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

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.

Adrenal insufficiency in patients with cirrhosis, severe sepsis and septic shock

“…5 Indeed, hydrocortisone replacement may reverse the blunt response to vasopressor and improve the outcomes of septic patients with adrenal dysfunction. 42,43 These hemodynamic effects of hydrocortisone in this setting may result from inhibition of cytokines and nitric oxide, 44 which also mediates the hemodynamic impairment in liver cirrhosis and portal hypertension. 10 Considering the recent interest in the anti-inflammatory treatment in various liver diseases, a subset of patients with cirrhosis in some clinical settings may benefit from glucocorticoids because of their anti-inflammatory effects and benefits in patients with cirrhosis and adrenal dysfunction.…”

Adrenal Crises in Children: Perspectives and Research Directions

“…These doses are based on consensus opinion rather than trial evidence, as are the recommended fluid resuscitation regimens [37]. However, it is known that hydrocortisone doses in this range will produce cortisol concentrations within the maximal physiological rather than immunosuppressive level and this suggests that these doses will be sufficient [41]. Moreover, these recommendations are supported by clinical experience from the successful treatment of patients in AC [41].…”

A Homozygous L299P Mutation in the <i>CYP11B1</i> Gene Leads to Complete Virilization in 46,XX Individuals with 11-Beta-Hydroxylase Deficiency

“…As to the actions of glucocorticoids, they seem to exert anti-inflammatory rather than immunosuppressive effects in severe septic infections, and their administration has proven beneficial in septic shock patients without adrenal insufficiency [20]. Additionally, decreased mortality has been observed in acutely ill patients who demonstrated functional adrenal insufficiency with lower random cortisol levels or attenuated cortisol response to CRH when glucocorticoids were supplemented [21].…”