Immunologic and Hemodynamic Effects of "Low-Dose" Hydrocortisone in Septic Shock: A Double-Blind, Randomized, Placebo-Controlled, Crossover Study

Am J Respir Crit Care Med. 2003 Feb 15;167(4):512-20. doi: 10.1164/rccm.200205-446OC. Epub 2002 Nov 8.

Abstract

Within the last few years, increasing evidence of relative adrenal insufficiency in septic shock evoked a reassessment of hydrocortisone therapy. To evaluate the effects of hydrocortisone on the balance between proinflammatory and antiinflammation, 40 patients with septic shock were randomized in a double-blind crossover study to receive either the first 100 mg of hydrocortisone as a loading dose and 10 mg per hour until Day 3 (n = 20) or placebo (n = 20), followed by the opposite medication until Day 6. Hydrocortisone infusion induced an increase of mean arterial pressure, systemic vascular resistance, and a decline of heart rate, cardiac index, and norepinephrine requirement. A reduction of plasma nitrite/nitrate indicated inhibition of nitric oxide formation and correlated with a reduction of vasopressor support. The inflammatory response (interleukin-6 and interleukin-8), endothelial (soluble E-selectin) and neutrophil activation (expression of CD11b, CD64), and antiinflammatory response (soluble tumor necrosis factor receptors I and II and interleukin-10) were attenuated. In peripheral blood monocytes, human leukocyte antigen-DR expression was only slightly depressed, whereas in vitro phagocytosis and the monocyte-activating cytokine interleukin-12 increased. Hydrocortisone withdrawal induced hemodynamic and immunologic rebound effects. In conclusion, hydrocortisone therapy restored hemodynamic stability and differentially modulated the immunologic response to stress in a way of antiinflammation rather than immunosuppression.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / immunology
  • Anti-Inflammatory Agents / pharmacology*
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Down-Regulation
  • Female
  • Hemodynamics / drug effects*
  • Humans
  • Hydrocortisone / administration & dosage
  • Hydrocortisone / blood
  • Hydrocortisone / immunology
  • Hydrocortisone / pharmacology*
  • Immune System / drug effects*
  • Immunologic Factors / blood
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Nitric Oxide / blood
  • Shock, Septic / drug therapy*
  • Shock, Septic / immunology
  • Statistics, Nonparametric

Substances

  • Anti-Inflammatory Agents
  • Immunologic Factors
  • Nitric Oxide
  • Hydrocortisone