Plasma cortisol levels before and during low-dose hydrocortisone therapy and their relationship to hemodynamic improvement in patients with septic shock

• Published in: Intensive care medicine Vol. 26; no. 12; pp. 1747 - 1755
• Main Authors: OPPERT, Michael, REINICKE, Albrecht, GRÄF, Klaus-Jürgen, BARCKOW, Detlef, FREI, Ulrich, ECKARDT, Kai-Uwe
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01.12.2000; Berlin Springer Nature B.V; Springer-Verlag
• Subjects: Adrenocorticotropic Hormone; Adult; Aged; Aged, 80 and over; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; Cardiac Output - drug effects; Catecholamines; Drug Administration Schedule; Drug dosages; Drug Monitoring; Drug Therapy, Combination; Emergency and intensive care: infection, septic shock; Female; Hemodynamics; Hemodynamics - drug effects; Hormones; Humans; Hydrocortisone - administration & dosage; Hydrocortisone - blood; Hydrocortisone - pharmacology; Infections; Inflammation; Infusions, Intravenous; Intensive care; Intensive care medicine; Male; Medical sciences; Middle Aged; Mortality; Observational studies; Original; Plasma; Prospective Studies; Pulmonary arteries; Sepsis; Shock, Septic - drug therapy; Shock, Septic - metabolism; Shock, Septic - mortality; Shock, Septic - physiopathology; Steroids; Treatment Outcome; Vasoconstrictor Agents - therapeutic use; Berlin Germany; Germany; Shock; Human; Corticosteroid; Concentration factor; Low dose; Cardiovascular disease; Hydrocortisone; Biological activity; Blood plasma; Infection; Sepsis syndrome; Chemotherapy; Treatment; Adrenal hormone; Bacteriosis; Hemodynamics; Pharmacokinetics
• ISSN: 0342-4642; 1432-1238
• DOI: 10.1007/s001340000685

To compare cortisol levels during "low-dose" hydrocortisone therapy to basal and ACTH-stimulated endogenous levels and to assess whether clinical course and the need for catecholamines depend on cortisol levels and/or pretreatment adrenocortical responsiveness. Prospective observational study in a medical ICU of a university hospital. Twenty consecutive patients with septic shock and a cardiac index of 3.5 l/min or higher, started on "low-dose" hydrocortisone therapy (100 mg bolus, 10 mg/h for 7 days and subsequent tapering) within 72 h of the onset of shock. Basal total and free plasma cortisol levels ranged from 203 to 2169 and from 17 to 372 nmol/l. In 11 patients cortisol production was considered "inadequate" because there was neither a response to ACTH of at least 200 nmol/l nor a baseline level of at least 1000 nmol/l. Following the initiation of hydrocortisone therapy total and free cortisol levels increased 4.2- and 8.5-fold to median levels of 3,587 (interquartile range 2,679-5,220) and 1,210 (interquartile range 750-1,846) nmol/l on day 1, and thereafter declined to median levels of 1,310 nmol/l and 345 nmol/l on day 7. Patients with "inadequate" steroid production could be weaned from vasopressor therapy significantly faster, although their plasma free cortisol concentrations during the hydrocortisone treatment period did not differ. (a) During proposed regimens of "low-dose" hydrocortisone therapy, initially achieved plasma cortisol concentrations considerably exceed basal and ACTH stimulated levels. (b) Cortisol concentrations decline subsequently, despite continuous application of a constant dose. (c) "Inadequate" endogenous steroid production appears to sensitize patients to the hemodynamic effects of a "therapeutic rise" in plasma cortisol levels.