Excessive unbound cefazolin concentrations in critically ill patients receiving veno-arterial extracorporeal membrane oxygenation (vaECMO): an observational study

Hendrik Booke,Ute Chiriac,Anka C Röhr,Otto R Frey,Tomas Holubec,Elisabeth H Adam,Kai Zacharowski

doi:10.1038/s41598-021-96654-4

Abstract

The scope of extracorporeal membrane oxygenation (ECMO) is expanding, nevertheless, pharmacokinetics in patients receiving cardiorespiratory support are fairly unknown leading to unpredictable drug concentrations. Currently, there are no clear guidelines for antibiotic dosing during ECMO. This study aims to evaluate the pharmacokinetics (PK) of cefazolin in patients undergoing ECMO treatment. Total and unbound plasma cefazolin concentration of critically ill patients on veno-arterial ECMO were determined. Observed PK was compared to dose recommendations calculated by an online available, free dosing software. Concentration of cefazolin varied broadly despite same dosage in all patients. The mean total and unbound plasma concentration were high showing significantly (p = 5.8913 E−09) greater unbound fraction compared to a standard patient. Cefazolin clearance was significantly (p = 0.009) higher in patients with preserved renal function compared with CRRT. Based upon the calculated clearance, the use of dosing software would have led to lower but still sufficient concentrations of cefazolin in general. Our study shows that a “one size fits all” dosing regimen leads to excessive unbound cefazolin concentration in these patients. They exhibit high PK variability and decreased cefazolin clearance on ECMO appears to compensate for ECMO- and critical illness-related increases in volume of distribution.

Highlights

The scope of extracorporeal membrane oxygenation (ECMO) is expanding, pharmacokinetics in patients receiving cardiorespiratory support are fairly unknown leading to unpredictable drug concentrations
It is unknown to what extent the pharmacokinetics of cefazolin in ECMO patients differ from those of non-ECMO patients, there are no clear guidelines for antibiotic dosing during ECMO treatment
Our study shows excessive unbound cefazolin concentrations in patients receiving extracorporeal cardiorespiratory support

Summary

Introduction

The scope of extracorporeal membrane oxygenation (ECMO) is expanding, pharmacokinetics in patients receiving cardiorespiratory support are fairly unknown leading to unpredictable drug concentrations. Our study shows that a “one size fits all” dosing regimen leads to excessive unbound cefazolin concentration in these patients They exhibit high PK variability and decreased cefazolin clearance on ECMO appears to compensate for ECMO- and critical illness-related increases in volume of distribution. Extracorporeal membrane oxygenation (ECMO) is a well-established device for cardiorespiratory support in the most critically ill patients, which evolved quickly over the past decades and is routinely performed in high volume cardiac surgery centers[1]. It is a highly invasive system only used in the most critically ill patients more than 50% of ECMO-survival in cardiac patients is reported with increasing tendency over the last years[2]. Increased volume of distribution (Vd) (due to extracorporeal circulation and systemic inflammation)

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