The role of the activated clotting time in heparin administration and neutralization for cardiopulmonary bypass.

Precise guidelines for heparin administration and neutralization during cardiopulmonary bypass (CPB) are not established. To a large extent, the uncertainty originates from a disparity between the heparin dosage, the plasma heparin concentration, and the clinical heparin effect. We investigated these relationships in 44 consecutive patients at New York University Medical Center. Following serial loading doses of heparin (2 and 4 mg/kg) there was a wide variation in both the measured clinical heparin effect (activated clotting time--ACT) and the plasma heparin concentration. When the Act was compared to the heparin concentration, there was no linear relationship noted after heparin does commonly employed for CPB. The calculated heparin sensitivity varied over a fourfold range and was not related to the baseline antithrombin III activity. At the completion of CPB, heparin was neutralized with a 2 mg/kg protamine dose regardless of the total heparin dose. Heparin levels fell from 4.17 +/- 1.29 to 0.19 +/- 0.20 units/ml. Additional protamine was given to 49% of the patients as the ACT had not returned to pre-heparin levels. The total protamine dose rarely exceeded 3 mg/kg. This technique resulted in the administration of 30% to 50% less protamine than predicted by other commonly used protocols. In the subsequent 4 hours after protamine administration, heparin levels remained insignificant. Mild heparin rebound was found in two patients (4.5%) but was not associated with excessive bleeding. Following bypass a comparison of heparin levels and ACTs demonstrated the ACT to be a poor indicator of residual circulating heparin. These data show: (1) that neither the heparin dosage nor the plasma heparin concentration can accurately predict the magnitude of the clinical heparin effect in patients undergoing CPB and emphasize the importance of the ACT as the best available measurement of safe anticoagulation, (2) heparin "rebound" was not clinically significant, and (3) heparin was neutralized with 2 to 3 mg/kg protamine in virtually all patients, regardless of the total heparin dose.