What is the management of compromised corticosteroid (corticosteroid) function?

Management of Compromised Corticosteroid Function

The management of critical illness-related corticosteroid insufficiency (CIRCI) should include intravenous hydrocortisone at doses <400 mg/day for ≥3 days for patients with septic shock that is not responsive to fluid and moderate to high-dose vasopressor therapy. 1

Diagnosis of CIRCI

• CIRCI is characterized by an exaggerated and protracted proinflammatory response due to adrenal insufficiency together with tissue corticosteroid resistance 2
• Clinical signs and symptoms include hypotension refractory to fluid resuscitation, decreased sensitivity to catecholamines, fever, confusion, and persistent hypoxia 1
• Laboratory findings may include hypoglycemia, hyponatremia, hyperkalemia, and metabolic acidosis 1
• Diagnosis can be made by either:
  • A delta total serum cortisol of <9 μg/dL after adrenocorticotropic hormone (250 μg) administration 3
  • A random plasma total cortisol of <10 μg/dL 3
• Plasma total cortisol is preferred over plasma free cortisol or salivary cortisol for diagnosis 1

Treatment Recommendations by Condition

Septic Shock

• For septic shock not responsive to fluid and moderate to high-dose vasopressor therapy:
  • Use IV hydrocortisone <400 mg/day for ≥3 days at full dose 4, 1
  • Long course and low dose is preferred over high dose and short course 4
  • Treatment can be given as either divided doses (50 mg IV every 6 hours) or as a continuous infusion (240 mg/24h) 2

Sepsis Without Shock

• Corticosteroids are not recommended for patients with sepsis without shock 4
• The HYPRESS trial showed no difference in rates of progression to septic shock or mortality with hydrocortisone versus placebo 4

Acute Respiratory Distress Syndrome (ARDS)

• For early moderate to severe ARDS (PaO₂/FiO₂ <200 and within 14 days of onset):
  • Use IV methylprednisolone 1 mg/kg/day 1
  • For late persistent ARDS (after day 6 of onset), use 2 mg/kg/day 4
  • Methylprednisolone is preferred due to greater penetration into lung tissue and longer residence time 4
  • Treatment should be followed by slow tapering over 13 days 4

Major Trauma

• Corticosteroids are not recommended for patients with major trauma 4
• Analysis of 19 trials showed no significant effect on mortality (RR 1.00,95% CI 0.89-1.13) 4

Cardiac Arrest

• Corticosteroids may be beneficial in the setting of cardiac arrest 4
• Studies show improved rates of return to spontaneous circulation and better neurological outcomes at hospital discharge 4

Administration Guidelines

• When administering corticosteroids for CIRCI:
  • Taper slowly (6-14 days) rather than stopping abruptly to avoid rebound inflammation 4
  • Monitor for potential adverse effects including hyperglycemia, hypernatremia, secondary infections, and gastrointestinal bleeding 1
  • For patients on long-term corticosteroids, consider alternate-day therapy once the disease process is controlled to minimize HPA axis suppression 5

Special Considerations

• Infection surveillance is recommended during corticosteroid treatment as it blunts the febrile response 4
• For patients with known adrenal insufficiency undergoing major surgery:
  • Administer hydrocortisone 100 mg IV on induction
  • Follow with continuous infusion of hydrocortisone 200 mg/24h
  • Double oral hydrocortisone doses for 48h or up to a week following major surgery 1

Common Pitfalls

• Abrupt discontinuation of corticosteroids can lead to deterioration from a reconstituted inflammatory response 4
• Dexamethasone is not recommended for treating CIRCI due to its prolonged suppressive effect on adrenal activity 5, 2
• The adrenocorticotropic hormone stimulation test should not be used to identify which patients with septic shock or ARDS should receive glucocorticoids 2