What are the relative potencies and durations of action of commonly used intravenous glucocorticoids (hydrocortisone, methylprednisolone, dexamethasone) and their typical dosing intervals?

Potency and Duration of Action of IV Steroids

For clinical practice, hydrocortisone has the shortest duration of action (biological half-life 8-12 hours), methylprednisolone has intermediate duration (12-36 hours), and dexamethasone has the longest duration (36-72 hours), with relative anti-inflammatory potencies of 1:5:25-30 respectively.

Relative Potencies

The three commonly used IV glucocorticoids differ substantially in their anti-inflammatory potency:

• Hydrocortisone: Baseline potency of 1 (reference standard) 1
• Methylprednisolone: 5 times more potent than hydrocortisone 1
• Dexamethasone: 25-30 times more potent than hydrocortisone 1

Critical conversion principle: When switching between agents, methylprednisolone 4 mg = hydrocortisone 20 mg = dexamethasone 0.75 mg in terms of anti-inflammatory effect 1

Duration of Action and Dosing Intervals

Hydrocortisone

• Biological half-life: 8-12 hours 1
• Plasma half-life: Approximately 90 minutes 2
• Recommended dosing interval: Every 4-6 hours when sustained high blood levels are needed 2
• Typical IV dose for stress/sepsis: 200-300 mg/day, given either as continuous infusion or as boluses every 6 hours 3
• Rationale for frequent dosing: The short 90-minute plasma half-life necessitates either continuous infusion or frequent bolus administration to maintain therapeutic levels 2

Methylprednisolone

• Biological half-life: 12-36 hours 1
• Typical dosing interval: Every 12-24 hours 3
• Standard pulse therapy: 500-1000 mg/day IV for 1-3 days for severe inflammatory conditions 3, 4
• For lupus nephritis: 250-500 mg/day for 3 consecutive days, or total dose 500-2500 mg depending on severity 3, 4
• For Behçet's syndrome: 1 g/day for up to 7 days 3

Dexamethasone

• Biological half-life: 36-72 hours 1
• Typical dosing interval: Once daily 5
• Standard dose for sepsis: 6 mg once daily 5
• Advantage: Longest duration allows once-daily dosing 5
• Disadvantage: Much longer half-life increases risk of adverse effects, particularly neurodevelopmental effects in neonates, and makes it unsuitable for physiologic replacement therapy 2

Clinical Implications by Indication

Sepsis and Septic Shock

• Hydrocortisone is preferred: 200-300 mg/day as continuous infusion or divided every 6 hours 3
• Continuous infusion is superior to intermittent boluses for maintaining physiologic cortisol concentrations 2
• Duration typically 7-14 days, or less if rapidly improving 3

Severe Autoimmune Disease (Lupus, Vasculitis)

• Methylprednisolone is preferred: 500-1000 mg/day for 3 consecutive days as pulse therapy 3, 4
• Follow with oral prednisone 0.3-0.5 mg/kg/day, rapidly tapered to ≤7.5 mg/day by 3-6 months 3
• The intermediate duration allows once or twice daily dosing while providing sustained immunosuppression 3

Acute Severe Asthma

• Hydrocortisone may be more effective: 200 mg every 4 hours showed shorter time to recovery compared to methylprednisolone 125 mg every 12 hours (median 30 vs 36 hours hospital stay, p=0.01) 6
• Alternative: Methylprednisolone, hydrocortisone, or dexamethasone at equivalent doses show similar efficacy in pediatric populations 7

COVID-19 ARDS

• Dexamethasone showed trend toward better outcomes: 6 mg once daily demonstrated better clinical status scores at 28 days compared to equivalent doses of methylprednisolone or hydrocortisone (p=0.003) 5

Common Pitfalls to Avoid

Do not assume plasma half-life equals duration of action: The biological effects persist far longer than plasma levels, particularly for methylprednisolone and dexamethasone 1

Do not use 1:1 conversion between methylprednisolone and prednisone: Methylprednisolone is 1.25 times more potent than prednisone 4

Do not stop corticosteroids abruptly after prolonged use: Inflammation may recur, especially with abrupt discontinuation 3. Patients receiving >14 days may require tapering and evaluation of hypothalamic-pituitary-adrenal axis function 3

Do not use dexamethasone for physiologic replacement: Its long half-life makes it unsuitable for mimicking natural cortisol rhythm and increases risk of over-replacement 2

Monitor for recurrence after discontinuation: Carefully observe all patients after stopping corticosteroids, as deterioration may occur requiring reinitiation 3

Adjust for liver disease: Cortisone and prednisone require hepatic conversion to active 11-beta-hydroxyl forms; this conversion may be impaired in liver disease 1