Piperacillin Population Pharmacokinetics in Children Supported With Extracorporeal Membrane Oxygenation
Adrien Arsène, Mehdi Oualha, Jérôme Rambaud, Sihem Benaboud, Saik Urien, Marion Grimaud, Sylvain Renolleau, Pierre-Louis Léger, Déborah Hirt, Jean-Marc Tréluyer, Agathe BérangerObjective:
To characterize piperacillin population pharmacokinetics (PK) in critically ill children with and without extracorporeal membrane oxygenation (ECMO) support and to optimize piperacillin dosing regimens to attain the PK target of 100% free time above minimum inhibitory concentration (fT > minimum inhibitory concentration).
Design:
Post hoc secondary analysis of a two-center, population PK modeling and simulation study (registered at clinicaltrials.gov, NCT02539407).
Settings:
PICUs at tertiary care centers, September 2015–November 2021.
Patients:
Thirty-three children supported with ECMO and 50 non-ECMO control patients treated with piperacillin (± tazobactam).
Interventions:
Administration of piperacillin at 300 mg/kg/d by continuous infusion or 75 mg/kg every 6 hours by intermittent infusion.
Measurements and Main Results:
A one-compartment linear-elimination model described best the piperacillin data. Clearance was driven by body weight and estimated glomerular filtration rate (eGFR). In a typical 11-kg patient, ECMO circuit volume-to-weight ratio increased the volume of distribution by 34%. Monte Carlo simulations across eGFR strata (30–60, 60–90, 90–150, 150–200, 200–300 mL/min/1.73 m 2 ) showed that a continuous infusion of 300 mg/kg/d allowed greater than or equal to 90% of target attainment in all groups. Patients with an eGFR greater than 200 mL/min/1.73 m 2 required 400 mg/kg/d to have 90% of target attainment.
Conclusions:
Continuous infusion of 300 mg/kg/d piperacillin reliably achieves PK target across all renal‐function ranges in children undergoing support with ECMO. Dose escalation to 400 mg/kg/d is required for augmented renal clearance (eGFR > 200 mL/min/1.73 m 2 ).