Pharmacokinetic Research in Pediatric Extracorporeal Therapies: Current State and Future Directions

Abstract

Extracorporeal life support (ECLS), including extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT), are life-saving therapies for critically ill children. Despite this, these modalities carry frustratingly high mortality rates. One driver of mortality may be altered drug disposition due to a combination of underlying illness, patient-circuit interactions, and drug-circuit interactions. Children receiving ECMO and/or CRRT routinely receive 20 or more drugs, and data supporting optimal dosing is lacking for most of these medications. The Pediatric Paracorporeal and Extracorporeal Therapies Summit (PPETS) gathered an international group of experts in the fields of ECMO, CRRT, and other ECLS modalities to discuss the current state of these therapies, disseminate innovative support strategies, share clinical experiences, and foster future collaborations. Here, we summarize the conclusions of PPETS and put forward a pathway to optimize pharmacokinetic (PK) research in this population. We must prioritize specific medications for in-depth study to improve drug use in ECLS and patient outcomes. Based on frequency of use, potential for adverse outcomes if dosed inappropriately, and lack of existing PK data, a list of high priority drugs was compiled for future research. Researchers must additionally reconsider study designs, emphasizing pooling of resources through multi-center studies and the use of innovative PK modeling techniques. Finally, the integration of validated PK models into clinical practice must be streamlined to deliver optimal medication use at the bedside. Focusing on the proposed list of highlighted medications and key methodological considerations will maximize the impact of future research.