What is the management of an elevated anion gap?

From the Guidelines

The management of an elevated anion gap should focus on identifying and treating the underlying cause, with a particular emphasis on addressing life-threatening complications such as those associated with ethylene glycol poisoning, where extracorporeal treatment (ECTR) is recommended if the glycolate concentration is > 12 mmol/L or the anion gap is > 27 mmol/L, as suggested by the EXTRIP workgroup 1.

Key Considerations

• Initial management should include a thorough assessment of the patient's acid-base status through arterial blood gas analysis, comprehensive metabolic panel, and targeted testing based on clinical suspicion.
• For metabolic acidosis due to lactic acidosis, treatment involves optimizing tissue perfusion with intravenous fluids, treating infection if present, and discontinuing medications that may contribute to lactic acid production.
• In diabetic ketoacidosis, insulin administration, aggressive fluid resuscitation with normal saline, and electrolyte replacement are essential.
• For toxic alcohol ingestions like methanol or ethylene glycol, fomepizole or ethanol infusion may be used to block alcohol metabolism, along with hemodialysis for severe cases, with the decision to use ECTR guided by criteria such as EG concentration, osmol gap, and clinical indications like coma, seizures, or acute kidney injury (AKI) 1.

Decision Making for ECTR

• The EXTRIP workgroup recommends ECTR in addition to supportive care for patients with ethylene glycol poisoning under specific conditions, including high EG concentrations, significant osmol gaps, elevated glycolate concentrations, or severe clinical features 1.
• The choice between different ECTR modalities, such as intermittent hemodialysis or continuous kidney replacement therapy (CKRT), should be based on availability and the patient's clinical condition, with intermittent hemodialysis preferred when available 1.
• Cessation of ECTR is recommended when the anion gap is < 18 mmol/L or suggested when the EG concentration is < 4 mmol/L, with the decision individualized based on the patient's response to treatment and clinical status 1.

Clinical Application

• Clinicians should estimate the time to reach a safe EG concentration based on the initial EG concentration, the use of antidotes (fomepizole or ethanol), and the presence of AKI, to decide if ECTR would be cost-effective in the specific scenario 1.
• The osmol gap can be used as a surrogate for EG concentration in the absence of direct measurement, but its limitations, including variability and potential for overestimation, should be considered 1.
• Supportive care, including airway management, hemodynamic support, and correction of electrolyte abnormalities, is crucial across all causes of elevated anion gap metabolic acidosis.

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 consists of blocking the formation of toxic metabolites using inhibitors of alcohol dehydrogenase, such as fomepizole injection, and correction of metabolic abnormalities Hemodialysis should be considered in addition to fomepizole injection in the case of renal failure, significant or worsening metabolic acidosis, or a measured ethylene glycol or methanol concentration of greater than or equal to 50 mg/dL.

The management of an elevated anion gap due to ethylene glycol or methanol poisoning involves:

• Blocking the formation of toxic metabolites using inhibitors of alcohol dehydrogenase, such as fomepizole injection
• Correction of metabolic abnormalities
• Hemodialysis in cases of renal failure, significant or worsening metabolic acidosis, or high ethylene glycol or methanol concentrations (> 50 mg/dL) 2

From the Research

Management of Elevated Anion Gap

The management of an elevated anion gap involves identifying and treating the underlying cause of the acidosis.

• The treatment approach varies depending on the etiology, which can include lactic acidosis, ketoacidosis, toxin or drug ingestion, and uremia 3.
• For lactic acidosis, treatment is controversial, and the use of bicarbonate to increase pH is rarely successful 3.
• Ketoacidosis is typically treated by addressing the underlying cause, such as diabetes or alcohol use, and correcting fluid and electrolyte imbalances 3.
• In cases of toxin-induced anion gap acidosis, such as methanol or ethylene glycol poisoning, treatment involves alcohol infusion to decrease the formation of toxic metabolites and dialysis to remove the toxins 3, 4, 5, 6.
• Salicylate toxicity is usually associated with a mild metabolic acidosis and respiratory alkalosis, and treatment involves addressing the underlying cause and providing supportive care 3.
• Uremia is associated with a mild acidosis due to decreased ammonia secretion and an anion gap caused by the retention of unmeasured anions, and treatment involves addressing the underlying renal dysfunction 3.

Diagnostic Approach

A systematic approach to diagnosing elevated anion gap metabolic acidosis is essential, and includes:

• Calculating the anion gap and osmolal gap to help identify the underlying cause 4, 5, 6.
• Considering the patient's clinical presentation, medical history, and laboratory results to guide the diagnostic evaluation 4, 5.
• Ruling out common causes of anion gap acidosis, such as lactic acidosis, ketoacidosis, and toxin or drug ingestion 3, 4, 5, 7.
• Using the osmolal gap to help diagnose toxic alcohol ingestion, even in the absence of metabolic acidosis 5, 6.