Fludrocortisone Plus Hydrocortisone Superior to Hydrocortisone Alone in Septic Shock

Results of a study published in the JAMA Internal Medicine suggest that the addition of fludrocortisone plus hydrocortisone was superior to treatment with hydrocortisone alone among patients with septic shock receiving norepinephrine.

Researchers conducted a multicenter, prospective study between 2016 and 2020 to compare the effectiveness of fludrocortisone plus hydrocortisone vs hydrocortisone alone for the treatment of septic shock. Eligible patients were adults hospitalized with septic shock receiving norepinephrine. The primary outcome was a composite of in-hospital mortality or discharge to hospice care. Secondary outcomes included vasopressor- and hospital-free days at day 28.

Among 88,275 patients included in the final analysis, 85,995 (97.4%) received hydrocortisone alone (median age, 67 [IQR, 57-76) years) and 2280 (2.6%) received fludrocortisone plus hydrocortisone (median age 64 [IQR, 54-73] years). For patients in both groups, the median time from norepinephrine initiation to hydrocortisone initiation was 0 (IQR, 0-1) days.

The median duration of treatment was 3 (IQR, 1-4) and 3 (IQR, 2-6) days among patients in the hydrocortisone plus fludrocortisone and hydrocortisone alone groups, respectively.

Overall, in-hospital mortality or discharge to hospice care occurred among 1076 (47.2%) and 43,669 (50.8%) patients in the fludrocortisone plus hydrocortisone vs hydrocortisone alone groups, respectively (adjusted risk difference [ARD], -3.7%; 95% CI, -4.2% to -3.1%; P <.001).

Further analysis at day 28 showed that vasopressor-free days were higher among patients in the fludrocortisone plus hydrocortisone vs hydrocortisone alone groups (mean, 13.8 vs 8.7 days; ARD, 0.9; 95% CI, 0.8-1.1; P <.001). Similar results were observed between the groups for hospital-free days.

Similar rates were observed between patients in the fludrocortisone plus hydrocortisone vs hydrocortisone alone groups for the occurrence of hypernatremia (11.4% vs 11.3%) and health care-associated infection (1.4% vs 1.0%).

Study limitations include potential unmeasured residual confounding due to the observational design and potential immortal time bias.

According to the researchers, “[C]linicians seeking to optimize use of corticosteroids in septic shock should consider adding fludrocortisone when initiating hydrocortisone treatment.””

Disclosures: Multiple authors declared affiliations with pharmaceutical, biotech, and/or device companies. Please see the original reference for a full list of disclosures.