Use of antifibrinolytics in pediatric cardiac surgery: Where are we now?

Abstract

Summary Fibrinolytic activation is a major and preventable source of bleeding in neonates and children undergoing cardiac surgery with cardiopulmonary bypass. Based on the existing literature (adult and pediatric; cardiac and noncardiac), prophylactic administration of antifibrinolytic agents can help reduce fibrinolytic activation, and consequently reduces perioperative bleeding and the requirement for blood product transfusion. Due to the increased risk of renal failure and mortality reported in adults undergoing cardiac surgery, aprotinin should not be considered as a safe option in neonates and children. Further well‐designed studies would be required before the prophylactic administration of aprotinin could be considered in pediatric cardiac surgery. The lysine analogs, tranexamic acid and ϵ‐aminocaproic acid,, should be considered as safe and effective antifibrinolytic agents. Although no major side effects have been reported following the administration of lysine analogs in children undergoing cardiac surgery, high‐dose tranexamic acid should not be recommended in order to avoid the increased risk of clinical seizures. Despite the recent advances made in our understanding of the pharmacokinetics of tranexamic acid and ϵ‐aminocaproic acid,, the optimal plasmatic concentration to be targeted remains unknown. Further studies are therefore urgently needed to better define the optimal dose regimen to be used in neonates and children. In the meantime, the dose regimen published in the most recent pharmacokinetic studies can be used. Although no studies have assessed the effect of massive bleeding and transfusion on the plasmatic concentrations of the lysine analogs, additional boluses might be considered in the presence of bleeding and/or when signs of fibrinolytic activations are observed on viscoelastic hemostatic assays.

Hemostatic Management of Extracorporeal Circuits Including Cardiopulmonary Bypass and Extracorporeal Membrane Oxygenation

“…Faraoni et al reviewed the evidence of TXA use in pediatric cardiac surgery. 29,30 The evidence comes mainly from small prospective trials, but it appears to be an effective agent for reducing the need for blood transfusion.…”

“…26 Aprotinin is another antifibrinolytic agent used in cardiac surgery that reversibly binds with the active serine residue of various proteases in plasma. 29 Aprotinin was previously suspended from the market due to increased risk of renal failure and mortality suggested by two large multicenter studies. 24,28 In the BART study, Fergusson et al performed a multicenter blinded trial of 2,331 patients comparing aprotinin, TXA, and EACA.…”

“…The safety of aprotinin has been reevaluated in several retrospective studies in adult cardiac surgery. 29 In a reexamination of data, the EMA (European Medicines Agency) lifted the suspension of aprotinin (https://www.ema.europa.eu/en/news/ european-medicines-agency-recommends-lifting-suspension-aprotinin). Aprotinin is not currently available in the United States but is available in Canada and Europe on a named-patient basis.…”

Safety and efficacy of tranexamic acid in paediatric cardiac surgery: study protocol for a double-blind randomised controlled trial

“…An additional priming volume of 60 µg/mL was also suggested. Therefore, on the basis of the existing literature, the present study indicates that a TXA loading dose of 30 mg/kg followed by a continuous infusion of 10 mg/(kg·h) can be used in infants <1 year of age, while a loading dose of 10 mg/kg followed by a continuous infusion of 10 mg/(kg·h) can be used in older patients; this is recommended by Faraoni et al 24 as an expert opinion.…”

Individualized Perioperative Antifibrinolytic Therapy: The Next Goal in Cardiac Surgery?

“…9 In the setting of cardiac surgery with CPB, TXA and EACA are thought to be equivalent in their general ability to reduce bleeding and transfusion requirements in adult cardiac surgery. 8,10 Despite having similar structures, mechanisms of action, and pharmacodynamics including intravenous application, renal elimination, and comparable plasma half-time of about 2-to-3 hours, 8,11 their relevant pharmacokinetics and dosing regimens differ. 8,10 Of note, TXA is thought to be about 6 to-10 times more potent on a molecular basis.…”