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. 2025 Jul 1;15(1):20391.
doi: 10.1038/s41598-025-08630-x.

L-shape association between serum chloride and 365-day mortality in critically ill patients with sepsis based on the MIMIC-IV database

Zhichao Zhao  1 , Fangfang Huang  1 , Jiaqi Shen  1 , Wenqian Lv  1 , Yabo Huang  1 , Jiale Pan  1 , Ting Shen  2
Affiliations

L-shape association between serum chloride and 365-day mortality in critically ill patients with sepsis based on the MIMIC-IV database

Zhichao Zhao et al. Sci Rep. .

Abstract

This study investigated the association between serum chloride levels and mortality risk in critically ill patients with sepsis. This retrospective cohort study utilized data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. Patients were stratified into four groups based on serum chloride quartiles. The primary outcome was 365-day mortality, while secondary outcomes included 30-day and 90-day mortality. Kaplan-Meier curves were constructed to compare survival probabilities across serum chloride quartiles. Multivariable Cox proportional hazards regression and restricted cubic spline regression analyses were employed to assess the relationship between serum chloride and mortality in sepsis patients. Subgroup and sensitivity analyses were also performed to validate the findings. A total of 17,743 patients (58.26% male) were included in the study. Kaplan-Meier survival curves revealed that sepsis patients in the lowest serum chloride quartile exhibited the highest mortality (log-rank P < 0.001). Multivariable Cox regression analysis demonstrated that serum chloride was independently associated with a decreased risk of 365-day mortality (HR 0.95, 95% CI 0.94-0.97). Compared with patients in the lowest quartile, those in the highest quartile of serum chloride had significantly lower 365-day mortality (HR 0.66, 95% CI 0.58-0.75), similar trends were observed for 30-day and 90-day mortality. Restricted cubic spline regression modeling indicated a non-linear relationship between serum chloride and mortality risk, with a threshold effect identified at 105 mmol/L (P for non-linearity < 0.05). Subgroup analyses further revealed an interaction between acute kidney injury and mortality in sepsis patients. Sensitivity analysis confirmed the stability of the results. Our study demonstrated an L-shaped association between serum chloride levels and 365-day mortality in sepsis patients, with higher serum chloride levels corresponding to a lower mortality risk. However, abnormal chloride levels are often secondary to disease severity, emphasizing the need for targeted interventions addressing the underlying pathology rather than chloride levels alone.

Keywords: 365-Day mortality; MIMIC-IV database; Sepsis; Serum chloride.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The use of the MIMIC database for research purposes has been approved by the Committee on the Use of Human Subjects (COUHES) at the Massachusetts Institute of Technology (MIT), and no additional ethical approval was required for this study. The data used in this study were de-identified, i.e., all personal health information (PHI) was removed or encrypted to protect patient privacy. Therefore, this retrospective analysis did not require informed consent from individual patients.

Figures

Fig. 1
Fig. 1
Flowchart of our sepsis patients.
Fig. 2
Fig. 2
Kaplan–Meier survival analysis curves for mortality (A: 30-day mortality, B: 90-day mortality, and C: 365-day mortality).
Fig. 3
Fig. 3
Restricted cubic spline curve for the chloride hazard ratio (A: 30-day mortality, B: 90-day mortality, and C: 365-day mortality).
Fig. 4
Fig. 4
Subgroup analysis of serum chloride on the effect of 365-day mortality in the sepsis population.
See this image and copyright information in PMC

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