Vancomycin Dosing and Pharmacokinetics in Postoperative Pediatric Cardiothoracic Surgery Patients.

Abstract

This study compared vancomycin trough concentrations and pharmacokinetic parameters in pediatric cardiothoracic surgery (CTS) patients versus those in controls receiving 20 mg/kg/dose, intravenously, every 8 hours. A retrospective study was conducted in children <18 years of age, following CTS, versus an age-and sex-matched control group. The primary objective was to determine differences in trough concentrations between groups. Secondary objectives included comparisons of pharmacokinetics between groups and development of vancomycin-associated acute kidney injury (AKI), defined as a doubling in serum creatinine from baseline. Also dosing projections were developed to target an area-under-the-curve-to-minimum inhibitory concentration (AUC:MIC) ratio of ≥400. Twenty-seven patients in each group were evaluated. Mean trough concentrations were significantly different between groups (CTS: 18.4 mg/L; control: 8.8 mg/L; p < 0.01). Vancomycin-associated acute kidney injury AKI was significantly higher in the CTS group than in controls (25.9% versus 0%, respectively, p<0.01). There were significant differences in vancomycin elimination rates, with a high degree of variability, but no statistical differences in other parameters. Based on dosing projections, CTS patients would require 21 to 88 mg/kg/day, with a dosage interval determined by the child's glomerular filtration rate to achieve the target AUC:MIC ≥400. Vancomycin dosage of 20 mg/kg/dose intravenously every 8 hours achieved significantly higher trough concentrations in CTS patients than in controls. Pharmacokinetic parameters were highly variable in CTS patients, indicating more individualization of dosage is needed. A future prospective study is needed to determine whether the revised dosage projections achieve the AUC:MIC target and to determine whether these regimens are associated with less vancomycin-associated AKI.