Corticosteroids in sepsis

Sepsis is a major health and socioeconomic burden worldwide. Although international guidelines have helped reduce crude mortality rates from sepsis by optimizing infection control and support of vital organ function, there are still no specific therapies for sepsis, other than corticosteroids. The aims of this narrative review were to provide readers with the most recent data on corticosteroids, as well as up-to-date evidence regarding their effects in patients with sepsis. Corticosteroids regulate the function of most cell types involved in host response to infections, through both genomic and non-genomic effects, reprogramming immune cells (via regulation of mitochondrial metabolism) toward anti-inflammatory types, restoring endothelial cell function and endothelium integrity, facilitating epithelium repair, and restoring vascular smooth muscle function, as well as organ perfusion. In patients with sepsis, these effects are achieved using supraphysiological doses of corticosteroids, equating to approximately 200 mg/day of hydrocortisone equivalent for 5–15 days, depending on the clinical context. The molecular and cellular effects of corticosteroids translate into prevention and reversal of the need for vasopressor, respiratory, and renal supportive therapies, as well as acceleration of organ function resolution, shorter intensive care unit (ICU) and hospital stays, and improved short- and mid-term survival. Remaining gaps in knowledge and evidence to inform practice include insufficient data about the effects of corticosteroids in children, a lack of reliable biomarkers to distinguish those patients who can benefit from treatment, and inadequate information about the effects of corticosteroids on the long-term sequelae of sepsis.