Cefuroxime Pharmacokinetics in Pediatric Cardiovascular Surgery Patients Undergoing Cardiopulmonary Bypass

• Published in: Journal of cardiothoracic and vascular anesthesia Vol. 25; no. 3; pp. 425 - 430
• Main Authors: Knoderer, Chad A., PharmD, Saft, Sarah A., PharmD, Walker, Scott G., MD, Rodefeld, Mark D., MD, Turrentine, Mark W., MD, Brown, John W., MD, Healy, Daniel P., PharmD, Sowinski, Kevin M., PharmD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-06-2011
• Subjects: Anesthesia & Perioperative Care; cardiopulmonary bypass; Cardiopulmonary Bypass - methods; Cardiovascular Surgical Procedures - methods; cefuroxime; Cefuroxime - blood; Cefuroxime - pharmacokinetics; Child, Preschool; chromatography; Critical Care; Female; Humans; Infant; liquid; Male; pediatric; pharmacokinetics; Prospective Studies; cardiopulmonary bypass; pharmacokinetics; cefuroxime; liquid; chromatography; pediatric
• ISSN: 1053-0770; 1532-8422
• DOI: 10.1053/j.jvca.2010.07.022

Objectives The objective of this study was to determine the pharmacokinetics of cefuroxime in children undergoing cardiopulmonary bypass (CPB) for cardiovascular surgery. Design A prospective study. Setting A tertiary pediatric teaching hospital. Participants Infants and children undergoing CPB were enrolled in the study. Intervention An initial dose (mean, 24.2 ± 1.6 mg/kg) of cefuroxime was administered before surgical incision, and a second dose (mean, 14.4 ± 7.9 mg/kg) was administered in the CPB prime solution. Serial blood samples were obtained before, during, and after the CPB process. Samples were shipped on dry ice to the analytic laboratory and concentrations determined by a validated high-performance liquid chromatography method. A 2-compartment pharmacokinetic model was fitted to the data using maximum a priori–Bayesian estimation, with weight as a covariate. Monte Carlo simulations of a single-dose (25 mg/kg pre-CPB) approach and a 2-dose (25 mg/kg pre- and 12.5-mg/kg prime solution dose) approach were performed. Measurements and Main Results Fifteen subjects (9 males/6 females) were enrolled in the study, with median (range) age and weight of 11 (3-34) months and 9.5 (4.5-15.4) kg, respectively. The median (range) duration of CPB was 136 (71-243) minutes. Median and range cefuroxime pharmacokinetic parameters were as follows: maximum concentration (Cmax) dose, 1: 328 (150-512) μg/mL; systemic clearance, 0.050 (0.041-0.058) L/h/kg; steady-state volume of distribution, 0.213 (0.081-0.423) L/kg; volume of distribution in the central compartment, 0.081 (0.046-0.162) L/kg; and elimination half-life, 3.76 (1.03-6.81) hours. The median 8-hour post–dose-simulated cefuroxime concentrations were 26.5 and 16.0 mg/L for the 2-dose and single-dose regimens, respectively. Conclusion Manufacturers recommend that pediatric doses of cefuroxime (25-50 mg/kg) can be used in infants and children undergoing CPB to maintain adequate serum concentrations for surgical-site infection prophylaxis. A second intraoperative dose, administered through the CPB circuit, provides no additional prophylactic advantage.