[Cortisol in critically ill patients with sepsis: physiologic functions and therapeutic implications].
Modern immunology reveals that cortisol interacts with the immune response at virtually all levels exerting both suppressive and permissive effects. A pre-requisite for the defense against 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 are substantially altered in the course of a septic shock. Patients with septic shock may suffer from relative adrenocortical insufficiency resulting in a relative deficiency of cortisol production. In addition, the number and the affinity of cellular glucocorticoid receptors are decreased by which cortisol action at cellular level is reduced. Since septic shock and adrenal insufficiency are sharing hemodynamic abnormalities such as hyperdynamic circulation and peripheral vasodilation, the administration of stress doses of hydrocortisone appears to be a rational therapeutic 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 stress doses of hydrocortisone given in patients with septic shock have been demonstrated to reduce the time to shock reversal. The most important hemodynamic effect was an increase in systemic vascular resistance. Earlier weaning from vasopressor therapy was associated with a trend towards improvements in organ function and towards decreased mortality, respectively. Large-scale trials are on the way investigating the benefit of stress doses of hydrocortisone on the mortality of septic shock. The focus of this review are changes in glucocorticoid physiology and regulation during septic shock. Effects of stress doses of hydrocortisone on immune response and vascular tone in the course of a septic shock are being discussed.
Briegel
J
J
Klinik für Anästhesiologie, Klinikum der Universität München, Bundesrepublik Deutschland. josef.briegel@ana.med.uni-muenchen.de
D000309:Adrenal Insufficiency / Q000503:physiopathology; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000917:Antibody Formation; D003422:Critical Care; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000096:biosynthesis / Q000378:metabolism / Q000627:therapeutic use*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012772:Shock, Septic / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology*; D014666:Vasomotor System / Q000187:drug effects / Q000503:physiopathology
D000893:Anti-Inflammatory Agents; D011965:Receptors, Glucocorticoid; D006854:Hydrocortisone
Cortisol bei kritisch kranken Patienten mit Sepsis: Physiologische Funktionen und therapeutische Implikationen.