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

Intensive Care Med. 2000 Dec;26(12):1747-55. doi: 10.1007/s001340000685.

Abstract

Objectives: 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.

Design and setting: Prospective observational study in a medical ICU of a university 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 onset of shock.

Measurements and 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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Adrenocorticotropic Hormone
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / pharmacology
  • Cardiac Output / drug effects
  • Drug Administration Schedule
  • Drug Monitoring
  • Drug Therapy, Combination
  • Female
  • Hemodynamics / drug effects*
  • Humans
  • Hydrocortisone / administration & dosage*
  • Hydrocortisone / blood*
  • Hydrocortisone / pharmacology
  • Inflammation
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Prospective Studies
  • Shock, Septic / drug therapy*
  • Shock, Septic / metabolism*
  • Shock, Septic / mortality
  • Shock, Septic / physiopathology
  • Treatment Outcome
  • Vasoconstrictor Agents / therapeutic use

Substances

  • Anti-Inflammatory Agents
  • Vasoconstrictor Agents
  • Adrenocorticotropic Hormone
  • Hydrocortisone