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Evevident

APROCCHSS

Hydrocortisone plus fludrocortisone for adults with septic shock

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.

Practice impact

Steroids became a standard consideration for septic shock requiring ongoing vasopressors.

Evidence

Study design

Randomized, double-blind, placebo-controlled trial.

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 / CI 95% CI 0.78-0.99 / p=0.03

Key results

  • 90-day mortality: 43.0% with hydrocortisone/fludrocortisone vs 49.1% with placebo.
  • Vasopressor-free days and organ-failure-free days favored steroid therapy.
  • Hyperglycemia was more common with steroids.

Harms

  • Hyperglycemia was more common with corticosteroids.
  • Steroids can increase neuromuscular weakness and infection concerns, though major excess harms were not the primary signal.

Clinical Use

When to cite

  • When considering hydrocortisone in refractory septic shock on vasopressors.

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

Among patients with septic shock, the use of hydrocortisone plus fludrocortisone resulted in lower 90-day all-cause mortality than placebo.