Cortisol in critically ill patients with sepsis - pathophysiology and therapeutic implications

Modern immunology reveals that cortisol interacts with the immune response at virtually all levels exerting both suppressive and permissive effects. A prerequisite for the defense against severe infections is the functional i ntegrity of the hypothalamic-pituitary-adrenal axis (HPAA) resulting in ade quate cortisol production. There is increasing evidence that cortisol physi ology and regulation are substantially altered in the course of a septic sh ock. Patients with septic shock may suffer from relative adrenocortical ins ufficiency resulting in a relative deficiency of cortisol production. In ad dition, the number and the affinity of cellular glucocorticoid receptors ar e decreased by which cortisol action at cellular level is reduced. Since se ptic shock and adrenal insufficiency are sharing hemodynamic abnormalities such as hyperdynamic circulation and peripheral vasodilation, the administr ation of stress doses of hydrocortisone appears to be a rational therapeuti c approach in patients with septic shock. Controlled studies have shown that stress doses of hydrocortisone attenuate the systemic inflammatory response. In two recent double-blind studies str ess doses of hydrocortisone given in patients with septic shock have been d emonstrated to reduce the time to shock reversal. The most important hemody namic effect was an increase in systemic vascular resistance. Earlier weani ng from vasopressor therapy was associated with a trend towards improvement s in organ function and towards decreased mortality, respectively. Large-sc ale trials are on the way investigating the benefit of stress doses of hydr ocortisone on the mortality of septic shock. The focus of this review are c hanges in glucocorticoid physiology and regulation during septic shock. Eff ects of stress doses of hydrocortisone on immune response and vascular tone in the course of a septic shock are being discussed.