Background: This study aimed to investigate the linear and nonlinear relationships between ionized calcium levels and 28-day mortality in patients with sepsis in the intensive care unit (ICU) and to provide clinicians with a direction for laboratory index testing and a basis for a calcium supplementation program. Methods: The data of patients with sepsis were extracted from the Medical Information Mart for Intensive Care (MIMIC-IV;) database, iCa served as the exposure variable, and 28-day mortality served as the outcome variable. The relationship between iCa and 28-day mortality was investigated using multivariate binary logistic regression models, with adjustment for covariates. A generalized additive model (GAM) and smoothed curve fitting were used to investigate the non-linear relationship between iCa and 28-day mortality. A two-piecewise linear model was used to calculate the OR and 95% CI on either side of the inflection point. Results: Patients with sepsis (n = 20,417) were included in the analysis, with an overall 28-day mortality rate of 19.73%. Sepsis patients were grouped into quartiles (Q1 - Q4) according to ionized calcium levels, and after complete adjustment, the short-term mortality rate of sepsis patients in Q2 - Q4 was significantly lower than that in the Q1 group (OR:0.78, 95% CI: 0.70 - 0.87. OR: 0.74, 95% CI: 0.66 - 0.83. OR: 0.81, 95% CI: 0.72 - 0.9. iCa and 28-day mortality displayed a U-shaped relationship among patients with sepsis. When iCa levels were less than 1.14 mmol/L, each unit increase corresponded to a 79% reduction in the risk of 28-day sepsis mortality(OR: 0.21, 95% CI: 0.13 - 0.35). Conversely, when iCa exceeded 1.14 mmol/L, each unit increase was linked to an 85% increase in the 28-day mortality risk (OR: 1.85, 95% CI: 1.08 - 3.16). Conclusion: The relationship between iCa and 28-day mortality in patients with sepsis showed a U-shaped curve with an inflection point of 1.14 mmol/L, which is in the range of mild hypocalcemia.

The authors have declared no competing interest.

Guangzhou municipal science and technology bureau [2023A04J0464]. National Famous Elderly Chinese Medicine Expert Huang Jianling Famous Doctor Inheritance Workshop [Letter of Human Resource Education on Chinese Medicine (2022) No. 75]. The National Natural Science Foundation of China [82305164]. Top Talents Project of Guangdong Provincial Hospital of Chinese Medicine (BJ2022YL15).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

None declared.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes