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Need for restoration of cortisol serum levels for successful antimicrobial therapy in experimental sepsis


It is postulated that clinical benefit of low-dose hydrocortisone in septic shock is related to reversal of relative adrenal insufficiency [1]. This was proved in an animal model of sepsis.


Sixty-nine Wistar male rats were assigned to the following groups: A, sham-operation; B, sepsis; C, bilateral adrenalectomy and sepsis; D, bilateral adrenalectomy, sepsis and hydrocortisone treatment; E, bilateral adrenalectomy, sepsis and ertapenem treatment; and F, bilateral adrenalectomy, sepsis, hydrocortisone and ertapenem treatment. Sepsis was induced by the i.p. infusion of 1×106 cfu/ml of Escherichia coli after adrenalectomy. Hydrocortisone 10 mg/kg was infused i.v. bid starting 1 hour after bacterial challenge. Ertapenem 5 mg/kg was infused i.v. once daily starting 1 hour after bacterial challenge. Survival was recorded. In a separate set of experiments in 18 rats, animal sacrifice was performed to measure the free cortisol concentration.


Survival is shown in Figure 1. Experiments in each animal were starting at 7:00 am. At 8:00 am, respective mean free cortisol of groups A, C and D was 1.81, 0.55 and 2.05 μg/dl; at 1:00 pm they were 0.92, 0.47 and 1.40 μg/dl.

Figure 1
figure 1

Survival of rats.


Even when effective antimicrobial treatment is administered, administration of hydrocortisone at a regimen restoring normal secretion is mandatory for survival.


  1. Annane D, et al.: JAMA. 2002, 288: 862-871. 10.1001/jama.288.7.862

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Doulias, T., Pistiki, A., Christopoulos, P. et al. Need for restoration of cortisol serum levels for successful antimicrobial therapy in experimental sepsis. Crit Care 17 (Suppl 2), P70 (2013).

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  • Hydrocortisone
  • Septic Shock
  • Adrenal Insufficiency
  • Cortisol Serum
  • Cortisol Concentration