Intensive Care Medicine

, Volume 40, Issue 8, pp 1106–1114 | Cite as

Acute respiratory distress syndrome in patients with malignancies

  • Elie Azoulay
  • Virginie Lemiale
  • Djamel Mokart
  • Frédéric Pène
  • Achille Kouatchet
  • Pierre Perez
  • François Vincent
  • Julien Mayaux
  • Dominique Benoit
  • Fabrice Bruneel
  • Anne-Pascale Meert
  • Martine Nyunga
  • Antoine Rabbat
  • Michael Darmon
Original

Abstract

Purpose

Little attention has been given to ARDS in cancer patients, despite their high risk for pulmonary complications. We sought to describe outcomes in cancer patients with ARDS meeting the Berlin definition.

Methods

Data from a cohort of patients admitted to 14 ICUs between 1990 and 2011 were used for a multivariable analysis of risk factors for hospital mortality.

Results

Of 1,004 included patients (86 % with hematological malignancies and 14 % with solid tumors), 444 (44.2 %) had neutropenia. Admission SOFA score was 12 (10–13). Etiological categories were primary infection-related ARDS (n = 662, 65.9 %; 385 bacterial infections, 213 invasive aspergillosis, 64 Pneumocystis pneumonia); extrapulmonary septic shock-related ARDS (n = 225, 22.4 %; 33 % candidemia); noninfectious ARDS (n = 76, 7.6 %); and undetermined cause (n = 41, 4.1 %). Of 387 (38.6 %) patients given noninvasive ventilation (NIV), 276 (71 %) subsequently required endotracheal ventilation. Hospital mortality was 64 % overall. According to the Berlin definition, 252 (25.1 %) patients had mild, 426 (42.4 %) moderate and 326 (32.5 %) severe ARDS; mortality was 59, 63 and 68.5 %, respectively (p = 0.06). Mortality dropped from 89 % in 1990–1995 to 52 % in 2006–2011 (p < 0.0001). Solid tumors, primary ARDS, and later admission period were associated with lower mortality. Risk factors for higher mortality were allogeneic bone-marrow transplantation, modified SOFA, NIV failure, severe ARDS, and invasive fungal infection.

Conclusions

In cancer patients, 90 % of ARDS cases are infection-related, including one-third due to invasive fungal infections. Mortality has decreased over time. NIV failure is associated with increased mortality. The high mortality associated with invasive fungal infections warrants specific studies of early treatment strategies.

Keywords

Neutropenia Bronchoscopy Pneumonia Invasive aspergillosis Candidemia Pneumocystis 

Notes

Acknowledgments

French Ministry of Health.

Conflicts of interest

Elie Azoulay is in the board of Gilead and has received research grant from MSD and Pfizer.

Supplementary material

134_2014_3354_MOESM1_ESM.docx (723 kb)
Supplementary material 1 (DOCX 722 kb)

References

  1. 1.
    Azoulay E, Mokart D, Lambert J, Lemiale V, Rabbat A, Kouatchet A, Vincent F, Gruson D, Bruneel F, Epinette-Branche G, Lafabrie A, Hamidfar-Roy R, Cracco C, Renard B, Tonnelier JM, Blot F, Chevret S, Schlemmer B (2010) Diagnostic strategy for hematology and oncology patients with acute respiratory failure: randomized controlled trial. Am J Respir Crit Care Med 182:1038–1046PubMedCrossRefGoogle Scholar
  2. 2.
    Maschmeyer G, Beinert T, Buchheidt D, Cornely OA, Einsele H, Heinz W, Heussel CP, Kahl C, Kiehl M, Lorenz J, Hof H, Mattiuzzi G (2009) 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 45:2462–2472PubMedCrossRefGoogle Scholar
  3. 3.
    Azevedo LC, Caruso P, Silva UV, Torelly AP, Silva E, Rezende E, Netto JJ, Piras C, Lobo SM, Knibel MF, Teles JM, Lima RA, Ferreira BS, Friedman G, Rea-Neto A, Dal-Pizzol F, Bozza FA, Salluh JI, Soares M (2014) Outcomes for patients with cancer admitted to the ICU requiring ventilatory support: results from a prospective multicenter study. ChestGoogle Scholar
  4. 4.
    Azoulay E, Thiery G, Chevret S, Moreau D, Darmon M, Bergeron A, Yang K, Meignin V, Ciroldi M, Le Gall JR, Tazi A, Schlemmer B (2004) The prognosis of acute respiratory failure in critically ill cancer patients. Medicine (Baltimore) 83:360–370CrossRefGoogle Scholar
  5. 5.
    Azoulay E, Kouatchet A, Jaber S, Lambert J, Meziani F, Schmidt M, Schnell D, Mortaza S, Conseil M, Tchenio X, Herbecq P, Andrivet P, Guerot E, Lafabrie A, Perbet S, Camous L, Janssen-Langenstein R, Collet F, Messika J, Legriel S, Fabre X, Guisset O, Touati S, Kilani S, Alves M, Mercat A, Similowski T, Papazian L, Meert AP, Chevret S, Schlemmer B, Brochard L, Demoule A (2013) Noninvasive mechanical ventilation in patients having declined tracheal intubation. Intensive Care Med 39:292–301PubMedCrossRefGoogle Scholar
  6. 6.
    Burghi G, Lemiale V, Seguin A, Lambert J, Lacroix C, Canet E, Moreau AS, Ribaud P, Schnell D, Mariotte E, Schlemmer B, Azoulay E (2011) Outcomes of mechanically ventilated hematology patients with invasive pulmonary aspergillosis. Intensive Care Med 37:1605–1612PubMedCrossRefGoogle Scholar
  7. 7.
    Groeger JS, Lemeshow S, Price K, Nierman DM, White P Jr, Klar J, Granovsky S, Horak D, Kish SK (1998) Multicenter outcome study of cancer patients admitted to the intensive care unit: a probability of mortality model. J Clin Oncol 16:761–770PubMedGoogle Scholar
  8. 8.
    Groeger JS, White P Jr, Nierman DM, Glassman J, Shi W, Horak D, Price K (1999) Outcome for cancer patients requiring mechanical ventilation. J Clin Oncol 17:991–997PubMedGoogle Scholar
  9. 9.
    Azoulay E, Alberti C, Bornstain C, Leleu G, Moreau D, Recher C, Chevret S, Le Gall JR, Brochard L, Schlemmer B (2001) Improved survival in cancer patients requiring mechanical ventilatory support: impact of noninvasive mechanical ventilatory support. Crit Care Med 29:519–525PubMedCrossRefGoogle Scholar
  10. 10.
    Mokart D, van Craenenbroeck T, Lambert J, Textoris J, Brun JP, Sannini A, Chow-Chine L, Hamouda S, Fouche L, Ettori F, Faucher M, Blache JL (2012) Prognosis of acute respiratory distress syndrome in neutropenic cancer patients. Eur Respir J 40:169–176PubMedCrossRefGoogle Scholar
  11. 11.
    Tate RM, Repine JE (1983) Neutrophils and the adult respiratory distress syndrome. Am Rev Respir Dis 128:552–559PubMedGoogle Scholar
  12. 12.
    Ognibene FP, Martin SE, Parker MM, Schlesinger T, Roach P, Burch C, Shelhamer JH, Parrillo JE (1986) Adult respiratory distress syndrome in patients with severe neutropenia. N Engl J Med 315:547–551PubMedCrossRefGoogle Scholar
  13. 13.
    Mokart D, Guery BP, Bouabdallah R, Martin C, Blache JL, Arnoulet C, Mege JL (2003) Deactivation of alveolar macrophages in septic neutropenic ARDS. Chest 124:644–652PubMedCrossRefGoogle Scholar
  14. 14.
    Azoulay E, Darmon M, Delclaux C, Fieux F, Bornstain C, Moreau D, Attalah H, Le Gall JR, Schlemmer B (2002) Deterioration of previous acute lung injury during neutropenia recovery. Crit Care Med 30:781–786PubMedCrossRefGoogle Scholar
  15. 15.
    Villar J, Perez-Mendez L, Blanco J, Anon JM, Blanch L, Belda J, Santos-Bouza A, Fernandez RL, Kacmarek RM (2013) A universal definition of ARDS: the PaO2/FiO2 ratio under a standard ventilatory setting—a prospective, multicenter validation study. Intensive Care Med 39:583–592PubMedCrossRefGoogle Scholar
  16. 16.
    Azoulay E, Attalah H, Harf A, Schlemmer B, Delclaux C (2001) Granulocyte colony-stimulating factor or neutrophil-induced pulmonary toxicity: myth or reality? Systematic review of clinical case reports and experimental data. Chest 120:1695–1701PubMedCrossRefGoogle Scholar
  17. 17.
    Azoulay E, Fieux F, Moreau D, Thiery G, Rousselot P, Parrot A, Le Gall JR, Dombret H, Schlemmer B (2003) Acute monocytic leukemia presenting as acute respiratory failure. Am J Respir Crit Care Med 167:1329–1333PubMedCrossRefGoogle Scholar
  18. 18.
    Sharma S, Nadrous HF, Peters SG, Tefferi A, Litzow MR, Aubry MC, Afessa B (2005) Pulmonary complications in adult blood and marrow transplant recipients: autopsy findings. Chest 128:1385–1392PubMedCrossRefGoogle Scholar
  19. 19.
    Azoulay E, Mokart D, Pene F, Lambert J, Kouatchet A, Mayaux J, Vincent F, Nyunga M, Bruneel F, Laisne LM, Rabbat A, Lebert C, Perez P, Chaize M, Renault A, Meert AP, Benoit D, Hamidfar R, Jourdain M, Darmon M, Schlemmer B, Chevret S, Lemiale V (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 31:2810–2818PubMedCrossRefGoogle Scholar
  20. 20.
    Mokart D, Lambert J, Schnell D, Fouche L, Rabbat A, Kouatchet A, Lemiale V, Vincent F, Lengline E, Bruneel F, Pene F, Chevret S, Azoulay E (2013) Delayed intensive care unit admission is associated with increased mortality in patients with cancer with acute respiratory failure. Leuk Lymphoma 54:1724–1729PubMedCrossRefGoogle Scholar
  21. 21.
    Phua J, Badia JR, Adhikari NK, Friedrich JO, Fowler RA, Singh JM, Scales DC, Stather DR, Li A, Jones A, Gattas DJ, Hallett D, Tomlinson G, Stewart TE, Ferguson ND (2009) Has mortality from acute respiratory distress syndrome decreased over time?: a systematic review. Am J Respir Crit Care Med 179:220–227PubMedCrossRefGoogle Scholar
  22. 22.
    Schmidt M, Zogheib E, Roze H, Repesse X, Lebreton G, Luyt CE, Trouillet JL, Brechot N, Nieszkowska A, Dupont H, Ouattara A, Leprince P, Chastre J, Combes A (2013) The PRESERVE mortality risk score and analysis of long-term outcomes after extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. Intensive Care Med 39:1704–1713PubMedCrossRefGoogle Scholar
  23. 23.
    Soubani AO, Shehada E, Chen W, Smith D (2014) The outcome of cancer patients with acute respiratory distress syndrome. J Crit Care 29:183 e7–183 e12CrossRefGoogle Scholar
  24. 24.
    Turkoglu M, Erdem GU, Suyani E, Sancar ME, Yalcin MM, Aygencel G, Aki Z, Sucak G (2013) Acute respiratory distress syndrome in patients with hematological malignancies. Hematology 18:123–130PubMedCrossRefGoogle Scholar
  25. 25.
    Ferguson ND, Fan E, Camporota L, Antonelli M, Anzueto A, Beale R, Brochard L, Brower R, Esteban A, Gattinoni L, Rhodes A, Slutsky AS, Vincent JL, Rubenfeld GD, Thompson BT, Ranieri VM (2012) The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material. Intensive Care Med 38:1573–1582PubMedCrossRefGoogle Scholar
  26. 26.
    Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS (2012) Acute respiratory distress syndrome: the Berlin definition. JAMA 307:2526–2533PubMedGoogle Scholar
  27. 27.
    Pene F, Percheron S, Lemiale V, Viallon V, Claessens YE, Marque S, Charpentier J, Angus DC, Cariou A, Chiche JD, Mira JP (2008) Temporal changes in management and outcome of septic shock in patients with malignancies in the intensive care unit. Crit Care Med 36:690–696PubMedCrossRefGoogle Scholar
  28. 28.
    Legrand M, Max A, Peigne V, Mariotte E, Canet E, Debrumetz A, Lemiale V, Seguin A, Darmon M, Schlemmer B, Azoulay E (2012) Survival in neutropenic patients with severe sepsis or septic shock. Crit Care Med 40:43–49PubMedCrossRefGoogle Scholar
  29. 29.
    De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, Pappas PG, Maertens J, Lortholary O, Kauffman CA, Denning DW, Patterson TF, Maschmeyer G, Bille J, Dismukes WE, Herbrecht R, Hope WW, Kibbler CC, Kullberg BJ, Marr KA, Munoz P, Odds FC, Perfect JR, Restrepo A, Ruhnke M, Segal BH, Sobel JD, Sorrell TC, Viscoli C, Wingard JR, Zaoutis T, Bennett JE (2008) Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) consensus group. Clin Infect Dis 46:1813–1821PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R (2013) Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 39:165–228PubMedCrossRefGoogle Scholar
  31. 31.
    Vesin A, Azoulay E, Ruckly S, Vignoud L, Rusinova K, Benoit D, Soares M, Azeivedo-Maia P, Abroug F, Benbenishty J, Timsit JF (2013) Reporting and handling missing values in clinical studies in intensive care units. Intensive Care Med 39:1396–1404PubMedCrossRefGoogle Scholar
  32. 32.
    Guerin C, Reignier J, Richard JC, Beuret P, Gacouin A, Boulain T, Mercier E, Badet M, Mercat A, Baudin O, Clavel M, Chatellier D, Jaber S, Rosselli S, Mancebo J, Sirodot M, Hilbert G, Bengler C, Richecoeur J, Gainnier M, Bayle F, Bourdin G, Leray V, Girard R, Baboi L, Ayzac L (2013) Prone positioning in severe acute respiratory distress syndrome. N Engl J Med 368:2159–2168PubMedCrossRefGoogle Scholar
  33. 33.
    Hernu R, Wallet F, Thiolliere F, Martin O, Richard JC, Schmitt Z, Wallon G, Delannoy B, Rimmele T, Demaret C, Magnin C, Vallin H, Lepape A, Baboi L, Argaud L, Piriou V, Allaouchiche B, Aubrun F, Bastien O, Lehot JJ, Ayzac L, Guerin C (2013) An attempt to validate the modification of the American-European consensus definition of acute lung injury/acute respiratory distress syndrome by the Berlin definition in a university hospital. Intensive Care Med 39:2161–2170PubMedCrossRefGoogle Scholar
  34. 34.
    Azoulay E, Canet E, Raffoux E, Lengline E, Lemiale V, Vincent F, de Labarthe A, Seguin A, Boissel N, Dombret H, Schlemmer B (2012) Dexamethasone in patients with acute lung injury from acute monocytic leukaemia. Eur Respir J 39:648–653PubMedCrossRefGoogle Scholar
  35. 35.
    Moreau AS, Lengline E, Seguin A, Lemiale V, Canet E, Raffoux E, Schlemmer B, Azoulay E (2014) Respiratory events at the earliest phase of acute myeloid leukemia. Leuk LymphomaGoogle Scholar
  36. 36.
    Pene F, Aubron C, Azoulay E, Blot F, Thiery G, Raynard B, Schlemmer B, Nitenberg G, Buzyn A, Arnaud P, Socie G, Mira JP (2006) Outcome of critically ill allogeneic hematopoietic stem-cell transplantation recipients: a reappraisal of indications for organ failure supports. J Clin Oncol 24:643–649PubMedCrossRefGoogle Scholar
  37. 37.
    Depuydt PO, Benoit DD, Vandewoude KH, Decruyenaere JM, Colardyn FA (2004) Outcome in noninvasively and invasively ventilated hematologic patients with acute respiratory failure. Chest 126:1299–1306PubMedCrossRefGoogle Scholar
  38. 38.
    Delclaux C, L’Her E, Alberti C, Mancebo J, Abroug F, Conti G, Guerin C, Schortgen F, Lefort Y, Antonelli M, Lepage E, Lemaire F, Brochard L (2000) Treatment of acute hypoxemic non hypercapnic respiratory insufficiency with continuous positive airway pressure delivered by a face mask: a randomized controlled trial. JAMA 284:2352–2360PubMedCrossRefGoogle Scholar
  39. 39.
    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 36:2766–2772PubMedCrossRefGoogle Scholar
  40. 40.
    Hilbert G, Gruson D, Vargas F, Valentino R, Gbikpi-Benissan G, Dupon M, Reiffers J, Cardinaud JP (2001) Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure. N Engl J Med 344:481–487PubMedCrossRefGoogle Scholar
  41. 41.
    Azoulay E, Lemiale V (2012) Non-invasive mechanical ventilation in hematology patients with hypoxemic acute respiratory failure: a false belief? Bone Marrow Transplant 47:469–472PubMedCrossRefGoogle Scholar
  42. 42.
    Ullmann AJ, Lipton JH, Vesole DH, Chandrasekar P, Langston A, Tarantolo SR, Greinix H, Morais de Azevedo W, Reddy V, Boparai N, Pedicone L, Patino H, Durrant S (2007) Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med 356:335–347PubMedCrossRefGoogle Scholar
  43. 43.
    Cordonnier C, Pautas C, Maury S, Vekhoff A, Farhat H, Suarez F, Dhedin N, Isnard F, Ades L, Kuhnowski F, Foulet F, Kuentz M, Maison P, Bretagne S, Schwarzinger M (2009) Empirical versus preemptive antifungal therapy for high-risk, febrile, neutropenic patients: a randomized, controlled trial. Clin Infect Dis 48:1042–1051PubMedCrossRefGoogle Scholar
  44. 44.
    Chiumello D, Taccone P, Berto V, Marino A, Migliara G, Lazzerini M, Gattinoni L (2012) Long-term outcomes in survivors of acute respiratory distress syndrome ventilated in supine or prone position. Intensive Care Med 38:221–229PubMedCrossRefGoogle Scholar
  45. 45.
    Gattinoni L, Pesenti A, Carlesso E (2013) Body position changes redistribute lung computed-tomographic density in patients with acute respiratory failure: impact and clinical fallout through the following 20 years. Intensive Care Med 39:1909–1915PubMedCrossRefGoogle Scholar
  46. 46.
    Peigne V, Rusinova K, Karlin L, Darmon M, Fermand JP, Schlemmer B, Azoulay E (2009) Continued survival gains in recent years among critically ill myeloma patients. Intensive Care Med 35:512–518PubMedCrossRefGoogle Scholar
  47. 47.
    Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, Kern WV, Marr KA, Ribaud P, Lortholary O, Sylvester R, Rubin RH, Wingard JR, Stark P, Durand C, Caillot D, Thiel E, Chandrasekar PH, Hodges MR, Schlamm HT, Troke PF, de Pauw B (2002) Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 347:408–415PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2014

Authors and Affiliations

  • Elie Azoulay
    • 1
    • 13
  • Virginie Lemiale
    • 1
  • Djamel Mokart
    • 2
  • Frédéric Pène
    • 3
  • Achille Kouatchet
    • 4
  • Pierre Perez
    • 5
  • François Vincent
    • 6
  • Julien Mayaux
    • 7
  • Dominique Benoit
    • 8
  • Fabrice Bruneel
    • 9
  • Anne-Pascale Meert
    • 10
  • Martine Nyunga
    • 11
  • Antoine Rabbat
    • 3
  • Michael Darmon
    • 12
  1. 1.Intensive Care Unit of the Saint-Louis University HospitalParisFrance
  2. 2.Intensive Care Unit of Institut Paoli CalmetteMarseilleFrance
  3. 3.Intensive Care Unit of Cochin University HospitalParisFrance
  4. 4.Intensive Care Unit of Angers University HospitalAngersFrance
  5. 5.Intensive Care Unit of Nancy University HospitalNancyFrance
  6. 6.Intensive Care Unit of Bobigny University HospitalBobignyFrance
  7. 7.Intensive Care Unit of Pitié-Salpêtrière University HospitalParisFrance
  8. 8.Intensive Care Unit of Ghent University HospitalGhentBelgium
  9. 9.Intensive Care Unit of Versailles HospitalVersaillesFrance
  10. 10.Intensive Care Unit of Brussels University HospitalBrusselsBelgium
  11. 11.Intensive Care Unit of Roubaix HospitalRoubaixFrance
  12. 12.Intensive Care Unit of Saint-Etienne Teaching HospitalSaint-ÉtienneFrance
  13. 13.Sorbonne Paris-Cité, Medical School, AP-HP, Hôpital Saint-Louis, Medical ICUParis-Diderot UniversityParisFrance

Personalised recommendations