Corticosteroid Therapy in Critical Illness

Corticosteroids have long been employed as adjunctive therapy in critically ill patients, particularly those with sepsis and septic shock, to modulate excessive inflammation and support cardiovascular function. These hormones, broadly divided into glucocorticoids and mineralocorticoids, act via intracellular receptors to influence gene expression and exert rapid non-genomic effects on immune cells, vascular tone and metabolic pathways. In sepsis, endogenous corticosteroid production may be inadequate or delayed—a condition termed critical-illness-related corticosteroid insufficiency—leading to vasopressor dependence, refractory hypotension and disordered immune responses. Exogenous administration of moderate-dose hydrocortisone, often in combination with a mineralocorticoid such as fludrocortisone, can restore haemodynamic stability, shorten duration of shock and modulate cytokine release. However, patient selection, timing, dosing and duration remain subjects of ongoing debate. Recent investigations have explored optimal infusion strategies to reduce glycaemic fluctuations, the role of corticosteroids in mitigating post-shock organ dysfunction and strategies to overcome tissue resistance to glucocorticoids. Across diverse critical-care settings, the global significance of corticosteroid therapy lies in its potential to reduce mortality, shorten intensive-care stays and improve longer-term outcomes while balancing the risks of hyperglycaemia, immunosuppression and neuromuscular weakness.

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Corticosteroid Therapy in Critical Illness publication trend

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Technical terms

Glucocorticoids: A class of corticosteroids that primarily regulate metabolism and suppress inflammatory and immune responses through genomic and non-genomic mechanisms.

Mineralocorticoids: Corticosteroids that control salt and water balance by acting on renal and extrarenal receptors to influence vascular tone and fluid homeostasis.

Septic shock: A subset of sepsis characterised by profound circulatory, cellular and metabolic abnormalities, leading to persistent hypotension despite adequate fluid resuscitation and requiring vasopressors.

Critical-illness-related corticosteroid insufficiency (CIRCI): A state in which endogenous corticosteroid production or tissue responsiveness is inadequate to meet the heightened demands of critical illness, contributing to refractory shock.

Vasopressor dependence: The requirement for pharmacological agents, such as noradrenaline, to maintain adequate mean arterial pressure in the setting of circulatory failure.

References

1. Hydrocortisone-associated death and hospital length of stay in patients with sepsis: A retrospective cohort of large-scale clinical care data. Biomedicine & Pharmacotherapy (2023).
2. The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J‐SSCG 2016). Acute Medicine & Surgery (2018).
3. Effect of mode of hydrocortisone administration on glycemic control in patients with septic shock: a prospective randomized trial. Critical Care (2007).
4. Septic serum induces glucocorticoid resistance and modifies the expression of glucocorticoid isoforms receptors: a prospective cohort study and in vitro experimental assay. Critical Care (2013).
5. Updating the evidence for the role of corticosteroids in severe sepsis and septic shock: a Bayesian meta-analytic perspective. Critical Care (2010).