What is the recommended use of corticosteroids, such as hydrocortisone (corticosteroid), in patients with sepsis and septic shock, particularly those with adrenal insufficiency or impaired renal function, and underlying medical conditions like diabetes, hypertension, or chronic obstructive pulmonary disease (COPD)?

Corticosteroid Use in Sepsis and Septic Shock

Primary Recommendation

Use intravenous hydrocortisone 200-300 mg/day in patients with septic shock requiring vasopressors despite adequate fluid resuscitation; do not use corticosteroids in sepsis without shock. 1

Clinical Decision Algorithm

Step 1: Identify Septic Shock vs. Sepsis Alone

• Septic shock criteria: Vasopressor requirement to maintain mean arterial pressure ≥65 mmHg AND serum lactate >2 mmol/L despite adequate fluid resuscitation 1
• Sepsis criteria: SOFA score ≥2 with confirmed or suspected infection 1
• Critical distinction: Corticosteroids are conditionally recommended for septic shock but NOT recommended for sepsis without shock 1

Step 2: Initiate Corticosteroids in Septic Shock

When to start:

• Begin hydrocortisone immediately when septic shock is confirmed (vasopressor-dependent hypotension despite fluids) 1
• Do not delay treatment waiting for ACTH stimulation test results 1, 2
• Patients with higher SOFA scores and refractory shock derive the greatest mortality benefit 1

Dosing regimen:

• Hydrocortisone 200-300 mg/day is the standard dose 1, 2
• Administration options: continuous IV infusion OR 50 mg IV bolus every 6 hours 1
• If using continuous infusion, give 50-100 mg bolus first 1
• Duration: 7-14 days at full dose, or less if rapidly improving 1

Step 3: Consider Mineralocorticoid Supplementation

• Adding fludrocortisone 50 mcg/day enterally may be helpful but is speculative 1, 2
• No clear evidence of superiority over hydrocortisone alone 1

Expected Benefits and Limitations

Mortality benefit:

• Approximately 2% absolute reduction in 28-day mortality (low certainty evidence) 1
• Benefit is modest and confidence intervals cross the line of no difference 1
• Patients at highest risk of death (high SOFA scores, refractory shock) likely benefit most 1

Hemodynamic effects:

• Accelerates shock reversal and reduces vasopressor requirements 1, 2, 3
• Increases vascular sensitivity to catecholamines 2, 3

Monitoring Requirements

During treatment:

• Monitor and treat hyperglycemia, hypernatremia, and hypokalemia 1
• Continue routine sepsis monitoring including serial SOFA scores 1
• Watch for superinfections, though risk is not clearly increased 1

After discontinuation:

• Critical pitfall: Inflammation may recur after stopping corticosteroids, especially if stopped abruptly 1
• Monitor closely for recurrence of shock or need for mechanical ventilation 1
• If deterioration occurs after stopping, consider reinitiating corticosteroids 1

Tapering Strategy

For courses >14 days:

• Gradual taper is recommended to prevent adrenal insufficiency 1, 4
• Evaluate hypothalamic-pituitary-adrenal axis function if uncertain 1

For courses 7-14 days:

• Tapering approach is unclear; can consider stopping without taper if rapidly improving 1
• Monitor for signs of adrenal insufficiency (fatigue, weakness, hypotension) 1, 4

Special Populations

Adrenal insufficiency:

• While relative adrenal insufficiency is common in septic shock (approximately 50% of patients), treatment decisions should be based on clinical criteria (shock requiring vasopressors) rather than ACTH stimulation test results alone 1, 5, 6
• Delta cortisol <9 μg/dL after 250 μg cosyntropin or random cortisol <10 μg/dL may guide decisions but are not required 1

Diabetes, hypertension, COPD:

• These comorbidities do not contraindicate corticosteroid use in septic shock 1
• Intensify glucose monitoring in diabetic patients 1
• The underlying conditions do not change the risk-benefit calculation 1

Impaired renal function:

• No dose adjustment needed for hydrocortisone 7
• Monitor electrolytes more closely (hypernatremia, hypokalemia) 1

Patient-Centered Decision Making

This is a weak recommendation where both approaches are reasonable: 1

• Patients who prioritize avoiding death over quality of life concerns would likely choose corticosteroids 1, 8
• Patients who value avoiding functional deterioration and maximizing quality of life over small mortality reduction may reasonably decline steroids 1
• The absolute mortality benefit is small (approximately 2%), and quality of life data are lacking 1

Common Pitfalls to Avoid

1. Do not use corticosteroids in sepsis without shock - no evidence of benefit and potential for harm 1, 8
2. Do not stop corticosteroids abruptly after prolonged use - risk of rebound inflammation and adrenal crisis 1, 4
3. Do not delay treatment waiting for ACTH test - initiate based on clinical criteria (vasopressor-dependent shock) 1, 5
4. Do not use high-dose corticosteroids - doses >400 mg/day hydrocortisone are not recommended 1, 3