The role of glucocorticoids as adjunctive treatment for sepsis in the modern era

Glucocorticoids have been used as adjunctive therapy in patients with sepsis and septic shock for more than four decades. The rationale for the use of glucocorticoids is that this class of drugs downregulates the proinflammatory response and limits the anti-inflammatory response while preserving innate immunity. Between 1976 and 2017, 22 randomised placebo-controlled trials have been published evaluating the benefit of glucocorticoids in patients with community-acquired pneumonia, sepsis, and septic shock. These studies produced conflicting results. In 2018, two large randomised controlled trials (RCTs) were published evaluating the role of hydrocortisone in patients with septic shock. The Activated Protein C and Corticosteroids for Human Septic Shock (APROCCHSS) trial reported a reduction in 90-day mortality whereas the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock (ADRENAL) trial reported no mortality benefit. This Viewpoint critically appraises these two RCTs and evaluates the use of glucocorticoids in the treatment of sepsis and septic shock in the modern era.