Intensive Care Medicine

, Volume 43, Issue 12, pp 1808–1819 | Cite as

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

  • Elie Azoulay
  • Peter Pickkers
  • Marcio Soares
  • Anders Perner
  • Jordi Rello
  • Philippe R. Bauer
  • Andry van de Louw
  • Pleun Hemelaar
  • Virginie Lemiale
  • Fabio Silvio Taccone
  • Ignacio Martin Loeches
  • Tine Sylvest Meyhoff
  • Jorge Salluh
  • Peter Schellongowski
  • Katerina Rusinova
  • Nicolas Terzi
  • Sangeeta Mehta
  • Massimo Antonelli
  • Achille Kouatchet
  • Andreas Barratt-Due
  • Miia Valkonen
  • Precious Pearl Landburg
  • Fabrice Bruneel
  • Ramin Brandt Bukan
  • Frédéric Pène
  • Victoria Metaxa
  • Anne Sophie Moreau
  • Virginie Souppart
  • Gaston Burghi
  • Christophe Girault
  • Ulysses V. A. Silva
  • Luca Montini
  • François Barbier
  • Lene B. Nielsen
  • Benjamin Gaborit
  • Djamel Mokart
  • Sylvie Chevret
  • for the Efraim investigators and the Nine-I study group
Seven-Day Profile Publication

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.

Keywords

Noninvasive ventilation High flow oxygen Hematological malignancies Transplantation Systemic diseases Pneumocystis 

Notes

Acknowledgements

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.

Compliance with ethical standards

Conflicts of interest

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

Supplementary material

134_2017_4947_MOESM1_ESM.doc (378 kb)
Supplementary material 1 (DOC 378 kb)
134_2017_4947_MOESM2_ESM.doc (100 kb)
Supplementary material 2 (DOC 100 kb)

References

  1. 1.
    Harpaz R, Dahl RM, Dooling KL (2016) Prevalence of immunosuppression among US adults, 2013. JAMA 316(23):2547–2548CrossRefPubMedGoogle Scholar
  2. 2.
    Fernandez-Ruiz M, Kumar D, Humar A (2014) Clinical immune-monitoring strategies for predicting infection risk in solid organ transplantation. Clin Transl Immunol 3(2):e12CrossRefGoogle Scholar
  3. 3.
    Winthrop KL, Novosad SA, Baddley JW et al (2015) Opportunistic infections and biologic therapies in immune-mediated inflammatory diseases: consensus recommendations for infection reporting during clinical trials and postmarketing surveillance. Ann Rheum Dis 74(12):2107–2116CrossRefPubMedGoogle Scholar
  4. 4.
    Azoulay E, Pene F, Darmon M et al (2015) Managing critically ill hematology patients: time to think differently. Blood Rev 29(6):359–367CrossRefPubMedGoogle Scholar
  5. 5.
    Puxty K, McLoone P, Quasim T, Sloan B, Kinsella J, Morrison DS (2015) Risk of critical illness among patients with solid cancers: a population-based observational study. JAMA Oncol 1(8):1078–1085CrossRefPubMedGoogle Scholar
  6. 6.
    Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67(1):7–30CrossRefPubMedGoogle Scholar
  7. 7.
    Morrison VA (2014) Immunosuppression associated with novel chemotherapy agents and monoclonal antibodies. Clin Infect Dis 59(Suppl 5):S360–S364CrossRefPubMedGoogle Scholar
  8. 8.
    Novosad SA, Winthrop KL (2014) Beyond tumor necrosis factor inhibition: the expanding pipeline of biologic therapies for inflammatory diseases and their associated infectious sequelae. Clin Infect Dis 58(11):1587–1598CrossRefPubMedGoogle Scholar
  9. 9.
    Canet E, Zafrani L, Azoulay E (2016) The critically ill kidney transplant recipient: a narrative review. Chest 149(6):1546–1555CrossRefPubMedGoogle Scholar
  10. 10.
    Dumas G, Geri G, Montlahuc C et al (2015) Outcomes in critically ill patients with systemic rheumatic disease: a multicenter study. Chest 148(4):927–935CrossRefPubMedGoogle Scholar
  11. 11.
    Frat JP, Ragot S, Girault C et al (2016) Effect of non-invasive oxygenation strategies in immunocompromised patients with severe acute respiratory failure: a post hoc analysis of a randomised trial. Lancet Respir Med 4(8):646–652CrossRefPubMedGoogle Scholar
  12. 12.
    Lemiale V, Resche-Rigon M, Mokart D et al (2017) High-flow nasal cannula oxygenation in immunocompromised patients with acute hypoxemic respiratory failure: a Groupe de Recherche Respiratoire en Reanimation Onco-Hematologique Study. Crit Care Med 45(3):e274–e280CrossRefPubMedGoogle Scholar
  13. 13.
    Mokart D, Geay C, Chow-Chine L et al (2016) High-flow oxygen therapy in cancer patients with acute respiratory failure. Intensive Care Med 41(11):2008–2010CrossRefGoogle Scholar
  14. 14.
    Lemiale V, Mokart D, Resche-Rigon M et al (2015) Effect of noninvasive ventilation vs oxygen therapy on mortality among immunocompromised patients with acute respiratory failure: a randomized clinical trial. JAMA 314(16):1711–1719CrossRefPubMedGoogle Scholar
  15. 15.
    Papazian L, Corley A, Hess D et al (2016) Use of high-flow nasal cannula oxygenation in ICU adults: a narrative review. Intensive Care Med 42(9):1336–1349CrossRefPubMedGoogle Scholar
  16. 16.
    Mokart D, Lambert J, Schnell D et al (2013) Delayed intensive care unit admission is associated with increased mortality in patients with cancer with acute respiratory failure. Leuk Lymphoma 54(8):1724–1729CrossRefPubMedGoogle Scholar
  17. 17.
    Burghi G, Lemiale V, Seguin A et al (2011) Outcomes of mechanically ventilated hematology patients with invasive pulmonary aspergillosis. Intensive Care Med 37(10):1605–1612CrossRefPubMedGoogle Scholar
  18. 18.
    Contejean A, Lemiale V, Resche-Rigon M et al (2017) 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 6(1):102CrossRefGoogle Scholar
  19. 19.
    Azoulay E, Mokart D, Pene F et al (2013) 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 31(22):2810–2818CrossRefPubMedGoogle Scholar
  20. 20.
    Azoulay E, Lemiale V, Mokart D et al (2014) Acute respiratory distress syndrome in patients with malignancies. Intensive Care Med 40(8):1106–1114CrossRefPubMedGoogle Scholar
  21. 21.
    Adda M, Coquet I, Darmon M, Thiery G, Schlemmer B, Azoulay E (2008) Predictors of noninvasive ventilation failure in patients with hematologic malignancy and acute respiratory failure. Crit Care Med 36(10):2766–2772CrossRefPubMedGoogle Scholar
  22. 22.
    Gristina GR, Antonelli M, Conti G et al (2011) Noninvasive versus invasive ventilation for acute respiratory failure in patients with hematologic malignancies: a 5-year multicenter observational survey. Crit Care Med 39(10):2232–2239CrossRefPubMedGoogle Scholar
  23. 23.
    Azoulay E, Mokart D, Lambert J et al (2010) Diagnostic strategy for hematology and oncology patients with acute respiratory failure: randomized controlled trial. Am J Respir Crit Care Med 182(8):1038–1046CrossRefPubMedGoogle Scholar
  24. 24.
    Vincent JL, Moreno R, Takala J et al (1996) The SOFA (Sepsis-related organ failure assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 22(7):707–710CrossRefPubMedGoogle Scholar
  25. 25.
    Del Sorbo L, Ranieri VM, Ferguson ND (2016) The Berlin definition met our needs: yes. Intensive Care Med 42(5):643–647CrossRefPubMedGoogle Scholar
  26. 26.
    Amos SM, Duong CP, Westwood JA et al (2011) Autoimmunity associated with immunotherapy of cancer. Blood 118(3):499–509CrossRefPubMedGoogle Scholar
  27. 27.
    Hilbert G, Gruson D, Vargas F et al (2001) Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure. N Engl J Med 344(7):481–487CrossRefPubMedGoogle Scholar
  28. 28.
    Rano A, Agusti C, Benito N et al (2002) Prognostic factors of non-HIV immunocompromised patients with pulmonary infiltrates. Chest 122(1):253–261CrossRefPubMedGoogle Scholar
  29. 29.
    Antonelli M, Conti G, Rocco M et al (1998) A comparison of noninvasive positive-pressure ventilation and conventional mechanical ventilation in patients with acute respiratory failure. N Engl J Med 339(7):429–435CrossRefPubMedGoogle Scholar
  30. 30.
    Wohlfarth P, Ullrich R, Staudinger T et al (2014) Extracorporeal membrane oxygenation in adult patients with hematologic malignancies and severe acute respiratory failure. Crit Care 18(1):R20CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany and ESICM 2017

Authors and Affiliations

  • Elie Azoulay
    • 1
  • Peter Pickkers
    • 2
  • Marcio Soares
    • 3
  • Anders Perner
    • 4
  • Jordi Rello
    • 5
  • Philippe R. Bauer
    • 6
  • Andry van de Louw
    • 7
  • Pleun Hemelaar
    • 2
  • Virginie Lemiale
    • 1
  • Fabio Silvio Taccone
    • 8
  • Ignacio Martin Loeches
    • 9
    • 10
  • Tine Sylvest Meyhoff
    • 4
  • Jorge Salluh
    • 3
  • Peter Schellongowski
    • 11
  • Katerina Rusinova
    • 12
  • Nicolas Terzi
    • 13
  • Sangeeta Mehta
    • 14
  • Massimo Antonelli
    • 15
  • Achille Kouatchet
    • 16
  • Andreas Barratt-Due
    • 17
  • Miia Valkonen
    • 18
  • Precious Pearl Landburg
    • 19
  • Fabrice Bruneel
    • 20
  • Ramin Brandt Bukan
    • 21
  • Frédéric Pène
    • 22
  • Victoria Metaxa
    • 23
  • Anne Sophie Moreau
    • 24
  • Virginie Souppart
    • 1
  • Gaston Burghi
    • 25
  • Christophe Girault
    • 26
  • Ulysses V. A. Silva
    • 27
  • Luca Montini
    • 15
  • François Barbier
    • 28
  • Lene B. Nielsen
    • 29
    • 30
  • Benjamin Gaborit
    • 31
  • Djamel Mokart
    • 32
  • Sylvie Chevret
    • 33
  • for the Efraim investigators and the Nine-I study group
  1. 1.Medical Intensive Care Unit, APHP, Hôpital Saint-Louis, Famirea Study Group, ECSTRA team, and Clinical Epidemiology, UMR 1153Center of Epidemiology and Biostatistics, Sorbonne Paris Cité, CRESS, INSERM, Paris Diderot Sorbonne UniversityParisFrance
  2. 2.The Department of Intensive Care Medicine (710)Radboud University Medical CenterNijmegenThe Netherlands
  3. 3.The Department of Critical Care and Graduate Program in Translational MedicineD’Or Institute for Research and Education, Programa de Pós-Graduação em Clínica MédicaRio De JaneiroBrazil
  4. 4.Department of Intensive CareRigshospitalet, University of CopenhagenCopenhagenDenmark
  5. 5.CIBERES, Universitat Autonòma de Barcelona, European Study Group of Infections in Critically Ill Patients (ESGCIP)BarcelonaSpain
  6. 6.Pulmonary and Critical Care MedicineMayo ClinicRochesterUSA
  7. 7.Division of Pulmonary and Critical CarePenn State University College of MedicineHersheyUSA
  8. 8.Department of Intensive CareHôpital Erasme, Université Libre de Bruxelles (ULB)BrusselsBelgium
  9. 9.Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO)St. James’s HospitalDublinIreland
  10. 10.Department of Clinical Medicine, Trinity College, Wellcome Trust-HRB Clinical Research FacilitySt James HospitalDublinIreland
  11. 11.Department of Medicine IMedical University of ViennaViennaAustria
  12. 12.Department of Anesthesiology and Intensive Care Medicine and Institute for Medical Humanities, 1st Faculty of MedicineCharles University in Prague and General University HospitalPragueCzech Republic
  13. 13.CHU Grenoble Alpes, Service de réanimation médicale, Faculté de Médecine de Grenoble, INSERM, U1042Université Grenoble-AlpesGrenobleFrance
  14. 14.Department of Medicine and Interdepartmental Division of Critical Care Medicine, Sinai Health SystemUniversity of TorontoTorontoCanada
  15. 15.Agostino Gemelli University HospitalUniversità Cattolica del Sacro CuoreRomeItaly
  16. 16.Department of Medical Intensive Care MedicineUniversity Hospital of AngersAngersFrance
  17. 17.Department of Emergencies and Critical CareOslo University HospitalOsloNorway
  18. 18.Division of Intensive Care Medicine, Department of Anesthesiology, Intensive Care and Pain MedicineUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
  19. 19.Department of Critical CareUniversity Medical Center GroningenGroningenThe Netherlands
  20. 20.Center Hospitalier de Versailles, Medical-Surgical Intensive Care UnitLe ChesnayFrance
  21. 21.Department of Anesthesiology IHerlev University HospitalHerlevDenmark
  22. 22.Medical ICU, Cochin HospitalAssistance Publique-Hôpitaux de Paris and University Paris DescartesParisFrance
  23. 23.King’s College HospitalLondonUK
  24. 24.Critical Care Center, CHU Lille, School of MedicineUniversity of LilleLilleFrance
  25. 25.Terapia Intensiva, Hospital MacielMontevideoUruguay
  26. 26.Normandie Univ, UNIROUEN, EA-3830, Department of Medical Intensive CareRouen University HospitalRouenFrance
  27. 27.ICU, Fundação Pio XII, Hospital de Câncer de BarretosBarretosBrazil
  28. 28.Medical Intensive Care UnitLa Source Hospital, CHR OrléansOrléansFrance
  29. 29.Intensive Care DepartmentUniversity of Southern DenmarkOdenseDenmark
  30. 30.Department of Anaesthesia and Intensive CareOdense University HospitalOdenseDenmark
  31. 31.Medical Intensive Care UnitHôtel Dieu-HME-University Hospital of NantesNantesFrance
  32. 32.Réanimation Polyvalente et Département d’Anesthésie et de RéanimationInstitut Paoli-CalmettesMarseilleFrance
  33. 33.ECSTRA Team, Biostatistics and Clinical Epidemiology, UMR 1153, INSERM, Paris Diderot Sorbonne University and Service de Biostatistique et Information Médicale AP-HP, Hôpital Saint-LouisParisFrance

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