Are corticosteroids beneficial or harmful in adult patients with catecholamine‑refractory septic shock?

Corticosteroids in Septic Shock: A Conditional Lifeline for Refractory Cases

Corticosteroids are neither universal saviors nor villains in sepsis—they are a narrowly indicated rescue therapy reserved exclusively for adult patients with catecholamine-refractory septic shock whose blood pressure remains below target (MAP ≥65 mmHg) despite adequate fluid resuscitation and moderate-to-high dose vasopressors. 1

When Steroids Are Indicated: The Critical Threshold

Hydrocortisone 200 mg/day IV should be administered only when:

• Hypotension persists despite ≥30 mL/kg crystalloid resuscitation within the first 3 hours 1
• Norepinephrine requirements exceed 0.1–0.2 µg/kg/min for more than 60 minutes 1
• Mean arterial pressure remains <65 mmHg despite these interventions 2

This narrow indication reflects a conditional recommendation (Grade 2C) from the Surviving Sepsis Campaign, meaning the benefit is confined to the highest-risk subset of patients 2, 1.

The Evidence: Mortality Benefit Only in Refractory Shock

The mortality advantage of hydrocortisone is not universal—it emerges only in the sickest patients:

• The landmark French Annane trial (2002) demonstrated a 10% absolute mortality reduction (53% vs 63%, hazard ratio 0.67, p=0.02) in patients with vasopressor-unresponsive shock and relative adrenal insufficiency 1
• In stark contrast, the CORTICUS trial showed no mortality benefit when hydrocortisone was given to all septic shock patients regardless of vasopressor responsiveness 1
• The baseline mortality difference between these trials (61% in Annane vs 31% in CORTICUS) underscores that benefit is linked to higher-risk patients 1

Key physiologic benefits consistently observed across trials:

• Accelerated shock reversal with a hazard ratio ≈1.9 for earlier vasopressor discontinuation 1, 3
• Reduced total vasopressor requirements and duration 1, 4
• Restoration of vascular responsiveness to catecholamines 5, 6

When Steroids Are Contraindicated: Avoiding Harm

Do not administer corticosteroids in the following scenarios:

• Sepsis without shock: No benefit has been demonstrated, and the risk of superinfection outweighs any potential gain (Grade 1D) 2, 7
• Hemodynamically stable patients: If adequate fluid resuscitation and vasopressor therapy restore blood pressure, hydrocortisone provides no benefit and should be withheld 2, 1
• High-dose regimens (>400 mg/day): These increase adverse events without additional benefit and should be avoided 1, 7

Dosing, Administration, and Tapering Protocol

Standard regimen:

• Hydrocortisone 200 mg/day as a continuous IV infusion (preferred) or 50 mg IV every 6 hours 2, 1, 7
• Maintain full dose for at least 3 days before considering reduction 1, 7
• Begin tapering only after vasopressors are discontinued, reducing gradually over 6–14 days to avoid rebound inflammation and hemodynamic deterioration 1, 7

Fludrocortisone should not be added: A 2024 propensity-weighted analysis found no improvement in shock-free days, shock duration, or mortality when combined with hydrocortisone 1.

Critical Pitfalls to Avoid

• ACTH stimulation testing is not recommended for patient selection; the CORTICUS trial proved that test results do not predict shock resolution or mortality benefit (Grade 2B) 2, 1, 7
• Abrupt discontinuation is contraindicated because it precipitates hemodynamic and immunologic rebound 1, 7
• Etomidate use for intubation may suppress the hypothalamic-pituitary-adrenal axis and worsen outcomes when used before hydrocortisone initiation 1

Adverse Effects and Monitoring

Low-dose hydrocortisone (200 mg/day) does not significantly increase superinfection rates, whereas high-dose regimens (>400 mg/day) are associated with excess harm 1. However, vigilance is required:

• Monitor blood glucose regularly for hyperglycemia 7
• Assess serum sodium for hypernatremia 1
• Surveillance for secondary infections, gastrointestinal bleeding, and psychiatric effects 7

The Bottom Line: A Nuanced Tool, Not a Panacea

Corticosteroids are a conditional rescue therapy for the most severely ill septic shock patients whose vasopressor requirements remain refractory despite optimal resuscitation. 1 The benefit is real but narrow: faster shock reversal and reduced vasopressor duration, with a potential mortality advantage in the highest-risk subset 1, 3. For the majority of septic shock patients who respond to initial fluid and vasopressor therapy, hydrocortisone offers no benefit and should be withheld 2, 8. The key is recognizing the critical threshold—persistent hypotension despite adequate fluids and moderate-to-high dose norepinephrine—and reserving hydrocortisone for those who cross it 1, 7.