title: Nicardipine intravenous bolus dosing for acutely decreasing arterial blood pressure during general anesthesia for cardiac operations: pharmacokinetics, pharmacodynamics, and associated effects on left ventricular function.
abstract: The objective of this study was to evaluate the efficacy of nicardipine, a dihydropyridine calcium channel antagonist, administered as an IV bolus dose to acutely decrease arterial pressure in anesthetized cardiac surgical patients. We performed a double-blind, randomized, self-controlled, dose-ranging study in 40 adult cardiac surgical patients to determine the pharmacokinetics 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 used to assess left ventricular preload, afterload, and global systolic function. Plasma nicardipine concentration was measured using high-performance liquid chromatography. Nicardipine selectively decreased arterial pressure in 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 small decreases in left ventricular end-systolic wall stress and small increases in global left ventricular systolic function without changes in left ventricular end-diastolic cavity area or cardiac output. The time course for nicardipine bolus was consistent with a two-compartment pharmacokinetic model with rapid redistribution from a small central compartment.
  
  
  CONCLUSIONS
  Nicardipine was effective for selectively decreasing arterial blood pressure acutely, but had no effects on ventricular preload or cardiac output. The absence of dose-dependent changes in cardiac output, left ventricular systolic performance, and left ventricular afterload despite significant decreases in arterial pressure suggested that nicardipine had a small negative inotropic action.
authors.affiliation: Department of Anesthesia, University of Pennsylvania, Philadelphia 19104-4283, USA. cheungal@mail.med.upenn.edu
authors.forename: A T
authors.initials: AT
authors.lastname: Cheung
authors.forename: D V
authors.initials: DV
authors.lastname: Guvakov
authors.forename: S J
authors.initials: SJ
authors.lastname: Weiss
authors.forename: J S
authors.initials: JS
authors.lastname: Savino
authors.forename: I S
authors.initials: IS
authors.lastname: Salgo
authors.forename: Q C
authors.initials: QC
authors.lastname: Meng
mesh_terms: D000368:Aged; D000768:Anesthesia, General; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D002302:Cardiac Output / Q000187:drug effects; D006348:Cardiac Surgical Procedures; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D017548:Echocardiography, Transesophageal; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D009529:Nicardipine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D011446:Prospective Studies; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D009529:Nicardipine