When should stress dose steroids, such as hydrocortisone (corticosteroid), be considered in critically ill, unresponsive patients, especially those with a history suggestive of adrenal insufficiency?

Stress Dose Steroids in Unresponsive Patients

In critically ill, unresponsive patients with suspected adrenal insufficiency, immediately administer hydrocortisone 100 mg IV bolus without waiting for diagnostic confirmation, followed by continuous IV infusion of 200 mg over 24 hours (or 50 mg IV every 6 hours), plus aggressive fluid resuscitation with 0.9% saline at 1 L/hour. 1, 2

When to Suspect Adrenal Insufficiency in Unresponsive Patients

Never delay treatment for diagnostic testing if adrenal crisis is suspected—mortality is high if untreated. 3, 1

Key clinical scenarios demanding immediate consideration:

• Unexplained hypotension refractory to fluids and vasopressors, particularly in septic shock 4, 5
• Altered mental status, confusion, or coma with unexplained collapse 3, 1
• History of chronic steroid use (≥20 mg/day prednisone or equivalent for ≥3 weeks) 3
• Severe gastrointestinal symptoms (vomiting, diarrhea) with hypotension 3, 1
• Hyponatremia (present in 90% of newly diagnosed adrenal insufficiency cases) 3
• Recent etomidate exposure for intubation (suppresses adrenal axis and increases 28-day mortality when combined with septic shock) 4

Immediate Management Protocol

Step 1: Emergency Treatment (Do Not Delay)

Administer immediately upon suspicion:

• Hydrocortisone 100 mg IV bolus 1, 5, 6
• 0.9% saline infusion at 1 L/hour (minimum 2-3 liters total) 1
• Draw blood for cortisol, ACTH, electrolytes, and glucose before hydrocortisone if possible, but do not delay treatment 3, 1

Critical pitfall: If you need to perform diagnostic testing later but must treat now, use dexamethasone 4 mg IV instead of hydrocortisone—it provides equivalent stress coverage (~200 mg hydrocortisone) but doesn't interfere with cortisol assays 3, 5. However, dexamethasone lacks mineralocorticoid activity and is inadequate for primary adrenal insufficiency 4, 3.

Step 2: Continuous Stress Dosing

Preferred method: Continuous IV infusion of hydrocortisone 200 mg over 24 hours (preceded by the initial 100 mg bolus) is superior to intermittent bolus dosing for maintaining physiologic cortisol levels during major stress 4, 2. This approach:

• Maintains stable cortisol concentrations in the range observed during major stress 2
• Avoids hyperglycemic peaks associated with bolus administration 4
• Reduces risk of hypernatremia 4

Alternative if continuous infusion unavailable: Hydrocortisone 50 mg IV every 6 hours (200 mg total daily) 1, 5, 6

Step 3: Supportive Care

• Frequent vital sign monitoring (blood pressure, heart rate) 1
• Serial electrolyte monitoring (sodium, potassium) 1
• Identify and treat precipitating cause (infection, trauma, etc.) 1

Specific Clinical Contexts

Septic Shock

The Surviving Sepsis Campaign guidelines recommend:

• Do NOT use ACTH stimulation testing to decide who receives hydrocortisone in septic shock 4
• Consider hydrocortisone only in vasopressor-dependent septic shock (not sepsis without shock) 4
• Hydrocortisone improves shock reversal but mortality benefit is uncertain in low-risk patients 4
• Taper steroids when vasopressors are no longer required (grade 2D recommendation) 4

Dosing: Hydrocortisone 200 mg/day as continuous infusion or divided doses for ≥7 days 6

Perioperative Patients

For patients with known or suspected adrenal insufficiency undergoing surgery 4:

• Minor stress: Double usual daily dose for 1-2 days 3
• Moderate stress: Hydrocortisone 50-75 mg daily 3
• Major stress: Hydrocortisone 100-150 mg daily 3

Continuous IV infusion is superior to intramuscular administration for maintaining appropriate plasma cortisol during the perioperative period 4.

Pediatric Patients

Evidence is insufficient to support routine use of stress-dose steroids in children with septic shock 4. However, stress-dose corticosteroids may be considered in children with septic shock unresponsive to fluids and requiring vasoactive support 4.

Diagnostic Considerations (After Stabilization)

Once the patient is stabilized, diagnostic workup can proceed:

• Random cortisol <250 nmol/L (<9 μg/dL) with elevated ACTH in acute illness is diagnostic of primary adrenal insufficiency 3
• Cosyntropin stimulation test: Peak cortisol <500 nmol/L (<18 μg/dL) at 30 or 60 minutes confirms adrenal insufficiency 3
• Do not rely on electrolyte abnormalities alone—hyperkalemia occurs in only ~50% of cases 3

Tapering and Transition

After 24-48 hours of IV therapy and clinical improvement:

• Taper stress-dose corticosteroids over 3-5 days 1
• Transition to oral maintenance therapy: hydrocortisone 15-25 mg daily in divided doses (typically 2/3 morning, 1/3 early afternoon) 1
• For primary adrenal insufficiency: Add fludrocortisone 0.05-0.1 mg daily when hydrocortisone dose falls below 50 mg daily 1

Common pitfall: Tapering too quickly before clinical stabilization increases risk of recurrent crisis 1.

Critical Pitfalls to Avoid

• Never wait for diagnostic confirmation in unstable patients with suspected adrenal crisis 3, 1
• Inadequate fluid resuscitation alongside corticosteroids—both are essential 1
• Using dexamethasone for primary adrenal insufficiency—it lacks mineralocorticoid activity 4, 3
• Failing to identify precipitating cause (infection, trauma, medication non-compliance) 1
• Abrupt cessation of steroids rather than gradual taper 4
• Assuming normal electrolytes exclude adrenal insufficiency—10-20% have normal electrolytes at presentation 3

Long-Term Prevention

For patients with confirmed adrenal insufficiency 1:

• Patient education on stress dosing (double or triple dose during illness) 3, 1
• Emergency injectable hydrocortisone 100 mg IM kit with self-injection training 1
• Medical alert bracelet indicating adrenal insufficiency 1
• Endocrine consultation for ongoing management 3