Glucocorticoids in sepsis: dissecting facts from fiction

Inadequate intracellular glucocorticoid activity, referred to as critical illness-related corticosteroid insufficiency, typically results in an exaggerated proinflammatory response [1]. Patients with severe sepsis or septic shock are therefore frequently treated with exogenous glucocorticoids. While there are large geographic variations in the prescription of glucocorticoids for sepsis, up to 50% of intensive care unit patients receive such therapy [2]. Despite over 30 years of investigation and over 20 meta-analyses, the use of glucocorticoids in patients with sepsis remains extremely controversial and recommendations are conflicting.The most important recent studies are that of Annane and colleagues [3] and the Corticosteroid Therapy of Septic Shock (CORTICUS) study [4]. Both of these studies have important limitations: 24% patients received etomidate in the study by Annane and colleagues, whereas 19% received etomidate in the CORTICUS study. The benefit of steroids in the study by Annane and colleagues may have been restricted largely to those patients who received etomidate [5]. Furthermore, only patients with 'refractory septic shock' were enrolled in the Annane study whereas, as a result of an overwhelming selection bias, only approximately 5% of eligible patients were enrolled in the CORTICUS study [6]. A more recent study found no benefit from a 7-day course of 40 mg of prednisolone in patients hospitalized with community-acquired pneumonia [7].In the study by Annane and colleagues [3], patients received 50 mg of hydrocortisone intravenously every 6 hours for 7 days, whereas in the CORTICUS study [4], patients received this dose for 5 days, followed by a tapering off over a further 5 days. Recently, two longitudinal studies in patients with severe community-acquired pneumonia found high levels of circulating inflammatory cytokines 3 weeks after clinical resolution of sepsis [8,9]. These data suggest that patients with severe sepsis may have prolonged immune