Cefepime Pharmacokinetics in Patients Receiving Extracorporeal Membrane Oxygenation

Data on the effect of extracorporeal membrane oxygenation (ECMO) on cefepime concentration and protein binding are limited. This study aimed to describe the pharmacokinetics of cefepime in patients receiving ECMO, with or without renal replacement therapy.

Participants receiving ECMO were prospectively enrolled in the thoracic and lung transplant intensive care unit at the University of Florida Health-Shands Hospital in Gainesville, FL. Serum samples for drug quantification were collected at 1, 2, 4, 6, and 8 hours after the completion of cefepime infusion, pre- and post-ECMO oxygenator. The total and free drug concentrations in the ultrafiltrate were measured using liquid chromatography-tandem mass spectrometry at the University of Florida Infectious Disease Pharmacokinetics Laboratory.

Six patients who underwent venovenous ECMO were enrolled in the study. The median [interquartile range (IQR)] age and weight were 56.5 years (48-61.8) and 80.6 kg (75.4-90.6), respectively, and 67% were female. All patients received 2 g of cefepime infused over 30 minutes, with dosing intervals per renal function. The median (IQR) time between ECMO initiation and pharmacokinetic sampling was 3.5 days (2.5-24.7). None of the patients underwent renal replacement therapy during sampling. Minimal differences in cefepime concentrations pre- and postoxygenator were observed (<20% difference for all paired samples; median 3.5%). The median (IQR) protein-binding rates for cefepime both pre- [6.2% (2.6-10.8)] and post- [8.7% (2.5-13.4)] oxygenator were lower than previously published estimates of 20%.

No differences in pre- or post-ECMO oxygenator cefepime concentrations were observed. The median protein-binding values were less than previously published values.