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Cefepime Extraction by Extracorporeal Life Support Circuits.

Danielle J Green1, Kevin M Watt1,2, Douglas N Fish3

  • 1Division of Pediatric Critical Care, Department of Pediatrics, University of Utah, Salt Lake City, Utah.

The Journal of Extra-Corporeal Technology
|February 6, 2023
PubMed
Summary
This summary is machine-generated.

Extracorporeal life support (ECLS) circuits significantly alter cefepime levels. Continuous renal replacement therapy (CRRT) rapidly clears cefepime, necessitating dosing adjustments for critically ill patients. ECMO shows minimal cefepime adsorption.

Keywords:
cefepimedrug extraction.extracorporeal membrane oxygenationpharmacologyrenal replacement therapy

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Area of Science:

  • Pharmacokinetics and critical care medicine
  • Drug disposition in extracorporeal circuits
  • Antimicrobial dosing optimization

Background:

  • Extracorporeal life support (ECLS) is vital for critically ill patients but associated with high mortality and complications.
  • Altered drug disposition in ECLS circuits can lead to suboptimal antimicrobial dosing, impacting treatment success.
  • Cefepime, a common antibiotic, requires specific drug concentrations above the minimum inhibitory concentration for efficacy.

Purpose of the Study:

  • To investigate the ex vivo extraction of cefepime by continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO) circuits.
  • To determine the impact of CRRT and ECMO on cefepime concentrations in a simulated physiologic environment.
  • To inform cefepime dosing strategies for patients undergoing ECLS and CRRT.

Main Methods:

  • Ex vivo study using closed-loop CRRT and ECMO circuit configurations.
  • Circuits primed with a human blood-plasma mixture, dosed with cefepime to achieve therapeutic concentrations.
  • Serial blood samples collected over time, with cefepime concentrations quantified using validated assays.

Main Results:

  • Cefepime was rapidly cleared by CRRT (dialysis, hemofiltration, hemodiafiltration), with >96% eliminated within 2 hours.
  • ECMO circuits showed minimal cefepime adsorption, with mean recovery of 39.2% at 24 hours compared to 52.2% in standard control.
  • Cefepime was minimally adsorbed by either CRRT or ECMO circuits, indicating clearance is primarily due to the CRRT modality.

Conclusions:

  • Cefepime is significantly cleared by CRRT, requiring substantial dosing adjustments in patients supported by this therapy.
  • ECMO circuits demonstrate minimal extraction of cefepime, suggesting less impact on drug levels compared to CRRT.
  • Optimized cefepime dosing is crucial for critically ill patients on ECLS, particularly those also requiring CRRT, to ensure therapeutic efficacy.