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黃靜芝
139 articles
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  • NCBISkip to main contentSkip to navigationResourcesAll ResourcesChemicals & BioassaysBioSystemsPubChem BioAssayPubChem CompoundPubChem Structure SearchPubChem SubstanceAll Chemicals & Bioassays Resources...DNA & RNABLAST (Basic Local Alignment Search Tool)BLAST (Stand-alone)E-UtilitiesGenBankGenBank: BankItGenBank: SequinGenBank: tbl2asnGenome WorkbenchInfluenza VirusNucleotide DatabasePopSetPrimer-BLASTProSplignReference Sequence (RefSeq)RefSeqGeneSequence Read Archive (SRA)SplignTrace ArchiveUniGeneAll DNA & RNA Resources...Data & SoftwareBLAST (Basic Local Alignment Search Tool)BLAST (Stand-alone)Cn3DConserved Domain Search Service (CD Search)E-UtilitiesGenBank: BankItGenBank: SequinGenBank: tbl2asnGenome ProtMapGenome WorkbenchPrimer-BLASTProSplignPubChem Structure SearchSNP Submission ToolSplignVector Alignment Search Tool (VAST)All Data & Software Resources...Domains & StructuresBioSystemsCn3DConserved Domain Database (CDD)Conserved Domain Search Service (CD Search)Structure (Molecular Modeling Database)Vector Alignment Search Tool (VAST)All Domains & Structures Resources...Genes & ExpressionBioSystemsDatabase of Genotypes and Phenotypes (dbGaP)E-UtilitiesGeneGene Expression Omnibus (GEO) Database Gene Expression Omnibus (GEO) DatasetsGene Expression Omnibus (GEO) ProfilesGenome WorkbenchHomoloGeneOnline Mendelian Inheritance in Man (OMIM)RefSeqGeneUniGeneAll Genes & Expression Resources...Genetics & MedicineBookshelfDatabase of Genotypes and Phenotypes (dbGaP)Genetic Testing RegistryInfluenza VirusOnline Mendelian Inheritance in Man (OMIM)PubMedPubMed Central (PMC)PubMed Clinical QueriesRefSeqGeneAll Genetics & Medicine Resources...Genomes & MapsDatabase of Genomic Structural Variation (dbVar)GenBank: tbl2asnGenomeGenome ProjectGenome Data Viewer (GDV)Genome ProtMapGenome WorkbenchInfluenza VirusNucleotide DatabasePopSetProSplignSequence Read Archive (SRA)SplignTrace ArchiveAll Genomes & Maps Resources...HomologyBLAST (Basic Local Alignment Search Tool)BLAST (Stand-alone)BLAST Link (BLink)Conserved Domain Database (CDD)Conserved Domain Search Service (CD Search)Genome ProtMapHomoloGeneProtein ClustersAll Homology Resources...LiteratureBookshelfE-UtilitiesJournals in NCBI DatabasesMeSH DatabaseNCBI HandbookNCBI Help ManualNCBI News & BlogPubMedPubMed Central (PMC)PubMed Clinical QueriesAll Literature Resources...ProteinsBioSystemsBLAST (Basic Local Alignment Search Tool)BLAST (Stand-alone)BLAST Link (BLink)Conserved Domain Database (CDD)Conserved Domain Search Service (CD Search)E-UtilitiesProSplignProtein ClustersProtein DatabaseReference Sequence (RefSeq)All Proteins Resources...Sequence AnalysisBLAST (Basic Local Alignment Search Tool)BLAST (Stand-alone)BLAST Link (BLink)Conserved Domain Search Service (CD Search)Genome ProtMapGenome WorkbenchInfluenza VirusPrimer-BLASTProSplignSplignAll Sequence Analysis Resources...TaxonomyTaxonomyTaxonomy BrowserTaxonomy Common TreeAll Taxonomy Resources...Training & TutorialsNCBI Education PageNCBI HandbookNCBI Help ManualNCBI News & BlogAll Training & Tutorials Resources...VariationDatabase of Genomic Structural Variation (dbVar)Database of Genotypes and Phenotypes (dbGaP)Database of Single Nucleotide Polymorphisms (dbSNP)SNP Submission ToolAll Variation Resources...How ToAll How ToChemicals & BioassaysDNA & RNAData & SoftwareDomains & StructuresGenes & ExpressionGenetics & MedicineGenomes & MapsHomologyLiteratureProteinsSequence AnalysisTaxonomyTraining & TutorialsVariationAbout NCBI Accesskeys PubMed US National Library of Medicine National Institutes of Health Search databasePubMedAll DatabasesAssemblyBiocollectionsBioProjectBioSampleBioSystemsBooksClinVarConserved DomainsdbGaPdbVarGeneGenomeGEO DataSetsGEO ProfilesGTRHomoloGeneIdentical Protein GroupsMedGenMeSHNCBI Web SiteNLM CatalogNucleotideOMIMPMCPopSetProbeProteinProtein ClustersPubChem BioAssayPubChem CompoundPubChem SubstancePubMedSNPSparcleSRAStructureTaxonomyToolKitToolKitAllToolKitBookghUniGeneSearch termSearch Create RSSRSS SettingsSearch: 30535516Number of items displayed:510152050100Feed name:Create RSSCreate alertAdvancedHelp Result Filters Format: AbstractFormatSummarySummary (text)AbstractAbstract (text)MEDLINEXMLPMID ListApplySend to jQuery(document).ready( function () { jQuery("#send_to_menu input[type='radio']").click( function () { var selectedValue = jQuery(this).val().toLowerCase(); 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Find out why...Add to ClipboardAdd to CollectionsOrder articlesAdd to My BibliographyGenerate a file for use with external citation management software.Create File Intensive Care Med. 2019 Jan;45(1):62-71. doi: 10.1007/s00134-018-5478-0. Epub 2018 Dec 10.Early extubation followed by immediate noninvasive ventilation vs. standard extubation in hypoxemic patients: a randomized clinical trial.Vaschetto R1,2, Longhini F3, Persona P4, Ori C5, Stefani G5, Liu S6, Yi Y6, Lu W7, Yu T7, Luo X8, Tang R8, Li M9, Li J9, Cammarota G1, Bruni A10, Garofalo E10, Jin Z11, Yan J11, Zheng R12, Yin J12, Guido S1, Della Corte F1,2, Fontana T13, Gregoretti C14, Cortegiani A14, Giarratano A14, Montagnini C1, Cavuto S15, Qiu H6, Navalesi P16.Author information1Azienda Ospedaliero Universitaria "Maggiore Della Carità", Anestesia e Terapia Intensiva, Corso Mazzini 18, Novara, Italy.2Università del Piemonte Orientale, via Solaroli 17, Novara, Italy.3Ospedale Sant'Andrea, Anestesia e Rianimazione, Corso Abbiate 21, Vercelli, Italy.4Emergency Department, Azienda Ospedaliera di Padova, Via Giustiniani 2, Padua, Italy.5Department of Medicine, DIMED, University of Padova, Via Giustiniani 2, Padua, Italy.6Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China.7Department of Critical Care Medicine, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, Anhui, China.8Department of Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China.9Department of Critical Care Medicine, Xuzhou Central Hospital, Xuzhou, 221009, Jiangsu, China.10Anestesia e Rianimazione, Dipartimento di Scienze Mediche e Chirurgiche, Università "Magna Graecia", Viale Europa (Loc. Germaneto), Catanzaro, Italy.11Department of Critical Care Medicine, Zhenjiang First People's Hospital, Zhenjiang, 212002, Jiangsu, China.12Department of Critical Care Medicine, Northern Jiangsu People's Hospital, Yangzhou, 225000, Jiangsu, China.13Azienda Sanitaria Locale del Verbano Cusio Ossola, Anestesia e Rianimazione, Piazza Vittime dei Lager Nazifascisti 1, Domodossola, Italy.14Department of Biopathology and Medical Biotechnologies (DIBIMED), Section of Anesthesia, Analgesia, Intensive Care and Emergency, Policlinico Paolo Giaccone, University of Palermo, Via del Vespro 129, Palermo, Italy.15Azienda Unità Sanitaria Locale di Reggio Emilia-IRCCS, S.C. Infrastruttura Ricerca e Statistica, Via Amendola 2, Reggio Emilia, Italy.16Anestesia e Rianimazione, Dipartimento di Scienze Mediche e Chirurgiche, Università "Magna Graecia", Viale Europa (Loc. Germaneto), Catanzaro, Italy. pnavalesi@unicz.it.AbstractPURPOSE: Noninvasive ventilation (NIV) may facilitate withdrawal of invasive mechanical ventilation (i-MV) and shorten intensive care unit (ICU) length of stay (LOS) in hypercapnic patients, while data are lacking on hypoxemic patients. We aim to determine whether NIV after early extubation reduces the duration of i-MV and ICU LOS in patients recovering from hypoxemic acute respiratory failure.METHODS: Highly selected non-hypercapnic hypoxemic patients were randomly assigned to receive NIV after early or standard extubation. Co-primary end points were duration of i-MV and ICU LOS. Secondary end points were treatment failure, severe events (hemorrhagic, septic, cardiac, renal or neurologic episodes, pneumothorax or pulmonary embolism), ventilator-associated pneumonia (VAP) or tracheobronchitis (VAT), tracheotomy, percent of patients receiving sedation after study enrollment, hospital LOS, and ICU and hospital mortality.RESULTS: We enrolled 130 consecutive patients, 65 treatments and 65 controls. Duration of i-MV was shorter in the treatment group than for controls [4.0 (3.0-7.0) vs. 5.5 (4.0-9.0) days, respectively, p = 0.004], while ICU LOS was not significantly different [8.0 (6.0-12.0) vs. 9.0 (6.5-12.5) days, respectively (p = 0.259)]. Incidence of VAT or VAP (9% vs. 25%, p = 0.019), rate of patients requiring infusion of sedatives after enrollment (57% vs. 85%, p = 0.001), and hospital LOS, 20 (13-32) vs. 27(18-39) days (p = 0.043) were all significantly reduced in the treatment group compared with controls. There were no significant differences in ICU and hospital mortality or in the number of treatment failures, severe events, and tracheostomies.CONCLUSIONS: In highly selected hypoxemic patients, early extubation followed by immediate NIV application reduced the days spent on invasive ventilation without affecting ICU LOS.KEYWORDS: Acute respiratory failure; Extubation; Hypoxemia; Noninvasive ventilation; WeaningPMID: 30535516 DOI: 10.1007/s00134-018-5478-0 Share on FacebookShare on TwitterShare on Google+LinkOut - more resourcesFull Text SourcesSpringerMedicalClinicalTrials.gov Supplemental Content Full text links Save itemsAdd to FavoritesView more optionsCreate collection...Manage collections...loadingSimilar articlesNoninvasive ventilation after early extubation in patients recovering from hypoxemic acute respiratory failure: a single-centre feasibility study.[Intensive Care Med. 2012]Noninvasive ventilation after early extubation in patients recovering from hypoxemic acute respiratory failure: a single-centre feasibility study.Vaschetto R, Turucz E, Dellapiazza F, Guido S, Colombo D, Cammarota G, Della Corte F, Antonelli M, Navalesi P. Intensive Care Med. 2012 Oct; 38(10):1599-606. Epub 2012 Jul 24.Noninvasive ventilation immediately after extubation improves weaning outcome after acute respiratory failure: a randomized controlled trial.[Crit Care. 2013]Noninvasive ventilation immediately after extubation improves weaning outcome after acute respiratory failure: a randomized controlled trial.Ornico SR, Lobo SM, Sanches HS, Deberaldini M, Tófoli LT, Vidal AM, Schettino GP, Amato MB, Carvalho CR, Barbas CS. Crit Care. 2013 Mar 4; 17(2):R39. Epub 2013 Mar 4.[Study of timing of invasive and noninvasive sequential ventilation in patients with acute respiratory distress syndrome].[Zhonghua Wei Zhong Bing Ji Jiu...][Study of timing of invasive and noninvasive sequential ventilation in patients with acute respiratory distress syndrome].Wang X, Xu S, Liu G, Caikai S. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2014 May; 26(5):330-4. Review Non-invasive ventilation as a strategy for weaning from invasive mechanical ventilation: a systematic review and Bayesian meta-analysis.[Intensive Care Med. 2018]Review Non-invasive ventilation as a strategy for weaning from invasive mechanical ventilation: a systematic review and Bayesian meta-analysis.Yeung J, Couper K, Ryan EG, Gates S, Hart N, Perkins GD. Intensive Care Med. 2018 Dec; 44(12):2192-2204. Epub 2018 Oct 31.Review Automated weaning and SBT systems versus non-automated weaning strategies for weaning time in invasively ventilated critically ill adults.[Cochrane Database Syst Rev. 2014]Review Automated weaning and SBT systems versus non-automated weaning strategies for weaning time in invasively ventilated critically ill adults.Burns KE, Lellouche F, Nisenbaum R, Lessard MR, Friedrich JO. Cochrane Database Syst Rev. 2014 Sep 9; (9):CD008638. Epub 2014 Sep 9.See reviews...See all...Related informationArticles frequently viewed togetherArticles frequently viewed togetherMedGenRelated information in MedGenSearch details 30535516[uid]Search See more... Recent ActivityClearTurn OffTurn On30535516[uid] (1)PubMedEarly extubation followed by immediate noninvasive ventilation vs. standard extu...Early extubation followed by immediate noninvasive ventilation vs. standard extubation in hypoxemic patients: a randomized clinical trial.Intensive Care Med. 2019 Jan;45(1):62-71. doi: 10.1007/s00134-018-5478-0. Epub 2018 Dec 10.PubMedYour browsing activity is empty.Activity recording is turned off.Turn recording back onSee more... 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  • Intensive Care Med. 2019 Jan;45(1):62-71. doi: 10.1007/s00134-018-5478-0. Epub 2018 Dec 10.
  • NCBISkip to main contentSkip to navigationResourcesAll ResourcesChemicals & BioassaysBioSystemsPubChem BioAssayPubChem CompoundPubChem Structure SearchPubChem SubstanceAll Chemicals & Bioassays Resources...DNA & RNABLAST (Basic Local Alignment Search Tool)BLAST (Stand-alone)E-UtilitiesGenBankGenBank: BankItGenBank: SequinGenBank: tbl2asnGenome WorkbenchInfluenza VirusNucleotide DatabasePopSetPrimer-BLASTProSplignReference Sequence (RefSeq)RefSeqGeneSequence Read Archive (SRA)SplignTrace ArchiveUniGeneAll DNA & RNA Resources...Data & SoftwareBLAST (Basic Local Alignment Search Tool)BLAST (Stand-alone)Cn3DConserved Domain Search Service (CD Search)E-UtilitiesGenBank: BankItGenBank: SequinGenBank: tbl2asnGenome ProtMapGenome WorkbenchPrimer-BLASTProSplignPubChem Structure SearchSNP Submission ToolSplignVector Alignment Search Tool (VAST)All Data & Software Resources...Domains & StructuresBioSystemsCn3DConserved Domain Database (CDD)Conserved Domain Search Service (CD Search)Structure (Molecular Modeling Database)Vector Alignment Search Tool (VAST)All Domains & Structures Resources...Genes & ExpressionBioSystemsDatabase of Genotypes and Phenotypes (dbGaP)E-UtilitiesGeneGene Expression Omnibus (GEO) Database Gene Expression Omnibus (GEO) DatasetsGene Expression Omnibus (GEO) ProfilesGenome WorkbenchHomoloGeneOnline Mendelian Inheritance in Man (OMIM)RefSeqGeneUniGeneAll Genes & Expression Resources...Genetics & MedicineBookshelfDatabase of Genotypes and Phenotypes (dbGaP)Genetic Testing RegistryInfluenza VirusOnline Mendelian Inheritance in Man (OMIM)PubMedPubMed Central (PMC)PubMed Clinical QueriesRefSeqGeneAll Genetics & Medicine Resources...Genomes & MapsDatabase of Genomic Structural Variation (dbVar)GenBank: tbl2asnGenomeGenome ProjectGenome Data Viewer (GDV)Genome ProtMapGenome WorkbenchInfluenza VirusNucleotide DatabasePopSetProSplignSequence Read Archive (SRA)SplignTrace ArchiveAll Genomes & Maps Resources...HomologyBLAST (Basic Local Alignment Search Tool)BLAST (Stand-alone)BLAST Link (BLink)Conserved Domain Database (CDD)Conserved Domain Search Service (CD Search)Genome ProtMapHomoloGeneProtein ClustersAll Homology Resources...LiteratureBookshelfE-UtilitiesJournals in NCBI DatabasesMeSH DatabaseNCBI HandbookNCBI Help ManualNCBI News & BlogPubMedPubMed Central (PMC)PubMed Clinical QueriesAll Literature Resources...ProteinsBioSystemsBLAST (Basic Local Alignment Search Tool)BLAST (Stand-alone)BLAST Link (BLink)Conserved Domain Database (CDD)Conserved Domain Search Service (CD Search)E-UtilitiesProSplignProtein ClustersProtein DatabaseReference Sequence (RefSeq)All Proteins Resources...Sequence AnalysisBLAST (Basic Local Alignment Search Tool)BLAST (Stand-alone)BLAST Link (BLink)Conserved Domain Search Service (CD Search)Genome ProtMapGenome WorkbenchInfluenza VirusPrimer-BLASTProSplignSplignAll Sequence Analysis Resources...TaxonomyTaxonomyTaxonomy BrowserTaxonomy Common TreeAll Taxonomy Resources...Training & TutorialsNCBI Education PageNCBI HandbookNCBI Help ManualNCBI News & BlogAll Training & Tutorials Resources...VariationDatabase of Genomic Structural Variation (dbVar)Database of Genotypes and Phenotypes (dbGaP)Database of Single Nucleotide Polymorphisms (dbSNP)SNP Submission ToolAll Variation Resources...How ToAll How ToChemicals & BioassaysDNA & RNAData & SoftwareDomains & StructuresGenes & ExpressionGenetics & MedicineGenomes & MapsHomologyLiteratureProteinsSequence AnalysisTaxonomyTraining & TutorialsVariationAbout NCBI Accesskeys PubMed US National Library of Medicine National Institutes of Health Search databasePubMedAll DatabasesAssemblyBiocollectionsBioProjectBioSampleBioSystemsBooksClinVarConserved DomainsdbGaPdbVarGeneGenomeGEO DataSetsGEO ProfilesGTRHomoloGeneIdentical Protein GroupsMedGenMeSHNCBI Web SiteNLM CatalogNucleotideOMIMPMCPopSetProbeProteinProtein ClustersPubChem BioAssayPubChem CompoundPubChem SubstancePubMedSNPSparcleSRAStructureTaxonomyToolKitToolKitAllToolKitBookghUniGeneSearch termSearch Create RSSRSS SettingsSearch: 30535516Number of items displayed:510152050100Feed name:Create RSSCreate alertAdvancedHelp Result Filters Format: AbstractFormatSummarySummary (text)AbstractAbstract (text)MEDLINEXMLPMID ListApplySend to jQuery(document).ready( function () { jQuery("#send_to_menu input[type='radio']").click( function () { var selectedValue = jQuery(this).val().toLowerCase(); 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Find out why...Add to ClipboardAdd to CollectionsOrder articlesAdd to My BibliographyGenerate a file for use with external citation management software.Create File Intensive Care Med. 2019 Jan;45(1):62-71. doi: 10.1007/s00134-018-5478-0. Epub 2018 Dec 10.Early extubation followed by immediate noninvasive ventilation vs. standard extubation in hypoxemic patients: a randomized clinical trial.Vaschetto R1,2, Longhini F3, Persona P4, Ori C5, Stefani G5, Liu S6, Yi Y6, Lu W7, Yu T7, Luo X8, Tang R8, Li M9, Li J9, Cammarota G1, Bruni A10, Garofalo E10, Jin Z11, Yan J11, Zheng R12, Yin J12, Guido S1, Della Corte F1,2, Fontana T13, Gregoretti C14, Cortegiani A14, Giarratano A14, Montagnini C1, Cavuto S15, Qiu H6, Navalesi P16.Author information1Azienda Ospedaliero Universitaria "Maggiore Della Carità", Anestesia e Terapia Intensiva, Corso Mazzini 18, Novara, Italy.2Università del Piemonte Orientale, via Solaroli 17, Novara, Italy.3Ospedale Sant'Andrea, Anestesia e Rianimazione, Corso Abbiate 21, Vercelli, Italy.4Emergency Department, Azienda Ospedaliera di Padova, Via Giustiniani 2, Padua, Italy.5Department of Medicine, DIMED, University of Padova, Via Giustiniani 2, Padua, Italy.6Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China.7Department of Critical Care Medicine, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, Anhui, China.8Department of Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China.9Department of Critical Care Medicine, Xuzhou Central Hospital, Xuzhou, 221009, Jiangsu, China.10Anestesia e Rianimazione, Dipartimento di Scienze Mediche e Chirurgiche, Università "Magna Graecia", Viale Europa (Loc. Germaneto), Catanzaro, Italy.11Department of Critical Care Medicine, Zhenjiang First People's Hospital, Zhenjiang, 212002, Jiangsu, China.12Department of Critical Care Medicine, Northern Jiangsu People's Hospital, Yangzhou, 225000, Jiangsu, China.13Azienda Sanitaria Locale del Verbano Cusio Ossola, Anestesia e Rianimazione, Piazza Vittime dei Lager Nazifascisti 1, Domodossola, Italy.14Department of Biopathology and Medical Biotechnologies (DIBIMED), Section of Anesthesia, Analgesia, Intensive Care and Emergency, Policlinico Paolo Giaccone, University of Palermo, Via del Vespro 129, Palermo, Italy.15Azienda Unità Sanitaria Locale di Reggio Emilia-IRCCS, S.C. Infrastruttura Ricerca e Statistica, Via Amendola 2, Reggio Emilia, Italy.16Anestesia e Rianimazione, Dipartimento di Scienze Mediche e Chirurgiche, Università "Magna Graecia", Viale Europa (Loc. Germaneto), Catanzaro, Italy. pnavalesi@unicz.it.AbstractPURPOSE: Noninvasive ventilation (NIV) may facilitate withdrawal of invasive mechanical ventilation (i-MV) and shorten intensive care unit (ICU) length of stay (LOS) in hypercapnic patients, while data are lacking on hypoxemic patients. We aim to determine whether NIV after early extubation reduces the duration of i-MV and ICU LOS in patients recovering from hypoxemic acute respiratory failure.METHODS: Highly selected non-hypercapnic hypoxemic patients were randomly assigned to receive NIV after early or standard extubation. Co-primary end points were duration of i-MV and ICU LOS. Secondary end points were treatment failure, severe events (hemorrhagic, septic, cardiac, renal or neurologic episodes, pneumothorax or pulmonary embolism), ventilator-associated pneumonia (VAP) or tracheobronchitis (VAT), tracheotomy, percent of patients receiving sedation after study enrollment, hospital LOS, and ICU and hospital mortality.RESULTS: We enrolled 130 consecutive patients, 65 treatments and 65 controls. Duration of i-MV was shorter in the treatment group than for controls [4.0 (3.0-7.0) vs. 5.5 (4.0-9.0) days, respectively, p = 0.004], while ICU LOS was not significantly different [8.0 (6.0-12.0) vs. 9.0 (6.5-12.5) days, respectively (p = 0.259)]. Incidence of VAT or VAP (9% vs. 25%, p = 0.019), rate of patients requiring infusion of sedatives after enrollment (57% vs. 85%, p = 0.001), and hospital LOS, 20 (13-32) vs. 27(18-39) days (p = 0.043) were all significantly reduced in the treatment group compared with controls. There were no significant differences in ICU and hospital mortality or in the number of treatment failures, severe events, and tracheostomies.CONCLUSIONS: In highly selected hypoxemic patients, early extubation followed by immediate NIV application reduced the days spent on invasive ventilation without affecting ICU LOS.KEYWORDS: Acute respiratory failure; Extubation; Hypoxemia; Noninvasive ventilation; WeaningPMID: 30535516 DOI: 10.1007/s00134-018-5478-0 Share on FacebookShare on TwitterShare on Google+LinkOut - more resourcesFull Text SourcesSpringerMedicalClinicalTrials.gov Supplemental Content Full text links Save itemsAdd to FavoritesView more optionsCreate collection...Manage collections...loadingSimilar articlesNoninvasive ventilation after early extubation in patients recovering from hypoxemic acute respiratory failure: a single-centre feasibility study.[Intensive Care Med. 2012]Noninvasive ventilation after early extubation in patients recovering from hypoxemic acute respiratory failure: a single-centre feasibility study.Vaschetto R, Turucz E, Dellapiazza F, Guido S, Colombo D, Cammarota G, Della Corte F, Antonelli M, Navalesi P. Intensive Care Med. 2012 Oct; 38(10):1599-606. Epub 2012 Jul 24.Noninvasive ventilation immediately after extubation improves weaning outcome after acute respiratory failure: a randomized controlled trial.[Crit Care. 2013]Noninvasive ventilation immediately after extubation improves weaning outcome after acute respiratory failure: a randomized controlled trial.Ornico SR, Lobo SM, Sanches HS, Deberaldini M, Tófoli LT, Vidal AM, Schettino GP, Amato MB, Carvalho CR, Barbas CS. Crit Care. 2013 Mar 4; 17(2):R39. Epub 2013 Mar 4.[Study of timing of invasive and noninvasive sequential ventilation in patients with acute respiratory distress syndrome].[Zhonghua Wei Zhong Bing Ji Jiu...][Study of timing of invasive and noninvasive sequential ventilation in patients with acute respiratory distress syndrome].Wang X, Xu S, Liu G, Caikai S. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2014 May; 26(5):330-4. Review Non-invasive ventilation as a strategy for weaning from invasive mechanical ventilation: a systematic review and Bayesian meta-analysis.[Intensive Care Med. 2018]Review Non-invasive ventilation as a strategy for weaning from invasive mechanical ventilation: a systematic review and Bayesian meta-analysis.Yeung J, Couper K, Ryan EG, Gates S, Hart N, Perkins GD. Intensive Care Med. 2018 Dec; 44(12):2192-2204. Epub 2018 Oct 31.Review Automated weaning and SBT systems versus non-automated weaning strategies for weaning time in invasively ventilated critically ill adults.[Cochrane Database Syst Rev. 2014]Review Automated weaning and SBT systems versus non-automated weaning strategies for weaning time in invasively ventilated critically ill adults.Burns KE, Lellouche F, Nisenbaum R, Lessard MR, Friedrich JO. Cochrane Database Syst Rev. 2014 Sep 9; (9):CD008638. Epub 2014 Sep 9.See reviews...See all...Related informationArticles frequently viewed togetherArticles frequently viewed togetherMedGenRelated information in MedGenSearch details 30535516[uid]Search See more... Recent ActivityClearTurn OffTurn On30535516[uid] (1)PubMedEarly extubation followed by immediate noninvasive ventilation vs. standard extu...Early extubation followed by immediate noninvasive ventilation vs. standard extubation in hypoxemic patients: a randomized clinical trial.Intensive Care Med. 2019 Jan;45(1):62-71. doi: 10.1007/s00134-018-5478-0. Epub 2018 Dec 10.PubMedYour browsing activity is empty.Activity recording is turned off.Turn recording back onSee more... 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  • Intensive Care Med.
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  • Overview and Recommendations Background Weaning from mechanical ventilation refers to liberating patients from the dependency of mechanical ventilation, transitioning patients to spontaneous breathing, and extubation (removal of the endotracheal tube). Prompt liberation from mechanical ventilation is preferable if possible to avoid adverse outcomes. Evaluation The rapid shallow breathing index has the highest accuracy for detecting weaning outcomes in mechanically ventilated patients compared to other measures. Assess ventilated patients with respiratory failure daily for weaning readiness with a spontaneous breathing trial (SBT) (Strong recommendation). Consider a SBT if the following criteria are met (Weak recommendation): evidence of reversal of underlying cause of respiratory failure adequate oxygenation, defined as: partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) > 150 to 200 PaO2 ≥ 60 mm Hg on FiO2 ≤ 0.4 positive end-expiratory pressure (PEEP) ≤ 5-10 cm water pH ≥ 7.25 hemodynamic stability, defined as: absence of active myocardial ischemia absence of clinically significant hypotension ability to initiate inspiration Management The duration of mechanical ventilation may be reduced by ≥ 1 of several strategies, such as: use of lower tidal volumes (6 mL/kg of ideal body weight) daily interruption of sedative infusion and interruption of sedative infusion prior to spontaneous breathing trial (SBT) avoidance or minimization of sedative use in mechanically ventilated patients early physical and occupational therapy conservative strategy of fluid management in patients with acute lung injury employing strategies for prevention of ventilator-associated pneumonia A general algorithm for weaning and extubation includes: Performing a daily assessment of readiness to attempt SBT (Strong recommendation). If the patient is ready, attempt a SBT. If the SBT is successful, assess the airway anatomy for the ability to protect the airway once the tube is removed, cough strength, quantity of airway secretions, presence of a cuff leak, and mentation. If factors are adequate, extubate. If factors are inadequate, resume ventilatory support and continue with daily assessments of readiness. If the SBT is failed, resume ventilatory support. If the patient is not ready, resume ventilatory support and continue with daily assessments of readiness. Perform SBTs when patients are awake and not taking sedatives, if possible (Strong recommendation). SBTs are initiated by switching the ventilator from full respiratory support modes to partial ventilatory support modes such as: pressure support (PS) mode continuous positive airway pressure (CPAP) mode ventilation with T-piece (with no positive end-expiratory pressure) A successful SBT lasting 30-120 minutes should prompt consideration for ventilator liberation (Strong recommendation). A successful SBT is defined as breathing spontaneously or with little to no ventilatory support and none of the following: respiratory rate > 35 breaths/minute for > 5 minutes oxygen saturation < 90% heart rate ≥ 140 beats/minute sustained change in heart rate of 20% systolic blood pressure of > 180 mm Hg or < 90 mm Hg increased anxiety diaphoresis For patients with respiratory failure who have a failed SBT (Strong recommendation): determine and correct reversible causes for failed SBT perform subsequent SBT every 24 hours provide a stable, nonfatiguing, and comfortable form of ventilatory support to patients failing SBT Related Summaries Mechanical ventilation Prevention of ventilator-associated pneumonia Noninvasive positive pressure ventilation (NPPV) in adults High-flow nasal cannula oxygen in adults Management of the difficult to wean adult patient in the intensive care unit Overview weaning from mechanical ventilation refers to liberating patients from dependency of mechanical ventilation, transitioning patients to spontaneous breathing, and extubation (removal of the endotracheal tube) prompt liberation from mechanical ventilation is preferable if possible to avoid adverse outcomes, such as mortality ventilator-associated pneumonia, lung injury, and diaphragmatic dysfunction longer hospital stay general algorithm for weaning and extubation perform daily assessment of readiness to attempt a spontaneous breathing trial (SBT) (ACCP/AARC/ACCCM Grade A) if patient ready according to readiness criteria, attempt SBT with pressure support, CPAP, or T-piece ventilationif successful SBT (spontaneous breathing for ≥ 30 minutes), assess airway anatomy for ability to protect airway once tube removed, cough strength, quantity of airway secretions, presence of cuff leak, and mentation if factors adequate, extubate if factors inadequate, resume ventilatory support and continue with daily assessments of readiness if failed SBT, resume ventilatory support if patient not ready, resume ventilatory support and continue with daily assessments of readiness rapid shallow breathing index has highest accuracy for detecting weaning outcome in mechanically ventilated patients compared to other measures (level 1 [likely reliable] evidence) approach to SBTs SBTs are initiated by switching ventilator from full respiratory support modes to partial ventilatory support modes such as pressure support (PS) mode continuous positive airway pressure (CPAP) mode ventilation with T-piece (with no positive end-expiratory pressure) pressure support ventilation (PSV) and T-tube may have similar rates of intensive care unit mortality and weaning success in adults with respiratory failure requiring invasive mechanical ventilation for ≥ 24 hours (level 2 [mid-level] evidence) 30 minute SBT and 120 minute SBT have similar rates of extubation success and reintubation rates (level 1 [likely reliable] evidence) criteria for successful SBT include breathing spontaneously or with little to no ventilatory support and none of the following respiratory rate > 35 breaths/minute for > 5 minutes oxygen saturation < 90% heart rate ≥ 140 beats/minute sustained change in heart rate of 20% systolic blood pressure of > 180 mm Hg or < 90 mm Hg increased anxiety diaphoresis for patients with respiratory failure who have failed SBT determine and correct reversible causes for failed SBT and perform subsequent SBT every 24 hours (ACCP/AARC/ACCCM Grade A) provide stable, nonfatiguing, and comfortable form of ventilatory support to patients failing SBT (ACCP/AARC/ACCCM Grade B) adjunctive therapies high-flow nasal cannula oxygen therapy reduces reintubation and postextubation respiratory failure compared to conventional oxygen therapy in critically ill patients at low risk for reintubation after mechanical ventilation (level 1 [likely reliable] evidence) noninvasive ventilation recommended for patients at high risk for extubation failure who have been receiving mechanical ventilation for > 24 hours, and who have passed a spontaneous breathing trial (ATS/ACCP Strong recommendation, Moderate-quality evidence ) noninvasive ventilation following extubation may increase hospital survival and reduce ventilator-associated pneumonia in hard-to-wean patients (level 2 [mid-level] evidence) noninvasive positive pressure ventilation (NPPV) in patients with respiratory failure within 48 hours of extubation is NOT effective for preventing reintubation or reducing mortality (level 1 [likely reliable] evidence) other considerations daily interruption of sedatives may reduce duration of mechanical ventilation but not reintubation or in-hospital mortality in critically ill patients (level 2 [mid-level] evidence) protocolized weaning has been used for discontinuation of mechanical ventilation but unclear which aspect(s) effective in reducing duration of intubation automated weaning and spontaneous breathing trial system may reduce weaning time compared to nonautomated weaning strategies in critically ill adults (level 2 [mid-level] evidence) decision to extubate should be based on airway patency and patient's ability to protect airway due to risk of postextubation upper airway obstruction (ACCP/AARC/ACCCM Grade C) extubation failure associated with increased mortality compared to successful extubation in patients weaned from mechanical ventilation consider administering systemic steroids ≥ 4 hours prior to extubation for adults who fail cuff leak test but are otherwise ready for extubation; repeat cuff leak test not required after administration of steroids (ATS/ACCP Conditional recommendation, Moderate-quality evidence ) weaning strategies for patients requiring prolonged mechanical ventilation should be slow-paced and include gradual lengthening of SBTs (ACCP/AARC/ACCCM Grade C) Background weaning from mechanical ventilation is the process by which patients are liberated from dependency of mechanical ventilation and transitioned to spontaneous breathing, followed by extubation (removal of the endotracheal tube)(1, 3) about 40% of the duration of mechanical ventilation is spent on weaning the patient from the ventilator weaning may be considered after the underlying condition causing respiratory distress has been identified and is improving prompt liberation from mechanical ventilation is preferable in most cases to avoid adverse outcomes, such as mortality ventilator-associated pneumonia, lung injury, and diaphragmatic dysfunction longer hospital stay premature weaning may also lead to complications, such as loss of airway impaired gas exchange aspiration respiratory muscle fatigue pulmonary edema some patients may require gradual or prolonged weaning involves gradually increasing the strength-to-load ratio of the respiratory system to achieve spontaneous breathing when required, prolonged weaning associated with increased risk of poor outcomes weaning often characterized as(1) simple - patient has successful first spontaneous breathing trial (SBT) and mechanical ventilation is discontinued without issue difficult - patient has up to 3 unsuccessful SBTs but is able to discontinue mechanical ventilation within 7 days of first unsuccessful SBT prolonged - patient has up to 3 unsuccessful SBTs or ≥ 7 days of mechanical ventilation following first unsuccessful SBT Recommendations from Professional Organizations American College of Chest Physicians, American Association for Respiratory Care, and American College of Critical Care Medicine (ACCP/AARC/ACCCM) 2001 Task Force recommendations for weaning and discontinuing ventilatory support (2) assess ventilated patients with respiratory failure for weaning potential during spontaneous breathing trial (SBT) (ACCP/AARC/ACCCM Grade A) although some assessments may be made while patient is receiving ventilatory support, formal assessments during SBT preferred consider SBT if following criteria are met (ACCP/AARC/ACCCM Grade B) evidence of reversal of underlying cause of respiratory failure adequate oxygenation, defined as partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) > 150 to 200 PaO2 ≥ 60 mm Hg on FiO2 ≤ 0.4 positive end-expiratory pressure (PEEP) ≤ 5 cm water pH ≥ 7.25 hemodynamic stability, defined as absence of active myocardial ischemia absence of clinically significant hypotension ability to initiate inspiration additional criteria to consider include adequate hemoglobin (≥ 8 g/dL) heart rate ≤ 140 beats/minute systolic blood pressure 90-160 mm Hg adequate mentation (arousable, Glasgow Coma Scale ≥ 13, no continuous sedation infusion) stable metabolic status (acceptable electrolytes and phosphorus) clinical discretion (belief that discontinuation from mechanical ventilation may be possible) adequate cough absence of fever significant respiratory acidosis excessive trachea-bronchial secretions neuromuscular blocking agents no or minimal vasopressor or inotrope brief initial period of spontaneous breathing may be used to determine patient's readiness for formal SBT (ACCP/AARC/ACCCM Grade A) assess the following criteria to determine patient tolerance of SBT respiratory pattern adequacy of gas exchange hemodynamic stability subjective comfort patients tolerating SBT lasting 30-120 minutes should be considered for ventilator discontinuation after successful discontinuation of ventilatory support, extubation should be based on airway patency and patient's ability to protect airway due to risk of postextubation upper airway obstruction (ACCP/AARC/ACCCM Grade C) for patients with respiratory failure who have failed SBT (ACCP/AARC/ACCCM Grade A) determine and correct reversible causes for failed SBT perform subsequent SBT every 24 hours provide stable, nonfatiguing, and comfortable form of ventilatory support to patients failing SBT treat postsurgical patients with anesthesia and ventilator management strategies conducive to early extubation (ACCP/AARC/ACCCM Grade A) intensive care units (ICUs) should develop and implement weaning/discontinuation and sedation optimization protocols for use by nonphysician healthcare providers (ACCP/AARC/ACCCM Grade A) weaning strategies for patients requiring prolonged mechanical ventilation should be slow-paced and include gradually lengthening SBTs (ACCP/AARC/ACCCM Grade C) British Thoracic Society/Intensive Care Society (BTS/ICS) 2016 guideline for ventilatory management of acute hypercapnic respiratory failure recommendations for weaning all patients should have documented weaning plan (BTS/ICS Grade B) start spontaneous breathing as soon as possible (BTS/ICS Grade C) transfer from controlled to assisted mechanical ventilation as soon as possible (BTS/ICS Grade C) assess extubation suitability daily (BTS/ICS Grade C) assess readiness for extubation using 30 minute spontaneous breathing trial (BTS/ICS Grade B) consider upper airway patency, bulbar function, sputum load, and cough effectiveness before attempting extubation (BTS/ICS Grade D) in patients with severe airflow obstruction, chronic hypercapnia or poor triggering due to weak muscles may require continuation of controlled mechanical ventilation (BTS/ICS Grade C) before weaning begins, primary cause of acute respiratory failure should be treated, pH normalized, chronic hypercapnia corrected, and fluid overload addressed (BTS/ICS Grade D) in patients with left ventricular dysfunction, consider brain natriuretic peptide (BNP)-directed fluid management strategy (BTS/ICS Grade B) factors increasing risk of extubation failure should be identified to provide appropriate supportive strategies such as noninvasive ventilation or cough assist (BTS/ICS Grade B) systematic approach to weaning is preferred, but protocols should be used with caution (BTS/ICS Grade B) and computerized weaning is not recommended (BTS/ICS Grade D) Reference - Thorax 2016 Apr;71 Suppl 2:ii1 American Thoracic Society/American College of Chest Physicians (ATS/ACCP) guideline on liberation from mechanical ventilation in critically ill adults for acutely hospitalized adults on mechanical ventilation for > 24 hours consider conducting initial spontaneous breathing trial with inspiratory pressure augmentation (5-8 cm H2O) rather than with T-piece or continuous positive airway pressure (CPAP) (ATS/ACCP Conditional recommendation, Moderate-quality evidence ) consider protocols for minimization of sedation (ATS/ACCP Conditional recommendation, Low-quality evidence ) if high risk of extubation failure, and spontaneous breathing trial passed, extubate to preventive noninvasive ventilation (ATS/ACCP Strong recommendation, Moderate-quality evidence ) extubation to noninvasive ventilation may be avoided in select patients for patient-specific factors such as inability to receive ventilation through mask or similar interface apply noninvasive ventilation immediately after extubation for maximum benefit consider protocolized rehabilitation directed toward early mobilization (ATS/ACCP Conditional recommendation, Low-quality evidence ) consider ventilator liberation protocol (ATS/ACCP Conditional recommendation, Low-quality evidence ) protocol may be personnel or computer driven insufficient evidence to recommend any ventilator liberation protocol over another consider cuff leak test in mechanically ventilated patients who meet extubation criteria and are at high risk for postextubation stridor (ATS/ACCP Conditional recommendation, Very low-quality evidence ) consider administering systemic steroids ≥ 4 hours prior to extubation for adults who fail cuff leak test but are otherwise ready for extubation; repeat cuff leak test not required after administration of steroids (ATS/ACCP Conditional recommendation, Moderate-quality evidence ) Reference - Chest 2017 Jan;151(1):160, commentary can be found in Chest 2017 May;151(5):1179, author reply can be found in Chest 2017 May;151(5):1180 Reducing Duration of Mechanical Ventilation prompt liberation from mechanical ventilation is preferable if possible to avoid adverse outcomes, such as(1, 3) mortality ventilator-associated pneumonia, lung injury, and diaphragmatic dysfunction longer hospital stay duration of mechanical ventilation may be reduced by ≥ 1 of several strategies, such as(1) use of lower tidal volumes (6 mL/kg of ideal body weight) daily interruption of sedative infusion and interruption of sedative infusion prior to spontaneous breathing trial (SBT) avoidance or minimization of sedative use in mechanically ventilated patients early physical and occupational therapy conservative strategy of fluid management in patients with acute lung injury strategies for prevention of ventilator-associated pneumonia treat postsurgical patients with anesthesia and ventilator management strategies conducive to early extubation (ACCP/AARC/ACCCM Grade A)(2) delayed extubation associated with increased risk of pneumonia and longer intensive care unit (ICU) and hospital stays in patients with acute brain injury based on prospective cohort study 136 intubated patients with acute brain injuries admitted to critical care units were evaluated daily for extubation using readiness criteria and followed to hospital discharge 99 patients (73%) were extubated within 48 hours of meeting readiness criteria and the remaining 37 patients (27%) had delayed extubation (within 2-19 days of meeting readiness criteria) comparing patients with delayed vs. early extubation pneumonia in 38% vs. 21% (p < 0.05) median days in ICU 8.6 vs. 3.8 (p < 0.05) median days in hospital 19.9 vs. 13.2 (p < 0.001) Reference - Am J Respir Crit Care Med 2000 May;161(5):1530 Algorithm for Weaning from Mechanical Ventilation general algorithm for weaning and extubation(1) perform daily assessment of readiness to attempt a spontaneous breathing trial (SBT) if patient ready, attempt SBT if successful SBT, assess airway anatomy for ability to protect airway once tube removed, cough strength, quantity of airway secretions, presence of cuff leak, and mentation if factors adequate, extubate if factors inadequate, resume ventilatory support and continue with daily assessments of readiness if failed SBT, resume ventilatory support if patient not ready, resume ventilatory support and continue with daily assessments of readiness intensive care units (ICUs) should develop and implement weaning/discontinuation and sedation optimization protocols for use by nonphysician healthcare providers (ACCP/AARC/ACCCM Grade A)(2) Assessing Readiness for Spontaneous Breathing Trial (SBT) Readiness criteria weaning may be considered after the underlying condition causing respiratory distress has been identified and is improving, although there is no consensus definition for improvement(1, 3) assess ventilated patients with respiratory failure daily for weaning potential during SBT (ACCP/AARC/ACCCM Grade A)(2) although some assessments may be made while patient is receiving ventilatory support, formal assessments during SBT preferred(2) consider SBT if following criteria are met (ACCP/AARC/ACCCM Grade B)(2) evidence of reversal of underlying cause of respiratory failure adequate oxygenation, defined as partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) > 150 to 200 PaO2 ≥ 60 mm Hg on FiO2 ≤ 0.4 positive end-expiratory pressure (PEEP) ≤ 5 cm water pH ≥ 7.25 hemodynamic stability, defined as absence of active myocardial ischemia absence of clinically significant hypotension ability to initiate inspiration additional criteria to consider include(2) adequate hemoglobin (≥ 8 g/dL) heart rate ≤ 140 beats/minute systolic blood pressure 90-160 mm Hg adequate mentation (arousable, Glasgow Coma Scale ≥ 13, no continuous sedation infusion) stable metabolic status (acceptable electrolytes and phosphorus) clinical discretion (belief that discontinuation from mechanical ventilation may be possible) adequate cough absence of fever significant respiratory acidosis excessive trachea-bronchial secretions neuromuscular blocking agents no or minimal vasopressor or inotrope SBT in addition to daily screening for respiratory function increases extubation success and decreases duration of mechanical ventilation in adults in intensive care unit (ICU) (level 1 [likely reliable] evidence) based on randomized trial 300 adults in the ICU were randomized to daily screening of respiratory function and SBT vs. daily screening only comparing daily respiratory screening and SBT vs. screening only, screening and SBT associated with higher rate of successful extubation (risk ratio 2.13, 95% CI 1.55-2.92) lower duration of mechanical ventilation (median 4.5 days vs. median 6 days, p = 0.003) lower rate of complications (20% vs. 41%, p = 0.001) no significant difference in mortality (38% vs. 40%) Reference - N Engl J Med 1996 Dec 19;335(25):1864 full-text, editorial can be found in N Engl J Med 1996 Dec 19;335(25):1916, commentary can be found in N Engl J Med 1997 May 29;336(22):1610 daily evaluation for readiness to wean plus spontaneous breathing test may decrease duration of mechanical ventilation compared to standard weaning protocol in children (level 2 [mid-level] evidence) based on randomized trial without intention-to-treat analysis 312 children aged 28 days to 15 years admitted to ICU and receiving mechanical ventilation for ≥ 24 hours randomized to daily evaluation for readiness to wean plus spontaneous breathing test vs. standard weaning protocol intervention protocol daily evaluation to determine if weaning readiness criteria met, including FiO2 ≤ 50% PEEP ≤ 25 cm H2O peak inspiratory pressure ≤ 25 cm H2O no new infiltrates on chest x-ray presence of respiratory drive no continuous sedation no neuromuscular blockers in last 24 hours electrolytes within normal limits hemodynamic stability hemoglobin ≥ 8 g/dL spontaneous breathing test if above criteria met PEEP 5 cm H2O, pressure support ventilation 10 cm H2O, and maintenance of pretest FiO2 for 2 hours children who failed test (defined as any sign of intolerance, such as increased respiratory effort, arterial blood oxygen saturation < 90%, or hypotension) continued mechanical ventilation and were reevaluated/retested after 24 hours children who passed spontaneous breathing test were extubated standard weaning protocol consisted of weaning and extubation at discretion of attending physician, and no spontaneous breathing test 18 children were excluded after randomization for ineligibility 34 children who died prior to weaning were not included in analysis median time to extubation 3.5 days for daily evaluation vs. 4.7 days for standard protocol (p = 0.0127) no significant differences between groups in need for reintubation or noninvasive mechanical ventilation Reference - Crit Care Med 2011 Nov;39(11):2526, editorial can be found in Crit Care Med 2011 Nov;39(11):2581 Predicting weaning success rapid shallow breathing index (RSBI = respiratory rate [RR]/tidal volume [Vtidal]) as a predictor of weaning success RSBI has highest accuracy for detecting weaning outcome in mechanically ventilated patients compared to other measures (level 1 [likely reliable] evidence) based on diagnostic cohort study 100 patients ready to wean from mechanical ventilation (mean 8 days of ventilation) were evaluated with several indexes for assessing weaning outcome, including 2 indexes newly developed prior to this study RSBI quantified while patient breathed spontaneously for 1 minute compliance, rate, oxygenation, and pressure (CROP) index = dynamic compliance × maximal inspiratory pressure (Plmax) × (partial pressure of arterial oxygen [PaO2]/partial pressure of alveolar oxygen [PAO2])/respiratory rate cutoff values for predicting successful weaning for each index were derived from the first 36 patients who were weaned (24 successful and 12 unsuccessful) validation cohort included remaining 64 patients who were weaned (36 successful and 28 unsuccessful) for detection of successful or failed weaning Index Accuracy:Index Cutoff Value for Successful WeaningSensitivity Specificity RSBI≤ 105 breaths/minute/L0.970.64CROP ≥ 13 mL/breath/minute0.810.57Minute ventilation≤ 15 L/minute0.780.18Respiratory rate≤ 38 breaths/minute0.920.36Tidal volume≥ 325 mL0.970.54Tidal volume/patient's weight≥ 4 mL/kg0.940.39Maximal inspiratory pressure≤ -15 cm H2O10.11Dynamic compliance≥ 22 mL/cm H2O0.720.5Static compliance≥ 33 mL/cm H2O0.750.36PaO2/PAO2≥ 0.350.810.29 Abbreviations: CROP, compliance, rate, oxygenation, and pressure; PaO2, partial pressure of arterial oxygen; PAO2, partial pressure of alveolar oxygen; RSBI, rapid shallow breathing index. Reference - N Engl J Med 1991 May 23;324(21):1445 full-text, editorial can be found in N Engl J Med 1991 May 23;324(21):1496, commentary can be found in N Engl J Med 1991 Nov 14;325(20):1442RSBI associated with high negative predictive value for weaning success in clinically stable mechanically ventilated patients (level 2 [mid-level] evidence) based on diagnostic study without validation 70 clinically stable patients (mean age 69 years) on mechanical ventilation (mean 17 days) who exhibited criteria for weaning were evaluated with RSBI and weaning was attempted when appropriate RSBI calculated from patients breathing spontaneously with pressure support ventilation (PSV) = 0 and positive end-expiratory pressure (PEEP) = 0 for 1 minute patients with RSBI < 105 were extubated within 2 hours patients with RSBI > 105 were reventilated and RSBI was evaluated the following day weaning success defined as tolerated spontaneous respiration for 48 hours 7 patients were excluded because RSBI was always > 105 during the trial period successful weaning in 77% for detecting weaning success, RSBI < 105 had sensitivity 78% specificity 71% positive predictive value 26% negative predictive value 96% Reference - Tanaffos 2012;11(3):28 full-text Approach to Spontaneous Breathing Trials (SBTs) Methods of SBTs SBTs assess the ability of the patient to breath while receiving little to no ventilatory support(1) perform SBTs when patients are awake and not taking sedatives, if possible(1) SBTs are initiated by switching ventilator from full respiratory support modes to partial ventilatory support modes such as(1) pressure support (PS) mode continuous positive airway pressure (CPAP) mode ventilation with T-piece (with no positive end-expiratory pressure) American Thoracic Society/American College of Chest Physicians (ATS/ACCP) recommendations on liberation from mechanical ventilation in critically ill adults for acutely hospitalized patients ventilated more than 24 hours, consider conducting initial SBT with inspiratory pressure support (5-8 cm water) rather than without (T-piece or CPAP) (ATS/ACCP Conditional recommendation, Moderate-quality evidence ) Reference - ATS/ACCP clinical practice guideline on liberation from mechanical ventilation in critically ill adults ( Am J Respir Crit Care Med 2017 Jan 1;195(1):115) Comparing T-tube, pressure support ventilation (PSV), and intermittent mandatory ventilation (IMV) weaning methods PSV and T-tube may have similar rates of intensive care unit (ICU) mortality and weaning success in adults with respiratory failure requiring invasive mechanical ventilation for ≥ 24 hours (level 2 [mid-level] evidence) based on Cochrane review with wide confidence intervals systematic review of 9 randomized trials comparing PSV vs. T-tube weaning in 1,208 adults with respiratory failure requiring invasive mechanical ventilation for ≥ 24 hours results for ICU mortality, weaning success, and reintubation limited by confidence intervals that cannot exclude clinically relevant differences weaning success defined as absence of requirement for ventilatory support within 48 hours after extubation no significant differences in ICU mortality (risk ratio [RR] 0.81, 95% CI 0.53-1.23) in analysis of 5 trials with 725 adults weaning success (RR 1.07, 95% CI 0.97-1.17) in analysis of 9 trials with 935 adults reintubation (RR 0.92, 95% CI 0.66-1.26) in analysis of 7 trials with 823 adults pneumonia in analysis of 2 trials with 118 adults PSV associated with increase in successful trials of spontaneous breathing (RR 1.09, 95% CI 1.02-1.17, NNT 14) in analysis of 4 trials with 940 adults Reference - Cochrane Database Syst Rev 2014 May 27;(5):CD006056 T-tube system associated with higher SBT success at 2 hours but no significant difference in successful extubation or rate of reintubation after SBT success comparing T-tube system or PSV in adults intubated for > 48 hours (level 1 [likely reliable] evidence) based on randomized trial 484 patients (median age 64 years) intubated for > 48 hours and meeting weaning parameters were randomized to SBT by either T-tube system vs. PSV with 7 cm water for 2 hours mechanical ventilation was resumed if patients had any of respiratory rate > 35 breaths/minute arterial oxygen saturation < 90% heart rate > 140 beats/minute sustained change in heart rate > 20% systolic blood pressure > 200 mm Hg or < 80 mm Hg agitation, anxiety, or diaphoresis patients with successful trial were extubated comparing T-tube system vs. PSV 2-hour trial success in 22% vs. 14% (p = 0.03) successful extubation in 57% vs. 68% (not significant) extubation > 48 hours in 63% vs. 70% (not significant) reintubation in 18.7% vs. 18.5% (not significant) Reference - Am J Respir Crit Care Med 1997 Aug;156(2 Pt 1):459 once-daily SBT with T-tube may be associated with higher successful weaning rate compared to IMV and PSV approaches in hard-to-wean patients (level 2 [mid-level] evidence) based on small randomized trial with baseline differences 130 intubated patients having respiratory distress during a 2-hour SBT were randomized to 1 of 4 weaning techniques IMV ventilator rate initially set at mean 10 breaths/minute, then decreased, if possible, ≥ twice daily by 2-4 breaths/minute PSV ventilator pressure initially set at 18 cm of water, then reduced, if possible, by 2-4 cm of water ≥ twice daily intermittent SBTs - ≥ twice daily with either a T-tube or continuous positive airway pressure (CPAP) of ≤ 5 cm once-daily SBT with T-tube patients in IMV group had significantly shorter duration of mechanical ventilation prior to weaning than other groups patients who tolerated the weaning techniques (no signs of distress during 2-hour trials) were extubated once-daily SBT associated with higher likelihood of successful weaning compared to intermittent mandatory ventilation (relative risk of successful weaning with SBT 2.83, 95% CI 1.36-5.89) PSV (relative risk of successful weaning with SBT 2.05, 95% CI 1.04-4.04) no significant difference in successful weaning comparing once-daily SBT to intermittent SBTs Reference - N Engl J Med 1995 Feb 9;332(6):345 full-text PSV associated with reduced rates of weaning failure compared to synchronized intermittent mandatory ventilation (SIMV) or T-piece in hard-to-wean patients (level 2 [mid-level] evidence) based on subgroup analysis of randomized trial 109 patients who failed to tolerate a SBT were randomized to 1 of 3 weaning approaches SIMV with or without positive end-expiratory pressure (PEEP) PSV with or without PEEP T-piece criteria for extubation was different across groups weaning failure defined as inability to be separated from ventilator after 21 days of weaning reintubation/reconnection to ventilator needed within 48 hours of extubation/disconnection from ventilator weaning failure occurred in overall (p = 0.05, pairwise comparisons not reported) 23% with PSV 42% with SIMV 43% with T-piece in subgroup of 97 patients excluding those with weaning termination for complications unrelated to the weaning process (p < 0.025, pairwise comparisons not reported) 8% with PSV 39% with SIMV 33% with T-piece PSV associated with significantly shorter weaning duration and length of stay in ICU Reference - Am J Respir Crit Care Med 1994 Oct;150(4):896 SBT with T-piece may be associated with higher rate of left ventricular heart failure than with PSV with or without PEEP in hard-to-wean patients (level 2 [mid-level] evidence) based on prospective cohort study 14 intubated patients who failed previous T-piece breathing trial were monitored by Swan-Ganz catheter during 3 additional SBTs with each of the following in random order PSV with PEEP PSV without PEEP T-piece rates of successful SBT 79% with PSV with PEEP 57% with PSV without PEEP 0% with T-piece rates of left ventricular heart failure (defined as pulmonary artery occlusion pressure ≥ 18 mm Hg) during SBT 50% with PSV and PEEP 64% with PSV without PEEP 79% with T-piece SBT with T-piece associated with elevated respiratory parameters (p < 0.05 for all comparisons vs. PSV with or without PEEP) higher work of breathing higher esophageal pressure time product higher rapid shallow breathing index elevated hemodynamic parameters (p < 0.05 for all comparisons) higher systolic blood pressure (vs. PSV with or without PEEP) higher heart rate (vs. PSV with PEEP) higher pulmonary artery occlusion pressure (vs. PSV with PEEP) Reference - Intensive Care Med 2010 Jul;36(7):1171 SBT duration duration of SBT should be ≥ 30 minutes(3) monitor patients closely during first few minutes as detrimental effects of ventilator muscle overload usually occur early(2) SBT tolerance lasting 30-120 minutes should prompt consideration for ventilator liberation (ACCP/AARC/ACCCM Grade A)(2) 30-minute SBT and 120-minute SBT have similar rates of extubation success and reintubation rates (level 1 [likely reliable] evidence) based on randomized trial 526 adults (median age 64 years) on mechanical ventilation and meeting criteria for SBT randomized to T-tube system for 30 minutes vs. 120 minutes mechanical ventilation was resumed if patients had any of respiratory rate > 35 breaths/minute arterial oxygen saturation < 90% heart rate > 140 beats/minute sustained change in heart rate > 20% systolic blood pressure > 200 mm Hg or < 80 mm Hg agitation, anxiety, or diaphoresis patients with successful trial were extubated no significant differences in successful trial extubation > 48 hours reintubation rate mortality Reference - Am J Respir Crit Care Med 1999 Feb;159(2):512 Successful SBT criteria brief initial period of spontaneous breathing may be used to determine patient's readiness for formal SBT (ACCP/AARC/ACCCM Grade A)(2) assess the following criteria to determine patient tolerance of SBT respiratory pattern adequacy of gas exchange hemodynamic stability subjective comfort patients tolerating SBT lasting 30-120 minutes should be considered for ventilator discontinuation criteria for successful SBT include breathing spontaneously or with little to no ventilatory support and none of the following(1) respiratory rate > 35 breaths/minute for > 5 minutes oxygen saturation < 90% heart rate ≥ 140 beats/minute sustained change in heart rate of 20% systolic blood pressure of > 180 mm Hg or < 90 mm Hg increased anxiety diaphoresis Failed SBT for patients with respiratory failure who have failed SBT(2) determine and correct reversible causes for failed SBT (ACCP/AARC/ACCCM Grade A) perform subsequent SBT every 24 hours (ACCP/AARC/ACCCM Grade A) provide stable, nonfatiguing, and comfortable form of ventilatory support to patients failing SBT (ACCP/AARC/ACCCM Grade B) Adjunctive Therapies High-flow nasal cannula oxygen therapy high-flow nasal cannula oxygen therapy reduces reintubation and postextubation respiratory failure compared to conventional oxygen therapy in critically ill patients at low risk for reintubation after mechanical ventilation (level 1 [likely reliable] evidence) based on randomized trial 527 critically ill adults (mean age 51 years, 60% male) receiving mechanical ventilation for ≥ 12 hours and at low risk for reintubation were randomized after successful spontaneous breathing trial to high-flow nasal cannula oxygen therapy vs. conventional oxygen therapy low risk for reintubation defined as < 65 years old; body mass index < 30 kg/m2; Acute Physiology and Chronic Health Evaluation (APACHE) II score < 12 on day of extubation; adequate secretions management; simple weaning; ≤ 1 comorbidity; and absence of heart failure, moderate-to-severe chronic obstructive pulmonary disease, airway patency problems, prolonged mechanical ventilation (> 7 days) high-flow oxygen therapy provided for 24 hours with initial flow rate of 10 L/minute titrated up in 5 L/minute increments until patient experienced discomfort in both groups, oxygen therapy adjusted to maintain target peripheral capillary oxygen saturation (SpO2) > 92% all patients were included in analysis comparing high-flow oxygen therapy vs. conventional oxygen therapy all-cause reintubation within 72 hours in 4.9% vs. 12.2% (p = 0.004, NNT 14) postextubation respiratory failure in 8.3% vs. 14.4% (p = 0.03, NNT 17) respiratory infection in 2.3% vs. 4.9% (p = 0.07) in-hospital mortality 3.8% vs. 5% (not significant) no significant differences in ventilator-associated pneumonia, sepsis, time to reintubation, length of intensive care unit stay, length of hospitalization, or intensive care unit mortality Reference - JAMA 2016 Apr 5;315(13):1354, editorial can be found in JAMA 2016 Apr 5;315(13):1340 Noninvasive positive pressure ventilation (NPPV) American Thoracic Society/American College of Chest Physicians (ATS/ACCP) recommendations on liberation from mechanical ventilation in critically ill adults for patients at high risk for extubation failure who have been receiving mechanical ventilation for > 24 hours, and who have passed a spontaneous breathing trial, extubation to preventive noninvasive ventilation recommended (ATS/ACCP Strong recommendation, Moderate-quality evidence ) Reference - ATS/ACCP clinical practice guideline on liberation from mechanical ventilation in critically ill adults ( Am J Respir Crit Care Med 2017 Jan 1;195(1):115) noninvasive ventilation following extubation may increase hospital survival and reduce ventilator-associated pneumonia (VAP) in hard-to-wean patients (level 2 [mid-level] evidence) based on systematic review with confidence intervals that do not exclude clinically meaningful differences systematic review of 16 randomized trials evaluating noninvasive ventilation (NPPV or continuous positive airway pressure [CPAP]) vs. standard care for mechanically ventilated patients noninvasive ventilation was used following extubation in hard-to-wean patients in 5 trials in critically ill patients in the intensive care unit (ICU) in 6 trials postoperatively in 5 trials when used for hard-to-wean patients, noninvasive ventilation following extubation associated with increased hospital survival (odds ratio [OR] for death 0.55, 95% CI 0.31-0.98) in analysis of 4 trials with 279 patients reduced risk of VAP (OR 0.12, 95% CI 0.05-0.31) in analysis of 4 trials with 191 patients no significant differences in ICU survival (OR 0.83, 95% CI 0.44-1.58) in analysis of 3 trials with 246 patients reintubation (OR 0.96, 95% CI 0.5-1.83) in analysis of 2 trials with 181 patients when used following extubation in the ICU, noninvasive ventilation associated with no significant differences in hospital survival (OR for survival 1.24, 95% CI 0.78-1.98) in analysis of 4 trials with 479 patients ICU survival (OR 1.24, 95% CI 0.84-1.85) in analysis of 5 trials with 700 patients VAP (OR 0.72, 95% CI 0.42-1.25) in analysis of 3 trials with 349 patients reintubation (OR 0.72, 95% CI 0.51-1.02) in analysis of 6 trials with 740 patients Reference - Br J Anaesth 2012 Sep;109(3):305 full-text NPPV may reduce need for reintubation in patients at increased risk for extubation failure (level 2 [mid-level] evidence) based on 3 randomized trials with limitations randomized trial without blinding162 mechanically ventilated patients who tolerated a spontaneous breathing trial wean and who had increased risk for extubation failure were randomized after extubation to noninvasive positive pressure ventilation (NPPV) for 24 hours vs. conventional management with supplemental oxygenNPPV also used in both groups as rescue therapy for patients with respiratory failure who did not need immediate reintubationfor patients in NPPV group, rescue therapy defined as reinstitution or continuation of NPPV after 24 hours for ≤ 4 hourscomparing NPPV vs. conventional carerespiratory failure after extubation in 16% vs. 33% (p = 0.029, NNT 6)immediate reintubation required in 11% vs. 10% (not significant)rescue NPPV delivered to 4 patients (all of whom avoided reintubation) vs. 19 patients (9 of whom avoided reintubation)overall reintubation rate 11% vs. 22% (not significant)intensive care unit mortality 3% vs. 14% (p = 0.015, NNT 9)Reference - Am J Respir Crit Care Med 2006 Jan 15;173(2):164 randomized trial without blinding97 patients requiring mechanical ventilation for > 48 hours and who had increased risk for extubation failure were randomized (after successful weaning trial) to NPPV for ≥ 8 hours/day in first 48 hours vs. standard medical therapyreintubation required in 8.3% NPPV vs. 24.5% standard therapy patients (p = 0.027, NNT 7)Reference - Crit Care Med 2005 Nov;33(11):2465, editorial can be found in Crit Care Med 2005 Nov;33(11):2685 small randomized trial 40 patients mechanically ventilated for ≥ 72 hours due to acute respiratory failure randomized to noninvasive ventilation vs. oxygen mask immediately prior to extubation weaning failure defined as reintubation within 48 hours comparing noninvasive ventilation vs. oxygen mask weaning failure in 5% vs. 39% (p = 0.016, NNT 3) hospital mortality in 0% vs. 22.2% (p = 0.041, NNT 5) Reference - Crit Care 2013 Mar 4;17(2):R39 full-text NPPV in patients with respiratory failure within 48 hours of extubation is NOT effective for preventing reintubation or reducing mortality (level 1 [likely reliable] evidence) based on 2 randomized trials 221 adults who had mechanical ventilation for > 48 hours and who subsequently had respiratory failure within 48 hours of extubation were randomized to noninvasive positive pressure ventilation (NPPV) via full facial mask vs. standard medical therapyno significant difference in rate of reintubation (48% in both groups)mortality while in intensive care unit (ICU) higher in NPPV group (25% vs. 14%) (p = 0.048, NNH 9)Reference - N Engl J Med 2004 Jun 10;350(24):2452, editorial can be found in N Engl J Med 2004 Jun 10;350(24):2512, commentary can be found in N Engl J Med 2004 Sep 16;351(12):1257, ACP J Club 2004 Nov-Dec;141(3):71 81 patients with cardiac or respiratory disease who required ventilatory support > 2 days and developed respiratory distress within 48 hours of extubation were randomized to standard therapy (oxygen to maintain pulse oximetry at least 95%) vs. standard therapy plus NPPV by face maskcomparing standard therapy vs. NPPV plus standard therapy, no significant differences inrates of reintubation (69% vs. 72%)hospital mortality (31% vs. 31%)length of ICU or hospital stayReference - JAMA 2002 Jun 26;287(24):3238, commentary can be found in JAMA 2002 Nov 27;288(20):2540 in patients not meeting extubation criteria, extubation plus noninvasive ventilation associated with similar mortality as continued intubation until criteria met (level 2 [mid-level] evidence) based on systematic review without assessment of trial quality systematic review of 78 randomized trials with 7,365 adults comparing noninvasive ventilation (NIV) to any other intervention for treating or preventing acute respiratory failure in nonintubated patients or for facilitating extubation of intubated patients not yet meeting criteria for extubation no significant difference in mortality in analysis of 7 trials comparing extubation plus NIV vs. continued intubation for weaning in 509 intubated patients not meeting extubation criteria Reference - Crit Care Med 2015 Apr;43(4):880, editorial can be found in Crit Care Med 2015 Apr;43(4):927 weaning with early extubation to noninvasive ventilation does not shorten time to liberation from any ventilation compared to standard invasive weaning in adults on mechanical ventilation with unsuccessful spontaneous breathing trial (level 1 [likely reliable] evidence) based on randomized trial 364 adults (mean age 63 years) on invasive mechanical ventilation for ≥ 48 hours with unsuccessful spontaneous breathing trial were randomized to 1 of 2 protocolized weaning interventionsearly extubation to noninvasive ventilationstandard weaning consisting of continued invasive ventilation until successful spontaneous breathing trial, followed by extubation most common reasons for mechanical ventilation were pneumonia (36%) and respiratory failure after surgery (21%) 96.1% in noninvasive ventilation group and 96.7% in standard weaning group received assigned intervention primary outcome was time to successful liberation from any mechanical ventilation, minimal clinically important difference defined as 1 day 11% died before liberation from ventilation, 88% were included in analysis of primary outcome comparing weaning with early extubation to noninvasive ventilation vs. standard invasive weaningmean time to successful liberation from mechanical ventilation 4.3 days vs. 4.5 days (not significant)median duration of total ventilation 3 days vs. 4 days (incidence rate ratio 0.8, 95% CI 0.62-1)need for antibiotics for presumed respiratory infection in 60.4% vs. 70.3% (p < 0.05, NNT 11)reintubation in 37% vs. 28.7% (not significant)adverse events in 24.7% vs. 25.8% (no p value reported) no significant differences in survival at 30 days, rates of tracheostomy, dysrhythmias, or nonrespiratory infection, and health-related quality of life at 3 and 6 months Reference - Breathe trial ( JAMA 2018 Oct 22 early online), editorial can be found in JAMA 2018 Oct 22 early online noninvasive ventilation immediately after early extubation associated with reduced mortality and reduced risk of ventilator-associated pneumonia (VAP) in critically ill adults with chronic obstructive pulmonary disease (COPD) on mechanical ventilation (level 2 [mid-level] evidence) based on Cochrane review of trials with clinical heterogeneity systematic review of 16 randomized or quasi-randomized trials comparing early extubation plus immediate noninvasive ventilation vs. continued invasive positive-pressure ventilation weaning in 994 intubated adults with respiratory failure (mostly with COPD) clinical heterogeneity included whether or not defined extubation criteria were used to prompt early extubation, and variability in defined extubation criteria when used in patients with COPD, early extubation plus immediate noninvasive ventilation associated with reduced mortality in analysis of 9 trials with 632 adultsrisk ratio (RR) 0.36 (95% CI 0.24-0.56)NNT 6-10 with mortality in 23% of invasive weaning groupreduced weaning failure rate in analysis of 3 trials with 351 adultsRR 0.52 (95% CI 0.36-0.74)NNT 5-11 with weaning failure in 38% of invasive weaning groupreduced VAP in analysis of 9 trials with 632 adultsRR 0.22 (95% CI 0.13-0.37)NNT 4-6 with VAP in 30% of invasive weaning groupreduced reintubation in analysis of 3 trials with 430 adultsRR 0.49 (95% CI 0.35-0.7)NNT 5-10 with reintubation in 35% of invasive weaning groupreduced tracheostomy (0% with early extubation plus noninvasive weaning vs. 10% with invasive weaning, p = 0.02, NNT 10) in 1 trial with 264 adultssignificant decrease in length of intensive care unit (ICU) stay (8 trials with 608 patients), hospital stay (6 trials with 524 patients), and total duration of ventilation (5 trials with 277 patients) in mixed populationsearly extubation plus immediate noninvasive ventilation associated with reduced VAP in analysis of 5 trials with 321 adults, results limited by significant heterogeneityRR 0.38 (95% 0.15-0.93)NNT 4-48 with VAP in 30% of invasive weaning groupreduced tracheostomy in analysis of 6 trials with 308 adults RR 0.23 (95% CI 0.09-0.57)NNT 6-11 with tracheostomy in 21% of invasive weaning groupnonsignificant decrease in length of ICU stay (5 trials with 299 patients) and total duration of ventilation (2 trials with 108 patients)no significant differences between groups in mortality, weaning failure rate, length of hospital stay, and reintubation Reference - Cochrane Database Syst Rev 2013 Dec 9;(12):CD004127, some results from same systematic review also published in BMJ 2011 Jan 13;342:c7237 full-text similar reduction in incidence of VAP with extubation to noninvasive ventilation compared to continued invasive weaning reported in Br J Anaesth 2013 Jun;110(6):896 Protocolized Weaning protocolized weaning(1, 3) has been used for discontinuation of mechanical ventilation but unclear which aspect(s) effective in reducing duration of intubation usually consists of objective criteria to judge readiness to wean guidelines to gradually reduce support criteria to judge readiness for extubation American Thoracic Society/American College of Chest Physicians (ATS/ACCP) recommendations on liberation from mechanical ventilation in critically ill adults for acutely hospitalized patients who have been mechanically ventilated for > 24 hours consider protocolized physical therapy directed toward early mobilization (ATS/ACCP Conditional recommendation, Low-quality evidence ) consider ventilator liberation protocol Reference - ATS/ACCP clinical practice guideline on liberation from mechanical ventilation in critically ill adults ( Am J Respir Crit Care Med 2017 Jan 1;195(1):115) protocolized weaning may decrease duration of mechanical ventilation compared to nonprotocolized weaning in adults in intensive care unit (ICU) (level 2 [mid-level] evidence) based on Cochrane review of trials with unclear or no blinding systematic review of 17 randomized trials comparing protocolized vs. nonprotocolized weaning for duration of mechanical ventilation in 2,434 critically ill adults protocolized weaning associated with shorter duration on mechanical ventilation in analysis of 14 trials with 2,205 adults, results limited by significant heterogeneity and did not vary by type of ICU, approach, or protocol weaning duration in analysis of 8 trials with 989 adults, results limited by significant heterogeneity and did not vary by type of ICU, approach, or protocol length of ICU stay in analysis of 9 trials with 1,378 adults no significant differences in mortality, reintubation, self-extubation, or tracheostomy Reference - Cochrane Database Syst Rev 2014 Nov 6;(11):CD006904 protocolized weaning may reduce total duration of mechanical ventilation in children (level 2 [mid-level] evidence) based on Cochrane review of trials with methodologic limitations systematic review of 3 randomized trials comparing protocolized vs. nonprotocolized weaning from mechanical ventilation in 321 patients aged 28 days to 18 years in pediatric intensive care unit (PICU) protocolized weaning defined as algorithm for removal of children from invasive mechanical ventilation all trials had unclear allocation concealment, lack of intention-to-treat analysis, or small sample size protocolized weaning significantly or nonsignificantly reduced total duration of mechanical ventilation in all trials no significant differences in hospital and PICU lengths of stay, PICU mortality, or adverse effects Reference - Cochrane Database Syst Rev 2013 Jul 31;(7):CD009082 computer-driven protocolized weaning including spontaneous breathing trials may reduce duration of mechanical ventilation (level 2 [mid-level] evidence) based on randomized trial without blinding 144 patients with mechanical ventilation randomized to computer-driven protocolized weaning including spontaneous breathing trials vs. conventional management computer-driven protocol included automatic gradual reduction in pressure support, automatic spontaneous breathing trials, and message when spontaneous breathing trial passed compliance to recommended modes of ventilation in 92% of computer-driven group and 92% of conventional management group spontaneous breathing trials performed on 51% of days in conventional management group comparing computer-driven weaning protocol vs. conventional management median weaning duration 3 days vs. 5 days (p = 0.01) median duration of mechanical ventilation 7.5 days vs. 12 days (p = 0.003) median duration of intensive care unit (ICU) stay 12 days vs. 15.5 days (p = 0.02) ventilator associated-pneumonia in 17.6% patients vs. 15.7% patients (not significant) noninvasive ventilation required by 19% vs. 37% (p = 0.02) no significant differences in other complications, including reintubation, self-extubation, or tracheostomy Reference - Am J Respir Crit Care Med 2006 Oct 15;174(8):894 Automated Weaning automated weaning refers to closed-loop circuits that automatically adjust the level of support to the intubated patient(3) automated weaning and spontaneous breathing trial system may reduce weaning time compared to nonautomated weaning strategies in critically ill adults (level 2 [mid-level] evidence) based on Cochrane review of trials with unclear or lack of blinding of outcome assessor systematic review of 10 randomized and quasi-randomized trials comparing automated weaning and spontaneous breathing trial (SBT) systems vs. nonautomated weaning strategies in 654 critically ill adults requiring mechanical ventilation automated weaning and SBT system evaluated in all trials was SmartCare weaning time defined as time from randomization to extubation SmartCare associated with decrease in weaning time (mean difference [MD] -2.68 days, 95% CI -3.99 to -1.37 days) in analysis of 7 trials with 495 adults, results limited by significant heterogeneity time to successful extubation (MD -0.99 days, 95% CI -1.89 to -0.09 days) in analysis of 7 trials with 516 adults duration of ventilation (MD -1.68 days, 95% CI -3.33 to -0.03 days) in analysis of 7 trials with 521 adults, results limited by significant heterogeneity intensive care unit (ICU) length of stay (MD -5.7 days, 95% CI -10.54 to -0.85 days) in analysis of 6 trials with 499 adults, results limited by significant heterogeneity ventilation requirement for > 21 days in analysis of 3 trials with 258 adults risk ratio 0.39 (95% CI 0.18-0.86) NNT 8-48 with ventilation requirement for > 21 days in 15% of nonautomated weaning strategy group no significant differences in mortality in analysis of 6 trials with 470 adults time to first successful SBT in analysis of 2 trials with 175 adults, results limited by significant heterogeneity adverse events including reintubation, self-extubation, tracheostomy, and pneumothorax Reference - Cochrane Database Syst Rev 2014 Sep 9;(9):CD008638 automated weaning may reduce total ventilation duration compared to nonautomated weaning in critically ill adults and children (level 2 [mid-level] evidence) based on Cochrane review of trials without blinding systematic review of 21 randomized trials comparing automated weaning vs. nonautomated weaning in 1,676 critically ill adults or children 19 trials evaluated adults, 2 trials evaluated children automated weaning associated with shorter total weaning duration in analysis of 16 trials with 1,246 patients, results suggest greater benefit with SmartCare/pressure support (PS) system compared to Adaptive Support Ventilation and in mixed or medical intensive care populations compared to surgical patients shorter ventilation duration in analysis of 14 trials with 1,246 patients decreased risk of prolonged mechanical ventilation (> 21 days) in analysis of 7 trials with 753 patients risk ratio 0.51 (95% CI 0.27-0.95) NNT 18-250 with prolonged mechanical ventilation in 8% of nonautomated weaning group decreased risk of tracheostomy in analysis of 9 trials with 962 patients risk ratio 0.67 (95% CI 0.5-0.9) NNT 12-59 with tracheostomy in 17% of nonautomated weaning group no significant differences in mortality, hospital length of stay, reintubation, and self-extubation Reference - Cochrane Database Syst Rev 2014 Jun 10;(6):CD009235 automated weaning and SBT systems have limited evidence for use in postoperative period based on Cochrane review systematic review of randomized and quasi-randomized trials comparing automated weaning and SBT systems vs. nonautomated mechanical ventilation discontinuation strategies in adults in postoperative setting 1 trial comparing SmartCare vs. standardized written protocol in 300 patients met inclusion criteria no significant differences in time to first successful SBT, successful extubation, total duration of mechanical ventilation, ICU and hospital length of stay, tracheostomy, reintubation, and use of noninvasive ventilation following extubation mean time to first spontaneous breathing trial 0.04 days vs. 0.38 days (p = 0.01) Reference - Cochrane Database Syst Rev 2014 Feb 13;(2):CD008639 Sedation Optimization Strategies excessive sedation reported to reduce success of spontaneous breathing trials (SBTs) and increase duration of mechanical ventilation(3) American Thoracic Society/American College of Chest Physicians (ATS/ACCP) recommendations on liberation from mechanical ventilation in critically ill adults for acutely hospitalized patients ventilated for more than 24 hours, consider protocols attempting to minimize sedation (ATS/ACCP Conditional recommendation, Low-quality evidence ) Reference - ATS/ACCP clinical practice guideline on liberation from mechanical ventilation in critically ill adults ( Am J Respir Crit Care Med 2017 Jan 1;195(1):115 or Chest 2017 Jan;151(1):160) daily sedation interruption may not reduce mortality, length of hospitalization, or duration of mechanical ventilation in critically ill adults (level 2 [mid-level] evidence) based on Cochrane review with wide confidence intervals and limited by heterogeneity systematic review of 9 randomized trials comparing daily sedation interruption vs. no daily sedation interruption in 1,282 critically ill adults requiring mechanical ventilation no significant differences in mortality (risk ratio [RR] 0.88, 95% CI 0.75-1.05) in analysis of 9 trials with 1,278 adults, but wide confidence intervals cannot rule out clinically relevant differences length of intensive care unit (ICU) stay in analysis of 9 trials with 1,282 adults, results limited by significant heterogeneity length of hospital stay in analysis of 8 trials with 1,232 adults duration of mechanical ventilation in analysis of 9 trials with 1,282 adults, results limited by significant heterogeneity daily sedation interruption associated with decreased tracheostomy in analysis of 6 trials with 1,061 adults RR 0.73 (95% CI 0.57-0.92) NNT 10-53 with tracheostomy in 24% of no daily sedation interruption group Reference - Cochrane Database Syst Rev 2014 Jul 9;(7):CD009176 daily interruption of sedatives may reduce duration of mechanical ventilation but not reintubation or in-hospital mortality in critically ill patients (level 2 [mid-level] evidence) based on randomized trial with unclear blinding 128 adults in medical ICU (median age 59 years) on continuous sedative infusion were randomized to daily interruption of sedatives vs. usual sedation care comparing daily interruption vs. usual care median duration of mechanical ventilation 4.9 days vs. 7.3 day (p = 0.004) median duration in ICU 6.4 days vs. 9.9 days (p = 0.02) no significant differences in reintubation or in-hospital mortality Reference - N Engl J Med 2000 May 18;342(20):1471 full-text addition of spontaneous awakening trial to SBT may be associated with improved short- and long-term outcomes (level 2 [mid-level] evidence) based on randomized trial without blinding 335 adults (mean age 62 years) intubated for ≥ 12 hours were randomized to 1 of 2 weaning techniques daily spontaneous awakening trial (SAT) safety screen and SAT if successful, followed by SBT safety screen and trial if successful sedation per usual care plus daily SBT safety screen and SBT if successful 150 patients (90%) passed SAT safety screen and had SBT comparing SAT-SBT vs. daily SBT only mean ventilator-free days 14.7 vs. 11.6 (p = 0.02) median time to discharge from ICU 9.1 days vs. 12.9 days (p = 0.01) hospital 14.9 days vs. 19.2 days (p = 0.04) reintubation in 13.8% vs. 12.5% (not significant) SAT-SBT associated with reduced mortality within 1 year (hazard ratio 0.68, 95% CI 0.5-0.92) Reference - Lancet 2008 Jan 12;371(9607):126 no sedation in critically ill patients having mechanical ventilation associated with more ventilation-free days (level 2 [mid-level] evidence) based on randomized trial without intention-to-treat analysis 140 critically ill adults having mechanical ventilation and expected to need ventilation for > 24 hours were randomized to no sedation vs. sedation (propofol 20 mg/mL for 48 hours then midazolam 1 mg/mL thereafter) with daily interruption until awake all patients received bolus doses of morphine 2.5 or 5 mg patients dying or extubated within 48 hours not included in analysis (21% with no sedation, 17% with sedation) comparing no sedation vs. interrupted sedation mean time without ventilation 13.8 days vs. 58 days (p = 0.019) ICU mortality 22% vs. 38% (p = 0.06, NNT 7) mean ICU stay 13.1 days vs. 22.8 days (p = 0.0316) mean duration of hospital stay 34 days vs. 58 days (p = 0.004) agitated delirium in 20% vs. 7% (p = 0.04, NNH 7) no significant differences in accidental extubations, need for computed tomography (CT) or magnetic resonance imaging (MRI) brain scans, or ventilator-associated pneumonia Reference - Lancet 2010 Feb 6;375(9713):475, commentary can be found in Lancet 2010 Apr 3;375(9721):1159; author reply 1160 Decision to Extubate consider extubation if patient tolerates 30- to 120-minute spontaneous breathing trial (ACCP/AARC/ACCCM Grade A)(2) decision to extubate should be based on airway patency and patient's ability to protect airway due to risk of postextubation upper airway obstruction (ACCP/AARC/ACCCM Grade C)(2) airway anatomy should also be assessed for cough strength, quantity of airway secretions, presence of cuff leak, and mentation(1, 2) if factors are adequate, consider extubation if factors are inadequate, resume ventilatory support and continue with daily assessments of readiness American Thoracic Society/American College of Chest Physicians (ATS/ACCP) recommendations on liberation from mechanical ventilation in critically ill adults for mechanically ventilated patients who meet extubation criteria and at high risk for post-extubation stridor, cuff leak test suggested (ATS/ACCP Conditional recommendation, Very low-quality evidence ) for adults with failed cuff leak test but otherwise ready for extubation, consider giving systemic steroids ≥ 4 hours before extubation; repeat cuff leak test not required (ATS/ACCP Conditional recommendation, Moderate-quality evidence ) Reference - ATS/ACCP clinical practice guideline on liberation from mechanical ventilation in critically ill adults (Am J Respir Crit Care Med 2017 Jan 1;195(1):115 or Chest 2017 Jan;151(1):160) factors associated with increased risk of postextubation upper airway obstruction include(2, 3) longer duration of mechanical ventilation female gender trauma repeated or traumatic intubation lack of cuff leak (< 110 mL) premature extubation Extubation Failure and Reintubation about 5%-15% reintubation reported within 48 hours of extubation(1, 2) extubation failure reported in about 5%-8% of patients postoperatively and in up to 23% of critically ill patients(1, 2) reintubation associated with(1) increased mortality prolonged hospital stay decreased likelihood of returning home increased risk of tracheostomy risk factors for extubation failure include(2, 3) failure of ≥ 2 consecutive spontaneous breathing trials chronic heart failure or > 1 comorbid condition other than heart failure partial pressure of arterial carbon dioxide (PaCO2) > 45 mm Hg after extubation weak cough postextubation stridor ≥ 65 years old Acute Physiology and Chronic Health Evaluation (APACHE) II score > 12 on day of extubation intubation in medical, pediatric, or multispecialty intensive care unit pneumonia as indication for mechanical ventilation heart rate variability poor sleep quality muscle weakness diaphragmatic dysfunction timing of extubationovernight extubation may not increase risk of in-hospital death or reintubation and might shorten duration of hospital stay compared to daytime extubation in analysis excluding palliative extubations (level 2 [mid-level] evidence)based on retrospective cohort study2,241 adults in intensive care having mechanical ventilation with ≥ 1 extubation at 1 hospital were stratified by time of first extubation attempt9.1% had overnight extubation (defined as occurring from 7 PM to 6:59 AM)hospital had multidisciplinary assessment for extubation, rigorously protocolized extubation algorithms, and expert airway managers available at all times of day for assessment of high-risk extubationspatients excluded for tracheostomy without trial of extubation and for palliative extubationsmean age 45 years in overnight extubation group and 51 years in daytime extubation group (p < 0.001)daytime extubation group had significantly higher rate of comorbiditiesanalyses were adjusted for age, sex, body mass index, admission type, comorbidities, and additional confounders including routine postoperative and unplanned extubationscomparing overnight extubation vs. daytime extubationin-hospital death in 3.4% vs. 5.9% (adjusted odds ratio [OR] 0.72, 95% CI 0.28-1.84)reintubation in 6.9% vs. 12.4% (adjusted OR 0.78, 95% CI 0.43-1.41)median duration of hospital stay 6 days vs. 13 days (p < 0.001)median duration of ICU stay 2 days vs. 4 days (p < 0.001)median duration of mechanical ventilation 1 day vs. 2 days (p < 0.001)consistent results in analysis defining overnight extubation as occurring from 5 PM to 6:59 AMReference - Anesth Analg 2019 May;128(5):918overnight extubation may be associated with increased intensive care unit (ICU) or in-hospital mortality compared to daytime extubation in patients having mechanical ventilation (level 2 [mid-level] evidence) based on retrospective cohort study 97,844 adults (mean age 58 years, 59% female) having mechanical ventilation in United States intensive care units (ICUs) registered in Project IMPACT database were assessed exclusion criteria included death, tracheostomy, or limitations on resuscitations or therapy before first extubation 20.1% had overnight extubation defined as extubation occurring between 7 PM and 6:59 AM propensity score for likelihood of overnight extubation was calculated for each patient using individual patient and ICU characteristics patients having overnight extubation were matched to patients having daytime extubation in propensity score-matched cohorts including 4,518 patient pairs extubated after mechanical ventilation for < 12 hours 5,761 patient pairs extubated after mechanical ventilation for ≥ 12 hours comparing overnight vs. daytime extubation in propensity score-matched analysis of patients with mechanical ventilation for < 12 hours reintubation in 5.9% vs. 5.6% (not significant) ICU mortality 5.6% vs. 4.6% (p = 0.03) in-hospital mortality 8.3% vs. 7% (p = 0.01) median duration of ICU stay 1.1 days vs. 1.4 days (p < 0.001) comparing overnight vs. daytime extubation in propensity score-matched analysis of patients with mechanical ventilation for ≥ 12 hours reintubation in 14.6% vs. 12.4% (p < 0.001) ICU mortality 11.2% vs. 6.1% (p < 0.001) in-hospital mortality 16% vs. 11.1% (p < 0.001) median duration of ICU stay 4.9 days vs. 4.9 days (not significant) Reference - JAMA Intern Med 2016 Nov 1;176(11):1651 full-text, editorial can be found in JAMA Intern Med 2016 Nov 1;176(11):1660 extubation failure associated with increased mortality compared to successful extubation in patients weaned from mechanical ventilation based on cohort study 287 intubated patients who had an extubation trial included 40 patients (15%) had extubation failure (need for reintubation within 72 hours) among 247 patients who had successful initial extubation, 15 had late reintubation (within 7 days) mortality in hospital 43% of patients with failed extubation 53% of patients with successful initial extubation but with late reintubation 9% of patients with successful initial extubation and no late reintubation factors associated with increased mortality failed extubation (odds ratio [OR] 7.3, 95% CI 4.6-11.7) ≥ 1 comorbidity present (OR 5.2, 95% CI 3.4-8) acute renal failure with need for dialysis (OR 3.8, 95% CI 2-7) higher APACHE score at start of weaning (OR 1.14, 95% CI 1.1-1.9 for each unit change in score) Reference - Chest 1997 Jul;112(1):186 pneumonia as indication for mechanical ventilation and positive fluid balance each associated with increased risk of reintubation following successful extubation in patients on mechanical ventilation based on retrospective cohort study 900 consecutive patients who were on mechanical ventilation and had successful extubation included 121 patients (13.4%) were reintubated factors associated with increased risk of reintubation in multivariate analysis pneumonia as reason for initiating mechanical ventilation (odds ratio [OR] 1.77, 95% CI 1.1-2.84) positive fluid balance within 24 hours prior to extubation (OR 1.7, 95% CI 1.15-2.53) increasing rapid shallow breathing index (RSBI) (OR 1.01, 95% CI 1.003-1.015 per unit increase) combination of RSBI > 57 breaths/minute/L plus positive fluid balance had highest association with risk of reintubation (OR 3, 95% CI 1.8-4.8) Reference - Chest 2006 Dec;130(6):1664 myasthenic crisis, atelectasis, and Glasgow Coma Score 7-9T each associated with increased risk of extubation failure in neurocritical patients based on systematic review of observational studies systematic review of 9 cohort studies evaluating risk factors for extubation failure in 928 neurocritical patients on mechanical ventilation 8.2%-43.5% incidence of extubation failure across studies risk factors for extubation failure myasthenic crisis (odds ratio [OR] 9.46, 95% CI 2.78-32.18) in analysis of 2 trials with 72 patients atelectasis (OR 5.96, 95% CI 1.69-21.03) in analysis of 3 trials with 105 patients Glasgow Coma Scale (GCS) 7-9T (OR 4.96, 95% CI 1.61-15.26 compared to GCS 10-11T) in analysis of 3 trials with 693 patients pneumonia without myasthenic crisis (OR 4.23, 95% CI 1.18-15.18) in analysis of 5 trials with 521 patients pneumonia with myasthenic crisis (OR 4.19, 95% CI 1.57-11.14) in analysis of 7 trials with 593 patients mechanical ventilation > 24 hours (OR 2.63, 95% CI 1.34-5.15) in analysis of 2 trials with 409 patients inability to follow commands (OR 2.06, 95% CI 1.14-3.73) in analysis of 2 trials with 332 patients Reference - PLoS One 2014;9(12):e112198 full-text inadequate cough, inability to complete simple tasks, and excessive secretions each associated with increased risk of failed extubation in intubated patients based on prospective cohort study 88 intubated patients with successful spontaneous breathing trial evaluated for cough peak flow (CPF), endotracheal secretions, and ability to complete 4 simple tasks prior to extubation simple tasks include opening eyes following observer with eyes grasping a hand sticking out tongue 14 patients (16%) failed first extubation trial increased risk of risk of failed extubation trial in patients with CPF < 60 L/minute (risk ratio [RR] 4.8, 95% CI 1.4-16.2) inability to complete tasks (RR 4.3, 95% CI 1.9-10.4) secretions > 2.5 mL/hour (RR 3, 95% CI 1-8.8) failure rate was 100% for patients who met all 3 risk factors and 3% for patients who met no risk factors Reference - Intensive Care Med 2004 Jul;30(7):1334 prediction of extubation success diaphragmatic excursion-time index may have moderate sensitivity and specificity for predicting successful extubation in patients having mechanical ventilation (level 2 [mid-level] evidence) based on prognostic cohort study without validation 73 adults having mechanical ventilation had diaphragm excursion measurements assessed by ultrasound at 3 time points (all performed by single ultrasonographer) during assist-control mode of mechanical ventilation (AC) following 30 minutes of spontaneous breathing trial on pressure support ventilation (SBT) after extubation (4-24 hours following extubation) excursion-time index (diaphragm excursion measurement [cm] × inspiratory time [seconds]) was calculated for each patient at each time point extubation failure defined as requiring reintubation or noninvasive ventilation within 48 hours successful extubation in 73% mean excursion-time indices, comparing extubation success vs. failure 1.57 vs. 1.8, measured at AC (not significant) 2.42 vs. 1.64, measured at SBT (p < 0.03) 2.36 vs. 1.38, measured after extubation (p < 0.01) mean change in excursion-time index between AC and SBT was +59% in patients with extubation success vs. -3.9% in patients with extubation failure vs. (p < 0.01) for prediction of successful extubation, decrease in excursion-time index < 3.8% between AC and SBT had sensitivity 79.2% specificity 75% positive predictive value 89.4% negative predictive value 57.6% Reference - Chest 2018 May;153(5):1213 Postextubation Stridor stridor occurs secondary to narrowing of upper airways(3) steroids or epinephrine can treat postextubation stridor(3) American Thoracic Society/American College of Chest Physicians (ATS/ACCP) recommendations on liberation from mechanical ventilation in critically ill adults consider cuff leak test in mechanically ventilated patients who meet extubation criteria and are at high risk for postextubation stridor (ATS/ACCP Conditional recommendation, Very low-quality evidence ) consider administering systemic steroids ≥ 4 hours prior to extubation for adults who fail cuff leak test but are otherwise ready for extubation; repeat cuff leak test not required after administration of steroids (ATS/ACCP Conditional recommendation, Moderate-quality evidence ) Reference - Chest 2017 Jan;151(1):160 , commentary can be found in Chest 2017 May;151(5):1179, author reply can be found in Chest 2017 May;151(5):1180 cuff leak test(3) performed using the average of 3 values of 6 consecutive breaths during mechanical ventilation taken 24 hours before extubation value < 110 mL is common threshold suggesting high risk for stridor after extubation steroids and/or epinephrine may be given to patients with low cuff leak volumes 24 hours prior to extubation systemic corticosteroids prior to extubation may reduce risk of postextubation airway events and reintubation in mechanically ventilated patients who fail cuff leak test (level 2 [mid-level] evidence) based on systematic review limited by clinical heterogeneity systematic review of 11 trials comparing prophylactic systemic corticosteroids to placebo or no treatment in 2,472 mechanically ventilated patients 6 trials selected patients at high risk of airway obstruction estimated by cuff leak test, 5 trials used unselected patients trials varied in corticosteroids used (dexamethasone in 5 trials, methylprednisolone in 4 trials, and hydrocortisone in 2 trials) total corticosteroid dose used (100-1,000 mg equivalent dose of hydrocortisone) cuff leak volume cutoff values (< 110 mL in 3 trials, < 24% of tidal volume in 2 trials, and < 25% of tidal volume in 1 trial) corticosteroids associated with (in analysis of 6 trials with 659 patients at high risk of airway obstruction based on cuff leak test) reduced postextubation airway events (defined as airway obstruction, stridor, or laryngeal edema) risk ratio (RR) 0.34 (95% CI 0.24-0.48) NNT 4-6 with postextubation events in 34% of control group reduced reintubation RR 0.35 (95% CI 0.2-0.64) NNT 10-22 with reintubation in 13% of control group corticosteroids not associated with reduced risk of postextubation stridor or reintubation in analysis of 5 trials with 1,813 unselected patients, results limited by significant heterogeneity in regression analysis, increased duration of mechanical ventilation associated with reduced effect of corticosteroids on reintubation rate (p = 0.04) and nonsignificantly reduced effect of corticosteroids on rate of postextubation airway events (p = 0.07) Reference - Chest 2017 May;151(5):1002 lower cuff leak volume associated with postextubation stridor in intubated patients based on prospective cohort study 100 consecutive intubated patients had cuff leak volume measured within 24 hours of extubation 6 patients (6%) had postextubation stridor cuff leak volume 180 mL in patients with postextubation stridor vs. 360 mL in patients without (p = 0.012) Reference - Chest 1996 Oct;110(4):1035 Prolonged Mechanical Ventilation prolonged mechanical ventilation defined as up to 3 unsuccessful spontaneous breathing trials (SBTs) or ≥ 7 days of mechanical ventilation following first unsuccessful SBT(1) weaning strategies for patients requiring prolonged mechanical ventilation should be slow-paced and include gradual lengthening of SBTs (ACCP/AARC/ACCCM Grade C)(2) patients requiring prolonged mechanical ventilation should have 3 months of failed weaning attempts before consideration of permanent ventilation unless patient has clearly irreversible disease, such as high spinal cord injury or advanced amyotrophic lateral sclerosis (ACCP/AARC/ACCCM Grade B)(2) 59% 1-year mortality in critically ill patients having prolonged mechanical ventilation based on systematic review of observational studies systematic review of 124 observational studies assessing long-term survival of 318,621 critically ill patients having prolonged mechanical ventilation, including mechanical ventilation ≥ 14 days mechanical ventilation with admission to specialized ventilator weaning unit in acute care hospital or postacute care hospital mechanical ventilation ≥ 96 hours plus tracheostomy procedure 43 studies were high-quality observational studies according to Newcastle-Ottawa Scale 59% 1-year mortality in analysis of 39 studies with 139,560 patients 57% of patients successfully liberated from mechanical ventilation in analysis of 80 studies with 13,170 patients Reference - Lancet Respir Med 2015 Jul;3(7):544 long-term mortality associated with increasing age, vasopressor use, thrombocytopenia, acute kidney disease with or without dialysis, failed ventilation liberation, and preexisting kidney disease in patients having prolonged mechanical ventilation based on systematic review of observational studies systematic review of 14 observational studies evaluating association between patient-level prognostic factors and risk of long-term mortality in patients receiving prolonged mechanical ventilation long-term mortality defined as ≥ 6 months from meeting criteria for receiving prolonged mechanical ventilation prolonged mechanical ventilation included mechanical ventilation for ≥ 14 days, mechanical ventilation with admission to ventilator weaning unit, or mechanical ventilation for ≥ 4 days associated with tracheostomy placement prognostic factors assigned relative strength of evidence (strong, moderate, or weak) based on number of articles in which factor showed independent association with presence of outcome and methodologic strength of article factors that showed strong strength of evidence for association (≥ 2 high-quality studies showing positive association and no studies showing negative association) included increasing age vasopressor requirement thrombocytopenia acute kidney injury or dialysis-dependent renal failure inability to liberate from ventilator preexisting kidney disease Reference - Crit Care Med 2017 Jan;45(1):69
  • 概述和建議 相關摘要 概觀 背景 專業組織的建議 減少機械通氣的持續時間 機械通氣斷奶算法 評估自發呼吸試驗(SBT)的準備情況 自發呼吸試驗(SBTs)的方法 輔助治療 協議化斷奶 自動斷奶 鎮靜優化策略 拔管的決定
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  • ScienceDirect Visit ScienceDirect to see if you have access via your institution. Article Tools PDF (1 MB) Download Images(.ppt) About Images & Usage Email Article Add to My Reading List Export Citation Create Citation Alert Cited by in Scopus (4) Request Permissions Order Reprints (100 minimum order)   Article Related Video if(typeof addthis == "undefined") { $.getScript("//s7.addthis.com/js/250/addthis_widget.js#pubid=xa-4faab26f2cff13a7"); } Linked Articles Is Topographic Classification Effective for Lymph Node Metastasis in Patients Affected by Non-Small Cell Lung Cancer?Marco Chiappetta, Maria Teresa Congedo, Dania Nachira, Elisa Meacci, Stefano MargaritoraDOI: https://doi.org/10.1016/j.chest.2017.06.054CHEST, Vol. 152, Issue 6ResponseAhmed H. El-Sherief, Charles T. Lau, Nancy A. Obuchowski, Atul C. Mehta, Thomas W. Rice, Eugene H. BlackstoneDOI: https://doi.org/10.1016/j.chest.2017.10.021CHEST, Vol. 152, Issue 6 Related Articles Misclassification of Lymph Nodes in Lung Cancer Staging: Can We Improve?DOI: https://doi.org/10.1016/j.chest.2016.10.050Chest, Vol. 151, Issue 4Sonographic Features of Lymph Nodes During Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Comparison With MediastinoscopyDOI: https://doi.org/10.1016/j.chest.2017.08.690CHEST, Vol. 152, Issue 4Lymph Nodes in Lung Cancer: Location, Location, and Location?DOI: https://doi.org/10.1378/chest.14-2767CHEST, Vol. 147, Issue 5 View All Article Related Audio if(typeof addthis == "undefined") { $.getScript("//s7.addthis.com/js/250/addthis_widget.js#pubid=xa-4faab26f2cff13a7"); } < Previous Article Next Article > April 2017Volume 151, Issue 4, Pages 776–785 Copyright © 2018 Elsevier Inc. All rights reserved. | Privacy Policy | Terms & Conditions | Use of Cookies | About Us | Help & Contact | Accessibility The content on this site is intended for health professionals. Advertisements on this site do not constitute a guarantee or endorsement by the journal, Association, or publisher of the quality or value of such product or of the claims made for it by its manufacturer. $.ajax({ url: "https://journal.chestnet.org/ssoSessionCheck", type: "GET", dataType: "jsonp", success: function (data) { if(data.RefreshSession) { location.reload(); } }, error : function (){ console.warn("can't validate CSAS session."); } }); setTimeout(clearSsoUrlsFun,10000); var iFramesList = document.getElementById("sso-urls-div").getElementsByTagName("iframe"); var renderedIFramesCount = 0; var numberOfIFrames = iFramesList.length; var skipRefresh = false; for (var i = 0; i < iFramesList.length; i++) { var iFrame = iFramesList[i]; iFrame.addEventListener("load", function() { renderedIFramesCount = renderedIFramesCount + 1; if (renderedIFramesCount >= numberOfIFrames) { clearSsoUrlsFun(); } }); } function clearSsoUrlsFun() { if (skipRefresh == false && numberOfIFrames > 0) { skipRefresh = true; $.ajax({ url: "https://journal.chestnet.org/action/clearSsoUrls", type: "GET", dataType: "jsonp", error : errorCallingAjx }); } } function errorCallingAjx(){ console.log("can't delete sso urls .") } a#fixed_hdr_link,a#fixed_hdr_link:hover{text-decoration:none}#jbs-fixed-hdr{background-color:#f8f8f8;border-bottom:.125rem solid #ebebeb;left:0;padding:.75em 0 1.25em;position:fixed;top:0;z-index:3;width:100%;height:30px;overflow:hidden;display:none}#jbs-fixed-hdr #jbs-article-toolbar-title{margin-top:10px;max-width:75%!important;display:inline-block;white-space:nowrap;overflow:hidden;text-overflow:ellipsis;float:left;font-size:13px;}#jbs-fixed-hdr #fixed_hdr-group-right{float:left;width:130px;white-space:nowrap;margin-right:3em;border:1px solid gray;border-radius:5px;padding:4px 0 0 6px;margin-top:-5px;background-color:#E8E8E8;}#jbs-fixed-hdr #fixed_hdr-group-right:hover{background-color:#DCDCDC}#fixedHdrContainer{width:960px;text-align:left}#fixed_hdr_pdf_link{display:inline-block;position:absolute;top:20px;margin-left:8px;cursor:pointer;font-size:12px;}a#fixed_hdr_link{white-space:nowrap;font-weight:700} Download PDF if ($(".denialInfo").length) { } else { function initStickyHdr() { document.getElementById("jbs-article-toolbar-title").innerHTML = document.title; $(window).scroll(function (){ if ($(this).scrollTop() > 300){ $("#jbs-fixed-hdr").css("display","block"); } else { $("#jbs-fixed-hdr").css("display","none"); } }); } setTimeout(initStickyHdr,2000); } function clickPDF() { document.querySelector(".articleToolsContainer ul li.toolPdf a.pdfLink").click(); } Can High-flow Nasal Cannula Reduce the Rate of Endotracheal Intubation in Adult Patients With Acute Respiratory Failure Compared With Conventional Oxygen Therapy and Noninvasive Positive Pressure Ventilation? Ni, Yue-Nan et al.
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2 annotations
 tourist destinations 763
  • 臨床閱讀常用詞彙表 A Absolute risk increase (ARI) 絕對風險增加比 絕對風險在實驗組與對照組間不良結果(或擬觀察之結果)差異之絕對值,算法為實驗組事件發生率與對照組事件發生率差值之絕對值,當觀察一個臨床處置(如裝支架)所致之死亡率或發生率的降低時,即是著重於絕對風險差;反之,如係觀察如止痛劑對疼痛緩解之成效,則是著重於絕對風險增加比 Absolute Risk Reduction (ARR) 絕對風險差 Absolute risk 絕對風險 Algorithm 決策演析圖 以步驟流程方式呈現針對某一臨床問題/處置的治療或操作指引 Allocation concealment 分組隱匿 分組隱匿是指在臨床試驗中,為不管是臨床照護相關人員(如醫師、護理人員或其他相關人員)或病患,都不知道下一個收案的病患會被分到對照組或控制組的那一組。分組隱匿為確保隨機對照試驗的正確執行之重要原則之一。 Appraisal of Guidelines for Research & Evaluation (AGREE) 臨床指引品質評估(機構) AGREE為目前國際上主要的臨床指引品質評估機構之一,1998年歐盟支持的一個生物醫學及健康研究計畫下開始進行指引品質評估的研議,發展出AGREE指引品質評估工具,其後於2004年7月於英國成立The AGREE Research Trust (ART)以提升AGREE指引評估工具在國際間之推廣運用。 B Blinding 盲法 盲法,係研究過程中,使部分或全部的研究相關人員包括醫療照護人員、病人、結果分析人員等,均不知道那一個受試者或病人被分配至那一組接受試驗或治療的研究設計方法。 C Campbell Collaboration (C2) 坎貝爾合作組織 坎貝爾合作組織,為實證社會科學之重要國際性組織,任務功能類似實證醫學界的考科藍合作組織(Cochrane Collaboration),主要以推展針對社會科學及教育等專業領域的實證研究及應用推廣。 Canadian Medical Association (CMA) 加拿大醫學會 加拿大醫學會,其下所建置的Infobase資訊平台收集加拿大國內完整的各科臨床指引。 Case-control study 病例對照研究 病例對照研究係針對研究者有興趣的特定疾病或試驗結果,比較族群中有該疾病或結果(試驗組)與無該疾病或結果(對照組)的二群人,找出疾病或結果與其先前暴露的危險因子之關連性。對少數或罕見且既往暴露可被準確量測的疾病,病例對照研究有助於相關性的確定,且一般上多都採回溯性研究方式進行,但也不全然只能採回溯性研究方式進行。(資料來源Green S, Higgins J, editors. Glossary. Cochrane Handbook for Systematic Reviews of Interventions 4.2.5 [updated May 2005]. http://www.cochrane.dk/cochrane/handbook/handbook.htm [(accessed 30/08/2006)]. Clinical pathways 臨床路徑 臨床路徑,係將特定之臨床治療的時間、流程、內容等建立標準模式,讓符合該特定臨床表徵的病患在住院接受治療期間均依該標準模式進行其治療計畫,標準化的模式可作為醫療人員照顧病患之參考與指標,且不易因人員的素質差異,影響到醫療品質的穩定。 Clinical practice guidelines (CPG) 臨床診療指引 臨床診療指引,定義為“以系統性方法發展的醫療建議或陳述,用以協助醫師與病人決定在特定的臨床情況下適當之醫療照護”。美國IOM對好的臨床指引之規範包括指引內容清楚、有效、可信、具臨床應用性及彈性、提供證據強度、結果可預期、多專業參與指引發展、定期檢討及適當的文件形式等。(Institute of Medicine (1990). Clinical Practice Guidelines: Directions for a New Program, M.J. Field and K.N Lohr (eds.) Washington, DC: National Academy Press) Cochrane Collaboration 考科藍合作組織 考科藍合作組織,為實證醫學重要之國際性組織,主要成立目的在推展系統性文獻回顧研究之進行,在合作組織之下,目前全球共有13個考科藍中心(Cochrane Center)及15個子機構,肩負起實證研究的重要任務;針對各個不同領域另有共有52個文獻回顧研究團隊(Review Groups)(2008.12更新) Cochrane Controlled Trials Register (CCTR) 臨床試驗註冊資料庫 詳參Cochrane Library Cochrane Library 考科藍圖書館 考科藍圖書館,收錄考科藍協作所有研究成果、臨床試驗註冊、系統文獻回顧資料庫等資料,包含下列子資料庫: 1. Cochrane Database of Systematic Reviews, CDSR (Cochrane Reviews):CDSR收錄所有由Cochrane Review Groups所完成或進行中(protocol)的系統性文獻回顧研究。 2. Database of Abstracts of Reviews of Effects, DARE (Other Reviews):DARE收錄所有非由Cochrane所review的系統性文獻回顧研究之”摘要”,並提供文獻品質之評核,DARE主要由設於英國約克大學、隸屬英國NHS的Centre for Reviews and Dissemination (CRD)負責資料庫定期更新。 3. Cochrane Central Register of Controlled Trials, CENTRAL (Clinical Trials):CENTRAL臨床試驗註冊資料庫收錄詳細的臨床試驗主題、文獻書目、摘要,不含全文,資料來源包含發表於MEDLINE、EMBASE及其他期刊等資料庫,以及未發表的參考文獻來源如僅於研討會發表之文獻報告,約3/5的資料由MEDLINE取得,其他則由包括各Cochrane Review Groups依其主要興趣領域所收集的臨床試驗文獻,整個收到的資料再由US Cochrane Center作統整再納入Cochrane Library。 4. Cochrane Database of Methodology Reviews (Methods Reviews):收錄針對研究方法的相關文獻研究,目前一併收錄在CDSR資料庫裏。 5. The Cochrane Methodology Register (Methods Studies):CMR以已發表的書目格式收錄與執行臨床對照試驗方法有關的報告,其中又以系統性回顧文獻研究方法學相關的文章為主,包括期刊、參考書、研討會等由MEDLINE蒐尋或以人工蒐尋所得之文獻,僅臚列文章標題、文章發行書目、摘要(部份),沒有收錄全文。本資料庫由UK Cochrane Center負責維護。 6. Health Technology Assessment Database (Technology Assessments):醫療科技評估資料庫,文獻主要來自英國NHS的Centre for Reviews and Dissemination (CRD)所進行的研究。 7. NHS Economic Evaluation Database (Economic Evaluations):NHS EED經濟效益評估資料庫,收錄超過5000篇以上與成本效益評估分析有關係統性文獻回顧研究摘要。文獻主要來自英國NHS的Centre for Reviews and Dissemination (CRD)所進行的研究。 http://www3.interscience.wiley.com/cgi-bin/mrwhome/106568753/ProductDescriptions.html)(資料來源: The Cochrane Library /About Cochrane/Product Descriptions) Cohort study 世代研究 世代研究,是一種觀察性研究方法(observational study),一群界定清楚的人 (the cohort) 被追蹤一段時間。檢驗結果( outcome) 在不同次群組之間是否有差異,例如有(或沒有)暴露在某種介入之次群組,觀察其結果發生率。世代研究大多是前瞻性的,但也有少數是回溯性的(必須相關記錄非常清楚)。(資料來源:彰基醫圖電子報第3期) Confidence Interval (CI) 信賴區間 信賴區間,用來表示估計值的準確度,或可能蓋括母群體未知參數在內的隨機區間,一般常用95%CI表示真實數值有95%機率會落在該估計區間。 Conflict of interest (or competing interests) 利益衝突 利益衝突定義為”在某一些情形下,針對某一議題(如病人福祉或研究的效度等)原本的專業判斷可能被其他因素(如錢財收益)不正當地影響”。(資料來源University of York. NHS Centre for Reviews and Dissemination. Undertaking systematic reviews of research on effectiveness: CRD guidelines for those carrying out or commissioning reviews. 1996. (CRD Report 4)) Consensus development conference 共識發展會議 共識發展會議,由美國國家衛生院所發展用以輔助作複雜醫療衛生議題的決策,後來亦成為共識法指引發展方式之一種,共識發展會議係由各相關專家、團體、代表等以投票、排序或其他達成共識的互動方法(通常會有公開討論式的論壇),針對臨床介入或研究發現進行評估,再將這些多元團體的決議整合出最終的指引建議。(資料參考:NHS R&D HTA programme Health Technology Assessment 2(3), 1998) Cost-Benefit Analysis (CBA) 成本利益分析 成本利益分析,指在經濟分析中,將臨床治療或干預的效益,轉換為金錢並進一步比較取可獲得之利益最高者,一般而言,預防性的干預較可能作到CBA分析。 Cost-Effectiveness Analysis (CEA) 成本效果分析 成本效果分析,指在經濟分析中,比較各不同的治療選擇間,所多花費的成本是否值回臨床上的效果。 Cost-minimization Analysis (CMA) 最小成本分析 最小成本分析,在經濟分析中,當療效沒有差別時,由不同的治療方法中選擇成本最低。 Cost-Utility Analysis (CUA) 成本效用分析 成本效用分析,可視為成本效益分析之一,在效益的比較進一步比較其臨床效果及生活品質方面的結果,通常以品質調整生命年數Quality-Adjusted Life Years (QALY)作其分析比較基準。 Critical Appraisal Skills Program (CASP) 由英國NHS的公共衛生資源部門所發展的文獻評讀工具,其中critical appraisal tools針對各種不同研究設計提供不同的評讀表單資源 Critical appraisal 嚴格的文獻評讀
1 annotations
  • Rationale: The role of pre- and post-lung transplant pulmonary rehabilitation is to maintain and improve exercise capacity, lung mechanics, peripherial- and respiratory muscle function. Aims: Follow-up the changes of functional and quality of life markers in pre- and post-transplant pulmonary rehabilitation. Materials and Methods: 28 patients (16 COPD FEV1:18±6 %pred, 7 IPF TLC: 46±11 %pred, 4 bronchiectasis FEV1: 28±4 %pred, alveolitis fibrotisans TLC: 31 %pred). participated in a pre- and 8 took part in a post-transplant rehabilitation program (primary diagnosis: 5 COPD, 3 IPF). The rehabilitation program consisted of chest wall-stretching, controlled breathing techniques and personalized exercises of 20-30 minutes by cycling and treadmill 2-3 times per day for 4
  • Rationale: The role of pre- and post-lung transplant pulmonary rehabilitation is to maintain and improve exercise capacity, lung mechanics, peripherial- and respiratory muscle function. Aims: Follow-up the changes of functional and quality of life markers in pre- and post-transplant pulmonary rehabilitation. Materials and Methods: 28 patients (16 COPD FEV1:18±6 %pred, 7 IPF TLC: 46±11 %pred, 4 bronchiectasis FEV1: 28±4 %pred, alveolitis fibrotisans TLC: 31 %pred). participated in a pre- and 8 took part in a post-transplant rehabilitation program (primary diagnosis: 5 COPD, 3 IPF). The rehabilitation program consisted of chest wall-stretching, controlled breathing techniques and personalized exercises of 20-30 minutes by cycling and treadmill 2-3 times per day for 4 weeks. Lung function, chest expansion (CE), 6 minutes walking distance (6MWD), modified Medical Research Council Dyspnea Scale (mMRC), COPD Assessment Test (CAT), breath holding time, grip strength were measured.Results: Pre-transplant pulmonary rehabilitation resulted significant improvement in CE (3,06±1,76 vs. 4,40±1,03 cm, p<0,05), CAT (21±6 vs. 16±6), breath holding time (18±9 vs. 30±15 sec), 6MWD (295±99 vs. 332±98m), p<0,05. FEV1, FVC, mMRC, grip strength did not change significantly. Post-transplant rehabilitation resulted significant improvement in CE (3,67±2,76 vs. 5,63±2,06 cm), CAT (17±7 vs. 8±4), breath holding time (26±6 vs. 42±16 sec), FEV1 (53±27 vs. 73±26 %pred) and FVC (56±21 vs. 73±21 %pred), p<0.05. The 6MWD, mMRC and grip strength did not change significantly.Conclusion: Our results underline the importance of perioperative pulmonary rehabilitation in the complex management of lung transplantation.
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  • Lung transplantation is an established treatment for patients with end-stage lung disease. It has been observed that despite near-normal lung function, exercise intolerance and reductions in quality of life (QOL) often persist up to years after transplantation. Several modifiable pre- and posttransplant factors are known to contribute to these persisting impairments. Physiological changes associated with severe and chronic lung disease, limb muscle dysfunction, inactivity/deconditioning, and nutritional depletion can affect exercise capacity and physical functioning in candidates for lung transplantation. After transplantation, extended hospital and intensive care unit stay, prolonged sedentary time, persisting inactivity, immunosuppressant medications and episodes of organ rejection may all impact lung recipients' recovery. Available evidence will be reviewed and content will be proposed (both evidence and experience based) for rehabilitation interventions prior to transplantation, during hospitalization after transplantation, and in both the immediate (≤12 months after hospital discharge) and long-term (>12 months after hospital discharge) posttransplant phase. Outpatient rehabilitation programs including supervised exercise training have been shown to be effective in improving limb muscle dysfunction, exercise capacity, and QOL both before and after transplantation if offered appropriately. Unmet research needs included the absence of sufficiently powered randomized controlled trials measuring the effects of rehabilitation interventions on crucial long-term outcomes such as sustained improvements in QOL, participation in daily activity, survival, incidence of morbidities and cost-effectiveness. Remotely monitored (telehealth) home-based exercise or pedometer-based walking interventions might be interesting alternatives to supervised outpatient rehabilitation interventions in the long-term posttransplant phase and warrant further investigation.
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  • series
  • Safety and efficacy of antifibrotic drugs in IPF patients undergoing LTx were investigated in a single-centre retrospective cohort analysis. Results A total of nine patients, receiving antifibrotic therapy for 419 ± 315 days until subsequent LTx, were included. No major side effects were noted. Significant weight loss occurred during antifibrotic treatment (p = 0.0062). FVC tended to stabilize after 12 weeks of treatment in most patients. A moderate decline in FVC, TLC and DLCO was noted during the whole pretransplant time period of antifibrotic therapy. Functional exercise capacity and lung allocation score remained unchanged. No post-operative thoracic wound healing problems, nor severe early anastomotic airway complications were attributable to prior antifibrotic treatment. None of the patients developed chronic lung allograft dysfunction after a median follow-up of 19.8 (11.2–26.5) months; and post-transplant survival was 100% after 1 year and 80% after 2 years. Conclusions Antifibrotic drugs can probably be safely administered in IPF patients, possibly attenuating disease progression over time, while awaiting LTx. KeywordsAntifibroticsIPFLung transplantationNintedanibPirfenidoneSafety BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive and lethal disease characterized by chronic, fibrosing interstitial pneumonitis of unknown cause, associated with a histopathologic and/or radiologic pattern of usual interstitial pneumonia (UIP) [1]. The course of the disease is unpredictable. Most patients demonstrate a slow, gradual progression; some patients remain stable; while others have an accelerated decline, sometimes due to repeated exacerbations. Consequently, respiratory failure is the most common cause of death in IPF. Once diagnosed, timely referral to an expert centre is therefore essential to assess eligibility for pharmacological therapy and/or lung transplantation (LTx) [2].In October 2014, the US Food and Drug Administration (FDA) approved two anti-fibrotic drugs for IPF - pirfenidone and nintedanib - based on the results of large randomized clinical trials (CAPACITY-1, CAPACITY-2 and ASCEND with pirfenidone; TOMORROW, INPULSIS-1 and INPULSIS-2 with nintedanib) demonstrating a reduction in the rate of decline in forced vital capacity (FVC) in mild to moderate IPF [3, 4, 5]. Post-hoc analysis also demonstrated a risk reduction for IPF-related mortality with pirfenidone compared to placebo (HR 0.32, 95% CI 0.14–0.76, p = 0.006) [6], a same trend which was also observed with nintedanib (HR 0.70; 95% CI 0.46–1.08; p = 0.0954) [7].Despite these positive findings, it should be emphasized that both antifibrotic drugs do not represent a ‘cure’ for IPF, but only aim to attenuate the decline in FVC, at best resulting in temporary disease stabilization. Moreover, side effects (typically nausea, anorexia, malaise, or rash for pirfenidone; and diarrhea for nintedanib) or adverse events (mainly toxic hepatitis) may force some patients to reduce or even stop treatment, which may again accelerate disease progression. Hence, early evaluation and referral for LTx, which presently remains the only definitive treatment option for well-selected IPF patients, is highly recommendable, particularly since IPF patients have the highest waiting list mortality, due to disease progression. The recent introduction of the lung allocation score (LAS) in some countries may nevertheless decrease future waiting list mortality in IPF. Implementation of the LAS indeed has already led to a substantial increase in the proportion of LTx performed for IPF, making it the most common indication for LTx and reducing waiting list time for IPF in these countries [8].With increasing use of antifibrotics following recent FDA approval, questions arise about their safety in IPF patients undergoing LTx, yet safety data in this specific setting are currently lacking. The antifibrotic properties of pirfenidone result from inhibition of transforming growth factor (TGF)-β expression, thus attenuating myofibroblast differentiation and fibroblast activity [9]. Nintedanib is a tyrosine kinase inhibitor, which blocks receptors for platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF), thus inhibiting downstream signaling in (myo-)fibroblasts [10]. Both antifibrotics may hence theoretically impair post-operative wound healing and/or cause bronchial anastomotic complications following LTx. Nintedanib, by inhibition of VEGF and PDGF, may in theory also result in an increased peri-operative bleeding risk. Moreover, it is unclear whether antifibrotic treatment, when effectively achieving disease stabilization for several months, would influence LAS or may even interfere with referral for LTx, given an upper age limit for LTx used in most centres.In the current study we therefore report on safety and efficacy of pretransplant antifibrotics in IPF patients undergoing LTx. Pretransplant pulmonary function, functional exercise capacity; and immediate and long-term post-operative outcomes, including the early post-operative course, presence of bronchial anastomotic complications, chronic lung allograft dysfunction (CLAD) and survival, were retrospectively assessed. Methods Study design and population This is a single-centre, retrospective analysis of IPF patients undergoing LTx in a large volume transplant centre at a tertiary care hospital. The current study was approved by the Leuven University Hospital Ethical Review Board (S51577) and patients gave informed consent. IPF diagnosis was confirmed in by a multidisciplinary board discussion, including an expert chest physician specialized in interstitial lung disease (ILD) (WW), an experienced chest imaging radiologist and a specialized lung-pathologist (EKV). For the current study, we included all IPF patients up to December 2015 who had undergone LTx in our centre whilst being treated with either pirfenidone or nintedanib. There were no IPF patients receiving antifibrotic drugs who died on the waiting list before LTx. Pirfenidone was initiated between September 2008 and September 2013; and patients were subsequently transplanted between November 2008 and April 2015. Nintedanib was started between August 2010 and January 2012; and patients were transplanted between March 2011 and October 2014. In Belgium, pirfenidone was approved for mild to moderate IPF (FVC >50%predicted (%pred) and Diffusion Capacity (DLCO) >35%pred) in December 2012 and nintedanib has been approved for mild to severe IPF (FVC ≥50%pred and DLCO ≥30%pred) since December 2015. Patients in whom antifibrotic therapy was initiated before these respective dates thus received the drugs in the context of clinical trials, thereafter patients received open-label treatment according to reimbursement rules. All IPF patients were evaluated on regular intervals (every 3 to 4 months) at a specialized outpatient ILD consultation by a specialized physician (WW) and nurse, who checked compliance and tolerance of their antifibrotic therapy. Data collection Data were retrospectively collected from the patients’ electronical medical files, including clinical and demographical variables, duration of antifibrotic treatment, laboratory results, anastomotic problems (scored according to MDS classification as previously reported, [11]), evolution of pulmonary function and functional exercise capacity. The estimated annual decline in pulmonary function parameters (FVC, Total Lung Capacity (TLC) and DLCO) was calculated based on the difference in pulmonary function parameters between the start of antifibrotic therapy (‘baseline’) and at the time of LTx, adjusted for the number of months therapy was taken (monthly decline) and extrapolated to 1 year (monthly decline x12). The same approach was used regarding the decrease in six minute walking test (6MWT) between start of therapy and LTx. LAS was retrospectively assessed at start of antifibrotic therapy, at LTx listing (data summarized in Table 1) and at LTx. However, we used LAS at start of antifibrotic therapy for further statistical analyses regarding pre-LTx evolution of LAS, because most patients were initiated on antifibrotics before LTx listing.Table 1 Recipient and donor demographics of the IPF treatment group and historical control group IDRecipient Gender (M/F)Recipient Age (Years)Anti-fibrotic DrugCardio-Pulmonary RehabilitationTime on Therapy (Days)FVC at start (%pred)TLC at start (%pred)DLCO at start (%pred)6MWT at start (m)Time on WL (Days)LAS at listingType of LTx (S/SS)Donor Gender (M/F)Donor Age (Years)Type of DonorCMV Donor/Recipient1F62PFDno73591724652976232SSF17DBDD+/R+2M61PFDCPR54571613737917931SSF67DCD cat IIID-/R-3M51PFDCPR3878880475522935SSM37DBDD+/R-4M63PFDCPR5395245323845130SSM55DBDD-/R+5M55PFDCPR1885652356312529SSM23DBDD+/R-6M64PFDno11562483950316333SSM35DCD cat VD+/R+7M64PFDno6579562826741937SF42DBDD+/R-8M65NINno100380695859815531SSM62DBDD+/R-9M56NINno1945856292757432SSM39DCD cat IIID-/R- Mean or Median60.1 ± 4.9  419 ± 31570.8 ± 14.559.9 ± 11.739.0 ± 9.8457.6 ± 135.6155 (40–299)32.2 ± 2.5  43.6 ± 17.1  1M57/no/////27933SSF48DCD cat IIID-/R+2M62/no/////15335SSF66DBDD+/R+3M55/no/////1734SSM74DBDD+/R+4M59/CPR/////27432SSM22DCD cat IIID-/R+5M59/CPR/////25329SSM57DBDD-/R-6M65/CPR/////11226SM37DBDD+/R+ Mean or Median59.5 ± 3.6a       203 (88–275)a31.5 ± 3.4a  50.7 ± 19.a  IDIschemic Time 1th/2nd Lung (min)Immuno-suppressive RegimenTime to Extubation (Hours)PGD at 72 hTime on ICU (Days)Time in Hospital (Days)AR or LB Episodes (Number)Most Severe AR or LB (Grade)Respiratory infection before Discharge (Presence = 1)Respiratory Pathogen before DischargeAnastomotic Complications (Details in Text)1187/320rATG/FK/MMF/CS340616000/02432/580rATG/FK/MMF/CS203720111 E. coli, S. viridans M2aD0aS0 (POD 30)3498/694No ATG, FK/MMF/CS370416221 A. baumanii, E. coli, S. aureus M3bD2cS2f (POD 204)4417/631rATG/FK/MMF/CS6511326110/M2aD0aS0 (POD 30)5366/515rATG/FK/MMF/CS412617001 C. freundii 06385/582rATG/FK/MMF/CS371416320/07341rATG/CsA/AZA/CS332321001 H. influenza, MRSA 08180/356rATG/FK/MMF/CS17831028131 H. influenza, S. pneumoniae M1aD0aS0 (POD 90)9239/356rATG/FK/MMF/CS382523120/0 338 ± 113/504 ± 142 37 (33.5–53)2 (0.5–2.5)6.4 ± 3.220.3 ± 4.61 (0–1.5)1 (0–2)   1404/626rATG/FK/MMF/CS720719120/02220/412rATG/FK/MMF/CS161725231 S. aureus M3bD0aS0 (POD 30)3288/431rATG/FK/MMF/CS432360253111 P. aeruginosa, K. pneumoniae, M3bD2bS0 (POD 40)4276/423rATG/FK/MMF/CS4821532111 E. faecalis M2aD0aS0 (POD 14)5209/439rATG/CsA/AZA/CS4822332001 K. oxytoca M3aD0S0 (POD 17)6186rATG/CsA/AZA/CS241820210/0 264 ± 79a/466 ± 90a 48 (22–162)a1.5 (0.8–2.3)a20.0 ± 20.6b63.5 ± 93a1 (0.75–2.0)a1 (0.75–2.25)a   IDTime of Follow-up(Months)Status (Dead = 1)Last FVC Post-LTx (%pred)Last FEV1 Post-LTx (%pred)Last FEV1/FVC Post-LTx (%pred)17.701451478628.601069066316.90706877421.90906758525.80939380627.1012312679719.8111010776813.8011911575956.3013214184 19.8 (11.2–26.5) 109 ± 23.1106 ± 29.175.7 ± 8.8114.901177666223.501049976337.00676173438.601079267552.401045843612.21798281 30.3 (14.2–42.1) 96.3 ± 19.178.0 ± 16.467.7 ± 13.3 Data are expressed as mean ± SD, median (interquartile range) or as total values where appropriate Abbreviations: 6MWT 6 min walking test, AR Acute (cellular) Rejection, AZA azathioprine, cat category, CMV Cytomegalovirus, CPR Cardio-Pulmonary Rehabilitation, CS corticosteroids, CsA cyclosporine A, D donor, DBD donation after brain death, DCD donation after cardiac death, DLCO diffusion capacity, F Female, FK tacrolimus, FVC Forced Vital Capacity, ICU Intensive Care Unit, ID identification, LAS lung allocation score, LB lymphocytic bronchiolitis, LTx lung transplantation, M male, MDS severity of anastomotic complication according to MDS classification, MMF mycophenolate mofetil, NIN nintedanib, PFD pirfenidone, PGD primary graft dysfunction, R recipient, rATG rabbit Anti-Thymocyte Globulin, S single, SS sequential single, TLC Total Lung Capacity, WL waiting list a:p > 0.05 (not statistically significant compared to treated group), b:p = 0.021 compared to treated group Historical controls We additionally identified a comparable group of historical controls (n = 6), which consisted of IPF patients who did not receive antifibrotic therapy before LTx, but were transplanted in the same era (7/2010 to 9/2014), had comparable age and lung function at the time of LTx compared to the treatment group: FVC 57.0 (43.0–69.8) %pred (p = 0.69 vs. treatment), TLC 53.0 (42.5–71.0) %pred (p = 1.0 vs. treatment) and DLCO 21.5 (17.0–29.2) %pred (p = 0.11 vs. treatment). Given the small number of available patients, it was impossible to match both groups any further regarding concurrent emphysema (but TLC and DLCO were comparable between both groups, thus excluding major differences due to emphysema), pulmonary hypertension (was not routinely assessed in non-treated IPF patients, no comparison possible with treated group who were all screened at start of antifibrotic therapy) or cardiovascular disease (but major cardiovascular disease is generally an exclusion-criterion to proceed to LTx in any patient). Reasons for not starting antifibrotic therapy in these matched historical controls were: absence of consent (n = 3), DLCO too low for study-inclusion (n = 2) and pending approval by the health care authorities whilst awaiting LTx (n = 1). These historical controls were only used as comparator for the IPF group treated with antifibrotics regarding the annual pre-transplant decline in pulmonary function; and some mportant early post-transplant outcome parameters, including rates of PGD, infection, rejection and anastomotic complications. These historical patients were not the main aim of this study, which focusses on reporting safety and efficacy of antifibrotics in IPF patients undergoing LTx. Statistical analysis All analyses were performed using Graphpad Prism 5a software (San Diego, USA). Results are expressed as mean (± standard deviation) or median (interquartile range) where appropriate. Group means were compared using paired or unpaired t-test; Mann-Whitney test or Wilcoxon signed rank test for normally or not-normally distributed variables, respectively. All reported p-values are two-tailed and p < 0.05 was considered significant. Results Patients’ characteristics A total of 9 IPF patients were treated with antifibrotics and subsequently underwent LTx: pirfenidone n = 7 (n = 2 study vs. n = 5 open-label treatment), nintedanib n = 2 (both in study). All patients, but one, underwent bilateral LTx and all, but one, were male. Age at LTx was 60.1 ± 4.9 years. Five patients were on continuous oxygen therapy (4 (3.5–4.0) Liters/min) before LTx, while 4 were not (Table 1). Antifibrotic therapy had been initiated 362 (152–578) days before listing for LTx in 6/9 patients, whereas in 3/9 patients antifibrotics were started 48 (27–354) days after transplant listing. In all 9 cases antifibrotic therapy was continued until the day of transplant procedure. Total duration of antifibrotic therapy until LTx was 419 ± 315 days, or 13.8 ± 10.3 months. All patients received the full, recommended dose (i.e. 801 mg tid for pirfenidone and 150 mg bid for nintedanib). Nausea was reported as main side-effect of antifibrotic therapy in 9/9 patients; and 7/9 patients lost weight during treatment (n = 6 pirfenidone, n = 1 nintedanib), in one patient (on pirfenidone) weight remained stable and one patient (on nintedanib) gained 1 kg. Overall, body mass index (BMI) decreased from 27.3 ± 3.2 kg/m2 to 25.8 ± 3.3 kg/m2 (p = 0.0063) during antifibrotic treatment, with an absolute weight loss of 329 ± 360 g per month of treatment (p = 0.0062). None of the patients developed toxic hepatitis, nor discontinued their therapy due to other severe side-effects or adverse events. No acute IPF exacerbations occurred in any of the patients during antifibrotic treatment. Evolution of pretransplant pulmonary function, functional exercise capacity, pulmonary hypertension, renal function and LAS Spirometry was performed at the start of antifibrotic treatment (‘baseline’) and during subsequent follow-up. Consecutive spirometry after six months of antifibrotic therapy was only available in 6/9 patients, as 3 patients (n = 2 pirfenidone, n = 1 nintedanib) underwent LTx within 6 months after initiating therapy (Fig. 1). In these 6/9 patients (n = 5 pirfenidone, n = 1 nintedanib), the absolute decline in FVC after 12 weeks of treatment compared to baseline was −7.0%pred (−1.8 to −11.5), with 4/6 (66.6%) patients having <10% decline in FVC %pred; and only 2/6 (33.3%) patients demonstrating a ≥10% decline in FVC %pred (p = 0.063 vs. start). Nevertheless, an overall absolute decrease in FVC, TLC and DLCO during the whole pretransplant antifibrotic treatment period (i.e. 419 ± 315 days or 59 ± 44 weeks) was observed in these 6/9 patients (Fig. 2). Fig. 1 Forced Vital Capacity in IPF patients with at least 6 months antifibrotic therapy before transplantation. Forced Vital Capacity (FVC) (%predicted) is given at the start of antifibrotic therapy (start), 3 months before and respectively 3, 6, 9 and 12 months (mo) after start. Dotted lines connect values in patients (n = 6/9) with consecutive measurements at different time points; p-values (Wilcoxon signed rank test) above each time point are given compared to start; or compared another time point (time-frame indicated by full line) Fig. 2 Pretransplant evolution of pulmonary function and functional exercise capacity following treatment with antifibrotic drugs. Forced Vital Capacity (FVC) (a), Total Lung Capacity (TLC) (b), Diffusion capacity (DLCO) (c) (all in (%predicted) and 6 min walk test (6MWT, meter) (d) at start of antifibrotic therapy (start) and at the moment of lung transplantation (LTx) in the included IPF patients. Dotted lines connect values in patients (n = 6/9) with a consecutive measurement at six months and just before transplantation; p-values (Wilcoxon signed rank test) are given for patients that had consecutive measurements The calculated annual decline during treatment for all included patients was: FVC 322.0 (148.3–1074.0) mL or 6.6 (0–23.8) %pred, TLC 360.0 (157.5–1818.0) mL or 6.0 (2.0–25.7) %pred; and DLCO 0.77 (0.40–1.96) mmol/min/Kpa or 7.5 (4.7–18.6) %pred. Interestingly, the measured annual rate of decline in the matched historical controls (without antifibrotic therapy) during the year preceding LTx appeared to be somewhat more severe compared to the group with antifibrotics, although no significant differences were seen: FVC 460.0 (215.0–732.5) mL or 13.0 (4.8–18.0) %pred (p = 0.69); TLC 945.0 mL (362.5–1490) or 10.0%pred (2.0–20.0) (p = 1.0); and DLCO 1.26 (0.38–2.09) mmol/min/Kpa or 14.0 (4.0–24.8) %pred (p = 0.94). 6MWT was performed before the start of antifibrotic therapy and consecutive 6MWT was available in 5/9 patients (all on pirfenidone), of whom 3/5 were enrolled in a pretransplant cardio-pulmonary rehabilitation (CPR) program upon transplant listing and 2/5 were not. 6MWT overall increased with 54 (−260.0–95.5) m after 12 weeks of treatment compared to baseline (p = 0.62), with an improved in 4/5 patients of 74.5 (21.8–95.8) m, while one patient demonstrated a decline of 531 m (patient n°5 in Table 1, no CPR, concomitant decline in FVC of 12%pred during these 12 weeks of treatment). During the whole pretransplant time period of antifibrotic treatment (59 ± 44 weeks), 6MWT did not significantly change compared to baseline (p = 0.89): 6MWT improved compared to baseline in 2/5 patients (+63 m (no CPR) and +142 m (with CPR), respectively), while 6MWT deteriorated in 3/5 patients (one no CPR, two with CPR), in whom there was an absolute decline of −172 (34–531) meters or a monthly decline of −5.2 (2.7–85.7) meters during treatment (Fig. 2). In the historical controls, unfortunately, 6MWD was only available upon listing for LTx, thus no consecutive 6MWT were available for further comparison. Transthoracic echocardiography performed before start of antifibrotic therapy (pulmonary arterial pressure (PAP) 31.1 ± 7.4 mmHg) and consecutive echocardiography was available in 4/9 patients, in whom PAP tended to increase during antifibrotic treatment (PAP +9.5 (2.0–15.5) mmHg: p = 0.090). Renal function remained stable during antifibrotic treatment: serum creatinine was 0.96 ± 0.14 mg/dL at start versus 0.95 ± 0.17 mg/dL at LTx (p = 0.97), estimated glomerular filtration rate was 83 ± 13 mL/min/1.73 m2 at start versus 82 ± 14 mL/min/1.73 m2 at LTx (p = 0.83). No hepatic dysfunction was observed in any patient during treatment. LAS did not significantly change during antifibrotic treatment: 32.2 ± 2.5 at start of therapy versus 32.3 ± 1.0 at LTx (p = 0.13). Post-transplant outcomes Patients receiving antifibrotics were listed for 155 (40–299) days before subsequent LTx. Transplant procedures were overall uneventful and only one patient (who had received pirfenidone, had the highest pretransplant PAP of 48 mmHg and underwent single sided LTx) required peri-operative support with veno-arterial extracorporeal membrane oxygenation. There were no bleeding problems (i.e. no need for re-thoracotomy for hemothorax, no additional transfusion of blood products for blood loss) in any patient, including those on nintedanib. Overall, patients were extubated after 37.0 (33.5–53.0) hours of ventilation, discharged from the intensive care unit after 6.4 ± 3.2 days and discharged home after a hospital stay of 20.3 ± 4.6 days. There were no problems with post-operative thoracic wound healing or dehiscence in any patient. All patients, but one, received post-operative induction therapy with anti-thymocyte globulin for 3 days; and post-operative immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil and steroids in all patients, except one (transplanted in 2008) who received cyclosporine, azathioprine and steroids (our standard regimen before 2010). No major side effects due to possible drug-interactions with prior antifibrotics were seen in the first days post-LTx. A total of 4/9 patients were included in a clinical trial immediately following LTx: 2 in a therapeutic trial with azithromycin (AZI003, NCT01915082), 1 in an ex-vivo normothermic machine perfusion trial (EXPANDLung, NCT01963780) and 1 in a Diaphragm Pacing trial (NCT02411383), which may obviously influence early and/or late outcomes (including post-transplant evolution of pulmonary function, anastomotic airway complications, primary graft dysfunction (PGD), rejection, infection, CLAD) in these transplant recipients compared to those not included in a trial or historical controls. Overall, incidence of PGD (PGD ≥ 2 in 5/9 patients), early post-operative infection (5/9 patients) and acute cellular rejection (4/9 patients) or lymphocytic bronchiolitis (4/9) during the first 6 months were comparable to findings in the historical controls (all p > 0.5) (Table 1). Anastomotic airway complications were present in 4/9 patients: in two patients (prior pirfenidone) mild anastomotic necrosis without dehiscence or airway narrowing was noted upon discharge after LTx (post-operative day (POD) 30; MDS classification M2aD0aS0 for right-sided anastomosis and M0aD0aS0 for left-sided anastomosis in both patients), with spontaneous and uncomplicated resolution thereafter. In a third patient (initially no anastomotic complications, prior nintedanib), there was mild protrusion of cartilage on POD 90 (M0aD0aS0 for right-sided anastomosis and M1aD0aS0 for left-sided anastomosis), with spontaneous and uncomplicated resolution thereafter. In the fourth patient (initially no anastomotic complications, prior pirfenidone), following infection with Aspergillus fumigatus at POD 186, late-onset (POD 204) anastomotic necrosis occurred with bronchial narrowing and extensive dehiscence (M0aD0aS0 for right-sided anastomosis and M3bD2cS2f for left-sided anastomosis). Despite antifungal treatment, he developed severe symptomatic anastomotic stenosis, which finally required surgical sleeve-resection and reconstruction of the left main bronchus on POD 410. Thereafter, no other problems occurred and the patient currently has a stable pulmonary function at POD 525. The observed anastomotic airway complications, however, did not appear to be more severe or prevalent compared to previously reported data from our centre [11] or to the historical controls, of whom 4/6 controls had early anastomotic airway complications (ranging from M2aD0aS0 to M3bD2bS0; Table 1). Overall, long-term outcome in our cohort was good: after a median follow-up of 19.8 (11.2–26.5) months, currently all patients have a stable pulmonary function (Table 1) and none of the patients has developed CLAD. One patient (who underwent single sided LTx), unfortunately, has died because of non-squamous large cell lung carcinoma of his native IPF lung on POD 615, all other patients are alive and ambulatory at present. Overall survival was 100% after 1 year and 80% after 2 years, respectively. DiscussionLittle is known about safety of antifibrotic therapy with pirfenidone or nintedanib in patients undergoing LTx. Actually only 11 IPF patients receiving pirfenidone; and none receiving nintedanib, included in the large randomized trials with these drugs (comprising a total of 2832 study-subjects) were reported as having been transplanted during antifibrotic treatment, yet detailed outcome data for these patients are lacking [3, 4, 5, 6, 7]. Only 1 case report has currently been published on pretransplant pharmacological bridging with pirfenidone, allowing stabilization of respiratory function and subsequent single sided LTx in IPF. Anastomic airway complications, however, were not reported in this case [12]. Next to this, there have been two abstracts reporting on this topic, which did not yet result in peer-reviewed papers, but in which, apparently, pirfenidone therapy was not linked to adverse post-transplant events, however follow-up was limited and detailed outcome data missing [13, 14]. In the current case series, we therefore report on pre-operative evolution and post-transplant outcomes of 9 IPF patients, treated with either pirfenidone or nintedanib for a mean of 13.4 months until subsequent LTx and with a median post-transplant follow-up of 19.8 months.According to the same definitions used in larger IPF trials [6, 15], we noted relative stabilization (i.e. < 10% change) of FVC during the first 12 weeks of antifibrotic treatment. Importantly, this early stabilization, or perhaps better attenuated rate of decline, in FVC may by no means be a reason to deny subsequent LTx to eligible patients, because further decline in FVC, lung volumina and DLCO is to be expected despite antifibrotic treatment, as was obvious from our results. The estimated annual decline in FVC during treatment in our cohort, however, would be around 6.6%pred, which corroborates recent findings that both pirfenidone and nintedanib reduce the proportion of patients with a ≥10% decline in FVC %pred after 1 year of treatment [5, 6]. As they may attenuate disease progression, these antifibrotics may thus allow for valuable added time on the LTx waiting list. Next to FVC, 6MWT has also been shown to be a valid outcome measure, both in IPF, in whom the clinically important difference in 6MWT distance is reported to be 24–45 m [3, 4, 5] and in whom 6MWT is associated with changes in pulmonary function and quality-of-life [16]; and in patients awaiting LTx, in whom it is associated with post-transplant survival [17]. A reduction of the decline in 6MWT was also observed in treated patients compared to placebo in pooled analyses of IPF trials [3, 4, 5], which may partly explain why 6MWT overall remained relatively stable during treatment in our cohort, next to the obvious beneficial effects of cardio-pulmonary rehabilitation is some patients. Although the LAS is actually not used in Belgium for prioritizing organ allocation, the calculated LAS (which includes FVC and 6MWT among other parameters) did not significantly change during pretransplant antifibrotic treatment in our cohort. An average LAS of 32 at the time of LTx in our study may seem fairly low for IPF patients, yet LAS was quite comparable between our treated patients and historical controls; and was in the same range (median of ±35) as previously described for IPF patients at LTx listing [18]. We therefore believe that our cohort indeed reflects the general population of IPF patients transplanted during the past 5–10 years. However, in the last few years, as seen in the US, an increase in LAS is also noted in our centre, with more sicker patients (LAS > 40) being listed for LTx [19].No serious side effects were noted during antifibrotic therapy. However, significant weight loss occurred, which is most likely due to drug-induced anorexia or possibly due to respiratory cachexia in end-stage lung disease. Post-operatively, no problems with bleeding or thoracic wound healing were observed. One patient, treated with nintedanib; and three patients who had received pirfenidone developed, mostly mild and uneventful, anastomic airway complications. Intervention for anastomotic stenosis was needed for one case, which only occurred late-onset after prior fungal infection. Overall, it is unlikely that any of these anastomotic problems were directly related to prior antifibrotic treatment given the time of onset/clinical context of anastomotic complications, comparable anastomotic problems in the historical controls; and rather short half-life of both drugs (for pirfenidone 3 h, for nintedanib 9.5 h) [20, 21]. The short half-life of both antifibrotic drugs is important, as drug-interactions with calcineurin inhibitors, by altered hepatic (CYP3A4) metabolisation leading to changes in tacrolimus/cyclosporine trough levels, are a feared iatrogenic adverse event in LTx. However, hepatic metabolism of pirfenidone primarily occurs through the CYP1A2 enzyme; whereas nintedanib is mainly a substrate of P-glycoprotein (P-gp) and only weakly interferes with CYP3A4. This probably also explains why no major side effects due to drug-interactions with peri-operatively used drugs were noted in our cohort. Finally, long-term outcomes regarding pulmonary function and overall survival were overall good in our current case series, suggesting that antifibrotic agents can probably be safely given without deleterious effects on peri-operative or medium-term outcomes.Possible limitations of the current study, of course, are its retrospective design, the small number of included patients; and historical controls as comparator for some outcomes, which of course limits interpretations regarding antifibrotic drug efficacy and safety. Also, disease severity ranged from mild to severe IPF, which may bias the observed effects of pretransplant antifibrotic therapy; and post-transplant evolution, including pulmonary function, may be biased by inclusion of some patients in various randomized clinical trials. Larger, preferably prospective, case-series are therefore undeniably needed to confirm our findings, especially for nintedanib additional safety data are needed before firmer conclusions can be made regarding its safety. ConclusionIn summary, we conclude that antifibrotic drugs are probably safe in IPF patients undergoing LTx. By attenuating disease progression while awaiting LTx, these antifibrotics may perhaps further help to reduce the number of IPF patients dying on the waiting list. Abbreviations 6MWT:  Six minute walking test BMI:  Body mass index CLAD:  Chronic lung allograft dysfunction CPR:  Cardio-pulmonary rehabilitation DLCO:  Diffusion capacity FDA:  Food and Drug Administration FGF:  Fibroblast growth factor FVC:  Forced vital capacity ILD:  Interstitial lung disease IPF:  Idiopathic pulmonary fibrosis LAS:  Lung allocation score LTx:  Lung transplantation MDS:  Macroscopic Diameter Sutures (MDS Classification) PDGF:  Platelet-derived growth factor PGD:  Primary graft dysfunction POD:  Post-operative day TGF- β:  Transforming growth factor –beta TLC:  Total lung capacity UIP:  Usual interstitial pneumonia VEGF:  Vascular endothelial growth factor Declarations AcknowledgmentsNot applicable. Funding RV is supported by the Starting Grant (STG/15/023) and JY is supported by the Clinical Research Fund (KOF), UZLeuven, Belgium. WW and RV are senior research fellows of the Research Foundation Flanders (FWO), Belgium (12G8715N). GMV is supported by the FWO (G.0723.10, G.0679.12 and G.0679.12). Availability of data and materials The datasets generated during and/or analyzed during the current study are not publicly available due to local Biobanking and legislation policy, but are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. The authors confirm that that the work described has not been published previously, that it is not under consideration for publication elsewhere, that its publication is approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out, and that, if accepted, it will not be published elsewhere in the same form in English or in any other language, without the written consent of the copyright holder. Authors’ contributions ID: performed data collection, wrote the paper and helped with its critical appraisal. WW: is responsible ILD physician during pretransplant period and helped with critical appraisal of the manuscript. JY: is responsible ILD physician during pretransplant period and helped with critical appraisal of the manuscript. EV: is responsible ILD pathologist during pretransplant period and helped with critical appraisal of the manuscript. GV: is responsible ILD physician during pretransplant period and responsible LTx physician during post-LTx period, helped with critical appraisal of the manuscript. RV: is responsible LTx physician during post-LTx period, performed design of the study, data collection, statistical analyses, and helped with critical appraisal of the manuscript. All authors read and approved the final manuscript. Consent for publication All patients gave informed consent for scientific publication of the data presented in this paper. Ethics approval and consent to participate The current study was approved by the Leuven University Hospital Ethical Review Board (S51577) and patients gave informed consent. 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. Authors’ Affiliations(1)Department of Respiratory Diseases, Interstitial Lung Disease and Lung Transplant Unit, University Hospitals Leuven, Leuven, Belgium(2)KULeuven, Department of Clinical and Experimental Medicine, Division of Respiratory Diseases, Laboratory of Respiratory Diseases, Lung Transplantation Unit, KU Leuven, Leuven, Belgium(3)KULeuven, Department of Histopathology, Leuven, Belgium ReferencesRaghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, et al. ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183(6):788–824.View ArticlePubMedGoogle ScholarNational Clinical Guideline Centre (UK). Diagnosis and management of suspected idiopathic pulmonary fibrosis: idiopathic pulmonary fibrosis, National Institute for Health and Care Excellence: clinical guidelines. 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J Heart Lung Transplant. 2016;35(4S):883.Google ScholarTaniguchi H, Kondoh Y, Ebina M, Azuma A, Ogura T, Taguchi Y, Pirfenidone Clinical Study Group in Japan, et al. The clinical significance of 5% change in vital capacity in patients with idiopathic pulmonary fibrosis: extended analysis of the pirfenidone trial. Respir Res. 2011;12:93.View ArticlePubMedPubMed CentralGoogle ScholarNathan SD, du Bois RM, Albera C, Bradford WZ, Costabel U, Kartashov A, et al. Validation of test performance characteristics and minimal clinically important difference of the 6-min walk test in patients with idiopathic pulmonary fibrosis. Respir Med. 2015;109(7):914–22.View ArticlePubMedGoogle ScholarCastleberry AW, Englum BR, Snyder LD, Worni M, Osho AA, Gulack BC, et al. The utility of preoperative six-minute-walk distance in lung transplantation. Am J Respir Crit Care Med. 2015;192(7):843–52.View ArticlePubMedGoogle ScholarEgan TM, Murray S, Bustami RT, Shearon TH, McCullough KP, Edwards LB, et al. Development of the new lung allocation system in the United States. Am J Transplant. 2006;6(5 Pt 2):1212–27.View ArticlePubMedGoogle ScholarEgan TM, Edwards LB. Effect of the lung allocation score on lung transplantation in the United States. J Heart Lung Transplant. 2016;35(4):433–9.View ArticlePubMedGoogle ScholarESBRIET® (pirfenidone) hard capsules, for oral use. electronic Medicines Compendium. Genentech. Accessed 12 Dec 2015.Google ScholarOFEV® (nintedanib) capsules, for oral use. electronic Medicines Compendium. Boehringer Ingelheim. Accessed 12 Dec 2015.Google ScholarCopyright© The Author(s). 2016 Download PDF Export citations Papers, Zotero, Reference Manager, RefWorks (.RIS) Download Citations Download References Download Both EndNote (.ENW) Download Citations Download References Download Both Mendeley, JabRef (.BIB) Download Citations Download References Download Both Section Infectious, Rare and Idiopathic Pulmonary Diseases Metrics Article accesses: 1765 Citations: 14 more information Altmetric Attention Score: 32 Share this article Share on Twitter Share on Facebook Share on LinkedIn Share on Weibo Share on Google Plus
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  • 搜尋結果The University of Tokyowww.u-tokyo.ac.jp/en/頁庫存檔翻譯這個網頁TopicsOctober 24, 2017 GLP-GEfIL Program Celebrates Its First Graduates. Vote Now in the University of Tokyo Slogan Competition. NoticesOctober 23, 2017 ...Graduate SchoolsThe University of Tokyo has 15 Graduate Schools that offer ...About UTokyoHome > About UTokyo ... To learn more about the University of ...FacultiesFaculty of Engineering - Faculty of Science - Faculty of MedicineProspective StudentsHome > Prospective Students ... Students from all over the ...AcademicsFaculties - Graduate Schools - Student Exchange ProgramsUndergraduate Programs in ...Programs in English at Komaba ... Course (GSC ...u-tokyo.ac.jp 的其他相關資訊 »「The university of tokyo」的圖片搜尋結果更多符合「The university of tokyo」的圖片檢舉圖片感謝您的意見。 檢舉其他相片請檢舉令人反感的圖片。 取消完成if (document.querySelector("#taw").clientHeight == 0 && document.querySelector("#topstuff").clientHeight == 0){var positiveClientHeight = function(element){return element.clientHeight>0;};var firstVisibleElement = Array.from(document.querySelector("#rso").children) .find(positiveClientHeight);var sectionWithHeaderElement = firstVisibleElement && firstVisibleElement .querySelector("div g-section-with-header");if(sectionWithHeaderElement){sectionWithHeaderElement.style.marginTop = "0";} } 东京大学| The University of Tokyowww.u-tokyo.ac.jp/zh/頁庫存檔類似內容轉為繁體網頁东京大学的官方网站。您可以了解到大学的介绍、本科学部和研究生院等的介绍,研究活动、国际活动、招生信息以及其他东京大学的信息。University of Tokyo - Wikipediahttps://en.wikipedia.org/wiki/University_of_Tokyo頁庫存檔類似內容翻譯這個網頁The University of Tokyo (東京大学, Tōkyō daigaku), abbreviated as Todai (東大, Tōdai) or UTokyo, is a public research university located in Bunkyo, Tokyo, often ...‎History · ‎Academics · ‎Rankings and reputation · ‎CampusUniversity of Tokyo World University Rankings | THEhttps://www.timeshighereducation.com/...university.../university-tokyo頁庫存檔翻譯這個網頁Find the latest world ranking position for University of Tokyo and key information for prospective students here today.The University of Tokyo | Top Universitieshttps://www.topuniversities.com/universities/university-tokyo頁庫存檔翻譯這個網頁Established in 1877, the University of Tokyo was ranked the 34th best university in the world in the QS World University Rankings® 2016-2017. Home to 10 ...The University of Tokyo | Courserahttps://zh-tw.coursera.org/utokyo頁庫存檔類似內容翻譯這個網頁The University of Tokyo was established in 1877 as the first national university in Japan. As a leading research university, UTokyo offers courses in essentially ....mfr{margin-top:1em;margin-bottom:1em}#brs{}#brs{margin-bottom:28px}#brs .med{color:#222;height:auto;padding-bottom:8px}.brs_col{font-size:14px;margin-top:-1px;padding-bottom:1px;display:inline-block;line-height:20px;vertical-align:top;max-width:100%;box-sizing:border-box}#brs ._e4b{margin:0;clear:both}#brs a{padding:3px 32px 3px 0;display:inline-block;float:left}#brs a{text-decoration:none}g-section-with-header{display:block;margin:40px 0}._ojo{padding:0 0px 12px 0px}The university of tokyo的相關搜尋university of tokyo rankinguniversity of tokyo addressuniversity of tokyo physicstokyo university mbauniversity of tokyo international programuniversity of kyototokyo university computer sciencetokyo university hospitaltoyo universityjapan university rankingif (document.querySelector("#taw").clientHeight == 0 && document.querySelector("#topstuff").clientHeight == 0){var positiveClientHeight = function(element){return 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2 annotations