Hydrocortisone 

1. Overview

Hydrocortisone is a short-acting glucocorticoid with mineralocorticoid activity, widely used in ICU for:

• Septic shock
• Adrenal insufficiency
• ARDS (selected cases)
• Anaphylaxis (adjunct)
• Neurocritical care (limited role)
• CIRCI (Critical Illness Related Corticosteroid Insufficiency)

Equivalent to endogenous Cortisol

2. Pharmacology

A. Mechanism of Action

• Anti-inflammatory effects:
• ↓ Capillary permeability
• ↑ Vascular responsiveness to catecholamines (key in shock)

Critical point: Restores vasopressor sensitivity

B. Mineralocorticoid Activity

• Retains sodium & water
• Promotes potassium excretion
  → Important in septic shock (volume + vascular tone)

C. Pharmacokinetics

3. Physiological Role in Critical Illness

Stress Response

• Normal stress → cortisol ↑ (up to 6–10×)
• Critical illness → may have:
• Absolute deficiency
• Relative deficiency (CIRCI)

4. Indications in ICU 

 A. Septic Shock (MOST IMPORTANT)

As per Surviving Sepsis Campaign 2021

Indication:

• Septic shock NOT responding to fluids + vasopressors

Dose:

• Hydrocortisone 200 mg/day IV
• 50 mg IV q6h
  OR
  Continuous infusion

Benefits:

• ↓ Time to shock reversal
• ↓ Vasopressor requirement
• No consistent mortality benefit

Key Trials:

• ADRENAL trial
• APROCCHSS trial

 APROCCHSS showed mortality benefit (with fludrocortisone)

B. CIRCI (Critical Illness Related Corticosteroid Insufficiency)

C. Adrenal Crisis / Known Adrenal Insufficiency

Dose:

• 100 mg IV bolus → 200 mg/day infusion

D. ARDS (Selected Cases)

Evidence evolving (DEXA-ARDS used dexamethasone)

Hydrocortisone role:

• Early moderate–severe ARDS
• Reduces inflammation
• May shorten ventilation duration

E. Anaphylaxis (Adjunct)

• Prevents biphasic reaction
• NOT first-line (epinephrine is)

F. Neurocritical Care

Not routinely used in:

• Traumatic brain injury (harmful)

 Used in:

• Adrenal insufficiency in neuro ICU
• Vasopressor-resistant hypotension

G. Severe CAP

• Recent evidence (e.g., CAPE-COD trial) → benefit of steroids
• Guidelines (ERS/ATS updates, Surviving Sepsis):

 Indicated in:

• Severe CAP requiring ICU care
• High inflammatory markers (CRP >150 mg/L)

 Benefits:

• ↓ Mortality
• ↓ Need for mechanical ventilation
• ↓ Progression to shock

5. Dosing in ICU

6. Mode of Administration

• Intermittent bolus (q6h)
  OR
• Continuous infusion (preferred by some → stable levels)

7. Adverse Effects 

Metabolic

• Hyperglycemia (VERY COMMON)
• Hypernatremia
• Hypokalemia

Cardiovascular

• Fluid retention → edema
• Hypertension

Infectious

• Secondary infections
• Immunosuppression

Neuromuscular

• ICU-acquired weakness
• Steroid myopathy

GI

• Stress ulcers
• GI bleeding

Neuropsychiatric

• Delirium
• Steroid psychosis

8. Important ICU Considerations

A. Tapering

• Not required if ≤7 days
• If prolonged → gradual taper to avoid adrenal suppression

B. Monitoring

• Blood glucose (VERY IMPORTANT)
• Electrolytes
• Infection markers
• Hemodynamics

C. Combination Therapy

• With vasopressors → synergistic
• With Fludrocortisone:
• May improve mortality (APROCCHSS)

D. Steroid Equivalence 

9. Hydrocortisone vs Dexamethasone