Ethylene Glycol Poisoning

Ethylene glycol, a common component of antifreeze, is itself relatively non-toxic. It is metabolized via alcohol dehydrogenase and subsequent enzymatic steps to a series of toxic organic acids, including oxalic acid. This is directly nephrotoxic and combines with calcium to form calcium oxalate crystals that deposit in the renal tubules, causing acute kidney injury.

It shares a very similar mechanism, antidote, and general management approach to methanol poisoning, differing principally in the specific target organ of toxicity, kidney rather than optic nerve, and in certain distinctive diagnostic clues.

Toxicity progresses through recognizable, though overlapping, stages:

• Stage 1 (0.5 to 12 hours): neurological toxicity resembling alcohol intoxication, including ataxia, slurred speech, and confusion, without the smell of alcohol on the breath (a useful, though not entirely reliable, distinguishing clue from simple ethanol intoxication).
• Stage 2 (12 to 24 hours): cardiopulmonary toxicity, with tachycardia, hypertension or hypotension, and, in severe cases, pulmonary edema and cardiovascular collapse, reflecting the systemic effects of accumulating toxic acid metabolites and severe acidosis.
• Stage 3 (24 to 72 hours): renal toxicity, with flank pain and acute kidney injury from calcium oxalate crystal deposition within the renal tubules.

Hypocalcemia can occur as calcium is consumed in oxalate crystal formation, occasionally causing tetany or QT prolongation as an additional feature.

• A serum ethylene glycol level confirms exposure, though, as with methanol, this is not always rapidly available and clinical and surrogate marker based decision making is often required.
• Venous or arterial blood gas shows a high anion gap metabolic acidosis, evolving as with methanol poisoning; the osmolar gap is similarly useful early, narrowing as metabolism proceeds.
• Urine microscopy is a distinctive and valuable diagnostic clue: calcium oxalate crystals, classically described as envelope shaped or needle shaped, may be visible, supporting the diagnosis when present, though their absence does not exclude poisoning.
• Urine fluorescence under a Wood's lamp has historically been described as a diagnostic aid, reflecting fluorescein sometimes added to antifreeze products, though this finding is unreliable and should not be relied upon in isolation.
• Calcium, renal function, and lactate should be checked. Some ethylene glycol metabolites can cause a falsely elevated lactate reading on certain point of care and laboratory assays, an important pitfall to be aware of when interpreting an apparently very high lactate in this context.

Differentials mirror those for methanol poisoning: diabetic ketoacidosis and other high anion gap metabolic acidoses, methanol poisoning itself, and simple ethanol intoxication.

Management follows the same core principles as methanol poisoning, given the shared mechanism.

• Fomepizole (or, where unavailable, an ethanol infusion titrated to a target level) blocks alcohol dehydrogenase, preventing further generation of toxic metabolites.
• Sodium bicarbonate corrects the metabolic acidosis.
• Hemodialysis is indicated for severe poisoning, significant acidosis, renal impairment, or high ethylene glycol levels, removing both parent compound and toxic metabolites while correcting acid base disturbance.
• Calcium replacement is given for symptomatic hypocalcemia (tetany, significant QT prolongation), though asymptomatic mild hypocalcemia is generally not aggressively corrected given a theoretical concern about promoting further calcium oxalate crystal formation.
• Pyridoxine and thiamine are sometimes given as adjuncts, since they act as cofactors that can help shunt metabolism toward less toxic metabolite pathways.

Referral: poison control or toxicology service urgently for all suspected cases; nephrology and ICU where hemodialysis or significant renal impairment is present.