Background Persistent acute respiratory distress syndrome (ARDS)is characterized by excessive fibroproliferation, ongoing inflammation,prolonged mechanical ventilation, and a substantial risk ofdeath. Because previous reports suggested that corticosteroidsmay improve survival, we performed a multicenter, randomizedcontrolled trial of corticosteroids in patients with persistentARDS.
Methods We randomly assigned 180 patients with ARDS of at leastseven days' duration to receive either methylprednisolone orplacebo in a double-blind fashion. The primary end point wasmortality at 60 days. Secondary end points included the numberof ventilator-free days and organ-failure–free days, biochemicalmarkers of inflammation and fibroproliferation, and infectiouscomplications.
Results At 60 days, the hospital mortality rate was 28.6 percentin the placebo group (95 percent confidence interval, 20.3 to38.6 percent) and 29.2 percent in the methylprednisolone group(95 percent confidence interval, 20.8 to 39.4 percent; P=1.0);at 180 days, the rates were 31.9 percent (95 percent confidenceinterval, 23.2 to 42.0 percent) and 31.5 percent (95 percentconfidence interval, 22.8 to 41.7 percent; P=1.0), respectively.Methylprednisolone was associated with significantly increased60- and 180-day mortality rates among patients enrolled at least14 days after the onset of ARDS. Methylprednisolone increasedthe number of ventilator-free and shock-free days during thefirst 28 days in association with an improvement in oxygenation,respiratory-system compliance, and blood pressure with fewerdays of vasopressor therapy. As compared with placebo, methylprednisolonedid not increase the rate of infectious complications but wasassociated with a higher rate of neuromuscular weakness.
Conclusions These results do not support the routine use ofmethylprednisolone for persistent ARDS despite the improvementin cardiopulmonary physiology. In addition, starting methylprednisolonetherapy more than two weeks after the onset of ARDS may increasethe risk of death. (ClinicalTrials.gov number, NCT00295269
[ClinicalTrials.gov]
.)
Source Information
The members of the Writing Committee (Kenneth P. Steinberg, M.D., Leonard D. Hudson, M.D., Richard B. Goodman, M.D., and Catherine Lee Hough, M.D., University of Washington, Seattle; Paul N. Lanken, M.D., University of Pennsylvania, Philadelphia; Robert Hyzy, M.D., University of Michigan, Ann Arbor; and B. Taylor Thompson, M.D., and Marek Ancukiewicz, Ph.D., Massachusetts General Hospital, Boston) of the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network assume responsibility for the overall content and integrity of the article.
Address reprint requests to Dr. Steinberg at the Division of Pulmonary and Critical Care Medicine, Harborview Medical Center, Box 359762, 325 Ninth Ave., Seattle, WA 98104, or at steinkp{at}u.washington.edu.
Corticosteroids in ARDS
Marik P., Pastores S., Annane D., Speich R., Schmid C., Stocker R., Okamoto H., DiNubile M. J., Steinberg K. P., Hudson L. D., Thompson B. T., the NHBLI ARDS Clinical Trials Network
Extract |
Full Text |
PDF
N Engl J Med 2006;
355:316-319, Jul 20, 2006.
Correspondence
This article has been cited by other articles:
Mackay, A, Al-Haddad, M
(2009). Acute lung injury and acute respiratory distress syndrome. Contin Educ Anaesth Crit Care Pain
9: 152-156
[Full Text]
Webster, N. R., Galley, H. F.
(2009). Immunomodulation in the critically ill. Br J Anaesth
103: 70-81
[Abstract][Full Text]
Resch, M., Kurz, K., Schneider-Brachert, W., Tintelnot, K., Birner, C., Schichtl, T., Lubnow, M., Hart, C., Jilek, C., Bertz, S., Hilker, M., Riegger, G. A J, Luchner, A., Muller, T.
(2009). Extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS) in fulminant blastomycosis in Germany. BMJ Case Reports
2009: bcr0720080392-bcr0720080392
[Abstract][Full Text]
Maldonado, F., Parambil, J. G., Yi, E. S., Decker, P. A., Ryu, J. H.
(2009). Haemosiderin-laden macrophages in the bronchoalveolar lavage fluid of patients with diffuse alveolar damage. Eur Respir J
33: 1361-1366
[Abstract][Full Text]
Levitt, J. E., Gould, M. K., Ware, L. B., Matthay, M. A.
(2009). Analytic Review: The Pathogenetic and Prognostic Value of Biologic Markers in Acute Lung Injury. J Intensive Care Med
24: 151-167
[Abstract]
Silva, P. L., Garcia, C. S. N. B., Maronas, P. A., Cagido, V. R., Negri, E. M., Damaceno-Rodrigues, N. R., Ventura, G. M., Bozza, P. T., Zin, W. A., Capelozzi, V. L., Pelosi, P., Rocco, P. R. M.
(2009). Early short-term versus prolonged low-dose methylprednisolone therapy in acute lung injury. Eur Respir J
33: 634-645
[Abstract][Full Text]
Phua, J., Badia, J. R., Adhikari, N. K. J., Friedrich, J. O., Fowler, R. A., Singh, J. M., Scales, D. C., Stather, D. R., Li, A., Jones, A., Gattas, D. J., Hallett, D., Tomlinson, G., Stewart, T. E., Ferguson, N. D.
(2009). Has Mortality from Acute Respiratory Distress Syndrome Decreased over Time?: A Systematic Review. Am. J. Respir. Crit. Care Med.
179: 220-227
[Abstract][Full Text]
Sessler, C. N.
(2009). Hypoxemic Respiratory Failure. ACCP Pulmonary Med Brd Rev
25: 401-414
[Full Text]
Marik, P. E.
(2009). Critical Illness-Related Corticosteroid Insufficiency. Chest
135: 181-193
[Abstract][Full Text]
Kim, Y. J., Pack, K. M., Jeong, E., Na, J. O., Oh, Y-M., Lee, S. D., Kim, W. S., Kim, D. S., Kim, W. D., Shim, T. S.
(2008). Pulmonary tuberculosis with acute respiratory failure. Eur Respir J
32: 1625-1630
[Abstract][Full Text]
Kamiyama, K., Matsuda, N., Yamamoto, S., Takano, K.-i., Takano, Y., Yamazaki, H., Kageyama, S.-i., Yokoo, H., Nagata, T., Hatakeyama, N., Tsukada, K., Hattori, Y.
(2008). Modulation of glucocorticoid receptor expression, inflammation, and cell apoptosis in septic guinea pig lungs using methylprednisolone. Am. J. Physiol. Lung Cell. Mol. Physiol.
295: L998-L1006
[Abstract][Full Text]
Sibila, O., Luna, C. M., Agusti, C., Baquero, S., Gando, S., Patron, J. R., Morato, J. G., Absi, R., Bassi, N., Torres, A.
(2008). Effects of glucocorticoids in ventilated piglets with severe pneumonia. Eur Respir J
32: 1037-1046
[Abstract][Full Text]
Sibila, O., Agusti, C., Torres, A.
(2008). Corticosteroids in severe pneumonia. Eur Respir J
32: 259-264
[Abstract][Full Text]
Ali, N. A., O'Brien, J. M. Jr., Hoffmann, S. P., Phillips, G., Garland, A., Finley, J. C. W., Almoosa, K., Hejal, R., Wolf, K. M., Lemeshow, S., Connors, A. F. Jr., Marsh, C. B., for The Midwest Critical Care Consortium,
(2008). Acquired Weakness, Handgrip Strength, and Mortality in Critically Ill Patients. Am. J. Respir. Crit. Care Med.
178: 261-268
[Abstract][Full Text]
Babu, R. V., Cardenas, V. Jr, Sharma, G.
(2008). Acute Respiratory Distress Syndrome From Chlorine Inhalation During a Swimming Pool Accident: A Case Report and Review of the Literature. J Intensive Care Med
23: 275-280
[Abstract]
Checkley, W., Brower, R., Korpak, A., Thompson, B. T., for the Acute Respiratory Distress Syndrome Networ,
(2008). Effects of a Clinical Trial on Mechanical Ventilation Practices in Patients with Acute Lung Injury. Am. J. Respir. Crit. Care Med.
177: 1215-1222
[Abstract][Full Text]
Adhikari, N. K J, Scales, D. C
(2008). Corticosteroids for acute respiratory distress syndrome. BMJ
336: 969-970
[Full Text]
Matthay, M. A.
(2008). Treatment of Acute Lung Injury: Clinical and Experimental Studies. Proc Am Thorac Soc
5: 297-299
[Abstract][Full Text]
Liu, K. D., Matthay, M. A.
(2008). Advances in Critical Care for the Nephrologist: Acute Lung Injury/ARDS. CJASN
3: 578-586
[Abstract][Full Text]
Sprung, C. L., Annane, D., Keh, D., Moreno, R., Singer, M., Freivogel, K., Weiss, Y. G., Benbenishty, J., Kalenka, A., Forst, H., Laterre, P.-F., Reinhart, K., Cuthbertson, B. H., Payen, D., Briegel, J., the CORTICUS Study Group,
(2008). Hydrocortisone Therapy for Patients with Septic Shock. NEJM
358: 111-124
[Abstract][Full Text]
Bream-Rouwenhorst, H. R., Beltz, E. A., Ross, M. B., Moores, K. G.
(2008). Recent developments in the management of acute respiratory distress syndrome in adults. Am J Health Syst Pharm
65: 29-36
[Abstract][Full Text]
Tidswell, M.
(2008). Nonventilatory Interventions in ALI/ARDS: Recent Work. J Intensive Care Med
23: 70-72
Schuster, K. M., Alouidor, R., Barquist, E. S.
(2008). Nonventilatory Interventions in the Acute Respiratory Distress Syndrome. J Intensive Care Med
23: 19-32
[Abstract]
Cooper, M. S., Stewart, P. M.
(2007). Adrenal Insufficiency in Critical Illness. J Intensive Care Med
22: 348-362
[Abstract]
Dombrowsky, H., Uhlig, S.
(2007). Steroids and histone deacetylase in ventilation-induced gene transcription. Eur Respir J
30: 865-877
[Abstract][Full Text]
Hyzy, R., Huang, S., Myers, J., Flaherty, K., Martinez, F.
(2007). Acute Exacerbation of Idiopathic Pulmonary Fibrosis. Chest
132: 1652-1658
[Abstract][Full Text]
Benfield, R., DuBose, J., Demetriades, D.
(2007). Prevention and treatment of post-traumatic acute respiratory distress syndrome. Trauma
9: 255-266
[Abstract]
Alam, N., Park, B. J., Wilton, A., Seshan, V. E., Bains, M. S., Downey, R. J., Flores, R. M., Rizk, N., Rusch, V. W., Amar, D.
(2007). Incidence and Risk Factors for Lung Injury After Lung Cancer Resection. Ann. Thorac. Surg.
84: 1085-1091
[Abstract][Full Text]
Ware, L. B.
(2007). Clinical Year in Review III: Asthma, Lung Transplantation, Cystic Fibrosis, Acute Respiratory Distress Syndrome. Proc Am Thorac Soc
4: 489-493
[Full Text]
Salluh, J. I. F., Soares, M.
(2007). Methylprednisolone Infusion in Early Severe ARDS: It Is Pretty, But Is It Art?. Chest
132: 1096-1096
[Full Text]
Meduri, G. U.
(2007). There Is No Illumination in Speculation: Additional Data in Support of Methylprednisolone Treatment in ARDS. Chest
132: 1097-1100
[Full Text]
Savel, R. H., Goldstein, E. B., Lehman, H., Kupfer, Y., Annane, D.
(2007). Methylprednisolone Infusion in Early Severe ARDS. Chest
132: 1096-1097
[Full Text]
Meduri, G. U., Marik, P. E., Pastores, S. M., Annane, D., Calfee, C. S., Matthay, M. A.
(2007). Corticosteroids in ARDS: A Counterpoint. Chest
132: 1093-1094
[Full Text]
Thomas, Z., Fraser, G. L
(2007). An Update on the Diagnosis of Adrenal Insufficiency and the Use of Corticotherapy in Critical Illness. The Annals of Pharmacotherapy
41: 1456-1465
[Abstract][Full Text]
Leaver, S. K, Evans, T. W
(2007). Acute respiratory distress syndrome. BMJ
335: 389-394
[Full Text]
Matute-Bello, G., Wurfel, M. M., Lee, J. S., Park, D. R., Frevert, C. W., Madtes, D. K., Shapiro, S. D., Martin, T. R.
(2007). Essential Role of MMP-12 in Fas-Induced Lung Fibrosis. Am. J. Respir. Cell Mol. Bio.
37: 210-221
[Abstract][Full Text]
Schweickert, W. D., Hall, J.
(2007). ICU-Acquired Weakness. Chest
131: 1541-1549
[Abstract][Full Text]
Supinski, G. S., Callahan, L. A.
(2007). Free radical-mediated skeletal muscle dysfunction in inflammatory conditions. J. Appl. Physiol.
102: 2056-2063
[Abstract][Full Text]
Annane, D.
(2007). Glucocorticoids for ARDS: Just Do It!. Chest
131: 945-946
[Full Text]
Meduri, G. U., Golden, E., Freire, A. X., Taylor, E., Zaman, M., Carson, S. J., Gibson, M., Umberger, R.
(2007). Methylprednisolone Infusion in Early Severe ARDS*Results of a Randomized Controlled Trial. Chest
131: 954-963
[Abstract][Full Text]
Milbrandt, E. B., Ishizaka, A., Angus, D. C.
(2007). Update in Critical Care 2006. Am. J. Respir. Crit. Care Med.
175: 638-648
[Full Text]
Calfee, C. S., Matthay, M. A.
(2007). Nonventilatory Treatments for Acute Lung Injury and ARDS. Chest
131: 913-920
[Abstract][Full Text]
Wurfel, M. M.
(2007). Microarray-based Analysis of Ventilator-induced Lung Injury. Proc Am Thorac Soc
4: 77-84
[Abstract][Full Text]
Gropper, M. A.
(2007). Handbook of ICU Therapy, 2nd ed.. Anesth. Analg.
104: 244-245
[Full Text]
Russell, J. A.
(2006). Management of Sepsis. NEJM
355: 1699-1713
[Full Text]
Arafah, B. M.
(2006). Hypothalamic Pituitary Adrenal Function during Critical Illness: Limitations of Current Assessment Methods. J. Clin. Endocrinol. Metab.
91: 3725-3745
[Abstract][Full Text]
Schuller, D., Schuster, D. P., Morizio, A., Kupfer, Y., Tessler, S., Amaral, A. C.K.B., Amado, V. M., Wiedemann, H. P., Wheeler, A. P., Hayden, D.
(2006). Fluid-Management Strategies in Acute Lung Injury. NEJM
355: 1175-1176
[Full Text]
Marik, P., Pastores, S., Annane, D., Speich, R., Schmid, C., Stocker, R., Okamoto, H., DiNubile, M. J., Steinberg, K. P., Hudson, L. D., Thompson, B. T., the NHBLI ARDS Clinical Trials Network,
(2006). Corticosteroids in ARDS.. NEJM
355: 316-317
[Full Text]
Snelson, C
(2006). No mortality benefit seen with methylprednisolone in ARDS. Thorax
61: 639-639
[Full Text]
(2006). Are Corticosteroids Beneficial in ARDS?. JWatch General
2006: 1-1
[Full Text]
Suter, P. M.
(2006). Lung Inflammation in ARDS--friend or foe?. NEJM
354: 1739-1742
[Full Text]
Previous
