The effect of tranexamic acid on myocardial injury in cardiac surgical patients: a systematic review and meta-analysis
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. 2022
Tranexamic acid (TXA) is one of the most commonly used antifibrinolytic agents for surgical patients. However, the effect of TXA on myocardial injury remains controversial. We systemically reviewed literature regarding the effectiveness of TXA on myocardial injury in patients who have undergone a cardiac surgery. We included all randomized controlled trials (RCTs) comparing TXA and control (saline) in cardiac surgical patients. Relevant studies were identified by a comprehensive electronic literature search from database inception to 15 August 2021. A standardized data extraction form was used to collect methodological and outcome variables from each eligible study. We conducted a meta-analysis to estimate the pooled effect size of TXA administration on myocardial injury. In total, eight RCTs were identified, with 292 patients in the TXA group, and 241 patients in saline or control group. The meta-analysis demonstrated that patients in the TXA group had lower levels of CK-MB and cTnI within 24 h postoperatively (CK-MB: P = 0.005; cTnI: P = 0.01), compared with the saline group. No significant difference was found with respect to AST level (P = 0.71) between TXA and saline groups within 24 h postoperatively. TXA administration was found to be associated with less myocardial injury among patients who have undergone cardiac surgery. High-quality randomized controlled trials are warranted to further examine the cardioprotective effects of TXA.
Tranexamic acid reduces postoperative blood loss in Chinese pediatric patients undergoing cardiac surgery: A PRISMA-compliant systematic review and meta-analysis
BACKGROUND Tranexamic acid has been increasingly used for blood conservation in cardiac surgery. However, the evidence supporting the routine use of tranexamic acid in Chinese pediatric patients undergoing cardiac surgery remains weak. This meta-analysis aimed to systematically review the efficacy of tranexamic acid when applying to Chinese pediatric patients undergoing cardiac surgery. PARTICIPANTS Chinese pediatric patients undergoing cardiac surgery. INTERVENTIONS Tranexamic acid or control drugs (saline/blank). METHODS PUBMED, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP Data till May 4, 2021, database search was updated on August 1. Primary outcomes of interest included postoperative bleeding, allogeneic transfusion, and reoperation for bleeding. Secondary outcomes of interest included postoperative recovery. For continuous/dichotomous variables, treatment effects were calculated as weighted mean difference (WMD)/odds ratio and 95% confidence interval. RESULTS A database search yielded 15 randomized controlled trials including 1641 patients, where 8 studies were allocated into non-cyanotic congenital group, 5 were allocated into cyanotic congenital group, and the other 2 were allocated into combined cyanotic/non-cyanotic group. This meta-analysis demonstrate that tranexamic acid administration can reduce the postoperative 24 hours blood loss in non-cyanotic, cyanotic, and combined cyanotic/non-cyanotic patients, the red blood cell transfusion in non-cyanotic and cyanotic patients, and the fresh frozen plasma transfusion in non-cyanotic and combined cyanotic/non-cyanotic patients. CONCLUSION This meta-analysis demonstrates that tranexamic acid is highly effective in reducing the blood loss in Chinese pediatric cardiac surgery, but it behaves poorly when it comes to the transfusion requirement. To further confirm this, more well-designed and adequately-powered randomized trials are needed.
Prophylactic Use of Antifibrinolytics During Pediatric Cardiac Surgery With Cardiopulmonary Bypass on Postoperative Bleeding and Transfusion: A Systematic Review and Meta-Analysis
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2022
OBJECTIVES To determine the effect of intraoperative antifibrinolytics, including tranexamic acid (TXA), aminocaproic acid (EACA), or aprotinin, on bleeding in children undergoing cardiac surgery with cardiopulmonary bypass (CPB). DATA SOURCES Relevant articles were systematically searched from Ovid MEDLINE, Ovid EMBASE, CINAHL, Cochrane Library, and Web of Science to November 15, 2021. STUDY SELECTION Abstracts were screened, and full texts were reviewed using predetermined inclusion and exclusion criteria using the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. DATA EXTRACTION A standardized data extraction tool was used. DATA SYNTHESIS Sixty-eight studies including 28,735 patients were analyzed. TXA compared with placebo resulted in a mean decrease in chest tube output of 9.1 mL/kg (95% CI, 6.0-12.3 mL/kg), I2 equals to 65.2%, p value of less than 0.001, platelet requirement of 2.9 mL/kg (95% CI, 0.1-5.8 mL/kg), I2=72.5%, p value less than 0.001 and plasma requirement of 4.0 mL/kg (95% CI, 0.6-7.2 mL/kg), I2 equals to 94.5%, p value less than0.001. Aprotinin compared with placebo resulted in a mean decrease in chest tube output of 4.3 mL/kg (2.4-6.2 mL/kg), I2 equals to 66.3%, p value of less than 0.001, platelet transfusion of 4.6 mL/kg (95% CI, 0.6-8.6 mL/kg), I2 equals to 93.6%, p value of less than 0.001, and plasma transfusion of 7.7 mL/kg (95% CI, 2.1-13.2 mL/kg), I2 equals to 95.3%, p value of less than 0.001. EACA compared with placebo resulted in a mean decrease in chest tube output of 9.2 mL/kg (2.3-21.0 mL/kg), I2 equals to 96.4%, p value of less than 0.001, RBC transfusion of 7.2 mL/kg (95% CI, 2.4-12.1 mL/kg), I2 equals to 94.5%, p value equals to 0.002, and platelet transfusion of 10.7 mL/kg (95% CI, 2.9-18.5 mL/kg), I2 equals to 0%, p value of less than 0.001. No statistical difference was observed in chest tube output when TXA was compared with aprotinin. Subgroup analysis of cyanotic patients showed a significant decrease in chest tube output, platelet requirement, and plasma requirement for patients receiving aprotinin. Overall, the quality of evidence was moderate. CONCLUSIONS Antifibrinolytics are effective at decreasing blood loss and blood product requirement in children undergoing cardiac surgery with CPB although the quality of evidence is only moderate.
Children undergoing cardiac surgery with cardiopulmonary bypass, (68 studies, n= 28,735).
Intraoperative antifibrinolytics, including tranexamic acid (TXA), aminocaproic acid (EACA), or aprotinin.
TXA compared with placebo resulted in a mean decrease in chest tube output of 9.1 mL/kg (95% Confidence Interval (CI): 6.0-12.3 mL/kg), platelet requirement of 2.9 mL/kg (95% CI: 0.1-5.8 mL/kg), and plasma requirement of 4.0 mL/kg (95% CI: 0.6-7.2 mL/kg). Aprotinin compared with placebo resulted in a mean decrease in chest tube output of 4.3 mL/kg (2.4-6.2 mL/kg), platelet transfusion of 4.6 mL/kg (95% CI: 0.6-8.6 mL/kg), and plasma transfusion of 7.7 mL/kg (95% CI: 2.1-13.2 mL/kg). EACA compared with placebo resulted in a mean decrease in chest tube output of 9.2 mL/kg (2.3-21.0 mL/kg), red blood cell transfusion of 7.2 mL/kg (95% CI: 2.4-12.1 mL/kg), and platelet transfusion of 10.7 mL/kg (95% CI: 2.9-18.5 mL/kg). Overall, the quality of evidence was moderate.
Efficacy and safety of aprotinin in paediatric cardiac surgery: A systematic review and meta-analysis
European journal of anaesthesiology. 2021
BACKGROUND The relicensing of aprotinin in Europe and Canada has stimulated discussions on its usefulness in paediatric cardiac surgery. OBJECTIVE To systematically evaluate the available evidence on the efficacy and safety of aprotinin in paediatric cardiac surgery. DESIGN Systematic review of all randomised and observational studies comparing aprotinin with tranexamic acid, epsilon aminocaproic acid, placebo or no drug in paediatric cardiac surgery. Meta-analyses were performed on efficacy and safety outcomes. DATA SOURCES PubMed, Cochrane Central Register of Controlled Trials, Web of Science and Embase were searched from January 2000 to March 2021. ELIGIBILITY CRITERIA Studies that enrolled children under 18 years undergoing cardiac surgery with cardiopulmonary bypass. RESULTS Thirty-two studies enrolling a total of 63 894 paediatric cardiac procedures were included. Aprotinin significantly reduced total blood loss [mean difference -4.70 ml kg-1, 95% confidence interval (CI), -7.88 to -1.53; P = 0.004], postoperative transfusion requirements and the incidence of surgical re-exploration for bleeding [odds ratio (OR) 0.74, 95% CI, 0.56 to 0.97; P = 0.03]. Aprotinin had no effects on 30-day mortality (OR 1.02, 95% CI, 0.93 to 1.11; P = 0.73) and on other safety outcomes, except for the incidence of renal replacement therapy (RRT), which was significantly increased in patients given aprotinin (OR 1.29, 95% CI, 1.08 to 1.54; P = 0.006). Findings from observational and randomised controlled trials did not largely differ. A sub-group analysis in neonates showed that aprotinin significantly reduced packed red blood cell transfusions and the incidence of postoperative surgical re-exploration for bleeding and/or tamponade. When compared with lysine analogues, aprotinin was more effective at reducing bleeding and transfusion without increasing the risk of side effects. CONCLUSION This meta-analysis suggests that aprotinin is effective and well tolerated in paediatric cardiac surgery. Given the large heterogeneity of the results and the risk of selection bias in observational studies, large randomised controlled trials are warranted.
Intravenous Tranexamic Acid Decreases Blood Transfusion in Off-Pump Coronary Artery Bypass Surgery: A Meta-analysis
The heart surgery forum. 2020;23(1):E039-e049
BACKGROUND Tranexamic acid (TXA) has been widely used during on-pump coronary artery bypass graft (CABG) surgery owing to its antifibrinolytic effect. However, the efficacy and safety of TXA in off-pump CABG surgery remains unconfirmed, especially intravenous (IV) administration. OBJECTIVE The aim of this study was to evaluate the effectiveness and safety of IV administration of TXA in off-pump CABG settings. METHODS AND RESULTS A comprehensive literature search was performed to identify randomized controlled trials (RCTs) that compared IV use of TXA with placebo in the reduction of postoperative 24-hour blood transfusion, as well as postoperative death and thrombotic events. The combined estimations were compiled with a fixed-effects model or, if heterogeneity existed, a random-effects model. Funnel plots and Egger's test were used to assess potential publication bias. Subgroup analyses were used to explore possible sources of heterogeneity. In total, 12 RCTs met the inclusion criteria. IV administration of TXA significantly reduced the risk of packed red blood cell (PRBC) transfusion [risk ratio (RR) = 0.61, 95% confidence interval (CI) 0.503 to 0.756, P < .001, I2 = 0.0%) during the 24 hours after surgery. However, there was no statistical significance in platelet (RR = 0.613, 95% CI 0.112 to 3.348, P = .572, I2 = 0.0%) or total fresh frozen plasma (FFP) (RR = 0.511, 95% CI 0.246 to 1.063, P = .073, I2 = 0.0%) transfusion. Also, no significant difference was found in major adverse events (death or thrombotic complications) (RR = 0.917, 95% CI 0.532 to 1.581, P = .756, I2 = 0.0%) between the 2 groups. Interestingly, further subgroup analysis demonstrated that IV TXA decreased the risk of prothrombin time (PT)- and international normalized ratio (INR)-guided FFP transfusion (RR = 0.462, 95% CI 0.296 to 0.721, P = .001, I2 = 0.0%). CONCLUSION IV TXA was effective in reducing allogeneic blood component transfusion (PRBCs and PT- or INR-guided FFP transfusion), without increasing the incidence of postoperative death or thrombotic complications in off-pump CAB surgery.
Different dose regimes and administration methods of tranexamic acid in cardiac surgery: a meta-analysis of randomized trials
BMC anesthesiology. 2019;19(1):129
BACKGROUND The efficacy of tranexamic acid (TXA) to reduce perioperative blood loss and allogeneic blood transfusion in cardiac surgeries has been proved in previous studies, but its adverse effects especially seizure has always been a problem of concern. This meta-analysis aims to provide information on the optimal dosage and delivery method which is effective with the least adverse outcomes. METHODS We searched Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE for all relevant articles published before 2018/12/31. Inclusion criteria were adult patients undergoing elective heart surgeries, and only randomized control trials comparing TXA with placebo were considered. Two authors independently assessed trial quality and extracted relevant data. RESULTS We included 49 studies with 10,591 patients into analysis. TXA significantly reduced transfusion rate (RR 0.71, 95% CI 0.65 to 0.78, P<0.00001). The overall transfusion rate was 35%(1573/4477) for patients using TXA and 49%(2190/4408) for patients in the control group. Peri-operative blood loss (MD - 246.98 ml, 95% CI - 287.89 to - 206.06 ml, P<0.00001) and re-operation rate (RR 0.62, 95% CI 0.49 to 0.79, P<0.0001) were also reduced significantly. TXA usage did not increase risk of mortality, myocardial infarction, stroke, pulmonary embolism and renal dysfunction, but was associated with a significantly increase in seizure attack (RR 3.21, 95% CI 1.04 to 9.90, P = 0.04).The overall rate of seizure attack was 0.62%(21/3378) for patients using TXA and 0.15%(5/3406) for patients in the control group. In subgroup analysis, TXA was effective for both on-pump and off-pump surgeries. Topical application didn't reduce the need for transfusion requirement, while intravenous delivery no matter as bolus injection alone or bolus plus continuous infusion were effective. Intravenous high-dose TXA didn't further decrease transfusion rate compared with low-dose regimen, and increased the risk of seizure by 4.83 times. No patients in the low-dose group had seizure attack. CONCLUSIONS TXA was effective in reducing transfusion requirement in all kinds of cardiac surgeries. Low-dose intravenous infusion was the most preferable delivery method which was as effective as high-dose regimen in reducing transfusion rate without increasing the risk of seizure.
The safety and efficiency of intravenous administration of tranexamic acid in coronary artery bypass grafting (CABG): a meta-analysis of 28 randomized controlled trials
BMC anesthesiology. 2019;19(1):104
BACKGROUND The safety and efficiency of intravenous administration of tranexamic acid (TXA) in coronary artery bypass grafting (CABG) remains unconfirmed. Therefore, we conducted a meta-analysis on this topic. METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PUBMED and EMBASE for randomized controlled trials on the topic. The results of this work are synthetized and reported in accordance with the PRISMA statement. RESULTS Twenty-eight studies met our inclusion criteria. TXA reduced the incidence of postoperative reoperation of bleeding (relative risk [RR], 0.46; 95% confidence interval [CI]; 0.31-0.68), the frequency of any allogeneic transfusion (RR, 0.64; 95% CI, 0.52-0.78) and the postoperative chest tube drainage in the first 24 h by 206 ml (95% CI - 248.23 to - 164.15). TXA did not significantly affect the incidence of postoperative cerebrovascular accident (RR, 0.93; 95%CI, 0.62-1.39), mortality (RR, 0.82; 95%CI, 0.53-1.28), myocardial infarction (RR, 0.90; 95%CI, 0.78-1.05), acute renal insufficiency (RR, 1.01; 95%CI, 0.77-1.32). However, it may increase the incidence of postoperative seizures (RR, 6.67; 95%CI, 1.77-25.20). Moreover, the subgroup analyses in on-pump and off-pump CABG, the sensitivity analyses in trials randomized more than 99 participants and sensitivity analyses that excluded the study with the largest number of participants further strengthened the above results. CONCLUSIONS TXA is effective to reduce reoperation for bleeding, blood loss and the need for allogeneic blood products in patients undergoing CABG without increasing prothrombotic complication. However, it may increase the risk of postoperative seizures.
Exclusion criteria and adverse events in perioperative trials of tranexamic acid in cardiac surgery: a systematic review and meta-analysis
Canadian journal of anaesthesia = Journal canadien d'anesthesie. 2019
PURPOSE Tranexamic acid (TXA) reduces perioperative blood loss and transfusion requirement following cardiac surgery. Nevertheless, TXA remains underutilized because of concerns regarding development of adverse events. We conducted a systematic review to determine which patients are commonly excluded from TXA cardiac surgery clinical trials to determine if there are patient groups lacking safety data on TXA. METHODS The databases Medline, EMBASE, and the Cochrane Central Register of Controlled Trials were searched until September 2017. Eligible studies were randomized-controlled trials (RCTs) administering systemic TXA perioperatively to patients undergoing any cardiac surgery. Our primary outcome was the exclusion criteria for each RCT, and the secondary endpoint was TXA safety. A descriptive synthesis was performed to analyze the exclusion criteria. TXA safety was assessed with meta-analysis. PRINCIPAL FINDINGS Seventy eligible RCTs were included. The most common reasons for excluding patients from TXA cardiac surgery trials were major hepatic, renal, or cardiac comorbidities (76% of studies). Meta-analysis showed that TXA did not increase the risk of adverse events compared with placebo or no intervention (risk ratio, 0.97; 95% confidence interval, 0.88 to 1.07), including thrombosis and seizure. CONCLUSION We found that systemic TXA is safe to use in cardiac surgery. Certain patient groups are frequently excluded from TXA cardiac surgery trials, and may consequently have limited efficacy and safety data on TXA. Further research in these patient groups may be needed; nevertheless, for many patient populations there are sufficient data to inform evidence-based guidelines for TXA use in cardiac surgery. TRIAL REGISTRATION PROSPERO (CRD42017060971); registered 4 April, 2017.
The effect of tranexamic acid to reduce blood loss and transfusion on off-pump coronary artery bypass surgery: a systematic review and cumulative meta-analysis
Journal of Clinical Anesthesia. 2017;44:23-31.
STUDY OBJECTIVE To assess the safety and efficacy of tranexamic acid (TA) on off-pump coronary artery bypass (OPCAB) surgery. DESIGN Meta-analysis. SETTING Operating room, OPCAB surgery, all surgeries were elective measurements. Searching the following data sources respectively: PubMed/MEDLINE, the Cochrane Library, EMBASE and reference lists of identified articles, we performed a meta-analysis of postoperative 24h blood loss, postoperative allogeneic transfusion, re-operation for massive bleeding, postoperative mortality, and postoperative thrombotic complications. MAIN RESULTS Using electronic databases, we selected 15 randomized control trials (RCTs), carried out between 2003 and 2016, with a total of 1250 patients for our review. TA significantly reduced the postoperative 24h blood loss (mean difference -213.32ml, 95% confidence intervals, -247.20ml to -179.43ml; P<0.0001). And, TA also significantly reduced the risk of packed red blood cell (PRBCs) transfusion (risk ratio 0.62; 95% confidence intervals 0.51 to 0.76; P<0.0001) and fresh frozen plasma (FFP) transfusion (0.65; 0.52 to 0.81; P<0.001). There were no statistical significance on platelet transfusion (risk difference -0.00, 95% confidence interval -0.02 to 0.02; P=0.73) and re-operation (0.00, -0.02 to 0.02; P=1.00). No association was found between TA and morbility (risk difference -0.00, 95% confidence interval -0.02 to 0.02; P=0.99) and thrombotic complications (-0.01, -0.01 to 0.02; P=0.70). CONCLUSIONS TA reduced the probability of receiving a PRBCs and FFP transfusion during OPCAB surgery. And no association with postoperative death and thrombotic events was found. However, further trials with an appropriate sample size are required to confirm TA safety in OPCAB surgery.
Seizures associated with tranexamic acid for cardiac surgery: a meta-analysis of randomized and non-randomized studies
The Journal of Cardiovascular Surgery. 2017;58((4):):633-641
BACKGROUND We focused whether tranexamic acid (TXA) therapy for adult cardiac surgery is associated with an increase in the risk of seizures and performed a meta-analysis of randomized controlled trials (RCTs) and non-randomized observational studies. METHODS MEDLINE and EMBASE were searched through December 2016 using PubMed and OVID. Eligible studies were RCTs and non-randomized observational studies of TXA versus control (no TXA, placebo, or active control such as low-dose TXA, aprotinin, and epsilon aminocaproic acid) enrolling adult patients undergoing cardiac surgery and reporting the postoperative incidence of seizures as an outcome. Study-specific estimates were combined using inverse variance-weighted averages of logarithmic odds ratios in the random-effects model. RESULTS Of 90 potentially relevant articles screened initially, 16 reports of eligible studies were identified and included. A pooled analysis of all 16 studies (enrolling 45,235 patients) demonstrated that TXA therapy was associated with a statistically significant increase in the seizures incidence (odds ratio, 4.13; 95% confidence interval, 2.59 to 6.57; P < 0.00001). A subgroup analysis indicated a statistically significant increase in the seizures incidence with TXA therapy in all subgroups of 5 RCTs, 5 adjusted observational studies, and 6 unadjusted observational studies with no statistically significant subgroup differences (P = 0.36; I2 = 1.5%). CONCLUSIONS The results of the present meta-analysis of 16 studies enrolling 45,235 patients confirmed that TXA therapy for adult cardiac surgery is associated with a 4.1-fold increase in the risk of seizure.