CORTICUS (2008)

Despite advances, septic shock remains a major cause of mortality. Previous studies on corticosteroids in sepsis yielded conflicting results, prompting the need for a large, well-designed trial to definitively assess their role.

CORTICUS was a multicenter, randomized, double-blind, placebo-controlled trial. It enrolled 251 patients with septic shock who were unresponsive to fluid resuscitation and vasopressors, randomizing them to receive hydrocortisone or placebo. The primary endpoint was 28-day all-cause mortality.

There was no significant difference in 28-day mortality between the hydrocortisone group (39.2%) and the placebo group (36.1%) (p=0.51). However, patients receiving hydrocortisone had a significantly faster reversal of shock (median 3.3 days vs 5.8 days, p<0.001) and a reduced need for vasopressors. The incidence of superinfection and hyperglycemia was higher in the hydrocortisone group.

Hydrocortisone in septic shock does not improve 28-day mortality but may facilitate earlier vasopressor weaning and shock reversal, albeit with increased adverse events.

The study was not powered to detect small differences in mortality, and the definition of 'unresponsive to vasopressors' might have varied across centers.