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Effects of cardiopulmonary bypass on the disposition of cefazolin in patients undergoing cardiothoracic surgery

The aim of the study was to evaluate the disposition of plasma unbound cefazolin in patients undergoing cardiothoracic surgery with cardiopulmonary bypass (CPB). Adult patients undergoing cardiothoracic surgery with CPB were enrolled in the study. Cefazolin sodium was given intravenously before skin...

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Autores principales: Asada, Mizuho, Nagata, Masashi, Mizuno, Tomohiro, Uchida, Tokujiro, Kurashima, Naoki, Takahashi, Hiromitsu, Makita, Koshi, Arai, Hirokuni, Echizen, Hirotoshi, Yasuhara, Masato
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218359/
https://www.ncbi.nlm.nih.gov/pubmed/30410768
http://dx.doi.org/10.1002/prp2.440
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author Asada, Mizuho
Nagata, Masashi
Mizuno, Tomohiro
Uchida, Tokujiro
Kurashima, Naoki
Takahashi, Hiromitsu
Makita, Koshi
Arai, Hirokuni
Echizen, Hirotoshi
Yasuhara, Masato
author_facet Asada, Mizuho
Nagata, Masashi
Mizuno, Tomohiro
Uchida, Tokujiro
Kurashima, Naoki
Takahashi, Hiromitsu
Makita, Koshi
Arai, Hirokuni
Echizen, Hirotoshi
Yasuhara, Masato
author_sort Asada, Mizuho
collection PubMed
description The aim of the study was to evaluate the disposition of plasma unbound cefazolin in patients undergoing cardiothoracic surgery with cardiopulmonary bypass (CPB). Adult patients undergoing cardiothoracic surgery with CPB were enrolled in the study. Cefazolin sodium was given intravenously before skin incision (1 g) and at the beginning of CPB (2 g). Thereafter, an additional dose (1 g) was given every 4 hours. Seven to ten blood samples were collected before and during surgery. Plasma total and unbound (ultrafiltrated) cefazolin concentrations were analyzed using an HPLC‐UV method. Plasma protein binding was analyzed with the Langmuir model. Twenty‐seven patients (aged 70 ± 12 years, body weight 62 ± 12 kg, mean ± SD) with GFR >30 mL min(−1) completed the study. There was a significant (P < 0.001) increase in median plasma unbound fraction of cefazolin from 21% before skin incision to 45% during CPB (P < 0.001), which was accompanied by a significant (P < 0.001) reduction in median plasma albumin concentration from 36 to 27 g L(−1). Plasma concentrations of unbound cefazolin exceeded the assumed target thresholds of 2 μg mL(−1) in all samples and of 8 μg mL(−1) in all but one of 199 samples. The increased plasma unbound fraction of cefazolin would be attributable to dilutional reduction of serum albumin at the beginning of CPB and to saturable plasma protein binding of cefazolin. These data reveal CPB may alter the plasma protein binding and possibly distribution of cefazolin. Further studies are warranted to reappraise the protocol of antimicrobial prophylaxis with cefazolin in patients undergoing surgery with CPB.
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spelling pubmed-62183592018-11-08 Effects of cardiopulmonary bypass on the disposition of cefazolin in patients undergoing cardiothoracic surgery Asada, Mizuho Nagata, Masashi Mizuno, Tomohiro Uchida, Tokujiro Kurashima, Naoki Takahashi, Hiromitsu Makita, Koshi Arai, Hirokuni Echizen, Hirotoshi Yasuhara, Masato Pharmacol Res Perspect Original Articles The aim of the study was to evaluate the disposition of plasma unbound cefazolin in patients undergoing cardiothoracic surgery with cardiopulmonary bypass (CPB). Adult patients undergoing cardiothoracic surgery with CPB were enrolled in the study. Cefazolin sodium was given intravenously before skin incision (1 g) and at the beginning of CPB (2 g). Thereafter, an additional dose (1 g) was given every 4 hours. Seven to ten blood samples were collected before and during surgery. Plasma total and unbound (ultrafiltrated) cefazolin concentrations were analyzed using an HPLC‐UV method. Plasma protein binding was analyzed with the Langmuir model. Twenty‐seven patients (aged 70 ± 12 years, body weight 62 ± 12 kg, mean ± SD) with GFR >30 mL min(−1) completed the study. There was a significant (P < 0.001) increase in median plasma unbound fraction of cefazolin from 21% before skin incision to 45% during CPB (P < 0.001), which was accompanied by a significant (P < 0.001) reduction in median plasma albumin concentration from 36 to 27 g L(−1). Plasma concentrations of unbound cefazolin exceeded the assumed target thresholds of 2 μg mL(−1) in all samples and of 8 μg mL(−1) in all but one of 199 samples. The increased plasma unbound fraction of cefazolin would be attributable to dilutional reduction of serum albumin at the beginning of CPB and to saturable plasma protein binding of cefazolin. These data reveal CPB may alter the plasma protein binding and possibly distribution of cefazolin. Further studies are warranted to reappraise the protocol of antimicrobial prophylaxis with cefazolin in patients undergoing surgery with CPB. John Wiley and Sons Inc. 2018-11-05 /pmc/articles/PMC6218359/ /pubmed/30410768 http://dx.doi.org/10.1002/prp2.440 Text en © 2018 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Asada, Mizuho
Nagata, Masashi
Mizuno, Tomohiro
Uchida, Tokujiro
Kurashima, Naoki
Takahashi, Hiromitsu
Makita, Koshi
Arai, Hirokuni
Echizen, Hirotoshi
Yasuhara, Masato
Effects of cardiopulmonary bypass on the disposition of cefazolin in patients undergoing cardiothoracic surgery
title Effects of cardiopulmonary bypass on the disposition of cefazolin in patients undergoing cardiothoracic surgery
title_full Effects of cardiopulmonary bypass on the disposition of cefazolin in patients undergoing cardiothoracic surgery
title_fullStr Effects of cardiopulmonary bypass on the disposition of cefazolin in patients undergoing cardiothoracic surgery
title_full_unstemmed Effects of cardiopulmonary bypass on the disposition of cefazolin in patients undergoing cardiothoracic surgery
title_short Effects of cardiopulmonary bypass on the disposition of cefazolin in patients undergoing cardiothoracic surgery
title_sort effects of cardiopulmonary bypass on the disposition of cefazolin in patients undergoing cardiothoracic surgery
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218359/
https://www.ncbi.nlm.nih.gov/pubmed/30410768
http://dx.doi.org/10.1002/prp2.440
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