An initial heparin dose of 600 U/kg in neonatal CPB was associated with a smaller F1+2 increase and greater initial ACT response than 400 U/kg, and larger studies are needed to establish clinical benefit and safety.
Key Findings
Results
The 600 U/kg initial heparin dose produced a much smaller rise in prothrombin fragment 1+2 (ΔF1+2), the primary endpoint, than the 400 U/kg dose.
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 was -3.38 nmol/L; 95% CI, -4.58 to -2.18; P <0.001.
76 neonates undergoing CPB were randomized 1:1 (n = 38 per group) in a single-center, single-blind RCT.
A complete-case sensitivity analysis supported the primary finding.
Results
A higher proportion of neonates reached the ACT target after the initial heparin bolus with 600 U/kg.
ACT target achievement was 84.2% with 600 U/kg vs 44.7% with 400 U/kg (P < 0.001).
Results
Surgical preparation time was shorter and supplemental heparin use was lower with 600 U/kg, while total heparin dose did not differ significantly.
Median surgical preparation time was 31.50 vs 36.50 min (P = 0.028).
Supplemental heparin use was lower in the 600 U/kg group.
Total heparin dose did not differ significantly between groups.
Results
The 600 U/kg group had lower 72-hour chest drainage, lower albumin use, and shorter mechanical ventilation duration.
P values were 0.036 for 72-hour chest drainage, 0.028 for albumin use, and 0.031 for mechanical ventilation duration.
These were secondary endpoints.
Results
Transfusion requirements and most other clinical outcomes did not differ significantly between doses.
Red-cell, plasma, and platelet transfusion requirements did not differ significantly.
One in-hospital death occurred in the 600 U/kg group and none in the 400 U/kg group.
Background
Current neonatal CPB anticoagulation largely relies on adult-derived 400 U/kg dosing, which frequently fails to achieve adequate anticoagulation, and neonatal-specific guidelines and high-quality evidence are lacking.
Neonatal hemostatic immaturity complicates anticoagulation during CPB.
The trial was designed to evaluate 600 U/kg to refine neonatal anticoagulation.
Conclusions
The authors conclude that 600 U/kg was associated with a smaller F1+2 increase and greater initial ACT response, but clinical benefit and safety remain to be established.
The study was single-center with 76 patients.
Larger studies are needed to establish clinical benefit and safety.
Trial registration: ChiCTR2300069157.
What This Means
Newborns having heart surgery on a heart-lung machine need a blood thinner called heparin to keep blood from clotting in the circuit. Doses for newborns have mostly been borrowed from adult practice (400 units per kilogram), even though newborn blood clots differently and this dose often does not reach the intended level of blood thinning. This trial randomly assigned 76 newborns to receive either 400 or 600 units per kilogram as the first dose.
The higher dose was associated with much less clotting activity during bypass, measured by a blood marker called F1+2. It also more often reached the target blood-thinning level after the first dose (84% vs 45%), shortened preparation time before surgery, and reduced the need for extra heparin top-ups, without increasing total heparin use. The higher-dose group also had less chest drainage over 72 hours, used less albumin, and spent less time on a ventilator. Transfusion needs and most other outcomes were similar. One death occurred in the higher-dose group and none in the lower-dose group.
This research suggests that a higher starting heparin dose may control clotting better in newborns during bypass. However, the study was small and from a single center, and the clinical benefits and safety, including bleeding and death, need confirmation in larger studies before conclusions are drawn about practice.
Wang H, Liu Q, Gao P, Liu J, Jin Y, Gao T, et al.. (2026). Optimization of Anticoagulation Strategy During Cardiopulmonary Bypass in Neonates with Congenital Heart Disease: A Randomized Controlled Trial.. Drug design, development and therapy. https://doi.org/10.2147/DDDT.S634756