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Comment & Response
June 2019

Future Directions for Corticosteroids in Treatment of Sepsis

Author Affiliations
  • 1Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, Molecular and Behavioral Neuroscience Institute, Ann Arbor, Michigan
JAMA Intern Med. 2019;179(6):845. doi:10.1001/jamainternmed.2019.0859

To the Editor In their systematic review and meta-analysis of corticosteroids for treatment of sepsis, Fang and colleagues1 suggest that future studies should address the identification of patients who will derive the most benefit from corticosteroid use to enable a personalized medicine approach. I suggest additional directions for this field.

First, the ability of corticosteroids to increase blood pressure and reverse shock could explain their mortality benefit. Therefore, basic and clinical studies should focus on the mechanism of this effect. Corticosteroids act via 2 receptors: the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), which have differing tissue distributions and biologic properties. Even the so-called low-dose hydrocortisone treatment described in the included trials will result in clinically significant activation of both GR and MR, and 3 trials included additional MR-directed therapy with fludrocortisone. In contrast, dexamethasone and betamethasone have very little MR activity. Activity at either receptor may increase blood pressure via different mechanisms. Future trials designed to more specifically target one or the other receptor (eg, dexamethasone vs fludrocortisone) would improve understanding of the mechanism of corticosteroid effects in patients with sepsis. This understanding would enable a more targeted treatment that limits adverse effects.

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