# Optimizing Drug Therapy in ECMO-Supported Critically Ill Adults: A Narrative Review and Clinical Guide

## TL;DR

This review provides guidance on adjusting drug doses for critically ill adults on ECMO, highlighting how ECMO affects drug behavior and the need for personalized treatment.

## Contribution

The paper offers a practical clinical guide for optimizing pharmacotherapy in ECMO patients based on current evidence.

## Key findings

- Hydrophilic drugs like β-lactams show minimal ECMO-related changes, with dosing mainly influenced by kidney function.
- Lipophilic and protein-bound drugs such as fentanyl and midazolam require higher doses and monitoring due to ECMO circuit effects.
- Individualized dosing with therapeutic drug monitoring is crucial for effective treatment in ECMO patients.

## Abstract

Extracorporeal membrane oxygenation (ECMO) is increasingly used to support critically ill adults with severe cardiac or respiratory failure, but ECMO circuits and the physiological disturbances of critical illness significantly alter drug pharmacokinetics (PK) and pharmacodynamics (PD), complicating dosing and monitoring. This narrative review synthesizes current clinical evidence on ECMO-related PK/PD alterations and provides practical guidance for optimizing pharmacotherapy in adult intensive care. A structured literature search (January–May 2025) was conducted across PubMed/MEDLINE, EMBASE, Scopus, Cochrane Library, Sage Journals, ScienceDirect, Taylor & Francis Online, SpringerLink, and specialized databases, focusing on seven therapeutic classes commonly used in ECMO patients. Eligible studies included clinical trials, observational studies, systematic reviews, and practice guidelines in adults, while pediatric and preclinical data were excluded. Evidence quality varied substantially across drug classes. Hydrophilic, low-protein-bound agents such as β-lactams, aminoglycosides, fluconazole, and caspofungin generally showed minimal ECMO-specific PK alterations, with dose adjustment mainly driven by renal function. Conversely, lipophilic and highly protein-bound drugs including fentanyl, midazolam, propofol, voriconazole, and liposomal amphotericin B exhibited substantial circuit adsorption and variability, often requiring higher loading doses, prolonged infusions, and rigorous therapeutic drug monitoring. No ECMO-specific data were identified for certain neuromuscular blockers, antivirals, and electrolytes. Overall, individualized dosing guided by therapeutic drug monitoring (TDM), organ function, and validated PK principles remains essential to optimize therapy in this complex population.