What is the recommended treatment for critical illness-related corticosteroid (CS) insufficiency?

Treatment of Critical Illness-Related Corticosteroid Insufficiency (CIRCI)

For critical illness-related corticosteroid insufficiency, intravenous hydrocortisone at doses <400 mg/day for ≥3 days is recommended 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 dysregulated systemic inflammation resulting from inadequate intracellular glucocorticoid-mediated anti-inflammatory activity relative to the severity of critical illness. 1

• The task force was unable to reach agreement on a single definitive test for CIRCI diagnosis, but the following may be used: 1

  • Delta cortisol (change in baseline cortisol at 60 min of <9 μg/dl) after cosyntropin (250 μg) administration
  • Random plasma cortisol of <10 μg/dl

• Plasma total cortisol is preferred over plasma free cortisol or salivary cortisol for diagnosis (conditional recommendation, very low quality evidence) 1

• Clinical signs and symptoms of CIRCI include: 1

  • Hypotension refractory to fluid resuscitation
  • Decreased sensitivity to catecholamines
  • Fever, confusion, persistent hypoxia
  • Laboratory findings may include hypoglycemia, hyponatremia, hyperkalemia, and metabolic acidosis

Treatment Recommendations by Condition

1. Septic Shock

• For septic shock not responsive to fluid and moderate to high-dose vasopressor therapy (>0.1 μg/kg/min of norepinephrine or equivalent): 1

  • Intravenous hydrocortisone <400 mg/day for ≥3 days at full dose (conditional recommendation, low quality evidence)
  • Long course and low dose is preferred over high dose and short course

• For sepsis without shock: 1

  • Corticosteroids are not recommended (conditional recommendation, moderate quality evidence)

2. Acute Respiratory Distress Syndrome (ARDS)

• For early moderate to severe ARDS (PaO2/FiO2 < 200 and within 14 days of onset): 1
  • IV methylprednisolone 1 mg/kg/day (conditional recommendation, moderate quality evidence)

3. Major Trauma

• For patients with major trauma: 1
  • Corticosteroids are not suggested (conditional recommendation, low quality evidence)

4. Community-Acquired Pneumonia (CAP)

• For hospitalized patients with CAP: 1
  • Corticosteroids for 5-7 days at a daily dose <400 mg IV hydrocortisone or equivalent (conditional recommendation, moderate quality evidence)

5. Influenza

• For adults with influenza: 1
  • Corticosteroids are not recommended (conditional recommendation, very low quality evidence)

Perioperative Management

For patients with known adrenal insufficiency undergoing surgery: 1

• Major surgery under anesthesia:

  • Hydrocortisone 100 mg IV on induction, followed by continuous infusion of hydrocortisone 200 mg/24h
  • Postoperatively: Continue IV infusion while nil by mouth, then double oral hydrocortisone doses for 48h or up to a week following major surgery

• Labor and vaginal delivery:

  • Hydrocortisone 100 mg IV at onset of labor, followed by continuous infusion of hydrocortisone 200 mg/24h
  • Resume enteral administration with doubled doses for 24h with rapid recovery

Monitoring and Adverse Effects

• Monitor for potential adverse effects of corticosteroid therapy: 1, 2

  • Hyperglycemia (most common)
  • Hypernatremia
  • Secondary infections (though risk appears minimal with low-dose, short-duration therapy)
  • Gastrointestinal bleeding
  • Psychiatric effects ranging from euphoria to psychosis

• Blood pressure determinations and serum electrolyte monitoring should be performed regularly 3

Special Considerations

• In patients on corticosteroid therapy subjected to unusual stress, increased dosage of rapidly acting corticosteroids before, during, and after the stressful situation is indicated 2

• Gradual tapering of corticosteroids is recommended to prevent drug-induced adrenal insufficiency 2, 3

• Patients on immunosuppressant doses of corticosteroids should avoid exposure to chickenpox or measles 3

• For patients with prolonged critical illness (weeks), be aware of the risk of developing central adrenal insufficiency due to sustained high systemic glucocorticoid availability causing negative feedback inhibition at the hypothalamus/pituitary 4

Pitfalls and Caveats

• Too rapid withdrawal of corticosteroids may result in secondary adrenocortical insufficiency 2, 3

• Corticosteroids may mask signs of infection and decrease resistance to new infections 2

• The adrenocorticotropic hormone (ACTH) stimulation test should not be used to identify which patients with septic shock should receive glucocorticoids 5

• Dexamethasone is not recommended for treating CIRCI 5