Fludocortisone Dosing in CIRCI
Fludrocortisone at 50 μg daily should be added to hydrocortisone therapy in patients with septic shock and CIRCI who demonstrate relative adrenal insufficiency (non-responders to cosyntropin stimulation test). 1
Evidence for Fludrocortisone in CIRCI
The landmark trial by Annane et al. demonstrated that the combination of hydrocortisone (50 mg IV every 6 hours) plus fludrocortisone (50 μg tablet once daily) for 7 days significantly reduced 28-day mortality in septic shock patients with relative adrenal insufficiency (hazard ratio 0.67, P=0.02). 1 This combination also accelerated vasopressor withdrawal compared to placebo (57% vs 40%, P=0.001). 1
Current Guideline Recommendations
The 2017 SCCM/ESICM guidelines for CIRCI do not specifically recommend routine fludrocortisone use in septic shock. 2, 3 These guidelines suggest using IV hydrocortisone <400 mg/day for ≥3 days in patients with vasopressor-dependent septic shock, but they do not mandate mineralocorticoid supplementation. 2, 3
The 2008 consensus statement recommended hydrocortisone 200 mg/day in four divided doses or as continuous infusion (240 mg/day) for ≥7 days in septic shock, without specific mention of adding fludrocortisone. 4
Clinical Context and Practical Application
When hydrocortisone doses ≥200 mg/day are used, fludrocortisone may not be necessary because hydrocortisone at these doses provides sufficient mineralocorticoid activity. 4, 5 However, when lower doses of hydrocortisone are employed or when patients demonstrate persistent hypotension despite adequate glucocorticoid replacement, adding fludrocortisone 50 μg daily is reasonable based on the Annane trial data. 1
Dosing Algorithm for CIRCI:
- Primary regimen: Hydrocortisone 50 mg IV every 6 hours (200 mg/day total) 4, 5
- Add fludrocortisone 50 μg daily if patient is a non-responder to cosyntropin test (delta cortisol <9 μg/dL) 1, 2
- Duration: Continue for 7 days at full dose, then taper (do not stop abruptly) 4, 3
- Monitor: Blood pressure, serum sodium, potassium, and vasopressor requirements 1
Important Caveats
Fludrocortisone is NOT indicated in primary adrenal insufficiency management during acute adrenal crisis in CIRCI. 2 During acute crisis, IV hydrocortisone 100 mg every 6-8 hours provides adequate mineralocorticoid effect at these high doses. 2 Fludrocortisone becomes relevant only after stabilization or when using lower maintenance doses of hydrocortisone.
The evidence for fludrocortisone in CIRCI comes from a single landmark trial 1, and subsequent guidelines have not universally adopted this as standard practice. 2, 3 The decision to add fludrocortisone should be based on the patient's response to initial hydrocortisone therapy and their adrenal function testing results.
Dexamethasone should NOT be used for CIRCI as it lacks mineralocorticoid activity and is not recommended by consensus guidelines. 4 If dexamethasone is used temporarily (e.g., to allow cortisol testing), it must be switched to hydrocortisone ± fludrocortisone for definitive treatment. 5