Therapeutic Drug Monitoring of Vancomycin in Pediatric Patients With Extracorporeal Membrane Oxygenation Support

J Pediatr Pharmacol Ther. Jul-Aug 2018;23(4):305-310. doi: 10.5863/1551-6776-23.4.305.

Abstract

Objectives: Determine pharmacokinetic (PK) parameters and optimal dosage of vancomycin for children on extracorporeal membrane oxygenation (ECMO).

Methods: Retrospective PK study of vancomycin in pediatric patients on ECMO who received IV vancomycin 40 to 60 mg/kg/day every 6 hours. Patients were analyzed according to the presence of acute kidney injury (AKI) and requirement of renal replacement therapy (RRT).

Results: Data from 40 children, with a median age of 2.7 years of age (1 month to 14 years) were evaluated. Thirty-two patients (80%) received vancomycin. Vancomycin therapeutic drug monitoring was performed in 29 patients. The subgroup without AKI or RRT were 15. With initial doses, vancomycin trough levels were within therapeutic range in 53% of patients. After dose change, 93% of patients achieved therapeutic levels. The adjusted dose was 40 (34-60) mg/kg/day every 6 hours. Estimated PK parameters were clearance (CL) 1.67 (1-1.67) mL/kg/min; volume of distribution (Vd) 0.73 (0.7-0.9) L/kg; and half-life (t½) 6.2 (4.9-8.06) hours. In the AKI subgroup, 11 patients, the initial median dose was 40 (30-45) mg/kg/day every 8 (6-12) hours. Trough concentrations of vancomycin were within therapeutic range in 27% of patients. After dose modifications, 63% of patients achieved target trough concentration. The final adjusted dose was 20 mg/kg/day (15-30) every 12 (12-24) hours. Estimated PK parameters were Vd 1.16 (0.68-1.6) L/kg; CL 0.83 (0.38-1) mL/kg/min; and a t½ of 23.6 (16.2-31) hours.

Conclusions: In patients without AKI or RRT, Vd of vancomycin was similar and CL was lower compared to pediatric critically ill patients without ECMO. Treatment could be started at 40 mg/kg/day every 6 hours. In patients with AKI, the use of lower doses should be used.

Keywords: acute kidney injury; extracorporeal membrane oxygenation; pediatric; pharmacokinetics; renal replacement therapy; therapeutic drug monitoring; vancomycin.