In a patient with infective endocarditis who develops septic shock refractory to adequate fluid resuscitation and high‑dose vasopressors, should stress‑dose hydrocortisone be administered?

Hydrocortisone for Septic Shock in Infective Endocarditis

Direct Recommendation

In a patient with infective endocarditis who develops septic shock refractory to adequate fluid resuscitation (≥30 mL/kg crystalloid) and moderate-to-high dose vasopressors (norepinephrine >0.1–0.2 µg/kg/min for >60 minutes), administer intravenous hydrocortisone 200 mg/day. 1, 2

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Clinical Decision Algorithm

Step 1: Confirm Septic Shock Criteria

• Infection confirmed (infective endocarditis in this case) 1
• Hypotension requiring vasopressors to maintain MAP ≥65 mmHg after adequate fluid resuscitation 1, 2
• Adequate fluid resuscitation completed: at least 30 mL/kg crystalloid within first 3 hours 2

Step 2: Assess Vasopressor Requirements

• First-line vasopressor: Norepinephrine titrated to MAP ≥65 mmHg 1, 2
• Threshold for hydrocortisone: Norepinephrine dose >0.1–0.2 µg/kg/min for more than 60 minutes, OR requirement for two vasopressors 2, 3
• Do NOT give hydrocortisone if hemodynamic stability is achieved with fluids and single low-dose vasopressor 1, 2

Step 3: Initiate Hydrocortisone if Criteria Met

• Dose: 200 mg/day intravenous hydrocortisone 1, 2, 4
• Administration: Continuous infusion (preferred) or 50 mg IV every 6 hours 1, 2, 4
• Duration: Maintain full dose for at least 3 days before considering any reduction 1, 2, 4

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Evidence Base and Strength

Mortality Evidence

The evidence for mortality benefit is mixed and context-dependent:

• The CORTICUS trial (2008) showed no overall mortality benefit from hydrocortisone in septic shock (34.3% vs 31.5%, p=0.51), regardless of ACTH stimulation test results 5
• However, earlier French trials demonstrated mortality reduction specifically in patients with vasopressor-unresponsive shock and relative adrenal insufficiency (53% vs 63%, HR 0.67, p=0.02) 2
• The key difference: baseline mortality was 61% in the French trial versus 31% in CORTICUS, indicating benefit is confined to the most severely ill, refractory-shock population 2

Consistent Physiologic Benefits

Despite mortality uncertainty, hydrocortisone reliably accelerates shock reversal:

• Faster vasopressor discontinuation (HR ≈1.9) across multiple trials 2, 5
• Reduced total vasopressor requirements 2, 5
• These benefits are high-certainty evidence and form the basis for the conditional recommendation 2

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Dosing and Administration Details

Standard Regimen

• 200 mg/day is the evidence-based dose; doses >400 mg/day provide no additional benefit and increase harm 1, 2, 4
• Continuous infusion is preferred over intermittent boluses for steady plasma levels 1, 2, 4
• Alternative: 50 mg IV every 6 hours if continuous infusion unavailable 1, 2, 4

Duration and Tapering

• Minimum 3 days at full dose before considering taper 1, 2, 4
• Begin taper only after vasopressors discontinued, not before 1, 2, 4
• Taper gradually over 6–14 days to avoid rebound inflammation and hemodynamic deterioration 2, 4
• Never stop abruptly—this causes reconstituted inflammatory response and shock relapse 2, 6, 7

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Critical Contraindications and Pitfalls

Do NOT Use Hydrocortisone If:

• Hemodynamic stability achieved with fluids and low-dose single vasopressor 1, 2
• Sepsis without shock (no vasopressor requirement)—no benefit demonstrated 1, 6, 4

Avoid These Common Errors:

1. Do NOT use ACTH stimulation testing to decide on hydrocortisone—it does not predict benefit and delays treatment 1, 2, 4
2. Do NOT use etomidate for intubation in patients who may need hydrocortisone—it suppresses adrenal function and worsens outcomes 2, 4, 7
3. Do NOT add fludrocortisone—2024 analysis showed no improvement in shock-free days or mortality with combination therapy 2
4. Do NOT use high-dose regimens (>400 mg/day)—associated with increased harm without additional benefit 1, 2, 4

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Monitoring During Treatment

Essential Parameters:

• Blood glucose: Hyperglycemia is the most common adverse effect; monitor regularly 6, 4
• Serum sodium: Check for hypernatremia, especially after 48–72 hours 4
• Infection surveillance: Hydrocortisone blunts febrile response; remain vigilant for superinfection 6, 5
• Clinical response: Reassess after 2–3 days to determine if therapy should continue 4

Adverse Effects to Watch:

• Superinfection risk: CORTICUS showed increased episodes of new sepsis and septic shock with hydrocortisone 5
• However, meta-analyses of low-dose regimens (200 mg/day) show no significant increase in superinfection rates 2
• The risk-benefit ratio favors treatment in truly refractory shock 2

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Special Considerations for Infective Endocarditis

While the evidence base for hydrocortisone in septic shock does not specifically address infective endocarditis as a distinct subgroup, the same principles apply:

• IE patients with vasopressor-refractory shock meet criteria for hydrocortisone 1, 2
• The underlying infection source (endocarditis) does not contraindicate steroid use 1
• Source control remains paramount—hydrocortisone is adjunctive therapy, not a substitute for appropriate antibiotics and surgical evaluation when indicated 1

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Strength of Recommendation

The Surviving Sepsis Campaign gives this a Grade 2C recommendation (conditional recommendation, low-quality evidence) 1, 2. This reflects:

• Consistent physiologic benefit (shock reversal) but uncertain mortality benefit 2, 5
• Benefit confined to refractory shock—not all septic shock patients 2
• Low risk when used at appropriate doses (200 mg/day) with proper monitoring 2

In clinical practice, the decision threshold is clear: if your patient with IE-related septic shock requires norepinephrine >0.1–0.2 µg/kg/min for >60 minutes despite adequate fluids, start hydrocortisone 200 mg/day. 1, 2, 4