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Use of early corticosteroid therapy on ICU admission in patients affected by severe pandemic (H1N1)v influenza A infection

I. Martin-Loeches| T. Lisboa| A. Rhodes| R. P. Moreno| E. Silva| C. Sprung| J. D. Chiche| D. Barahona| M. Villabon| C. Balasini| R. M. Pearse| R. Matos| J. Rello
Original
Volume 37, Issue 2 / February , 2011

Pages 272 - 283

Abstract

Introduction

Early use of corticosteroids in patients affected by pandemic (H1N1)v influenza A infection, although relatively common, remains controversial.

Methods

Prospective, observational, multicenter study from 23 June 2009 through 11 February 2010, reported in the European Society of Intensive Care Medicine (ESICM) H1N1 registry.

Results

Two hundred twenty patients admitted to an intensive care unit (ICU) with completed outcome data were analyzed. Invasive mechanical ventilation was used in 155 (70.5%). Sixty-seven (30.5%) of the patients died in ICU and 75 (34.1%) whilst in hospital. One hundred twenty-six (57.3%) patients received corticosteroid therapy on admission to ICU. Patients who received corticosteroids were significantly older and were more likely to have coexisting asthma, chronic obstructive pulmonary disease (COPD), and chronic steroid use. These patients receiving corticosteroids had increased likelihood of developing hospital-acquired pneumonia (HAP) [26.2% versus 13.8%, p < 0.05; odds ratio (OR) 2.2, confidence interval (CI) 1.1–4.5]. Patients who received corticosteroids had significantly higher ICU mortality than patients who did not (46.0% versus 18.1%, p < 0.01; OR 3.8, CI 2.1–7.2). Cox regression analysis adjusted for severity and potential confounding factors identified that early use of corticosteroids was not significantly associated with mortality [hazard ratio (HR) 1.3, 95% CI 0.7–2.4, p = 0.4] but was still associated with an increased rate of HAP (OR 2.2, 95% CI 1.0–4.8, p < 0.05). When only patients developing acute respiratory distress syndrome (ARDS) were analyzed, similar results were observed.

Conclusions

Early use of corticosteroids in patients affected by pandemic (H1N1)v influenza A infection did not result in better outcomes and was associated with increased risk of superinfections.

Keywords

References

  1. Rello J, Rodríguez A, Ibañez P, Socias L, Cebrian J, Marques A, Guerrero J, Ruiz-Santana S, Marquez E, Del Nogal-Saez F, Alvarez-Lerma F, Martínez S, Ferrer M, Avellanas M, Granada R, Maraví-Poma E, Albert P, Sierra R, Vidaur L, Ortiz P, Prieto del Portillo I, Galván B, León-Gil C: H1N1 SEMICYUC Working Group (2009) Intensive care adult patients with severe respiratory failure caused by Influenza A (H1N1)v in Spain. Crit Care 13:R148
    • View reference on publisher's website
    • View reference on PubMed
  2. Kumar A, Zarychanski R, Pinto R, Cook DJ, Marshall J, Lacroix J, Stelfox T, Bagshaw S, Choong K, Lamontagne F, Turgeon AF, Lapinsky S, Ahern SP, 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 RA: Canadian Critical Care Trials Group H1N1 Collaborative (2009) Critically ill patients with 2009 influenza A(H1N1) infection in Canada. JAMA 302:1872–1879
    • View reference on publisher's website
    • View reference on PubMed
  3. The ANZIC Influenza Investigators (2009) Critical care services and 2009 H1N1 influenza in Australia and New Zealand. N Engl J Med 361:1925–1934
    • View reference on publisher's website
  4. Estenssoro E, Ríos FG, Apezteguía C, Reina R, Neira J, Ceraso DH, Orlandi C, Valentini R, Tiribelli N, Brizuela M, Balasini C, Mare S, Domeniconi G, Ilutovich S, Gomez A, Giuliani J, Barrios C, Valdez P (2010) Pandemic 2009 Influenza A(H1N1) in Argentina: a study of 337 patients on mechanical ventilation. Am J Respir Crit Care Med. doi:10.1164/rccm.201001-0037OC
  5. Davis WB, Wilson HE, Wall RL (1986) Eosinophilic alveolitis in acute respiratory failure. A clinical marker for a non-infectious etiology. Chest 90:7–10
    • View reference on publisher's website
    • View reference on PubMed
  6. Luce JM, Montgomery AB, Marks JD, Turner J, Metz CA, Murray JF (1988) Ineffectiveness of high-dose methylprednisolone in preventing parenchymal lung injury and improving mortality in patients with septic shock. Am Rev Respir Dis 138:62–68
    • View reference on PubMed
  7. Bernard GR, Luce JM, Sprung CL, Rinaldo JE, Tate RM, Sibbald WJ, Kariman K, Higgins S, Bradley R, Metz CA (1987) High dose corticosteroids in patients with the adult respiratory distress syndrome. N Engl J Med 317:1565–1570
    • View reference on publisher's website
    • View reference on PubMed
  8. Calfee CS, Matthay MA (2007) Nonventilatory treatments for acute lung injury and ARDS. Chest 131:913–920
    • View reference on publisher's website
    • View reference on PubMed
  9. 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 34:61–69
  10. Agarwal R, Nath A, Aggarwal AN, Gupta D (2007) Do glucocorticoids decrease mortality in acute respiratory distress syndrome? A meta-analysis. Respirology 12:585–590
    • View reference on publisher's website
    • View reference on PubMed
  11. Tang BM, Craig JC, Eslick GD, Seppelt I, McLean AS (2009) Use of corticosteroid in acute lung injury and acute respiratory distress syndrome: a systematic review and meta-analysis. Crit Care Med 37:1594–1603
    • View reference on publisher's website
    • View reference on PubMed
  12. Webb SAR, Seppelt IM, for the ANZIC Influenza Investigators (2009) Pandemic (H1N1) 2009 influenza (“swine flu”) in Australian and New Zealand intensive care. Crit Care Resusc 11:170–172
  13. Bermejo-Martin JF, Ortiz de Lejarazu R, Pumarola T, Rello J, Almansa R, Ramírez P, Martin-Loeches I, Varillas D, Gallegos MC, Serón C, Micheloud D, Gomez JM, Tenorio-Abreu A, Ramos MJ, Molina ML, Huidobro S, Sanchez E, Gordón M, Fernández V, Del Castillo A, Marcos MA, Villanueva B, López CJ, Rodríguez-Domínguez M, Galan JC, Cantón R, Lietor A, Rojo S, Eiros JM, Hinojosa C, Gonzalez I, Torner N, Banner D, Leon A, Cuesta P, Rowe T, Kelvin DJ (2009) Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza. Crit Care 13:R201
    • View reference on publisher's website
    • View reference on PubMed
  14. Domínguez-Cherit G, Lapinsky SE, Macias AE, Pinto R, Espinosa-Perez L, De la Torre A, Poblano-Morales M, Baltazar-Torres JA, Bautista E, Martinez A, Martinez MA, Rivero E, Valdez R, Ruiz-Palacios G, Hernández M, Stewart TE, Fowler RA (2009) Critically ill patients with 2009 influenza A(H1N1) in Mexico. JAMA 302:1880–1887
    • View reference on publisher's website
    • View reference on PubMed
  15. WHO Guidelines for pharmacological management of pandemic Influenza A(H1N1) 2009 and other Influenza viruses. http://www.who.int/csr/resources/publications/swineflu/h1n1_guidelines_pharmaceutical_mngt.pdf
  16. Writing Committee of the WHO Consultation on Clinical Aspects of Pandemic (H1N1) 2009 Influenza, Bautista E, Chotpitayasunondh T, Gao Z, Harper SA, Shaw M, Uyeki TM, Zaki SR, Hayden FG, Hui DS, Kettner JD, Kumar A, Lim M, Shindo N, Penn C, Nicholson KG (2010) Clinical aspects of pandemic 2009 influenza A (H1N1) virus infection. N Engl J Med 362:1708–1719
  17. Salluh JI, Póvoa P (2010) Corticosteroids for H1N1 associated acute lung injury: is it just wishful thinking? Intensive Care Med 36:1098–1099
  18. Quispe-Laime AM, Bracco JD, Barberio PA, Campagne CG, Rolfo VE, Umberger R, Meduri GU (2010) H1N1 influenza A virus-associated acute lung injury: response to combination oseltamivir and prolonged corticosteroid treatment. Intensive Care Med 36:33–41
  19. Infection prevention and control in health care for confirmed or suspected cases of pandemic (H1N1) 2009 and influenza-like illnesses. World Health Organization, June 2009. http://www.who.int/csr/resources/publications/SwineInfluenza_infectioncontrol.pdf
  20. Jamieson DJ, Honein MA, Rasmussen SA, Williams JL, Swerdlow DL, Biggerstaff MS, Lindstrom S, Louie JK, Christ CM, Bohm SR, Fonseca VP, Ritger KA, Kuhles DJ, Eggers P, Bruce H, Davidson HA, Lutterloh E, Harris ML, Burke C, Cocoros N, Finelli L, MacFarlane KF, Shu B, Olsen SJ (2009) Novel Influenza A (H1N1) Pregnancy Working Group. H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet 374:451–458
  21. 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: 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–S72
    • View reference on publisher's website
    • View reference on PubMed
  22. Cate TR (2001) Viral pneumonia due to influenza and parainfluenza viruses and adenoviruses. In: Marrie J Community-acquired pneumonia. Kluwer, New York, pp 593–616
  23. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, Acute Dialysis Quality Initiative workgroup (2004) Acute renal failure—definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 8:R204–R212
  24. Obesity and overweight (http://www.who.int/dietphysicalactivity/publications/facts/obesity/en. Accesed 20th March 2010)
  25. Metnitz PG, Moreno RP, Almeida E, Jordan B, Bauer P, Campos RA, Iapichino G, Edbrooke D, Capuzzo M, Le Gall JR (2005) SAPS 3—from evaluation of the patient to evaluation of the intensive care unit. Part 1: objectives, methods and cohort description. Intensive Care Med 31:1336–1344
  26. Moreno RP, Metnitz PG, Almeida E, Jordan B, Bauer P, Campos RA, Iapichino G, Edbrooke D, Capuzzo M, Le Gall JR (2005) SAPS 3—from evaluation of the patient to evaluation of the intensive care unit. Part 2: development of a prognostic model for hospital mortality at ICU admission. Intensive Care Med 31:1345–1355
  27. Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a severity of disease classification system. Crit Care Med 13:818–829
    • View reference on publisher's website
    • View reference on PubMed
  28. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, Reinhart CK, Suter PM, Thijs LG (1996) The SOFA (Sepsis-Related Organ Failure Assessment) score to describe organ dysfunction/failure. Intensive Care Med 22:707–710
  29. Chrousor GP (1995) The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N Engl J Med 332:1351–1362
    • View reference on publisher's website
  30. Annane D, Sébille V, Troché G, Raphaël JC, Gajdos P, Bellissant E (2000) A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. JAMA 283:1038–1045
    • View reference on publisher's website
    • View reference on PubMed
  31. Marik PE, Pastores SM, Annane D, Meduri GU, Sprung CL, Arlt W, Keh D, Briegel J, Beishuizen A, Dimopoulou I, Tsagarakis S, Singer M, Chrousos GP, Zaloga G, Bokhari F, Vogeser M, American College of Critical Care Medicine (2008) Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med 36:1937–1949
  32. Montón C, Ewig S, Torres A, El-Ebiary M, Filella X, Rañó A, Xaubet A (1999) Role of glucocorticoids on inflammatory response in nonimmunosuppressed patients with pneumonia: a pilot study. Eur Respir J 14:218–220
    • View reference on publisher's website
    • View reference on PubMed
  33. Barnes PJ (2006) Corticosteroid effects on cell signalling. Eur Respir J 27: 413–426
  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 301:2362–2375
    • View reference on publisher's website
    • View reference on PubMed
  35. Minneci PC, Deans KJ, Eichacker PQ, Natanson C (2009) The effects of steroids during sepsis depend on dose and severity of illness: an updated meta-analysis. Clin Microbiol Infect 15:308–318
    • View reference on publisher's website
    • View reference on PubMed
  36. Sligl WI, Milner DA Jr, Sundar S, Mphatswe W, Majumdar SR (2009) Safety and efficacy of corticosteroids for the treatment of septic shock: a systematic review and meta-analysis. Clin Infect Dis 49:93–101
    • View reference on publisher's website
    • View reference on PubMed
  37. 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(2):S27–S72
    • View reference on publisher's website
    • View reference on PubMed
  38. 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 171:242–248
    • View reference on publisher's website
    • View reference on PubMed
  39. Snijders D, Daniels JM, de Graaff CS, van der Werf TS, Boersma WG (2010) Efficacy of corticosteroid in community-acquired pneumonia—a randomized double blinded clinical trial. Am J Respir Crit Care Med. doi:10.1164/rccm.200905-0808OC
  40. Summary of probable SARS cases with onset of illness from 1 November 2002 to 7 August 2003. [http://www.who.int/csr/sars/country/country2003_08_15.pdf]
  41. Zhong NS, Zheng BJ, Li YM, Poon Xie ZH, Chan KH, Li PH, Tan SY, Chang Q, Xie JP, Liu XQ, Xu J, Li DX, Yuen KY, Peiris Guan Y (2003) Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People’s Republic of China, in February, 2003. Lancet 362:1353–1358
    • View reference on publisher's website
    • View reference on PubMed
  42. CDC SARS Investigative Team (2003) Update: outbreak of severe acute respiratory syndrome–worldwide, 2003. MMWR Morb Mortal Wkly Rep 52:269–272
  43. Cameron MJ, Bermejo-Martin JF, Danesh A, Muller MP, Kelvin DJ (2008) Human immunopathogenesis of severe acute respiratory syndrome (SARS). Virus Res 133:13–19
    • View reference on publisher's website
    • View reference on PubMed
  44. Cameron MJ, Ran L, Xu L, Danesh A, Bermejo-Martin JF, Cameron CM, Muller MP, Gold WL, Richardson SE, Poutanen SM, Willey BM, DeVries ME, Fang Y, Seneviratne C, Bosinger SE, Persad D, Wilkinson P, Greller LD, Somogyi R, Humar A, Keshavjee S, Louie M, Loeb MB, Brunton J, McGeer AJ, Canadian SARS Research Network, Kelvin DJ (2007) Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome. J Virol 81:8692–8706
  45. 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 (2006) Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat Med 12:1203–1207
  46. Li XW, Jiang RM, Guo JZ (2003) Glucocorticoid in the treatment of severe acute respiratory syndrome patients: a preliminary report. Chin J Intern Med 42:378–381
  47. Tsang OT, Chau TN, Choi KW, Tso EY, Lim W, Chiu MC, Tong WL, Lee PO, Lam BH, Ng TK, Lai JY, Yu WC, Lai ST (2003) Coronavirus-positive nasopharyngeal aspirate as predictor for severe acute respiratory syndrome mortality. Emerg Infect Dis 9:1381–1387
    • View reference on PubMed
  48. Lee N, Allen Chan KC, Hui DS, Ng EK, Wu A, Chiu RW, Wong VW, Chan PK, Wong KT, Wong E, Cockram CS, Tam JS, Sung JJ, Lo YM (2004) Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients. J Clin Virol 31:304–309
    • View reference on publisher's website
    • View reference on PubMed
  49. Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, Weiss YG, Benbenishty J, Kalenka A, Forst H, Laterre PF, Reinhart K, Cuthbertson BH, Payen D, Briegel J, CORTICUS Study Group (2008) Hydrocortisone therapy for patients with septic shock. N Engl J Med 358:111–124
    • View reference on publisher's website
    • View reference on PubMed
  50. Moreno R, Sprung C, Annane D, Keh D, Singer M, Briegel J, Freivogel K, Weiss Y, Benbenishty J, Kalenka A, Forst H, Laterre P, Reinhart K, Cuthberson B, Payen D (2007) Organ dysfunction/failure in patients with septic shock: results of the CORTICUS study. Intensive Care Med 33:S186
  51. Dehoux MS, Boutten A, Ostinelli J, Seta N, Dombret MC, Crestani B, Deschenes M, Trouillet JL, Aubier M (1994) Compartmentalized cytokine production within the human lung in unilateral pneumonia. Am J Respir Crit Care Med 150:710–716
    • View reference on PubMed
  52. Garcia-Vidal C, Calbo E, Pascual V, Ferrer C, Quintana S, Garau J (2007) Effects of systemic steroids in patients with severe community-acquired pneumonia. Eur Respir J 30:951–956
    • View reference on publisher's website
    • View reference on PubMed
  53. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. (2005) Am J Respir Crit Care Med 171:388–416
  54. Pea F, Viale P (2009) Bench-to-bedside review: appropriate antibiotic therapy in severe sepsis and septic shock—does the dose matter? Crit Care 13:214
    • View reference on publisher's website
    • View reference on PubMed
  55. Ariano RE, Sitar DS, Zelenitsky SA, Zarychanski R, Pisipati A, Ahern S, Kanji S, Rello J, Kumar A (2010) Enteric absorption and pharmacokinetics of oseltamivir in critically ill patients with pandemic (H1N1) influenza. CMAJ 182:357–363
    • View reference on PubMed

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