Ethylene Glycol
Ethylene glycol is considered to be a toxic alcohol. Common sources of ethylene glycol include automotive antifreeze, engine coolants and deicing fluids. Ethylene glycol is most commonly ingested by adults who drink antifreeze or adulterated spirits in an attempt to commit suicide. Children most commonly ingest it unintentionally. Ingestion of 1 g/kg of ethylene glycol is considered to be a lethal dose in adults. Ethylene glycol is rapidly and completely absorbed from the GI tract after oral ingestion. Peak serum ethylene glycol concentration occurs in one to two hours after ingestion. The estimated serum half-life ranges between 3 and 9 hours.
Ethylene glycol itself is non-toxic. However, it is quickly metabolized by alcohol dehydrogenase and aldehyde dehydrogenase to glycolic and oxalic acids, which are toxic. These acids also cause a high anion gap metabolic acidosis. Oxalic acid also binds with calcium and precipitates in tissue, particularly the kidney causing further damage.
Initially patients who ingest ethylene glycol may shows signs of intoxication and CNS depression depending on the amount consumed. Higher molecular weight alcohols, such as ethylene glycol, have more intoxicating effects than lower molecular weight alcohols such as methanol. Cranial nerve palsies have been attributed to ethylene glycol poisoning. If left untreated ethylene glycol toxicity will lead to a profound metabolic acidosis, renal failure and death. Neurologic dysfunction develops in the first 12 hours, followed by cardiac and pulmonary dysfunction in 12 to 24 hours and acute kidney injury after 48 to 72 hours after exposure. Hypocalcemia and tetany may occur following formation of calcium oxalate crystals. Coingestion of ethanol can delay the onset of symptoms. Ethylene glycol toxicity can be prevented and/or treated with fomepizole and hemodialysis.
Most hospital laboratories do not measure ethylene glycol levels. However, other laboratory tests are helpful in making the diagnosis of methanol poisoning. Electrolytes reveal a low bicarbonate and elevated anion gap, consistent with metabolic acidosis. Anion gap rises as ethylene glycol is metabolized to glycolic and oxalic acids.
Measurement of serum osmolality and calculation of the osmolal gap are also useful. Serum osmolality increases 1.60 Osm/kg of water for each 10 mg/dL increase in serum ethylene glycol concentration. Accumulation of the alcohol increases the serum osmolality and the osmolal gap, which is the difference between the serum osmolality, measured by freezing-point depression and calculated serum osmolarity. The osmolal gap varies during the course of intoxication. Accumulation of the parent alcohol initially elevates the osmolal gap, but as metabolism progresses, osmolal gap decreases.
The expected normal osmolal gap is -10 to +10 mOsm per kilogram of water. An osmolal gap greater than 10 mOsm/kg is consistent with ingestion of a foreign substance (see Osmolality for further details). A normal osmolal gap cannot be used to rule out toxic alcohol ingestion because some patients with toxic alcohol poisonings have osmolal gaps within the normal range.
The formation of oxalate crystals in urine is a late finding in ethylene glycol poisoning. Two types of calcium oxalate crystals may be seen: needle-shaped monohydrate crystals, which may be misinterpreted as hippurate crystals, and envelope-shaped dihydrate crystals.
Reference
Kraut JA and Mullins ME. Toxic Alcohols. New Engl J Med 2018;378:270-80.
