What is the role of corticosteroids (steroids) in the management of sepsis?

Corticosteroids in Sepsis

Consider using low-dose corticosteroids (hydrocortisone 200 mg/day for 5-7 days) in patients with septic shock requiring vasopressors, as they may reduce mortality by approximately 2% and accelerate shock reversal, though both using and not using steroids are reasonable options. 1

Clinical Decision Framework

When to Use Corticosteroids

Initiate corticosteroids in patients with:

• Septic shock requiring ≥0.5 μg/kg/min of norepinephrine to maintain adequate perfusion pressure 2
• SOFA score ≥2 with infection and vasopressor dependence 1
• Patients at highest risk of death (high SOFA scores, refractory shock) derive the greatest mortality benefit 1

Do NOT routinely use in:

• Sepsis without shock (absence of vasopressor requirement) 1
• Patients who can maintain blood pressure without significant vasopressor support 2

Dosing and Duration

Recommended regimen:

• Hydrocortisone 200 mg/day (most commonly studied agent) 1, 2
• Duration: 5-7 days of continuous therapy 2, 3
• Consider adding fludrocortisone 50 μg enterally daily, though its specific role remains uncertain 1, 2
• Administer via intermittent intravenous injection (most common practice pattern) 4

Early discontinuation criteria:

• Poor hemodynamic response after 2 days AND cortisol increment >250 nmol/L after ACTH stimulation test 2

Evidence Quality and Magnitude of Benefit

The BMJ guideline provides a weak recommendation based on moderate-quality evidence, acknowledging that both treatment approaches are reasonable 1. The mortality benefit is modest:

• Approximately 2% absolute reduction in 28-day mortality (confidence interval crosses line of no difference) 1
• Long-course, low-dose regimens show more consistent benefit (RR 0.87,95% CI 0.78-0.97) 3
• Shock reversal by day 7 increased significantly (RR 1.31,95% CI 1.14-1.51) 3
• SOFA scores improved by day 7 (mean difference -1.53) 3
• ICU length of stay reduced in survivors (mean difference -2.19 days) 3

Patient-Centered Decision Making

Patients who prioritize avoiding death over quality of life concerns would likely choose corticosteroids 1. Conversely, those who place higher value on avoiding functional deterioration and maximizing quality of life may reasonably decline steroids 1.

Important caveat: No trials have reported quality of life outcomes, creating uncertainty about long-term functional impact 1

Safety Profile

Corticosteroids do NOT increase:

• Gastroduodenal bleeding (RR 1.24,95% CI 0.92-1.67) 3
• Superinfection rates (RR 1.02,95% CI 0.87-1.20) 3
• Neuromuscular weakness (RR 0.62,95% CI 0.21-1.88) 3

Corticosteroids DO increase:

• Hyperglycemia (RR 1.26,95% CI 1.16-1.37) - maintain blood glucose <150 mg/dL 2, 3
• Hypernatremia (RR 1.64,95% CI 1.28-2.09) - monitor electrolytes closely 3

Role of ACTH Stimulation Testing

Testing is NOT required to initiate therapy 1. The decision should be based primarily on clinical status (vasopressor dependence) rather than cortisol levels 4. While patients with relative adrenal insufficiency may derive greater benefit, the diagnosis is highly dependent on cut-off values and definitions, making universal testing impractical 5. Most US practitioners (65%) base their decision on clinical status rather than serum cortisol analysis 4.

Mechanism of Benefit

Corticosteroids work through multiple pathways in septic shock:

• Restore cardiovascular homeostasis and increase pressor sensitivity 5, 6
• Terminate systemic and tissue inflammation through genomic and non-genomic effects 2, 6
• Counteract peripheral cortisol resistance that develops during sepsis 5
• Inhibit pro-inflammatory cytokine production and reduce free radical generation 6

Common Pitfalls to Avoid

• Do not use high-dose, short-course regimens (up to 42g hydrocortisone equivalent for 1-2 days) - these have been shown ineffective or harmful 5
• Do not withhold therapy while awaiting ACTH stimulation test results in vasopressor-dependent shock 2
• Do not continue beyond 7 days in patients with poor response and adequate cortisol response to ACTH 2
• Do not use in sepsis without shock - no evidence of benefit and potential for harm 1