title: Gluco- and mineralocorticoid biological effects of a 7-day treatment with low doses of hydrocortisone and fludrocortisone in septic shock.
abstract: OBJECTIVE
  The benefits of low-dose steroids in septic shock remain controversial. We investigated if these low doses were able to induce their expected hormonal effects by analyzing the biological modifications observed during the study, which first demonstrated the survival benefit of low-dose steroids.
  
  
  METHODS
  This was a multicenter, placebo-controlled, randomized, double-blind study in which 299 septic shock patients received a 7-day treatment with a combination of hydrocortisone (50 mg intravenously four times daily) and fludrocortisone (50 μg orally once daily) or matching placebos. Gluco- and mineralocorticoid biological effects observed during the 7 days of treatment were compared between groups.
  
  
  RESULTS
  Steroids significantly decreased eosinophil counts from day 2 to day 7. Steroids significantly increased plasma glucose from day 2 (compared with placebos: +0.8 mmol/l) to day 7 (+1.8 mmol/l) and cholesterol from day 3 (+0.54 mmol/l) to day 7 (+0.39 mmol/l). Steroids significantly increased plasma sodium from day 3 (+2 mmol/l) to day 7 (+5 mmol/l) and significantly decreased plasma potassium on day 7 (-0.2 mmol/l). Steroids significantly decreased urinary sodium/potassium ratio from day 2 (-47 %) to day 7 (-57 %) and sodium fractional excretion from day 3 (-25 %) to day 7 (-66 %). Steroids significantly increased urine output on day 4 and 5 and osmolar clearance from day 4 to day 7, and decreased free-water clearance from day 4 to day 7, this effect being significant on day 4 and 6.
  
  
  CONCLUSIONS
  In septic shock, low-dose steroids induced both gluco- and mineralocorticoid biological effects and seemed to improve renal function. Most of these effects appeared after 2-3 days of treatment and lasted at least until the end of treatment.
authors.affiliation: Department of Clinical Pharmacology, University Hospital, Rennes 1 University, Rennes, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Laviolle
authors.forename: Djillali
authors.initials: D
authors.lastname: Annane
authors.forename: Claire
authors.initials: C
authors.lastname: Fougerou
authors.forename: Eric
authors.initials: E
authors.lastname: Bellissant
mesh_terms: D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001786:Blood Glucose / Q000032:analysis; D001834:Body Water / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004804:Eosinophils / Q000166:cytology; D005438:Fludrocortisone / Q000008:administration & dosage*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage*; D007958:Leukocyte Count; D009994:Osmolar Concentration; D011188:Potassium / Q000097:blood / Q000652:urine; D012772:Shock, Septic / Q000188:drug therapy*; D012964:Sodium / Q000097:blood / Q000652:urine; D014556:Urine
chemical_list: D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D002784:Cholesterol; D012964:Sodium; D011188:Potassium; D005438:Fludrocortisone; D006854:Hydrocortisone