Does ethylene glycol (antifreeze) cause metabolic acidosis?

From the Guidelines

Yes, ethylene glycol causes metabolic acidosis, as it is metabolized into glycolate and oxalate, leading to metabolic acidemia, as stated in the 2023 study by the EXTRIP workgroup 1. When ethylene glycol is ingested, it is metabolized by alcohol dehydrogenase into glycoaldehyde, which is further converted to glycolic acid, glyoxylic acid, and finally oxalic acid. These metabolites, particularly glycolic acid, lead to a severe anion gap metabolic acidosis.

Key Points to Consider

• The EXTRIP workgroup recommends extracorporeal treatment (ECTR) in addition to supportive care for patients with ethylene glycol poisoning, especially if the glycolate concentration is > 12 mmol/L or anion gap > 27 mmol/L 1.
• Treatment for ethylene glycol poisoning includes fomepizole or ethanol to block alcohol dehydrogenase, preventing toxic metabolite formation, as well as hemodialysis for severe cases with significant acidosis, renal failure, or high ethylene glycol levels 1.
• Sodium bicarbonate may be needed to correct acidosis, and prompt treatment is essential as the acidosis develops within 4-12 hours after ingestion and can be life-threatening.
• The formation of calcium oxalate crystals from oxalic acid can also cause renal damage, further complicating the acidosis through impaired acid excretion.

Recommendations

• The most effective treatment approach is to use fomepizole (15 mg/kg loading dose, followed by 10 mg/kg every 12 hours) or ethanol (loading dose to achieve blood level of 100-150 mg/dL, then maintenance infusion) in combination with hemodialysis for severe cases, as recommended by the EXTRIP workgroup 1.
• It is crucial to monitor patients closely and adjust treatment as needed to prevent complications and improve outcomes.

From the FDA Drug Label

These metabolites can induce metabolic acidosis, nausea/vomiting, seizures, stupor, coma, calcium oxaluria, acute tubular necrosis, blindness, and death. Glycolate and oxalate are the metabolic byproducts primarily responsible for the metabolic acidosis and renal damage seen in ethylene glycol toxicosis.

Yes, ethylene glycol can cause acidosis, as its metabolites, such as glycolic and oxalic acids, can induce metabolic acidosis 2, 2.

• The main toxic metabolites of ethylene glycol are glycolate and oxalate.
• These metabolites are responsible for the metabolic acidosis and renal damage associated with ethylene glycol poisoning.

From the Research

Ethylene Glycol and Acidosis

• Ethylene glycol intoxication is known to produce a severe metabolic acidosis with an increased anion gap 3.
• The accumulation of toxic metabolites, such as glycolic acid, glyoxylic acid, and oxalic acid, is responsible for the potentially fatal acidosis and renal failure that characterizes ethylene glycol poisoning 4.
• Studies have shown that patients with ethylene glycol poisoning often present with elevated anion and osmolal gaps, indicating a high level of metabolic acidosis 5, 6.

Mechanism of Acidosis

• Ethylene glycol is metabolized to glycoaldehyde by alcohol dehydrogenase, which is then oxidized to glycolic acid, glyoxylic acid, and finally oxalic acid 4.
• Glycolic acid and lactic acid are important contributors to the acidosis caused by ethylene glycol intoxication in humans 3.
• The prevention of ethylene glycol metabolism is accomplished by the use of antidotes that inhibit alcohol dehydrogenase, such as ethanol or fomepizole 4, 7.

Treatment and Outcomes

• Treatment of ethylene glycol poisoning consists of emergent stabilization, correction of metabolic acidosis, inhibition of further metabolism, and enhancing elimination of both unmetabolized parent compound and its metabolites 4.
• Hemodialysis treatment with a bicarbonate dialysate is an efficient method for removing glycolic acid and resolving acidemia 3.
• Fomepizole monotherapy without extracorporeal treatments is safe and effective in patients with minimal metabolic acidemia (anion gap <28 mmol/L) 7.