Ethylene glycol is the dihydroxy alcohol derivative of aliphatic hydrocarbons and is most often encountered in various antifreeze solutions and coolants. Ethylene glycol is also incorporated into solvents, industrial humectants, brake fluid, paints and lacquers, glass cleaners, and cosmetics. As little as a mouthful of a 99% antifreeze solution ingestion in either a child or adult may lead to toxic signs and symptoms
This clear, colorless, sweet-tasting liquid is rapidly and completely absorbed upon ingestion with peak blood levels occurring in 1-4 hours. It has a half-life of 2.5 to 4.5 hours (this may be extended to as long as 17 hours in the presence of ethanol at levels of 100-200 mg/dL). The elimination half-life of ethylene glycol with fomepizole treatment is 11 to 14.75 hours. Ethylene glycol is non-toxic, but is metabolized by alcohol dehydrogenase, found in the hepatocytes, into four toxic byproducts: glycoaldehyde, glycolate, glycolic acid, and glyoxylate. These four breakdown products are responsible for the tissue destruction (from calcium oxalate crystals) and metabolic toxicity (high anion gap metabolic acidosis, lactic acidosis, and hypocalcemia). Ethylene glycol has a volume of distribution (0.54-0.8 L/kg) similar to that of total body water. Ethylene glycol is filtered by the renal glomeruli and is passively reabsorbed. Approximately 20% of ethylene glycol is excreted unchanged in the urine. The lethal dose in adults is 1-1.5 mL/kg .
Phase 1 (Minutes – 12 hours):
CNS toxicity predominates with inebriation (w/o odor of E-OH), coma, nystagmus, paralysis, and seizures. Nausea, vomiting, and papilledema may also occur. An osmolar gap 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 excessive delay may be encountered in determination of results. Ethylene glycol levels > 20 mg/dL are considered toxic, but levels < 20mg/dL may be toxic 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. After determining a patients osmolal gap, an osmolal gap of >10 mOsmol may indicate presence of low molecular weight substance in serum such as ethylene glycol. Absence of a gap does not rule out an ingestion of a toxic alcohol. Osmolal gap may be present within the first hour of ingestion as this results from the presence of EG itself, not the toxic byproducts. As metabolism decreases the ethylene glycol concentration, the serum osmolal gap will decrease despite worsening toxicity.
Electrolytes may be used to determine the presence of an anion gap.
A normal anion gap is 8-16 mEq/L. Absence of a gap does not rule out an 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.
Oxalic acid and other byproducts of ethylene glycol metabolism can result in metabolic acidosis. Arterial blood gases determined and any acidosis corrected Oxalic acid combines with calcium from the body to form calcium oxalate crystals in the kidneys. This can result in hypocalcemia, hematuria, and proteinuria. Renal function tests and urinalysis should be done on symptomatic patients. Calcium oxalate dehydrate crystals (octahedral, or tent-shaped) are typical in presence of high concentrations of calcium or oxalate and of more diagnostic significance than monohydrate crystals (dumbbell-shaped) which are too similar to sodium urate crystals to be diagnostic for ethylene glycol intoxication. Calcium replacement should be given to patients with hypocalcemia which may cause prolongation of QTc interval. Many radiator antifreezes contain fluorosceine, the urine or emesis may exhibit fluorescence under ultraviolet light.
TreatmentDecontamination is generally of little value, however lavage may be beneficial if performed within 60 minutes of ingestion.
Indications for antidotal therapy can include a history or suspicion of ethylene glycol ingestion, acidosis, an unexplained osmolal gap > 10 mOsm/L, oxalate crystals in urine, elevated ethylene glycol levels, and other factors.
Antidotal therapy is based on inhibiting or blocking alcohol dehydrogenase from metabolizing ethylene glycol into toxic byproducts. Ethanol will competitively inhibit alcohol dehydrogenase but it must be monitored frequently, causes hypoglycemia in children, and may exacerbate CNS depressants coingested in suicidal situations. Fomepizole blocks alcohol dehydrogenase with few side effects and is considered the drug of choice for antidotal therapy for ethylene glycol or methanol toxicity.
In patients who are symptomatic, hemodialysis should be considered. Hemodialysis efficiently clears ethylene glycol and toxic byproducts and corrects acidosis, but treatment with fomepizole and ethanol should continue. Both fomepizole and ethanol will be dialyzed and doses need to be adjusted accordingly.
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
Patients with serious signs and symptoms associated with ethylene glycol intoxication or a history of significant ingestion even in the absence of symptoms should be admitted to an intensive care setting. Fomepizole, ethanol, and dialysis therapy should be continued until serum ethylene glycol levels are zero and acidosis has resolved. Suicidal patients should receive psychiatric evaluation prior to discharge.
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