Drug Des Devel Ther. 2026 Oct 15;20:634756. doi: 10.2147/DDDT.S634756. eCollection 2026.
ABSTRACT
PURPOSE: Neonatal hemostatic immaturity complicates anticoagulation during cardiopulmonary bypass (CPB). Current practice largely follows the strategy of 400 U/kg from adult protocols, as neonatal-specific guidelines and high-quality evidence remain lacking, which frequently fails to achieve adequate anticoagulation. This single-center randomized controlled trial evaluated the initial heparin dose of 600 U/kg to refine neonatal CPB anticoagulation.
PATIENTS AND METHODS: In this prospective, randomized, controlled, single-blind trial, 76 neonates undergoing CPB were assigned to receive an initial heparin dose of either 600 U/kg (n = 38) or 400 U/kg (n = 38). The primary endpoint was the pre- to post-CPB change in prothrombin fragment 1+2 (ΔF1+2). Secondary endpoints included the proportion of neonates achieving the ACT threshold after the initial heparin bolus, perioperative coagulation measures, postoperative blood loss, transfusion requirements, and adverse clinical outcomes.
RESULTS: Mean ΔF1+2 was 0.70 vs 4.08 nmol/L in the 600 and 400 U/kg groups, respectively (treatment-minus-control mean difference, -3.38 nmol/L; 95% confidence interval, -4.58 to -2.18; P <0.001). ACT target achievement rate after the initial dose was higher in the 600 U/kg group (84.2% vs 44.7%, P < 0.001). Surgical preparation time was shorter (median 31.50 vs 36.50 mins, P = 0.028), and supplemental heparin use was lower, while total heparin dose did not differ significantly. Secondary endpoints showed lower 72-hour chest drainage and albumin use and shorter mechanical ventilation duration (P = 0.036, 0.028, and 0.031, respectively). Red-cell, plasma, and platelet transfusion requirements and most other clinical outcomes did not differ significantly. One in-hospital death occurred with 600 U/kg and none with 400 U/kg. Complete-case sensitivity analysis supported the primary finding.
CONCLUSION: An initial heparin dose of 600 U/kg in neonatal CPB was associated with a smaller F1+2 increase and greater initial ACT response. Larger studies are needed to establish clinical benefit and safety.
CLINICAL TRIAL REGISTRY NUMBER: ChiCTR2300069157.
PMID:42899169 | PMC:PMC13679529 | DOI:10.2147/DDDT.S634756
