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Acute hypoxemic respiratory failure in immunocompromised patients: the Efraim multinational prospective cohort study

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In immunocompromised patients with acute hypoxemic respiratory failure (ARF), initial management aims primarily to avoid invasive mechanical ventilation (IMV).


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).


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).


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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This study was performed on behalf of the “Caring for critically ill immunocompromised patients—Multinational Network (Nine-I). This group includes critical care specialists from 16 countries in Europe, the USA, Canada and South America. The primary aim of this group is to improve and standardize practices in the management of critically ill immunocompromised patients.

Contributors: Antoine Rabbat, Hôpital Cochin, Paris, France; Isabelle Vinatier, CHD de Vendée, La Roche Sur Yon, France; Michael Darmon, CHU, Saint-Etienne, France; Kada Klouche, Laura Platon, CHU, Montpellier, France; Martine Nyunga, CHG Victor Provo, Roubaix, France; Alexandre Demoule, Julien Mayaux, CHU Pitié-Salpétrière, Paris, France; Florent Wallet, CHU, Lyon Sud, France; Akli Chermak, CH Sud Essonne, Etampes, France; Amelie Seguin Réanimation Medicale - CHU de Caen, Caen, France; Caroline Lemaitre, Elise Artaud-Macari, University Hospital, Medical Intensive Care, Rouen, France; Jonas Nelsen, Rigshospitalet, Copenhagen, Denmark; Ann M. Moeller, Herlev University Hospital, UCPH, Herlev, Denmark; Thomas Kaufmann, Department of Critical Care, Groningen, the Netherlands; Dennis Bergmans, Department of Critical Care, Maastricht, the Netherlands; Angélique Spoelstra de Man, Department of Critical Care, Amsterdam, the Netherlands; Ana Paula Pierre de Moraes, Hospital de Câncer do Maranhao, Brazil; William Viana, Hospital Copa d’Or, Brazil; Guilliana Moralez, Hospital GetulioVargas, Rio de Janeiro, Brazil; Thiago Lishoa, Hospital Santa Rita, Santa Casa de Misericordia, Porte Allegre, Brazil; Thiago Domingos Correa, ICU, Hospital Israelita Albert Einstein, São Paulo, Brazil; Belen Encina, Val Hebron, Barcelona, Spain; Gabriel Moreno, Department of Critical Care, Bellitge, Spain; Emilio Rodriguez Luis, Department of Critical Care, Santiago de compostella, Spain; Llorenç Socias Crespi, Department of Critical Care, Palma, Spain; Yadav Hemang, Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA; Anne-Pascale Meert, Institut Jules Bordet, Brussels, Belgique; Dominique Benoit, Ghent University Hospital, Ghent, Belgique; Nina Buchtele, Department of Medicine I, Vienna, Austria; Thomas Staudinger, Department of Medicine I, Vienna, Austria; Gottfried Heinz, Department of Medicine II, Vienna, Austria; Gürkan Sengölge, Department of Medicine III, Vienna, Austria; Christian Zauner, Department of Medicine III, Vienna, Austria; Peter Jaksch, Department of Thoracic Surgery, Vienna, Austria; Karin Amrein, Department of Internal Medicine, Graz, Austria; Aisling Mc Mahon, Department of Critical Care, St James, Dublin, Ireland; Brian Marsh, Department of Critical Care, Mater misericordia, Dublin, Ireland; Balik Martin, Department of Critical Care, Prague, Czech Republic; Karvunidis Thomas, Department of Critical Care, Pielsa, Czech Republic; Pål Klepstad, St. Olavs Hospital, Trondheim, Norway; Anne Kuitunen, Department of Critical Care, Tempere, Finland; Gilda Cinnella, Antonella Cotoia, Ospedali Riuniti, Department of Critical Care, Foggia, Italy; Sumech Shah, Mount Sinai Hospital, Canada.

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Correspondence to Elie Azoulay.

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The authors declare no conflict of interest in relation to this study.

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The members of the Efraim investigators and the Nine-I study group are listed in the Acknowledgements and in ESM 2.

All authors substantially contributed to the design of the study, acquisition, analysis, and interpretation of data, drafted and revised the manuscript for important intellectual content, approved the final version, and agreed to be accountable for all aspects of the work.

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Azoulay, E., Pickkers, P., Soares, M. et al. Acute hypoxemic respiratory failure in immunocompromised patients: the Efraim multinational prospective cohort study. Intensive Care Med 43, 1808–1819 (2017).

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