Inconclusive evidence for the efficacy of tranexamic acid in reducing transfusions, postoperative infection or hematoma formation after primary shoulder arthroplasty: A meta-analysis with trial sequential analysis
Shoulder & elbow. 2021;13(1):38-50
BACKGROUND Tranexamic acid efficacy on clinically relevant adverse outcomes in patients undergoing shoulder arthroplasty has been contradictory. The aim of this review was to analyze whether tranexamic acid administration could decrease transfusions, infection and hematoma formation in patients undergoing shoulder arthroplasty. METHODS PubMed, EMBASE, and the Cochrane Library were searched up to May 2019 for randomized controlled trials comparing tranexamic acid to placebo in shoulder arthroplasty. Random-effect models were performed to meta-analyze the evidence. Trial sequential analysis was used to calculate and to establish the conclusiveness of the evidence derived from the meta-analysis. RESULTS Four randomized controlled trials comprising 375 patients were included. Meta-analysis showed no effect of tranexamic acid on transfusion rate (RR = 0.48 (adjusted 95% CI 0.05 to 3.85)). The possible effect of tranexamic acid on hematoma formation or infection rates after shoulder arthroplasty is non-estimable with the current evidence. The sample size necessary to reliably determine if tranexamic acid decreases transfusions, infection rates and hematoma formation is not available from the current literature as determined by the trial sequential analysis. DISCUSSION While tranexamic acid has proven its efficacy in decreasing blood loss in shoulder arthroplasty, this meta-analysis of randomized controlled trials clarifies that there is currently no conclusive evidence for a positive effect of tranexamic acid upon transfusion rate, infection rates or hematoma formation in patients undergoing primary shoulder arthroplasty.
Complications of Tranexamic Acid in Orthopedic Lower Limb Surgery: A Meta-Analysis of Randomized Controlled Trials
BioMed research international. 2021;2021:6961540
OBJECTIVE Tranexamic acid (TXA) is increasingly used in orthopedic surgery to reduce blood loss; however, there are concerns about the risk of venous thromboembolic (VTE) complications. The aim of this study was to evaluate TXA safety in patients undergoing lower limb orthopedic surgical procedures. DESIGN A meta-analysis was performed on the PubMed, Web of Science, and Cochrane Library databases in January 2020 using the following string (Tranexamic acid) AND ((knee) OR (hip) OR (ankle) OR (lower limb)) to identify RCTs about TXA use in patients undergoing every kind of lower limb surgical orthopedic procedures, with IV, IA, or oral administration, and compared with a control arm to quantify the VTE complication rates. RESULTS A total of 140 articles documenting 9,067 patients receiving TXA were identified. Specifically, 82 studies focused on TKA, 41 on THA, and 17 on other surgeries, including anterior cruciate ligament reconstruction, intertrochanteric fractures, and meniscectomies. The intravenous TXA administration protocol was studied in 111 articles, the intra-articular in 45, and the oral one in 7 articles. No differences in terms of thromboembolic complications were detected between the TXA and control groups neither in the overall population (2.4% and 2.8%, respectively) nor in any subgroup based on the surgical procedure and TXA administration route. CONCLUSIONS There is an increasing interest in TXA use, which has been recently broadened from the most common joint replacement procedures to the other types of surgeries. Overall, TXA did not increase the risk of VTE complications, regardless of the administration route, thus supporting the safety of using TXA for lower limb orthopedic surgical procedures.
Use of tranexamic acid does not influence perioperative outcomes in ambulatory foot and ankle surgery-a prospective triple blinded randomized controlled trial
International orthopaedics. 2021
STUDY OBJECTIVE TXA is an antifibrinolytic medication widely used to reduce perioperative blood loss, but it has been seldom used during foot and ankle surgery. Our study evaluates the impact of TXA use on blood loss, post-operative pain, peri-operative opioid consumption, and wound healing in ambulatory outpatient foot and ankle procedures. DESIGN Prospective, triple-blinded, randomized controlled trial. SETTING Peri-operative environment of a major academic health centre in New York City. PATIENTS A total of 100 participants who were scheduled for ambulatory foot and ankle surgery with a single surgeon. INTERVENTIONS Patients receive either 10 mg/kg TXA (TXA group) or 10 ml/kg of normal saline (placebo group) intravenously prior to skin incision. MEASUREMENTS Primary outcome was intra-operative blood loss. Secondary outcomes were peri-operative opioid consumption and wound complications between post-operative days 14 and 21. MAIN RESULTS We found no difference between TXA and placebo groups in terms of intra-operative blood loss, p value 0.71, 95% CI (63.13-19.80). There was no difference between the two groups in terms of post-operative morphine milliequivalents (MME). The incidence of wound complications was 16.3% in the TXA group compared to 15.7% in the placebo group with OR 1.04, p value 0.93, 95% CI (0.32-2.77). No adverse events associated with TXA were reported. CONCLUSIONS The use of TXA during foot and ankle surgery was not associated with any benefits in perioperative outcomes in our outpatient ambulatory surgical population. Considering potential risks, we do not support the routine use of TXA in this surgical model.
Effects of Local Administration of Tranexamic Acid on Reducing Postoperative Blood Loss in Surgeries for Closed, Sanders III-IV Calcaneal Fractures: A Randomized Controlled Study
Indian journal of orthopaedics. 2021;55(Suppl 2):418-425
PURPOSE To investigate whether local administration of tranexamic acid (TXA) is effective in postoperative blood loss reduction in surgeries for Sanders III-IV calcaneal fractures. METHODS Calcaneal fracture patients who were hospitalized in our hospital from August 2014 to April 2018 and underwent open reduction internal fixation (ORIF) via lateral approach with an L-shaped incision were included in the present study. 53 Patients were randomly divided into three groups, groups A (17), B (17) and C (19). Twenty milliliters of 10 mg/ml and 20 mg/ml TXA solution were perfused into the incision of patients in group A and group B, respectively. Twenty milliliters of saline were perfused into the incision of patients in group C as control. The volume of postoperative drainage, postoperative blood test, coagulation test, and wound complications were analyzed to evaluate the effectiveness of local administration of TXA on blood loss reduction. RESULTS The amount of drainage at 24 and 48 h after the procedure was 110 ± 170, 30 ± 10 ml and 130 ± 160, 20 ± 17 ml for patients in group A and group B, respectively. The corresponding numbers for patients in group C were 360 ± 320, 20 ± 10 ml. The difference between group A and group C was statistically significant, so was the difference between group B and group C. No statistically significant difference was found between group A and group B. Postoperative blood test results revealed that the levels of hemoglobin and hematocrit were significantly higher in group A and group B when each compared to that of group C. In contrast, no difference was found between group A and group B. No significant difference was found between each experimental group and the control group in terms of platelet counts, prothrombin time (P.T.), activated partial prothrombin time (APTT), and wound complications. CONCLUSION Local administration of TXA is effective in the reduction of postoperative blood loss in surgeries for Sanders III-IV types of calcaneal fractures without notably associated side effects.
Oral tranexamic acid for an additional 24 hours postoperatively versus a single preoperative intravenous dose for reducing blood loss in total knee arthroplasty: results of a randomized controlled trial (TRAC-24)
The bone & joint journal. 2021;103-b(10):1595-1603
AIMS: In total knee arthroplasty (TKA), blood loss continues internally after surgery is complete. Typically, the total loss over 48 postoperative hours can be around 1,300 ml, with most occurring within the first 24 hours. We hypothesize that the full potential of tranexamic acid (TXA) to decrease TKA blood loss has not yet been harnessed because it is rarely used beyond the intraoperative period, and is usually withheld from 'high-risk' patients with a history of thromboembolic, cardiovascular, or cerebrovascular disease, a patient group who would benefit greatly from a reduced blood loss. METHODS TRAC-24 was a prospective, phase IV, single-centre, open label, parallel group, randomized controlled trial on patients undergoing TKA, including those labelled as high-risk. The primary outcome was indirect calculated blood loss (IBL) at 48 hours. Group 1 received 1 g intravenous (IV) TXA at the time of surgery and an additional 24-hour postoperative oral regime of four 1 g doses, while Group 2 only received the intraoperative dose and Group 3 did not receive any TXA. RESULTS Between July 2016 and July 2018, 552 patients were randomized to either Group 1 (n = 241), Group 2 (n = 243), or Group 3 (n = 68), and 551 were included in the final analysis. The blood loss did differ significantly between the two intervention groups (733.5 ml (SD 384.0) for Group 1 and 859.2 ml (SD 363.6 ml) for Group 2; mean difference -125.8 ml (95% confidence interval -194.0 to -57.5; p < 0.001). No differences in mortality or thromboembolic events were observed in any group. CONCLUSION These data support the hypothesis that in TKA, a TXA regime consisting of IV 1 g perioperatively and four oral 1 g doses over 24 hours postoperatively significantly reduces blood loss beyond that achieved with a single IV 1 g perioperative dose alone. TXA appears safe in patients with history of thromboembolic, cardiovascular, and cerebrovascular disease. Cite this article: Bone Joint J 2021;103-B(10):1595-1603.
Efficacy and Systemic Absorption of Peri-articular Versus Intra-articular Administration of Tranexamic Acid in Total Knee Arthroplasty: A Prospective Randomized Controlled Trial
Arthroplasty today. 2021;11:1-5
BACKGROUND Tranexamic acid (TXA) is widely accepted as an effective method for reducing blood loss after total knee arthroplasty (TKA). As different routes of local TXA administration have been proposed to minimize systemic complications, we aimed to investigate the effectiveness and systemic absorption of peri-articular (PA) and intra-articular (IA) administration of TXA after primary TKA. METHODS In a randomized controlled trial of patients scheduled for unilateral primary TKA, 108 were assigned to receive PA-TXA (15 mg/kg), IA-TXA (2 g), or no TXA injection. We assessed total blood loss, blood transfusion rate, and hemoglobin level changes 48 hours after surgery. Postoperative serum TXA levels, complications, and clinical symptoms of venous thromboembolism events were also evaluated. RESULTS Total blood loss, hemoglobin level decreases, and blood transfusion rates in both TXA groups were significantly lower than those in the control group (P < .05), without significant differences between PA and IA groups 48 hours after surgery. Serum TXA levels in the IA group were significantly higher than those in the PA cohort at 2 hours (28.2 mg/L vs 15.6 mg/L, P < .01) and 24 hours (4.4 mg/L vs 1.7 mg/L, P < .01) postoperatively. No wound complications were found in both TXA groups, but 14% of the control group developed subcutaneous ecchymoses. No evidence of venous thromboembolism events was reported. CONCLUSIONS PA-TXA is an excellent alternative route of local TXA injection to decrease postoperative blood loss after TKA. PA-TXA demonstrated lower levels of postoperative serum TXA, which may be beneficial for high-risk patients.
Oral tranexamic acid for an additional 24 hours postoperatively versus a single preoperative intravenous dose for reducing blood loss in total hip arthroplasty: results of a randomized controlled trial (TRAC-24)
The bone & joint journal. 2021;103-b(7):1197-1205
AIMS: A typical pattern of blood loss associated with total hip arthroplasty (THA) is 200 ml intraoperatively and 1.3 l in the first 48 postoperative hours. Tranexamic acid (TXA) is most commonly given as a single preoperative dose only and is often withheld from patients with a history of thromboembolic disease as they are perceived to be "high-risk" with respect to postoperative venous thromboembolism (VTE). The TRanexamic ACid for 24 hours trial (TRAC-24) aimed to identify if an additional 24-hour postoperative TXA regime could further reduce blood loss beyond a once-only dose at the time of surgery, without excluding these high-risk patients. METHODS TRAC-24 was a prospective, phase IV, single centre, open label, parallel group, randomized controlled trial (RCT) involving patients undergoing primary unilateral elective THA. The primary outcome measure was the indirect calculated blood loss (IBL) at 48 hours. The patients were randomized into three groups. Group 1 received 1 g intravenous (IV) TXA at the time of surgery and an additional oral regime for 24 hours postoperatively, group 2 only received the intraoperative dose, and group 3 did not receive any TXA. RESULTS A total of 534 patients were randomized, with 233 in group 1, 235 in group 2, and 66 in group 3; 92 patients (17.2%) were considered high-risk. The mean IBL did not differ significantly between the two intervention groups (848.4 ml (SD 463.8) for group 1, and 843.7 ml (SD 478.7) for group 2; mean difference -4.7 ml (95% confidence interval -82.9 to 92.3); p = 0.916). No differences in mortality or incidence of VTE were observed between any group. CONCLUSION The addition of oral TXA for 24 hours postoperatively does not reduce blood loss beyond that achieved with a single 1 g IV perioperative dose alone. There may be a clinically relevant difference in patients with a normal BMI, which warrants further investigation. Critically, there were no safety issues in patients with a history of thromboembolic, cardiovascular, or cerebrovascular disease. Cite this article: Bone Joint J 2021;103-B(7):1197-1205.
Patients undergoing total hip arthroplasty enrolled in the TRAC-24 trial (n= 534).
Intravenous tranexamic acid at the time of surgery and an additional oral regime postoperatively (Group 1, n= 233); intraoperative dose alone (Group 2, n= 235).
Did not receive TXA (n= 66).
92 patients (17.2%) were considered high-risk. The mean indirect calculated blood loss did not differ significantly between the two intervention groups (848.4 ml (SD 463.8) for group 1, and 843.7 ml (SD 478.7) for group 2; mean difference -4.7 ml. No differences in mortality or incidence of venous thromboembolism were observed between any group.
Tranexamic acid attenuates early post-operative systemic inflammatory response and nutritional loss and avoids reduction of fibrinogen in total hip arthroplasty within an enhanced recovery after surgery pathway
International orthopaedics. 2021
PURPOSE Total hip arthroplasty (THA) is an intervention with significant inflammatory response. The impact of additional doses of tranexamic acid (TXA) on inflammatory response, trauma and nutrition parameters, and coagulation and fibrinolysis changes has rarely been reported. METHODS A prospective double-blind randomized trial was performed on elective primary THA. Ninety-nine adult patients were recruited consecutively from 2019 to 2020. They were randomized to receive single-dose of TXA before incision, another dose of TXA at three hours post-operatively, or another two doses of TXA at three and six hours post-operatively. The primary outcomes included changes in white blood cell (WBC) counts, creatine kinase (CK), haemoglobin(Hb), and albumin(Alb); the secondary outcomes included coagulation and fibrinolysis parameters. RESULTS Compared with single-dose TXA, patients received three dose TXA had significantly reduced WBC counts and fibrinogen/fibrin degradation product (FDP) levels, increased albumin and fibrinogen levels, and prolonged PT on post-operative day (POD) three. Though patients received three dose TXA had a tendency that increased Hb, decreased CK, reduced D-D, and prolonged APTT on POD3, it is not statistically significant. And the other measured outcomes on POD1 and POD2W shared a similar statistical result, except PT. The PT is significantly prolonged on POD2W in three dose group compared with single dose. CONCLUSION Three-dose TXA contribute to attenuate early post-operative systemic inflammatory response and nutritional loss, increase fibrinogen, reduce FDP levels, and prolong PT in THA patients within an ERAS pathway, which may associate with reduced early post-operative haemorrhagic tendency, thrombosis risks, and hypercoagulability.
Tranexamic Acid in Shoulder Arthroplasty. A Comprehensive Review
Objectives: Total shoulder arthroplasty (TSA) represents a major orthopedic procedure with significant blood loss and transfusion rates up to 43%. Tranexamic acid (TXA), a synthetic amino acid derivative, functioning by inhibiting the conversion of plasminogen to plasmin, has been proven to reduce blood loss in total knee or hip arthroplasty. However, very few studies exist regarding shoulder arthroplasty. The aim of the present review is to evaluate its effectiveness in shoulder arthroplasty. Materials and methods: A meticulous electronic search was performed to find articles reporting the results of TXA administration in TSA or reverse total shoulder arthroplasty (RTSA). Patients' demographics, dose and timing of TXA administration, the type of control group, mean hemoglobin reduction, transfusion rate and total blood loss were evaluated. A total of eight studies including 981 patients were identified. Five hundred and thirty patients (group 1) received TXA, while the remaining 451 comprised the control group (group 2). Results:The mean postoperative reduction in hemoglobin in group 1 was found to be 2.14 g/dL (SD=0.62), compared to 2.71 g/dL (SD=0.57) of group 2; p-value <0.0001. Transfusion rate in group 1 was found to be 1.9%, compared to 4.9% in group 2; p-value=0.009. Total blood loss was found to be 714.6 mL (SD=410.4) in group 1, compared to 911.8 mL (SD=529.7) in group 2; p-value <0.0001. Conclusion:The present review has shown that TXA administration in shoulder arthroplasty has effectively reduced blood loss, postoperative hemoglobin decline and need for transfusion. More research is needed, since optimization of route, timing and dosage of TXA remain to be determined.
Clinical Effectiveness of Intraoperative Tranexamic Acid Use in Shoulder Surgery: A Systematic Review and Meta-analysis
The American journal of sports medicine. 2021;:363546520981679
BACKGROUND Tranexamic acid (TXA) is widely used across surgical specialties to reduce perioperative bleeding. It has been shown to be effective in spinal surgery and lower limb arthroplasty. Among all languages, there are no systematic reviews or meta-analyses investigating its clinical effectiveness for all types of shoulder surgery. PURPOSE To investigate the clinical effectiveness of TXA in all types of shoulder surgery, including open and arthroscopic procedures. To investigate the effect of TXA on bleeding and non-bleeding-related outcomes. STUDY DESIGN Systematic review and meta-analysis. METHODS A protocol for the study was designed and registered with PROSPERO (CRD42020185482). The literature search included the MEDLINE, Embase, PsycINFO, and Cochrane Library databases. All randomized controlled trials evaluating the use of TXA against placebo, in all types of shoulder surgery, were included. Assessments were undertaken for risk of bias and certainty of evidence. The primary outcome was total blood loss. Secondary outcomes included those not directly related to bleeding. Data from comparable outcomes were pooled and analyzed quantitatively or descriptively, as appropriate. RESULTS Eight randomized controlled trials were included in the systematic review, and data from 7 of these studies were pooled in the meta-analysis. Pooled analysis demonstrated a significant reduction in 2 of 3 outcomes measuring perioperative bleeding with TXA compared with controls: estimated total blood loss (mean difference, -209.66 mL; 95% CI, -389.11 to -30.21; P = .02) and postoperative blood loss as measured by drain output (mean difference, -84.8 mL; 95% CI, -140.04 to -29.56; P = .003). Hemoglobin reduction was reduced but not statistically significant (mean difference, -0.33 g/dL; 95% CI -0.69 to 0.03; P = .07). This result became significant with sensitivity analysis excluding arthroscopic procedures. CONCLUSION This systematic review and meta-analysis indicated that TXA was effective in reducing blood loss in shoulder surgery. Larger randomized controlled trials with low risk of bias for specific surgical shoulder procedures are required. CLINICAL RELEVANCE TXA can be used across shoulder surgery to reduced perioperative blood loss. The use of TXA may have other beneficial features, including reduced postoperative pain and reduced operative time.