Anion gap physiology and faults of the correction formula

Abstract

Purpose: The anion gap is a calculated fundamental laboratory parameter used to identify and monitor acid-base disturbances. A recently popularized correction formula transforms the resulting integer to compensate for hypoalbuminemia and improve diagnostic yield. Clinical pharmacists should be aware of the underlying biochemistry, interpretation, and limitations of this formula to discern drug- and disease-related etiologies.

Summary: The anion gap is utilized in most care settings, ranging from outpatient monitoring to inpatient intensive care units. Supported by decades of experience, the original anion gap derives its value from its simplicity. Applying the anion gap in metabolic acidosis can help narrow differential diagnosis and detect concomitant acid-base disorders. To account for hypoalbuminemia and potential missed diagnoses, a correction formula was developed to improve sensitivity. Yet, the law of electroneutrality ensures that hypoalbuminemia is already accounted for in the original anion gap, and the proposed correction formula was derived from samples unrepresentative of human physiology. Evidence from clinical trials shows no benefit from applying the correction formula.

Conclusion: There is no advantage to correcting the anion gap, and such correction may increase the risk of misinterpretation or error. Clinicians should understand these limitations when diagnosing or trending acid-base disturbances.

Keywords: acid-base equilibrium; anion gap; chemical phenomena; correction formula; homeostasis; metabolic acidosis.