APROCCHSS
Hydrocortisone plus fludrocortisone for adults with septic shock
On this page
Overview
Hydrocortisone plus fludrocortisone reduced 90-day mortality in severe septic shock.
Clinical takeaway
APROCCHSS supports corticosteroids for refractory septic shock, especially when framed alongside ADRENAL and modern sepsis resuscitation evidence.
Key result
90-day mortality was 43.0% with steroids vs 49.1% with placebo (RR 0.88; 95% CI 0.78-0.99; p=0.03).
Practice impact
Steroids became a standard consideration for septic shock requiring ongoing vasopressors.
Evidence
Study design
Multicenter, double-blind, randomized, placebo-controlled trial; originally 2-by-2 factorial with drotrecogin alfa (activated), continued as a two-group parallel design after drotrecogin alfa was withdrawn.
Enrollment
1,241
Follow-up
90 days for the primary outcome.
Geography
France
Clinical question
Does hydrocortisone plus fludrocortisone improve survival in adults with septic shock?
Population
- Adults with septic shock requiring vasopressors and mechanical ventilation or high severity criteria.
Intervention
Hydrocortisone 50 mg IV every 6 hours plus fludrocortisone 50 micrograms enterally daily for 7 days.
Comparator
Placebo.
Primary outcome
90-day all-cause mortality.
Hydrocortisone plus fludrocortisone reduced 90-day mortality in adults with severe septic shock.
Relative risk / 0.88 / 95% CI 0.78-0.99 / p=0.03
Key results
- 90-day mortality: 43.0% with hydrocortisone/fludrocortisone vs 49.1% with placebo (RR 0.88; 95% CI 0.78-0.99; p=0.03).
- 28-day mortality was not significantly different (33.7% vs 38.9%; p=0.06).
- Vasopressor-free days (17 vs 15; p<0.001) and organ-failure-free days (14 vs 12; p=0.003) to day 28 favored steroid therapy.
- Hyperglycemia was more common with steroids.
Harms
- Hyperglycemia was more common with corticosteroids; the rate of serious adverse events did not differ significantly.
- Steroids can increase neuromuscular weakness and infection concerns, though major excess harms were not the primary signal.
Clinical Use
Practice impact
- Supports stress-dose steroids in septic shock with persistent vasopressor requirement despite fluids and vasopressors.
Applicability
- Most relevant to severe or refractory septic shock, not uncomplicated sepsis.
Limitations
- Single-country trial and a selected high-severity population.
- Interpret alongside ADRENAL, which did not show a mortality benefit with hydrocortisone alone but did hasten shock resolution.
Common misinterpretations
- Do not use this trial to justify steroids for all sepsis; the population was septic shock.
Citation
Annane D, Renault A, Brun-Buisson C, et al. Hydrocortisone plus Fludrocortisone for Adults with Septic Shock. N Engl J Med. 2018;378(9):809-818. doi:10.1056/NEJMoa1705716
In this trial involving patients with septic shock, 90-day all-cause mortality was lower among those who received hydrocortisone plus fludrocortisone than among those who received placebo.
- PMID
- 29490185