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

Hydrocortisone in Septic Shock

Hydrocortisone should not be used in septic shock patients if adequate fluid resuscitation and vasopressor therapy can restore hemodynamic stability, but should be administered at 200 mg/day when vasopressors alone cannot stabilize blood pressure. 1, 2

Patient Selection for Hydrocortisone Therapy

When to Use Hydrocortisone:

• Only in patients with septic shock who remain hemodynamically unstable despite:
  • Adequate fluid resuscitation
  • Vasopressor therapy 1, 2

When NOT to Use Hydrocortisone:

• Patients with sepsis without shock 2
• Patients with septic shock who respond adequately to fluids and vasopressors 1

The definition of "poorly responsive to vasopressors" is often interpreted as requiring two vasopressors before initiating hydrocortisone, which aligns with common clinical practice 3.

Dosing and Administration

Recommended Regimen:

• Intravenous hydrocortisone 200 mg/day 1, 2
• Administration options:
  • Continuous infusion (preferred) 1
  • Divided doses (e.g., 50 mg every 6 hours) 4

Duration and Discontinuation:

• Continue until vasopressors are no longer required 1, 2
• Taper hydrocortisone when discontinuing rather than stopping abruptly 1, 2

Clinical Benefits and Outcomes

Established Benefits:

• Faster shock reversal 5
• May reduce vasopressor requirements 2
• May reduce ICU length of stay by approximately 4.5 days 2

Mortality Impact:

• Evidence on mortality benefit is mixed:
  • The CORTICUS trial showed no significant difference in 28-day mortality (34.3% vs 31.5%, p=0.51) 5
  • More recent guidelines suggest potential mortality benefit in specific subgroups 2

Potential Adverse Effects

• Hyperglycemia (monitor blood glucose levels) 2
• Hypernatremia 2
• Increased risk of superinfection, including new sepsis and septic shock 5
• Muscle weakness 6

Important Clinical Considerations

ACTH Stimulation Test:

• Not recommended to identify patients who should receive hydrocortisone 1
• The CORTICUS trial showed no benefit of selecting patients based on cortisol response to ACTH 5

Contraindications:

• Sepsis without shock - a randomized trial (HYPRESS) showed no benefit of hydrocortisone in preventing progression to septic shock in patients with severe sepsis 6

Algorithm for Hydrocortisone Use in Septic Shock

1. Initiate standard septic shock management:

   • Fluid resuscitation
   • Vasopressor therapy to target MAP ≥65 mmHg

2. Assess response to initial therapy:

   • If hemodynamically stable with fluids and single vasopressor → DO NOT give hydrocortisone
   • If requiring escalating or multiple vasopressors despite adequate fluid resuscitation → START hydrocortisone

3. When starting hydrocortisone:

   • Administer 200 mg/day as continuous infusion or divided doses
   • Monitor for hyperglycemia and other adverse effects
   • Do not perform ACTH stimulation test

4. When discontinuing hydrocortisone:

   • Begin tapering when vasopressors are no longer required
   • Gradually reduce dose over several days rather than abrupt discontinuation

This approach aligns with the most recent Surviving Sepsis Campaign guidelines and focuses on using hydrocortisone only in patients who truly need it, while avoiding unnecessary exposure to potential adverse effects.