Pediatric Critical Care Medicine
OBJECTIVES: Describe the pharmacokinetics of antithrombin in pediatric patients undergoing ventricular assist device therapy and provide dosing recommendations for antithrombin in this population.
DESIGN: A retrospective population pharmacokinetic study was designed.
SETTING: Large tertiary care children's hospital Subject inclusion criteria consisted of less than 19 years old.
PATIENTS: Subjects less than 19 years old undergoing therapy with a HeartWare ventricular assist device (HeartWare, Framingham, MA) or Berlin EXCOR ventricular assist device (Berlin GmbH, Berlin, Germany), who received a dose of antithrombin with a postdose antithrombin activity level from January 1, 2011, to June 30, 2017.
INTERVENTIONS: Population pharmacokinetic analysis and simulation using NONMEM v.7.4 (Icon, PLC, Dublin, Ireland).
MEASUREMENTS AND MAIN RESULTS: A total of 41 patients met study criteria (median age, 5.8 years [interquartile range, 1.6-9.9 yr]), and 53.7% underwent therapy with the pulsatile Berlin EXCOR pediatric ventricular assist device (Berlin Heart GmbH, Berlin, Germany). All patients received unfractionated heparin continuous infusion at a mean ± SD dose of 29 ± 14 U/kg/hr. A total of 181 antithrombin doses (44.1 ± 24.6 U/kg/dose) were included, and baseline antithrombin activity levels were 77 ± 12 U/dL. Antithrombin activity levels were drawn a median 19.9 hours (interquartile range, 8.8-41.6 hr) after antithrombin dose. A one-compartment proportional error model best fit the data, with allometric scaling of fat-free mass providing a better model fit than actual body weight. Unfractionated heparin and baseline antithrombin were identified as significant covariates. A 50 U/kg dose of antithrombin had a simulated half-life 13.2 ± 6.6 hours.
CONCLUSIONS: Antithrombin should be dosed on fat-free mass in pediatric ventricular assist device patients. Unfractionated heparin dose and baseline antithrombin activity level should be considered when dosing antithrombin in pediatric ventricular assist device patients.
Antithrombins, Body Composition, Body Weights and Measures, Computer Simulation, Dose-Response Relationship, Drug, Female, Half-Life, Heart-Assist Devices, Heparin, Hospitals, Pediatric, Humans, Male, Retrospective Studies, Tertiary Care Centers