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.

Agostino Gemelli University Hospital Università Cattolica del Sacro Cuore Rome Italy

Center Hospitalier de Versailles Medical Surgical Intensive Care Unit Le Chesnay France

CHU Grenoble Alpes Service de réanimation médicale Faculté de Médecine de Grenoble INSERM U1042 Université Grenoble Alpes Grenoble France

CIBERES Universitat Autonòma de Barcelona European Study Group of Infections in Critically Ill Patients Barcelona Spain

Critical Care Center CHU Lille School of Medicine University of Lille Lille France

Department of Anaesthesia and Intensive Care Odense University Hospital Odense Denmark

Department of Anesthesiology 1 Herlev University Hospital Herlev Denmark

Department of Anesthesiology and Intensive Care Medicine and Institute for Medical Humanities 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Czech Republic

Department of Clinical Medicine Trinity College Wellcome Trust HRB Clinical Research Facility St James Hospital Dublin Ireland

Department of Critical Care University Medical Center Groningen Groningen The Netherlands

Department of Emergencies and Critical Care Oslo University Hospital Oslo Norway

Department of Intensive Care Hôpital Erasme Université Libre de Bruxelles Brussels Belgium

Department of Intensive Care Medicine Multidisciplinary Intensive Care Research Organization St James's Hospital Dublin Ireland

Department of Intensive Care Rigshospitalet University of Copenhagen Copenhagen Denmark

Department of Medical Intensive Care Medicine University Hospital of Angers Angers France

Department of Medicine 1 Medical University of Vienna Vienna Austria

Department of Medicine and Interdepartmental Division of Critical Care Medicine Sinai Health System University of Toronto Toronto ON Canada

Division of Intensive Care Medicine Department of Anesthesiology Intensive Care and Pain Medicine University of Helsinki and Helsinki University Hospital Helsinki Finland

Division of Pulmonary and Critical Care Penn State University College of Medicine Hershey PA USA

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

ICU Fundação Pio XII Hospital de Câncer de Barretos Barretos Brazil

Intensive Care Department University of Southern Denmark Odense Denmark

King's College Hospital London SE5 9RS UK

Medical ICU Cochin Hospital Assistance Publique Hôpitaux de Paris and University Paris Descartes Paris France

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

Medical Intensive Care Unit Hôtel Dieu HME University Hospital of Nantes Nantes France

Medical Intensive Care Unit La Source Hospital CHR Orléans Orléans France

Normandie Univ UNIROUEN EA 3830 Department of Medical Intensive Care Rouen University Hospital 76000 Rouen France

Pulmonary and Critical Care Medicine Mayo Clinic Rochester MN USA

Réanimation Polyvalente et Département d'Anesthésie et de Réanimation Institut Paoli Calmettes Marseille France

Terapia Intensiva Hospital Maciel Montevideo Uruguay

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

The Department of Intensive Care Medicine Radboud University Medical Center Nijmegen The Netherlands

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