In adult patients with sepsis‑induced shock refractory to adequate fluid resuscitation and high‑dose norepinephrine, what does the Indian Surviving Sepsis Campaign guideline recommend for the use, dose, and duration of hydrocortisone (and optional fludrocortisone) therapy?

Steroids in Sepsis: Savior or Villain?

The Verdict: Conditional Savior in Refractory Shock Only

Hydrocortisone 200 mg/day IV should be administered only to adult patients with septic shock whose blood pressure remains below target (MAP ≥65 mmHg) despite adequate fluid resuscitation (≥30 mL/kg crystalloid) and vasopressor therapy—this is a conditional recommendation that positions steroids as a rescue therapy, not a routine intervention. 1, 2

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When Steroids Are Indicated: The Narrow Window

Mandatory Prerequisites Before Considering Steroids

• Adequate fluid resuscitation must be completed first: Minimum 30 mL/kg crystalloid bolus within the first 3 hours 1, 2
• Vasopressor therapy must be optimized: Norepinephrine as first-line agent, targeting MAP ≥65 mmHg 1, 3
• Hemodynamic instability must persist: Only when adequate fluid and vasopressor therapy fail to restore stability should hydrocortisone be considered 1, 2

The Critical Decision Point

Avoid hydrocortisone if adequate fluid resuscitation and vasopressor therapy restore hemodynamic stability (Grade 2C recommendation). 1 This is the pivotal distinction—steroids are reserved exclusively for vasopressor-refractory shock, not for all septic shock patients.

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Evidence-Based Dosing Protocol

Standard Regimen

• Hydrocortisone 200 mg per day administered as continuous IV infusion (preferred) or as 50 mg IV every 6 hours 1, 2
• Continuous infusion is favored for steady plasma levels, though clinical outcomes are similar to intermittent dosing (Grade 2D) 1, 2, 4
• Duration: Maintain full dose for at least 3 days before considering reduction 2

Fludrocortisone: Not Recommended

Do not add fludrocortisone to hydrocortisone. A 2024 propensity-weighted analysis found no improvement in shock-free days, shock duration, or mortality when fludrocortisone was combined with hydrocortisone. 5 This contradicts older meta-analyses 6, 7 that suggested benefit, but the most recent high-quality evidence from 2024 takes precedence and shows no added value. 5

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Clinical Benefits: What Steroids Actually Achieve

Mortality Benefit—Only in the Sickest Patients

• Mortality reduction demonstrated in refractory shock: The French Annane trial showed 53% mortality with hydrocortisone vs 63% with placebo (hazard ratio 0.67, p=0.02) among patients with vasopressor-unresponsive shock 2
• No benefit in less severe shock: The CORTICUS trial showed no overall mortality benefit when hydrocortisone was given to all septic shock patients regardless of vasopressor responsiveness 2
• Baseline mortality matters: Benefit is confined to higher-risk patients (61% mortality in French trial vs 31% in CORTICUS) 2

Physiologic Improvements—Consistent Across Studies

• Accelerated shock reversal: Hazard ratio ≈1.9 for earlier vasopressor discontinuation 2
• Reduced vasopressor requirements: Consistently observed across major trials 2, 8
• Faster resolution of shock: Improved time to hemodynamic stability 8

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Tapering Protocol: Avoiding Rebound Deterioration

When to Begin Tapering

• Start tapering only after vasopressors are discontinued (Grade 2D) 1, 2
• Never taper abruptly: Gradual reduction over 6–14 days is mandatory to avoid rebound inflammation and hemodynamic deterioration 2

The Danger of Abrupt Discontinuation

Abrupt discontinuation is contraindicated because it precipitates hemodynamic and immunologic rebound effects. 2 This is a strong recommendation based on physiologic principles and clinical experience.

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Critical Pitfalls to Avoid

Do Not Use ACTH Stimulation Testing

The ACTH stimulation test should not be used to identify patients who should receive hydrocortisone (Grade 2B). 1, 2 The CORTICUS trial definitively showed that test results do not predict faster shock resolution or mortality benefit. 2

Do Not Give Steroids for Sepsis Without Shock

Corticosteroids should not be administered for sepsis in the absence of shock (Grade 1D). 1 The benefit is strictly limited to patients requiring vasopressor support. 2

Avoid High-Dose Regimens

High-dose hydrocortisone (>400 mg/day) provides no additional benefit and increases adverse events. 2 Meta-analyses confirm that low-dose regimens (200 mg/day) carry no significant increase in superinfection rates, whereas high-dose regimens are associated with excess harm. 2, 8

Etomidate Caution

Etomidate use for intubation can suppress the hypothalamic-pituitary-adrenal axis and may be associated with increased mortality when used before steroid administration. 9 Consider alternative induction agents in patients likely to require hydrocortisone.

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Algorithmic Approach to Steroid Use in Septic Shock

Step 1: Initial Resuscitation (First 3 Hours)

• Administer ≥30 mL/kg crystalloid 1, 2
• Initiate norepinephrine if MAP <65 mmHg persists 1, 3
• Place arterial catheter for continuous BP monitoring 3, 2

Step 2: Assess Vasopressor Response (After 60 Minutes)

• If MAP ≥65 mmHg achieved: Do NOT give hydrocortisone 1
• If MAP <65 mmHg despite moderate-to-high dose norepinephrine (>0.1–0.2 µg/kg/min): Proceed to Step 3 2

Step 3: Optimize Vasopressor Therapy Before Steroids

• Add vasopressin 0.03 units/minute to norepinephrine 3, 2
• Consider epinephrine 0.05–2 mcg/kg/min if target MAP not achieved 3
• Add dobutamine 2.5–20 mcg/kg/min if persistent hypoperfusion with adequate MAP 3, 2

Step 4: Initiate Hydrocortisone for Refractory Shock

• Only if MAP <65 mmHg persists after Steps 1–3: Start hydrocortisone 200 mg/day IV continuous infusion 2
• Do not add fludrocortisone 5
• Do not perform ACTH stimulation test 2

Step 5: Maintenance and Monitoring

• Continue full dose for ≥3 days 2
• Monitor for hyperglycemia (most common adverse effect) 2
• Assess for shock reversal and vasopressor weaning 2

Step 6: Tapering

• Begin taper only after vasopressors discontinued 2
• Gradual reduction over 6–14 days 2
• Never stop abruptly 2

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Safety Profile: Balancing Risks and Benefits

Low Risk with Physiologic Dosing

• No significant increase in superinfection rates with 200 mg/day regimens 2, 8
• Hyperglycemia is the most common adverse effect but manageable with insulin 2
• No increased risk of gastrointestinal bleeding in most studies 8

High Risk with Inappropriate Use

• High-dose regimens (>400 mg/day) increase harm without added benefit 2
• Use in non-shock sepsis provides no benefit and exposes patients to unnecessary risk 1, 2

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Real-World Practice Variation

A 2024 Japanese multicenter study revealed considerable variation in steroid use for septic shock: only 35% of patients received steroids, with inconsistent criteria for patient selection and administration method (intermittent vs continuous). 4 This highlights the ongoing controversy and the need for adherence to evidence-based protocols.

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The Bottom Line: Context-Dependent Therapy

Steroids are neither universal savior nor villain—they are a conditional rescue therapy for the subset of septic shock patients who remain hemodynamically unstable despite optimal fluid resuscitation and vasopressor support. 1, 2 The key is patient selection: hydrocortisone 200 mg/day benefits only those with refractory shock, accelerates vasopressor weaning, and may reduce mortality in the sickest patients, but offers no advantage (and potential harm) when used indiscriminately in all septic shock cases. 2, 8