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Delivery of Cardioactive Therapeutics in a Porcine Myocardial Infarction Model
Published on: February 10, 2023
Vancomycin sequestration during cardiopulmonary bypass surgery
N Krivoy1, B Yanovsky, A Kophit
1Clinical Pharmacology Unit, Rambam Medical Center and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. N_Krivoy@rambam.health.gov.il
Objective:
The present study was designed to analyze vancomycin disposition in adult patients undergoing coronary bypass grafting during and following cardiopulmonary bypass (CPB).
Methods:
Coronary bypass surgery was performed on 11 adults with a mean age (SD) of 62.9 (9.0) years old, who received a mean (SD) vancomycin prophylactic dose of 12.7 (1.0) mg/kg in a mean period of 41 (0.7) min. Using a two-compartment open model for pharmacokinetic analysis, the following parameters were obtained: alpha half-life, minutes (t(1/2alpha)); beta half-life, hours (t(1/2beta)); apparent volume of distribution, (V(d) l/kg); volume of the central compartment, (V(c) l/kg), constant between the "central to the peripheral" compartment, (k(12)); constant between the "peripheral to the central" compartment, (k(21)); total area under the concentration-time curve, (AUC mg/lxh) and a vancomycin clearance, (Cl(van) ml/min), respectively.
Results:
The mean (SD) calculated pharmacokinetic parameters were: t(1/2alpha)17.6 (6) min, t(1/2beta) 8.4 (3.8) h, V(d) 0.803 (0.259) l/kg, V(c) 0.270 (0.162) l/kg, k(12) 0.03 (0.015), k(21) 0.012 (0.012), total AUC 10377.2 (3687.6) mg/lxh. The mean (SD) vancomycin clearance by the CPB machine was 9.51 (2.66) l/h, and the mean (SD) total vancomycin sequestrated by CPB was 331.7 (84) mg. A significant difference (6.3%; p = 0.001) was measured between the mean measured AUC during CPB (1088.1 +/- 253.9) and the same calculated parameter (1160.2 +/- 282). Five minutes after starting CPB, a decrease in vancomycin level was detected; this difference was found to be nearly 11% in absolute values.
Conclusions:
This confirmatory study demonstrated that the vancomycin blood concentrations obtained during the study allow recommending a safety prophylactic dose of 12mg/kg in adults who undergo open-heart surgery under CPB conditions. Sequestration of vancomycin by the oxygenator or/and tubing system of the CPB machine had occurred and had been measured in this study.
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