Antifibrinolytics to reduce bleeding after pediatric cardiac surgery
Lindsey Loveland Baptist MD, Susan Nicolson MD, James Dinardo MD, and Vivian Nasr MD
Original article
Siemens K, Sangaran DP, Hunt BJ, Murdoch IA, Tibby SM. Antifibrinolytic Drugs for the Prevention of Bleeding in Pediatric Cardiac Surgery on Cardiopulmonary Bypass: A Systematic Review and Meta-analysis. Anesth Analg. 2022 May 1;134(5):987-1001. doi: 10.1213/ANE.0000000000005760. PMID: 34633994.
Bleeding is one of the commonest complications affecting children undergoing cardiac surgery with cardiopulmonary bypass (CPB). Post-CPB bleeding is associated with hemodynamic instability, increased transfusion requirement and delayed sternal closure. The pathogenesis of bleeding is complex. Children have different hemostatic systems from adults with maturation with age. CPB leads to greater hemodilution in young children and exposure to artificial surfaces causes activation of platelets and coagulation, decreased platelet count and function, reduced fibrinogen levels and fibrinolytic activation.
We have discussed the issues of priming the bypass circuit with fresh frozen plasma as a proposed intervention to reduce bleeding in a previous PAAD. Antifibrinolytic drugs are often part of a multi-faceted approach aimed at reducing post-CPB bleeding. Three antifibrinolytic drugs have been used – aprotinin (APO), tranexamic acid (TXA), and epsilon-aminocaproic acid (EACA). Siemens and colleagues conducted a systematic review in pediatric patients, 0-18 years of age with no bleeding disorder, to assess the efficacy of each agent vs placebo with the primary outcome mediastinal bleeding in the first 24h after CPB. Secondary endpoints were blood product transfusion, safety (thromboses, anaphylaxis, renal and neurologic dysfunction, seizure) and mortality. Final analysis only included randomized controlled trials, published in English, from 1980-2019. Systemic review and meta-analysis included 30 articles: 14 using APO, 12 using TXA, and 4 using EACA. All the studies were small (n – range 11-100, median =25) with a wide age/weight range, a heterogenous group of surgical procedures and a variety of dosing regimens resulting in low to moderate methodological quality. All three antifibrinolytic agents demonstrated an overall reduction of 24-hour blood loss, blood product use, and surgical chest re-exploration compared to control. The studies did not have adequate power to detect differences in safety or mortality. There was inadequate data to make dosing recommendations.
A clinically available quantitative test to determine fibrinolytic activity is needed to determine which patients would benefit from an antifibrinolytic. In such patients, pharmacokinetic and pharmacodynamic studies are needed to understand age-specific minimal effective drug concentrations and dosing regimens to achieve and maintain those concentrations. These dosing strategies could be used in large RCT to access relative efficacy, safety and cost-effectiveness of the 3 antifibrinolytic drugs. Until more data is available, all 3 drugs have benefit and using the drug with the most favorable safety profile and availability at your institution should guide your choice – but use one.
1. Faraoni D, Willems A, Melot C, De Hert S, Van der Linden P. Efficacy of tranexamic acid in paediatric cardiac surgery: a systematic review and meta-analysis. Eur J Cardiothorac Surg. 2012 Nov;42(5):781-6. doi: 10.1093/ejcts/ezs127. Epub 2012 Apr 24. PMID: 22531271.