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Immunologic and Hemodynamic Effects of "Low-Dose" Hydrocortisone in Septic Shock

A Double-Blind, Randomized, Placebo-controlled, Crossover Study

Department of Anesthesiology and Intensive Care Medicine; Institute of Medical Immunology, Charité, Humboldt University; and Vivantes Klinikum Neukoelln, Berlin, Germany

Correspondence and requests for reprints should be addressed to Didier Keh, M.D., Department of Anesthesiology and Intensive Care Medicine, Charité-Campus Virchow Clinic, Humboldt University, Augustenburger Platz 1, D-13353 Berlin, Germany. E-mail: didier.keh{at}charite.de

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.

Key Words: sepsis • glucocorticoids • immune system

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