Pharmacotherapy during pediatric extracorporeal membrane oxygenation: a review

ABSTRACT

Introduction: Pediatric critical illness and associated alterations in organ function can change drug pharmacokinetics (PK). Extracorporeal membrane oxygenation (ECMO), a life-saving therapy for severe cardiac and/or respiratory failure, causes additional PK alterations that affect drug disposition.

Areas covered: The purposes of this review are to discuss the PK changes that occur during ECMO, the associated therapeutic implications, and to review PK literature relevant to pediatric ECMO. We discuss various classes of drugs commonly used for pediatric patients on ECMO, including sedatives, analgesics, antimicrobials and cardiovascular drugs. Finally, we discuss future areas of research and recommend strategies for future pediatric ECMO pharmacologic investigations.

Expert opinion: Clinicians caring for pediatric patients treated with ECMO must have an understanding of PK alterations that could lead to either therapeutic failures or increased drug toxicity during this life-saving therapy. Limited data currently exist for optimal drug dosing in pediatric populations who are treated with ECMO. While there are clear challenges to conducting and analyzing data associated with clinical pharmacokinetic-pharmacodynamic studies of children on ECMO, we present techniques to address these challenges. Improved understanding of the physiology and drug disposition during ECMO combined with PK-PD modeling will allow for more adaptable and individualized dosing schemes.

KEYWORDS:

• ECMO
• pharmacokinetics
• pharmacodynamics
• pediatric

Article highlights

• Extracorporeal membrane oxygenation (ECMO) is a life-saving therapy for severe cardiac and/or respiratory failure that has unique effects on drug disposition.

• Drug sequestration by ECMO circuit components is increased with lipophilic drugs and drugs that are highly protein-bound. Drug sequestration is likely affected by the circuit age, circuit fluid prime composition, modified surface coatings for circuit tubing, and by the presence and characteristics of active drug metabolites.

• Currently, there is limited non-neonatal and non-infant pediatric pharmacokinetic (PK) data to provide dosing guidance for many drugs commonly used during ECMO.

• Sedatives, analgesics, and antimicrobial drugs have the most pediatric-specific PK data available.

• Insights from large animal models of pediatric ECMO and collaborative opportunistic or adaptive human clinical studies should be combined with pharmacokinetic-pharmacodynamic modeling so that more targeted dosing strategies can be developed for pediatric patients treated with ECMO.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.