Age-related differences in heparin sensitivity and heparin-protamine interactions in cardiac surgery patients

Objective: The present study was conducted to determine how children and adults differ (if at all) with respect to sensitivity to heparin activity and heparin-protamine interactions during cardiac surgery requiring cardiopulmonary bypass (CPB). Design: A prospective study of both children and adults undergoing CPB. Setting: A tertiary care academic medical center between July 1992 and October 1994. Participants: Ninety patients who had cardiac or aortic arch surgery using CPB. The median age of the entire study sample was 15.8 years (range 2 months to 72 years).Intervention: Data were obtained using the Medtronic Hemotec Hepcon Hemostasis Management System (Englewood, CO). An ex vivo heparin dose-response (HDR) curve was generated for each patient before skin incision to determine the target heparin concentration (THC) needed to achieve an activated coagulation time (ACT) of at least 480 seconds. Protamine dose was determined on the basis of whole blood heparin concentration estimated by means of a heparin-protamine titration. Measurements and Main Results: The study population was divided into four groups based on age: infants (<1 year), preschool (1 to 5 years), school-age (5 to 14 years) and adults (>14 years). The mean ± SD THC for the preschool group was 4.0 ± 1.1; for infants, 3.3 ± 0.7; for school-age, 3.1 ± 0.7; and for adults, 3.4 ± 0.7. The initial dose of heparin needed to achieve this THC (mean ± SD) was significantly higher in infants (578 ± 220 U/kg) and preschool children (477 ± 159 U/kg) than in school-age children (327 ± 57 U/kg) and adults (332 ± 64 U/kg). The ratio of protamine to heparin was significantly higher in adults (1.4 ± 0.5) and school-age children (1.3 ± 0.6) than in infants (1.1 ± 0.7) and preschool children (1.1 ± 0.4). Conclusions: Pre-school children are less sensitive to heparin but also display a wider range of sensitivity. The data in this study support the use of 300 U/kg of heparin before CPB in patients ≥5 years but suggest that heparin requirements may be greater in the younger patient who may require as much as 500 U/kg to achieve what is believed to be an appropriate target heparin concentration for initiating CPB.