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Population pharmacokinetics of intravenous sufentanil in critically ill patients supported with extracorporeal membrane oxygenation therapy

BACKGROUND: Sufentanil is commonly used for analgesia and sedation during extracorporeal membrane oxygenation (ECMO). Both ECMO and the pathophysiological changes derived from critical illness have significant effects on the pharmacokinetics (PK) of drugs, yet reports of ECMO and sufentanil PK are s...

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Autores principales: Hahn, Jongsung, Yang, Seungwon, Min, Kyoung Lok, Kim, Dasohm, Jin, Byung Hak, Park, Changhun, Park, Min Soo, Wi, Jin, Chang, Min Jung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615282/
https://www.ncbi.nlm.nih.gov/pubmed/31288863
http://dx.doi.org/10.1186/s13054-019-2508-4
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author Hahn, Jongsung
Yang, Seungwon
Min, Kyoung Lok
Kim, Dasohm
Jin, Byung Hak
Park, Changhun
Park, Min Soo
Wi, Jin
Chang, Min Jung
author_facet Hahn, Jongsung
Yang, Seungwon
Min, Kyoung Lok
Kim, Dasohm
Jin, Byung Hak
Park, Changhun
Park, Min Soo
Wi, Jin
Chang, Min Jung
author_sort Hahn, Jongsung
collection PubMed
description BACKGROUND: Sufentanil is commonly used for analgesia and sedation during extracorporeal membrane oxygenation (ECMO). Both ECMO and the pathophysiological changes derived from critical illness have significant effects on the pharmacokinetics (PK) of drugs, yet reports of ECMO and sufentanil PK are scarce. Here, we aimed to develop a population PK model of sufentanil in ECMO patients and to suggest dosing recommendations. METHODS: This prospective cohort PK study included 20 patients who received sufentanil during venoarterial ECMO (VA-ECMO). Blood samples were collected for 96 h during infusion and 72 h after cessation of sufentanil. A population PK model was developed using nonlinear mixed effects modelling. Monte Carlo simulations were performed using the final PK parameters with two typical doses. RESULTS: A two-compartment model best described the PK of sufentanil. In our final model, increased volume of distribution and decreased values for clearance were reported compared with previous PK data from non-ECMO patients. Covariate analysis showed that body temperature and total plasma protein level correlated positively with systemic clearance (CL) and peripheral volume of distribution (V2), respectively, and improved the model. The parameter estimates of the final model were as follows: CL = 37.8 × EXP (0.207 × (temperature − 36.9)) L h(−1), central volume of distribution (V1) = 229 L, V2 = 1640 × (total plasma protein/4.5)(2.46) L, and intercompartmental clearance (Q) = 41 L h(−1). Based on Monte Carlo simulation results, an infusion of 17.5 μg h(−1) seems to reach target sufentanil concentration (0.3–0.6 μg L(−1)) in most ECMO patients except hypothermic patients (33 °C). In hypothermic patients, over-sedation, which could induce respiratory depression, needs to be monitored especially when their total plasma protein level is low. CONCLUSIONS: This is the first report on a population PK model of sufentanil in ECMO patients. Our results suggest that close monitoring of the body temperature and total plasma protein level is crucial in ECMO patients who receive sufentanil to provide effective analgesia and sedation and promote recovery. TRIAL REGISTRATION: Clinicaltrials.gov NCT02581280, December 1st, 2014.
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spelling pubmed-66152822019-07-18 Population pharmacokinetics of intravenous sufentanil in critically ill patients supported with extracorporeal membrane oxygenation therapy Hahn, Jongsung Yang, Seungwon Min, Kyoung Lok Kim, Dasohm Jin, Byung Hak Park, Changhun Park, Min Soo Wi, Jin Chang, Min Jung Crit Care Research BACKGROUND: Sufentanil is commonly used for analgesia and sedation during extracorporeal membrane oxygenation (ECMO). Both ECMO and the pathophysiological changes derived from critical illness have significant effects on the pharmacokinetics (PK) of drugs, yet reports of ECMO and sufentanil PK are scarce. Here, we aimed to develop a population PK model of sufentanil in ECMO patients and to suggest dosing recommendations. METHODS: This prospective cohort PK study included 20 patients who received sufentanil during venoarterial ECMO (VA-ECMO). Blood samples were collected for 96 h during infusion and 72 h after cessation of sufentanil. A population PK model was developed using nonlinear mixed effects modelling. Monte Carlo simulations were performed using the final PK parameters with two typical doses. RESULTS: A two-compartment model best described the PK of sufentanil. In our final model, increased volume of distribution and decreased values for clearance were reported compared with previous PK data from non-ECMO patients. Covariate analysis showed that body temperature and total plasma protein level correlated positively with systemic clearance (CL) and peripheral volume of distribution (V2), respectively, and improved the model. The parameter estimates of the final model were as follows: CL = 37.8 × EXP (0.207 × (temperature − 36.9)) L h(−1), central volume of distribution (V1) = 229 L, V2 = 1640 × (total plasma protein/4.5)(2.46) L, and intercompartmental clearance (Q) = 41 L h(−1). Based on Monte Carlo simulation results, an infusion of 17.5 μg h(−1) seems to reach target sufentanil concentration (0.3–0.6 μg L(−1)) in most ECMO patients except hypothermic patients (33 °C). In hypothermic patients, over-sedation, which could induce respiratory depression, needs to be monitored especially when their total plasma protein level is low. CONCLUSIONS: This is the first report on a population PK model of sufentanil in ECMO patients. Our results suggest that close monitoring of the body temperature and total plasma protein level is crucial in ECMO patients who receive sufentanil to provide effective analgesia and sedation and promote recovery. TRIAL REGISTRATION: Clinicaltrials.gov NCT02581280, December 1st, 2014. BioMed Central 2019-07-09 /pmc/articles/PMC6615282/ /pubmed/31288863 http://dx.doi.org/10.1186/s13054-019-2508-4 Text en © The Author(s). 2019 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
Hahn, Jongsung
Yang, Seungwon
Min, Kyoung Lok
Kim, Dasohm
Jin, Byung Hak
Park, Changhun
Park, Min Soo
Wi, Jin
Chang, Min Jung
Population pharmacokinetics of intravenous sufentanil in critically ill patients supported with extracorporeal membrane oxygenation therapy
title Population pharmacokinetics of intravenous sufentanil in critically ill patients supported with extracorporeal membrane oxygenation therapy
title_full Population pharmacokinetics of intravenous sufentanil in critically ill patients supported with extracorporeal membrane oxygenation therapy
title_fullStr Population pharmacokinetics of intravenous sufentanil in critically ill patients supported with extracorporeal membrane oxygenation therapy
title_full_unstemmed Population pharmacokinetics of intravenous sufentanil in critically ill patients supported with extracorporeal membrane oxygenation therapy
title_short Population pharmacokinetics of intravenous sufentanil in critically ill patients supported with extracorporeal membrane oxygenation therapy
title_sort population pharmacokinetics of intravenous sufentanil in critically ill patients supported with extracorporeal membrane oxygenation therapy
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615282/
https://www.ncbi.nlm.nih.gov/pubmed/31288863
http://dx.doi.org/10.1186/s13054-019-2508-4
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