Protamine dosage effects on complement activation and sonoclot coagulation analysis after cardiac surgery

Background: An optimal dosage and infusion regime for protamine reversal of heparin after cardiopulmonary bypass is important. Methods: Protamine dosages of either 2mg/kg or 4mg/kg bodyweight were compared in 40 patients after first time coronary arterial bypass grafting. Protamine was infused with a syringe driver over 20 minutes. Arterial blood sampling was performed prior to and during surgery, before and at 0.3, 0.6, 1, 3, 6 and 25h after the protamine infusion. C3a-desArg and C4a-desArg were analysed by radioimmunoassay. Coagulation was assayed with Sonoclot and activated clotting time. Results: Significantly higher inter-group plasma levels of C3a-desArg were seen with the greater protamine dose from 0.30.6h, but none for C4a-desArg. Sonoclot parameters and leucocyte count differed significantly between the groups up to 6h, indicating hypercoagulabilty with the higher protamine dose. Significantly longer ACT in the low protamine dosage group indicited unblocked heparin with nonsignificant increased drainage bleeding and transfusions. There were no signs of allergic or anaphylactic reactions in any of the groups. Conclusion: Keeping the protamine dose low, minimizes complement activation with less viscoelastic signs of hypercoagulability. However there is an increased risk for drainage bleeding and unnecessary transfusion if heparin is not fully reversed with protamine post cardiopulmonary bypass. The present study was underpowered to detect significant differences in bleeding.