Unit conversion table: Table. Unit conversion table: Alcohols.
Ethylene glycol is a sweet-tasting, clear liquid with ethanol-like smell, used mainly as an automobile antifreeze, a heat transfer liquid, and a solvent, usually in the form of 95% solutions. It may be ingested as an ethanol substitute. Ethylene glycol is rapidly absorbed, not protein-bound, distributed in total body water, and metabolized in the liver by alcohol dehydrogenase. Approximately 22% of ethylene glycol is eliminated in an unchanged form in the urine. The half-life is 3 hours. When coingested with ethanol, the elimination is purely renal and the half-life increases to 17 to 20 hours.
Mechanism of toxicity: Alcohol dehydrogenase converts ethylene glycol to glycoaldehyde, which leads to the formation of glycolic, glyoxylic, and oxalic acids. These metabolites may cause fatal toxicity by inducing a severe anion gap metabolic acidosis and renal injury (direct cytotoxic effect, formation of calcium oxalate crystals in renal tubules; usually resolves with no permanent sequelae). The organic acids and oxalate crystals are also damaging to other tissues. Lactic acidosis further worsens the metabolic acidosis.
Toxic dose: The minimum ethylene glycol serum concentration that causes serious toxicity is unknown, although serum levels >8 mmol/L (~50 mg/dL) are usually associated with symptoms of intoxication. If left untreated, the estimated lethal dose of 95% ethylene glycol (eg, antifreeze) is 1 to 1.5 mL/kg (~100 mL). Prompt recognition and early treatment can lead to survival in patients with much larger ingestions.
1. Symptoms of early poisoning are the same as in ethanol poisoning and may raise no suspicion of poisoning, particularly in persons with prior alcohol abuse.
2. Symptoms of late poisoning occur after a delay of 4 to 12 hours, when toxic metabolites appear, and include anion gap metabolic acidosis, Kussmaul breathing, nausea, vomiting, agitation, confusion, altered mental status that may progress to profound coma, seizures, anisocoria, hypotension, cardiac conduction problems or arrhythmias, oliguria progressing to anuria and acute kidney injury (reversible), and hypocalcemia (sometimes with tetany). Cerebral and pulmonary edema may also occur.
Clinical diagnosis is often based on symptoms, history of antifreeze ingestion, and a combined anion gap metabolic acidosis and an osmolar gap (see Formulas in Alcohols). Examination of the urine may reveal oxalate or hippurate crystals. The urine may fluoresce under a Wood lamp, as many antifreeze manufacturers add fluorescein to their products.
1. Specific testing of serum ethylene glycol levels >8 mmol/L (about 50 mg/dL) is usually associated with significant toxicity. However, lower levels do not exclude intoxication, as ethylene glycol may have already been metabolized. Glycolic acid levels may be a better measure of toxicity but are not readily available. Glycolic acid levels <10 mmol/L would suggest an alternative etiology in symptomatic patients. In the absence of laboratory testing for either ethylene glycol or glycolic acid, significant intoxication with ethylene glycol is unlikely in asymptomatic patients with a normal anion gap and osmolar gap.
2. Other suggested investigations include serum K, Na, Ca, glucose, urea/blood urea nitrogen, and osmolality (to calculate anion and osmolar gaps), creatinine, and aminotransferase levels; urinalysis with microscopy (oxalate crystals) and Wood lamp examination for the presence of fluorescein added to antifreeze; arterial blood gas analysis (in the setting of acidosis, blood ethylene glycol levels may be low, as the substance has already been metabolized; severity of the poisoning is estimated on the basis of the severity of acidosis and the anion gap), pulse oximetry, and electrocardiography (ECG) monitoring. High beta-hydroxybutyrate levels may suggest alcoholic ketoacidosis as the cause or contributor to the anion gap.
1. Decontamination: Gastric aspiration may only be useful within 30 minutes of ingestion of large volumes of polyethylene glycol. Activated charcoal would not adsorb ethylene glycol but may be useful for coingested toxins.
2. Antidotes and specific therapies:
1) Ethanol and fomepizole (dosage and administration: see Methyl Alcohol) block ethylene glycol from being metabolized into toxic organic acids. We recommend their use if the ethylene glycol level is >3.2 mmol/L (20 mg/dL), or if the patient has an osmolar gap >10 mOsm/L and serum bicarbonate <20 mEq/L, pH <7.3 or oxalate crystals in the urine.
2) Pyridoxine (vitamin B6) may theoretically enhance the conversion of toxic glyoxylic acid to nontoxic glycine. It may be given in a dose of 50 mg IV or IM every 6 hours until ethylene glycol toxicity is resolved.
3) Thiamine (vitamin B1) 100 mg IV may be given every 12 hours (until serum toxic alcohol is undetectable) to theoretically minimize glyoxylic acid exposure.
Despite lack of clinical evidence for benefit, there is little risk to administering either of these vitamin cofactors in ethylene glycol metabolism. We recommend continuing these agents until serum ethylene glycol is undetectable.
4) If toxic alcohol levels are unavailable and the contents of the product ingested are unknown, we recommend treating for methanol toxicity as well (see Methyl Alcohol)
3. Accelerated elimination: Hemodialysis can remove ethylene glycol and its toxic metabolites as well as correct electrolytes and acidosis and replace renal function in cases of ethylene glycol/oxalate-induced acute kidney injury. Indications for dialysis include:
1) Persistent acidosis unresponsive to bicarbonate and/or an osmolar gap >10.
2) Ethylene glycol ingestion accompanied by acute kidney injury or chronic kidney disease.
3) Ethylene glycol concentration >8 mmol/L (50 mg/dL).
4) Clinical worsening despite ethanol or fomepizole.
4. Supportive care is aimed at maintaining vital parameters and correcting any disturbances.
1) Ensure airway patency. Intubate and assist ventilation if necessary.
2) Observe for the development of coma, arrhythmia, kidney injury, and hypotension.
3) Intravenous calcium gluconate or calcium chloride can be used to treat symptomatic hypocalcemia. Theoretically, administration of calcium may hasten calcium oxalate crystal formation, and this risk must be balanced against that of untreated hypocalcemia in asymptomatic patients.
4) Sodium bicarbonate infusion may be used to correct metabolic acidosis when pH is <7.3. It also has the advantage of increasing the renal elimination of glycolate and inhibiting precipitation of calcium oxalate crystals.