Diagnosis of Critical Illness-Related Corticosteroid Insufficiency (CIRCI) 

• Definition: postulated to be a relative adrenal insufficiency due to impairment in the HPA axis stress response in critical illness. 
• Clinical presentation: consider CIRCI in the patient with refractory septic/distributive shock (SBP<90 at least 1 hour after adequate fluid resuscitation and moderate-high dose vasopressor administration) or if patient is at risk for adrenal insufficiency (chronic steroids, pre-existing AI, or use of medications known to impair HPA axis such as etomidate for intubation).  
• Lab testing: there are no clear guidelines for testing for CIRCI. 
  • The American College of Critical Care Medicine and Surviving Sepsis guidelines recommend against checking a cosyntropin stimulation test for the following reasons: 
    • Tests of cortisol levels and response to ACTH stimulation are unreliable in critically ill patients. 
    • Multiple studies have demonstrated that baseline cortisol and cosyntropin stimulation test results fail to predict which patients will respond to steroids. See Endocrine: Adrenal Insufficiency. 

Treatment for Adrenal Insufficiency 

• Dose: hydrocortisone 50mg IV q6h or 100mg IV q8h. 
  • Fludricortisone included in earlier trials (French), but not included in more recent trials. Showed no additional benefit over hydrocortisone alone in the COIITSS trial, which randomized patients with relative adrenal insufficiency to hydrocort+fludrocort or hydrocort alone. 
• Duration: no consensus. Treat for 3-7 days. Surviving Sepsis makes no recommendation. ACCM recommend at least 7 days and CORTICUS treated for 5 days. 
• Taper: no consensus. CORTICUS tapered over 6 days. ACCM and Surviving Sepsis recommend tapering but do not specify duration. 
• Other considerations: remember to monitor for hyperglycemia and start stress ulcer prophylaxis. Of note, in COVID-19, we use dexamethasone for severe COVID-19 pneumonia complicated by hypoxemic respiratory failure – this is not for adrenal insufficiency. 

Evidence 

2019 Cochrane review: 

• Included 61 studies with total of >12,000 patients. 
• Lower 28-day mortality with low dose steroids than placebo (RR 0.91, CI 0.84-0.99), decreased length of ICU stay (mean difference 1.07 days); increased rate of hyperglycemia and hyponatremia in steroid group. 

French trial (Annane et al. 2002 RCT): 

• 300 patients with septic shock refractory to volume and pressors were assigned within eight hours to either placebo or 50mg hydrocortisone q6h plus 50mcg fludrocortisone. 
• Lower 28-day mortality, faster shock reversal. No benefit in patients with adequate adrenal reserve. 

CORTICUS study: 

• RCT of 500 patients with septic shock randomized within 72 hours of onset. 
• The study showed no mortality benefit but earlier shock reversal, regardless of response to cosyntropin. The steroid group had more hypernatremia, hyperglycemia, and new infection (not statistically significant). 
• Conclusion: consider hydrocortisone early for septic shock refractory to fluids and vasopressors. 

Keywords: CORTICUS, adrenal insufficiency, steroids, glucocorticoids, septic shock, corticosteroids 

Annane D, Bellissant E, Bollaert PE, et al. Corticosteroids for treating sepsis in children and adults. Cochrane Database Syst Rev. 2019;12(12):CD002243. Published 2019 Dec 6. doi:10.1002/14651858.CD002243.pub4 

Annane D, Sébille V, Charpentier C, et al. Effects of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock.  JAMA 2002;288:862-871. 

Casserly B, Gerlach H, et al. Low-dose steroids in adult septic shock: results of the Surviving Sepsis Campaign. Intensive Care Med. 2012 Dec;38(12):1946-54 

Marik PE,Pastores SM. Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: Consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med 2008; 36:1937-1949 

Sprung CL, Annane D, Keh D, et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008;358:111-124.