To determine whether corticosteroids are efficacious in severe septic shock, we conducted a prospective study of 59 patients randomly assigned to a methylprednisolone, dexamethasone, or control group. Patients were treated 17.5 +/- 5.4 hours (mean +/- S.E.M.) after the onset of shock, and 55 patients required vasopressor agents. Early in the hospital course, reversal of shock was more likely in patients who received corticosteroids than in those who did not. Four (19 per cent) of 21 methylprednisolone-treated, 7 (32 per cent) of 22 dexamethasone-treated, and none of 16 control patients had reversal of shock 24 hours after drug administration (corticosteroid groups vs. control group, P less than 0.05). Patients treated with corticosteroids within four hours after the onset of shock had a higher incidence of shock reversal (P less than 0.05). At 133 hours after drug administration, 17 (40 per cent) of 43 corticosteroid-treated patients had died, and 11 (69 per cent) of 16 control patients had died (P less than 0.05). However, these differences in reversal of shock and survival disappeared later in the course. Overall, 16 (76 per cent) of 21 patients receiving methylprednisolone, 17 (77 per cent) of 22 patients receiving dexamethasone, and 11 (69 per cent) of 16 controls in the hospital died. We conclude that corticosteroids do not improve the overall survival of patients with severe, late septic shock but may be helpful early in the course and in certain subgroups of patients.
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(2007). Prednisolone Dose-Dependently Influences Inflammation and Coagulation during Human Endotoxemia. J. Immunol.
178: 1845-1851
[Abstract][Full Text]
Aneja, R., Carcillo, J. A
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[Abstract][Full Text]
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(2006). Relative Adrenal Insufficiency in the ICU: Can We at Least Make the Diagnosis?. Am. J. Respir. Crit. Care Med.
174: 1282-1284
[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.
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[Abstract][Full Text]
Cepkova, M., Matthay, M. A.
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[Abstract]
The National Heart, Lung, and Blood Institute Acut,
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354: 1671-1684
[Abstract][Full Text]
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(2006). Using the high-dose corticotropin test to diagnose relative adrenal insufficiency in vasopressor-dependent septic shock. Am J Health Syst Pharm
63: 466-471
[Full Text]
Trow, T. K.
(2005). Clinical Year in Review II: Pulmonary Infections, Diagnostic Imaging, Pleural Diseases, and Neuromuscular Disease. Proc Am Thorac Soc
2: 175-178
[Full Text]
Bernard, G. R.
(2005). Acute Respiratory Distress Syndrome: A Historical Perspective. Am. J. Respir. Crit. Care Med.
172: 798-806
[Abstract][Full Text]
Iwamura, H., Sato, M., Wakitani, K.
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311: 1256-1263
[Abstract][Full Text]
Annane, D., Bellissant, E., Bollaert, P. E., Briegel, J., Keh, D., Kupfer, Y.
(2004). Corticosteroids for severe sepsis and septic shock: a systematic review and meta-analysis. BMJ
329: 480-
[Abstract][Full Text]
Minneci, P. C., Deans, K. J., Banks, S. M., Eichacker, P. Q., Natanson, C.
(2004). Meta-Analysis: The Effect of Steroids on Survival and Shock during Sepsis Depends on the Dose. ANN INTERN MED
141: 47-56
[Abstract][Full Text]
Nylen, E. S., Muller, B.
(2004). Endocrine Changes in Critical Illness. J Intensive Care Med
19: 67-82
[Abstract]
Donald, S., Verschoyle, R. D., Greaves, P., Gant, T. W., Colombo, T., Zaffaroni, M., Frapolli, R., Zucchetti, M., D'Incalci, M., Meco, D., Riccardi, R., Lopez-Lazaro, L., Jimeno, J., Gescher, A. J.
(2003). Complete Protection by High-Dose Dexamethasone against the Hepatotoxicity of the Novel Antitumor Drug Yondelis (ET-743) in the Rat. Cancer Res.
63: 5902-5908
[Abstract][Full Text]
Sessler, C. N.
(2003). Steroids for Septic Shock: Back From the Dead? (Con). Chest
123
: 482S-489S
[Abstract][Full Text]
Balk, R. A.
(2003). Steroids for Septic Shock: Back From the Dead? (Pro). Chest
123
: 490S-499S
[Abstract][Full Text]
Bornstein, S. R., Briegel, J.
(2003). A New Role for Glucocorticoids in Septic Shock: Balancing the Immune Response. Am. J. Respir. Crit. Care Med.
167: 485-486
[Full Text]
Keh, D., Boehnke, T., Weber-Cartens, S., Schulz, C., Ahlers, O., Bercker, S., Volk, H.-D., Doecke, W.-D., Falke, K. J., 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: 512-520
[Abstract][Full Text]
Sartori, C., Matthay, M.A.
(2002). Alveolar epithelial fluid transport in acute lung injury: new insights. Eur Respir J
20: 1299-1313
[Abstract][Full Text]
Moore, F. A.
(2002). Treatment of Aspiration in Intensive Care Unit Patients. JPEN J Parenter Enteral Nutr
26: S69-S74
[Abstract]
Annane, D., Sebille, V., Charpentier, C., Bollaert, P.-E., Francois, B., Korach, J.-M., 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: 862-871
[Abstract][Full Text]
Kenyon, N. J., Albertson, T. E.
(2002). Steroids and Sepsis: Time for Another Reevaluation. J Intensive Care Med
17: 68-74
[Abstract]
Brower, R. G., Ware, L. B., Berthiaume, Y., Matthay, M. A.
(2001). Treatment of ARDS. Chest
120: 1347-1367
[Abstract][Full Text]
CRANDALL, E. D., MATTHAY, M. A.
(2001). Alveolar Epithelial Transport . Basic Science to Clinical Medicine. Am. J. Respir. Crit. Care Med.
163: 1021-1029
[Full Text]
Lockey, D. J, Manara, A. R
(2001). The role of steroids following major trauma. Trauma
3: 53-61
[Abstract]
Ware, L. B., Matthay, M. A.
(2000). The Acute Respiratory Distress Syndrome. NEJM
342: 1334-1349
[Full Text]
van Deuren, M., Brandtzaeg, P., van der Meer, J. W. M.
(2000). Update on Meningococcal Disease with Emphasis on Pathogenesis and Clinical Management. Clin. Microbiol. Rev.
13: 144-166
[Abstract][Full Text]
Beno, D. W. A., Kimura, R. E.
(1999). Nonstressed rat model of acute endotoxemia that unmasks the endotoxin-induced TNF-alpha response. Am. J. Physiol. Heart Circ. Physiol.
276: H671-H678
[Abstract][Full Text]
Kollef, M. H., Schuster, D. P.
(1995). The Acute Respiratory Distress Syndrome. NEJM
332: 27-37
[Full Text]
Kieft, H., Hoepelman, A. I. M., Zhou, W., Rozenberg-Arska, M., Struyvenberg, A., Verhoef, J.
(1993). The Sepsis Syndrome in a Dutch University Hospital: Clinical Observations. Arch Intern Med
153: 2241-2247
[Abstract]
Pfister, H.-W., Feiden, W., Einhaupl, K.-M.
(1993). Spectrum of Complications During Bacterial Meningitis in Adults: Results of a Prospective Clinical Study. Arch Neurol
50: 575-581
[Abstract]
O'Riordain, M. G., Collins, K. H., Pilz, M., Saporoschetz, I. B., Mannick, J. A., Rodrick, M. L.
(1992). Modulation of Macrophage Hyperactivity Improves Survival in a Burn-Sepsis Model. Arch Surg
127: 152-158
[Abstract]
Bone, R. C.
(1991). The Pathogenesis of Sepsis. ANN INTERN MED
115: 457-469
[Abstract]
Parrillo, J. E.
(1991). Management of Septic Shock: Present and Future. ANN INTERN MED
115: 491-493
[Abstract]
Greenman, R. L., Schein, R. M. H., Martin, M. A., Wenzel, R. P., Maclntyre, N. R., Emmanuel, G., Chmel, H., Kohler, R. B., McCarthy, M., Plouffe, J., Russell, J. A., XOMA Sepsis Study Group, , Hollender, E., Immerman, R., Pfaller, M., Sheetz, C., Jebson, P., Houston, A., Rehak, D., Empson, P., Ireland, J., Narain, S., Rashkin, J. E., Jacobs, R. A., Octavio, J., Coleman, R., Kenyon, V. S., Yangco, B. G., Toney, J. F., Edwards, J., Crislip, M., Quenzer, R. W., Trenholme, G. M., Schmitt, B. A., Grossman, J. E., Daley, C. L., Chambers, H. F., Iannini, P. B., Graziano, T., Dandurand, R., Schieiter, G., Kunkel, M., Pankey, G. A., Mayeur, B., Abadie-Kemmerly, S., Zachery, J., Meadors, M., Coco, J., Sanders, C. V., George, W. L., Gardner, S., Finegold, S., Bernard, G. R., Bogden, P., Bello, E., Ellrodt, A. G., Dauer, J., Riedinger, M. S., Meyers, B. R., Iberti, T., Rissing, J. P., Nelson, D., Luu, Q., Campbell, G. D., Olsen, K., Carvalho, A., Brown, A. E., Schmitt, H. J., Brown, S., Schentag, J. J., Wels, P. B., Wing, P. E., Welage, L. S., Quintiliani, R., Chandrasekar, P. H., Ratzan, K. R., Dunn, D. L., Gorelick, K., Wedel, N., Saks, S., Hannigan, J., Ackerman, S. K., Scannon, P. J., Salsburg, D., Webb, C. D.
(1991). A Controlled Clinical Trial of E5 Murine Monoclonal IgM Antibody to Endotoxin in the Treatment of Gram-Negative Sepsis. JAMA
266: 1097-1102
[Abstract]
Bone, R. C.
(1991). Sepsis, the Sepsis Syndrome, Multi-Organ Failure: A Plea for Comparable Definitions. ANN INTERN MED
114: 332-333
[Abstract]
Giraud, T., Dhainaut, J.-F., Schremmer, B., Regnier, B., Desjars, P., Loirat, P., Journois, D., Lanore, J.-J.
(1991). Adult Overwhelming Meningococcal Purpura: A Study of 35 Cases, 1977-1989. Arch Intern Med
151: 310-316
[Abstract]
Wakeford, J. H., Hardin, T. C.
(1991). Sepsis. Journal of Pharmacy Practice
4: 269-280
Parrillo, J. E., Parker, M. M., Natanson, C., Suffredini, A. F., Danner, R. L., Cunnion, R. E., Ognibene, F. P.
(1990). Septic Shock in Humans: Advances in the Understanding of Pathogenesis, Cardiovascular Dysfunction, and Therapy. ANN INTERN MED
113: 227-242
[Abstract]
Mayoral, J. L., Schweich, CyrilJ., Dunn, D. L.
(1990). Decreased Tumor Necrosis Factor Production During the Initial Stages of Infection Correlates With Survival During Murine Gram-negative Sepsis. Arch Surg
125: 24-28
[Abstract]
Knowlton, A. I.
(1989). Adrenal Insufficiency in the Intensive Care Setting. J Intensive Care Med
4: 35-45
[Abstract]
Harris, R. L., Musher, D. M., Bloom, K., Gathe, J., Rice, L., Sugarman, B., Williams, T. W. Jr, Young, E. J.
(1987). Manifestations of Sepsis. Arch Intern Med
147: 1895-1906
[Abstract]
Sprung, C. L., Schein, R. M. H.
(1986). Consent: Informed, Implied, and Deferred. JAMA
256: 1891-1892
[Abstract]