Albumin-Corrected Anion Gap Flags Early Death Risk in ICU COPD Patients

An elevated albumin-corrected anion gap (ACAG), a routine blood chemistry measure, is linked to a higher risk of death within 30 days among intensive care unit patients experiencing an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), according to a retrospective cohort study published in BMC Pulmonary Medicine. The association was strongest in the earliest phase of follow-up, while links to longer-term and in-hospital mortality faded after thorough statistical adjustment, and the marker’s added predictive power beyond existing severity scores proved modest.

Researchers drew on the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, identifying 585 adults diagnosed with AECOPD who had been admitted to an ICU. Patients were sorted into quartiles according to their ACAG levels. The primary outcomes were all-cause mortality at 30 and 365 days; secondary outcomes included in-hospital mortality, mechanical ventilation, ICU readmission, and lengths of ICU and hospital stay. The team used Kaplan–Meier survival curves, Cox proportional hazards models, and restricted cubic spline (RCS) analyses to probe the relationship, and also tested whether ACAG added prognostic value over the traditional anion gap and the Sequential Organ Failure Assessment (SOFA) score.

The burden of adverse outcomes in this population was substantial. All-cause mortality reached 25.4 percent (149 patients) at 30 days and 46.4 percent (272 patients) at 365 days, while 16.5 percent (97 patients) died in hospital.

After full adjustment for confounders, higher ACAG remained independently associated with 30-day mortality both as a continuous variable, with a hazard ratio of 1.054 per 1 mmol/L (95 percent confidence interval, 1.008–1.101; P = 0.020), and as a categorical variable, with patients in the highest quartile facing roughly twice the hazard of those in the lowest (Q4 versus Q1: hazard ratio, 1.922; 95 percent confidence interval, 1.140–3.242; P = 0.015). RCS analyses found no evidence of a nonlinear relationship, suggesting the risk rose in an approximately linear fashion with the gap value.

The picture changed over longer horizons. The fully adjusted association between ACAG and 365-day mortality was not statistically significant (hazard ratio per 1 mmol/L, 1.015; 95 percent confidence interval, 0.983–1.049; P = 0.353), and the same held for in-hospital mortality (odds ratio, 1.062; 95 percent confidence interval, 0.997–1.132; P = 0.063). Piecewise Cox analyses indicated that the association was concentrated during the early follow-up period, meaning the marker appears most informative for short-term risk rather than for predicting outcomes months later or before discharge.

On the question of whether ACAG improves on existing tools, the results were mixed. The corrected gap discriminated 30-day mortality better than the traditional, uncorrected anion gap, supporting the argument that accounting for albumin levels refines the acid–base signal. However, its incremental contribution beyond the SOFA score, a widely used measure of organ dysfunction, was modest, indicating that ACAG should complement rather than replace established severity assessments.

The authors conclude that elevated ACAG is independently associated with increased 30-day all-cause mortality in ICU patients with AECOPD, with the association most pronounced during early follow-up, but that it should not be regarded as a standalone prognostic tool.

The authors also note that the accepted manuscript was shared early to provide faster access to peer-reviewed research and remains subject to further edits before the final version of record is issued.

Subject of Research: Association between albumin-corrected anion gap and mortality outcomes in ICU patients with acute exacerbation of COPD

Article Title: Association between albumin-corrected anion gap and adverse outcomes in patients with acute exacerbation of chronic obstructive pulmonary disease in the intensive care unit

Article References: Peng, M., Cao, H., Wei, J., Chen, X., Li, S., Zhang, Y., Ma, W., & Li, Y. (2026). Association between albumin-corrected anion gap and adverse outcomes in patients with acute exacerbation of chronic obstructive pulmonary disease in the intensive care unit. BMC Pulmonary Medicine. https://doi.org/10.1186/s12890-026-04897-6

Image Credits: AI Generated

DOI: 10.1186/s12890-026-04897-6

Keywords: albumin-corrected anion gap, COPD exacerbation, intensive care unit, MIMIC-IV, 30-day mortality, risk stratification, SOFA score, anion gap, retrospective cohort study, BMC Pulmonary Medicine, Association, between