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Abstract: FR-PO631

A Validated Anion Gap Threshold for High Anion Gap Metabolic Acidosis

Session Information

Category: Fluid and Electrolytes

  • 902 Fluid and Electrolytes: Clinical


  • Chionh, Chang Yin, Changi General Hospital, Singapore, Singapore
  • Yeon, Wenxiang, Changi General Hospital, Singapore, Singapore
  • Poh, Cheng boon, Changi General Hospital, Singapore, Singapore
  • Koduri, Sreekanth, Changi General Hospital, Singapore, Singapore
  • Roy, Debajyoti M., Changi General Hospital, Singapore, Singapore

Group or Team Name

  • Changi REnal MEdicine REsearch (CREMERE) Group

The anion gap (AG), calculated by AG = [Na+]–[Cl]–[HCO3], is often used to screen for acid-base disorders but cut-off levels used by clinical texts were based on empirical data.

We recently sampled 300 healthy volunteers and the mean AG was 13±2mEq/L (manuscript in preparation). The proposed reference range (±2SD; central 95th percentile) was 9-17mEq/L. This study was to define a cut-off value for high AG metabolic acidosis (HAGMA).


Data from ICU patients from a prior study was used. Blood samples were classified into 2 groups: no HAGMA, or HAGMA present due to lactic acidosis, ketosis, citrate toxicity or severe uremia. The association of AG and HAGMA was tested by the Mann-Whitney U test. ROC analysis of AG was undertaken with optimal cut-off determined by Youden index.


From 1,545 blood samples, 400 had adequate data. The median age was 64.7yrs, weight 60.1kg, 31.6% were females and 170 had HAGMA. With HAGMA, median AG was 19mEq/L (IQR 17–22) vs 15mEq/L (IQR 13–17) without HAGMA (P<0.001).

AG has an AUC of 0.802 and the optimal cut-off was ≥17mEq/L (Fig. 1). The false negative rate (FNR) was 19.5%; false positive rate (FPR) 32.1%.

Other AG thresholds were analysed (Table 1). As HAGMA may be life-threatening, a lower FNR is desired. The best FNR of 13.2% was with AG ≥13mEq/L, corresponding to mean AG of healthy persons, but FPR increased to 53.0%.


The recommended AG cut-off for HAGMA is ≥13mEq/L. This provides the best sensitivity but at the expense of specificity. As false negatives can still occur, acid-base status should be evaluated clinically, aided by repeated measurements of AG.

Table 1: Sensitivity & Specificity of AG Thresholds for HAGMA
AG cut-offSpecificityFalse PositiveSensitivityFalse Negative
≥13 (Population Mean)20.0%53.0%53.0%13.2%
≥15 (Population Mean + 1SD)44.3%45.9%45.9%15.7%
≥17 (Population Mean + 2SD)73.5%32.1%32.1%19.5%

Fig. 1: ROC curve of AG for HAGMA