Intensive Care Medicine

, Volume 36, Issue 1, pp 33–41

H1N1 influenza A virus-associated acute lung injury: response to combination oseltamivir and prolonged corticosteroid treatment

  • Adolfo Maximo Quispe-Laime
  • Jonas Daniel Bracco
  • Patricia Alejandra Barberio
  • Claudio German Campagne
  • Verónica Edith Rolfo
  • Reba Umberger
  • Gianfranco Umberto Meduri
Original

Abstract

Purpose

During the 2009 H1N1 influenza A virus pandemic, a minority of patients developed rapidly progressive pneumonia leading to acute lung injury (ALI)—acute respiratory distress syndrome (ARDS). A recent meta-analysis provides support for prolonged corticosteroid treatment in ALI-ARDS. We prospectively evaluated the response to oseltamivir and prolonged corticosteroid treatment in patients with ALI-ARDS and suspected H1N1 influenza.

Methods

From June 24 through 12 July 2009, 13 patients with suspected H1N1 pneumonia and ALI-ARDS were admitted to the intensive care unit (ICU) of a tertiary care hospital. H1N1 influenza was confirmed with real-time reverse transcriptase-polymerase chain reaction assay in eight patients. Oseltamivir and corticosteroid treatment were initiated concomitantly at ICU admission; those with severe ARDS received methylprednisolone (1 mg/kg/day), and others received hydrocortisone (300 mg/day) for a duration of 21 ± 6 days.

Results

Patients with and without confirmed H1N1 influenza had similar disease severity at presentation and a comparable response to treatment. By day 7 of treatment, patients experienced a significant improvement in lung injury and multiple organ dysfunction scores (P < 0.001). Twelve patients (92%) improved lung function, were extubated, and discharged alive from the ICU. Hospital length of stay and mortality were 18.7 ± 9.6 days and 15%, respectively. Survivors were discharged home without oxygen supplementation.

Conclusions

In ARDS patients, with and without confirmed H1N1 influenza, prolonged low-to-moderate dose corticosteroid treatment was well tolerated and associated with significant improvement in lung injury and multiple organ dysfunction scores and a low hospital mortality. These findings provide the rationale for developing a randomized trial.

Keywords

H1N1 influenza A virus Acute respiratory distress syndrome Corticosteroid treatment Mechanical ventilation Mortality 

References

  1. 1.
    Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, Hernandez M, Quinones-Falconi F, Bautista E, Ramirez-Venegas A, Rojas-Serrano J, Ormsby CE, Corrales A, Higuera A, Mondragon E, Cordova-Villalobos JA (2009) Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico. N Engl J Med 361:680–689CrossRefPubMedGoogle Scholar
  2. 2.
    Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, Hernandez M, Quinones-Falconi F, Bautista E, Ramirez-Venegas A, Rojas-Serrano J, Ormsby CE, Corrales A, Higuera A, Mondragon E, Cordova-Villalobos JA (2009) Intensive-care patients with severe novel influenza A (H1N1) virus infection—Michigan, June 2009. MMWR Morb Mortal Wkly Rep 58:749–752Google Scholar
  3. 3.
    Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, Garten RJ, Gubareva LV, Xu X, Bridges CB, Uyeki TM (2009) Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 360:2605–2615CrossRefPubMedGoogle Scholar
  4. 4.
    Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, Garten RJ, Gubareva LV, Xu X, Bridges CB, Uyeki TM (2009) Hospitalized patients with novel influenza A (H1N1) virus infection—California, April–May, 2009. MMWR Morb Mortal Wkly Rep 58:536–541Google Scholar
  5. 5.
    Rello J, Rodriguez A, Ibanez P, Socias L, Cebrian J, group THNSw (2009) Intensive care adult patients with severe respiratory failure caused by Influenza A (H1N1)v in Spain. Crit Care 13:R148. http://ccforum.com/content/13/5/R148
  6. 6.
    Domínguez-Cherit G, Lapinsky S, Macias A, Pinto R, Espinosa-Perez L, de la Torre A, Poblano-Morales M, Baltazar-Torres J, Bautista E, Martinez A, Martinez M, Rivero E, Valdez R, Ruiz-Palacios G, Hernández M, Stewart T, Fowler R (2009) Critically ill patients with 2009 influenza A(H1N1) in Mexico. JAMA 302:1880–1887. doi:10.1001/jama.2009.1536 CrossRefPubMedGoogle Scholar
  7. 7.
    Kumar A, Zarychanski R, Pinto R, Cook D, Marshall J, Lacroix J, Stelfox T, Bagshaw S, Choong K, Lamontagne F, Turgeon A, Lapinsky S, Ahern S, Smith O, Siddiqui F, Jouvet P, Khwaja K, McIntyre L, Menon K, Hutchison J, Hornstein D, Joffe A, Lauzier F, Singh J, Karachi T, Wiebe K, Olafson K, Ramsey C, Sharma S, Dodek P, Meade M, Hall R, Fowler R, Collaborative ftCCCTGHN (2009) Critically ill patients with 2009 influenza A(H1N1) infection in Canada. JAMA 302:1872–1879. doi:10.1001/jama.2009.1496 CrossRefPubMedGoogle Scholar
  8. 8.
    Carter MJ (2007) A rationale for using steroids in the treatment of severe cases of H5N1 avian influenza. J Med Microbiol 56:875–883CrossRefPubMedGoogle Scholar
  9. 9.
    Van Reeth K, Van Gucht S, Pensaert M (2002) Correlations between lung proinflammatory cytokine levels, virus replication, and disease after swine influenza virus challenge of vaccination-immune pigs. Viral Immunol 15:583–594CrossRefPubMedGoogle Scholar
  10. 10.
    de Jong MD, Simmons CP, Thanh TT, Hien VM, Smith GJ, Chau TN, Hoang DM, Chau NV, Khanh TH, Dong VC, Qui PT, Cam BV, Ha do Q, Guan Y, Peiris JS, Chinh NT, Hien TT, Farrar J (2006) Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat Med 12:1203–1207CrossRefPubMedGoogle Scholar
  11. 11.
    Itoh Y, Shinya K, Kiso M, Watanabe T, Sakoda Y, Hatta M, Muramoto Y, Tamura D, Sakai-Tagawa Y, Noda T, Sakabe S, Imai M, Hatta Y, Watanabe S, Li C, Yamada S, Fujii K, Murakami S, Imai H, Kakugawa S, Ito M, Takano R, Iwatsuki-Horimoto K, Shimojima M, Horimoto T, Goto H, Takahashi K, Makino A, Ishigaki H, Nakayama M, Okamatsu M, Warshauer D, Shult PA, Saito R, Suzuki H, Furuta Y, Yamashita M, Mitamura K, Nakano K, Nakamura M, Brockman-Schneider R, Mitamura H, Yamazaki M, Sugaya N, Suresh M, Ozawa M, Neumann G, Gern J, Kida H, Ogasawara K, Kawaoka Y (2009) In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature 460:1021–1025PubMedGoogle Scholar
  12. 12.
    Rhen T, Cidlowski JA (2005) Antiinflammatory action of glucocorticoids—new mechanisms for old drugs. N Engl J Med 353:1711–1723CrossRefPubMedGoogle Scholar
  13. 13.
    Marik PE, Pastores S, Annane D, Meduri G, Sprung C, Arlt W, Keh D, Briegel J, Beishuizen A, Dimopoulou I, Tsagarakis S, Singer M, Chrousos GP, Zaloga GP, Bokhari F, Vogeser M (2008) Clinical practice guidelines for the diagnosis and management of corticosteroid insufficiency in critical illness: recommendations of an international task force. Crit Care Med 36:1937–1949CrossRefPubMedGoogle Scholar
  14. 14.
    Meduri GU, Tolley EA, Chrousos GP, Stentz F (2002) Prolonged methylprednisolone treatment suppresses systemic inflammation in patients with unresolving acute respiratory distress syndrome. Evidence for inadequate endogenous glucocorticoid secretion and inflammation-induced immune cell resistance to glucocorticoids. Am J Respir Crit Care Med 165:983–991PubMedGoogle Scholar
  15. 15.
    Meduri G, Annane D, Chrousos G, Marik P, Sinclair S (2009) Activation and regulation of systemic inflammation in ARDS: rationale for prolonged glucocorticoid therapy. Chest 136. doi:10.1378/chest.1308-2408
  16. 16.
    (August 7, 2009) Report to the President on US preparation for 2009-H1N1 Influenza. Office of the Press SecretaryGoogle Scholar
  17. 17.
    Yam LY, Lau AC, Lai FY, Shung E, Chan J, Wong V (2007) Corticosteroid treatment of severe acute respiratory syndrome in Hong Kong. J Infect 54:28–39CrossRefPubMedGoogle Scholar
  18. 18.
    Chen RC, Tang XP, Tan SY, Liang BL, Wan ZY, Fang JQ, Zhong N (2006) Treatment of severe acute respiratory syndrome with glucosteroids: the Guangzhou experience. Chest 129:1441–1452CrossRefPubMedGoogle Scholar
  19. 19.
    Cheng VC, Tang BS, Wu AK, Chu CM, Yuen KY (2004) Medical treatment of viral pneumonia including SARS in immunocompetent adult. J Infect 49:262–273CrossRefPubMedGoogle Scholar
  20. 20.
    Stockman LJ, Bellamy R, Garner P (2006) SARS: systematic review of treatment effects. PLoS Med 3:e343CrossRefPubMedGoogle Scholar
  21. 21.
    Confalonieri M, Urbino R, Potena A, Piattella M, Parigi P, Puccio G, Della Porta R, Giorgio C, Blasi F, Umberger R, Meduri GU (2005) Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study. Am J Respir Crit Care Med 171:242–248CrossRefPubMedGoogle Scholar
  22. 22.
    Annane D, Sebille V, Bellissant E (2006) Effect of low doses of corticosteroids in septic shock patients with or without early acute respiratory distress syndrome. Crit Care Med 34:22–30CrossRefPubMedGoogle Scholar
  23. 23.
    Meduri GU, Golden E, Freire AX, Taylor E, Zaman M, Carson SJ, Gibson MRU (2007) Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial. Chest 131:954–963CrossRefPubMedGoogle Scholar
  24. 24.
    Meduri GU, Marik PE, Chrousos GP, Pastores SM, Arlt W, Beishuizen A, Bokhari F, Zaloga G, Annane D (2008) Steroid treatment in ARDS: a critical appraisal of the ARDS network trial and the recent literature. Intensive Care Med 34:61–69CrossRefPubMedGoogle Scholar
  25. 25.
    Tang B, Craig J, Eslick G, Seppelt I, McLean A (2009) Use of corticosteroids in acute lung injury and acute respiratory distress syndrome: a systematic review and meta-analysis. Crit Care Med 37:1594–1603CrossRefPubMedGoogle Scholar
  26. 26.
    Tang B, Craig J, Eslick G, Seppelt I, McLean A (2009) World Health Organization. Pandemic (H1N1) 2009—update 58, 6 July 2009Google Scholar
  27. 27.
    Tang B, Craig J, Eslick G, Seppelt I, McLean A (2009) United States Centers for Disease Control and Prevention. Interim guidance on specimen collection, processing, and testing for patients with suspected swine-origin influenza A (H1N1) virus infection. http://www.cdc.gov/h1n1flu/specimencollection.htm
  28. 28.
    Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a severity of disease classification system. Crit Care Med 13:818–829CrossRefPubMedGoogle Scholar
  29. 29.
    Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG (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 22:707–710CrossRefPubMedGoogle Scholar
  30. 30.
    Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A, Spragg R (1994) The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 149:818–824PubMedGoogle Scholar
  31. 31.
    Murray JF, Matthay MA, Luce JM, Flick MR (1988) An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis 138:720–723PubMedGoogle Scholar
  32. 32.
    Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, Torres A, Whitney CG (2007) Infectious diseases society of America/American thoracic society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 44(Suppl 2):S27–S72CrossRefPubMedGoogle Scholar
  33. 33.
    Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaut P, Bellissant E (2002) Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288:862–871CrossRefPubMedGoogle Scholar
  34. 34.
    Annane D, Bellissant E, Bollaert PE, Briegel J, Confalonieri M, De Gaudio R, Keh D, Kupfer Y, Oppert M, Meduri GU (2009) Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review. JAMA 301:2362–2375CrossRefPubMedGoogle Scholar
  35. 35.
    Nawab Q, Golden E, Confalonieri M, Umberger R, Meduri G (2007) Glucocorticoid treatment in severe community-acquired pneumonia. Am J Respir Crit Care Med 175:A594Google Scholar
  36. 36.
    Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL (2008) Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 34:17–60CrossRefPubMedGoogle Scholar
  37. 37.
    Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 342:1301–1308CrossRefGoogle Scholar
  38. 38.
    Ferguson ND, Kacmarek RM, Chiche JD, Singh JM, Hallett DC, Mehta S, Stewart TE (2004) Screening of ARDS patients using standardized ventilator settings: influence on enrollment in a clinical trial. Intensive Care Med 30:1111–1116CrossRefPubMedGoogle Scholar
  39. 39.
    Meduri GU, Muthiah MP, Carratu P, Eltorky M, Chrousos GP (2005) Nuclear factor-kappaB—and glucocorticoid receptor alpha—mediated mechanisms in the regulation of systemic and pulmonary inflammation during sepsis and acute respiratory distress syndrome. Evidence for inflammation-induced target tissue resistance to glucocorticoids. Neuroimmunomodulation 12:321–338CrossRefPubMedGoogle Scholar
  40. 40.
    Meduri G, Marik P, Annane D (2009) Prolonged glucocorticoid treatment in ARDS: evidence supporting effectiveness and safety. Crit Care Med 37:1800–1803CrossRefPubMedGoogle Scholar

Copyright information

© Copyright jointly hold by Springer and ESICM 2009

Authors and Affiliations

  • Adolfo Maximo Quispe-Laime
    • 1
  • Jonas Daniel Bracco
    • 1
  • Patricia Alejandra Barberio
    • 1
  • Claudio German Campagne
    • 1
  • Verónica Edith Rolfo
    • 1
  • Reba Umberger
    • 2
  • Gianfranco Umberto Meduri
    • 2
    • 3
  1. 1.Medical Intensive Care Unit, Dr. Leonidas Lucero Acute Municipal HospitalUniversidad Nacional del SurBahia BlancaArgentina
  2. 2.Memphis Veterans Affairs Medical CenterMemphisUSA
  3. 3.Division of Pulmonary, Critical Care, and Sleep MedicineUniversity of Tennessee Health Science CenterMemphisUSA

Personalised recommendations