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

Objectives: To compare cortisol levels during "low-dose" hydrocortisone the rapy to basal and ACTH-stimulated endogenous levels and to assess whether c linical course and the need for catecholamines depend on cortisol levels an d/or pretreatment adrenocortical responsiveness. Design and setting: Prospective observational study in a medical ICU of a u niversity hospital. Patients: 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 on set of shock. Measurements and results: Basal total and free plasma cortisol levels range d from 203 to 2169 and from 17 to 372 nmol/l. In 11 patients cortisol produ ction was considered "inadequate" because there was neither a response to A CTH of at least 200 nmol/l nor a baseline level of at least 1000 nmol/l. Fo llowing the initiation of hydrocortisone therapy total and free cortisol le vels increased 4.2- and 8.5-fold to median levels of 3587 (interquartile ra nge 2679-5220) and 1210 (interquartile range 750-1846) nmol/l on day 1, and thereafter declined to median levels of 1310 nmol/l and 345 nmol/l on day 7. Patients with "inadequate'' steroid production could be weaned from vaso pressor therapy significantly faster, although their plasma free cortisol c oncentrations during the hydrocortisone treatment period did not differ. Conclusions: (a) During proposed regimens of ''low-dose" hydrocortisone the rapy, initially achieved plasma cortisol concentrations considerably exceed basal and ACTH stimulated levels. (b) Cortisol concentrations decline subs equently, despite continuous application of a constant dose. (c) "Inadequat e" endogenous steroid production appears to sensitize patients to the hemod ynamic effects of a "therapeutic rise" in plasma cortisol levels.