Randomized, Controlled Trial of Individualized Heparin and Protamine Management in Infants Undergoing Cardiac Surgery With Cardiopulmonary Bypass

Study Questions:

Are postoperative clinical outcomes improved in children less than 1 year of age undergoing cardiopulmonary bypass (CPB) with the use of individualized heparin management with Hemostasis Management System (HMS) Plus rather than traditional weight-based anticoagulation management using activated clotting time (ACT)?


This was a randomized, controlled trial of 90 infants less than 1 year of age undergoing CPB comparing weight-based anticoagulation management using ACT to individualized management with HMS. Use of the HMS device has demonstrated improved clinical outcomes in older children and adults. Randomization was stratified for neonates (<30 days) and infants (1-12 months). A standardized blood transfusion protocol was utilized and all members of the team except for perfusion were blinded to the treatment assignment. The HMS protocol was modified after the initial 33 patients due to a temporary hold on the study by the internal data safety committee. Patients were evaluated on perioperative laboratory data, blood loss, transfusion requirements, and clinical outcomes including duration of ventilation, intensive care, and hospital stay.


Using the manufacturer protocol, the HMS device routinely underestimated plasma anti-Xa levels, leading to an overestimated required heparin and protamine dose. Use of the HMS device with a modified protocol resulted in more stable anti-Xa levels on CPB. Patients in the modified HMS group received higher doses of heparin and protamine compared to the control group. Those in the modified HMS group demonstrated reduced need for transfusions, ventilation times, intensive care, and hospital stay. Clinical outcomes were poorer in the control group receiving lower doses of heparin and in the initial HMS protocol group that received the highest heparin doses.


Using a modified protocol for HMS over weight-based anticoagulation, patients demonstrated improved short-term clinical outcomes and required fewer transfusions. Worse clinical outcomes were demonstrated when the standard adult protocol for HMS was applied to this infant population. The device cannot be used safely for children less than 1 year of age with the manufacturer’s suggested protocol.


Anticoagulation management for the pediatric population has been largely adopted from the adult literature despite vast differences in the coagulation system, especially in the infant population. This study nicely demonstrates how both too much and too little heparinization and protamine reversal can negatively impact gross measures of clinical outcomes such as ventilator time and length of hospital stay. There is increasing literature linking these gross short-term clinical markers with long-term neurodevelopmental outcomes. Therefore, it is plausible that with improved titration of patient-specific anticoagulation, it is possible to dramatically impact both short- and long-term outcomes. As with many applications of adult technology to the pediatric population, the establishment of a best practices protocol is necessary before widespread application of this technology.

Clinical Topics: Anticoagulation Management, Cardiac Surgery, Congenital Heart Disease and Pediatric Cardiology, Invasive Cardiovascular Angiography and Intervention, Cardiac Surgery and CHD & Pediatrics, CHD & Pediatrics and Interventions, CHD & Pediatrics and Prevention

Keywords: Child, Blood Transfusion, Heart Diseases, Infant, Biological Markers, Protamines, Heparin, Blood Coagulation Tests, Cardiopulmonary Bypass, Hemostasis, Cardiac Surgical Procedures

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