Hydrocortisone plus fludrocortisone improved survival from septic shock (APROCCHSS trial)

Patients with septic shock who received hydrocortisone and fludrocortisone together had improved survival compared to patients receiving placebo, according to a large randomized trial (APROCCHSS) published in the New England Journal of Medicine.

From 2008-2015, investigators enrolled 1,241 patients in France with septic shock for less than 24 hours to receive either hydrocortisone 50 mg IV every 6 hours along with a daily dose of fludrocortisone 50 μg through a nasogastric tube, or placebo, for 7 days.

(The trial initially had two other arms testing activated protein C alone or with the steroid cocktail; the trial continued with the steroid vs placebo arms after aPC was withdrawn from the market for lack of efficacy.)

The enrollment criteria selected for patients with more-severe septic shock: SOFA scores of 3 or 4 for at least two organs for at least 6 hours, and receipt of vasopressors for at least 6 hours.

Patients receiving hydrocortisone and fludrocortisone had 43% mortality at 90 days (the primary outcome), compared to 49% for the placebo group. This corresponded to a number needed to treat of about six patients to help one survive to 90 days. Mortality was improved at other time points, as well.

Those receiving steroids also had two fewer days of vasopressor use or organ failure, and had one fewer day (non-significant) receiving mechanical ventilation.

Hyperglycemia occurred significantly more often in patients receiving steroids, but there were no increased infection rates or other adverse events noted in the steroid-treated group.

The long timeframe of the APROCCHSS trial (spanning the publication of the Process, Arise, and Promise trials and their meta-analysis showing no benefit of protocolized goal-directed therapy for sepsis), the high mortality rate relative to recent sepsis trials (at least partly due to its selection for more-severe septic shock), and its single-nation design invite caution rather than immediate global application of its conclusions to all patients in septic shock.

The study was also less than a third the size of the ADRENAL trial (n=3,800), which found clinical benefits of stress-dose hydrocortisone (but no reduction in mortality) in patients with septic shock requiring mechanical ventilation.

Nevertheless, the new French study results point in the same general direction as ADRENAL and CORTICUS: stress-dose corticosteroids and mineralocorticoids appear safe and generally beneficial for patients with septic shock. Hyperglycemia should be expected and managed to avoid its adverse effects.

Source: NEJM