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Abstract

The use of glucocorticoids (corticotherapy) in severe sepsis is one of the main controversial issues in critical care medicine. These agents were commonly used to treat sepsis until the end of the 1980s, when several randomized trials casted serious doubt on any benefit from high-dose glucocorticoids. Later, important progress in our understanding of the role played by the hypothalamic–pituitary–adrenal axis in the response to sepsis, and of the mechanisms of action of glucocorticoids led us to reconsider their use in septic shock. The present review summarizes the basics of the physiological response of the hypothalamic–pituitary–adrenal axis to stress, including regulation of glucocorticoid synthesis, the cellular mechanisms of action of glucocorticoids, and how they influence metabolism, cardiovascular homeostasis and the immune system. The concepts of adrenal insufficiency and peripheral glucocorticoid resistance are developed, and the main experimental and clinical data that support the use of low-dose glucocorticoids in septic shock are discussed. Finally, we propose a decision tree for diagnosis of adrenal insufficiency and institution of cortisol replacement therapy.

Magic bullets and surrogate biomarkers circa 2009*

“…Surprising was the fact that although early targeted corticosteroid therapy improved outcome, it had little impact on the circulating levels of IL-6, tumor necrosis factor-α, IL-1β, IL-2, macrophage inflammatory protein-1α, macrophage inflammatory protein-2, keratinocyte-derived cytokine, and monocyte chemoattractant protein-1, all bona fide inflammatory mediators, many with prognostic value in themselves. In addition, no significant reduction was observed on circulating numbers of neutrophils, platelets, or lymphocytes as is a common effect of corticosteroids and was observed earlier (13). …”

Stratification is the key: Inflammatory biomarkers accurately direct immunomodulatory therapy in experimental sepsis*

“…In both humans and laboratory animals, corticosteroids cause transient (up to 24 hours) lymphopenia and neutrophilia (27). These characteristic effects were absent in this study: approximately 15 hours after the first DEX injection (24 hours post-CLP time point), the lymphocyte (Fig.…”

New-Onset Atrial Fibrillation in Bacteremia Is Not Associated with C-Reactive Protein, but Is an Indicator of Increased Mortality during Hospitalization

“…On the other hand, the massive inflammatory chain of events during bacteremia may have overruled the anti-inflammatory action of a normal daily dose of methylprednisolone. Corticosteroid treatment is an unresolved issue in sepsis [45], and indeed it has not been evaluated yet whether patients who receive high doses of corticosteroids do have a lower incidence of new-onset AF than those without this treatment.…”