The objective of this study was to investigate whether serum anion gap (AG), which may serve as an indicator for multiple organic dysfunctions in the condition of hypoxia, could be utilized as a reliable prognostic marker for short-term mortality and a potential therapeutic target in patients with acute respiratory distress syndrome (ARDS). A retrospective cohort study was conducted using data from the Medical Information Mart for Intensive Care (MIMIC-IV) electronic database (version 2.2), including 11,227 confirmed patients with ARDS. Multivariate Cox proportional hazards analysis revealed a significant association between elevated AG levels and all-cause mortality. After adjusting for confounding factors, elevated AG levels were strongly correlated with 90-day mortality [adjusted hazard ratio (HR) 1.23
95% confidence interval (CI) 1.10-1.37
P <
0.001]. Restricted cubic splines and Kaplan-Meier curves demonstrated an increased risk of all-cause mortality with higher AG levels. Subgroup analysis results emphasized the significance of furosemide as a pivotal therapeutic option, which was further supported by subsequent Kaplan-Meier curves and Cox proportional hazards analysis showing its protective effects in patients with elevated serum AG levels. Even after adjusting for relevant confounding factors, furosemide continued to exhibit a significant protective effect in the group with the highest AG level (Q4: adjusted HR 0.57
95% CI 0.50-0.65
P <
0.001)
however, no significant protective effect was observed in the intermediate level groups (Q2 and Q3). In summary, this research demonstrated a significant association between heightened serum AG levels and increased mortality risk among ARDS patients, which was mitigated by administration of furosemide.