From the Guidelines
Treatment of high anion gap metabolic acidosis should focus on addressing the underlying cause, and for ethylene glycol poisoning, the EXTRIP workgroup recommends extracorporeal treatment (ECTR) if the glycolate concentration is > 12 mmol/L or anion gap > 27 mmol/L, as evidenced by the 2023 study published in Critical Care 1.
Key Considerations
- Identify and treat the specific etiology of high anion gap metabolic acidosis, which may include diabetic ketoacidosis (DKA), lactic acidosis, toxic ingestions, or renal failure.
- For toxic alcohol ingestions, such as ethylene glycol, administer fomepizole (15 mg/kg loading dose, then 10 mg/kg every 12 hours) or ethanol if fomepizole is unavailable, as recommended by the EXTRIP workgroup 1.
- Consider sodium bicarbonate therapy (1-2 mEq/kg IV) when pH falls below 7.1, particularly in cases of salicylate toxicity or when acidosis is severe enough to affect cardiac function.
- Hemodialysis may be necessary for severe cases, especially with renal failure, certain toxin ingestions, or when acidosis remains refractory to treatment, with the EXTRIP workgroup recommending intermittent hemodialysis over other types of ECTR 1.
Decision Making for ECTR
- The decision to initiate ECTR should be based on the presence of severe clinical features, such as coma, seizures, or acute kidney injury (AKI), as well as the level of glycolate concentration or anion gap, with the EXTRIP workgroup providing specific recommendations for these scenarios 1.
- The osmol gap can be used as a surrogate to predict the EG concentration, but it is a poor screening test for EG ingestion, especially at low osmol gap values, and should be interpreted with caution 1.
Monitoring and Adjustment
- Continuous monitoring of electrolytes, glucose, and acid-base status is essential during treatment, with adjustments made as necessary to normalize pH and eliminate the underlying cause.
- The dosage of antidotes, such as fomepizole or ethanol, may need to be adjusted during ECTR, as recommended by the EXTRIP workgroup 1.
From the FDA Drug Label
Treatment Guidelines If ethylene glycol or methanol poisoning is left untreated, the natural progression of the poisoning leads to accumulation of toxic metabolites, including glycolic and oxalic acids (ethylene glycol intoxication) and formic acid (methanol intoxication) These metabolites can induce metabolic acidosis, nausea/vomiting, seizures, stupor, coma, calcium oxaluria, acute tubular necrosis, blindness, and death. Treatment consists of blocking the formation of toxic metabolites using inhibitors of alcohol dehydrogenase, such as fomepizole injection, and correction of metabolic abnormalities In patients with high ethylene glycol or methanol concentrations (> 50 mg/dL), significant metabolic acidosis, or renal failure, hemodialysis should be considered to remove ethylene glycol or methanol and the respective toxic metabolites of these alcohols 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. Laboratory Tests In addition to specific antidote treatment with fomepizole, patients intoxicated with ethylene glycol or methanol must be managed for metabolic acidosis, acute renal failure (ethylene glycol), adult respiratory distress syndrome, visual disturbances (methanol), and hypocalcemia. Fluid therapy and sodium bicarbonate administration are potential supportive therapies
Treating high anion gap metabolic acidosis 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
- Consideration of hemodialysis in patients with significant metabolic acidosis, renal failure, or high ethylene glycol or methanol concentrations
- Supportive therapies, including fluid therapy and sodium bicarbonate administration, to manage metabolic acidosis and other complications 2 2
From the Research
Treating High Anion Gap Metabolic Acidosis
- High anion gap metabolic acidosis can be caused by various disorders, including diabetic or alcoholic ketoacidosis, acute kidney injury, chronic kidney disease, and lactic acidosis 3
- The diagnosis of high anion gap metabolic acidosis often involves calculating the anion gap and osmolal gap, as well as considering the patient's history and physical exam 4
- In some cases, the anion gap may be normal, even in the presence of ethylene glycol poisoning, due to concurrent ethanol ingestion 5
- Treatment of high anion gap metabolic acidosis may involve the use of fomepizole and ethanol to inhibit alcohol dehydrogenase, as well as hemodialysis to remove toxic metabolites 6
Diagnostic Approach
- The anion gap is a helpful calculation that divides metabolic acidoses into two categories: high anion gap metabolic acidosis and hyperchloremic metabolic acidosis 7
- Calculating the osmolal gap can also provide important clues for diagnosis, particularly in cases of ethylene glycol or methanol poisoning 3, 6
- It is essential to consider the patient's history, physical exam, and laboratory results when diagnosing and treating high anion gap metabolic acidosis 4, 7