In how many divided doses should the stress dose of hydrocortisone be administered to a child with nephrotic syndrome on chronic steroid therapy?

Stress Dose Hydrocortisone in Nephrotic Syndrome: Divided Dosing

Stress dose hydrocortisone should be administered in 3-4 divided doses per day when given to children with nephrotic syndrome who are on chronic steroid therapy and experiencing acute illness. 1

Rationale for Divided Dosing

The physiologic basis for dividing stress doses stems from mimicking the body's natural cortisol secretion pattern during acute stress:

• Hydrocortisone has a short half-life (8-12 hours), requiring multiple daily doses to maintain adequate cortisol coverage during periods of physiologic stress 1
• Standard stress dosing is 50-100 mg/m²/day divided into 3-4 doses (or approximately 2-3 times the maintenance dose), given every 6-8 hours to maintain consistent serum levels 1
• The European Society of Pediatric Nephrology recommends continuing stress dosing during acute illness rather than switching back to oral prednisolone until the child is stable 1

Clinical Context for Stress Dosing

Stress dose coverage becomes necessary in specific situations:

• During acute infections, surgery, or severe illness when children on chronic steroids cannot mount adequate endogenous cortisol response due to HPA axis suppression 1
• Children who have received daily steroids for >2 weeks are at risk for HPA suppression and require stress coverage 2
• Divided dosing (versus single daily dosing) causes more HPA suppression (100% vs 83%, p=0.02), making stress coverage even more critical for children who received divided-dose maintenance therapy 2

Practical Administration

When implementing stress dose hydrocortisone:

• Give intravenously if the child cannot take oral medications due to vomiting, respiratory distress, or altered mental status 1
• Monitor for signs of adrenal crisis: hypotension, hypoglycemia, hyponatremia, hyperkalemia 1
• Taper back to maintenance dosing gradually once the acute illness resolves, typically reducing by 50% every 1-2 days until reaching baseline 1

Critical Distinction from Maintenance Therapy

This divided dosing for stress coverage differs fundamentally from maintenance nephrotic syndrome treatment:

• Maintenance prednisone/prednisolone is given as a single morning dose (60 mg/m²/day or 2 mg/kg/day, maximum 60 mg) to minimize HPA suppression 3
• Recent evidence suggests divided-dose prednisolone achieves faster remission (8.02 vs 9.74 days, p=0.001) but causes greater HPA suppression 4, 2
• Guidelines uniformly recommend single daily dosing for maintenance to preserve HPA axis function 3

Common Pitfall to Avoid

Do not confuse stress dose hydrocortisone (divided 3-4 times daily) with maintenance prednisolone therapy (single daily dose). The former is for acute physiologic stress in chronically suppressed patients, while the latter is for ongoing disease management. Failing to provide adequate divided-dose stress coverage during acute illness can precipitate life-threatening adrenal crisis in children with HPA suppression from chronic steroid use 1.