Journal
INTENSIVE CARE MEDICINE
Volume 38, Issue 8, Pages 1306-1314Publisher
SPRINGER
DOI: 10.1007/s00134-012-2585-1
Keywords
Fludrocortisone; Glucocorticoid; Hydrocortisone; Mineralocorticoid; Randomized controlled trial; Septic shock
Categories
Funding
- GERMED [Ger-Inf-05R2]
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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. 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 mu g orally once daily) or matching placebos. Gluco- and mineralocorticoid biological effects observed during the 7 days of treatment were compared between groups. 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. 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.
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