Abstract
BACKGROUND: Static body mass index (BMI) is a known predictor of mortality in sepsis; however, the prognostic value of dynamic BMI trajectories across various admission BMI states remains unclear. This study aimed to quantify the dose-response relationship between ICU-acquired BMI changes and 30-day mortality and to determine BMI-specific thresholds for risk stratification. METHODS: This retrospective, multicenter cohort study analyzed 5,577 adult patients with sepsis from the MIMIC-IV database (2008-2022). To delineate the nature of the relationship between BMI change rate and 30-day mortality across distinct baseline BMI strata, we employed multivariable Cox proportional hazards regression coupled with restricted cubic splines. A two-segment linear regression model with a recursive algorithm was then applied to pinpoint inflection points for each BMI-defined subgroup. RESULTS: Among 5,577 ICU patients with sepsis (mean age 66.5 ± 15.8 years; 57.4% male), 2,068 deaths (37.1%) occurred within 30 days. BMI change during the ICU stay ranged from -39% to +49%. After multivariable adjustment, each 1% increase in BMI change rate was associated with a 2% higher 30-day mortality (hazard ratio [HR] 1.02; 95% confidence interval [CI] 1.02-1.02; p < 0.001). However, in the underweight subgroup (<18.5 kg/m²), no significant association was observed (HR 0.99; 95% CI 0.98-1.00; p = 0.093). Restricted cubic spline analyses revealed BMI-specific inflection points: -2% in underweight, +4% in normal-weight (18.5-24.9 kg/m²), and -1% in overweight/obese (≥25 kg/m²) patients (p for nonlinearity < 0.001 for all). Dynamic BMI metrics significantly outperformed admission BMI in predicting 30-day mortality (p < 0.001). CONCLUSION: In critically ill ICU patients with sepsis, the relationship between BMI change (%) and 30-day mortality is nonlinear and varies across baseline BMI. Among patients with an admission BMI ≥18.5 kg/m², an increase in BMI during the ICU stay is associated with higher mortality risk, indicating that weight gain is deleterious. Conversely, in patients with an admission BMI <18.5 kg/m², a decline in BMI markedly amplifies the risk of death. Tailored and dynamic weight management strategies accounting for baseline BMI trajectories may therefore help mitigate sepsis-related mortality.