***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: In this prospect i ve , r and omized , double-blind study , we have investigated the effect of an antifibrinolytic agent , tranexamic acid ( Cyklokapron ) , on  blood loss and transfusion requirements associated with total knee arthroplasty . Twenty-nine patients were allocated r and omly to receive either tranexamic acid 15 mg kg-1 or an equal volume of placebo a few minutes before a tourniquet was deflated . Blood loss during surgery , in the recovery room and on the surgical ward was recorded , together with the number of units of blood transfused in hospital . Mean blood loss during surgery was 428 ( SD 254 ) ml in the tranexamic acid group ( n = 15 ) compared with 415 ( 244 ) ml in the placebo group ( n = 13 ) . In the recovery room the tranexamic acid group lost 127 ( 95 ) ml and the placebo group 576 ( 245 ) ml ( P < 0.001 ) . On the ward the respective volumes were 293 ( 200 ) ml and 558 ( 293 ) ml ( P < 0.01 ) . Total blood loss was 847 ( 356 ) ml in the tranexamic acid group and 1549 ( 574 ) ml in the placebo group ( P < 0.001 ) . During the hospital stay the treatment group received 1.5 ( 1.3 ) units of blood compared with 3.3 ( 1.8 ) in the control group ( P < 0.005 ) . Two patients in the placebo group experienced a thrombotic complication compared with none in the treatment group . We conclude that tranexamic acid reduced perioperative blood loss and transfusion requirements associated with total knee arthroplasty BACKGROUND Abundant literature regarding the use of intravenous tranexamic acid ( TXA ) in primary total knee replacement is available . R and omized controlled trials have confirmed the efficacy of topical TXA compared with placebo , but the comparison between topical and intravenous TXA is unclear . The present study was design ed to verify noninferior efficacy and safety of topical intra-articular TXA compared with intravenous TXA in primary total knee replacement with cemented implants . METHODS A Phase-III , single-center , double-blind , r and omized , controlled clinical trial was performed to compare topical intra-articular TXA ( 3 g of TXA in 100 mL of physiological saline solution ) with two intravenous doses of TXA ( 15 mg/kg in 100 mL of physiological saline solution , one dose before tourniquet release and another three hours after surgery ) in a multimodal protocol for blood loss prevention . The primary outcome was the blood transfusion rate , and the secondary outcomes included visible blood loss ( as measured in the drain ) at twenty-four hours postoperatively and invisible blood loss ( as estimated from the Nadler formula ) at forty-eight hours postoperatively . The sample size of seventy-eight patients was calculated to give a statistical power of 99 % for demonstrating noninferiority . Thirty-nine patients each were allocated to receive topical intra-articular TXA ( the experimental group ) and intravenous TXA ( the control group ) ; there were no significant differences in demographics or preoperative laboratory values between the groups . Noninferiority was estimated by comparing the confidence intervals with a delta of 10 % . Student t and Mann-Whitney tests were used to assess the significance of any differences . RESULTS The transfusion rate was zero in both groups ; thus , noninferiority was demonstrated for the primary efficacy end point , suggesting equivalence . Noninferiority was also demonstrated for the secondary efficacy end points . Drain blood loss at twenty-four hours was 315.6 mL ( 95 % confidence interval [ CI ] , 248.5 to 382.7 mL ) in the experimental group and 308.1 mL ( 95 % CI , 247.6 to 368.5 mL ) in the control group ( p = 0.948 , Mann-Whitney ) . Also , estimated blood loss at forty-eight hours was 1259.0 mL ( 95 % CI , 1115.6 to 1402.3 mL ) in the experimental group and 1317.9 mL ( 95 % CI , 1175.4 to 1460.4 mL ) in the control group ( p = 0.837 , Mann-Whitney ) . No significant safety differences were seen between groups . CONCLUSIONS Topical administration of TXA according to the described protocol demonstrated noninferiority compared with intravenous TXA , with no safety concerns . This r and omized controlled trial supports the topical intra-articular administration of TXA in primary total knee replacement with cemented implants . LEVEL OF EVIDENCE Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence The ideal method of providing tranexamic acid ( TXA ) for decreasing hemoglobin drop after TKA is still controversial . In this clinical trial , 200 patients were r and omly allocated to four groups . In group 1,500 mg TXA was administered intravenously . In group 2 , the joint irrigated with 3 g of TXA in 100 cc of saline . In group 3 , 1.5 g of TXA was injected through the drain . Group 4 did not take TXA . Albeit all methods had a statistical effect on hemoglobin drop , drainage and number of transfused units when compared to controls , but intravenous injection of TXA seems to be much more effective in terms of reducing hemoglobin drop and transfused units ; and what 's more TXA injection by drain is more effective regarding to reducing postoperative drainage Purpose The surgical stress of total knee arthroplasty ( TKA ) procedure and the application of intra-operative pneumatic thigh tourniquet increases local fibrinolytic activity , which contributes significantly to post-operative blood loss .  Tranexamic acid , an antifibrinolytic drug , is commonly used to control post-operative blood loss . The recommended mode of administration of tranexamic acid is either oral or intravenous . However , the mechanism of action of the tranexamic acid points towards the possible effectiveness it may have following local/intra-articular application . This prospect i ve , double-blinded , r and omized preliminary study evaluated the efficacy of intra-articular tranexamic acid in reducing TKA-associated post-operative blood loss . Methods Fifty consenting patients with osteoarthritis of the knee scheduled for primary unilateral cemented-TKA were r and omly allocated to one of the two groups : Tranexamic Acid ( TA ) group ( n = 25 , 500 mg/5 ml tranexamic acid ) and the control group ( n = 25 , 5 ml 0.9 % saline ) . The drug and control solution were administered intra-articularly through the drain tube immediately after the wound closure . Parameters related to blood loss ( drop in haemoglobin , haematocrit differential ) and the drain output [ volume ( ml ) ] were compared between the two groups . Results On a comparative basis , TA-group obtained significant reduction in the drain output [ 95 % CI : 360.41–539.59 , p < 0.001 ] at 48 h post-operatively . Even though the control group received sixfold more blood transfusion than TA-group , it showed a greater drop in haemoglobin and haematocrit ( p < 0.05 ) . Conclusions Local application of tranexamic acid seems to be effective in reducing post-TKA blood loss as well as blood transfusion requirements . Level of evidence Therapeutic study , Level II Background The antifibrinolytic tranexamic acid reduces surgical blood loss , but studies have not identified an optimal regimen . Questions / purpose sWe studied different dosages , timings , and modes of administration to identify the most effective regimen of tranexamic acid in achieving maximum reduction of blood loss in TKA . Methods We prospect ively studied five regimens ( four intravenous , one local ; 40 patients each ) with a control group ( no tranexamic acid ) . The four intravenous ( 10-mg/kg dose ) regimens included ( 1 ) intraoperative dose ( IO ) given before tourniquet deflation , ( 2 ) additional preoperative dose ( POIO ) , ( 3 ) additional postoperative dose ( IOPO ) , and ( 4 ) all three doses ( POIOPO ) . The fifth regimen was a single local application ( LA ) . Two independent parameters of drain loss and total blood loss , calculated by the hemoglobin balance method , were evaluated statistically . Results Both parameters were reduced in all five regimens as against the control . A significant reduction in drain loss was seen in the POIO , IOPO , and POIOPO groups whereas total blood loss was significantly reduced in the POIO , POIOPO , and LA groups . The POIOPO group had the least drain loss ( 303 mL ) and least total blood loss ( 688 mL ) . The IO group had the greatest drain loss and the IOPO group the greatest total blood loss . Conclusions Single-dose tranexamic acid did not give effective results . The two-dose regimen of POIO was the least amount necessary for effective results . When compared against the control , this regimen produced reduction of drain loss and total blood loss , whereas the IOPO regimen did not . The three-dose regimen of POIOPO produced maximum effective reduction of drain loss and total blood loss . Level of Evidence Level I , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence Introduction Tranexamic acid ( TXA ) is becoming widely used in orthopedic surgery to reduce blood loss and transfusion requirements , but consensus is lacking regarding the optimal route and dose of administration . The aim of this study was to compare the efficacy and safety of topical and intravenous routes of TXA with routine hemostasis in patients undergoing primary total knee arthroplasty ( TKA ) . Material s and methods We performed a r and omized , multicenter , parallel , open-label clinical trial in adult patients undergoing primary TKA . Patients were divided into three groups of 50 patients each : Group 1 received 1 g topical TXA , Group 2 received 2 g intravenous TXA , and Group 3 ( control group ) had routine hemostasis . The primary outcome was total blood loss . Secondary outcomes were hidden blood loss , blood collected in drains , transfusion rate , number of blood units transfused , adverse events , and mortality . Results One hundred and fifty patients were included .  Total blood loss was 1021.57 ( 481.09 ) mL in Group 1 , 817.54 ( 324.82 ) mL in Group 2 and 1415.72 ( 595.11 ) mL in Group 3 ( control group ) . Differences in total blood loss between the TXA groups and the control group were clinical ly and statistically significant ( p < 0.001 ) . In an exploratory analysis differences between the two TXA groups were not statistically significant ( p = 0.073 ) Seventeen patients were transfused . Transfusion requirements were significantly higher in Group 3 ( p = 0.005 ) . No significant differences were found between groups regarding adverse events . Conclusion We found that 1 g of topical TXA and 2 g of intravenous TXA were both safe strategies and more effective than routine hemostasis to reduce blood loss and transfusion requirements after primary TKA.Level of evidence Purpose This study was undertaken to determine the efficacy of reinflation of the tourniquet after its early release in TKA compared to early release alone , in terms of surgical field visualization and operative time . We also question ed whether tourniquet reinflation after its early release is safe , with respect to post-operative blood loss , post-operative pain and other tourniquet-related complications . Methods Two hundred and six patients undergoing TKA were r and omly allocated to either the early release ( deflation ) group ( n = 105 ) or reinflation after early release ( reinflation ) group ( n = 101 ) . Efficacy was measured in terms of surgical field visualization , specifically the number of wound clearances , and operative time . Safety outcomes were drained volume , decline in haemoglobin on post-operative days 2 and 5 , the frequency of transfusion , knee and thigh pain visual analog scale , local wound complications , tourniquet site complications and other complications , including infection , deep vein thrombosis and pulmonary embolism . Results Surgical field visualization was better in the reinflation group ; however , the operative time did not differ between the two groups . There were no differences between the two groups in post-operative blood loss , decline in haemoglobin on days 2 and 5 , transfusion rate , pain level , local complications and other complications . Conclusion Reinflation of tourniquet is a safe alternative to its early release after deflation in that it improves surgical field visualization during TKA.Level of evidence Therapeutic study , Level In total knee arthroplasty ( TKA ) the total blood loss is composed of ' visible ' blood loss from the surgical field and wound drainage , and blood loss into the tissues which is hidden . Blood management should be aim ed at addressing the total blood loss . The measured loss is generally an underestimation of the ' true ' loss , which can be calculated . Sixty-three TKAs were prospect ively studied at the Avon Orthopaedic Centre , Bristol , UK . All but two TKAs were performed under a tourniquet . Thus the intraoperative blood loss was usually zero . 
    Output:
    
Conclusions Compared with intravenous administration TXA , topical administration TXA exhibits comparable effectiveness and safety in terms of reducing blood loss during TKA .