The altered adrenal axis and treatment with glucocorticoids during critical illness.

Critical illness is generally hallmarked by activation of the hypothalamic-pituitary-adrenal axis. The development of very high levels of cortisol has been associated with severe illness and a raised risk of death. Likewise, a response that is inadequate relative to the degree of stress, termed relative adrenal insufficiency (also known as critical-illness-related corticosteroid insufficiency) has been associated with increased mortality. Much controversy exists with regard to the definition and biochemical testing of an adequate adrenal response to critical illness, which hampers diagnosis. High doses of glucocorticoids have been shown to have no effect in this setting and might be harmful. Moderate doses have been advocated, however, for critically ill patients with inflammatory conditions, such as acute respiratory distress syndrome and septic shock syndrome. Initial results from proof-of-concept studies were promising but thus far have not been reproduced in large, multicenter trials, although the latter were underpowered to yield definite conclusions. The role of glucocorticoid therapy in intensive care, therefore, remains uncertain. Until the debate has been settled, we recommend that use of glucocorticoid therapy in critically ill patients should continue to be based on the clinician's judgment and that routine adjuvant use should be avoided.