Should an adult with septic shock who remains hypotensive despite adequate fluid resuscitation and requires vasopressor support receive low‑dose hydrocortisone (with possible fludrocortisone), and what is the recommended dosing and taper schedule?

Hydrocortisone for Vasopressor-Refractory Septic Shock

Administer intravenous hydrocortisone 200 mg/day only when septic shock persists despite adequate fluid resuscitation (≥30 mL/kg crystalloid) and moderate-to-high dose norepinephrine (>0.1–0.2 µg/kg/min) for more than 60 minutes, with a mean arterial pressure remaining below 65 mmHg. 1

Patient Selection Criteria

You must verify all three conditions before starting hydrocortisone:

• The patient has received at least 30 mL/kg of crystalloid fluid within the first 3 hours 1, 2
• Norepinephrine dose exceeds 0.1–0.2 µg/kg/min for more than 60 minutes 1
• Mean arterial pressure remains below 65 mmHg despite the above interventions 1, 2

Do not give hydrocortisone if hemodynamic stability is achieved with fluids and a single low-dose vasopressor—the benefit is confined to refractory shock only. 1

Dosing Regimen

Standard dose: Hydrocortisone 200 mg per day, administered as:

• Continuous intravenous infusion (preferred method) for steady plasma levels 1
• Alternative: 50 mg IV bolus every 6 hours if continuous infusion is not feasible 1, 2

Never exceed 400 mg/day—higher doses provide no additional benefit and increase harm. 1, 2

Duration and Tapering Protocol

Maintain the full 200 mg/day dose for at least 3 days before considering any dose reduction. 1, 2 Some evidence supports continuing full-dose therapy for 5–7 days. 2

Begin tapering only after vasopressors have been discontinued:

• Taper gradually over 6–14 days 1, 2
• Never stop hydrocortisone abruptly—this precipitates rebound inflammation and hemodynamic deterioration 1, 2
• Monitor for shock relapse during taper, which is associated with persistent infection and prior etomidate use 3

Fludrocortisone: Do Not Add

Do not combine fludrocortisone with hydrocortisone. A 2024 propensity-weighted analysis found no improvement in shock-free days, shock duration, or mortality when fludrocortisone was added to hydrocortisone. 1 This is a strong recommendation against combination therapy.

Expected Clinical Benefits

Physiologic improvements (high-certainty evidence):

• Accelerates shock reversal with a hazard ratio of approximately 1.9 for earlier vasopressor discontinuation 1, 4
• Reduces total vasopressor requirements 1, 4
• May shorten duration of mechanical ventilation 5

Mortality benefit (low-quality evidence):

• The French Annane trial (2002) showed mortality reduction in vasopressor-unresponsive shock: 53% vs 63% (hazard ratio 0.67, p=0.02) 1
• The CORTICUS trial (2008) showed no overall mortality benefit (34.3% vs 31.5%, p=0.51), confirming benefit is limited to the most severely ill patients 1, 4
• Greatest mortality benefit appears in patients with high vasopressor requirements, multiorgan failure, and primary lung infections 5

Contraindications and Critical Pitfalls

Do NOT use hydrocortisone in these situations:

• Sepsis without shock—no benefit has been demonstrated 1, 2
• Hemodynamically stable patients after initial fluid and low-dose vasopressor therapy 1
• Doses exceeding 400 mg/day—associated with increased harm 1, 2

Do NOT perform ACTH stimulation testing to decide on hydrocortisone therapy. The CORTICUS trial proved that test results do not predict shock resolution or mortality benefit, and testing delays treatment. 1, 4 This is a strong recommendation against the test.

Avoid etomidate for intubation in patients who may require hydrocortisone, as it suppresses adrenal cortisol synthesis and worsens outcomes. 1

Monitoring Requirements

Monitor these parameters regularly during hydrocortisone therapy:

• Blood glucose every 4–6 hours for hyperglycemia (most common adverse effect) 2
• Serum sodium after 48–72 hours for hypernatremia 1, 2
• Signs of superinfection, though low-dose hydrocortisone (200 mg/day) does not significantly increase infection rates 1, 5

The CORTICUS trial reported more episodes of superinfection including new sepsis and septic shock with hydrocortisone, though this finding is debated. 4

Practical Implementation Algorithm

1. Confirm septic shock: Infection + hypotension requiring vasopressors after ≥30 mL/kg crystalloid 1
2. Start norepinephrine as first-line vasopressor, targeting MAP ≥65 mmHg 6
3. Assess at 60 minutes: If norepinephrine >0.1–0.2 µg/kg/min and MAP <65 mmHg, start hydrocortisone 200 mg/day 1
4. Continue full dose for 3–5 days minimum 1, 2
5. Taper only after vasopressor cessation over 6–14 days 1, 2

The strength of recommendation is conditional (Grade 2C) based on low-quality mortality evidence, but the physiologic benefits of faster shock reversal are high-certainty. 1