In a patient with septic shock who remains hypotensive after adequate fluid resuscitation and requires vasopressor support, what is the recommended low‑dose corticosteroid regimen, including dose, route, duration, need for taper, and use of fludrocortisone?

Hydrocortisone for Vasopressor-Dependent Septic Shock

In patients with septic shock who remain hypotensive despite adequate fluid resuscitation and vasopressor support, administer hydrocortisone 200 mg/day as a continuous infusion (or divided doses of 50 mg IV every 6 hours), continue for at least 3 days at full dose, then taper gradually over 6-14 days when vasopressors are no longer required. 1, 2

Indications for Hydrocortisone

• Hydrocortisone is indicated only in patients with septic shock who remain hypotensive despite adequate fluid resuscitation (minimum 30 mL/kg crystalloid) and vasopressor therapy 1, 2
• The typical threshold for "adequate vasopressor therapy" is moderate-to-high dose norepinephrine, generally >0.1-0.2 mcg/kg/min 2
• In practical terms, most clinicians interpret "poorly responsive" as requiring two vasopressors or a single high-dose vasopressor 3
• Do not administer hydrocortisone in patients with sepsis who do not have septic shock 1

Dosing Regimen

Standard Dose

• 200 mg per day of hydrocortisone is the recommended dose 1, 2
• Administer as a continuous infusion (preferred method) or divided doses of 50 mg IV every 6 hours 1, 2
• The continuous infusion is preferred over intermittent boluses based on guideline recommendations, though both are acceptable 2

Duration and Tapering Protocol

• Continue full-dose hydrocortisone for at least 3 days before considering any dose reduction 2
• Begin tapering only when vasopressors are no longer required, not before 1, 2
• Taper gradually over 6-14 days rather than stopping abruptly to avoid rebound inflammation and hemodynamic deterioration 1, 2
• Never stop abruptly—this causes hemodynamic and immunologic rebound effects 1

The gradual taper is critical because abrupt discontinuation can lead to reconstituted inflammatory response and hemodynamic instability 1. Most providers (76%) wait until patients are completely off vasopressors before making the first dose change 3.

Fludrocortisone Considerations

• The utility of adding fludrocortisone to hydrocortisone compared with hydrocortisone alone remains unclear 4
• Some older recommendations suggested enteral fludrocortisone 50 mcg per day for 7 days, but this is not consistently supported by current high-quality evidence 5
• Current guidelines do not routinely recommend fludrocortisone 6

Diagnostic Testing: What NOT to Do

• Do not use the ACTH stimulation test to identify patients who should receive hydrocortisone 1, 2
• The ACTH stimulation test has no role in determining who should receive treatment or when to reduce the dose 1
• Random cortisol levels may be useful for diagnosing absolute adrenal insufficiency but not for relative adrenal insufficiency in septic shock 1

This represents a major shift from older practice patterns. The landmark 2008 CORTICUS trial demonstrated no mortality benefit in patients who did not respond to corticotropin testing, fundamentally changing the approach to corticosteroid use in septic shock 7.

Benefits and Risks

Documented Benefits

• Improved shock reversal and faster resolution of shock 1, 4
• May shorten duration of mechanical ventilation 4
• Reduces vasopressor requirements 4, 6

Documented Risks

• Increased risk of superinfection, including new sepsis and septic shock 1, 7
• Frequently leads to hyperglycemia requiring monitoring and management 2, 4
• Monitor serum sodium for hypernatremia, especially if treatment extends beyond 48-72 hours 2

The mortality benefit remains controversial, with major trials showing conflicting results 4, 7, 6. However, the mortality benefit appears greatest in patients with high vasopressor requirements, evidence of multiorgan failure, and primary lung infections 4.

Critical Pitfalls to Avoid

• Avoid etomidate for intubation in patients who may require hydrocortisone, as it suppresses the hypothalamic-pituitary-adrenal axis and may be associated with increased mortality 1, 2
• Do not use hydrocortisone doses >400 mg per day—higher doses provide no additional benefit and may increase harm 2
• Do not delay initiation in patients with escalating vasopressor requirements and evidence of multiorgan dysfunction 4
• Reassess clinical response after 2-3 days to determine if therapy should continue 2