Propranolol binding in plasma during cardiopulmonary bypass

The effect of cardiopulmonary bypass on the plasma binding of propranolol was examined in seven patients. The fraction of propranolol free in plasma doubled, increasing from 6.6 to 13.5 per cent (P less than 0.001) following the administration of heparin, 400 IU/kg. Once cardiopulmonary bypass was concluded and protamine, 8 mg/kg, given, the free fraction decreased from 13.4 to 8.7 per cent (P less than 0.005). There was a further significant decrease to 6.5 per cent over the next 3.1 hours (SE +/- 0.3). Those alterations in the free fraction, which would result in more drug being available for binding to receptor sites and for exerting its pharmacologic effect, were due principally to the changes in free fatty acid levels produced by heparin and protamine, but also to the hemodilution produced by the pump prime.