Effects of preoperative calcium entry blocker therapy on alpha-adrenergic responsiveness in patients undergoing...

Calcium entry blocking drugs (CaEBs) produce vasodilation and, in high doses, modify alpha adrenergic receptor function. Previous laboratory data suggested that CaEBs might alter the response to alpha-adrenergic stimulation. The authors tested the hypothesis that CaEB therapy altered alpha-adrenergic responsiveness in patients chronically treated with CaEBs. Twenty-six consenting patients with coronary artery disease were given a phenylephrine challenge before anesthesia induction and during cardiopulmonary bypass while the aorta was cross-clamped. A log dose response curve was constructed for each patient, and the ED30 (dose producing 30% increase in systemic vascular resistance) was calculated. Nine patients not treated with CaEB served as controls, and 17 patients were treated with nifedipine (n = 7) or diltiazem (n = 10). Mean ED30 was increased approximately three-fold in the CaEB treated groups compared to the control group. However, there was no statistical difference in the ED30 or phenylephrine dose response slopes between CaEB treated and untreated patients. In awake patients, ED30 correlated with nifedipine levels (R = 0.953, P = 0.01). There was a significant (P less than .02) shift in the ED30 from prior to anesthesia to during aortic cross-clamp and cardiopulmonary bypass; ED30 was approximately 50% less and correlated with CaEB level (R = 0.713, P = 0.03). Hemodynamic variables were not different between groups at any interval. Our data suggest that vascular responsiveness to phenylephrine in patients treated with CaEBs is diminished, but similar to that in untreated patients. Vascular responsiveness decreases in awake patients with increasing nifedipine levels.