J Extra Corpor Technol
Volume 54, Number 3, September 2022
|Page(s)||212 - 222|
|Published online||15 September 2022|
Cefepime Extraction by Extracorporeal Life Support Circuits
* Division of Pediatric Critical Care, Department of Pediatrics, University of Utah, Salt Lake City, Utah;
† Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, Utah;
‡ Department of Clinical Pharmacy, University of Colorado Anschutz Medical Campus, Aurora, Colorado;
§ Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah;
‖ American Red Cross, Salt Lake City, Utah;
¶ Department of Pathology, University of Arizona College of Medicine-Tucson, Tucson, Arizona;
# Division of Pediatric Nephrology, Department of Pediatrics, Duke University, Durham, North Carolina;
** Division of Pediatric Nephrology, Department of Pediatrics, East Carolina University, Greenville, North Carolina.
Address correspondence to: Kevin M. Watt, MD, PhD, Division of Pediatric Critical Care, Department of Pediatrics, University of Utah, 295 Chipeta Way, P.O. Box 581289, Salt Lake City, UT 84158. E-mail: email@example.com
Accepted: 23 June 2022
Extracorporeal life support (ECLS) devices are lifesaving for critically ill patients with multi-organ dysfunction. Despite this, patients supported with ECLS are at high risk for ECLS-related complications, including nosocomial infections, and mortality rates are high in this patient population. The high mortality rates are suspected to be, in part, a result of significantly altered drug disposition by the ECLS circuit, resulting in suboptimal antimicrobial dosing. Cefepime is commonly used in critically ill patients with serious infections. Cefepime dosing is not routinely guided by therapeutic drug monitoring and treatment success is dependent upon the percentage of time of the dosing interval that the drug concentration remains above the minimum inhibitory concentration of the organism. This ex vivo study measured the extraction of cefepime by continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO) circuits. Cefepime was studied in four closed-loop CRRT circuit configurations and a single closed-loop ECMO circuit configuration. Circuits were primed with a physiologic human blood–plasma mixture and the drug was dosed to achieve therapeutic concentrations. Serial blood samples were collected over time and concentrations were quantified using validated assays. In ex vivo CRRT experiments, cefepime was rapidly cleared by dialysis, hemofiltration, and hemodiafiltration, with greater than 96% cefepime eliminated from the circuit by 2 hours. In the ECMO circuits, the mean recovery of cefepime was similar in both circuit and standard control. Mean (standard deviation) recovery of cefepime in the ECMO circuits (n = 6) was 39.2% (8.0) at 24 hours. Mean recovery in the standard control (n = 3) at 24 hours was 52.2% (1.5). Cefepime is rapidly cleared by dialysis, hemofiltration, and hemodiafiltration in the CRRT circuit but minimally adsorbed by either the CRRT or ECMO circuits. Dosing adjustments are needed for patients supported with CRRT.
Key words: cefepime / extracorporeal membrane oxygenation / renal replacement therapy / pharmacology / drug extraction.
© 2022 AMSECT
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