In a large cohort study utilizing data from 7,627 sepsis patients in the eICU Collaborative Research Database, researchers uncovered a clear U-shaped relationship between corrected serum calcium (sCa) levels and 28-day mortality.

The overall 28-day mortality rate was 15.94%. Patients were divided into four groups based on corrected sCa, with the reference range set at 8.5–9.5 mg/dL.

After multivariable adjustment for confounders, the highest calcium group (>10.5 mg/dL) showed a significantly elevated mortality risk (HR 1.642, 95% CI 1.278–2.109) compared to the reference.

Restricted cubic spline and segmented regression analyses confirmed the non-linear pattern, identifying an inflection point at 9.08 mg/dL—the level associated with the lowest mortality risk.

Below this inflection point, each 1.0 mg/dL increase in corrected sCa was linked to a 7.0% reduction in mortality risk (HR 0.930), whereas above 9.08 mg/dL, each 1.0 mg/dL increase raised the risk by 21.3% (HR 1.213).

Kaplan–Meier survival curves further demonstrated poorer survival in both hypocalcemic and hypercalcemic extremes.

These findings position corrected serum calcium as an independent predictor of short-term mortality in sepsis, emphasizing the clinical value of routine monitoring and timely correction of abnormal levels to identify and intervene in high-risk patients early.

The U-shaped association suggests that both hypo- and hypercalcemia contribute to adverse outcomes, likely through mechanisms involving immune dysregulation, cardiovascular instability, and organ dysfunction in septic states.

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