What is the best strategy for administering stress dose steroids?

Stress Dose Steroids Strategy

For patients with adrenal insufficiency experiencing major physiological stress (septic shock, major surgery, trauma), administer hydrocortisone 50-100 mg IV bolus immediately, followed by continuous IV infusion of 200 mg over 24 hours—this is the only method that consistently maintains cortisol levels in the physiologic stress range. 1, 2, 3

Initial Dosing by Clinical Severity

Severe Stress (G3-4): Septic Shock, Major Surgery, Adrenal Crisis

• Hydrocortisone 50-100 mg IV bolus at onset, followed immediately by continuous infusion of 200 mg/24 hours 1, 2, 3
• If continuous infusion unavailable: hydrocortisone 50 mg IV/IM every 6 hours 1, 2
• Continue full-dose therapy for minimum 3 days or until vasopressors no longer required 4
• Research demonstrates continuous infusion is superior to bolus dosing for maintaining therapeutic cortisol concentrations during major stress 3

Moderate Stress (G2): Moderate Symptoms, Able to Perform ADLs

• Hydrocortisone 20-30 mg orally in morning, 10-20 mg in afternoon (2-3× maintenance dose) 1, 5
• Taper to maintenance over 5-10 days 1
• For patients unable to take oral: hydrocortisone 50 mg IV/IM every 6-8 hours 1, 5

Mild Stress (G1): Minor Illness, Febrile Episodes

• Double the usual maintenance dose (typically 30-40 mg/day total in divided doses) 5, 2
• Continue doubled dose for 48 hours after minor stress resolves 2
• Standard maintenance: hydrocortisone 15-20 mg daily (10 mg morning, 5 mg afternoon, 5 mg evening) 5, 2

Critical Dosing Principles

Why These Doses Matter

• Normal daily cortisol production: 20 mg/day 5
• During major stress: cortisol requirements increase five-fold to approximately 100 mg/day 5, 2
• Doses >400 mg/day for <3 days show no benefit and potential harm 4
• Continuous infusion maintains cortisol in the 400-600 nmol/L range seen during major stress, while bolus dosing creates peaks and troughs 3

Hydrocortisone is Preferred

• Hydrocortisone is the drug of choice because it provides mineralocorticoid activity at physiologic doses 2, 4
• Dexamethasone 8 mg = hydrocortisone 200 mg equivalent, but lacks mineralocorticoid activity and is inadequate for primary adrenal insufficiency 1
• Use dexamethasone only if diagnosis uncertain and ACTH stimulation testing needed 1

Steroid Equivalencies

• Hydrocortisone 20 mg = Prednisone 5 mg = Dexamethasone 0.75 mg 1, 5, 2
• Long-acting steroids (prednisone) carry risk of over-replacement; use only if adherence to short-acting regimen impossible 1

Tapering Strategy

When to Begin Taper

• Start taper when hemodynamically stable, tolerating oral intake, and vasopressors discontinued 2, 4
• Never stop abruptly after >few days of treatment—risk of adrenal crisis 4

Taper Protocol

• Switch to oral hydrocortisone at double maintenance dose when stable 2
• Continue doubled oral dose for 48 hours (minor stress) to 1 week (major surgery) 2
• Taper IV stress doses to oral maintenance over 5-7 days 1, 5
• For hypophysitis/immune checkpoint inhibitor toxicity: taper over 1-2 weeks once down to prednisone 5 mg equivalent 1

Taper Caution

• Recent data shows 37.4% of patients require increased vasopressors at 24 hours after taper initiation 6
• Monitor closely during taper; heterogeneity in practice suggests need for individualized approach based on hemodynamic stability 6

Special Populations

Perioperative Patients

• Minor surgery: Continue usual daily dose, no stress dosing needed 1, 7
• Major surgery: Hydrocortisone 50-100 mg IV at induction, then 200 mg/24h continuous infusion 1, 2
• Patients on chronic therapeutic steroids (not replacement) do not require stress doses if continuing usual daily dose 7

Obstetric Patients

• At onset active labor (contractions every 5 min for 1 hour OR cervical dilation >4 cm): hydrocortisone 100 mg IV bolus 2
• Follow with 200 mg/24h continuous infusion OR 50 mg IM every 6 hours 2

Pediatric Patients

• Hydrocortisone 2 mg/kg IV at induction for any surgery under general anesthesia 2
• Following major surgery: 2 mg/kg IV/IM every 4 hours or continuous infusion 2

Septic Shock (ICU Patients)

• Initiate only when shock refractory despite adequate fluids AND moderate-to-high dose vasopressors (>0.1 μg/kg/min norepinephrine equivalent) 4
• Do not use in sepsis without shock—no mortality benefit, potential harm 4
• Hydrocortisone <400 mg/day for ≥3 days at full dose shows mortality benefit 4

Primary vs. Secondary Adrenal Insufficiency

Primary Adrenal Insufficiency

• Requires both glucocorticoid and mineralocorticoid replacement 1, 5
• Add fludrocortisone 0.05-0.1 mg/day to hydrocortisone regimen 1, 5
• Dexamethasone is inadequate (no mineralocorticoid activity) 1

Secondary Adrenal Insufficiency (Hypophysitis)

• Glucocorticoid replacement only (mineralocorticoid axis intact) 1
• Always start corticosteroids BEFORE other hormone replacements (thyroid, testosterone, estrogen)—these accelerate cortisol clearance and can precipitate adrenal crisis 1, 5, 2
• Follow free T4 for thyroid replacement (TSH unreliable in central hypothyroidism) 1

Diurnal Dosing for Maintenance

Hydrocortisone Preferred for Physiologic Replacement

• Give 2/3 of daily dose in morning, 1/3 in early afternoon to recreate diurnal cortisol rhythm 1
• Typical regimen: 10 mg morning, 5 mg afternoon, 5 mg evening (or 15 mg morning, 5 mg afternoon) 1, 5, 2
• Avoid evening doses (disrupts sleep) 1

Critical Pitfalls to Avoid

Never Delay Treatment

• Treat suspected adrenal crisis immediately—do not wait for diagnostic confirmation 5, 4
• Mortality risk significantly higher in untreated adrenal insufficiency 5
• Adrenal crisis can occur even when plasma cortisol appears normal (relative adrenal insufficiency) 5, 2

Avoid Bolus-Only Regimens for Major Stress

• Intermittent bolus dosing creates subtherapeutic troughs between doses 3
• Only continuous infusion maintains cortisol consistently in stress range 3

Do Not Use High-Dose Short-Course Regimens

• Doses >400 mg/day for <3 days show no benefit and potential harm 4
• Lower doses for longer duration are superior 4

Avoid Deltoid Injection

• High incidence of subcutaneous atrophy with deltoid injection 8, 9, 10

Drug Interactions

• CYP3A4 inducers (phenytoin, rifampin) increase hydrocortisone clearance—may need higher doses 1
• Etomidate suppresses cortisol production; maintain high suspicion for adrenal crisis 1

Patient Education Requirements

Mandatory for All Patients

• Emergency hydrocortisone injection kit (100 mg) for self-administration 5, 2
• Medical alert bracelet/necklace identifying adrenal insufficiency 1, 5, 2
• Stress dosing instructions for sick days 1, 5
• When to seek emergency care for impending adrenal crisis 1
• Early endocrinology consultation appropriate for education and long-term management 1

Monitoring During Treatment

Expected Adverse Effects

• Hyperglycemia most common (90.9% vs 81.5% placebo) 4
• Hypernatremia may occur 4
• No increased risk of secondary infections (RR 1.02,95% CI 0.87-1.20) 4
• No increased risk of GI bleeding 4

Endocrine Consultation Timing

• Before surgery or high-stress treatments 1
• At diagnosis of adrenal insufficiency 1
• For recovery and weaning protocols after prolonged steroid use 5