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

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dc.contributor.author박민수-
dc.contributor.author위진-
dc.date.accessioned2019-10-28T02:06:49Z-
dc.date.available2019-10-28T02:06:49Z-
dc.date.issued2019-
dc.identifier.issn1364-8535-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/171491-
dc.description.abstractBACKGROUND: 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-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.languageEnglish-
dc.publisherBioMed Central Ltd-
dc.relation.isPartOfCritical Care-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.titlePopulation pharmacokinetics of intravenous sufentanil in critically ill patients supported with extracorporeal membrane oxygenation therapy-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Pediatrics (소아청소년과학교실)-
dc.contributor.googleauthorJongsung Hahn-
dc.contributor.googleauthorSeungwon Yang-
dc.contributor.googleauthorKyoung Lok Min-
dc.contributor.googleauthorDasohm Kim-
dc.contributor.googleauthorByung Hak Jin-
dc.contributor.googleauthorChanghun Park-
dc.contributor.googleauthorMin Soo Park-
dc.contributor.googleauthorJin Wi-
dc.contributor.googleauthorMin Jung Chang-
dc.identifier.doi10.1186/s13054-019-2508-4-
dc.contributor.localIdA01468-
dc.relation.journalcodeJ00652-
dc.identifier.eissn1466-609X-
dc.identifier.pmid31288863-
dc.subject.keywordAnaesthetics, intravenous-
dc.subject.keywordExtracorporeal membrane oxygenation-
dc.subject.keywordPharmacokinetics-
dc.subject.keywordSufentanil-
dc.subject.keywordTemperature-
dc.contributor.alternativeNamePark, Min Soo-
dc.contributor.affiliatedAuthor박민수-
dc.citation.volume23-
dc.citation.number1-
dc.citation.startPage248-
dc.identifier.bibliographicCitationCritical Care, Vol.23(1) : 248, 2019-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers

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