The Hypothalamic-Pituitary-Adrenal Axis in Critical Illness

Endocrinology and Metabolism Clinics of North America

Volumn 35, Issue 4, 2006, Pages 823-838

  Schuetz, Philipp ^a   Müller, Beat ^a  

^a UNIVERSITY HOSPITAL BASEL   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROSTANEDIONE; CORTICOTROPIN; CORTICOTROPIN RELEASING FACTOR; CYTOKINE; DEXAMETHASONE; FLUDROCORTISONE; GLUCOCORTICOID; HYDROCORTISONE; METHYLPREDNISOLONE; PRASTERONE; PRASTERONE SULFATE; PROTEIN; STERYL SULFATASE; TETRACOSACTIDE; VASOPRESSIN;

ADDISON DISEASE; ADRENAL CORTEX INSUFFICIENCY; ADRENAL INSUFFICIENCY; BRAIN MALARIA; CLINICAL TRIAL; COMA; CORTICOTROPIN TEST; CRITICAL ILLNESS; DRUG SAFETY; HORMONAL THERAPY; HORMONE ACTION; HORMONE BLOOD LEVEL; HORMONE RELEASE; HUMAN; HYPERCORTISOLISM; HYPERGLYCEMIA; HYPOPHYSIS FUNCTION; HYPOTHALAMUS HYPOPHYSIS ADRENAL SYSTEM; IMMUNE DEFICIENCY; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; SEPSIS; SEPTIC SHOCK; SEX DIFFERENCE; STRESS; TREATMENT OUTCOME; UNSPECIFIED SIDE EFFECT;

ADRENOCORTICOTROPIC HORMONE; CRITICAL ILLNESS; HUMANS; HYDROCORTISONE; HYPOTHALAMO-HYPOPHYSEAL SYSTEM; INTENSIVE CARE; PITUITARY-ADRENAL SYSTEM;

EID: 33751201225     PISSN: 08898529     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ecl.2006.09.013     Document Type: Review

References (119)

1. Vermes I., and Beishuizen A. The hypothalamic-pituitary-adrenal response to critical illness. Best Pract Res Clin Endocrinol Metab 15 4 (2001) 495-511
2. Ledingham I.M., and Watt I. Influence of sedation on mortality in critically ill multiple trauma patients. Lancet 1 8336 (1983) 1270
3. Absalom A., Pledger D., and Kong A. Adrenocortical function in critically ill patients 24 h after a single dose of etomidate. Anaesthesia 54 9 (1999) 861-867
4. Nylen E.S., and Muller B. Endocrine changes in critical illness. J Intensive Care Med 19 2 (2004) 67-82
5. Van den Berghe G. The neuroendocrine response to stress is a dynamic process. Best Pract Res Clin Endocrinol Metab 15 4 (2001) 405-419
6. Ho J.T., Al-Musalhi H., Chapman M.J., et al. Septic shock and sepsis: a comparison of total and free plasma cortisol levels. J Clin Endocrinol Metab 91 1 (2006) 105-114
7. Polderman K.H., van Zanten A., and Girbes A.R. Free cortisol and critically ill patients. N Engl J Med 351 4 (2004) 395-397 [author reply: 395-7]
8. Khan T., Kupfer Y., and Tessler S. Free cortisol and critically ill patients. N Engl J Med 351 4 (2004) 395-397 [author reply: 395-7]
9. Hamrahian A.H., Oseni T.S., and Arafah B.M. Measurements of serum free cortisol in critically ill patients. N Engl J Med 350 16 (2004) 1629-1638
10. Beishuizen A., Thijs L.G., and Vermes I. Patterns of corticosteroid-binding globulin and the free cortisol index during septic shock and multitrauma. Intensive Care Med 27 10 (2001) 1584-1591
11. Webster J.I., and Sternberg E.M. Role of the hypothalamic-pituitary-adrenal axis, glucocorticoids and glucocorticoid receptors in toxic sequelae of exposure to bacterial and viral products. J Endocrinol 181 2 (2004) 207-221
12. Prigent H., Maxime V., and Annane D. Science review: mechanisms of impaired adrenal function in sepsis and molecular actions of glucocorticoids. Crit Care 8 4 (2004) 243-252
13. Silverstein R., and Johnson D.C. Endogenous versus exogenous glucocorticoid responses to experimental bacterial sepsis. J Leukoc Biol 73 4 (2003) 417-427
14. Briegel J. Cortisol in critically ill patients with sepsis: physiologic functions and therapeutic implications. Wien Klin Wochenschr 112 8 (2000) 341-352
15. Manary M.J., Muglia L.J., Vogt S.K., et al. Cortisol and its action on the glucocorticoid receptor in malnutrition and acute infection. Metabolism 55 4 (2006) 550-554
16. Melby J.C., Edghal R.H., and Spink W.W. Secretion and metabolism of cortisol after injection of endotoxin. J Lab Clin Med 56 (1960) 50-62
17. Rinaldi S., Adembri C., Grechi S., et al. Low-dose hydrocortisone during severe sepsis: effects on microalbuminuria. Crit Care Med Jul (2006) 17
18. Alarifi A.A., van den Berghe G.H., Snider R.H., et al. Endocrine markers and mediators in critical illness. 3rd edition (2001), J.B. Lippincott, Philadelphia
19. Nylen E.S., and Alarifi A.A. Humoral markers of severity and prognosis of critical illness. Best Pract Res Clin Endocrinol Metab 15 4 (2001) 553-573
20. Munck A., Guyre P.M., and Holbrook N.J. Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr Rev 5 1 (1984) 25-44
21. Axelrod L. Corticosteroid therapy. In: Becker K.L. (Ed). Principles and practice of endocrinology and metabolism. 3rd edition (2001), Lippincott Williams & Wilkins, Philadelphia 751-764
22. Lynn L.D. Adrenocortical insufficiency. In: Becker K.L. (Ed). Principles and practice of endocrinology and metabolism. 3rd edition (2001), Lippincott Williams & Wilkins, Philadelphia 739-743
23. Manna P.R., Dyson M.T., Eubank D.W., et al. Regulation of steroidogenesis and the steroidogenic acute regulatory protein by a member of the cAMP response-element binding protein family. Mol Endocrinol 16 1 (2002) 184-199
24. Stocco D.M., and Clark B.J. Regulation of the acute production of steroids in steroidogenic cells. Endocr Rev 17 3 (1996) 221-244
25. Perrot D., Bonneton A., Dechaud H., et al. Hypercortisolism in septic shock is not suppressible by dexamethasone infusion. Crit Care Med 21 3 (1993) 396-401
26. Naito Y., Fukata J., Tamai S., et al. Biphasic changes in hypothalamo-pituitary-adrenal function during the early recovery period after major abdominal surgery. J Clin Endocrinol Metab 73 1 (1991) 111-117
27. Aun F., McIntosh T.K., Lee A., et al. The effects of surgery on the circadian rhythms of cortisol. Int Surg 69 2 (1984) 101-105
28. Voerman H.J., Strack van Schijndel R.J., Groeneveld A.B., et al. Pulsatile hormone secretion during severe sepsis: accuracy of different blood sampling regimens. Metabolism 41 9 (1992) 934-940
29. Steele B.W., Wang E., Palmer-Toy D.E., et al. Total long-term within-laboratory precision of cortisol, ferritin, thyroxine, free thyroxine, and thyroid-stimulating hormone assays based on a College of American Pathologists fresh frozen serum study: do available methods meet medical needs for precision?. Arch Pathol Lab Med 129 3 (2005) 318-322
30. Zaloga G.P., and Marik P. Hypothalamic-pituitary-adrenal insufficiency. Crit Care Clin 17 1 (2001) 25-41
31. O'Leary E., Hubbard K., Tormey W., et al. Laparoscopic cholecystectomy: haemodynamic and neuroendocrine responses after pneumoperitoneum and changes in position. Br J Anaesth 76 5 (1996) 640-644
32. Hinson J.P., Vinson G.P., Kapas S., et al. The role of endothelin in the control of adrenocortical function: stimulation of endothelin release by ACTH and the effects of endothelin-1 and endothelin-3 on steroidogenesis in rat and human adrenocortical cells. J Endocrinol 128 2 (1991) 275-280
33. Vermes I., Beishuizen A., Hampsink R.M., et al. Dissociation of plasma adrenocorticotropin and cortisol levels in critically ill patients: possible role of endothelin and atrial natriuretic hormone. J Clin Endocrinol Metab 80 4 (1995) 1238-1242
34. Morgenthaler N.G., Struck J., Christ-Crain M., et al. Pro-atrial natriuretic peptide is a prognostic marker in sepsis, similar to the APACHE II score: an observational study. Crit Care 9 1 (2005) R37-R45
35. Christ-Crain M., Morgenthaler N.G., Struck J., et al. Mid-regional pro-adrenomedullin as a prognostic marker in sepsis: an observational study. Crit Care 9 6 (2005) R816-R824
36. Davenport M.W., and Zipser R.D. Association of hypotension with hyperreninemic hypoaldosteronism in the critically ill patient. Arch Intern Med 143 4 (1983) 735-737
37. Zipser R.D., Davenport M.W., Martin K.L., et al. Hyperreninemic hypoaldosteronism in the critically ill: a new entity. J Clin Endocrinol Metab 53 4 (1981) 867-873
38. Wilmore D.W. Catabolic illness: strategies for enhancing recovery. N Engl J Med 325 10 (1991) 695-702
39. Souba W.W. Cytokine control of nutrition and metabolism in critical illness. Curr Probl Surg 31 7 (1994) 577-643
40. Weekers F., and Van den Berghe G. Endocrine modifications and interventions during critical illness. Proc Nutr Soc 63 3 (2004) 443-450
41. Vanhorebeek I., and Van den Berghe G. Hormonal and metabolic strategies to attenuate catabolism in critically ill patients. Curr Opin Pharmacol 4 6 (2004) 621-628
42. Schteingart D.E. Cushing syndrome. In: Becker K.L. (Ed). Principles and practice of endocrinology and metabolism. 3rd edition (2001), Lippincott Williams & Wilkins, Philadelphia 723-738
43. Arlt W. Dehydroepiandrosterone replacement therapy. Semin Reprod Med 22 4 (2004) 379-388
44. Hammer F., Subtil S., Lux P., et al. No evidence for hepatic conversion of dehydroepiandrosterone (DHEA) sulfate to DHEA: in vivo and in vitro studies. J Clin Endocrinol Metab 90 6 (2005) 3600-3605
45. Kim M.S., Shigenaga J., Moser A., et al. Suppression of DHEA sulfotransferase (Sult2A1) during the acute-phase response. Am J Physiol Endocrinol Metab 287 4 (2004) E731-E738
46. Hildebrand F., Pape H.C., Harwood P., et al. Are alterations of lymphocyte subpopulations in polymicrobial sepsis and DHEA treatment mediated by the tumour necrosis factor (TNF)-alpha receptor (TNF-RI)? A study in TNF-RI (TNF-RI(-/-)) knock-out rodents. Clin Exp Immunol 138 2 (2004) 221-229
47. Hildebrand F., Pape H.C., Hoevel P., et al. The importance of systemic cytokines in the pathogenesis of polymicrobial sepsis and dehydroepiandrosterone treatment in a rodent model. Shock 20 4 (2003) 338-346
48. Oberbeck R., Dahlweid M., Koch R., et al. Dehydroepiandrosterone decreases mortality rate and improves cellular immune function during polymicrobial sepsis. Crit Care Med 29 2 (2001) 380-384
49. Ben-Nathan D., Padgett D.A., and Loria R.M. Androstenediol and dehydroepiandrosterone protect mice against lethal bacterial infections and lipopolysaccharide toxicity. J Med Microbiol 48 5 (1999) 425-431
50. Angele M.K., Catania R.A., Ayala A., et al. Dehydroepiandrosterone: an inexpensive steroid hormone that decreases the mortality due to sepsis following trauma-induced hemorrhage. Arch Surg 133 12 (1998) 1281-1288
51. Matsuda A., Furukawa K., Suzuki H., et al. Dehydroepiandrosterone modulates toll-like receptor expression on splenic macrophages of mice after severe polymicrobial sepsis. Shock 24 4 (2005) 364-369
52. Arlt W., Hammer F., Sanning P., et al. Dissociation of serum dehydroepiandrosterone and dehydroepiandrosterone sulfate in septic shock. J Clin Endocrinol Metab 91 7 (2006) 2548-2554
53. Beishuizen A., Thijs L.G., and Vermes I. Decreased levels of dehydroepiandrosterone sulphate in severe critical illness: a sign of exhausted adrenal reserve?. Crit Care 6 5 (2002) 434-438
54. Luppa P., Munker R., Nagel D., et al. Serum androgens in intensive-care patients: correlations with clinical findings. Clin Endocrinol (Oxf) 34 4 (1991) 305-310
55. Nierman D.M., and Mechanick J.I. Hypotestosteronemia in chronically critically ill men. Crit Care Med 27 11 (1999) 2418-2421
56. Spratt D.I. Altered gonadal steroidogenesis in critical illness: is treatment with anabolic steroids indicated?. Best Pract Res Clin Endocrinol Metab 15 4 (2001) 479-494
57. Parker L.N., Levin E.R., and Lifrak E.T. Evidence for adrenocortical adaptation to severe illness. J Clin Endocrinol Metab 60 5 (1985) 947-952
58. Reincke M., Lehmann R., Karl M., et al. Severe illness: neuroendocrinology. Ann N Y Acad Sci 771 (1995) 556-569
59. Barquist E., and Kirton O. Adrenal insufficiency in the surgical intensive care unit patient. J Trauma 42 1 (1997) 27-31
60. Annane D., Sebille V., Troche G., et al. A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. JAMA 283 8 (2000) 1038-1045
61. Widmer I.E., Puder J.J., Konig C., et al. Cortisol response in relation to the severity of stress and illness. J Clin Endocrinol Metab 90 8 (2005) 4579-4586
62. Zaloga G.P. Sepsis-induced adrenal deficiency syndrome. Crit Care Med 29 3 (2001) 688-690
63. Chernow B., Alexander H.R., Smallridge R.C., et al. Hormonal responses to graded surgical stress. Arch Intern Med 147 7 (1987) 1273-1278
64. Mohler J.L., Michael K.A., Freedman A.M., et al. The serum and urinary cortisol response to operative trauma. Surg Gynecol Obstet 161 5 (1985) 445-449
65. Udelsman R., Norton J.A., Jelenich S.E., et al. Responses of the hypothalamic-pituitary-adrenal and renin-angiotensin axes and the sympathetic system during controlled surgical and anesthetic stress. J Clin Endocrinol Metab 64 5 (1987) 986-994
66. Donald R.A., Perry E.G., Wittert G.A., et al. The plasma ACTH, AVP, CRH and catecholamine responses to conventional and laparoscopic cholecystectomy. Clin Endocrinol (Oxf) 38 6 (1993) 609-615
67. Rothwell P.M., Udwadia Z.F., and Lawler P.G. Cortisol response to corticotropin and survival in septic shock. Lancet 337 8741 (1991) 582-583
68. Marik P.E., and Zaloga G.P. Adrenal insufficiency in the critically ill: a new look at an old problem. Chest 122 5 (2002) 1784-1796
69. Van den Berghe G., de Zegher F., and Bouillon R. Clinical review 95: acute and prolonged critical illness as different neuroendocrine paradigms. J Clin Endocrinol Metab 83 6 (1998) 1827-1834
70. Cooper M.S., and Stewart P.M. Corticosteroid insufficiency in acutely ill patients. N Engl J Med 348 8 (2003) 727-734
71. Ligtenberg J.J., and Zijlstra J.G. The relative adrenal insufficiency syndrome revisited: which patients will benefit from low-dose steroids?. Curr Opin Crit Care 10 6 (2004) 456-460
72. Rady M.Y., Johnson D.J., Patel B., et al. Cortisol levels and corticosteroid administration fail to predict mortality in critical illness: the confounding effects of organ dysfunction and sex. Arch Surg 140 7 (2005) 661-668 [discussion: 669]
73. Joosten K.F., de Kleijn E.D., Westerterp M., et al. Endocrine and metabolic responses in children with meningoccocal sepsis: striking differences between survivors and nonsurvivors. J Clin Endocrinol Metab 85 10 (2000) 3746-3753
74. Beishuizen A., and Thijs L.G. Relative adrenal failure in intensive care: an identifiable problem requiring treatment?. Best Pract Res Clin Endocrinol Metab 15 4 (2001) 513-531
75. Beishuizen A., Vermes I., Hylkema B.S., et al. Relative eosinophilia and functional adrenal insufficiency in critically ill patients. Lancet 353 9165 (1999) 1675-1676
76. Ligtenberg J.J., Tulleken J.E., van der Werf T.S., et al. Unraveling the mystery of adrenal failure in the critically ill. Crit Care Med 32 6 (2004) 1447-1448 [author reply: 1448]
77. Marik P.E. Unraveling the mystery of adrenal failure in the critically ill. Crit Care Med 32 2 (2004) 596-597
78. Marik P.E., and Zaloga G.P. Adrenal insufficiency during septic shock. Crit Care Med 31 1 (2003) 141-145
79. Dickstein G., Spigel D., Arad E., et al. One microgram is the lowest ACTH dose to cause a maximal cortisol response: there is no diurnal variation of cortisol response to submaximal ACTH stimulation. Eur J Endocrinol 137 2 (1997) 172-175
80. Dickstein G. On the term "relative adrenal insufficiency" or what do we really measure with adrenal stimulation tests?. J Clin Endocrinol Metab 90 8 (2005) 4973-4974
81. Annane D., Sebille V., Charpentier C., et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288 7 (2002) 862-871
82. Hockings G.I., Strakosch C.R., and Jackson R.V. Secondary adrenocortical insufficiency: avoiding potentially fatal pitfalls in diagnosis and treatment. Med J Aust 166 8 (1997) 400-401
83. Nye E.J., Grice J.E., Hockings G.I., et al. Adrenocorticotropin stimulation tests in patients with hypothalamic-pituitary disease: low dose, standard high dose and 8-h infusion tests. Clin Endocrinol (Oxf) 55 5 (2001) 625-633
84. McGill P.E., Greig W.R., Browning M.C., et al. Plasma cortisol response to synacthen (beta-1-24 Ciba) at different times of the day in patients with rheumatic diseases. Ann Rheum Dis 26 2 (1967) 123-126
85. Nathan R.S., Sachar E.J., Langer G., et al. Diurnal variation in the response of plasma prolactin, cortisol, and growth hormone to insulin-induced hypoglycemia in normal men. J Clin Endocrinol Metab 49 2 (1979) 231-235
86. Berneis K., Staub J.J., Gessler A., et al. Combined stimulation of adrenocorticotropin and compound-S by single dose metyrapone test as an outpatient procedure to assess hypothalamic-pituitary-adrenal function. J Clin Endocrinol Metab 87 12 (2002) 5470-5475
87. DeCherney G.S., DeBold C.R., Jackson R.V., et al. Diurnal variation in the response of plasma adrenocorticotropin and cortisol to intravenous ovine corticotropin-releasing hormone. J Clin Endocrinol Metab 61 2 (1985) 273-279
88. Keh D., Boehnke T., Weber-Cartens S., et al. 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 4 (2003) 512-520
89. Oppert M., Reinicke A., Graf K.J., et al. Plasma cortisol levels before and during "low-dose" hydrocortisone therapy and their relationship to hemodynamic improvement in patients with septic shock. Intensive Care Med 26 12 (2000) 1747-1755
90. Sessler C.N. Steroids for septic shock: back from the dead? (Con). Chest 123 5 Suppl (2003) 482S-9
91. Millo J. Corticosteroids for patients with septic shock. JAMA 289 1 (2003) 41 [author reply: 43-4]
92. Confalonieri M., Urbino R., Potena A., et al. Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study. Am J Respir Crit Care Med 171 3 (2005) 242-248
93. Briegel J. Hydrocortisone and the reduction of vasopressors in septic shock: therapy or only chart cosmetics?. Intensive Care Med 26 12 (2000) 1723-1726
94. Minneci P.C., Deans K.J., Banks S.M., et al. Meta-analysis: the effect of steroids on survival and shock during sepsis depends on the dose. Ann Intern Med 141 1 (2004) 47-56
95. Annane D., Bellissant E., Bollaert P.E., et al. Corticosteroids for severe sepsis and septic shock: a systematic review and meta-analysis. BMJ 329 7464 (2004) 480
96. Rady M.Y., Johnson D.J., Patel B., et al. Corticosteroids influence the mortality and morbidity of acute critical illness. Crit Care 10 4 (2006) R101
97. Bollaert P.E., Charpentier C., Levy B., et al. Reversal of late septic shock with supraphysiologic doses of hydrocortisone. Crit Care Med 26 4 (1998) 645-650
98. Annane D., Bellissant E., Bollaert P.E., et al. Corticosteroids for treating severe sepsis and septic shock. Cochrane Database Syst Rev 1 (2004) CD002243
99. Bone R.C., Fisher Jr. C.J., Clemmer T.P., et al. A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med 317 11 (1987) 653-658
100. Sprung C.L., Caralis P.V., Marcial E.H., et al. The effects of high-dose corticosteroids in patients with septic shock: a prospective, controlled study. N Engl J Med 311 18 (1984) 1137-1143
101. Frantz M.C., Prix N.J., Wichmann M.W., et al. Dehydroepiandrosterone restores depressed peripheral blood mononuclear cell function following major abdominal surgery via the estrogen receptors. Crit Care Med 33 8 (2005) 1779-1786
102. Jarrar D., Kuebler J.F., Wang P., et al. DHEA: a novel adjunct for the treatment of male trauma patients. Trends Mol Med 7 2 (2001) 81-85
103. Dhatariya K.K. Is there a role for dehydroepiandrosterone replacement in the intensive care population?. Intensive Care Med 29 11 (2003) 1877-1880
104. Gomez M.T., Magiakou M.A., Mastorakos G., et al. The pituitary corticotroph is not the rate limiting step in the postoperative recovery of the hypothalamic-pituitary-adrenal axis in patients with Cushing syndrome. J Clin Endocrinol Metab 77 1 (1993) 173-177
105. Henzen C., Suter A., Lerch E., et al. Suppression and recovery of adrenal response after short-term, high-dose glucocorticoid treatment. Lancet 355 9203 (2000) 542-545
106. Graber A.L., Ney R.L., Nicholson W.E., et al. Natural history of pituitary-adrenal recovery following long-term suppression with corticosteroids. J Clin Endocrinol Metab 25 (1965) 11-16
107. Symreng T., Karlberg B.E., Kagedal B., et al. Physiological cortisol substitution of long-term steroid-treated patients undergoing major surgery. Br J Anaesth 53 9 (1981) 949-954
108. Van den Berghe G., Wilmer A., Hermans G., et al. Intensive insulin therapy in the medical ICU. N Engl J Med 354 5 (2006) 449-461
109. Van Den Berghe G., Wouters D., Weekers F., et al. Intensive insulin therapy in critically ill patients. N Engl J Med 345 (2001) 1359-1367
110. Spencer M.T., and Bazarian J.J. Evidence-based emergency medicine/systematic review abstract: are corticosteroids effective in traumatic spinal cord injury?. Ann Emerg Med 41 3 (2003) 410-413
111. Galandiuk S., Raque G., Appel S., et al. The two-edged sword of large-dose steroids for spinal cord trauma. Ann Surg 218 4 (1993) 419-425 [discussion: 425-17]
112. Muller B., Peri G., Doni A., et al. High circulating levels of the IL-1 type II decoy receptor in critically ill patients with sepsis: association of high decoy receptor levels with glucocorticoid administration. J Leukoc Biol 72 4 (2002) 643-649
113. Warrell D.A., Looareesuwan S., Warrell M.J., et al. Dexamethasone proves deleterious in cerebral malaria: a double-blind trial in 100 comatose patients. N Engl J Med 306 6 (1982) 313-319
114. Roberts I., Yates D., Sandercock P., et al. Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Lancet 364 9442 (2004) 1321-1328
115. Edwards P., Arango M., Balica L., et al. Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury-outcomes at 6 months. Lancet 365 9475 (2005) 1957-1959
116. Sauerland S., and Maegele M. A CRASH landing in severe head injury. Lancet 364 9442 (2004) 1291-1292
117. LaRosa S.P. Use of corticosteroids in the sepsis syndrome: what do we know now?. Cleve Clin J Med 72 12 (2005) 1121-1127
118. Kass E.H. High-dose corticosteroids for septic shock. N Engl J Med 311 18 (1984) 1178-1179
119. Meduri G.U. A historical review of glucocorticoid treatment in sepsis: disease pathophysiology and the design of treatment investigation. Sepsis (1999) 312-338