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The anion gap as a predictive tool for morbidity and mortality
1Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Critical Reviews in Clinical Laboratory Sciences
|July 18, 2025
Summary
The anion gap is a key diagnostic tool for acid-base disorders and a significant predictor of morbidity and mortality across many patient groups. Despite variable reference intervals, its predictive value in clinical settings remains crucial.
Area of Science:
- Clinical Chemistry
- Medical Diagnostics
- Biomarker Research
Background:
- The anion gap has been integral to diagnosing acid-base disorders since the 1970s.
- Recent literature highlights its emerging role as a predictive marker for morbidity and mortality.
Purpose of the Study:
- To review the history, derivation, and reference interval issues of the anion gap.
- To conduct a literature review on its predictive utility in various clinical conditions.
Main Methods:
- A PubMed search for "ANION GAP" (up to 12/31/2022) identified 2,068 references.
- References were categorized into predictive and non-predictive uses, with predictive studies further classified by clinical cohort.
Main Results:
- An elevated anion gap significantly predicted morbidity/mortality in critical patients, general population, glycemia, intoxication, myeloma, renal function, and seizure cohorts.
- Published anion gap reference intervals showed high variability (upper limits 10–19 mmol/L; width 2–11 mmol/L).
Conclusions:
- The anion gap's benefits as a significant predictor of morbidity and mortality outweigh its identified flaws.
- Variability in equations and reference limits questions the necessity of a "normal range" for clinical management.
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