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

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. T...

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Autores principales:	Hendrik Booke, Otto R. Frey, Anka C. Röhr, Ute Chiriac, Kai Zacharowski, Tomas Holubec, Elisabeth H. Adam
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/50dee264d34a4e94a6aa66b22bf86e69
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spelling	oai:doaj.org-article:50dee264d34a4e94a6aa66b22bf86e692021-12-02T17:08:36ZExcessive unbound cefazolin concentrations in critically ill patients receiving veno-arterial extracorporeal membrane oxygenation (vaECMO): an observational study10.1038/s41598-021-96654-42045-2322https://doaj.org/article/50dee264d34a4e94a6aa66b22bf86e692021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96654-4https://doaj.org/toc/2045-2322Abstract 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.Hendrik BookeOtto R. FreyAnka C. RöhrUte ChiriacKai ZacharowskiTomas HolubecElisabeth H. AdamNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hendrik Booke Otto R. Frey Anka C. Röhr Ute Chiriac Kai Zacharowski Tomas Holubec Elisabeth H. Adam Excessive unbound cefazolin concentrations in critically ill patients receiving veno-arterial extracorporeal membrane oxygenation (vaECMO): an observational study
description	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.
format	article
author	Hendrik Booke Otto R. Frey Anka C. Röhr Ute Chiriac Kai Zacharowski Tomas Holubec Elisabeth H. Adam
author_facet	Hendrik Booke Otto R. Frey Anka C. Röhr Ute Chiriac Kai Zacharowski Tomas Holubec Elisabeth H. Adam
author_sort	Hendrik Booke
title	Excessive unbound cefazolin concentrations in critically ill patients receiving veno-arterial extracorporeal membrane oxygenation (vaECMO): an observational study
title_short	Excessive unbound cefazolin concentrations in critically ill patients receiving veno-arterial extracorporeal membrane oxygenation (vaECMO): an observational study
title_full	Excessive unbound cefazolin concentrations in critically ill patients receiving veno-arterial extracorporeal membrane oxygenation (vaECMO): an observational study
title_fullStr	Excessive unbound cefazolin concentrations in critically ill patients receiving veno-arterial extracorporeal membrane oxygenation (vaECMO): an observational study
title_full_unstemmed	Excessive unbound cefazolin concentrations in critically ill patients receiving veno-arterial extracorporeal membrane oxygenation (vaECMO): an observational study
title_sort	excessive unbound cefazolin concentrations in critically ill patients receiving veno-arterial extracorporeal membrane oxygenation (vaecmo): an observational study
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/50dee264d34a4e94a6aa66b22bf86e69
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Excessive unbound cefazolin concentrations in critically ill patients receiving veno-arterial extracorporeal membrane oxygenation (vaECMO): an observational study

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