Hydrocortisone Dosing in Septic Shock Based on ADRENAL Trial
For patients with septic shock requiring vasopressors despite adequate fluid resuscitation, administer hydrocortisone 200 mg per day intravenously, given either as 50 mg IV every 6 hours or as a continuous 200 mg infusion over 24 hours. 1, 2, 3
Patient Selection Criteria
Reserve hydrocortisone exclusively for patients with vasopressor-dependent septic shock after adequate fluid resuscitation has been completed. 2 Specifically:
- Initiate when patients require moderate-to-high dose vasopressors (≥0.1 μg/kg/min norepinephrine equivalent) 1, 2
- The patient must remain hypotensive despite adequate fluid resuscitation and ongoing vasopressor therapy 1, 3
- Do not administer hydrocortisone in sepsis without shock—it provides no benefit and may cause harm 1, 2, 3
Dosing Regimen from ADRENAL Trial
The ADRENAL trial, which enrolled 3,658 patients with septic shock, established the standard dosing protocol: 1, 4
- Total daily dose: 200 mg hydrocortisone per day 1, 2, 3
- Administration options:
- Duration: Minimum 7 days or until ICU discharge/shock resolution 1, 2
- Maintain full dose for at least 3 days before considering any taper 2, 3
Key ADRENAL Trial Findings
The ADRENAL trial demonstrated that hydrocortisone in septic shock: 4
- Did not significantly reduce 90-day mortality (odds ratio 0.86; 95% CI 0.70-1.06; P=0.166) 4
- Accelerated shock reversal and vasopressor discontinuation 1, 4
- Increased days alive and free of mechanical ventilation (57.0 vs 53.7 days; P=0.028) 4
- Increased days alive and free of ICU (54.3 vs 51.0 days; P=0.014) 4
Timing of Initiation
Early initiation (≤3 hours) versus late (>3 hours) may reduce time to vasopressor discontinuation (25 hours vs 37 hours; P=0.009), though both strategies yield comparable mortality outcomes. 2, 6 The speed of treatment initiation influences prognosis, so do not delay once the decision is made. 2
Tapering Strategy
Taper hydrocortisone gradually when vasopressors are no longer required. 1, 2 While no comparative studies exist between fixed-duration and clinically-guided regimens, abrupt cessation may cause hemodynamic and immunologic rebound effects. 1 Continue treatment until shock resolves, maintaining full dose for at least 3 days. 2, 3
Absolute Indications (Do Not Delay Treatment)
Certain patient populations require immediate hydrocortisone without testing: 2
- Absolute adrenal insufficiency (peak cortisol after ACTH stimulation <18 μg/dL) with catecholamine-resistant shock 1, 2
- Purpura fulminans or Waterhouse-Friderichsen syndrome 2
- Prior chronic steroid therapy 2
- Known pituitary or adrenal abnormalities 2
ACTH Testing Controversy
Do not use the ACTH stimulation test to determine treatment eligibility in septic shock. 1, 2 The CORTICUS trial found no difference in hemodynamic response to corticosteroids between ACTH responders and non-responders. 1 Random cortisol levels have not been demonstrated useful for identifying relative adrenal insufficiency in septic shock patients. 1
Monitoring Requirements
Monitor the following parameters during hydrocortisone therapy: 2
- Blood glucose levels (hyperglycemia is the most common adverse effect) 2
- Signs of new infection or superinfection (increased risk of new sepsis and septic shock) 2
- Serum sodium (hypernatremia risk) 1
- Hemodynamic parameters for shock reversal 2
Critical Pitfall to Avoid
Never use etomidate for intubation in septic shock patients. 1, 2 Etomidate suppresses the hypothalamic-pituitary-adrenal axis and was associated with increased 28-day mortality in a CORTICUS trial subanalysis. 1
Special Population: Cirrhosis with Septic Shock
In patients with cirrhosis and septic shock, relative adrenal insufficiency occurs in 49% and is associated with significantly higher 90-day mortality (26% vs 10%). 1 The same dosing applies: hydrocortisone 50 mg IV every 6 hours or 200 mg infusion for 7 days or until ICU discharge. 1