[Cortisol in critically ill patients with sepsis--physiological functions and therapeutic implications].
Modern immunology reveals that cortisol interacts with the immune response at virtually all levels exerting suppressive and permissive effects. A prerequisite for the defense of severe infections is the functional integrity of the hypothalamic-pituitary-adrenal axis (HPAA) resulting in adequate cortisol production. There is increasing evidence that cortisol physiology and regulation substantially change in the course of septic shock. Patients with septic shock may suffer from relative adrenocortical insufficiency resulting in a relative deficiency of cortisol. In addition, the number and the affinity of cellular glucocorticoid receptors are decreased which may reduce the cortisol action at the cellular level. Since septic shock and adrenal insufficiency are sharing hemodynamic abnormalities such as hyperdynamic shock and peripheral vasodilation, the administration of stress doses of hydrocortisone appears to be a rational therapeutic approach in patients with septic shock. Controlled studies reveal that stress doses of hydrocortisone attenuate the systemic inflammatory response. Recently, two double-blind studies demonstrated that stress doses of hydrocortisone given in patients with septic shock reduce the time to shock reversal. The most important hemodynamic effect was an increase in the systemic vascular resistance. The earlier weaning from vasopressor therapy was associated with a trend towards improvements in organ dysfunction and mortality, respectively. Large-scale trials are on the way to investigate the benefit of stress doses of hydrocortisone on mortality of septic shock. This paper will focus on changes in glucocorticoid physiology and regulation during septic shock and will discuss the effects of stress doses of hydrocortisone on immune response and vascular tone in the course of septic shock.
Briegel
Josef
J
Klinik für Anaesthesiologie, Klinikum der Universität München, Deutschland. josef.briegel@ana.med.uni-muenchen.de
D000309:Adrenal Insufficiency / Q000188:drug therapy / Q000276:immunology; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D016638:Critical Illness / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006854:Hydrocortisone / Q000097:blood* / Q000627:therapeutic use; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000502:physiology; D012772:Shock, Septic / Q000188:drug therapy / Q000276:immunology*; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy / Q000276:immunology*; D014662:Vasoconstrictor Agents / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D011965:Receptors, Glucocorticoid; D014662:Vasoconstrictor Agents; D006854:Hydrocortisone