Effect-Site Target-Controlled Infusion in the Obese: Model Derivation and Performance Assessment.

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dc.contributor.author Cortínez, Luis I en
dc.contributor.author Sepúlveda, Pablo en
dc.contributor.author Rolle, Augusto en
dc.contributor.author Cottin, Pauline en
dc.contributor.author Guerrini, Alexandre en
dc.contributor.author Anderson, Brian en
dc.date.accessioned 2019-03-06T03:48:28Z en
dc.date.issued 2018-10 en
dc.identifier.issn 0003-2999 en
dc.identifier.uri http://hdl.handle.net/2292/45787 en
dc.description.abstract BACKGROUND:The aim of this study is to derive a propofol pharmacokinetic (PK) pharmacodynamic (PD) model to perform effect-site target-controlled infusion (TCI) in obese patients, and to analyze its performance along with that of other available PK models. METHODS:In the first step of the study, a 3-compartment PK model linked to a sigmoidal inhibitory Emax PD model by a first-order rate constant (keo) was used to fit propofol concentration-bispectral index (BIS) data. Population modeling analysis was performed by nonlinear mixed effects regression in NONMEM (ICON, Dublin, Ireland). PK data from 3 previous studies in obese adult patients (n = 47), including PD (BIS) data from 1 of these studies (n = 20), were pooled and simultaneously analyzed. A decrease in NONMEM objective function (ΔOBJ) of 3.84 points, for an added parameter, was considered significant at the 0.05 level. In the second step of the study, we analyzed the predictive performance (median predictive errors [MDPE] and median absolute predictive errors [MDAPE]) of the current model and of other available models using an independent data set (n = 14). RESULTS:Step 1: The selected PKPD model produced an adequate fit of the data. Total body weight resulted in the best size scalar for volumes and clearances (ΔOBJ, -18.173). Empirical allometric total body weight relationships did not improve model fit (ΔOBJ, 0.309). A lag time parameter for BIS response improved the fit (ΔOBJ, 89.593). No effect of age or gender was observed. Step 2: Current model MDPE and MDAPE were 11.5% (3.7-25.0) and 26.8% (20.7-32.6) in the PK part and 0.4% (-10.39 to 3.85) and 11.9% (20.7-32.6) in the PD part. The PK model developed by Eleveld et al resulted in the lowest PK predictive errors (MDPE = <10% and MDAPE = <25%). CONCLUSIONS:We derived and validated a propofol PKPD model to perform effect-site TCI in obese patients. This model, derived exclusively from obese patient's data, is not recommended for TCI in lean patients because it carries the risk of underdosing. en
dc.format.medium Print en
dc.language eng en
dc.relation.ispartofseries Anesthesia and analgesia en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.subject Humans en
dc.subject Obesity, Morbid en
dc.subject Body Weight en
dc.subject Propofol en
dc.subject Anesthetics, Intravenous en
dc.subject Body Mass Index en
dc.subject Infusions, Intravenous en
dc.subject Prospective Studies en
dc.subject Reproducibility of Results en
dc.subject Consciousness en
dc.subject Nonlinear Dynamics en
dc.subject Models, Biological en
dc.subject Adult en
dc.subject Aged en
dc.subject Middle Aged en
dc.subject Female en
dc.subject Male en
dc.subject Drug Dosage Calculations en
dc.subject Consciousness Monitors en
dc.subject Intraoperative Neurophysiological Monitoring en
dc.title Effect-Site Target-Controlled Infusion in the Obese: Model Derivation and Performance Assessment. en
dc.type Journal Article en
dc.identifier.doi 10.1213/ane.0000000000002814 en
pubs.issue 4 en
pubs.begin-page 865 en
pubs.volume 127 en
dc.rights.holder Copyright: The author en
pubs.end-page 872 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Validation Studies en
pubs.subtype Journal Article en
pubs.elements-id 758665 en
pubs.org-id Medical and Health Sciences en
pubs.org-id School of Medicine en
pubs.org-id Anaesthesiology en
dc.identifier.eissn 1526-7598 en
pubs.record-created-at-source-date 2018-02-06 en
pubs.dimensions-id 29401079 en


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