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Background and Objective <p>Achieving optimal antibacterial dosing in critically ill patients is challenging owing to the pathophysiological changes that alter drug pharmacokinetics. Extracorporeal membrane oxygenation (ECMO) further complicates pharmacokinetics, hypothesized to act as another pharmacokinetic compartment influencing drug concentrations. Ensuring therapeutic antibacterial concentrations is crucial to prevent treatment failure and resistance. This systematic review aimed to identify and evaluate published population pharmacokinetic studies of antibacterials in critically ill adult ECMO patients.</p> Methods <p>A systematic search of PubMed, Embase, and Cochrane databases was conducted from database inception to March 2025. Studies were included if they were population pharmacokinetic analyses of antibacterial agents in adult (aged ≥ 18 years) ECMO patients; non-compartmental analyses and non-antibacterial agents were excluded. Data on study characteristics, patient demographics, ECMO parameters, pharmacokinetic models, and covariates were extracted.</p> Results <p>The search yielded 31 eligible population pharmacokinetic studies. Most studies indicated that ECMO-specific variables (mode, flow rate, oxygenator type) did not significantly influence the pharmacokinetics of the majority of antibacterials. Instead, pharmacokinetic variability was primarily driven by critical illness-related factors, notably renal function and presence of renal replacement therapy. Dosing recommendations frequently highlighted the need for individualized therapy and therapeutic drug monitoring.</p> Conclusions <p>Our findings indicate that ECMO itself does not consistently alter the pharmacokinetics of most antibacterials in critically ill adult patients. Observed pharmacokinetic variability and subsequent dosing recommendations are primarily attributable to critical illness factors. Therapeutic drug monitoring is recommended to optimize exposure but minimize toxicity. Further prospective studies with standardized reporting of covariates and clinical endpoints are needed to enhance the evidence base.</p> Clinical Trial Registration <p>PROSPERO Registration and date: CRD420251165914 (15 October, 2025).</p>

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Antibacterial Pharmacokinetics in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation (ECMO): A Systematic Review of Population Pharmacokinetic Studies

  • 期刊论文

  • 发表日期：

    2025年12月12日

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  • Chanelle Ren,
  • Frank Huang,
  • Vesa Cheng,
  • Jiao Xie,
  • Jason A. Roberts,
  • Mohd H. Abdul-Aziz

摘要

Background and Objective

Achieving optimal antibacterial dosing in critically ill patients is challenging owing to the pathophysiological changes that alter drug pharmacokinetics. Extracorporeal membrane oxygenation (ECMO) further complicates pharmacokinetics, hypothesized to act as another pharmacokinetic compartment influencing drug concentrations. Ensuring therapeutic antibacterial concentrations is crucial to prevent treatment failure and resistance. This systematic review aimed to identify and evaluate published population pharmacokinetic studies of antibacterials in critically ill adult ECMO patients.

Methods

A systematic search of PubMed, Embase, and Cochrane databases was conducted from database inception to March 2025. Studies were included if they were population pharmacokinetic analyses of antibacterial agents in adult (aged ≥ 18 years) ECMO patients; non-compartmental analyses and non-antibacterial agents were excluded. Data on study characteristics, patient demographics, ECMO parameters, pharmacokinetic models, and covariates were extracted.

Results

The search yielded 31 eligible population pharmacokinetic studies. Most studies indicated that ECMO-specific variables (mode, flow rate, oxygenator type) did not significantly influence the pharmacokinetics of the majority of antibacterials. Instead, pharmacokinetic variability was primarily driven by critical illness-related factors, notably renal function and presence of renal replacement therapy. Dosing recommendations frequently highlighted the need for individualized therapy and therapeutic drug monitoring.

Conclusions

Our findings indicate that ECMO itself does not consistently alter the pharmacokinetics of most antibacterials in critically ill adult patients. Observed pharmacokinetic variability and subsequent dosing recommendations are primarily attributable to critical illness factors. Therapeutic drug monitoring is recommended to optimize exposure but minimize toxicity. Further prospective studies with standardized reporting of covariates and clinical endpoints are needed to enhance the evidence base.

Clinical Trial Registration

PROSPERO Registration and date: CRD420251165914 (15 October, 2025).