The hypothalamic-pituitary-adrenal axis and low-dose glucocorticoids in the treatment of septic shock

Severe sepsis is the leading cause of death among patients in intensive care units. Recombinant activated protein C is the only substance known to directly improve morbidity and mortality. Adrenal insufficiency occurs frequently in patients with sepsis and is associated with poor outcome. Although high-dose glucocorticoids have not positively affected clinical outcome, small trials in which low-dose glucocorticoids were administered to patients with septic shock and relative adrenal insufficiency have shown decreased mortality. The main effect of glucocorticoids in low-doses apparently is exerted through correction of suppression of the hypothalamic-pituitary-adrenal axis. However, the therapeutic benefits of glucocorticoids may be related to their antiinflammatory properties and endogenous catecholamine-enhancing effects.