Clinical review: corticotherapy in sepsis

Helene Prigent, Virginie Maxime, Djillali Annane, Helene Prigent, Virginie Maxime, Djillali Annane

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.

Figures

Figure 1
Figure 1
Activation of the hypothalamic–pituitary–adrenal axis during acute stress. Activating effects are shown with plain arrows, and inhibitory effects with dotted arrows. The round symbols indicate the potential mechanisms that are involved in the axis dysfunction that occurs during sepsis either by failure of production or by tissue resistance to glucocorticoids. ACTH, adrenocorticotrophic hormone; AVP, arginine vasopressine; CBG, cortisol-binding globulin; CRH, corticotropin-releasing hormone; GRE, glucocorticoid responsive element; IFN, interferon; IL, interleukin; R, glucocorticoid receptor; ANS, autonomic nervous system; Th, T helper; TNF, tumour necrosis factor.
Figure 2
Figure 2
Strategy for detection and treatment of adrenal failure during sepsis. ACTH, adrenocorticotrophic hormone.

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