What is the role of hydrocortisone (corticosteroid) in managing septic shock?

Hydrocortisone in Septic Shock

Hydrocortisone should be used only in patients with septic shock who remain hypotensive despite adequate fluid resuscitation and moderate-to-high dose vasopressor therapy (>0.1 μg/kg/min norepinephrine or equivalent), administered as 200 mg/day intravenously for at least 3 days at full dose. 1, 2, 3

When to Initiate Hydrocortisone

Reserve hydrocortisone for vasopressor-unresponsive septic shock only:

• Do NOT use hydrocortisone if hemodynamic stability can be achieved with fluids and vasopressors alone 1
• Do NOT use hydrocortisone in sepsis without shock—this provides no benefit and may cause harm 1, 3
• Initiate hydrocortisone when patients require moderate-to-high dose vasopressors (>0.1 μg/kg/min norepinephrine equivalent) after adequate fluid resuscitation 1, 3

The evidence supporting this approach comes from multiple sources: The 2017 SCCM/ESICM guidelines analyzed 33 RCTs (4,268 patients) showing mortality benefit only with low-dose, long-duration therapy in severe shock 1. The landmark APROCCHSS trial (1,241 patients) demonstrated 90-day mortality reduction from 49.1% to 43.0% (P=0.03) with hydrocortisone plus fludrocortisone in refractory septic shock 4.

Dosing Protocol

Use low-dose, long-duration therapy:

• Hydrocortisone <400 mg/day (typically 200 mg/day) 1, 2, 3
• Continue for at least 3 days at full dose 1, 3
• Administer as continuous infusion (preferred) or divided doses every 6 hours 1, 2, 3
• Taper gradually over 6-14 days when vasopressors are no longer required—never stop abruptly 3

The Cochrane meta-analysis demonstrated that doses <400 mg/day for ≥3 days were superior to high-dose, short-course regimens 1. Continuous infusion is preferred over bolus dosing 1, 2.

Diagnostic Testing

Do NOT use the ACTH stimulation test to guide therapy:

• The ACTH stimulation test should not be used to identify which patients should receive hydrocortisone 1, 2, 3
• The CORTICUS trial showed the ACTH test did not predict shock reversal or mortality benefit 1, 5
• Base the decision on hemodynamic response to fluids and vasopressors, not cortisol levels 1

Expected Benefits

Hydrocortisone improves shock reversal but mortality benefit is conditional:

• Faster reversal of shock and reduced vasopressor requirements (17 vs 15 vasopressor-free days, P<0.001) 4
• More organ-failure-free days (14 vs 12 days, P=0.003) 4
• Mortality benefit demonstrated in the most recent high-quality trial (APROCCHSS) but not in earlier CORTICUS trial 5, 4
• The difference in outcomes relates to patient selection: APROCCHSS enrolled patients with refractory shock (baseline mortality 49%), while CORTICUS included less severe shock (baseline mortality 31%) 1

Risks and Monitoring

Monitor for specific adverse effects:

• Hyperglycemia (most common adverse effect) 1, 3, 4
• Hypernatremia 1, 3
• Increased risk of superinfection, including new sepsis and septic shock 2, 5
• No increased risk of gastrointestinal bleeding in meta-analyses 1

Critical Pitfalls to Avoid

Avoid these common errors:

• Do not use hydrocortisone in sepsis without shock—the HYPRESS trial showed no benefit and no difference in progression to shock (P=0.70) 1
• Do not use high-dose, short-course steroids—doses >400 mg/day or duration <3 days are ineffective or harmful 1, 3
• Avoid etomidate for intubation in patients who may require hydrocortisone, as it suppresses the HPA axis and may worsen outcomes 2, 3
• Do not stop hydrocortisone abruptly—taper over 6-14 days to prevent rebound inflammation and hemodynamic deterioration 3
• Do not delay vasopressor initiation while waiting to start hydrocortisone—the threshold for hydrocortisone use is failure to respond to vasopressors, not avoidance of them 1

Algorithm for Decision-Making

1. Confirm septic shock diagnosis (sepsis + hypotension requiring vasopressors after adequate fluid resuscitation) 1
2. Optimize fluid resuscitation and initiate vasopressors (norepinephrine first-line) 1
3. Assess vasopressor dose after adequate resuscitation: If requiring >0.1 μg/kg/min norepinephrine equivalent → START hydrocortisone 200 mg/day 1, 3
4. Continue for minimum 3 days at full dose, then taper over 6-14 days as vasopressors are weaned 1, 3