Introduction: Children with congenital heart disease (CHD) face a significant risk of considerable blood loss during and post-surgery, requiring blood transfusions that may increase morbidity and mortality rates. Tranexamic acid (TXA), an antifibrinolytic agent, is widely employed in adult cardiac surgery; however, its effectiveness and safety in pediatric populations are still ambiguous. This systematic review evaluated the evidence concerning the effectiveness of TXA in reducing blood loss and the necessity for transfusions in pediatric patients undergoing congenital heart surgery. Methods: This review complied with PRISMA guidelines. MEDLINE (via PubMed), Embase, CENTRAL and Web of Science were comprehensively searched from the databases' inception until May ۲۰۲۴. The terms included "tranexamic acid," "antifibrinolytics," "pediatric," "congenital heart surgery," "cardiopulmonary bypass," "blood loss," and "transfusion." The randomized controlled trials (RCTs) and observational cohort studies assessed TXA in comparison to placebo or standard care in patients aged ۱۸ years or younger. The exclusion criteria included case reports, reviews and studies involving adult patients or different antifibrinolytic agents. We employed Cochrane RoB ۲ for randomized controlled trials and ROBINS-I for observational studies to assess bias. We employed narrative synthesis and random-effects meta-analysis to determine the aggregated risk ratios (RR) or mean differences (MD) along with ۹۵% confidence intervals. Results: From ۱,۲۴۵ records, ۱۵ studies (۱۰ randomized controlled trials and ۵ cohort studies) comprising ۱,۸۲۷ pediatric patients were selected. The dosing protocols for TXA and the complexity of patients varied among studies. Tranexamic acid (TXA) significantly reduced ۲۴-hour postoperative blood loss (mean difference: -۷.۲ mL/kg; ۹۵% confidence interval: -۱۰.۱ to -۴.۳; ۸ studies, n=۷۱۲) and the likelihood of patients requiring a packed red blood cell transfusion (risk ratio: ۰.۷۲; ۹۵% confidence interval: ۰.۶۱ to ۰.۸۵; ۷ studies, n=۶۴۲), benefiting the TXA cohort. No significant increase in adverse events, especially seizures or thrombosis. Conclusion: This systematic review indicated that tranexamic acid significantly reduces blood loss and the need for transfusions in pediatric patients with congenital heart disease, without increasing short-term thrombotic or neurological complications. These findings support the utilization of TXA in at-risk populations. Due to the significant variability in dosing protocols, there is a necessity for additional high-quality, large-scale randomized controlled trials (RCTs) to standardize, enhance and validate the long-term safety of tranexamic acid (TXA) in neonates and infants with complex congenital heart disease.
