Corticosteroid Biology in Critical Illness: Modulatory Mechanisms and Clinical Implications
In recent years there has been renewed interest in the use of steroids in sepsis and septic shock, focusing on lower doses and longer courses with the aim of supplementing a presumed under-activity of the hypothalamic-pituitary-adrenal (HPA) axis due to relative adrenal insufficiency or target tissue glucocorticoid resistance. An international task force of the American College of Critical Care Medicine recently published guidelines for the diagnosis and treatment of what they termed “critical illness-related corticosteroid insufficiency” . This paper makes important recommendations regarding steroid therapy in sepsis and acute respiratory distress syndrome (ARDS). The authors also suggested biochemical definitions of relative adrenal insufficiency. A rational approach would be to use such definitions to make decisions regarding corticosteroid supplementation in critical illness. However, the authors concluded that the available literature provides no evidence to use such biochemical parameters as a basis for treating patients with supplemental steroids. This discordance, in large part, may arise from the fact that classical concepts of the HPA axis ignore many important nuances of glucocorticoid production, bioavailability and cellular action. The purpose of this chapter is to explore these nuances with particular focus on cellular and regional mechanisms of regulation of corticosteroid action, with specific reference to the context of critical illness.
KeywordsSeptic Shock Glucocorticoid Receptor Critical Illness Mineralocorticoid Receptor Relative Adrenal Insufficiency
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