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

Introduction

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.

Methods

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.

Results

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

Survival of rats.

Conclusion

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