Objectives Heparin rebound, the reappearance of anticoagulant activity after a dequate neutralization with protamine, is thought to contribute to excessive pos toperative bleeding after cardiac surgery. We have previo...Objectives Heparin rebound, the reappearance of anticoagulant activity after a dequate neutralization with protamine, is thought to contribute to excessive pos toperative bleeding after cardiac surgery. We have previously demon-strated tha t a significant amount of heparin is bound nonspecifically to plasma proteins an d is incompletely neutralized by protamine. The aim of this study was to investi gate whether clinically important bleeding attributable to heparin rebound can b e eliminated by infusion of small amounts of additional protamine for 6 hours po stoperatively and whether this treatment can reduce mediastinal blood loss. Meth ods Three hundred patients undergoing elective cardiac surgery were randomized t o receive either a continuous infusion of protamine sulphate(25 mg/h for 6 hours ) postoperatively or saline placebo. Serial blood samples were obtained to measu re thrombin clotting time and anti-factor Xa activity. Heparin bound nonspecifi cally to plasma proteins was measured after displacement with a chemically alter ed heparin with low affinity to antithrombin. Mediastinal blood loss and transfu sion requirements were recorded. Results Heparin rebound was demonstrated in eve ry patient in the placebo group as reflected by increased thrombin clotting time , anti-factor Xa activity, and protein-bound heparin between 1 and 6 hours aft er surgery. In contrast, heparin rebound was eliminated in the protamine infusio n group. The thrombin clotting time was normalized and both heparin concentratio n and protein-bound heparin were almost undetectable (P < .001). There was a mo dest 13%reduction in postoperative bleeding but this did not reduce blood trans fusions. No adverse events were attributable to the extra protamine. Conclusions Postoperative protamine infusion was able to almost totally abolish heparin reb ound. In the context of this study, protamine infusion resulted in reduced posto perative bleeding but the magnitude was insufficient to alter transfusion requir ements.展开更多
文摘Objectives Heparin rebound, the reappearance of anticoagulant activity after a dequate neutralization with protamine, is thought to contribute to excessive pos toperative bleeding after cardiac surgery. We have previously demon-strated tha t a significant amount of heparin is bound nonspecifically to plasma proteins an d is incompletely neutralized by protamine. The aim of this study was to investi gate whether clinically important bleeding attributable to heparin rebound can b e eliminated by infusion of small amounts of additional protamine for 6 hours po stoperatively and whether this treatment can reduce mediastinal blood loss. Meth ods Three hundred patients undergoing elective cardiac surgery were randomized t o receive either a continuous infusion of protamine sulphate(25 mg/h for 6 hours ) postoperatively or saline placebo. Serial blood samples were obtained to measu re thrombin clotting time and anti-factor Xa activity. Heparin bound nonspecifi cally to plasma proteins was measured after displacement with a chemically alter ed heparin with low affinity to antithrombin. Mediastinal blood loss and transfu sion requirements were recorded. Results Heparin rebound was demonstrated in eve ry patient in the placebo group as reflected by increased thrombin clotting time , anti-factor Xa activity, and protein-bound heparin between 1 and 6 hours aft er surgery. In contrast, heparin rebound was eliminated in the protamine infusio n group. The thrombin clotting time was normalized and both heparin concentratio n and protein-bound heparin were almost undetectable (P < .001). There was a mo dest 13%reduction in postoperative bleeding but this did not reduce blood trans fusions. No adverse events were attributable to the extra protamine. Conclusions Postoperative protamine infusion was able to almost totally abolish heparin reb ound. In the context of this study, protamine infusion resulted in reduced posto perative bleeding but the magnitude was insufficient to alter transfusion requir ements.
