Abstract P-114: PHARMACOKINETIC ANALYSIS OF UNFRACTIONATED HEPARIN IN CRITICALLY ILL CHILDREN DURING EXTRACORPOREAL MEMBRANE OXYGENATION: DO WE ACHIEVE THE TARGET?

Abstract

Aims & Objectives: We described the unfractionated heparin dosing regimens and resulting anti-Xa activities in children during the first week of ExtraCorporeal Membrane Oxygenation (ECMO). Methods We included children who were under ECMO for refractory hemodynamic failure related to (i) myocarditis or (ii) septic shock. Anti-Xa activity time-courses were analyzed using a non linear mixed effects approach with Monolix version 2016R. Results Au total of 12 children were included (septic shock, n = 6; myocarditis; n = 6) with a median age of 42 months (0–197), a median weight of 17.7 Kg (4.9–69). Bleeding occurred in 2 children and thrombosis in 4. Initial dosing ranging from 15 IU/kg/h to 215 IU/kg/h. Anti-Xa activity was in the target (0.4 to 0.6 IU/mL) in 96 samples (45 %), < 0,4 IU/mL in 81 samples (38 %) and > 0,6 IU/mL in 37 samples (17 %). All children observed at least one time an anti-Xa activity out of the target. Anti-Xa activity time-courses were well described by a one-compartment open model with first order elimination. Body weight (BW) was the main covariate explaining clearance (CL) and volume of distribution (V) between subject variabilities. Parameter estimates were CLi = CLTYP*(BW/70)3/4; Vi = VTYP*(BW(t)/70)1; where typical clearance (CLTYP) and typical volume of distribution (VTYP) were 2.42 L.h-1 and 5.1 L, respectively. Conclusions Unfractionated heparin standard dosing regimen and empirical adjustments are not appropriate to reach and maintain the target. PK modeling may help the physician to achieve the target range from the initial dose and during the maintenance doses.