High-dose corticosteroids are associated with higher mortality in patients with COVID-19 ARDS: Results from a nationwide observational study

BACKGROUND: Optimal corticosteroid dosing strategies remain unclear for severe coronavirus disease 2019 (COVID-19) patients admitted to the intensive care unit (ICU). This study compared mortality among patients treated with high-dose versus standard-dose corticosteroids. METHODS: This prospective cohort study included adult patients with COVID-19 ARDS, defined according to Berlin criteria for ARDS, across 22 centers in the Netherlands between March 2020 and January 2021. Mortality hazards were compared between patients receiving high-dose (>6 mg dexamethasone or equivalent) and standard-dose (6 mg dexamethasone or equivalent) corticosteroids using marginal structural models to adjust for time-varying confounding related to initiation of high-dose therapy. Models were constructed using pooled logistic regression with stabilized inverse probability of treatment weights to emulate a per-protocol analysis. RESULTS: Data from 848 patients were analyzed: 378(44.6%) received high-dose and 470 (55.4%) standard-dose corticosteroids. Among those treated with high-dose corticosteroids, 63 (16.7%) started therapy within the first day after ICU admission, and 315(83.3%) started at a median of 9 days(IQR = 4-14) after admission. During a median 28 days of follow-up, 183 patients in the high-dose and 154 in the standard-dose group died [incident rate = 2.12 per 100 person-days, 95% confidence interval (CI) = 1.81-2.43 and 1.41 per 100 person-days, 95%CI = 1.13-1.63, respectively]. In the marginal structural model, high-dose corticosteroids were associated with increased mortality (hazard ratio = 2.45, 95%CI = 1.97-3.05). Risk was higher in male patients or those with late initiation (>1 day) of therapy. CONCLUSION: In patients with COVID-19 ARDS, high-dose corticosteroids were associated with higher mortality during the first 28 days after ICU admission. TRIAL REGISTRATION: ClinicalTrials.govNCT05403359; https://clinicaltrials.gov/ct2/show/NCT05403359.