Duration of Action for Intravenous Hydrocortisone
Intravenous hydrocortisone demonstrates effects within one hour of administration and requires redosing every 4-6 hours to maintain therapeutic blood levels, with nearly complete excretion occurring within 12 hours. 1
Pharmacokinetic Profile
The FDA drug label provides the definitive pharmacokinetic parameters for IV hydrocortisone:
- Onset of action: Demonstrable effects are evident within 1 hour of IV injection 1
- Duration of effect: Effects persist for a variable period, but excretion of the administered dose is nearly complete within 12 hours 1
- Redosing interval: If constantly high blood levels are required, injections should be made every 4-6 hours 1
Clinical Application of Dosing Intervals
For stress-dose coverage in critical illness, continuous infusion is preferred over bolus dosing to maintain stable therapeutic levels. 2
Bolus Dosing Regimens
When continuous infusion is not practical, the following bolus schedules maintain adequate coverage:
- Every 6 hours: Hydrocortisone 50 mg IV or IM every 6 hours provides adequate perioperative coverage 2, 3
- Every 4 hours: In pediatric postoperative patients, hydrocortisone 2 mg/kg every 4 hours maintains therapeutic levels 2, 4
Continuous Infusion Protocols
For major surgery or septic shock requiring sustained high cortisol levels:
- Adult dosing: 100 mg IV bolus at induction, followed immediately by continuous infusion of 200 mg/24 hours 2, 5
- Pediatric dosing: Weight-based continuous infusion (25-150 mg/24 hours depending on weight) following initial 2 mg/kg bolus 2, 4
Half-Life Considerations
The elimination half-life of IV hydrocortisone averages 76.5 minutes (range 40-225 minutes), explaining why 4-6 hour dosing intervals are necessary for sustained effect. 6
This significant inter-individual variability in half-life (ranging from 40 to 225 minutes) means that some patients may require more frequent dosing to maintain adequate cortisol levels, particularly those with faster elimination rates 6. The time to reach plasma cortisol concentration below 100 nmol/L averages 289 minutes (approximately 4.8 hours), supporting the 4-6 hour redosing recommendation 6.
Common Pitfalls
- Inadequate dosing frequency: Administering boluses less frequently than every 6 hours risks subtherapeutic cortisol levels between doses 1
- Delayed initiation in septic shock: Starting hydrocortisone >12 hours after vasopressor initiation is associated with increased mortality; early administration is critical 7
- Assuming prolonged single-dose effect: Unlike dexamethasone (which provides 24-hour coverage with a single dose), hydrocortisone requires multiple daily doses or continuous infusion 3, 4