Immunologic and hemodynamic effects of "low-dose" hydrocortisone in septic shock: a double-blind, randomized, placebo-controlled, crossover study.
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.
Keh
Didier
D
Department of Anesthesiology and Intensive Care Medicine, Humbolt University, Berlin, Germany. didier.keh@charite.de
Boehnke
Thomas
T
Weber-Cartens
Steffen
S
Schulz
Christina
C
Ahlers
Olaf
O
Bercker
Sven
S
Volk
Hans-Dieter
HD
Doecke
Wolf-Dietrich
WD
Falke
Konrad J
KJ
Gerlach
Herwig
H
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015536:Down-Regulation; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000097:blood / Q000276:immunology / Q000494:pharmacology*; D007107:Immune System / Q000187:drug effects*; D007155:Immunologic Factors / Q000097:blood; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D012772:Shock, Septic / Q000188:drug therapy* / Q000276:immunology; D018709:Statistics, Nonparametric
D000893:Anti-Inflammatory Agents; D007155:Immunologic Factors; D009569:Nitric Oxide; D006854:Hydrocortisone