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Predictors of insufficient peak amikacin concentration in critically ill patients on extracorporeal membrane oxygenation
BACKGROUND: Amikacin infusion requires targeting a peak serum concentration (C(max)) 8–10 times the minimal inhibitory concentration, corresponding to a C(max) of 60–80 mg/L for the least susceptible bacteria to theoretically prevent therapeutic failure. Because drug pharmacokinetics on extracorpore...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098833/ https://www.ncbi.nlm.nih.gov/pubmed/30121083 http://dx.doi.org/10.1186/s13054-018-2122-x |
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author | Touchard, Cyril Aubry, Alexandra Eloy, Philippine Bréchot, Nicolas Lebreton, Guillaume Franchineau, Guillaume Besset, Sebastien Hékimian, Guillaume Nieszkowska, Ania Leprince, Pascal Luyt, Charles-Edouard Combes, Alain Schmidt, Matthieu |
author_facet | Touchard, Cyril Aubry, Alexandra Eloy, Philippine Bréchot, Nicolas Lebreton, Guillaume Franchineau, Guillaume Besset, Sebastien Hékimian, Guillaume Nieszkowska, Ania Leprince, Pascal Luyt, Charles-Edouard Combes, Alain Schmidt, Matthieu |
author_sort | Touchard, Cyril |
collection | PubMed |
description | BACKGROUND: Amikacin infusion requires targeting a peak serum concentration (C(max)) 8–10 times the minimal inhibitory concentration, corresponding to a C(max) of 60–80 mg/L for the least susceptible bacteria to theoretically prevent therapeutic failure. Because drug pharmacokinetics on extracorporeal membrane oxygenation (ECMO) are challenging, we undertook this study to assess the frequency of insufficient amikacin C(max) in critically ill patients on ECMO and to identify relative risk factors. METHODS: This was a prospective, observational, monocentric study in a university hospital. Patients on ECMO who received an amikacin loading dose for suspected Gram-negative infections were included. The amikacin loading dose of 25 mg/kg total body weight was administered intravenously and C(max) was measured 30 min after the end of the infusion. Independent predicators of C(max) < 60 mg/L after the first amikacin infusion were identified with mixed-model multivariable analyses. Various dosing simulations were performed to assess the probability of reaching 60 mg/L < C(max) < 80 mg/L. RESULTS: A total of 106 patients on venoarterial ECMO (VA-ECMO) (68%) or venovenous-ECMO (32%) were included. At inclusion, their median (1st; 3rd quartile) Sequential Organ-Failure Assessment score was 15 (12; 18) and 54 patients (51%) were on renal replacement therapy. Overall ICU mortality was 54%. C(max) was < 60 mg/L in 41 patients (39%). Independent risk factors for amikacin under-dosing were body mass index (BMI) < 22 kg/m(2) and a positive 24-h fluid balance. Using dosing simulation, increasing the amikacin dosing regimen to 30 mg/kg and 35 mg/kg of body weight when the 24-h fluid balance is positive and the BMI is ≥ 22 kg/m(2) or < 22 kg/m(2) (Table 3), respectively, would have potentially led to the therapeutic target being reached in 42% of patients while reducing under-dosing to 23% of patients. CONCLUSIONS: ECMO-treated patients were under-dosed for amikacin in one third of cases. Increasing the dose to 35 mg/kg of body weight in low-BMI patients and those with positive 24-h fluid balance on ECMO to reach adequate targeted concentrations should be investigated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13054-018-2122-x) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6098833 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-60988332018-08-23 Predictors of insufficient peak amikacin concentration in critically ill patients on extracorporeal membrane oxygenation Touchard, Cyril Aubry, Alexandra Eloy, Philippine Bréchot, Nicolas Lebreton, Guillaume Franchineau, Guillaume Besset, Sebastien Hékimian, Guillaume Nieszkowska, Ania Leprince, Pascal Luyt, Charles-Edouard Combes, Alain Schmidt, Matthieu Crit Care Research BACKGROUND: Amikacin infusion requires targeting a peak serum concentration (C(max)) 8–10 times the minimal inhibitory concentration, corresponding to a C(max) of 60–80 mg/L for the least susceptible bacteria to theoretically prevent therapeutic failure. Because drug pharmacokinetics on extracorporeal membrane oxygenation (ECMO) are challenging, we undertook this study to assess the frequency of insufficient amikacin C(max) in critically ill patients on ECMO and to identify relative risk factors. METHODS: This was a prospective, observational, monocentric study in a university hospital. Patients on ECMO who received an amikacin loading dose for suspected Gram-negative infections were included. The amikacin loading dose of 25 mg/kg total body weight was administered intravenously and C(max) was measured 30 min after the end of the infusion. Independent predicators of C(max) < 60 mg/L after the first amikacin infusion were identified with mixed-model multivariable analyses. Various dosing simulations were performed to assess the probability of reaching 60 mg/L < C(max) < 80 mg/L. RESULTS: A total of 106 patients on venoarterial ECMO (VA-ECMO) (68%) or venovenous-ECMO (32%) were included. At inclusion, their median (1st; 3rd quartile) Sequential Organ-Failure Assessment score was 15 (12; 18) and 54 patients (51%) were on renal replacement therapy. Overall ICU mortality was 54%. C(max) was < 60 mg/L in 41 patients (39%). Independent risk factors for amikacin under-dosing were body mass index (BMI) < 22 kg/m(2) and a positive 24-h fluid balance. Using dosing simulation, increasing the amikacin dosing regimen to 30 mg/kg and 35 mg/kg of body weight when the 24-h fluid balance is positive and the BMI is ≥ 22 kg/m(2) or < 22 kg/m(2) (Table 3), respectively, would have potentially led to the therapeutic target being reached in 42% of patients while reducing under-dosing to 23% of patients. CONCLUSIONS: ECMO-treated patients were under-dosed for amikacin in one third of cases. Increasing the dose to 35 mg/kg of body weight in low-BMI patients and those with positive 24-h fluid balance on ECMO to reach adequate targeted concentrations should be investigated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13054-018-2122-x) contains supplementary material, which is available to authorized users. BioMed Central 2018-08-19 /pmc/articles/PMC6098833/ /pubmed/30121083 http://dx.doi.org/10.1186/s13054-018-2122-x Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Touchard, Cyril Aubry, Alexandra Eloy, Philippine Bréchot, Nicolas Lebreton, Guillaume Franchineau, Guillaume Besset, Sebastien Hékimian, Guillaume Nieszkowska, Ania Leprince, Pascal Luyt, Charles-Edouard Combes, Alain Schmidt, Matthieu Predictors of insufficient peak amikacin concentration in critically ill patients on extracorporeal membrane oxygenation |
title | Predictors of insufficient peak amikacin concentration in critically ill patients on extracorporeal membrane oxygenation |
title_full | Predictors of insufficient peak amikacin concentration in critically ill patients on extracorporeal membrane oxygenation |
title_fullStr | Predictors of insufficient peak amikacin concentration in critically ill patients on extracorporeal membrane oxygenation |
title_full_unstemmed | Predictors of insufficient peak amikacin concentration in critically ill patients on extracorporeal membrane oxygenation |
title_short | Predictors of insufficient peak amikacin concentration in critically ill patients on extracorporeal membrane oxygenation |
title_sort | predictors of insufficient peak amikacin concentration in critically ill patients on extracorporeal membrane oxygenation |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098833/ https://www.ncbi.nlm.nih.gov/pubmed/30121083 http://dx.doi.org/10.1186/s13054-018-2122-x |
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