What is the role of hydrocortisone (Cortisol) infusion in the management of septic shock?

From the Guidelines

Hydrocortisone infusion is recommended for adult patients with septic shock who remain hemodynamically unstable despite adequate fluid resuscitation and vasopressor therapy. The standard regimen is 200-300 mg of hydrocortisone per day, typically administered as a continuous intravenous infusion of 8-10 mg/hour for 5-7 days, followed by gradual tapering. Alternatively, it can be given as intermittent boluses of 50 mg every 6 hours. Treatment should be initiated within the first 6 hours of shock onset for optimal benefit. Blood glucose levels should be monitored regularly during treatment as hyperglycemia is a common side effect. Hydrocortisone works by enhancing vascular tone, increasing sensitivity to catecholamines, and reducing inflammatory cytokine production, which collectively help stabilize blood pressure and improve tissue perfusion. It should be discontinued once vasopressors are no longer needed, and abrupt cessation should be avoided to prevent adrenal insufficiency. Patients with suspected or confirmed adrenal insufficiency may require longer treatment courses. Hydrocortisone is preferred over other corticosteroids for this indication due to its balanced glucocorticoid and mineralocorticoid effects.

Key Considerations

• The use of hydrocortisone in septic shock is supported by guidelines from the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM) 1.
• The recommended dose and duration of treatment is a long course and low dose, such as IV hydrocortisone <400 mg/day for at least 3 days at full dose 1.
• The latest Cochrane systematic review of the use of low-dose hydrocortisone for treating septic shock showed that corticosteroids significantly reduced the risk of death at 28 days compared with placebo 1.
• Hydrocortisone boluses and infusions were more likely than methylprednisolone boluses and placebo to reverse shock 1.

Monitoring and Side Effects

• Blood glucose levels should be monitored regularly during treatment as hyperglycemia is a common side effect.
• The risk of superinfection and gastrointestinal bleeding is not increased with the use of low-dose corticosteroids 1.
• Abrupt cessation of hydrocortisone should be avoided to prevent adrenal insufficiency.

Patient Selection

• Patients with septic shock that is not responsive to fluid and moderate- to high-dose vasopressor therapy are the primary candidates for hydrocortisone therapy 1.
• Patients with suspected or confirmed adrenal insufficiency may require longer treatment courses.

From the Research

Role of Hydrocortisone Infusion in Septic Shock

The use of hydrocortisone infusion in the management of septic shock is a topic of ongoing research and debate. Several studies have investigated the effects of hydrocortisone on patient outcomes, including mortality, shock reversal, and adverse events.

Effects on Mortality and Shock Reversal

• A study published in 2016 2 found no significant difference in 28-day mortality between patients receiving two different regimens of hydrocortisone (200 mg vs. 300 mg per day).
• Another study published in 2024 3 found no difference in shock-free days between patients receiving hydrocortisone alone and those receiving hydrocortisone plus fludrocortisone.
• A study published in 2008 4 found that hydrocortisone did not improve survival or reversal of shock in patients with septic shock, although it did hasten reversal of shock in some patients.
• A study published in 2020 5 found that very low-dose hydrocortisone (75-150 mg/day) was as effective as standard-dose hydrocortisone (200-400 mg/day) in reversing shock and may have caused fewer adverse events.

Effects on Glycemic Control and Adverse Events

• A study published in 2007 6 found that continuous hydrocortisone infusion reduced fluctuations in blood glucose levels and made it easier to achieve tight blood glucose control compared to bolus infusion.
• The study published in 2020 5 also found that low-dose hydrocortisone may have caused fewer adverse events, including secondary infections and hyperglycemia, compared to standard-dose hydrocortisone.

Administration Modalities

• The study published in 2016 2 found no significant difference in outcomes between patients receiving hydrocortisone as a bolus every 6 hours and those receiving a continuous infusion.
• The study published in 2007 6 found that continuous infusion of hydrocortisone was associated with better glycemic control and reduced nursing workload compared to bolus infusion.