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. 2023 May 1;183(5):451-459.
doi: 10.1001/jamainternmed.2023.0258.

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

Nicholas A Bosch  1 , Bijan Teja  2   3 , Anica C Law  1 , Brandon Pang  1 , S Reza Jafarzadeh  4 , Allan J Walkey  1
Affiliations

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

Nicholas A Bosch et al. JAMA Intern Med. .

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Bosch reported grants from Department of Defense (DOD), National Heart, Lung, and Blood Institute (NHLBI), and Gilead Sciences outside the submitted work. Dr Law reported grants from Doris Duke outside the submitted work. Dr Walkey reported grants from Gilead and Agency for Healthcare Research and Quality outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Flow Diagram
Among the 287 533 patients with septic shock who received norepinephrine but who did not receive hydrocortisone, 101 611 (35.3%) died. ICU indicates intensive care unit.
Figure 2.
Figure 2.. 28-Day Survival Among Patients With Septic Shock Treated With Hydrocortisone-Fludrocortisone or Hydrocortisone Alone
Shown are unadjusted Kaplan-Meier survival curves for the composite outcome of hospital death or discharge to hospice for patients in the 28 days after initiation of corticosteroid treatment among adult patients with septic shock.
See this image and copyright information in PMC

Comment in

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