Are steroids indicated in sepsis management guidelines?

Steroids in Sepsis Bundle Guidelines

Steroids are conditionally indicated in sepsis bundle guidelines, but only for patients with septic shock who remain hypotensive despite adequate fluid resuscitation and vasopressor therapy—they should NOT be used in sepsis without shock. 1, 2

Key Guideline Recommendations

When to Use Steroids

The Surviving Sepsis Campaign (2016) provides clear guidance on corticosteroid use 1:

• Do NOT use IV hydrocortisone if adequate fluid resuscitation and vasopressor therapy restore hemodynamic stability 1
• Suggest IV hydrocortisone 200 mg/day only when hemodynamic stability cannot be achieved with fluids and vasopressors (weak recommendation, moderate quality evidence) 1, 2
• Corticosteroids should NOT be administered for sepsis in the absence of shock (strong recommendation) 1

Dosing and Administration

The recommended regimen is hydrocortisone 200 mg/day for at least 3 days at full dose 2, 3:

• Administer as continuous infusion (preferred) or divided doses 1, 3
• Continue for minimum 5-7 days at full dose before tapering 2
• Taper gradually over 6-14 days when vasopressors are no longer required rather than stopping abruptly 2, 3

Diagnostic Testing

Do NOT use the ACTH stimulation test to identify which patients should receive hydrocortisone (weak recommendation, moderate quality evidence) 1, 3. This test has no role in guiding treatment decisions in septic shock 2.

Evidence Quality and Nuances

The evidence shows important contradictions that clinicians must understand:

Mortality benefit is uncertain but shock reversal is clear 1, 4:

• A 2023 patient-level meta-analysis (n=7,882) found no significant mortality reduction with hydrocortisone alone (RR 0.93,95% CI 0.82-1.04) 4
• However, hydrocortisone with fludrocortisone showed better results (RR 0.86,95% CI 0.79-0.92) 4
• All studies confirm improved shock reversal and reduced vasopressor requirements 1, 5

The quality of evidence is moderate to low 1, 2, which explains why this is a conditional rather than strong recommendation. The 2012 Surviving Sepsis guidelines noted that patients with baseline mortality >60% showed trends toward benefit, while those with <50% mortality showed no benefit 1.

Clinical Algorithm

Step 1: Patient has septic shock (sepsis + hypotension requiring vasopressors)

Step 2: Ensure adequate fluid resuscitation completed

Step 3: Assess vasopressor response:

• If hemodynamic stability achieved → Do NOT give steroids 1
• If persistent hypotension despite moderate-to-high dose vasopressors → Consider hydrocortisone 200 mg/day 1, 2

Step 4: If starting hydrocortisone:

• Give as continuous infusion 1, 3
• Continue minimum 3 days at full dose 2
• Monitor for hyperglycemia and hypernatremia 2, 4

Step 5: When vasopressors no longer needed:

• Taper over 6-14 days (not abruptly) 2, 3

Critical Pitfalls to Avoid

Do not use steroids in sepsis without shock 1, 3. The HYPRESS trial definitively showed no benefit and potential harm in this population 2.

Do not stop hydrocortisone abruptly 2, 3. Abrupt discontinuation can cause rebound inflammation and hemodynamic deterioration 2.

Avoid etomidate for intubation in patients who may need steroids, as it suppresses the hypothalamic-pituitary-adrenal axis and may worsen outcomes 1, 3.

Do not rely on ACTH stimulation testing to guide therapy decisions 1, 3. The CORTICUS trial showed this test does not predict treatment response 1.

Adverse Effects to Monitor

Hydrocortisone may increase risk of 2, 4:

• Hypernatremia (RR 2.01,95% CI 1.56-2.60) 4
• Hyperglycemia (RR 1.26,95% CI 1.16-1.37) 5
• Muscle weakness (RR 1.73,95% CI 1.49-1.99) 4

Importantly, hydrocortisone does NOT significantly increase risk of superinfection (RR 1.04,95% CI 0.95-1.15) or gastrointestinal bleeding (RR 1.11,95% CI 0.83-1.48) 4, 5.