Antifibrinolytic Drugs for the Prevention of Bleeding in Pediatric Cardiac Surgery on Cardiopulmonary Bypass: A Systematic Review and Meta-analysis

Abstract

BACKGROUND: Bleeding is one of the commonest complications affecting children undergoing cardiac surgery on cardiopulmonary bypass. Antifibrinolytic drugs are part of a multifaceted approach aimed at reducing bleeding, though sufficiently sized pediatric studies are sparse, and dosing algorithms are heterogeneous. Our objective was to evaluate the efficacy and safety of antifibrinolytic agents as well as the effectiveness of different dosing regimens in pediatric cardiac surgery using cardiopulmonary bypass. METHODS: We performed a systematic review and meta-analysis evaluating randomized controlled trials published between 1980 and 2019, identified by searching the databases MEDLINE, EMBASE, PubMed, and CENTRAL. All studies investigating patients <18 years of age without underlying hematological disorders were included. The primary outcome was postoperative bleeding; secondary end points included blood product transfusion, mortality, and safety (thromboses, anaphylaxis, renal or neurological dysfunction, and seizures). Different dosing regimens were compared. Studies were dual appraised, outcomes were reported descriptively and, if appropriate, quantitatively using the Review Manager 5 (REVMAN 5) software (The Cochrane Collaboration). RESULTS: Thirty of 209 articles were included, evaluating the following drugs versus control: aprotinin n = 14, tranexamic acid (TXA) n = 12, and epsilon-aminocaproic acid (EACA) n = 4. The number of participants per intervention group ranged from 11 to 100 (median, 25; interquartile range [IQR], 20.5) with a wide age span (mean, 13 days to 5.8 years) and weight range (mean, 3.1–26.3 kg). Methodological quality was low to moderate. All agents reduced mean 24-hour blood loss compared to control: aprotinin by 6.0 mL/kg (95% confidence interval [CI], −9.1 to −3.0; P = .0001), TXA by 9.0 mL/kg (95% CI, −11.3 to −6.8; P < .00001), and EACA by 10.5 mL/kg (95% CI, −21.1 to 0.0; P = .05). Heterogeneity was low for TXA (I2 = 29%; P = .19), moderate for aprotinin (I2 = 41%; P = .11), and high for EACA (I2 = 95%; P < .00001). All agents also reduced 24-hour blood product transfusion. There was no clear dose-response effect for TXA nor aprotinin. Studies were underpowered to detect significant differences in mortality, thromboses, anaphylaxis, and renal or neurological dysfunction. CONCLUSIONS: The available data demonstrate efficacy for all 3 antifibrinolytic drugs. Therefore, the agent with the most favorable safety profile should be used. As sufficient data are lacking, large comparative trials are warranted to assess the relative safety and appropriate dosing regimens in pediatrics.

Anti-inflammatory effect of tranexamic acid on adult cardiac surgical patients: A PRISMA-compliant systematic review and meta-analysis

“…Inflammation influenced the initiation and propagation of blood coagulation (31). TXA had reduced perioperative blood loss and transfusion requirements in cardiac surgical patients (32)(33)(34)(35)(36)(37). Coagulation, fibrinolysis, and inflammation are closely interconnected.…”

“…Inflammation influenced the initiation and propagation of blood coagulation ( 31 ). TXA had reduced perioperative blood loss and transfusion requirements in cardiac surgical patients ( 32 – 37 ).…”

Sonoclot® predicts operation time and blood loss after cardiopulmonary bypass in children

“…Moreover, Siemens et al. [ 20 ] reported that antifibrinolytic drugs, such as aprotinin, tranexamic acid, and epsilon-aminocaproic acid, reduced 24-h blood loss and blood product transfusion. These results suggest that preventive administration of FFP or PC in the CPB circuit might be useful to reduce bleeding after CPB.…”

The Year in Review: Anesthesia for Congenital Heart Disease 2021

“…There was also no difference is transfusion between patients who received continuous vs bolus dosing. 28 A review by Hovgesen et al 29 of 50 studies evaluating the efficacy of different TXA doses across all pediatric surgical disciplines also demonstrated efficacy of lower dose TXA. This research supports the use of the lowest efficacious dose of TXA and highlights the need for development of a standardized dosing regimen in pediatrics.…”