Safety and Efficacy of Tranexamic Acid in Hip Hemiarthroplasty for Fracture Neck Femur: a Systematic Review and Meta-analysis
Tripathy SK, Varghese P, Kumarasamy AKN, Mishra NP, Neradi D, Jain M, Sarkar S, Sen RK
Indian journal of orthopaedics. 2023;57(1):33-43
PURPOSE Although numerous systematic reviews and meta-analyses have established the efficacy of tranexamic acid (TXA) in hip fracture surgeries, the included studies in those reviews have included all types of surgical interventions ranging from fixation to arthroplasty. Hip hemiarthroplasty is usually indicated in the elderly patients with femoral neck fracture and these patients have associated severe comorbidities and cognitive impairment. These subsets of patients with femoral neck fracture needs appropriate perioperative care and judicious use of antifibrinolytics. There is no meta-analysis evaluating the safety and efficacy of intravenous TXA in these patients. METHODS Searches of PubMed, Embase and Cochrane Central Register of Controlled Trials databases revealed 102 studies on TXA in hip fracture surgeries. After screening, eight studies were found to be suitable for review. The primary objective of this meta-analysis was to compare blood transfusion rate between TXA vs. control in hip hemiarthroplasty. The secondary objectives were total blood loss, postoperative haemoglobin, surgical duration, length of hospital stay and side effects (VTE, readmission and 30 days mortality). RESULTS There were one RCT, one prospective cohort study and six retrospective studies. All studies recruited the elderly patients. Intravenous (IV) TXA administration resulted in significant reduction in requirement of blood transfusion (12.7% vs. 31.9%; OR 0.28; 95% CI 0.17-0.46; p < 00,001; I (2) = 73%). The TXA group had significantly decreased total blood loss (MD - 100.31; 95% CI - 153.79, - 46.83; p < 0.0002). The postoperative Hb in the TXA group was significantly higher than the control group (MD 0.53; 95% CI 0.35, 0.71; p < 0.00001). There was no significant difference in the incidences of VTE (0.97% vs. 0.73%, OR 1.27; p = 0.81; I (2) = 64%) and readmission rate (9.2% vs. 9.64%; OR 0.79; p = 0.54), but 30-d mortality rate was significantly lower in the TXA group (3.41% vs. 6.04%; OR 0.66; p = 0.03). CONCLUSIONS Intravenous TXA is efficacious in the reduction of blood loss and transfusion need in hip hemiarthroplasty surgery for hip fracture, without increased risk of VTE. The blood conservation protocol led to decreased 30 days mortality in these fragile elderly patients. LEVEL OF EVIDENCE III.
Efficacy and safety of tranexamic acid in elderly patients with femoral neck fracture treated with hip arthroplasty: A systematic review and meta-analysis
Zhao YK, Zhang C, Zhang YW, Li RY, Xie T, Bai LY, Chen H, Rui YF
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association. 2023
BACKGROUND Elderly patients with femoral neck fracture have high perioperative blood loss according to the trauma and hip arthroplasty surgery. Tranexamic acid is a fibrinolytic inhibitor and has been widely used in hip fracture patients to against perioperative anemia. The aim of the present meta-analysis was to evaluate the efficacy and safety of Tranexamic acid (TXA) in elderly patients with femoral neck fracture undergoing hip arthroplasty. METHODS We performed search using Pubmed, EMBASE, Cochrane Reviews, and Web of Science databases to identify all relevant research studies published from inception to June 2022. Randomized controlled studies and high-quality cohort studies that reported the perioperative use of TXA in patients with femoral neck fractures treated with arthroplasty, and made a comparison with the control group were included. Meta-analysis was performed using Review Manager 5.3 to assess the efficacy and safety of TXA. Subgroup analysis was conducted to further investigate the impact caused by surgery types and administration routes on the efficacy and safety outcomes. RESULTS Five randomized controlled trials (RCTs) and eight cohort studies published from January 2015 to June 2022 were included in this meta-analysis. The results showed significant reductions in the rate of allogeneic blood transfusion, total blood loss (TBL) and postoperative hemoglobin (Hb) drop in the TXA group compared with the control group, while no significant difference was found in the intraoperative blood loss, postoperative drainage, hospital length of stay (LOS), re-admission rate, and wound complications between the two groups. The incidence of thromboembolic events and mortality showed no significant difference. Subgroup analysis indicated that surgery types and administration routes did not change the overall tendency. CONCLUSION The current evidence shows that both intravascular administration (IV) and topical administration of TXA can significantly decrease the perioperative transfusion rate and TBL without increasing the risk of thromboembolic complications in elderly patients with femoral neck fracture.
The Use of Tranexamic Acid in Hip Fracture Surgery-A Systematic Review and Meta-analysis
Agius C, Cole E, Mifsud MG, Vasireddy A
Journal of orthopaedic trauma. 2022;36(12):e442-e448
OBJECTIVES To analyze the effect of intravenous tranexamic acid (TXA) on blood transfusion requirements in adult patients undergoing hip fracture surgery. Secondary aim was to evaluate the safety by assessing thromboembolic events. DATA SOURCES Cochrane Central Register of Controlled Trials, Medline, PubMed, and Embase were searched for randomized controlled trials published in English from 2010. STUDY SELECTION Studies eligible for inclusion were randomized controlled trials that analyzed the use of intravenous TXA on blood transfusion requirement in hip fracture surgery. DATA EXTRACTION Titles and abstracts were screened and assessed for eligibility by 2 independent reviewers. Quality and risk of bias was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach and the Cochrane risk-of-bias tool (RoB2). DATA SYNTHESIS Meta-analysis with random and fixed effect models was performed. Risk ratio (RR) was calculated for dichotomous outcomes and estimated with a 95% confidence interval (CI). For continuous data, the risk difference (RD) was estimated with a 95% CI. RESULTS A total of 13 trials involving 1194 patients were included. Pooled results showed that patients in the TXA group had significantly lower transfusion requirements (RR 0.50, 95%CI 0.30-0.84, P = 0.009). Similar findings were observed in the subcohort of patients with transfusion threshold of Hb < 8g/dL, (RR 0.42, 95%CI 0.31-0.56, P < 0.0001). This risk reduction was not observed in the subcohort of patients with transfusion threshold of Hb 8.1-10g/dL who received TXA (RR 0.77, 95%CI 0.51-1.18, P = 0.23) and no statistically significant differences were found for total thromboembolic events (RR 0.01, 95%CI -0.02-0.04, P = 0.47). CONCLUSION This meta-analysis demonstrated that intravenous TXA reduced blood transfusion rates and did not increase the risk of thromboembolic events. LEVEL OF EVIDENCE Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
Arthroscopic Rotator Cuff Repair Performed with Intraarticular Tranexamic Acid. Could it Provide Improved Visual Clarity and less Postoperative Pain? A prospective, double blind, randomized study of 63 patients
Bildik C, Pehlivanoglu T
Journal of shoulder and elbow surgery. 2022
BACKGROUND Tranexamic acid (TXA) was widely used in orthopedic surgery with the aim to reduce intra-/postoperative bleeding and bleeding related complications. The aim of the present study was to assess, whether intra-articular use of TXA during arthroscopic rotator cuff tear (RCT) repair could improve the visual clarity, shorten the duration of operation and provide superior pain management as compared to placebo. METHODS This study was conducted as prospective, randomized, double-blinded and placebo controlled. Patients with MRI confirmed RCT, above the age of 18 and a history of failed conservative treatment for at least 6 months were included. Patients with a history of coagulopathy, cardiac-renal-hepatic disease and those with a history of conservative treatment less than 6 months and acute RCT were excluded. Visual clarity as the primary outcome was assessed by using arthroscopic visual scale comprising 5 grades ranging from grade 1: best visual clarity, grade 5: worst visual clarity (need to do open surgery) after the procedure by the operating surgeon every 10 minutes throughout the video of the operation. Secondary outcomes were duration of operations and postoperative pain scores. RESULTS 63 patients were enrolled and randomized into two groups with similar demographic data (age-sex-intraoperative mean arterial pressure): TXA Group comprised 32 patients with a mean age of 56.46. Placebo group comprised 31 patients with a mean age of 57.83. TXA group was reported to have significantly superior visual clarity (mean arthroscopic visual score 1.5±0.5 vs. 2.86±1.7, p=.000) with significantly higher percentage of grade 1 visual clarity (78.1% vs. 32.2%, p=.000) and lower percentage of grade 4 visual clarity (0% vs. 3.2%, p=.003). Grade 5 visual clarity was recorded in none of the patients in either group. TXA group was found to have significantly shorter duration of operation (55.73 vs. 67.26, p=.001) and superior pain scores at the 8(th) and 24(th) postoperative hour (2.3 vs 3.6 and 1.6 vs. 2.4, p=.002 and p=.000). No complications were recorded in either of the groups. CONCLUSIONS The present study concluded, that during arthroscopic rotator cuff repair procedures, intra-articular use of TXA was able to provide superior arthroscopic visual clarity, while shortening total durations of operations significantly and providing significantly superior pain-management at the first 8(th) and 24(th) postoperative hours as compared to placebo. The present study also underlined the safety and efficacy of intra-articular TXA use in arthroscopic rotator cuff repair.
Clinical trial to determine whether the timing of tranexamic acid administration influences perioperative bleeding in total knee arthroplasty
Luis C, Pardo A, Moreno CE, Teixell C, Santiveri X, Bisbe E
Revista espanola de anestesiologia y reanimacion. 2022
BACKGROUND AND OBJECTIVES The ideal timing of tranexamic acid administration in total knee arthroplasty with tourniquet remains unclear. Our primary objective was to prove if administering it before surgical incision, instead of before releasing the tourniquet, reduces postoperative bleeding. A second objective was to determine whether a second dose reduces post-operative bleeding. MATERIAL AND METHODS A prospective, double-blind clinical trial was performed on 212 patients scheduled for total knee arthroplasty. They were randomised into 4 groups. Tranexamic acid was administered before the surgical incision in "pre-induction groups" (1 and 2), and just before the tourniquet release in "pre-release groups" (3 and 4). Groups 2 and 4 received a second dose 3h post-surgery. Main outcome was postoperative bleeding (visible blood loss and calculated total bleeding). Secondary outcomes were haemoglobin variations, complications and transfusion rate. RESULTS The mean calculated total bleeding was 1563ml (95%CI: 1445-1681) in preinduction groups versus 1576ml (95%CI: 1439-1713) in pre-release groups (P=0.9); 1579ml (95%CI: 1452-1706) in single-dose groups versus 1559ml (95%CI: 1431-1686) in double-dose groups (P=0.82). One patient was transfused. The mean haemoglobin at discharge was 10.4g/dl (95%CI: 10.2-10.7) in singledose groups versus 10.8 (95%CI: 10.6-11.1) in double-dose groups (P=0.06). CONCLUSIONS There were no differences in bleeding or transfusion regarding the time of tranexamic acid administration. The second dose had not impact on outcomes. TRIAL REGISTRATION EudraCT 2016-000071-24.
Combination of Intravenous and Intra-Articular Application of Tranexamic Acid and Epsilon-Aminocaproic Acid in Primary Total Knee Arthroplasty: A Prospective Randomized Controlled Trial
Zheng C, Ma J, Xu J, Si H, Liu Y, Li M, Shen B
Orthopaedic surgery. 2022
OBJECTIVE There were limited randomized controlled trials (RCTs) of epsilon-aminocaproic acid (EACA) versus tranexamic acid (TXA) in total knee arthroplasty (TKA). The aim of the study was to compare the efficacy and safety of TXA and EACA in the combination of intravenous (IV) and intra-articular (IA) administration on reducing blood loss in patients following primary TKA. METHODS From January 2020 to January 2021, a total of 181 patients undergoing a primary unilateral TKA were enrolled in this prospective randomized controlled trial. Patients in the TXA group (n = 90) received 20 mg/kg of intravenous TXA preoperatively, 1 g of intra-articular TXA intraoperatively, and three doses of 20 mg/kg intravenous TXA at 0, 3, 6 h postoperatively. Patients in the EACA group (n = 91) received 120 mg/kg of intravenous EACA preoperatively, 2 g of intra-articular EACA intraoperatively, and three doses of 40 mg/kg intravenous EACA at 0, 3, 6 h postoperatively. The primary outcomes were total blood loss (TBL), transfusion rates and drop of hemoglobin (HB) level. The secondary outcomes included postoperative hospital stays and postoperative complications. The chi-square tests and Fisher's exact tests were utilized to compare categorical variables, while the independent-samples t-tests and Mann-Whitney tests were used to compare continuous variables. RESULTS The patients who received TXA averaged less TBL than the patients who received EACA (831.83 ml vs 1065.49 ml, P = 0.015), and HB drop in TXA group was generally less than that of EACA group on postoperative day 1 and 3 (20.84 ± 9.48 g/L vs 24.99 ± 9.40 g/L, P = 0.004; 31.28 ± 11.19 vs 35.46 ± 12.26 g/L, P = 0.047). The length of postoperative stays in EACA group was 3.66 ± 0.81 day, which is longer than 2.62 ± 0.68 day in TXA group (P < 0.001). No transfusions were required in either group. The risk of nausea and vomiting in TXA group was significantly higher than that in EACA group (11/90 vs 0/91, P < 0.01). CONCLUSION Although the TBL and HB drop were slightly greater in EACA group, these results were not clinically important, given that no transfusions were required. EACA could be an alternative to TXA, especially for patients with severe nausea and vomiting after using TXA postoperatively. Further studies are needed to adjust dosage of EACA to make better comparison of the two drugs.
The optimal regimen, efficacy and safety of tranexamic acid and aminocaproic acid to reduce bleeding for patients after total hip arthroplasty: A systematic review and Bayesian network meta-analysis
Zheng C, Ma J, Xu J, Wu L, Wu Y, Liu Y, Shen B
Thrombosis research. 2022;221:120-129
OBJECTIVES We aimed to evaluate the optimal regimen, efficacy and safety of tranexamic acid (TXA) and aminocaproic acid (EACA) for patients after total hip arthroplasty (THA). METHODS The network meta-analysis was guided by the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline. The outcomes were total blood loss, transfusion rates, hemoglobin (HB) drop, and risk for pulmonary embolism (PE) or deep vein thrombosis (DVT). Subgroup analyses were performed among most effective regimens to determine the influences of timing and number of doses. RESULTS A total of 56 eligible RCTs with different regimens were assessed. For reducing total blood loss, all high doses of TXA and EACA except high dose of intra-articular (IA) TXA, as well as medium dose of combination of intravenous and intra-articular (combined IV/IA) TXA were most effective. All high doses of TXA, as well as medium dose of combined IV/IA TXA did not show inferiority in reducing transfusion rates and HB drop compared with other regimens. No regimens showed higher risk for PE or DVT compared with placebo, and no statistical differences were seen among most effective regimens in subgroup analyses. CONCLUSIONS As effective as high doses of EACA and TXA, medium dose (20-40 mg/kg or 1.5-3.0 g) of combined IV/IA TXA was enough to control bleeding for patients after THA without increasing risk for PE/DVT. TXA was at least 5 times more potent than EACA. Timing and number of doses had few influences on blood conserving efficacy. LEVEL OF EVIDENCE Level I.
The effect of antifibrinolytic agents in periacetabular osteotomy: A systematic review and meta-analysis
Kim CH, Lim EJ, Kim S, Kim JW
Orthopaedics & traumatology, surgery & research : OTSR. 2022;108(4):103271
BACKGROUND Periacetabular osteotomy (PAO) is a major hip preservation surgery for developmental dysplasia of the hip. It is inevitably associated with significant blood loss, so it requires frequent transfusions and could be a cause of perioperative morbidity. However, to date, a large number of studies has not evaluated the effect of antifibrinolytic agents in PAO. Therefore we performed a systematic review and meta-analysis to assess if antifibrinolytics would be effective in reducing blood loss and transfusion rate after PAO surgery. METHODS In this systematic review and meta-analysis, MEDLINE, Embase, and Cochrane Library databases were systematically searched for studies published before April 4, 2020, that investigated the effect of antifibrinolytic agents in PAO. A pooled analysis was designed to identify differences between antifibrinolytic and control groups focusing on blood loss, transfusion, operation time, postoperative venous thromboembolism (VTE), and length of hospital stay. RESULTS We included five studies involving 507 patients (antifibrinolytic group: 256; control group: 251). The pooled analysis showed that the control group had a greater total estimated blood loss (EBL) than the antifibrinolytic group (mean difference [MD]=-257.60mL, 95% confidence interval [CI] -389.68 to -125.53, p=0.0001), but there were no statistical differences in intraoperative EBL (MD=-46.46mL, 95% CI: -192.57 to 99.64, p=0.53). The allogenic transfusion rate was higher in the control group than in the antifibrinolytic group (odds ratio [OR] 0.21, 95% CI: 0.10-0.43, p<0.0001), but there was no difference in the autogenic transfusion rate (OR 0.35, 95% CI: 0.09-1.43, p=0.14). The pooled result showed no difference in operation time (MD=9.13min, 95% CI: -8.54 to 26.80, p=0.31). For the VTE rate, a pooled analysis was not conducted due to the lack of data. The length of hospital stay showed no differences (MD=-0.51 days, 95% CI: -1.17 to 0.16, p=0.13). CONCLUSIONS Antifibrinolytic use in PAO has positive effects in terms of reduced total EBL and allogenic transfusion rate. LEVEL OF EVIDENCE III; meta-analysis.
The effect of tranexamic acid in open reduction and internal fixation of pelvic and acetabular fracture: A systematic review and meta-analysis
Kim CH, Hwang J, Lee SJ, Yoon PW, Yoon KS
BACKGROUND Pelvic bone fractures may cause extensive bleeding; however, the efficacy of tranexamic acid (TXA) usage in pelvic fracture surgery remains unclear. In this systematic review and meta-analysis, we aimed to evaluate the efficacy of TXA in open reduction and internal fixation surgery for pelvic and acetabular fracture. METHODS MEDLINE, Embase, and Cochrane Library databases were systematically searched for studies published before April 22, 2020, that investigated the effect of TXA in the treatment of pelvic and acetabular fracture with open reduction and internal fixation. A pooled analysis was used to identify the differences between a TXA usage group and a control group in terms of estimated blood loss (EBL), transfusion rates, and postoperative complications. RESULTS We included 6 studies involving 764 patients, comprising 293 patients who received TXA (TXA group) and 471 patients who did not (control group). The pooled analysis showed no differences in EBL between the groups (mean difference -64.67, 95% confidence interval [CI] -185.27 to -55.93, P = .29). The study period transfusion rate showed no significant difference between the groups (odds ratio [OR] 0.77, 95% CI 0.19-3.14, P = .71, I2 = 82%), nor in venous thromboembolism incidence (OR 1.53, 95% CI 0.44-5.25, P = .50, I2 = 0%) or postoperative infection rates (OR 1.15, 95% CI 0.13-9.98, P = .90, I2 = 48%). CONCLUSIONS Despite several studies having recommended TXA administration in orthopedic surgery, our study did not find TXA usage to be more effective than not using TXA in pelvic and acetabular fracture surgery, especially in terms of EBL reduction, transfusion rates, and the risk of postoperative complications.
A randomised non-inferiority trial comparing the effectiveness of oral versus intravenous tranexamic acid in primary total hip and knee arthroplasty
DeFrancesco CJ, Reichel JF, Gbaje E, Popovic M, Freeman C, Wong M, DeMeo D, Liu J, Gonzalez Della Valle A, Ranawat A, et al
British journal of anaesthesia. 2022
BACKGROUND Tranexamic acid (TXA) reduces rates of blood transfusion for total hip arthroplasty (THA) and total knee arthroplasty (TKA). Although the use of oral TXA rather than intravenous (i.v.) TXA might improve safety and reduce cost, it is not clear whether oral administration is as effective. METHODS This noninferiority trial randomly assigned consecutive patients undergoing primary THA or TKA under neuraxial anaesthesia to either one preoperative dose of oral TXA or one preoperative dose of i.v. TXA. The primary outcome was calculated blood loss on postoperative day 1. Secondary outcomes were transfusions and complications within 30 days of surgery. RESULTS Four hundred participants were randomised (200 THA and 200 TKA). The final analysis included 196 THA patients (98 oral, 98 i.v.) and 191 TKA patients (93 oral, 98 i.v.). Oral TXA was non-inferior to i.v. TXA in terms of calculated blood loss for both THA (effect size=-18.2 ml; 95% confidence interval [CI], -113 to 76.3; P<0.001) and TKA (effect size=-79.7 ml; 95% CI, -178.9 to 19.6; P<0.001). One patient in the i.v. TXA group received a postoperative transfusion. Complication rates were similar between the two groups (5/191 [2.6%] oral vs 5/196 [2.6%] i.v.; P=1.00). CONCLUSIONS Oral TXA can be administered in the preoperative setting before THA or TKA and performs similarly to i.v. TXA with respect to blood loss and transfusion rates. Switching from i.v. to oral TXA in this setting has the potential to improve patient safety and decrease costs.