In a patient with refractory septic shock (or shock due to adrenal insufficiency or anaphylaxis), what is the recommended continuous intravenous hydrocortisone infusion regimen, including dose, initiation criteria, duration, tapering schedule, and monitoring?

Hydrocortisone Infusion in Refractory Septic Shock

Initiation Criteria

Hydrocortisone 200 mg/day IV should be started only when mean arterial pressure remains below 65 mmHg despite adequate fluid resuscitation (≥30 mL/kg crystalloid) and moderate-to-high dose norepinephrine (>0.1–0.2 µg/kg/min) for more than 60 minutes. 1

• Do not initiate hydrocortisone if hemodynamic stability is achieved with fluids and a single low-dose vasopressor. 2, 1
• Norepinephrine is the first-line vasopressor; hydrocortisone is reserved for vasopressor-refractory shock only. 2, 3
• Do not use the ACTH stimulation test to decide whether to start hydrocortisone—it does not predict shock reversal or mortality benefit and delays treatment. 2, 1, 3
• Do not administer hydrocortisone in sepsis without shock; no benefit has been demonstrated and harm may occur. 2, 3

Dosing Regimen

Administer hydrocortisone 200 mg per day as a continuous intravenous infusion (preferred method). 2, 1, 3

• Alternative regimen: hydrocortisone 50 mg IV every 6 hours if continuous infusion is not feasible. 2, 1
• Do not exceed 400 mg/day; higher doses provide no additional benefit and increase adverse effects. 1, 4
• Maintain the full 200 mg/day dose for at least 3 days before considering any dose reduction. 2, 1, 4

Duration and Tapering

Continue hydrocortisone at full dose (200 mg/day) for a minimum of 3 days, then begin tapering only after vasopressors have been discontinued. 2, 1, 4

• Taper gradually over 6–14 days rather than stopping abruptly to avoid rebound inflammation and hemodynamic deterioration. 2, 1, 4
• Abrupt discontinuation is contraindicated because it can precipitate hemodynamic collapse and reconstituted inflammatory response. 1, 4
• If vasopressors are restarted during the taper, return to full-dose hydrocortisone. 4

Fludrocortisone: Not Recommended

Do not add fludrocortisone to hydrocortisone. 1

• A 2024 propensity-weighted analysis found no improvement in shock-free days, shock duration, or mortality when fludrocortisone was combined with hydrocortisone. 1
• Recent retrospective data (2023) showed no difference in time to shock reversal or mortality with fludrocortisone plus hydrocortisone versus hydrocortisone alone. 5

Monitoring

Monitor blood glucose regularly for hyperglycemia, the most common adverse effect. 4, 3

• Check serum sodium for hypernatremia, especially after 48–72 hours of therapy. 1, 4
• Remain vigilant for superinfection, though low-dose hydrocortisone (200 mg/day) has not shown a significant increase in infection rates in major trials. 1, 3
• Monitor blood pressure and vasopressor requirements to guide tapering decisions. 4

Expected Clinical Benefits

Hydrocortisone accelerates shock reversal (hazard ratio ≈ 1.9 for earlier vasopressor discontinuation) and reduces total vasopressor requirements. 1

• These physiologic benefits are consistently observed across randomized trials and represent high-certainty evidence. 1
• Mortality benefit is confined to the most severely ill, vasopressor-refractory population; overall mortality evidence is low quality and conflicting. 1, 6
• The French Annane trial (2002) demonstrated mortality reduction (53% vs 63%, HR 0.67, p=0.02) in patients with vasopressor-unresponsive shock and relative adrenal insufficiency. 1
• The CORTICUS trial (2008) showed no overall mortality benefit in a broader septic shock population, confirming that benefit is limited to refractory cases. 1

Critical Pitfalls to Avoid

Avoid etomidate for rapid-sequence intubation in patients who may require hydrocortisone. 1, 4

• Etomidate suppresses adrenal cortisol synthesis and may worsen outcomes when used before hydrocortisone initiation. 1, 7

Do not use hydrocortisone in patients who achieve hemodynamic stability with fluids and low-dose vasopressors. 2, 1, 3

• The Surviving Sepsis Campaign gives a conditional recommendation (Grade 2C) that hydrocortisone is indicated only when adequate fluid resuscitation and vasopressor therapy fail to restore hemodynamic stability. 2

Do not use high-dose regimens (>400 mg/day). 1, 4

• High-dose corticosteroids are associated with increased harm without added benefit. 1, 8

Special Populations

Adrenal Insufficiency or Anaphylaxis

In suspected adrenal crisis or anaphylaxis with volume-resistant hypotension, give hydrocortisone 100 mg IV immediately without waiting for diagnostic confirmation, followed by 200 mg/24 hours as continuous infusion. 2, 4

• Never delay treatment for diagnostic procedures in suspected adrenal crisis—mortality is high if untreated. 4
• A random cortisol level <18 µg/dL in a patient with shock suggests absolute adrenal insufficiency and supports hydrocortisone use. 1

Pediatric Patients

In children with vasopressor-refractory septic shock, consider hydrocortisone 1 mg/kg every 6 hours (pediatric stress dose). 4

• Hydrocortisone is advised only for children with suspected or confirmed absolute adrenal insufficiency; it is not indicated for routine pediatric septic-shock management. 1

Strength of Recommendation

The Surviving Sepsis Campaign issues a conditional Grade 2C recommendation (low-quality evidence) for hydrocortisone in refractory septic shock. 2, 1, 3

• The recommendation is conditional because mortality benefit is uncertain and confined to the highest-risk subgroup, while physiologic benefits (faster shock reversal, reduced vasopressor requirements) are consistent and well-established. 1, 3