Applying Antimicrobial Pharmacokinetic Principles for Complex Patients: Critically Ill Adult Patients Receiving Extracorporeal Membrane Oxygenation and Renal Replacement Therapy

Purpose of Review Extracorporeal membrane oxygenation (ECMO) is establishing itself as the standard of care for managing critically ill patients who have exhausted conventional treatment in many adult ICUs around the world. The integration and combined extracorporeal effects of this device with renal replacement therapy (RRT) have not been well studied. This is especially challenging in the pursuit of achieving optimal antimicrobial exposures in this group of critically ill patients. The objective of this review is to discuss the available literature to support clinicians in navigating dosing challenges in this clinical scenario. Recent Findings The number of antimicrobial pharmacokinetic (PK) studies in patients on RRT and ECMO is growing. However, very few studies have been designed to describe the combined effects of the concurrent use of two extracorporeal circuits. Currently available literature consists of studies with small sample sizes and provides inconsistent findings. Nevertheless, it is clear that it is not a simple sum of the independent RRT- and ECMO-induced PK changes in addition to the PK changes arising from severe physiological derangement associated with a critical illness. Preliminary data suggest that improvements in target attainment may be achieved through understanding the potential PK changes secondary to specific drug physicochemical properties and the extracorporeal circuits. Thus, the availability of therapeutic drug monitoring plays a key role in this complex patient group to recognise ineffective and toxic serum antimicrobial concentrations. The data available to clinicians are insufficient to guide appropriate empirical drug dosing in patients on concurrent ECMO and RRT. Future studies should be designed and powered to evaluate specific RRT settings and relevant covariates within the ECMO population. Until further data becomes available, therapeutic drug monitoring is recommended to prevent subtherapeutic and toxic concentrations of antimicrobials in this patient population.