Non-linear relationship between ionised calcium and 28-day mortality in patients with sepsis: a retrospective cohort...

Sepsis is a life-threatening disease caused by a deregulated response to infection. This study aimed to investigate the linear and non-linear relationships between ionised calcium levels and 28-day mortality in patients with sepsis in the intensive care unit (ICU) and to generate hypotheses regarding laboratory index testing and calcium supplementation strategies.

A retrospective cohort study.

Adult patients admitted to the ICU, using data extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database.

A total of 17 955 adult patients with sepsis, defined according to the sepsis-3 criteria, were included. Patients lacking ionised calcium (iCa) data were excluded.

The exposure variable was iCa level measured within the first 24 hours of ICU admission, and the primary outcome was 28-day all-cause mortality. Covariates included demographics, vital signs, comorbidities, infection sites, organ support and medication use. Multivariable logistic regression models were applied with stepwise adjustment. Non-linear associations were assessed using generalised additive models (GAM) and two-piecewise linear regression. Sensitivity analyses using iCa quartiles and subgroup analyses stratified by Sequential Organ Failure Assessment (SOFA) score were also performed.

The overall 28-day mortality rate was 18.3%. After full adjustment, patients in quartiles Q2-Q4 had significantly lower mortality risks than those in Q1 (P for trend <0.001). A U-shaped association was observed, with an inflection point at 1.16 mmol/L (95% CI 1.12 to 1.19). Below this threshold, each 0.1 mmol/L decrease in iCa was associated with a 13% higher risk of mortality (OR=0.87; 95% CI 0.82 to 0.92; p<0.001); whereas, above this point, mortality increased by 6% per 0.1 mmol/L increment (OR=1.06; 95% CI 1.00 to 1.10; p=0.004). Subgroup analyses stratified by SOFA score (<10 vs ≥10) confirmed the robustness of the U-shaped relationship (p>0.05).

The relationship between ionised calcium and 28-day mortality in patients with sepsis showed a U-shaped curve with an inflection point of 1.16 mmol/L, which is in the range of mild hypocalcaemia.