Association Between Postoperative Albumin-Corrected Anion Gap (ACAG) and 28-Day Mortality Risk in the Intensive Care Unit (ICU) After Cardiac Surgery: A Retrospective Study Based on Two Large Databases, Medical Information Mart for Intensive Care IV (MIMIC-IV) and eICU Collaborative Research Database (eICU-CRD)

Q: What are the key findings of this study?

Higher postoperative albumin-corrected anion gap independently increased 28-day ICU mortality after cardiac surgery in both MIMIC-IV (HR 1.132, P<0.001) and eICU (HR 1.037, P<0.001) cohorts.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Cardiac surgery patients admitted to the Intensive Care Unit (n=4615). Intervention: Postoperative Albumin-Corrected Anion Gap (ACAG) vs. Lower ACAG (per 1-mmol/L increase or lowest quartile Q1). Primary outcome: 28-day all-cause mortality in the ICU (HR 1.132, 95% CI 1.099-1.167, p=<0.001).

Q: What does this research mean for the field?

Higher postoperative albumin-corrected anion gap is independently associated with increased 28-day ICU mortality following cardiac surgery, with levels exceeding 20 mmol/L indicating the highest risk. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To evaluate the association between early postoperative albumin-corrected anion gap (ACAG) and 28-day ICU mortality risk following cardiac surgery and assess its cross-center generalizability.

Mingliang Li; Yi Zheng; Dingyu Guo; Zijun Wu; Kangjin Peng; Sihao Yan; Xingyu Zhou; Zixing Huang; Xinyi Zhan; Shuozhong Wu; Junhao He; Lingpin Pang; Xishi Sun; Feng Yao

doi:10.21203/rs.3.rs-11177278/v1

October 22, 2026Open Access

Association Between Postoperative Albumin-Corrected Anion Gap (ACAG) and 28-Day Mortality Risk in the Intensive Care Unit (ICU) After Cardiac Surgery: A Retrospective Study Based on Two Large Databases, Medical Information Mart for Intensive Care IV (MIMIC-IV) and eICU Collaborative Research Database (eICU-CRD)

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Key result

Higher postoperative albumin-corrected anion gap linked to ~13% higher 28-day ICU mortality after cardiac surgery.

HR 1.132
95% CI 1.099-1.167
P<0.001
n=4,615

Why the study?

Existing scoring systems have limited efficacy in early risk identification after cardiac surgery, and the predictive value and cross-center generalizability of the Albumin-Corrected Anion Gap in the acute postoperative period remained unclear.

Does a higher postoperative Albumin-Corrected Anion Gap (ACAG) predict increased 28-day all-cause ICU mortality risk in adult patients after cardiac surgery?

Key Points

To evaluate the association between early postoperative albumin-corrected anion gap (ACAG) and 28-day ICU mortality risk following cardiac surgery and assess its cross-center generalizability.
Multicenter retrospective cohort study using the MIMIC-IV v3.1 database as the primary cohort (N=2,206) and the eICU-CRD database as an independent external validation cohort (N=2,409) among adult cardiac surgery patients.
ACAG was calculated from anion gap and serum albumin within 24 hours of ICU admission; the primary endpoint was 28-day all-cause ICU mortality.
Analyses utilized multivariable Cox regression models adjusted for confounders including SOFA and APACHE scores, restricted cubic splines (RCS), and the C-index.
ICU 28-day mortality was 12.5% (276 deaths) in the MIMIC cohort and 34.5% (831 deaths) in the eICU cohort.
Postoperative ACAG was an independent risk factor for death in both cohorts after multivariable adjustment (MIMIC: HR = 1.132, 95% CI: 1.099–1.167; eICU: HR = 1.037, 95% CI: 1.024–1.052; both P < 0.001).
Risk of death was significantly elevated in the highest quartile (eICU Q4 vs Q1: HR = 1.54, 95% CI: 1.24–1.93; ACAG > 20 mmol/L), demonstrating a linear association with mortality (nonlinear P = 0.401) and C-indices of 0.822 in MIMIC and 0.700 in eICU.

Study Design

Type

Cohort (n=4,615)

Multicenter

Yes

Structured PICO

Does a higher postoperative Albumin-Corrected Anion Gap (ACAG) predict increased 28-day all-cause ICU mortality risk in adult patients after cardiac surgery?

P

Population

4,615 adult patients undergoing cardiac surgery across two US critical care databases (2,206 in MIMIC-IV and 2,409 in eICU-CRD) with available postoperative anion gap and serum albumin measurements within 24 hours of ICU admission, followed for up to 28 days.

E

Exposure

Postoperative Albumin-Corrected Anion Gap (ACAG), calculated from averaged laboratory values within 24 hours after ICU admission as ACAG (mmol/L) = anion gap (mmol/L) + 2.5 × (4.4 − serum albumin [g/dL]), evaluated as a continuous variable and stratified by quartiles (high-risk threshold >20 mmol/L).

C

Comparator

Lowest ACAG quartile (Q1: ≤14 mmol/L in MIMIC-IV; ≤13.75 mmol/L in eICU-CRD) in quartile analyses.

O

Outcome

28-day all-cause mortality in the ICU after cardiac surgery.hard clinical

Main Result

Hazard Ratio: 1.132 (95% CI 1.099–1.167)

p-value: p=<0.001

Postoperative Albumin-Corrected Anion Gap (ACAG) within 24 hours of ICU admission is linearly and independently associated with 28-day ICU mortality after cardiac surgery across two large cohorts, with ACAG > 20 mmol/L serving as a bedside high-risk warning threshold.

Limitations

Retrospective design cannot completely exclude unmeasured confounders such as cardiopulmonary bypass time, intraoperative minimum temperature, and transfusion volume
Only the average ACAG within 24 hours after ICU admission was used, preventing evaluation of its dynamic trajectory
Differences in built-in APACHE scoring versions between databases (APACHE III in MIMIC-IV vs APACHE IV in eICU-CRD)
High heterogeneity (I² = 96.3%) in effect size between the two cohorts
Limited robustness to unmeasured confounding in the eICU validation cohort (E-value = 1.24)

Implication

May inform ICU risk stratification after cardiac surgery; leaves open prospective validation before clinical adoption.

Abstract

Background The 28-day mortality rate after cardiac surgery can reach 2%–22%, and existing scoring systems have limited efficacy in early risk identification. Albumin-Corrected Anion Gap (ACAG) can reflect signals of metabolic disorders; however, its predictive value in the acute postoperative period and its cross-center generalizability remain unclear. Methods This multicenter retrospective large cohort study used MIMIC-IV v3.1 as the study cohort and eICU as an independent external validation cohort. Kaplan-Meier survival curves, Cox nested models, restricted cubic spline (RCS), and C-index were used to evaluate the association between postoperative ACAG and 28-day mortality risk in the ICU and model discrimination. Results The MIMIC cohort included 2,206 patients (276 deaths, 12.5%) and the eICU cohort included 2,409 patients (831 deaths, 34.5%). After adjustment for confounders, ACAG was an independent risk factor for death in both cohorts (MIMIC: hazard ratio [HR] = 1.132, 95% confidence interval [CI]: 1.099–1.167; eICU: HR = 1.037, 95% CI: 1.024–1.052; both P < 0.001). Only the highest quartile group showed a significantly increased risk of death (eICU Q4 vs Q1: HR = 1.54, 95% CI: 1.24–1.93). RCS showed that ACAG was linearly positively associated with mortality risk (nonlinear P = 0.401). The C-index in MIMIC and eICU was 0.822 and 0.700, respectively. Conclusion Higher postoperative ACAG was significantly positively associated with 28-day all-cause mortality in the ICU after cardiac surgery. The risk of death was highest in the highest quartile group (ACAG > 20 mmol/L), and this threshold can serve as a clinical high-risk warning threshold.

Discussion

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Cite This Study

Li et al. (2026) conducted a cohort in Cardiac surgery patients admitted to the Intensive Care Unit (n=4,615). Postoperative Albumin-Corrected Anion Gap (ACAG) vs. Lower ACAG (per 1-mmol/L increase or lowest quartile Q1) was evaluated on 28-day all-cause mortality in the ICU (HR 1.132, 95% CI 1.099-1.167, p=<0.001). Higher postoperative albumin-corrected anion gap independently increased 28-day ICU mortality after cardiac surgery in both MIMIC-IV (HR 1.132, P<0.001) and eICU (HR 1.037, P<0.001) cohorts.

synapsesocial.com/papers/6ae28f3bcbadf70daf6c4432 https://doi.org/10.21203/rs.3.rs-11177278/v1

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Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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