Anion gap predicting 90-Day mortality and guiding furosemide use in ARDS.

Summary

Using MIMIC-IV data on 11,227 ARDS patients, higher serum anion gap independently predicted 90-day mortality. Furosemide use was associated with reduced mortality only in the highest anion gap quartile, suggesting potential benefit in a high–anion gap phenotype.

Key Findings

• Retrospective cohort of 11,227 ARDS patients from MIMIC-IV (v2.2).
• Elevated anion gap independently associated with higher 90-day mortality (adjusted HR 1.23; 95% CI 1.10–1.37; p<0.001).
• Furosemide showed a protective association only in the highest anion gap quartile (Q4: adjusted HR 0.57; 95% CI 0.50–0.65; p<0.001), with no significant effect in Q2–Q3.

Clinical Implications

In ARDS, routinely assess and trend anion gap to inform risk stratification. Consider conservative fluid strategy and cautious furosemide use in patients with very high anion gap while awaiting prospective validation; avoid overinterpreting causality given potential confounding.

Limitations

• Retrospective EHR-based study with potential residual confounding and ARDS misclassification
• Confounding by indication likely for furosemide; fluid balance and hemodynamic data may be limited

Future Directions

Prospective validation and randomized trials of diuretic strategies guided by anion gap or metabolic phenotype to establish causality and refine patient selection.