Continuous infusion of nimodipine during coronary artery surgery: haemodynamic and pharmacokinetic study

A continuous infusion of nimodipine 15 or 30 micrograms kg-1 h-1 was administered from the evening before operation to the second morning after operation to 14 patients undergoing elective coronary artery bypass grafting (CABG) surgery. Nimodipine was tolerated well by all seven patients who received the lower dose. However, of the seven patients who received the higher dose, in two patients the infusion had to be discontinued after induction of anaesthesia and immediately after surgery, respectively, because of excessive vasodilatation and hypotension. At steady state before cardiopulmonary bypass (CPB), total plasma nimodipine concentration was higher than expected on the basis of previous reports in non-surgical subjects. Similarly, mean clearance of nimodipine was lower than predicted, that is 0.53 (range 0.40-0.72) litre kg-1 h-1. Initiation of CPB decreased total plasma nimodipine concentration, but the unbound plasma concentration did not decrease because of the increase observed in the free fraction of nimodipine in plasma. As evaluated in a separate closed extracorporeal circuit, nimodipine was sequestered into the circuit. Addition of stored whole blood to the priming solution attenuated this sequestration. It is concluded that clearance of nimodipine, as assessed before CPB at steady state, was reduced in patients undergoing CABG and receiving a continuous infusion of nimodipine. Using this finding of decreased clearance in designing infusion schemes of nimodipine for cardiac-surgical patients, it should be possible to predict more accurately the desired plasma nimodipine concentration and therefore reduce the possibility of unexpected haemodynamic responses.