Treatment of Critical Illness-Related Corticosteroid Insufficiency (CIRCI)
For patients with septic shock that is not responsive to fluid resuscitation and moderate-to-high-dose vasopressor therapy, intravenous hydrocortisone at a dose of <400 mg/day should be administered for at least 3 days at full dose. 1, 2
Diagnosis of CIRCI
CIRCI is characterized by dysregulated systemic inflammation resulting from inadequate intracellular glucocorticoid-mediated anti-inflammatory activity for the severity of critical illness. Diagnosis can be challenging, but the following methods are recommended:
- 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
- Clinical presentation with refractory hypotension despite adequate fluid resuscitation and vasopressor therapy
Clinical Presentation
CIRCI should be suspected in patients presenting with:
- Cardiovascular signs: Hypotension refractory to fluid resuscitation, decreased sensitivity to catecholamines
- Neurological signs: Confusion, delirium, coma
- Respiratory signs: Persistent hypoxia
- Laboratory abnormalities: Hypoglycemia, hyponatremia, hyperkalemia, metabolic acidosis
Treatment Recommendations by Condition
1. Septic Shock
- Indication: Septic shock not responsive to fluid and moderate-to-high-dose vasopressor therapy
- Regimen: IV hydrocortisone <400 mg/day for ≥3 days at full dose 1
- Duration: Total treatment of 7-14 days depending on clinical response 2
- Formulation: Can be administered as divided doses (e.g., 50 mg every 6 hours) or continuous infusion (10 mg/hr) 3
2. Sepsis without Shock
- Not recommended to use corticosteroids in adult patients with sepsis without shock 1
3. Acute Respiratory Distress Syndrome (ARDS)
- Indication: Early moderate to severe ARDS (PaO2/FiO2 < 200 and within 14 days of onset)
- Regimen: IV methylprednisolone 1 mg/kg/day 1
- Duration: ≥14 days 3
4. Major Trauma
- Corticosteroids are not recommended for patients with major trauma 1
Monitoring During Treatment
- Hyperglycemia: Most common adverse effect; regular glucose monitoring is essential
- Electrolyte disturbances: Monitor for hypernatremia and hypokalemia
- Infections: Enhanced infection surveillance is recommended as glucocorticoid treatment can blunt febrile response
- Clinical response: Assess vasopressor requirements and hemodynamic stability
Tapering and Discontinuation
- Slow tapering over 6-14 days is recommended rather than abrupt discontinuation to prevent inflammatory rebound 2
- For courses >14 days, gradual reduction is particularly important to prevent adrenal insufficiency 2
- Consider reinitiating therapy for patients who deteriorate after stopping corticosteroids 2
Common Pitfalls and Caveats
Diagnostic challenges: No single test can reliably diagnose CIRCI. Clinical judgment combined with laboratory testing is essential.
Delayed treatment: Failure to recognize CIRCI can lead to prolonged shock and increased mortality. Consider early initiation of hydrocortisone in refractory shock.
Inappropriate use: Avoid corticosteroids in patients with sepsis without shock or major trauma, as evidence does not support benefit in these populations.
Abrupt discontinuation: Sudden cessation of corticosteroids can lead to adrenal crisis or inflammatory rebound. Always taper gradually.
Infection risk: While low-dose corticosteroids do not significantly increase superinfection risk, vigilant infection surveillance remains important.
Dexamethasone use: Dexamethasone is not recommended for CIRCI treatment 3.
By following these evidence-based recommendations, clinicians can appropriately diagnose and manage CIRCI, potentially improving outcomes in critically ill patients.