Development and Temporal External Validation of a 6-Hour Lactate Clearance–PaO 2 /FiO 2 Model for Predicting 28-Day Mortality in Sepsis-Associated ARDS

Abstract

Objective

We hypothesized that a simple model using 6- h lactate clearance (LCR) and PaO₂/FiO₂ ratio could accurately predict 28-day mortality in sepsis-associated ARDS and outperform conventional severity scores.

Methods

Using MIMIC-IV v2.2, adults meeting Sepsis-3 criteria within 24 h and developing ARDS (per Berlin definition) within 72 h were randomly divided 7:3 into derivation (n = 1089) and internal validation (n = 467) cohorts. Temporal external validation was performed using 312 consecutive patients from a Chinese tertiary ICU (2022-2025). Twenty-five candidate variables were reduced to eight via LASSO regression and included in a multivariable Cox proportional-hazards model.

Results

The 28-day mortality rate was 34.5%. Both 6- h LCR and PaO₂/FiO₂ were independently linked to 28-day mortality. The model showed AUCs of 0.82 (95% CI: 0.79-0.85), 0.80 (95% CI: 0.75-0.85), and 0.73 (95% CI: 0.67-0.79) at 28 days in the derivation, internal validation, and external validation sets, respectively, with calibration slopes of 0.98 and 1.02, and positive net benefit across risk thresholds of 5%–80%.

Conclusions

A model incorporating 6- h lactate clearance and PaO₂/FiO₂ alongside six clinical confounders provides accurate, well-calibrated prediction of 28-day mortality in sepsis-associated ARDS. The derived risk score formula is provided for prospective validation. External validation in a multinational ICU registry should be undertaken before clinical implementation.