Association between Sodium–Chloride Difference at ICU Admission and 30-Day Mortality: A Retrospective Cohort Study of Critically Ill Adults

Background The difference between serum sodium and chloride concentrations (SCD), may reflect the strong ion difference (SID) and has emerged as a potential marker of acid–base status. We investigated whether SCD assessed upon ICU admission holds predictive value for short-term outcomes in critically ill adults. Methods We retrospectively analyzed 1,726 consecutive patients admitted to a mixed (medical-surgical) ICU (median age 67 years; 70.7% male). SCD values on admission were studied in relation to 30-day mortality using Cox proportional hazards models and restricted cubic spline regression to explore non-linear trends. Internal validation was performed using bootstrap resampling with 1,000 iterations. Results SCD levels were significantly lower among non-survivors compared to survivors (median [IQR]: 31.5 [28.0–34.0] vs. 33.0 [31.0–36.0] mmol/L, p = 0.002). The mortality risk curve revealed a non-linear relationship with SCD. Despite no difference in SOFA scores on admission between groups stratified by SCD (<30 vs. ≥30 mmol/L), lower SCD was associated with increased risk of death (unadjusted HR 1.50, 95% CI 1.26–1.78; p < 0.001; and adjusted for age and SOFA score HR 1.43, 95% CI 1.18–1.73; p < 0.001). Bootstrap resampling confirmed the robustness of this finding (HR 1.45, 95% CI 1.19–1.77; p < 0.001). Conclusions Low SCD on admission may indicate elevated short-term mortality risk in ICU patients, independent of conventional severity scores. Our findings may provide a reasonable pathophysiological explanation for the prognostic significance of sodium-chloride interplay in critically ill patients.