Original Investigation 

March 27, 2023

Comparative Effectiveness of Fludrocortisone and Hydrocortisone vs Hydrocortisone Alone Among Patients With Septic Shock

Nicholas A. Bosch, Bijan Teja, Anica C. Law, et al

JAMA Intern Med. 2023;183(5):451-459. doi:10.1001/jamainternmed.2023.0258

Key Points

Question  What is the comparative effectiveness of fludrocortisone added to hydrocortisone vs hydrocortisone alone among patients with septic shock?

Findings  In this multicenter cohort study among 88 275 patients with septic shock receiving norepinephrine who initiated hydrocortisone treatment, the addition of fludrocortisone to hydrocortisone was associated with a 3.7% lower adjusted absolute risk difference in the primary composite outcome of mortality or discharge to hospice compared with initiation of hydrocortisone alone.

Meaning  Among patients with septic shock receiving norepinephrine who initiated hydrocortisone treatment, the addition of fludrocortisone was associated with lower rates of the composite of death or discharge to hospice compared with hydrocortisone alone.

Abstract

Importance  Patients with septic shock may benefit from the initiation of corticosteroids. However, the comparative effectiveness of the 2 most studied corticosteroid regimens (hydrocortisone with fludrocortisone vs hydrocortisone alone) is unclear.

Objective  To compare the effectiveness of adding fludrocortisone to hydrocortisone vs hydrocortisone alone among patients with septic shock using target trial emulation.

Design, Setting, and Participants  This retrospective cohort study from 2016 to 2020 used the enhanced claims-based Premier Healthcare Database, which included approximately 25% of US hospitalizations. Participants were adult patients hospitalized with septic shock and receiving norepinephrine who began hydrocortisone treatment. Data analysis was performed from May 2022 to December 2022.

Exposure  Addition of fludrocortisone on the same calendar day that hydrocortisone treatment was initiated vs use of hydrocortisone alone.

Main Outcome and Measures  Composite of hospital death or discharge to hospice. Adjusted risk differences were calculated using doubly robust targeted maximum likelihood estimation.

Results  Analyses included 88 275 patients, 2280 who began treatment with hydrocortisone-fludrocortisone (median [IQR] age, 64 [54-73] years; 1041 female; 1239 male) and 85 995 (median [IQR] age, 67 [57-76] years; 42 136 female; 43 859 male) who began treatment with hydrocortisone alone. The primary composite outcome of death in hospital or discharge to hospice occurred among 1076 (47.2%) patients treated with hydrocortisone-fludrocortisone vs 43 669 (50.8%) treated with hydrocortisone alone (adjusted absolute risk difference, −3.7%; 95% CI, −4.2% to −3.1%; P < .001).

Conclusions and Relevance  In this comparative effectiveness cohort study among adult patients with septic shock who began hydrocortisone treatment, the addition of fludrocortisone was superior to hydrocortisone alone.