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Population Pharmacokinetics of Vancomycin in Pediatric Extracorporeal Membrane Oxygenation*

Objectives: Describe the pharmacokinetics of vancomycin in pediatric patients undergoing extracorporeal membrane oxygenation and provide dosing recommendations to attain an area under the curve for 24 hours greater than 400 in this population. Design: Retrospective, population pharmacokinetic analysis. Setting: PICU of a large tertiary care children’s hospital. Interventions: Population pharmacokinetic analysis and simulation were performed with NONMEM v7.3 (Icon, PLC, Dublin, Ireland). Patients: Patients less than 19 years old who received IV vancomycin and had serum vancomycin concentration monitoring while undergoing extracorporeal membrane oxygenation from January 1, 2011, to June 30, 2017. Measurements and Main Results: A total of 93 patients met study criteria (male 51%, median age 0.64 yr [interquartile range 0.07–6.7 yr]). Mean estimated creatinine clearance was 65 ± 47 mL/min/1.73 m2. Patients received 1,116 vancomycin doses (14.6 ± 1.9 mg/kg/dose) and had 433 vancomycin serum concentrations (13.6 ± 6.9 mg/L) at 13.2 ± 10.7 hours after a dose. A two-compartment pharmacokinetic model with allometrically scaled weight on clearance (0.75) and volumes of distribution (1) was developed. Serum creatinine, postmenstrual age were significant covariates for clearance, patient age for central volume of distribution, and albumin for peripheral volume of distribution. Simulation identified a doses of 25–30 mg/kg/dose every 12–24 hours as having the highest percentage of patients with an area under the curve for 24 hours greater than 400 with the highest percentage trough concentrations in the less than 15 mg/L range. Conclusions: A vancomycin dose of 25–30 mg/kg/dose every 12–24 hours with serum concentration monitoring is a reasonable empiric dosing strategy to obtain an area under the curve for 24 hours greater than 400 in pediatric extracorporeal membrane oxygenation patients.