TY  - JOUR
A1  - Booke, Hendrik
A1  - Frey, Otto Roman
A1  - Röhr, Anka
A1  - Chiriac, Ute
A1  - Zacharowski, Kai
A1  - Holubec, Tomas
A1  - Adam, Elisabeth
T1  - Excessive unbound cefazolin concentrations in critically ill patients receiving veno-arterial extracorporeal membrane oxygenation (vaECMO): an observational study
T2  - Scientific report
N2  - 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.
KW  - Adverse effects
KW  - Bacterial infection
KW  - Clinical pharmacology
KW  - Continuous renal replacement therapy
KW  - Drug therapy
KW  - Heart failure
KW  - Infection
KW  - Pharmacokinetics
KW  - Pharmacology
KW  - Respiratory distress syndrome
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62629
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-626296
SN  - 2045-2322
N1  - Open Access funding enabled and organized by Projekt DEAL. This study received funding from the German research foundation.
VL  - 11
IS  - art. 16981
SP  - 1
EP  - 8
PB  - Macmillan Publishers Limited
CY  - [London]
ER  -