From the Guidelines
An increased anion gap is a critical laboratory finding that indicates the presence of unmeasured anions in the bloodstream, typically above 12 mEq/L, and is often associated with metabolic acidosis, with a higher mortality rate observed in patients with an anion gap over 28 mmol/L, as seen in a study of ethylene glycol poisoning 1.
Causes and Calculation
The anion gap is calculated using the formula: Anion Gap = Na⁺ + K⁺ - (Cl⁻ + HCO₃⁻), and an elevated gap suggests the accumulation of acids that dissociate into hydrogen ions and unmeasured anions. Common causes of an increased anion gap can be remembered using the mnemonic MUDPILES, which includes conditions such as methanol, uremia, diabetic ketoacidosis, and ethylene glycol poisoning.
Clinical Significance
In clinical practice, identifying an increased anion gap is crucial for distinguishing between different types of metabolic acidosis and guiding appropriate treatment. For instance, a study on ethylene glycol poisoning found that patients with an anion gap over 28 mmol/L had a significantly higher mortality rate of 20.4% compared to those with an anion gap below 28 mmol/L 1.
Management and Outcomes
Prompt recognition and management of the underlying cause of an increased anion gap are essential to improve patient outcomes. In the context of ethylene glycol poisoning, for example, extracorporeal treatment and correction of acidemia can significantly impact survival rates, with some patients surviving despite extreme acid-base abnormalities or high ethylene glycol concentrations 1.
- Key points to consider in managing increased anion gap include:
- Prompt identification of the underlying cause
- Calculation of the anion gap using the correct formula
- Recognition of the association between a high anion gap and increased mortality
- Appropriate treatment of the underlying condition, such as extracorporeal treatment for ethylene glycol poisoning
- Close monitoring of patient outcomes and adjustment of treatment as necessary
From the FDA Drug Label
The diagnosis of these poisonings may be difficult because ethylene glycol and methanol concentrations diminish in the blood as they are metabolized to their respective metabolites Hence, both ethylene glycol and methanol concentrations and acid base balance, as determined by serum electrolyte (anion gap) and/or arterial blood gas analysis, should be frequently monitored and used to guide treatment Treatment begins immediately upon suspicion of ethylene glycol or methanol ingestion based on patient history and/or anion gap metabolic acidosis, increased osmolar gap, visual disturbances, or oxalate crystals in the urine, OR a documented serum ethylene glycol or methanol concentration greater than 20 mg/dL
Increased anion gap is associated with metabolic acidosis caused by the accumulation of toxic metabolites, such as glycolic and oxalic acids (ethylene glycol intoxication) and formic acid (methanol intoxication) 2.
From the Research
Definition of Increased Anion Gap
An increased anion gap is identified when it exceeds the upper limit of normal for a particular clinical laboratory measurement, which is often 8-10 mEq/L 3. However, the normal range can vary, and a study found a reference interval of 7 to 18 mmol/L with a median of 13 mmol/L in healthy adults 4.
Causes of Increased Anion Gap
Some common causes of increased anion gap include:
- Lactic acidosis, which can be caused by various factors such as sepsis, shock, or medication 5
- Ketoacidosis, which is often associated with diabetic ketoacidosis (DKA) 6
- Other metabolic acidosis disorders, such as those caused by renal failure, poison intake, or certain medications 7
Calculation and Interpretation of Anion Gap
The anion gap is calculated by comparing the blood sodium concentration with the sum of the chloride and bicarbonate concentrations 7. It is essential to use an appropriate reference interval to avoid misclassification of anion gap values 4. The anion gap can be affected by various factors, including hypoalbuminemia and severe hyperglycemia, and correction factors may be necessary in these cases 7.
Clinical Significance of Increased Anion Gap
An increased anion gap can indicate the presence of a metabolic acidosis disorder, which can have significant clinical implications if left untreated 5, 6. Early diagnosis and management of these disorders are crucial to improve patient outcomes 6. The anion gap can provide vital clues that direct the clinician toward the correct diagnosis, and its calculation and interpretation should be done in conjunction with other clinical and laboratory findings 7.