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01-01-2008 | Clinical Commentary

Steroid treatment in ARDS: a critical appraisal of the ARDS network trial and the recent literature

Authors: G. Umberto Meduri, Paul E. Marik, George P. Chrousos, Stephen M. Pastores, Wiebke Arlt, Albertus Beishuizen, Faran Bokhari, Gary Zaloga, Djillali Annane

Published in: Intensive Care Medicine | Issue 1/2008

Abstract

Objectives

To compare the design and results of randomized trials investigating prolonged glucocorticoid treatment (≥ 7 days) in patients with acute lung injury–acute respiratory distress syndrome (ALI–ARDS), and review factors affecting response to therapy, including the role of secondary prevention.

Design

Trials were retrieved from the Cochrane Central Register of Controlled Trials (CENTRAL). Two investigators collected data on study characteristics, treatment intervention, and outcomes. The methodological quality of trials was determined and data were analyzed with Review Manager 4.2.3.

Measurements and results

Five selected trials (n = 518) consistently reported significant improvement in gas exchange, reduction in markers of inflammation, and decreased duration of mechanical ventilation and intensive care unit stay (all p < 0.05). Two early small clinical trials showed marked reductions in the relative risk (RR) of death with glucocorticoid therapy (RR = 0.14, 95% CI 0.04–0.53; p = 0.004, I² = 0%). Three subsequent larger trials, when combined, although nominally beneficial, did not reproduce the marked reductions observed in the earlier trials (RR = 0.84; 95% CI 0.68–1.03; p = 0.09, I² = 9.1%), but achieved a distinct reduction in the RR of death in the larger subgroup of patients (n = 400) treated before day 14 of ARDS [82/214 (38%) vs. 98/186 (52.5%), RR = 0.78; 95% CI 0.64–0.96; p = 0.02, I² = 0%].

Conclusions

Prolonged glucocorticoid treatment substantially and significantly improves meaningful patient-centered outcome variables, and has a distinct survival benefit when initiated before day 14 of ARDS.

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 12:321–338PubMedCrossRef

Meduri GU, Yates CR (2004) Systemic inflammation-associated glucocorticoid resistance and outcome of ARDS. Ann N Y Acad Sci 1024:24–53PubMedCrossRef

Parsons PE, Eisner MD, Thompson BT, Matthay MA, Ancukiewicz M, Bernard GR, Wheeler AP (2005) Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury. Crit Care Med 33:1–6PubMedCrossRef

Sinclair S, Bijoy J, Golden E, Carratu P, Umberger R, Meduri GU (2006) Interleukin-8 and soluble intercellular adhesion molecule-1 during acute respiratory distress syndrome and in response to prolonged methylprednisolone treatment. Minerva Pneumol 45:93–104

Bone RC, Maunder R, Slotman G, Silverman H, Hyers TM, Kerstein MD, Ursprung JJ (1989) An early test of survival in patients with the adult respiratory distress syndrome. The PaO₂/FiO₂ ratio and its differential response to conventional therapy. Prostaglandin E1 Study Group. Chest 96:849–851PubMedCrossRef

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 317:1565–1570PubMedCrossRef

Meduri GU (1997) Host defense response and outcome in ARDS. Chest 112:1154–1158PubMed

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 165:983–991PubMed

Meduri GU, Headley S, Golden E, Carson S, Umberger R, Kelso T, Tolley E (1998) Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome. A randomized controlled trial. JAMA 280:159–165PubMedCrossRef

10.

Meduri GU, Tolley EA, Chinn A, Stentz F, Postlethwaite A (1998) Procollagen types I and III aminoterminal propeptide levels during acute respiratory distress syndrome and in response to methylprednisolone treatment. Am J Respir Crit Care Med 158:1432–1441PubMed

11.

Wheeler A, Bernard GR, Schoenfeld D, Steinberg K (1998) Methylprednisolone for unresolving ARDS. JAMA 280:2074PubMedCrossRef

12.

Steinberg KP, Hudson LD, Goodman RB, Hough CL, Lanken PN, Hyzy R, Thompson BT, Ancukiewicz M (2006) Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 354:1671–1684PubMedCrossRef

13.

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 171:242–248PubMedCrossRef

14.

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 34:22–30PubMedCrossRef

15.

Meduri GU, Golden E, Freire AX, Taylor E , Zaman M , Carson SJ, Gibson M, Umberger R (2007) Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial. Chest 131:954–963PubMedCrossRef

16.

Meduri GU (1999) An historical review of glucocorticoid treatment in sepsis. Disease pathophysiology and the design of treatment investigation. Sepsis 3:21–38CrossRef

17.

Bower G, Matthay M (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 342:1301–1308CrossRef

18.

Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF Jr., Hite RD, Harabin AL (2006) Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 354:2564–2575PubMedCrossRef

19.

Rosenberg J, Lysz K (1977) An in vitro study of how much methylprednisolone is needed to produce immunosuppression. Proc Clin Dial Transplant Forum 7:23–28PubMed

20.

Keh D BT, Weber-Cartens S, Schulz C, Ahlers O, Bercker S, Volk HD, Doecke WD, Falke KJ, Gerlach H (2003) Immunologic and hemodynamic effects of “low-dose” hydrocortisone in septic shock: a double-blind, randomized, placebo-controlled, crossover study. Am J Respir Crit Care Med 167:512–520PubMedCrossRef

21.

Yates CR, Vysokanov A, Mukherjee A, Ludden TM, Tolley EA, Meduri GU, Dalton JT (2001) Time-variant increase in methylprednisolone clearance in patients with acute respiratory distress syndrome: A population pharmocokinetic study. J Clin Pharmacol 41:1–10

22.

Hesterberg TW, Last JA (1981) Ozone-induced acute pulmonary fibrosis in rats. Prevention of increased rates of collagen synthesis by methylprednisolone. Am Rev Respir Dis 123:47–52PubMed

23.

Hakkinen PJ, Schmoyer RL, Witschi HP (1983) Potentiation of butylated-hydroxytoluene-induced acute lung damage by oxygen. Effects of prednisolone and indomethacin. Am Rev Respir Dis 128:648–651PubMed

24.

Kehrer JP, Klein-Szanto AJ, Sorensen EM, Pearlman R, Rosner MH (1984) Enhanced acute lung damage following corticosteroid treatment. Am Rev Respir Dis 130:256–261PubMed

25.

Ashbaugh DG, Maier RV (1985) Idiopathic pulmonary fibrosis in adult respiratory distress syndrome. Diagnosis and treatment. Arch Surg 120:530–535PubMed

26.

Hooper RG, Kearl RA (1990) Established ARDS treated with a sustained course of adrenocortical steroids. Chest 97:138–143PubMedCrossRef

27.

Briegel J, Jochum M, Gippner-Steppert C, Thiel M (2001) Immunomodulation in septic shock: hydrocortisone differentially regulates cytokine responses. J Am Soc Nephrol 12(Suppl 17):S70–74PubMed

28.

Barber AE, Coyle SM, Fischer E, Smith C, van der Poll T, Shires GT, Lowry SF (1995) Influence of hypercortisolemia on soluble tumor necrosis factor receptor II and interleukin-1 receptor antagonist responses to endotoxin in human beings. Surgery 118:406–410PubMedCrossRef

29.

Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ, Hudson LD (2005) Incidence and outcomes of acute lung injury. N Engl J Med 353:1685–1693PubMedCrossRef

30.

Bollen CW, Uiterwaal CS, van Vught AJ (2006) Systematic review of determinants of mortality in high frequency oscillatory ventilation in acute respiratory distress syndrome. Crit Care 10:R34PubMedCrossRef

31.

Luecke T, Muench E, Roth H, Friess U, Paul T, Kleinhuber K, Quintel M (2006) Predictors of mortality in ARDS patients referred to a tertiary care centre: a pilot study. Eur J Anaesthesiol 23:403–410PubMedCrossRef

32.

Agarwal R, Aggarwal AN, Gupta D, Behera D, Jindal SK (2006) Etiology and outcomes of pulmonary and extrapulmonary acute lung injury/ARDS in a respiratory ICU in North India. Chest 130:724–729PubMedCrossRef

33.

Heffner JE, Brown LK, Barbieri CA, Harpel KS, DeLeo J (1995) Prospective validation of an acute respiratory distress syndrome predictive score. Am J Respir Crit Care Med 152(5 Pt 1):1518–1526PubMed

34.

Roca O, Sacanell J, Laborda C, Perez M, Sabater J, Burgueno MJ, Dominguez L, Masclans JR (2006) Cohort study on incidence of ARDS in patients admitted to the ICU and prognostic factors of mortality. Med Intensiva 30:6–12PubMedCrossRef

35.

Salim A, Martin M, Constantinou C, Sangthong B, Brown C, Kasotakis G, Demetriades D, Belzberg H (2006) Acute respiratory distress syndrome in the trauma intensive care unit: morbid but not mortal. Arch Surg 141:655–658PubMedCrossRef

36.

Leatherman JW, Fluegel WL, David WS, Davies SF, Iber C (1996) Muscle weakness in mechanically ventilated patients with severe asthma. Am J Respir Crit Care Med 153:1686–1690PubMed

37.

De Jonghe B, Bastuji-Garin S, Sharshar T, Outin H, Brochard L (2004) Does ICU-acquired paresis lengthen weaning from mechanical ventilation? Intensive Care Med 30:1117–1121PubMedCrossRef

38.

Meduri GU (2007) There is no illumination in speculation. Additional data in support of methylprednisolone treatment in ARDS. Chest 132:1097–1100CrossRef

39.

Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F, Cooper AB, Guest CB, Mazer CD, Mehta S, Stewart TE, Barr A, Cook D, Slutsky AS (2003) One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med 348:683–693PubMedCrossRef

40.

Jantz MA, Sahn SA (1999) Corticosteroids in acute respiratory failure. Am J Respir Crit Care Med 160:1079–1100PubMed

41.

Cronin L, Cook DJ, Carlet J, Heyland DK, King D, Lansang MA, Fisher CJ Jr (1995) Corticosteroid treatment for sepsis: a critical appraisal and meta-analysis of the literature. Crit Care Med 23:1430–1439PubMedCrossRef

42.

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 288:862–871PubMedCrossRef

Title: Steroid treatment in ARDS: a critical appraisal of the ARDS network trial and the recent literature
Authors: G. Umberto Meduri
Paul E. Marik
George P. Chrousos
Stephen M. Pastores
Wiebke Arlt
Albertus Beishuizen
Faran Bokhari
Gary Zaloga
Djillali Annane
Publication date: 01-01-2008
Publisher: Springer-Verlag
Published in: Intensive Care Medicine / Issue 1/2008
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-007-0933-3

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Steroid treatment in ARDS: a critical appraisal of the ARDS network trial and the recent literature

Abstract

Objectives

Design

Measurements and results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Objectives

Design

Measurements and results

Conclusions

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