Response to heparinization in adults and children undergoing cardiac operations

The activated clotting time is an unreliable index of anticoagulation status during cardiopulmonary bypass procedures. However, modern instrumentation (Hemotec Hepcon HMS) now allows the monitoring of free heparin levels via automated protamine titration. In the present study, the standard procedure of anticoagulation at Killingbeck Hospital, Leeds, was investigated. Twenty-two pediatric patients and 20 adult patients undergoing open heart procedures involving cardiopulmonary bypass were given empirical doses of heparin (3 mg/kg body weight bolus), and activated clotting time was maintained at a level greater than 450 seconds using the Hemochron Timer. Heparin neutralization was performed at the termination of the bypass period using an empirical equivalent (3 mg/kg) of protamine sulfate. Mean free heparin concentration (+/- standard deviation) fell from 2.26 (+/- 0.45) mg/kg to 1.39 (+/- 0.34) mg/kg over the period 10 to 40 minutes on bypass in children. In adults, free heparin level declined from 2.56 (+/- 0.58) mg/kg to 1.81 (+/- 0.58) mg/kg over the same period. The biological half-life for heparin was 60 minutes in adults and 35 minutes in pediatric patients. Empirical protamine dosing resulted in excess protamine administration when compared with Hepcon titrated dose requirements: for children: median (range), 80 (12 to 350) versus 33 (12 to 97) mg, p less than 0.001; and for adults: 350 (200 to 500) versus 130 (61 to 237) mg, p less than 0.001. In conclusion, empirical heparin administration (3 mg/kg) does not result in "steady-state" anticoagulation during cardiopulmonary bypass, and empirical administration of protamine takes no account of interindividual differences in heparin sensitivity and biological half-life, which may be assessed using the Hepcon HMS.