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


METHODS
Prospective observational study in a medical ICU of a university hospital.


METHODS
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.


RESULTS
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.


CONCLUSIONS
(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.
Department of Nephrology and Medical Intensive Care, Berlin, Germany.
M
M
Oppert
A
A
Reinicke
K J
KJ
Gräf
D
D
Barckow
U
U
Frei
K U
KU
Eckardt
D000324:Adrenocorticotropic Hormone; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002302:Cardiac Output / Q000187:drug effects; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000097:blood* / Q000494:pharmacology; D007249:Inflammation; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012772:Shock, Septic / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality / Q000503:physiopathology; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D014662:Vasoconstrictor Agents; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone