Role of the ionized-to-total calcium ratio in predicting sepsis mortality: a retrospective analysis from the MIMIC-IV database

Sepsis, an important cause of death in intensive care units (ICUs), frequently disrupts calcium homeostasis. Since ionized calcium does not consistently correlate with total calcium, we hypothesized that the ionized-to-total calcium ratio could serve as a prognostic marker. This study aimed to evaluate its association with sepsis mortality. Using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, we conducted a retrospective cohort study of ICU patients with sepsis who had both ionized and total calcium measured after ICU admission. Patients were stratified into quartiles by the ionized-to-total calcium ratio. Primary outcomes were 28-day and 180-day mortality. Cox proportional hazards models, restricted cubic spline (RCS) analyses, and subgroup analyses were performed. Among 10,323 sepsis patients, a higher ionized-to-total calcium ratio was associated with lower mortality. Compared with the bottom quartile, the top quartile was associated with reduced 28-day mortality (adjusted hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.55–0.71, p < 0.001) and 180-day mortality (adjusted HR 0.69, 95% CI 0.62–0.77, p < 0.001). RCS analyses suggested an apparent U-shaped pattern in unadjusted models that was attenuated after full adjustment, showing an overall inverse association. Subgroup analyses suggested a stronger association in patients with higher body mass index and, for 180-day mortality, in male patients. The ionized-to-total calcium ratio may complement early risk stratification in sepsis. Prospective studies are needed to validate these findings and clarify mechanisms, including citrate-related pathways.