What is the role of steroids, such as hydrocortisone (corticosteroid), in the management of septic shock, including indications, dosing, and the use of cortisol testing?

Steroids in Septic Shock: Indications, Mechanisms, and Management

Low-dose hydrocortisone should be administered to patients with septic shock who remain hemodynamically unstable despite adequate fluid resuscitation and moderate to high-dose vasopressor therapy (>0.1 μg/kg/min of norepinephrine or equivalent). 1, 2

Why We Use Steroids in Septic Shock

Corticosteroids are used in septic shock for several important reasons:

1. Shock Reversal: Corticosteroids consistently improve shock reversal with a relative risk of 1.12 (95% CI 1.02-1.23) at 28 days 2

2. Vasopressor Support: They enhance vascular sensitivity to catecholamines, allowing for faster weaning from vasopressors 2, 3

3. Addressing Relative Adrenal Insufficiency: Approximately half of patients with septic shock may have relative adrenal insufficiency or peripheral glucocorticoid resistance 4

4. Anti-inflammatory Effects: Cortisol antagonizes inflammatory cell migration and mediates cardiovascular tolerance to endotoxin 4

When to Use Steroids in Septic Shock

The decision to use steroids should follow a clear algorithm:

1. Start with standard septic shock management:

   • Adequate fluid resuscitation
   • Appropriate antimicrobial therapy
   • Source control

2. Assess response to initial therapy:

   • If the patient responds well to fluid resuscitation and low-dose vasopressors, steroids are NOT indicated 1, 2

3. Initiate steroids when:

   • Patient remains hemodynamically unstable despite adequate fluid resuscitation
   • Moderate to high-dose vasopressor therapy is required (>0.1 μg/kg/min of norepinephrine or equivalent) 1, 2
   • Early initiation (within 3 hours of meeting criteria) may reduce time needed to discontinue vasopressors 5

4. Do NOT use steroids in:

   • Patients with sepsis without shock 1, 2
   • Patients who respond adequately to fluid resuscitation and low-dose vasopressors 2

Which Steroids to Use and Dosing

Preferred Agent: Hydrocortisone is the preferred corticosteroid for septic shock 1, 2, 6

Dosing Regimen:

• Low-dose IV hydrocortisone <400 mg/day (typically 200 mg/day) 1, 2
• Administration options:
  • Continuous infusion (preferred for hemodynamic stability) 2, 6
  • Divided doses (e.g., 50 mg IV every 6 hours) 6, 7
• Duration: At least 3 days at full dose or until vasopressors are no longer required 1, 2
• Taper: Gradual tapering rather than abrupt discontinuation to prevent withdrawal symptoms 2, 6

Cortisol Testing in Septic Shock

Current guidelines do not recommend routine cortisol testing to guide steroid therapy:

• ACTH Stimulation Test: The American College of Critical Care Medicine does not recommend using cortisol response to ACTH to identify patients who should receive hydrocortisone 2

• Historical Context: Earlier studies (such as the 2002 study by Annane et al.) suggested benefit in non-responders to corticotropin testing 7, but more recent guidelines have moved away from this approach

• Current Approach: The decision to administer steroids should be based on clinical response to fluid resuscitation and vasopressor requirements rather than cortisol testing 1, 2

Monitoring and Adverse Effects

Potential Adverse Effects:

• Hyperglycemia (occurs in approximately 90.9% of patients) 1, 2
• Hypernatremia 1, 2, 6
• Secondary infections (though evidence suggests no significant increase in risk) 1, 3

Monitoring Requirements:

• Blood glucose levels
• Serum electrolytes
• Signs of secondary infections
• Hemodynamic parameters to assess response

Discontinuation

• Continue steroids until vasopressors are no longer required 2
• Taper gradually over several days rather than stopping abruptly 2, 6
• Monitor for signs of adrenal insufficiency during and after tapering

Special Considerations

• Contraindications: Avoid high-dose corticosteroids for septic shock management 4
• Traumatic Brain Injury: High doses of systemic corticosteroids should not be used for traumatic brain injury 6
• Fungal Infections: Use with caution in patients with systemic fungal infections 6
• Pediatric Patients: Limited evidence for use in pediatric septic shock; clinical trials are ongoing 1

By following these evidence-based recommendations, clinicians can optimize the use of steroids in septic shock to improve outcomes while minimizing potential adverse effects.