Ethylene Glycol                     
Revised 12/09

Ethylene glycol is used as antifreeze and coolant, it is also found in solvents, humectants, brake fluids, paints and lacquers. Ingestion of as little as one mouthful of a 99% EG antifreeze solution by either a child or adult may lead to toxic signs and symptoms.

Ethylene glycol’s major toxicities are a result of it’s metabolites: glycoaldehyde, oxalic acid, glycolic acid, and glyoxylate. These metabolites cause (1) tissue destruction, primarily from calcium oxalate crystal deposition, and (2) metabolic abnormalities, specifically a high anion-gap metabolic acidosis, lactic acidosis, and hypocalcemia. Oxalic acid combines with calcium to form calcium oxalate crystals, which deposit in the kidneys. This can result in hypocalcemia, hematuria, and proteinuria, increased creatinine and renal failure. The first enzyme in the metabolic pathway of EG is alcohol dehydrogenase. By blocking the action of this enzyme, the production of toxic metabolites can be stopped.

Clinical Symptoms
Phase 1 (Minutes – 12 hours): CNS toxicity predominates with inebriation (without odor of ethanol on the breath), coma, nystagmus, paralysis, and seizures. Nausea, vomiting, and papilledema may also occur. An elevated serum osmolarity is seen early in this phase. Calcium oxalate crystals may be present.

Phase 2 (12-24 hours ): Cardiopulmonary symptoms predominate with mild tachycardia and hypertension. Other effects include anion gap metabolic acidosis (possibly severe) with compensatory hyperventilation, hypoxia, CHF, and ARDS.

Phase 3 (>24 hours): This renal phase is characterized by acute tubular necrosis and renal failure. Oliguria, anuria, hematuria, and proteinuria are common.

Monitoring and Labs: Ethylene glycol levels are done by a relatively few laboratories so an excessive delay may occur before the hospital receives the laboratory results. If EG levels are not available within a few hours, treatment should be initiated until the lab results become available. Ethylene glycol levels > 20 mg/dL are considered toxic, but levels < 20mg/dL may still indicate a toxic amount of EG has been ingested if significant time has passed since the ingestion.

Serum osmolality, measured by freezing point depression, may be useful if ethylene glycol levels can not be done in a timely manner. A significantly elevated serum osmolality can be indicative of an EG ingestion. However, the absence of an elevated serum osmolarity does not rule out the ingestion of a toxic alcohol. An elevated serum osmolality may be present within the first hour of ingestion as this is a result of the presence of EG itself, not the toxic metabolites, in the serum. As metabolism decreases the ethylene glycol concentration, the serum osmolality will decrease despite worsening systemic toxicity.

Electrolytes may be used to determine the presence of an anion gap. A normal anion gap is 8-16 mEq/L. Absence of an anion gap does not rule out the ingestion of a toxic alcohol. The anion gap is mainly due to a decrease in serum bicarbonate levels and usually follows the development of acidosis which typically develops within 12 hours of ingestion.

Renal function tests and urinalysis should be done on symptomatic patients. The presence of calcium oxalate crystals in the urine may be help support the diagnosis of EG ingestion. However, the monohydrate form of calcium oxalate crystals are similar to sodium urate crystals and either crystal may be mistaken for the other.

Some brands of radiator antifreezes contain fluoroscein, a dye that flouresces under ultraviolet light. Urine or emesis from a patient who has ingested an automotive product with flourescene may exhibit this fluorescence. However, this effect is NOT diagnostic as both false positive and false negative results can be obtained.

Management: Indications for antidotal therapy can include (1) a history or suspicion of ethylene glycol ingestion, (2) an elevated anion-gap acidosis, (3) an unexplained serum osmolality >10 mOsm/L above the calculated serum osmolarity, (4) oxalate crystals in urine, (5) elevated ethylene glycol levels, and (6) other factors. Antidotal therapy is based on preventing the alcohol dehydrogenase enzyme from metabolizing ethylene glycol into toxic byproducts.

In patients who are symptomatic, hemodialysis should be considered. Hemodialysis efficiently clears ethylene glycol and toxic byproducts and corrects acidosis. Use of sodium bicarbonate enhances elimination of toxic byproduct by correction of acidosis.

Pyridoxine may inhibit metabolism of glycolic acid to oxalic acid by acting as cofactor in metabolism of glycolic acid to nonoxalate byproducts. Thiamine is recommended to stimulate the conversion of glyoxylate to alpha-hydroxy-beta-ketoadipate, a non-toxic metabolite.

References:

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Ethylene Glycol Exposure: An Evidence Based Consensus Guideline for Out of Hospital ManagementMay 3, 2005.