{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T17:40:05Z","timestamp":1793814005455,"version":"4.6.1"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Interdepartmental Division of Critical Care Medicine, University of Toronto"},{"name":"Interdepartmental Division of Critical Care Medicine, University of Toronto"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Despite the potential risks associated with sedation, there is a paucity of pharmacokinetic\/pharmacodynamic (PK\/PD) data for propofol and fentanyl in patients supported with venovenous extracorporeal membrane oxygenation (V-V ECMO).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Describe propofol and fentanyl PK\/PD profiles in patients receiving V-V ECMO.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Prospective, single-center, open-label PK\/PD study at the Toronto General Hospital intensive care unit between July 2022 and January 2023. Using high-performance liquid chromatography\/tandem mass spectrometry, propofol and fentanyl total concentrations were measured during V-V ECMO. Sequential PK\/PD modeling, using sex as a covariate, was conducted with processed electroencephalography (patient state index [PSI]) for sedation and expiratory occlusion pressure and airway occlusion pressure during the first 0.1 second for respiratory effort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eleven patients underwent 106 evaluations over a median follow-up of 146 (interquartile ranges, 116\u2013146) hours. Patients\u2019 average age was 43 (standard deviation, 13) years, and 55% were female. Propofol and fentanyl PKs were best described by a two-compartment model. Propofol PSI PD were described using an effect compartment, with a coefficient of determination of 0.78. There was a significant increase in propofol (P\u2009=\u20090.01) and fentanyl (P\u2009=\u20090.03) clearance within 10 minutes of ECMO initiation, plateauing after 8 hours of ECMO support. Despite this, patient oversedation (PSI &amp;lt;40) occurred in 74% of the observations. Female patients exhibited a higher sedative central volume of distribution and lower propofol clearance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ECMO initiation resulted in a time-limited increased sedative clearance. PSI accurately described sedative PD, but variable respiratory effort was observed irrespective of sedative plasma concentrations. Sex-based differences were found in sedative PK\/PD parameters.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1513\/annalsats.202407-795oc","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T18:02:13Z","timestamp":1728496933000},"page":"121-129","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":12,"title":["Propofol and Fentanyl Pharmacokinetics and Pharmacodynamics in Extracorporeal Membrane Oxygenation"],"prefix":"10.1093","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9205-9613","authenticated-orcid":false,"given":"Diana","family":"Morales Castro","sequence":"first","affiliation":[{"name":"Interdepartmental Division of Critical Care Medicine, Toronto General Hospital"},{"name":"Leslie Dan Faculty of Pharmacy, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Balzani","sequence":"additional","affiliation":[{"name":"Interdepartmental Division of Critical Care Medicine, Toronto General Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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