What is the onset of action for hydrocortisone (corticosteroid)?

Hydrocortisone Onset of Action

Intravenous hydrocortisone demonstrates clinical effects within one hour of administration, with peak plasma levels achieved at 10-20 minutes, while intramuscular administration reaches therapeutic levels within 11±5 minutes. 1, 2

Route-Specific Pharmacokinetics

Intravenous Administration

• IV hydrocortisone provides immediate bioavailability with demonstrable clinical effects evident within one hour after injection. 2
• Peak plasma levels occur at 10-20 minutes following IV administration. 1
• The highly water-soluble sodium succinate ester formulation permits rapid administration of high doses in small volumes, making it particularly useful when high blood levels are required urgently. 2
• Excretion of the administered dose is nearly complete within 12 hours, necessitating repeat injections every 4-6 hours if constantly high blood levels are required. 2

Intramuscular Administration

• IM hydrocortisone is rapidly absorbed with therapeutic levels reached within 11±5 minutes. 1
• The excretion pattern following IM injection is similar to that observed after IV administration. 2
• For perioperative stress coverage, IM administration of 100 mg hydrocortisone is recommended just before anesthesia induction. 3

Clinical Context and Timing Considerations

Emergency Situations (Adrenal Crisis, Cardiac Arrest)

• For adrenal crisis or emergency situations, IV or IM routes are strongly preferred due to their rapid onset of action. 1, 4
• In out-of-hospital cardiac arrest patients, hydrocortisone administration within 6 minutes of emergency department arrival was associated with significantly improved return of spontaneous circulation rates (90% vs 50%, P = 0.045). 5
• Delays in hydrocortisone administration during suspected adrenal crisis can be fatal; treatment should never be delayed while awaiting diagnostic confirmation. 4

Septic Shock Management

• In septic shock, early initiation of hydrocortisone (within 3 hours) reduced time to vasopressor discontinuation compared to late initiation (25 vs 37 hours, P = 0.009). 6
• Another study demonstrated that hydrocortisone initiation within 12 hours of vasopressor initiation resulted in shorter time to vasopressor discontinuation (40.7 vs 60.6 hours, P = 0.0002) and reduced ICU length of stay. 7
• Continuous infusion is preferred over repetitive bolus injections to avoid significant glucose fluctuations and maintain stable therapeutic levels. 3, 4
• The recommended dose is 200 mg/day as continuous infusion or divided doses for patients with septic shock unresponsive to fluid resuscitation and moderate-to-high dose vasopressors. 3

Surgical Stress Coverage

• For major surgery in patients with adrenal insufficiency, hydrocortisone 100 mg IV should be administered at induction, followed by immediate initiation of continuous infusion at 200 mg/24 hours. 3
• This dosing strategy ensures therapeutic levels are maintained throughout the perioperative period when cortisol demands are elevated. 3

Important Clinical Caveats

Delayed Anti-Inflammatory Effects

• Corticosteroids are not helpful for treating acute anaphylaxis due to their slow onset of anti-inflammatory action (4 to 6 hours). 3
• They are given in anaphylaxis primarily to help prevent biphasic or protracted reactions, not for immediate symptom relief. 3

Plasma Cortisol Levels During Therapy

• During "low-dose" hydrocortisone therapy (100 mg bolus followed by 10 mg/hour infusion), total plasma cortisol levels increase 4.2-fold and free cortisol levels increase 8.5-fold on day 1, reaching median levels of 3,587 nmol/L (total) and 1,210 nmol/L (free). 8
• These achieved levels considerably exceed both basal and ACTH-stimulated endogenous cortisol concentrations. 8
• Cortisol concentrations subsequently decline despite continuous application of a constant dose, reaching median levels of 1,310 nmol/L (total) and 345 nmol/L (free) by day 7. 8

Dosing Frequency Considerations

• Because excretion is nearly complete within 12 hours, injections should be administered every 4-6 hours if constantly high blood levels are required. 2
• For perioperative management, continuous infusion of 200 mg/24 hours is recommended over intermittent boluses to maintain stable therapeutic levels. 3