Time-varying associations between corticosteroid dose and hospital mortality in ARDS: a sliding-window analysis of MIMIC-IV

Corticosteroids are now recommended in guidelines for patients with acute respiratory distress syndrome (ARDS); however, optimal timing and dose remain uncertain. We assessed whether the association between corticosteroids and hospital mortality varies over time in the ICU. We performed a retrospective observational study of ARDS patients identified in the MIMIC-IV database (2008–2019). To analyze the time-varying association between corticosteroids and hospital mortality, we constructed overlapping three-day windows from ARDS days 0 to 14. We compared windows with no corticosteroid exposure (0 mg) to windows meeting cumulative prednisolone-equivalent dose thresholds chosen to approximate regimens from landmark clinical trials (≥ 30, ≥ 150, ≥270, ≥ 390 mg PE over 3 days). We estimated overlap-weighted, doubly robust adjusted risk differences (OWRD) for hospital mortality using augmented inverse probability weighting (AIPW). Of 987 included patients, 354 (35.9%) received corticosteroids, with 262 (74.1%) and 128 (36.2%) of treated patients meeting the ≥ 150 mg and ≥ 390 mg thresholds in at least one window. Early, low cumulative dosing (≥ 30 mg/3d) was not associated with a detectable difference in hospital mortality (e.g., days 0–2: OWRD 0.03, 95% CI − 0.05 to 0.10). Conversely, higher cumulative doses received later in the ICU stay (≥ 150–390 mg/3d after day 8) were associated with higher observed mortality (e.g., days 8–10: OWRD 0.25, 95% CI 0.11–0.39). However, estimates in late, high-dose windows were less precise due to limited covariate overlap and smaller sample sizes. In unselected ARDS, we found no evidence of benefit or harm from early lower-dose corticosteroids, but higher cumulative doses later in ICU stay were associated with higher mortality, possibly reflecting residual confounding and limited covariate overlap. These hypothesis generating findings support randomized studies testing corticosteroid timing and dose in ARDS.