Alveolar-arterial oxygen gradient nonlinearly impacts the 28-day mortality of patients with sepsis: Secondary data mining based on the MIMIC-IV database

Abstract

Objective: Lung is often implicated in sepsis, resulting in acute respiratory distress syndrome (ARDS). The alveolar-arterial oxygen gradient [D(A-a)O₂ ] reflects lung diffusing capacity, which is usually compromised in ARDS. But whether D(A-a)O₂ impacts the prognosis of patients with sepsis remains to be explored. Our study aims to investigate the association between D(A-a)O₂ and 28-day mortality in patients with sepsis using a large sample, multicenter Medical Information Mart for Intensive Care (MIMIC)-IV database.

Methods: We extracted a data of 35 010 patients with sepsis from the retrospective cohort MIMIC-IV database, by which the independent effects of D(A-a)O₂ on 28-day death risk was investigated, with D(A-a)O₂ as being the exposure variable and 28-day fatality being the outcome variable. Binary logistic regression and a two-piecewise linear model were employed to explore the relationship between D(A-a)O₂ and the 28-day death risk after confounding factors were optimized including demographic indicators, Charlson comorbidity index (CCI), Sequential Organ Failure Assessment (SOFA) score, drug administration, and vital signs.

Results: A total of 18 933 patients were finally included in our analysis. The patients' average age was 66.67 ± 16.01 years, and the mortality at 28 days was 19.23% (3640/18933). Multivariate analysis demonstrated that each 10-mmHg rise of D(A-a)O₂ was linked with a 3% increase in the probability of death at 28 days either in the unadjusted model or in adjustment for demographic variables (Odds ratio [OR]: 1.03, 95% CI: 1.02 to 1.03). But, each 10 mmHg increase in D(A-a)O₂ was associated with a 3% increase of death (OR: 1.03, 95% CI: 1.023 to 1.033) in the case of adjustment for all covariants. Through smoothed curve fitting and generalized summation models, we found that non-linear relationship existed between D(A-a)O₂ and the death at 28-day, which demonstrated that D(A-a)O₂ had no any impacts on the prognosis of patients with sepsis when D(A-a)O₂ was less than or equal to 300 mmHg, but once D(A-a)O₂ exceeded 300 mmHg, however, every 10 mmHg elevation of D(A-a)O₂ is accompanied by a 5% increase of the 28-day death (OR: 1.05; 95% CI:1.04 to 1.05, p < 0.0001).

Conclusion: Our findings suggests that D(A-a)O₂ is a valuable indicator for the management of sepsis patient, and it is recommended that D(A-a)O₂ be maintained less than 300 mmHg as far as possible during sepsis process.

Keywords: D(A-a)O2; MIMIC-IV database; mortality; sepsis.