Vancomycin sequestration during cardiopulmonary bypass surgery.
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.
Krivoy
N
N
Clinical Pharmacology Unit, Rambam Medical Center and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. N_Krivoy@rambam.health.gov.il
Yanovsky
B
B
Kophit
A
A
Zaher
A
A
Bar-El
Y
Y
Adler
Z
Z
Gaitini
L
L
Milo
S
S
D000368:Aged; D000900:Anti-Bacterial Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D002315:Cardiopulmonary Bypass; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010106:Oxygenators / Q000009:adverse effects*; D014640:Vancomycin / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D014640:Vancomycin