Heparin Dose-Response Curve for Heparin Dose Determination During Cardiopulmonary Bypass for Pediatric Cardiac Surgery: A Prospective Randomized Controlled Study.

OBJECTIVES

To determine whether individualized heparin dosing guided by a heparin dose-response (HDR) curve is noninferior to conventional weight-based dosing in achieving target activated clotting time (ACT) of ≥480 seconds before cardiopulmonary bypass (CPB) and to compare total heparin and protamine requirements, postoperative blood loss, and transfusion needs in children younger than 14 years undergoing cardiac surgery with cardiopulmonary bypass support.

DESIGN

Single-center, prospective, double-blinded, randomized controlled trial.

SETTING

Cardiothoracic operating theaters and intensive care unit of a tertiary care hospital in India.

PARTICIPANTS

Pediatric (<14 years) patients undergoing elective cardiac surgery with CPB support.

INTERVENTIONS: The HDR group received an initial test dose of 100 IU/kg of heparin, and an individualized ACT dose-response curve was constructed to determine the dose required to target an ACT of 480 seconds. Controls received standard 400 IU/kg of heparin. Protamine was given post-CPB per protocol in both groups.

MEASUREMENTS AND MAIN

RESULTS

In this noninferiority trial, HDR-guided anticoagulation was assessed against conventional weight-based dosing for first-pass attainment of ACT ≥480 seconds before CPB. Target ACT was achieved in 72.2% (26/36) of HDR patients versus 83.3% (30/36) of controls (p = 0.396). Although HDR was associated with lower heparin exposure (260 v 420 IU/kg; p < 0.001) and protamine use (4.1 v 4.8 mg/kg; p = 0.002), as well as reduced 24-hour blood loss (5.2 v 6.5 mL/kg; p = 0.03) and packed red blood cell transfusion (6.8 v 8.2 mL/kg; p = 0.04), it did not demonstrate superior first-attempt ACT attainment.

CONCLUSIONS

HDR-guided heparinization reduced heparin and protamine exposure and was associated with less bleeding and transfusion, but it did not improve first-pass ACT attainment. Because ACT is an imperfect surrogate for anticoagulant adequacy in children on CPB, these findings should be interpreted as ACT-guided dosing data rather than proof of equivalent anticoagulation. Larger multicenter studies with mechanistic and clinical endpoints are needed to confirm these results.