British Journal of Anaesthesia, 1995, Vol. 74, No. 5 526-533
© 1995 The Board of Management and Trustees of the British Journal of Anaesthesia
research-article |
Continuous infusion of nimodipine during coronary artery surgery: haemodynamic and pharmacokinetic study
Department of Anaesthesia, Cardiothoracic Anaesthesia Group, Helsinki University Central Hospital Haartmaninkatu 4, FIN-00290 Helsinki, Finland
Department of Thoracic and Cardiovascular Surgery, Helsinki University Central Hospital Haartmaninkatu 4, FIN-00290 Helsinki, Finland
Department of Neurology, Helsinki University Central Hospital Haartmaninkatu 4, FIN-00290 Helsinki, Finland
Clinical Pharmacology International Bayer AG, Aprather Weg, D-42096 Wuppertal, Germany
Correspondence to M. H.
A continuous infusion of nimodipine 15 or 30 µg kg1 h1 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 0.400.72) litre kg1 h1. 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. (Br. J. Anaesth. 1995; 74: 526533)
Presented in part at the Second International Conference on the Brain and Cardiac Surgery, Key West, Florida, September, 1992.