Elie Azoulay1, Peter Pickkers2, Marcio Soares3, Anders Perner4, Jordi Rello5, Philippe R Bauer6, Andry van de Louw7, Pleun Hemelaar2, Virginie Lemiale8, Fabio Silvio Taccone9, Ignacio Martin Loeches10,11, Tine Sylvest Meyhoff4, Jorge Salluh3, Peter Schellongowski12, Katerina Rusinova13, Nicolas Terzi14, Sangeeta Mehta15, Massimo Antonelli16, Achille Kouatchet17, Andreas Barratt-Due18, Miia Valkonen19, Precious Pearl Landburg20, Fabrice Bruneel21, Ramin Brandt Bukan22, Frédéric Pène23, Victoria Metaxa24, Anne Sophie Moreau25, Virginie Souppart8, Gaston Burghi26, Christophe Girault27, Ulysses V A Silva28, Luca Montini16, François Barbier29, Lene B Nielsen30,31, Benjamin Gaborit32, Djamel Mokart33, Sylvie Chevret34. 1. Medical Intensive Care Unit, APHP, Hôpital Saint-Louis, Famirea Study Group, ECSTRA team, and Clinical Epidemiology, UMR 1153, Center of Epidemiology and Biostatistics, Sorbonne Paris Cité, CRESS, INSERM, Paris Diderot Sorbonne University, Paris, France. elie.azoulay@sls.aphp.fr. 2. The Department of Intensive Care Medicine (710), Radboud University Medical Center, Nijmegen, The Netherlands. 3. The Department of Critical Care and Graduate Program in Translational Medicine, D'Or Institute for Research and Education, Programa de Pós-Graduação em Clínica Médica, Rio De Janeiro, Brazil. 4. Department of Intensive Care, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 5. CIBERES, Universitat Autonòma de Barcelona, European Study Group of Infections in Critically Ill Patients (ESGCIP), Barcelona, Spain. 6. Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA. 7. Division of Pulmonary and Critical Care, Penn State University College of Medicine, Hershey, PA, USA. 8. Medical Intensive Care Unit, APHP, Hôpital Saint-Louis, Famirea Study Group, ECSTRA team, and Clinical Epidemiology, UMR 1153, Center of Epidemiology and Biostatistics, Sorbonne Paris Cité, CRESS, INSERM, Paris Diderot Sorbonne University, Paris, France. 9. Department of Intensive Care, Hôpital Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium. 10. Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), St. James's Hospital, Dublin, Ireland. 11. Department of Clinical Medicine, Trinity College, Wellcome Trust-HRB Clinical Research Facility, St James Hospital, Dublin, Ireland. 12. Department of Medicine I, Medical University of Vienna, Vienna, Austria. 13. Department of Anesthesiology and Intensive Care Medicine and Institute for Medical Humanities, 1st Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic. 14. CHU Grenoble Alpes, Service de réanimation médicale, Faculté de Médecine de Grenoble, INSERM, U1042, Université Grenoble-Alpes, Grenoble, France. 15. Department of Medicine and Interdepartmental Division of Critical Care Medicine, Sinai Health System, University of Toronto, Toronto, ON, Canada. 16. Agostino Gemelli University Hospital, Università Cattolica del Sacro Cuore, Rome, Italy. 17. Department of Medical Intensive Care Medicine, University Hospital of Angers, Angers, France. 18. Department of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway. 19. Division of Intensive Care Medicine, Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 20. Department of Critical Care, University Medical Center Groningen, Groningen, The Netherlands. 21. Center Hospitalier de Versailles, Medical-Surgical Intensive Care Unit, Le Chesnay, France. 22. Department of Anesthesiology I, Herlev University Hospital, Herlev, Denmark. 23. Medical ICU, Cochin Hospital, Assistance Publique-Hôpitaux de Paris and University Paris Descartes, Paris, France. 24. King's College Hospital, London, SE5 9RS, UK. 25. Critical Care Center, CHU Lille, School of Medicine, University of Lille, Lille, France. 26. Terapia Intensiva, Hospital Maciel, Montevideo, Uruguay. 27. Normandie Univ, UNIROUEN, EA-3830, Department of Medical Intensive Care, Rouen University Hospital, 76000, Rouen, France. 28. ICU, Fundação Pio XII, Hospital de Câncer de Barretos, Barretos, Brazil. 29. Medical Intensive Care Unit, La Source Hospital, CHR Orléans, Orléans, France. 30. Intensive Care Department, University of Southern Denmark, Odense, Denmark. 31. Department of Anaesthesia and Intensive Care, Odense University Hospital, Odense, Denmark. 32. Medical Intensive Care Unit, Hôtel Dieu-HME-University Hospital of Nantes, Nantes, France. 33. Réanimation Polyvalente et Département d'Anesthésie et de Réanimation, Institut Paoli-Calmettes, Marseille, France. 34. ECSTRA Team, Biostatistics and Clinical Epidemiology, UMR 1153, INSERM, Paris Diderot Sorbonne University and Service de Biostatistique et Information Médicale AP-HP, Hôpital Saint-Louis, Paris, France.
Abstract
BACKGROUND: In immunocompromised patients with acute hypoxemic respiratory failure (ARF), initial management aims primarily to avoid invasive mechanical ventilation (IMV). METHODS: To assess the impact of initial management on IMV and mortality rates, we performed a multinational observational prospective cohort study in 16 countries (68 centers). RESULTS: A total of 1611 patients were enrolled (hematological malignancies 51.9%, solid tumors 35.2%, systemic diseases 17.3%, and solid organ transplantation 8.8%). The main ARF etiologies were bacterial (29.5%), viral (15.4%), and fungal infections (14.7%), or undetermined (13.2%). On admission, 915 (56.8%) patients were not intubated. They received standard oxygen (N = 496, 53.9%), high-flow oxygen (HFNC, N = 187, 20.3%), noninvasive ventilation (NIV, N = 153, 17.2%), and NIV + HFNC (N = 79, 8.6%). Factors associated with IMV included age (hazard ratio = 0.92/year, 95% CI 0.86-0.99), day-1 SOFA (1.09/point, 1.06-1.13), day-1 PaO2/FiO2 (1.47, 1.05-2.07), ARF etiology (Pneumocystis jirovecii pneumonia (2.11, 1.42-3.14), invasive pulmonary aspergillosis (1.85, 1.21-2.85), and undetermined cause (1.46, 1.09-1.98). After propensity score matching, HFNC, but not NIV, had an effect on IMV rate (HR = 0.77, 95% CI 0.59-1.00, p = 0.05). ICU, hospital, and day-90 mortality rates were 32.4, 44.1, and 56.4%, respectively. Factors independently associated with hospital mortality included age (odds ratio = 1.18/year, 1.09-1.27), direct admission to the ICU (0.69, 0.54-0.87), day-1 SOFA excluding respiratory score (1.12/point, 1.08-1.16), PaO2/FiO2 < 100 (1.60, 1.03-2.48), and undetermined ARF etiology (1.43, 1.04-1.97). Initial oxygenation strategy did not affect mortality; however, IMV was associated with mortality, the odds ratio depending on IMV conditions: NIV + HFNC failure (2.31, 1.09-4.91), first-line IMV (2.55, 1.94-3.29), NIV failure (3.65, 2.05-6.53), standard oxygen failure (4.16, 2.91-5.93), and HFNC failure (5.54, 3.27-9.38). CONCLUSION: HFNC has an effect on intubation but not on mortality rates. Failure to identify ARF etiology is associated with higher rates of both intubation and mortality. This suggests that in addition to selecting the appropriate oxygenation device, clinicians should strive to identify the etiology of ARF.
BACKGROUND: In immunocompromised patients with acute hypoxemic respiratory failure (ARF), initial management aims primarily to avoid invasive mechanical ventilation (IMV). METHODS: To assess the impact of initial management on IMV and mortality rates, we performed a multinational observational prospective cohort study in 16 countries (68 centers). RESULTS: A total of 1611 patients were enrolled (hematological malignancies 51.9%, solid tumors 35.2%, systemic diseases 17.3%, and solid organ transplantation 8.8%). The main ARF etiologies were bacterial (29.5%), viral (15.4%), and fungal infections (14.7%), or undetermined (13.2%). On admission, 915 (56.8%) patients were not intubated. They received standard oxygen (N = 496, 53.9%), high-flow oxygen (HFNC, N = 187, 20.3%), noninvasive ventilation (NIV, N = 153, 17.2%), and NIV + HFNC (N = 79, 8.6%). Factors associated with IMV included age (hazard ratio = 0.92/year, 95% CI 0.86-0.99), day-1 SOFA (1.09/point, 1.06-1.13), day-1 PaO2/FiO2 (1.47, 1.05-2.07), ARF etiology (Pneumocystis jirovecii pneumonia (2.11, 1.42-3.14), invasive pulmonary aspergillosis (1.85, 1.21-2.85), and undetermined cause (1.46, 1.09-1.98). After propensity score matching, HFNC, but not NIV, had an effect on IMV rate (HR = 0.77, 95% CI 0.59-1.00, p = 0.05). ICU, hospital, and day-90 mortality rates were 32.4, 44.1, and 56.4%, respectively. Factors independently associated with hospital mortality included age (odds ratio = 1.18/year, 1.09-1.27), direct admission to the ICU (0.69, 0.54-0.87), day-1 SOFA excluding respiratory score (1.12/point, 1.08-1.16), PaO2/FiO2 < 100 (1.60, 1.03-2.48), and undetermined ARF etiology (1.43, 1.04-1.97). Initial oxygenation strategy did not affect mortality; however, IMV was associated with mortality, the odds ratio depending on IMV conditions: NIV + HFNC failure (2.31, 1.09-4.91), first-line IMV (2.55, 1.94-3.29), NIV failure (3.65, 2.05-6.53), standard oxygen failure (4.16, 2.91-5.93), and HFNC failure (5.54, 3.27-9.38). CONCLUSION: HFNC has an effect on intubation but not on mortality rates. Failure to identify ARF etiology is associated with higher rates of both intubation and mortality. This suggests that in addition to selecting the appropriate oxygenation device, clinicians should strive to identify the etiology of ARF.
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