Corticosteroids in Septic Shock
Reserve IV hydrocortisone 200 mg/day (as continuous infusion or divided doses every 6 hours) for adult patients with septic shock who remain hemodynamically unstable despite adequate fluid resuscitation AND moderate-to-high dose vasopressors (>0.1 μg/kg/min norepinephrine equivalent), continuing for at least 3 days at full dose. 1, 2
When to Initiate Corticosteroids
Do NOT use corticosteroids if adequate fluid resuscitation and vasopressor therapy restore hemodynamic stability. 1 The Surviving Sepsis Campaign explicitly recommends against corticosteroid use when patients respond adequately to initial resuscitation. 1
Initiate corticosteroids only when:
- Fluid resuscitation is adequate AND
- Vasopressor requirements are moderate-to-high (>0.1 μg/kg/min norepinephrine or equivalent) AND
- Hemodynamic instability persists 1, 2
Never use corticosteroids for sepsis without shock - there is no mortality benefit and potential for harm. 1, 2
Dosing Regimen
Hydrocortisone is the preferred agent at 200 mg/day, administered as: 1, 2, 3
- Continuous IV infusion over 24 hours (preferred method) 2, 3, OR
- 50 mg IV bolus every 6 hours (if continuous infusion unavailable) 2, 3
Critical dosing principles:
- Doses must be <400 mg/day for ≥3 days at full dose - this is where mortality benefit exists 1, 2
- High-dose, short-course regimens (>400 mg/day for <3 days) do NOT improve outcomes 1, 3
- A Cochrane meta-analysis of 4,268 patients demonstrated survival benefits are dose-dependent: lower doses for longer duration are superior 1, 2
Duration and Tapering
Maintain full-dose therapy for at least 3-5 days before considering a taper. 1, 2, 3 Continue until vasopressors are no longer required. 1, 2
When vasopressors are discontinued, taper hydrocortisone gradually over 6-14 days rather than stopping abruptly to avoid rebound inflammation and hemodynamic deterioration. 2, 3 Abrupt cessation can lead to deterioration from reconstituted inflammatory response. 2
Evidence Quality and Nuances
The recommendation is based on conditional/weak evidence (Grade 2C). 1 However, corticosteroids consistently demonstrate:
- Faster shock reversal - 64.9% vs 47.5% at 7 days (RR 1.41,95% CI 1.22-1.64) 4
- Reduced time on vasopressors 4, 5, 6
- No increase in mortality (RR 1.00,95% CI 0.84-1.18) 4
The mortality benefit appears greatest in patients with high vasopressor requirements, multiorgan failure, and primary lung infections. 5
Monitoring and Adverse Effects
Expected adverse effects:
- Hyperglycemia (most common - 90.9% vs 81.5% in placebo) - monitor blood glucose closely 2, 3
- Hypernatremia - monitor serum sodium 2, 3
- NO increased risk of superinfection (RR 1.02,95% CI 0.87-1.20) 3 or gastrointestinal bleeding 1, 3
Critical Pitfalls to Avoid
Do NOT use ACTH stimulation testing to identify patients who should receive hydrocortisone - it has no role in clinical decision-making. 1, 2
Do NOT use corticosteroids in sepsis without shock - no benefit demonstrated and potential harm. 1, 2
Do NOT use high-dose, short-course regimens - they provide no benefit. 1, 3
Do NOT stop abruptly after several days of treatment - this can precipitate hemodynamic collapse. 2, 3
Avoid etomidate use prior to hydrocortisone initiation as it may worsen outcomes. 2