Nicardipine intravenous bolus dosing for acutely decreasing arterial bloodpressure during general anesthesia for cardiac operations: Pharmacokinetics, pharmacodynamics, and associated effects on left ventricular function

The objective of this study was to evaluate the efficacy of nicardipine, a dihydropyridine calcium channel antagonist, administered as an IV bolus dos e to acutely decrease arterial pressure in anesthetized cardiac surgical pa tients. We performed a double-blind, randomized, self-controlled, dose-rang ing study in 40 adult cardiac surgical patients to determine the pharmacoki netics and pharmacodynamics of nicardipine 0.25 mg, 0.50 mg, 1.00 mg, and 2 .00 mg administered as an IV bolus. Transesophageal echocardiography was us ed to assess left ventricular preload, afterload, and global systolic funct ion. Plasma nicardipine concentration was measured using high-performance l iquid chromatography. Nicardipine selectively decreased arterial pressure i n a dose-dependent manner with a maximum response within 100 s and recovery to half the maximum response within 3-7 min without associated changes in heart rate. The decreases in arterial pressure were associated with only sm all decreases In left ventricular end-systolic wall stress and small increa ses in global left ventricular systolic function without changes in left ve ntricular end-diastolic cavity area or cardiac output. The time course for nicardipine bolus was consistent with a two-compartment pharmacokinetic mod el with rapid redistribution from a small central compartment. Implications : Nicardipine was effective for selectively decreasing arterial blood press ure acutely, but had no effects on ventricular preload or cardiac output. T he absence of dose-dependent changes in cardiac output, left ventricular sy stolic performance, and left ventricular afterload despite significant decr eases in arterial pressure suggested that nicardipine had a small negative inotropic action.