Abstract
The pharmacokinetics of some beta-blockers are altered by cardiopulmonary bypass (CPB). The objective of this study was to compare the effect of coronary artery bypass graft (CABG) surgery employing CPB on the pharmacokinetics of propranolol and atenolol. We studied patients receiving oral propranolol with doses ranging from 80 to 240 mg (N = 11) or atenolol with doses ranging from 25 to 100 mg (N = 8) in the pre- and postoperative period of CABG with moderately hypothermic CPB (32 degrees C). On the day before and on the first day after surgery, blood samples were collected before beta-blocker administration and every 2 h thereafter. Plasma levels were determined using high-performance liquid chromatography and data were treated by pharmacokinetics-modelling. Statistical analysis was performed using ANOVA or the Friedman test, as appropriate, and P < 0.05 was considered to be significant. A prolongation of propranolol biological half-life from 5.41 +/- 0.75 to 11.46 +/- 1.66 h (P = 0.0028) and an increase in propranolol volume of distribution from 8.70 +/- 2.83 to 19.33 +/- 6.52 L/kg (P = 0.0032) were observed after CABG with CPB. No significant changes were observed in either atenolol biological half-life (from 11.20 +/- 1.60 to 11.44 +/- 2.89 h) or atenolol volume of distribution (from 2.90 +/- 0.36 to 3.83 +/- 0.72 L/kg). Total clearance was not changed by surgery. These CPB-induced alterations in propranolol pharmacokinetics may promote unexpected long-lasting effects in the postoperative period while the effects of atenolol were not modified by CPB surgery.
Highlights
Several β-adrenoreceptor antagonists (β-blockers) have been used for the treatment of angina, and the choice depends on the selectivity in relation to the type of βreceptors, antiarrhythmic actions, intrinsic sympathomimetic activity, potency, lipid solubility, blocking of α-adrenoceptors, oxidation phenotype, effects on serum lipids, and membrane-stabilizing activity [1]. β-adrenoreceptor antagonists improve acute outcomes and long-term prognosis in ischemic heart disease [2] and reduce perioperative events among high-risk patients undergoing major non-cardiac and vascular surgery [3,4]
Because it is known that the dose of propranolol necessary to obtain an adequate β-blockade effect in the postoperative period, in order to reduce heart rate to
Patients scheduled for coronary artery bypass graft (CABG) under moderate hypothermic CPB and receiving propranolol (N = 11) or atenolol (N = 8) preoperatively were enrolled in the study
Summary
Several β-adrenoreceptor antagonists (β-blockers) have been used for the treatment of angina, and the choice depends on the selectivity in relation to the type of βreceptors, antiarrhythmic actions, intrinsic sympathomimetic activity, potency, lipid solubility, blocking of α-adrenoceptors, oxidation phenotype, effects on serum lipids, and membrane-stabilizing activity [1]. β-adrenoreceptor antagonists improve acute outcomes and long-term prognosis in ischemic heart disease [2] and reduce perioperative events among high-risk patients undergoing major non-cardiac and vascular surgery [3,4]. Preoperative βblocker therapy has been shown to reduce the incidence of intraoperative ischemic events related to increases in heart rate and hemodynamic responses to surgical stimulation during coronary artery bypass graft (CABG) [5,6]. Because it is known that the dose of propranolol necessary to obtain an adequate β-blockade effect in the postoperative period, in order to reduce heart rate to
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