Association between anion gap and all-cause mortality of critically ill surgical patients: a retrospective cohort study

Abstract

Background: There are few widely accepted and operationally feasible models for predicting the mortality risk of patients in surgical intensive care unit (SICU). Although serum anion gap (AG) is known to be correlated with severe metabolic acidosis, no investigations have been reported about the association between AG level and the outcome during hospitalization in SICU. This study aimed to explore the predictive power of AG for 90-day all-cause mortality in SICU.

Methods: Data of the eligible patients in SICU from 2008 to 2019 was obtained from the Medical Information Mart for Intensive Care IV version 2.0 (MIMIC-IV v2.0) database. Baseline clinical data of the selected patients was compared in different groups stratified by the outcome during their admission via univariate analysis. Restricted cubic spline (RCS) was drawn to confirm the relationship of AG and the short-term mortality. Kaplan-Meier survival curve was plotted in different AG level groups. Univariate and multivariate Cox analyses were performed, and Cox proportional-hazards models were built to investigate an independent role of AG to predict 90-day all-cause mortality risk in SICU. Receiver operating characteristics (ROC) curves analysis was performed to evaluate the predictive value of AG on the 90-day prognosis of patients.

Results: A total of 6,395 patients were enrolled in this study and the 90-day all-cause mortality rate was 18.17%. Univariate analysis showed that elevated serum AG was associated with higher mortality (P < 0.001). RCS analysis indicated a positively linear relationship between serum AG and the risk of 90-day all-cause mortality in SICU (χ² = 4.730, P = 0.193). Kaplan-Meier survival analysis demonstrated that low-AG group (with a cutoff value of 14.10 mmol/L) had a significantly higher cumulative survival rate than the counterpart of high-AG group (χ² = 96.370, P < 0.001). Cox proportional-hazards models were constructed and confirmed the independent predictive role of AG in 90-day all-cause mortality risk in SICU after adjusting for 23 confounding factors gradually (HR 1.423, 1.246-1.625, P < 0.001). In the further subgroup analyses, a significant interaction was confirmed between AG and sepsis as well as surgery on the risk for the 90-day mortality. The ROC curve showed that the optimal cut-off value of AG for predicting 90-day mortality was 14.89 with sensitivity of 60.7% and specificity of 54.8%. The area under curve (AUC) was 0.602. When combined with SOFA score, the AUC of AG for predicting 90-day prognosis was 0.710, with a sensitivity and specificity of 70% and 62.5% respectively.

Conclusions: Elevated AG (≥ 14.10 mmol/L) is an independent risk factor for predicting severe conditions and poor prognosis of critical ill surgical patients.

Keywords: All-cause mortality; Anion gap; MIMIC-IV; Surgical intensive care unit.