},{"family":"Suda","given":"Ken"},{"family":"Miyasaka","given":"Dai"},{"family":"Ito","given":"Tomoyuki"},{"family":"Endo","given":"Naoto"}],"issued":{"date-parts":[["2012",12]]}}}],"schema":""} 20 201226/2625/25852 (261)914 (248)00Hourlier ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"NdpFUQAN","properties":{"formattedCitation":"{\\rtf \\super 22\\nosupersub{}}","plainCitation":"22"},"citationItems":[{"id":429,"uris":[""],"uri":[""],"itemData":{"id":429,"type":"article-journal","title":"Single tranexamic acid dose to reduce perioperative morbidity in primary total hip replacement: a randomised clinical trial","container-title":"Hip Int","page":"63-68","volume":"24","issue":"1","source":"PubMed","abstract":"INTRODUCTION: Although prophylactic tranexamic acid (TXA) is a safe, low-cost option to reduce bleeding in patients undergoing total hip replacement (THR), its optimal dose and duration is unknown. We compared the safety and effectiveness of TXA given as either a single injection or continuous infusion in THR patients, hypothesising that a second TXA dose would not offer any clinical advantages over the single injection.\nMATERIALS AND METHODS: One hundred and sixty-four patients undergoing unilateral THR were randomised. Exclusion criteria were history of thromboembolic events (TE), epilepsy, thrombophilia, and severe chronic renal failure. Patients received either a single dose of 30 mg/kg TXA on induction of surgery (one shot [OS] group), or a loading dose of 10 mg/kg TXA followed two hours later by a continuous infusion of 2 mg/kg per hour for 20 hours (one day [OD] group). The primary outcome was blood loss (BL) calculated from haematocrit levels. Secondary outcomes were mortality and TE events within 90 days postoperatively.\nRESULTS: All patients completed treatment, with none lost to follow-up. Mean BL was 1107 ± 508 ml in Group OS and 1047 ± 442 ml in Group OD (p = 0.43). No patients were transfused prior to Day 10 postoperatively. At final follow-up, no patients had died, and there were no occurrences of major TE.\nCONCLUSION: The 30 mg/kg TXA single shot was as safe as continuous infusion. As it is also less cumbersome, we recommend it as part of routine care in THR patients.","DOI":"10.5301/hipint.5000090","ISSN":"1724-6067","note":"PMID: 24062227","shortTitle":"Single tranexamic acid dose to reduce perioperative morbidity in primary total hip replacement","journalAbbreviation":"Hip Int","language":"eng","author":[{"family":"Hourlier","given":"Hervé"},{"family":"Fennema","given":"Peter"}],"issued":{"date-parts":[["2014",2]]}}}],"schema":""} 22 201479/7985/851047 (442)1107 (508)00Barrachina ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"B3cgxoC7","properties":{"formattedCitation":"{\\rtf \\super 21\\nosupersub{}}","plainCitation":"21"},"citationItems":[{"id":157,"uris":[""],"uri":[""],"itemData":{"id":157,"type":"article-journal","title":"Tranexamic acid compared with placebo for reducing total blood loss in hip replacement surgery: a randomized clinical trial","container-title":"Anesthesia & Analgesia","page":"986-995","volume":"122","issue":"4","source":"CrossRef","DOI":"10.1213/ANE.0000000000001159","ISSN":"0003-2999","shortTitle":"Tranexamic Acid Compared with Placebo for Reducing Total Blood Loss in Hip Replacement Surgery","language":"en","author":[{"family":"Barrachina","given":"Borja"},{"family":"Lopez-Picado","given":"Amanda"},{"family":"Remon","given":"Maria"},{"family":"Fondarella","given":"Ana"},{"family":"Iriarte","given":"Ibai"},{"family":"Bastida","given":"Rebeca"},{"family":"Rodríguez-Gascón","given":"Alicia"},{"family":"Achaerandio","given":"Maria Aranzazu"},{"family":"Iturricastillo","given":"Maria Carmen"},{"family":"Aizpuru","given":"Felipe"},{"family":"Valero","given":"Cesar Augusto"},{"family":"Tobalina","given":"Ricardo"},{"family":"Hernanz","given":"Roberto"}],"issued":{"date-parts":[["2016",4]]}}}],"schema":""} 21* 201637/3835/351276 (660)1377 (689)48Current trial%201784/8483/84919 (338)888 (366)33Meta-analysis forest plot for red blood cell transfusion330201568450References ADDIN ZOTERO_BIBL {"custom":[]} CSL_BIBLIOGRAPHY 1.Johansson T, Pettersson L-G, Lisander B: Tranexamic acid in total hip arthroplasty saves blood and money: a randomized, double-blind study in 100 patients. 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Hip Int 2014; 24:63–823.Borisov DB, Yudin SV, Lebedev LA, Vardanashvili VK, Istomina NA: Choice of a tranexamic acid dose regimen during endoprosthetic replacement of joints. Messenger Anesthesiol Resusc 2011; 8:41–4 ................
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