Is a high anion gap (anion gap) indicative of metabolic acidosis?

From the Guidelines

A high anion gap is a strong indicator of metabolic acidosis, particularly high anion gap metabolic acidosis (HAGMA), which can be caused by various conditions such as diabetic ketoacidosis, lactic acidosis, or certain poisonings like ethylene glycol poisoning, as suggested by the EXTRIP workgroup in their 2023 systematic review and recommendations 1.

Key Points to Consider

• The anion gap is calculated by subtracting the major measured anions (chloride and bicarbonate) from the major measured cation (sodium), with a normal value typically ranging from 8-12 mEq/L.
• A high anion gap suggests the presence of additional acids not routinely measured, which can be seen in conditions like diabetic ketoacidosis, lactic acidosis, or ethylene glycol poisoning.
• The EXTRIP workgroup recommends extracorporeal treatment (ECTR) if the anion gap is > 27 mmol/L in patients with ethylene glycol poisoning, as this indicates severe metabolic acidosis and potential for poor outcomes 1.
• Mortality in patients with an anion gap over 28 mmol/L was significantly higher, at 20.4%, as reported in a 2023 study on extracorporeal treatment for ethylene glycol poisoning 1.

Clinical Implications

• When the anion gap is high, it is essential to determine the specific cause of metabolic acidosis through additional clinical information and laboratory tests.
• Conditions like diarrhea or renal tubular acidosis can cause normal anion gap metabolic acidosis, where bicarbonate is lost or there's impaired acid excretion without accumulation of unmeasured anions.
• The presence of a high anion gap should prompt further investigation and potentially aggressive treatment, including ECTR, to manage the underlying condition and prevent poor outcomes.
• Clinicians should be aware of the potential for high anion gap metabolic acidosis in patients with certain poisonings, such as ethylene glycol, and consider ECTR as a treatment option based on the anion gap and other clinical indicators, as recommended by the EXTRIP workgroup 1.

From the Research

Metabolic Acidosis and Anion Gap

• Metabolic acidosis is a condition characterized by an excess of acid in the body, and it can be classified into two main subtypes: high anion gap metabolic acidosis and normal anion gap (or hyperchloremic) metabolic acidosis 2.
• A high anion gap is often associated with metabolic acidosis, and it can be caused by various factors such as lactic acidosis, diabetic ketoacidosis, and certain toxic ingestions 3, 4.

Causes of High Anion Gap Metabolic Acidosis

• Ketoacidosis, lactic acidosis, and renal failure are some of the possible causes of metabolic acidosis with a high anion gap 3.
• The anion gap can be useful in the differential diagnosis of metabolic acidosis, and it can help identify the underlying cause of the condition 5, 4.

Diagnostic Approach

• The diagnostic approach to metabolic acidosis should involve the calculation of the anion gap, as well as other laboratory tests such as plasma osmolality and osmolal gap calculations 4.
• The anion gap can be calculated using the formula: Anion Gap = Sodium - (Chloride + Bicarbonate), and it can be used to identify the presence of metabolic acidosis and to guide further diagnostic testing 4.

Clinical Significance

• Metabolic acidosis, especially with a high anion gap, can have significant clinical implications, including hemodynamic instability and respiratory failure 2, 6.
• The therapeutic approach to metabolic acidosis should involve the correction of the underlying cause, as well as the administration of alkalizing agents and other supportive therapies as needed 2, 4.