BACKGROUND: The impact of neutropenia in critically ill immunocompromised patients admitted in a context of acute respiratory failure (ARF) remains uncertain. The primary objective was to assess the prognostic impact of neutropenia on outcomes of these patients. Secondary objective was to assess etiology of ARF according to neutropenia. METHODS: We performed a post hoc analysis of a prospective multicenter multinational study from 23 ICUs belonging to the Nine-I network. Between November 2015 and July 2016, all adult immunocompromised patients with ARF admitted to the ICU were included in the study. Adjusted analyses included: (1) a hierarchical model with center as random effect; (2) propensity score (PS) matched cohort; and (3) adjusted analysis in the matched cohort. RESULTS: Overall, 1481 patients were included in this study of which 165 had neutropenia at ICU admission (11%). ARF etiologies distribution was significantly different between neutropenic and non-neutropenic patients, main etiologies being bacterial pneumonia (48% vs 27% in neutropenic and non-neutropenic patients, respectively). Initial oxygenation strategy was standard supplemental oxygen in 755 patients (51%), high-flow nasal oxygen in 165 (11%), non-invasive ventilation in 202 (14%) and invasive mechanical ventilation in 359 (24%). Before adjustment, hospital mortality was significantly higher in neutropenic patients (54% vs 42%; p = 0.006). After adjustment for confounder and center effect, neutropenia was no longer associated with outcome (OR 1.40, 95% CI 0.93-2.11). Similar results were observed after matching (52% vs 46%, respectively; p = 0.35) and after adjustment in the matched cohort (OR 1.04; 95% CI 0.63-1.72). CONCLUSION: Neutropenia at ICU admission is not associated with hospital mortality in this cohort of critically ill immunocompromised patients admitted for ARF. In neutropenic patients, main ARF etiologies are bacterial and fungal infections.

Anesthesiology Department Clinical Research in ICU CHU Nîmes University Montpellier Nîmes France

CIBERES Instituto de Salud Carlos 3 Barcelona Spain

Clinical Research Epidemiology In Pneumonia and Sepsis Barcelona Spain

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 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

Dept of Anesthesia Intensive Care and Emergency Medicine Fondazione Policlicnico Universitario A Gemelli IRCCS Università Cattolica del Sacro Cuore Rome Italy

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

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

Pulmonary and Critical Care Medicine Mayo Clinic Rochester MN USA

Réanimation Polyvalente Et Département D'Anesthésie Et de Réanimation Institut Paoli Calmettes 232 Bd Sainte Marguerite 13009 Marseille Cedex 09 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

Zobrazit více v PubMed

Brenner H. Long-term survival rates of cancer patients achieved by the end of the 20th century: a period analysis. Lancet. 2002;360(9340):1131–1135. doi: 10.1016/S0140-6736(02)11199-8. PubMed DOI

van Vilet M, van der Burgt MP, van der Velden WJ, van der Hoeven JG, de Haan AF, Donnelly JP, et al. Trends in the outcomes of Dutch haematological patients receiving intensive care support. Neth J Med. 2014;72(2):107–112. PubMed

Verdecchia A, Francisci S, Brenner H, Gatta G, Micheli A, Mangone L, et al. Recent cancer survival in Europe: a 2000–02 period analysis of EUROCARE-4 data. Lancet Oncol. 2007;8(9):784–796. doi: 10.1016/S1470-2045(07)70246-2. PubMed DOI

Darmon M, Bourmaud A, Georges Q, Soares M, Jeon K, Oeyen S, et al. Changes in critically ill cancer patients' short-term outcome over the last decades: results of systematic review with meta-analysis on individual data. Intensive Care Med. 2019;45(7):977–987. doi: 10.1007/s00134-019-05653-7. PubMed DOI

Darmon M, Azoulay E, Alberti C, Fieux F, Moreau D, Le Gall JR, et al. Impact of neutropenia duration on short-term mortality in neutropenic critically ill cancer patients. Intensive Care Med. 2002;28(12):1775–1780. doi: 10.1007/s00134-002-1528-7. PubMed DOI

Mokart D, Textoris J, Ettori F, Chetaille B, Blache JL. Acute respiratory distress syndrome (ARDS) in neutropenic patients. In: Azoulay E, editor. Pulmonary involvement in patients with hematological malignancies. Berlin, Heidelberg: Springer; 2011. pp. 477–490.

Azoulay E, Lemiale V, Mokart D, Pene F, Kouatchet A, Perez P, et al. Acute respiratory distress syndrome in patients with malignancies. Intensive Care Med. 2014;40(8):1106–1114. doi: 10.1007/s00134-014-3354-0. PubMed DOI

Azoulay E, Pickkers P, Soares M, Perner A, Rello J, Bauer PR, et al. Acute hypoxemic respiratory failure in immunocompromised patients: the Efraim multinational prospective cohort study. Intensive Care Med. 2017;43(12):1808–1819. doi: 10.1007/s00134-017-4947-1. PubMed DOI

Lagier D, Platon L, Chow-Chine L, Sannini A, Bisbal M, Brun JP, et al. Severity of Acute Respiratory Distress Syndrome in haematology patients: long-term impact and early predictive factors. Anaesthesia. 2016;71(9):1081–1090. doi: 10.1111/anae.13542. PubMed DOI

Mokart D, Darmon M, Resche-Rigon M, Lemiale V, Pene F, Mayaux J, et al. Prognosis of neutropenic patients admitted to the intensive care unit. Intensive Care Med. 2015;41(2):296–303. doi: 10.1007/s00134-014-3615-y. PubMed DOI

van Vilet M, Verburg IW, van den Boogaard M, de Keizer NF, Peek N, Blijlevens NM, et al. Trends in admission prevalence, illness severity and survival of haematological patients treated in Dutch intensive care units. Intensive Care Med. 2014;40(9):1275–1284. doi: 10.1007/s00134-014-3373-x. PubMed DOI

Contejean A, Lemiale V, Resche-Rigon M, Mokart D, Pene F, Kouatchet A, et al. Increased mortality in hematological malignancy patients with acute respiratory failure from undetermined etiology: a Groupe de Recherche en Reanimation Respiratoire en Onco-Hematologique (Grrr-OH) study. Ann Intensive Care. 2016;6(1):102. doi: 10.1186/s13613-016-0202-0. PubMed DOI PMC

Azoulay E, Schlemmer B. Diagnostic strategy in cancer patients with acute respiratory failure. Intensive Care Med. 2006;32(6):808–822. doi: 10.1007/s00134-006-0129-2. PubMed DOI

Azoulay E, Mokart D, Kouatchet A, Demoule A, Lemiale V. Acute respiratory failure in immunocompromised adults. Lancet Respir Med. 2019;7(2):173–186. doi: 10.1016/S2213-2600(18)30345-X. PubMed DOI PMC

Schnell D, Mayaux J, Lambert J, Roux A, Moreau AS, Zafrani L, et al. Clinical assessment for identifying causes of acute respiratory failure in cancer patients. Eur Respir J. 2013;42(2):435–443. doi: 10.1183/09031936.00122512. PubMed DOI

Tolsma V, Schwebel C, Azoulay E, Darmon M, Souweine B, Vesin A, et al. Sepsis severe or septic shock: outcome according to immune status and immunodeficiency profile. Chest. 2014;146(5):1205–1213. doi: 10.1378/chest.13-2618. PubMed DOI

Azoulay E, Mokart D, Pene F, Lambert J, Kouatchet A, Mayaux J, et al. Outcomes of critically ill patients with hematologic malignancies: prospective multicenter data from France and Belgium–a groupe de recherche respiratoire en reanimation onco-hematologique study. J Clin Oncol. 2013;31(22):2810–2818. doi: 10.1200/JCO.2012.47.2365. PubMed DOI

Maschmeyer G, Beinert T, Buchheidt D, Cornely OA, Einsele H, Heinz W, et al. Diagnosis and antimicrobial therapy of lung infiltrates in febrile neutropenic patients: Guidelines of the infectious diseases working party of the German Society of Haematology and Oncology. Eur J Cancer. 2009;45(14):2462–2472. doi: 10.1016/j.ejca.2009.05.001. PubMed DOI

Legrand M, Max A, Peigne V, Mariotte E, Canet E, Debrumetz A, et al. Survival in neutropenic patients with severe sepsis or septic shock. Crit Care Med. 2012;40(1):43–49. doi: 10.1097/CCM.0b013e31822b50c2. PubMed DOI

Mokart D, Saillard C, Sannini A, Chow-Chine L, Brun JP, Faucher M, et al. Neutropenic cancer patients with severe sepsis: need for antibiotics in the first hour. Intensive Care Med. 2014;40(8):1173–1174. doi: 10.1007/s00134-014-3374-9. PubMed DOI

Mokart D, van Craenenbroeck T, Lambert J, Textoris J, Brun JP, Sannini A, et al. Prognosis of acute respiratory distress syndrome in neutropenic cancer patients. Eur Respir J. 2012;40(1):169–176. doi: 10.1183/09031936.00150611. PubMed DOI

Duceau B, Picard M, Pirracchio R, Wanquet A, Pene F, Merceron S, et al. Neutropenic enterocolitis in critically ill patients: spectrum of the disease and risk of invasive fungal disease. Crit Care Med. 2019;47(5):668–676. doi: 10.1097/CCM.0000000000003687. PubMed DOI

Mokart D, Lambert J, Schnell D, Fouche L, Rabbat A, Kouatchet A, et al. Delayed intensive care unit admission is associated with increased mortality in patients with cancer with acute respiratory failure. Leuk Lymphoma. 2013;54(8):1724–1729. doi: 10.3109/10428194.2012.753446. PubMed DOI

Rello J, Sarda C, Mokart D, Arvaniti K, Akova M, Tabah A, et al. Antimicrobial Stewardship in Hematological Patients at the intensive care unit: a global cross-sectional survey from the Nine-I Investigators Network. Eur J Clin Microbiol Infect Dis. 2020;39(2):385–392. doi: 10.1007/s10096-019-03736-3. PubMed DOI

Bauer PR, Chevret S, Yadav H, Mehta S, Pickkers P, Bukan RB, et al. Diagnosis and outcome of acute respiratory failure in immunocompromised patients after bronchoscopy. Eur Respir J. 2019;54(1):1802442. doi: 10.1183/13993003.02442-2018. PubMed DOI

Pardo E, Lemiale V, Mokart D, Stoclin A, Moreau AS, Kerhuel L, et al. Invasive pulmonary aspergillosis in critically ill patients with hematological malignancies. Intensive Care Med. 2019;45(12):1732–1741. doi: 10.1007/s00134-019-05789-6. PubMed DOI

Legoff J, Zucman N, Lemiale V, Mokart D, Pene F, Lambert J, et al. Clinical significance of upper airway virus detection in critically ill hematology patients. Am J Respir Crit Care Med. 2019;199(4):518–528. doi: 10.1164/rccm.201804-0681OC. PubMed DOI

Martin-Loeches I, Lemiale V, Geoghegan P, McMahon MA, Pickkers P, Soares M, et al. Influenza and associated co-infections in critically ill immunosuppressed patients. Crit Care. 2019;23(1):152. doi: 10.1186/s13054-019-2425-6. PubMed DOI PMC

Azoulay E, Mokart D, Lambert J, Lemiale V, Rabbat A, Kouatchet A, et al. Diagnostic strategy for hematology and oncology patients with acute respiratory failure: randomized controlled trial. Am J Respir Crit Care Med. 2010;182(8):1038–1046. doi: 10.1164/rccm.201001-0018OC. PubMed DOI

Bouteloup M, Perinel S, Bourmaud A, Azoulay E, Mokart D, Darmon M. Outcomes in adult critically ill cancer patients with and without neutropenia: a systematic review and meta-analysis of the Groupe de Recherche en Reanimation Respiratoire du patient d'Onco-Hematologie (GRRR-OH) Oncotarget. 2017;8(1):1860–1870. doi: 10.18632/oncotarget.12165. PubMed DOI PMC

Georges Q, Azoulay E, Mokart D, Soares M, Jeon K, Oeyen S, et al. Influence of neutropenia on mortality of critically ill cancer patients: results of a meta-analysis on individual data. Crit Care. 2018;22(1):326. doi: 10.1186/s13054-018-2076-z. PubMed DOI PMC