In an adult with septic shock refractory to adequate fluid resuscitation and requiring high‑dose norepinephrine (≥0.5 µg/kg/min), should systemic corticosteroids be given?

Systemic Corticosteroids in Septic Shock

Yes, you should give hydrocortisone 200 mg/day IV to patients with septic shock who remain hypotensive (MAP <65 mmHg) despite adequate fluid resuscitation (≥30 mL/kg crystalloid) and high-dose norepinephrine (≥0.5 µg/kg/min or >0.1-0.2 µg/kg/min for >60 minutes), but only in this specific refractory population. 1, 2

When to Give Steroids: The Critical Threshold

The decision hinges on vasopressor responsiveness, not just the presence of septic shock:

• Give hydrocortisone when arterial pressure remains below target (MAP <65 mmHg) after at least 30 mL/kg crystalloid resuscitation AND moderate-to-high dose norepinephrine (>0.1-0.2 µg/kg/min) for more than 60 minutes 1, 2

• Do NOT give steroids if adequate fluid resuscitation and vasopressor therapy restore hemodynamic stability 3

• Do NOT give steroids in sepsis without shock—the benefit is confined to patients requiring vasopressor support 1, 2

This narrow indication reflects a critical evidence distinction: mortality benefit exists only in vasopressor-refractory shock, not in all septic shock patients 1, 4, 5.

Evidence Supporting This Approach

Mortality Benefit in the Right Population

• The French Annane trial (2002) demonstrated 53% mortality with hydrocortisone versus 63% with placebo (HR 0.67, p=0.02) specifically in patients with vasopressor-unresponsive shock and relative adrenal insufficiency 1

• The CORTICUS trial showed no mortality benefit when steroids were given to all septic shock patients regardless of vasopressor responsiveness, confirming that benefit is limited to refractory cases 1

• Baseline mortality differed dramatically between these trials (61% in Annane vs 31% in CORTICUS), underscoring that benefit is linked to higher-risk, vasopressor-dependent patients 1

Consistent Physiologic Benefits

• Hydrocortisone accelerates shock reversal (HR ≈1.9 for earlier vasopressor discontinuation) and reduces total vasopressor requirements across all major trials 1, 6, 7

• These hemodynamic improvements occur even when mortality benefit is absent, making steroids valuable for shortening ICU vasopressor duration 6

Dosing Protocol

Standard Regimen

• Hydrocortisone 200 mg/day administered as continuous IV infusion (preferred) or 50 mg IV every 6 hours 1, 2

• Continuous infusion is favored by guideline societies for steady plasma levels, though clinical outcomes are similar to intermittent dosing 1, 2

Duration and Tapering

• Maintain full dose for at least 3 days before considering reduction 1, 2

• Begin tapering only after vasopressors are discontinued—never before 1, 2

• Taper gradually over 6-14 days to avoid rebound inflammation and hemodynamic deterioration 1, 2

• Abrupt discontinuation is contraindicated and can precipitate hemodynamic collapse 1, 2

What NOT to Add

• Do NOT add fludrocortisone—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

Testing Errors

• Do NOT use ACTH stimulation testing to select patients—CORTICUS proved the test does not predict shock resolution or mortality benefit 1, 2

• Random cortisol levels are not useful for guiding steroid therapy in septic shock (though they may diagnose absolute adrenal insufficiency in other contexts) 1

Dosing Errors

• Avoid high-dose hydrocortisone (>400 mg/day)—it provides no additional benefit and increases adverse events 1, 2

• Low-dose regimens (200 mg/day) show no significant increase in superinfection rates, whereas high-dose regimens are harmful 1, 4, 5

Timing Errors

• Do not give steroids to patients whose blood pressure responds adequately to initial fluid and vasopressor therapy 3, 1

• Steroids are indicated only for vasopressor-refractory shock, not all septic shock 1, 4, 5

Drug Interaction

• Avoid etomidate for intubation in patients who may require hydrocortisone—it suppresses the HPA axis and worsens outcomes 1

Monitoring During Treatment

• Monitor serum sodium for hypernatremia, especially beyond 48-72 hours 2

• Monitor blood glucose for hyperglycemia (most common adverse effect) 2, 6

• Assess for superinfection, though risk is not significantly increased at low doses 1, 6

• Evaluate clinical response after 2-3 days to determine if therapy should continue 2

Special Populations

Patients with Escalating Vasopressor Requirements

• The mortality benefit appears greatest in patients with high vasopressor requirements, evidence of multiorgan failure, and primary lung infections 6

• Consider steroids earlier in patients requiring norepinephrine ≥0.5 µg/kg/min, as this represents severe refractory shock 1, 2

Pediatric Patients

• Use hydrocortisone only in children with suspected or proven "absolute" adrenal insufficiency, not for routine septic shock 3

• Pediatric dosing differs substantially: 1-2 mg/kg/day for stress coverage, up to 50 mg/kg/day titrated to shock reversal 2

Algorithm for Decision-Making

1. Confirm septic shock diagnosis (infection + hypotension requiring vasopressors to maintain MAP ≥65 mmHg after adequate fluid resuscitation) 3, 1

2. Administer ≥30 mL/kg crystalloid in first 3 hours 3, 1, 2

3. Initiate norepinephrine as first-line vasopressor, targeting MAP ≥65 mmHg 3, 1

4. Assess vasopressor responsiveness after 60 minutes of moderate-to-high dose norepinephrine (>0.1-0.2 µg/kg/min) 1, 2

5. If MAP remains <65 mmHg despite adequate fluid and vasopressor: Start hydrocortisone 200 mg/day IV 1, 2

6. If MAP ≥65 mmHg is achieved: Do NOT give steroids 3, 1

7. Continue hydrocortisone for at least 3 days, then taper over 6-14 days after vasopressors are stopped 1, 2