Corticosteroids in ARDS: A Counterpoint

Abstract

The review article by Calfee and Matthay (March 2007)1Calfee CS Matthay M Nonventilatory treatment for acute lung injury and ARDS.Chest. 2007; : 913-920Abstract Full Text Full Text PDF Scopus (159) Google Scholar provides an incomplete picture of the recent literature on prolonged glucocorticoid treatment in ARDS. Five randomized trials (n = 518) have been published investigating prolonged glucocorticoid (hydrocortisone, 200 to 240 mg/d; methylprednisolone, 1 mg/kg/d) treatment in early acute lung injury (ALI) [Pao2/fraction of inspired oxygen (Fio2) < 300],2Confalonieri M Urbino R Potena A et al.Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study.Am J Respir Crit Care Med. 2005; 171: 242-248Crossref PubMed Scopus (530) Google Scholar early ARDS (Pao2/Fio2 < 200),3Annane D Sebille V Bellissant E Effect of low doses of corticosteroids in septic shock patients with or without early acute respiratory distress syndrome.Crit Care Med. 2006; 34: 22-30Crossref PubMed Scopus (230) Google Scholar4Meduri GU Golden E Freire AX et al.Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial.Chest. 2007; 131: 954-963Abstract Full Text Full Text PDF PubMed Scopus (568) Google Scholar and unresolving ARDS (methylprednisolone, 2 mg/kg/d).5Meduri GU Headley S Golden E et al.Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial.JAMA. 1998; 280: 159-165Crossref PubMed Scopus (829) Google Scholar6The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome.N Engl J Med. 2006; 354: 1671-1684Crossref PubMed Scopus (1066) Google Scholar These trials consistently reported that prolonged glucocorticoid treatment was associated with significant improvement in Pao2/Fio2,2Confalonieri M Urbino R Potena A et al.Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study.Am J Respir Crit Care Med. 2005; 171: 242-248Crossref PubMed Scopus (530) Google Scholar3Annane D Sebille V Bellissant E Effect of low doses of corticosteroids in septic shock patients with or without early acute respiratory distress syndrome.Crit Care Med. 2006; 34: 22-30Crossref PubMed Scopus (230) Google Scholar4Meduri GU Golden E Freire AX et al.Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial.Chest. 2007; 131: 954-963Abstract Full Text Full Text PDF PubMed Scopus (568) Google Scholar5Meduri GU Headley S Golden E et al.Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial.JAMA. 1998; 280: 159-165Crossref PubMed Scopus (829) Google Scholar6The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome.N Engl J Med. 2006; 354: 1671-1684Crossref PubMed Scopus (1066) Google Scholar and a significant reduction in markers of systemic inflammation,2Confalonieri M Urbino R Potena A et al.Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study.Am J Respir Crit Care Med. 2005; 171: 242-248Crossref PubMed Scopus (530) Google Scholar3Annane D Sebille V Bellissant E Effect of low doses of corticosteroids in septic shock patients with or without early acute respiratory distress syndrome.Crit Care Med. 2006; 34: 22-30Crossref PubMed Scopus (230) Google Scholar4Meduri GU Golden E Freire AX et al.Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial.Chest. 2007; 131: 954-963Abstract Full Text Full Text PDF PubMed Scopus (568) Google Scholar5Meduri GU Headley S Golden E et al.Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial.JAMA. 1998; 280: 159-165Crossref PubMed Scopus (829) Google Scholar6The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome.N Engl J Med. 2006; 354: 1671-1684Crossref PubMed Scopus (1066) Google Scholar BAL neutrophilia,6The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome.N Engl J Med. 2006; 354: 1671-1684Crossref PubMed Scopus (1066) Google Scholar7Sinclair S Bijoy J Golden E et al.Interleukin-8 and soluble intercellular adhesion molecule-1 during acute respiratory distress syndrome and in response to prolonged methylprednisolone Treatment.Minerva Pneumologica. 2006; 45: 93-104Google Scholar duration of mechanical ventilation,2Confalonieri M Urbino R Potena A et al.Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study.Am J Respir Crit Care Med. 2005; 171: 242-248Crossref PubMed Scopus (530) Google Scholar3Annane D Sebille V Bellissant E Effect of low doses of corticosteroids in septic shock patients with or without early acute respiratory distress syndrome.Crit Care Med. 2006; 34: 22-30Crossref PubMed Scopus (230) Google Scholar4Meduri GU Golden E Freire AX et al.Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial.Chest. 2007; 131: 954-963Abstract Full Text Full Text PDF PubMed Scopus (568) Google Scholar5Meduri GU Headley S Golden E et al.Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial.JAMA. 1998; 280: 159-165Crossref PubMed Scopus (829) Google Scholar6The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome.N Engl J Med. 2006; 354: 1671-1684Crossref PubMed Scopus (1066) Google Scholar and ICU stay.2Confalonieri M Urbino R Potena A et al.Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study.Am J Respir Crit Care Med. 2005; 171: 242-248Crossref PubMed Scopus (530) Google Scholar4Meduri GU Golden E Freire AX et al.Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial.Chest. 2007; 131: 954-963Abstract Full Text Full Text PDF PubMed Scopus (568) Google Scholar5Meduri GU Headley S Golden E et al.Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial.JAMA. 1998; 280: 159-165Crossref PubMed Scopus (829) Google Scholar6The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome.N Engl J Med. 2006; 354: 1671-1684Crossref PubMed Scopus (1066) Google Scholar The magnitude of reduction in duration of mechanical ventilation (ventilator-free days) is shown in Table 1, and is far greater than the reduction observed with the recommended low-tidal-volume ventilation8Bower G Matthay M 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. 2000; 342: 1301-1308Crossref PubMed Scopus (10147) Google Scholar or conservative strategy of fluid management.9Wiedemann HP Wheeler AP Bernard GR et al.Comparison of two fluid-management strategies in acute lung injury.N Engl J Med. 2006; 354: 2564-2575Crossref PubMed Scopus (2636) Google ScholarTable 1Effect of Glucocorticoid Treatment on Ventilator-Free Days to Day 28*Data are presented as mean ± SD.Source/YearPlaceboGlucocorticoidp ValueMeduri et al5Meduri GU Headley S Golden E et al.Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial.JAMA. 1998; 280: 159-165Crossref PubMed Scopus (829) Google Scholar/19983.5 ± 6.211 ± 6.80.02Confalonieri et al2Confalonieri M Urbino R Potena A et al.Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study.Am J Respir Crit Care Med. 2005; 171: 242-248Crossref PubMed Scopus (530) Google Scholar/200510.1 ± 10.222 ± 6.30.001Annane et al3Annane D Sebille V Bellissant E Effect of low doses of corticosteroids in septic shock patients with or without early acute respiratory distress syndrome.Crit Care Med. 2006; 34: 22-30Crossref PubMed Scopus (230) Google Scholar/20063.1 ± 6.94.9 ± 8.40.09NHLBI ARDS6The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome.N Engl J Med. 2006; 354: 1671-1684Crossref PubMed Scopus (1066) Google Scholar†NHLBI ARDS = National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network./20066.8 ± 8.511.2 ± 9.40.001Meduri et al4Meduri GU Golden E Freire AX et al.Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial.Chest. 2007; 131: 954-963Abstract Full Text Full Text PDF PubMed Scopus (568) Google Scholar/20078.7 ± 10.216.5 ± 10.10.001* Data are presented as mean ± SD.† NHLBI ARDS = National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network. Open table in a new tab Overall, glucocorticoid treatment appears most effective when started at a lower dosage (1 mg/kg/d) early in the course of ALI-ARDS.2Confalonieri M Urbino R Potena A et al.Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study.Am J Respir Crit Care Med. 2005; 171: 242-248Crossref PubMed Scopus (530) Google Scholar4Meduri GU Golden E Freire AX et al.Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial.Chest. 2007; 131: 954-963Abstract Full Text Full Text PDF PubMed Scopus (568) Google Scholar Mortality is overall improved with prolonged glucocorticoid treatment (91 of 276 patients; 33%; vs 111 of 242 patients; 46%; relative risk [RR], 0.76; 95% confidence interval [CI], 0.62 to 0.93; p = 0.007), and the benefits are more significant when treatment is initiated before day 14 of ARDS (84 of 252 patients; 33%; vs 108 of 216 patients; 50%; RR, 0.71; 95% CI, 0.50 to 0.87; p = 0.001). The mortality benefit with glucocorticoid treatment is greater than the benefit observed with low-tidal-volume ventilation (9%),8Bower G Matthay M 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. 2000; 342: 1301-1308Crossref PubMed Scopus (10147) Google Scholar with number needed to treat to save one life of 6 for treatment initiated before day 14. Finally, the conclusion of the ARDS network trial6The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome.N Engl J Med. 2006; 354: 1671-1684Crossref PubMed Scopus (1066) Google Scholar that methylprednisolone treatment increases mortality in patients randomized after day 14 is challenged by the large imbalances in baseline characteristics (control vs methylprednisolone) in this small subgroup of patients for age (45 ± 13 years vs 52 ± 24 years), male gender (56% vs 35%), trauma (20% vs 13%), pneumonia (28% vs 44%), serum creatinine (1.0 ± 0.8 mg/dL vs 1.3 ± 1.3 mg/dL), APACHE (acute physiology and chronic health evaluation) III score (79 ± 22 vs 87 ± 25), compliance (26 ± 15 cm H2O vs 18 ± 7 cm H2O; p = 0.02), and lung injury score (2.7 ± 1.2 vs 3.7 ± 0.87; p = 0.001) [mean ± SD] that likely accounted for the uncharacteristically low mortality in the control group (8% vs 36%). These factors should be taken into consideration in analyzing the role of glucocorticoid treatment in ARDS, and should stimulate additional clinical investigation of this inexpensive and highly effective antiinflammatory therapy. Corticosteroids in ARDS: A CounterpointCHESTVol. 132Issue 3PreviewMeduri et al highlight the nature of the ongoing debate over the value of corticosteroids in acute lung injury/ARDS. The study by Confalonieri and colleagues1 was not included in our review because the study population had severe pneumonia, not ARDS. The retrospective study by Annane et al2 was a secondary analysis of a randomized controlled trial of corticosteroids in septic shock; benefit was noted in the subgroup of patients with sepsis-associated ARDS who failed to respond to a corticotropin stimulation test. Full-Text PDF