Use of the activated coagulation time and heparin dose-response curve for the determination of protamine dosage in vascular surgery

The activated coagulation time (ACT) can be used to construct a two-point heparin dose-response cuirve (HDRC) from the ACT values at baseline and 5 minutes after heparin administration. The ACT value at any subsequent time interval can then be used to estimate the residual heparin activity from the HDRC. The protamine dose is calculated to be the amount of residual heparin multiplied by a correction factor (1.3 was suggested for cardiac surgery). In vascular surgery, heparin and protamine dosing remain empirical, ACT monitoring is not standard, and use of the HDRC has not been previously investigated. Forty-five patients were prospectively randomized to one of three groups. ACT was measured before heparinization (1 mg/kg, 1 mg = 100 U), 5 minutes later, and then every 30 minutes until just prior to and after protamine administration. Group I received 1 mg/kg of protamine. In Groups II and III the residual heparin activity was interpolated from the HDRC and multiplied by 1.3 or 1.0, respectively, to derive the protamine dosage. Randomization created balanced groups with respect to demographic data. The individual peak effect of heparin ranged from 177% to 401% of control. The ACT returned to control after protamine in all groups. The protamine dose was significantly less when the HDRC was used (P < 0.05). Group III received the least protamine (0.64 ± 0.07 mb/kg, P < 0.05). No adverse protamine reactions or postoperative bleeding occurred. It is concluded that ACT monitoring and use of the HDRC provides a safe and easy method to individualize protamine dosage in vascular surgery.