How to Eyeball Anion Gap at the Bedside
Use the "Rule of 12" as your mental anchor: a normal anion gap is approximately 12 mEq/L (range 8-12 mEq/L with older methods, 3-11 mEq/L with modern ion-selective electrodes), so quickly subtract (Chloride + Bicarbonate) from Sodium and compare to 12—anything substantially above suggests unmeasured anions are present. 1, 2
The Basic Mental Math
- Calculate using: Na+ - (Cl- + HCO3-) = Anion Gap 3
- For quick bedside estimation, round your electrolytes to the nearest 5 and do the subtraction mentally 1
- If you include potassium in the calculation (Na+ + K+ - Cl- - HCO3-), add approximately 4 mEq/L to your expected normal range 3
Rapid Interpretation Thresholds
- Normal range: 8-12 mEq/L (older methods) or 3-11 mEq/L (modern ion-selective electrode methods) 1, 4
- Anion gap >24 mEq/L strongly suggests metabolic acidosis and warrants immediate investigation 1
- Anion gap >27 mEq/L in suspected toxic alcohol ingestion (especially ethylene glycol) mandates emergent hemodialysis 5, 6
- Anion gap 23-27 mEq/L with suspected ethylene glycol exposure should prompt consideration of hemodialysis 5
- Anion gap <3 mEq/L is abnormally low and may indicate hypoalbuminemia, hyperglobulinemia (e.g., multiple myeloma), or laboratory error 1, 4
Clinical Context Shortcuts
When the Gap is High (>12-16 mEq/L):
- If bicarbonate is also low, think HAGMA (high anion gap metabolic acidosis)—the classic differential is ketoacidosis (diabetic, alcoholic, starvation), lactic acidosis, renal failure, or toxic ingestions 7, 8
- In toxic alcohol poisoning cases, anion gaps of 32 [25-39] mEq/L are typical, with late ethylene glycol poisoning showing gaps of 37 [32-43] mEq/L 3
- Mortality jumps significantly when anion gap exceeds 28 mEq/L in ethylene glycol poisoning (20.4% vs 3.6% in early poisoning) 6
When the Gap is Low (<3 mEq/L):
- Consider hypoalbuminemia (most common cause), multiple myeloma with IgG paraproteinemia, or laboratory error 1, 4
- A low baseline anion gap can mask a coexisting high anion gap metabolic acidosis, creating a diagnostic pitfall 4
The Delta-Delta Check for Mixed Disorders
- Calculate Δ Anion Gap / Δ HCO3- to detect mixed acid-base disorders 7
- Δ Gap = (Observed AG - Normal AG); Δ HCO3- = (Normal HCO3- - Observed HCO3-) 7
- Ratio of ~1:1 suggests pure anion gap acidosis; <1 suggests coexisting non-gap acidosis; >1 suggests coexisting metabolic alkalosis 7
Common Pitfalls to Avoid
- Modern ion-selective electrode methods produce lower anion gap values (3-11 mEq/L) than older flame photometry methods (8-16 mEq/L)—using outdated reference ranges leads to misinterpretation 1
- Hypoalbuminemia lowers the anion gap by ~2.5 mEq/L for every 1 g/dL decrease in albumin, potentially masking a true HAGMA 8
- In hospitalized patients, 37.6% have elevated anion gaps and only 2.9% have decreased gaps, so an anion gap >24 mEq/L or <2 mEq/L should prompt quality control checks of electrolyte measurements 1
- The anion gap has poor predictive value when used indiscriminately without clinical context 6
Quick Quality Control Check
- If you're seeing frequent anion gaps >24 mEq/L or <2 mEq/L in your patient population, verify laboratory quality control and check for systematic issues like hypoalbuminemia or hyperglobulinemia 1
- Anion gaps with negative values are extremely rare and should trigger immediate laboratory verification 1