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. 2025 Aug 1:16:1578078.
doi: 10.3389/fendo.2025.1578078. eCollection 2025.

Association between serum anion gap trajectory and mortality in hospitalized patients with sepsis: an analysis of the MIMIC-IV database

Lijuan Jing  1 , Xiaopeng Shi  1 , Lijun Xu  1 , Xiangmei Zhao  1 , Faliang Li  1 , Lijie Qin  1
Affiliations

Association between serum anion gap trajectory and mortality in hospitalized patients with sepsis: an analysis of the MIMIC-IV database

Lijuan Jing et al. Front Endocrinol (Lausanne). .

Abstract

Background: Sepsis remains a leading cause of mortality in intensive care units (ICUs), with high morbidity and healthcare costs worldwide. The serum anion gap (AG), a marker of metabolic acidosis, has been associated with adverse outcomes in various critical illnesses. However, the prognostic value of longitudinal AG trajectories in sepsis remains underexplored. This study explored the link between dynamic AG trajectories and all-cause mortality in critically ill septic patients.

Methods: A retrospective cohort study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Adult patients meeting Sepsis-3 criteria for sepsis were included. Group-based trajectory modeling was used to identify AG trajectories during the initial five days of ICU admission. Patients were classified into three trajectory groups: normal-level-stable trajectory (Class 1), high-level-decline trajectory (Class 2), and progressive acidosis trajectory (Class 3). Cox proportional hazards models evaluated the link between AG trajectories and ICU/hospital mortality, controlling for demographic, laboratory, and clinical severity factors. Subgroup and sensitivity analyses were performed to validate the findings.

Results: Among 6,110 septic patients, three distinct AG trajectory groups were identified. Patients in Class 3 (decreasing high AG) had the highest mortality, with ICU mortality of 30.61% and hospital mortality of 35.85%, compared to Class 1 (ICU mortality: 14.46%, hospital mortality: 19.41%) and Class 2 (ICU mortality: 21.88%, hospital mortality: 31.88%). In fully adjusted models, Class 3 exhibited a significantly increased risk of ICU mortality [HR=1.72, (95% CI 1.43-2.07), P<0.001] and hospital mortality [HR=1.64, (95% CI 1.39-1.94), P<0.001] relative to Class 1. Subgroup analysis revealed a significant interaction between AG trajectories and heart failure status. Sensitivity analysis excluding patients with malignancies confirmed the robustness of the findings.

Conclusion: Continuous monitoring of AG levels is crucial for risk assessment and personalized treatment, as rising AG levels significantly increase mortality risk. These findings underscore the potential of AG trajectories as a dynamic biomarker to improve sepsis management and patient outcomes.

Keywords: anion gap; intensive care unit; mortality; sepsis; trajectory analysis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram of the screening and enrollment of study participants.
Figure 2
Figure 2
AG trajectory during the first 5 days in the ICU.
Figure 3
Figure 3
Kaplan-Meier survival estimates for ICU (A) and hospital (B) mortality by AG trajectory.
See this image and copyright information in PMC

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