Does low-dose hydrocortisone combined with fludrocortisone improve outcomes in septic shock? The Annane et al. study was the first large randomized controlled trial (RCT) that investigated the effects of low-dose hydrocortisone and fludrocortisone on mortality in patients with septic shock. A total of 299 patients with septic shock were randomly assigned to receive either hydrocortisone and fludrocortisone or a placebo. The study found a significant reduction in 28-day mortality in the treatment group (35.4% vs. 47.2%), suggesting that low-dose corticosteroids can improve survival in patients with septic shock who exhibit signs of adrenal insufficiency. The study was a milestone in the management of septic shock, supporting the use of corticosteroids as a part of treatment for patients with shock, resistant to fluid resuscitation and vasopressors.