Objectives: Determine the pharmacokinetic disposition of vancomycin in the pediatric ventricular assist device population.
Design: A retrospective, population pharmacokinetic study.
Setting: Large, quaternary care children's hospital.
Patients: Less than 19 years old initiated on vancomycin while undergoing ventricular assist device therapy from 2011 to 2018 in our institution.
Interventions: Patient data were summarized by using descriptive statistical methods, and population pharmacokinetic analysis was performed by using NONMEM (Icon, PLC, Dublin, Ireland). Simulation was performed to identify a vancomycin dosing strategy that resulted in a trough concentration less than 15 mg/L and an area under the curve0-24:minimum inhibitory concentration ratio of greater than 400.
Measurements and main results: A total of 69 patients (male 50.7%, median age 7.1 years [interquartile range, 2.4-11.9]) met study criteria (HeartWare [Framingham, MA] = 37, Berlin Heart [Berlin, Germany] = 22, Impella [Abiomed, Danvers, MA] = 4, RotaFlow [Maquet, Hirrlingen, Germany] right ventricular assist device = 3, HeartMate II [Abbott Laboratories, Abbott Park, IL] = 2, Berlin Heart biventricular assist device = 1). Patients received a median of 21 doses (interquartile range, 13-44 doses) of IV vancomycin (14.8 ± 1.8 mg/kg/dose) along with vancomycin as an intrathoracic irrigation (n = 48; 69.6%). The mean serum concentration was 12.2 ± 5.2 mg/L at 11.2 ± 6.9 hours after a dose. A one-compartment pharmacokinetic model best fit the data with allometric scaling on clearance and volume of distribution. Clearance was characterized by total body weight and serum creatinine, and volume of distribution was characterized by total body weight. Simulation identified doses greater than 15 mg/kg/dose with extended intervals were necessary to achieve endpoints.
Conclusions: Vancomycin dosing in pediatric ventricular assist device patients should be altered in comparison to nonventricular assist device patients and should be accompanied with frequent serum concentration monitoring.