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J Thorac Cardiovasc Surg 2004;128:211-219
© 2004 The American Association for Thoracic Surgery

Cardiopulmonary support and physiology

Can extra protamine eliminate heparin rebound following cardiopulmonary bypass surgery?

^a Department of Surgery, McMaster University, and the Henderson Research Centre, Hamilton, Ontario, Canada
^b Department of Pathology and Molecular Medicine, McMaster University, and the Henderson Research Centre, Hamilton, Ontario, Canada
^c Department of Clinical Epidemiology and Biostatistics, McMaster University, and the Henderson Research Centre, Hamilton, Ontario, Canada
^d Department of Medicine, McMaster University, and the Henderson Research Centre, Hamilton, Ontario, Canada

Received for publication August 7, 2003; revisions received December 3, 2003; accepted for publication December 11, 2003.

^* Address for reprints: Edward Young, PhD, Hamilton Regional Laboratory Medicine Program, Henderson General Hospital Site, 711 Concession Street, Hamilton, Ontario, Canada L8V 1C3
younged{at}hhsc.ca

OBJECTIVES: Heparin rebound, the reappearance of anticoagulant activity after adequate neutralization with protamine, is thought to contribute to excessive postoperative bleeding after cardiac surgery. We have previously demonstrated that a significant amount of heparin is bound nonspecifically to plasma proteins and is incompletely neutralized by protamine. The aim of this study was to investigate whether clinically important bleeding attributable to heparin rebound can be eliminated by infusion of small amounts of additional protamine for 6 hours postoperatively and whether this treatment can reduce mediastinal blood loss.

METHODS: Three hundred patients undergoing elective cardiac surgery were randomized to receive either a continuous infusion of protamine sulphate (25 mg/h for 6 hours) postoperatively or saline placebo. Serial blood samples were obtained to measure thrombin clotting time and anti-factor Xa activity. Heparin bound nonspecifically to plasma proteins was measured after displacement with a chemically altered heparin with low affinity to antithrombin. Mediastinal blood loss and transfusion requirements were recorded.

RESULTS: Heparin rebound was demonstrated in every 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 after surgery. In contrast, heparin rebound was eliminated in the protamine infusion group. The thrombin clotting time was normalized and both heparin concentration and protein-bound heparin were almost undetectable (P < .001). There was a modest 13% reduction in postoperative bleeding but this did not reduce blood transfusions. No adverse events were attributable to the extra protamine.

CONCLUSIONS: Postoperative protamine infusion was able to almost totally abolish heparin rebound. In the context of this study, protamine infusion resulted in reduced postoperative bleeding but the magnitude was insufficient to alter transfusion requirements.

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