1.
Is tranexamic acid clinically effective and safe to prevent blood loss in total knee arthroplasty? A meta-analysis of 34 randomized controlled trials
Wu Q, Zhang HA, Liu SL, Meng T, Zhou X, Wang P
European Journal of Orthopaedic Surgery & Traumatologie. 2015;25((3):):525-41.
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Full text
Abstract
BACKGROUND Tranexamic acid (TXA) is well established as a versatile intraarticular and intravenous (IV) antifibrinolytic agent that has been successfully used to control bleeding after total knee arthroplasty (TKA). The present meta-analysis aimed at assessing the effectiveness and safety of TXA in reducing blood loss and transfusion in TKA. METHODS We searched the PubMed, Medline, Embase, Cochrane Central Register of Controlled Trials, and Google Scholar databases from 1966 to December 2013. Only randomized controlled trials (RCTs) were included in the present study. Two independent reviewers identified the eligible studies, assessed their methodological quality, and extracted data. The data were using fixed-effects or random-effects models with standard mean differences and risk ratios for continuous and dichotomous variables, respectively. Subgroup analysis was performed according to the IV or intraarticular administration of TXA. RESULTS Thirty-four RCTs encompassing 2,594 patients met the inclusion criteria for our meta-analysis. Our meta-analysis indicated that when compared with the control group, the IV or intraarticular use of TXA significantly reduced total blood loss, postoperative blood loss, Hb loss, and transfusion rate as well as blood units transfused per patient after primary TKA, but did not reduce intraoperative blood loss. No significant difference in deep vein thrombosis (DVT), pulmonary embolism, or other adverse events among the study groups. CONCLUSIONS IV or intraarticular use of TXA for patients undergoing TKA is effective and safe for the reduction blood loss and blood transfusion requirements, yet does not increase the risk of postoperative DVT. LEVEL OF EVIDENCE Level II.
Clinical Commentary
Dr Antony Palmer, University of Oxford.
Tranexamic Acid for Reducing Blood Loss and Transfusion Rates in Total Knee Arthroplasty - commentary on 3 papers: 1) Hourlier H, Reina N, Fennema P. Single dose intravenous tranexamic acid as effective as continuous infusion in primary total knee arthroplasty: a randomised clinical trial. Archives of Orthopaedic & Trauma Surgery 2015, 135(4): 465-71; 2) Shemshaki H, Nourian SM, Nourian N, Dehghani M, Mokhtari M, Mazoochian F. One step closer to sparing total blood loss and transfusion rate in total knee arthroplasty: a meta-analysis of different methods of tranexamic acid administration. Archives of Orthopaedic & Trauma Surgery 2015, 135(4): 573-88; 3) Wu Q, Zhang HA, Liu SL, Meng T, Zhou X, Wang P. Is tranexamic acid clinically effective and safe to prevent blood loss in total knee arthroplasty? A meta-analysis of 34 randomized controlled trials. European Journal of Orthopaedic Surgery & Traumatologie 2015, 25(3): 525-41.
What is known?
Total Knee Arthroplasty (TKA) represents the mainstay of treatment for severe osteoarthritis with over 80,000 procedures performed in the UK last year. TKA gives rise to significant blood loss and tranexamic acid is proposed as a strategy for blood conservation. Tranexamic acid is a synthetic lysine analogue that competitively inhibits plasminogen activation and acts as an anti-fibrinolytic. It is increasingly used in elective surgery, supported by a number of studies that demonstrate a reduction in blood loss and transfusion rates. However, studies often reach conflicting conclusions as to the safety and efficacy of this agent. In addition, the optimal dosing strategy and route of delivery for TKA remains unknown.
What did this paper set out to examine?
These three publications include two meta-analyses of randomised controlled trials that compare tranexamic acid treatment to no treatment or placebo in patients undergoing unilateral TKA. Each meta-analysis includes data from over 30 trials. Outcomes include total blood loss, transfusion rate, and the incidence of vascular occlusive events. The authors also compare outcomes of intravenous and intraarticular tranexamic acid delivery. The third publication is a randomised controlled trial comparing the efficacy of a single intravenous bolus of tranexamic acid versus a continuous infusion in 106 patients undergoing unilateral TKA.
What did they show?
The meta-analyses conclude that tranexamic acid reduces total blood loss associated with TKA when given intravenously or intraarticularly. The effect is considered clinically relevant given there is also a reduction in blood transfusion rates (relative risk <0.5), although the authors did identity a high level of statistical heterogeneity between studies. There was no apparent increase in the risk of DVT (deep vein thrombosis) or PE (pulmonary embolism) in patients receiving tranexamic acid. When comparing intravenous and intraarticular delivery, there was no significant difference in outcomes. Results from the randomised controlled trial suggest that a single intraoperative bolus of tranexamic acid is as effective as a continuous infusion. There were no adverse events and no patient required a blood transfusion.
What are the implications for practice and for future work?
Tranexamic acid administration at the time of TKA appears safe and effective at reducing blood loss and the need for transfusion. An increasing body of evidence now supports its use in clinical practice, however, the optimal dose and route of administration remains unclear. Although outcomes do not appear to differ between intravenous and intraarticular delivery, intraarticular tranexamic acid may overcome systemic contraindications such as renal insufficiency. The finding that a single intravenous bolus is as effective as a continuous infusion warrants further investigation. Future research would benefit from a standardised protocol for tranexamic acid administration as a comparator for novel dosing regimes. Sources of heterogeneity that must be taken into consideration include surgical and anaesthetic technique, concurrent use of other pharmaceutical agents, transfusion thresholds, and the method of diagnosing adverse events. In addition, it is important that studies address patient reported outcome measures pertaining to joint function and quality of life.
2.
One step closer to sparing total blood loss and transfusion rate in total knee arthroplasty: a meta-analysis of different methods of tranexamic acid administration
Shemshaki H, Nourian SM, Nourian N, Dehghani M, Mokhtari M, Mazoochian F
Archives of Orthopaedic & Trauma Surgery. 2015;135((4):):573-88.
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-
-
Full text
Abstract
BACKGROUND Tranexamic acid (TXA) in orthopedics has recently been gaining favor due to its efficacy and ease of use, both in intravenous (IV) and intraarticular (IA) usage. However, because of safety concerns with IV administration, there has been a growing interest in the IA use of TXA to prevent bleeding. MATERIALS AND METHODS This study conducted a systematic review and meta-analysis that included 31 randomized, controlled trials in which the effect of systemic and topical TXA on total blood loss (TBL), rates of transfusion, and thromboembolic events was investigated. RESULTS Compared to the control, the IA administration of TXA led to the significant reduction of mean TBL (p < 0.001), rate of transfusion (p < 0.001), and reduction of rate of thromboembolic events (p = 0.29). Compared to the control group, the IV administration of TXA resulted in significant reduction of mean TBL (p < 0.001), rate of transfusion (p < 0.001), and rate of thromboembolic events (p = 0.66). Although no significant differences in efficacy and safety between the IA and IV administration of TXA were found, the IA method was safer than the IV method in that it reduced rate of transfusion and thromboembolic events. CONCLUSION This study showed that TXA leads to significant reductions in TBL and the rate of allogeneic transfusions. Generally, no significant difference was detected between IA and IV administration of TXA; however, more studies with focus on safety and efficacy are warranted.
Clinical Commentary
Dr Antony Palmer, University of Oxford.
Tranexamic Acid for Reducing Blood Loss and Transfusion Rates in Total Knee Arthroplasty - commentary on 3 papers: 1) Hourlier H, Reina N, Fennema P. Single dose intravenous tranexamic acid as effective as continuous infusion in primary total knee arthroplasty: a randomised clinical trial. Archives of Orthopaedic & Trauma Surgery 2015, 135(4): 465-71; 2) Shemshaki H, Nourian SM, Nourian N, Dehghani M, Mokhtari M, Mazoochian F. One step closer to sparing total blood loss and transfusion rate in total knee arthroplasty: a meta-analysis of different methods of tranexamic acid administration. Archives of Orthopaedic & Trauma Surgery 2015, 135(4): 573-88; 3) Wu Q, Zhang HA, Liu SL, Meng T, Zhou X, Wang P. Is tranexamic acid clinically effective and safe to prevent blood loss in total knee arthroplasty? A meta-analysis of 34 randomized controlled trials. European Journal of Orthopaedic Surgery & Traumatologie 2015, 25(3): 525-41.
What is known?
Total Knee Arthroplasty (TKA) represents the mainstay of treatment for severe osteoarthritis with over 80,000 procedures performed in the UK last year. TKA gives rise to significant blood loss and tranexamic acid is proposed as a strategy for blood conservation. Tranexamic acid is a synthetic lysine analogue that competitively inhibits plasminogen activation and acts as an anti-fibrinolytic. It is increasingly used in elective surgery, supported by a number of studies that demonstrate a reduction in blood loss and transfusion rates. However, studies often reach conflicting conclusions as to the safety and efficacy of this agent. In addition, the optimal dosing strategy and route of delivery for TKA remains unknown.
What did this paper set out to examine?
These three publications include two meta-analyses of randomised controlled trials that compare tranexamic acid treatment to no treatment or placebo in patients undergoing unilateral TKA. Each meta-analysis includes data from over 30 trials. Outcomes include total blood loss, transfusion rate, and the incidence of vascular occlusive events. The authors also compare outcomes of intravenous and intraarticular tranexamic acid delivery. The third publication is a randomised controlled trial comparing the efficacy of a single intravenous bolus of tranexamic acid versus a continuous infusion in 106 patients undergoing unilateral TKA.
What did they show?
The meta-analyses conclude that tranexamic acid reduces total blood loss associated with TKA when given intravenously or intraarticularly. The effect is considered clinically relevant given there is also a reduction in blood transfusion rates (relative risk <0.5), although the authors did identity a high level of statistical heterogeneity between studies. There was no apparent increase in the risk of DVT (deep vein thrombosis) or PE (pulmonary embolism) in patients receiving tranexamic acid. When comparing intravenous and intraarticular delivery, there was no significant difference in outcomes. Results from the randomised controlled trial suggest that a single intraoperative bolus of tranexamic acid is as effective as a continuous infusion. There were no adverse events and no patient required a blood transfusion.
What are the implications for practice and for future work?
Tranexamic acid administration at the time of TKA appears safe and effective at reducing blood loss and the need for transfusion. An increasing body of evidence now supports its use in clinical practice, however, the optimal dose and route of administration remains unclear. Although outcomes do not appear to differ between intravenous and intraarticular delivery, intraarticular tranexamic acid may overcome systemic contraindications such as renal insufficiency. The finding that a single intravenous bolus is as effective as a continuous infusion warrants further investigation. Future research would benefit from a standardised protocol for tranexamic acid administration as a comparator for novel dosing regimes. Sources of heterogeneity that must be taken into consideration include surgical and anaesthetic technique, concurrent use of other pharmaceutical agents, transfusion thresholds, and the method of diagnosing adverse events. In addition, it is important that studies address patient reported outcome measures pertaining to joint function and quality of life.