DESCRIPTION

Ethylene glycol is a sweet, odorless, and colorless liquid used in a wide range of consumer and commercial products.

FORMS AND USES

• Ethylene glycol (1,2-ethanediol, 1,2-dihydroxyethane, monoethylene glycol, glycol alcohol, glycol) is a common component of antifreeze used in heating and cooling systems, brake fluid, inks, and soybean foam.
• It is used as an industrial solvent in paints and plastics and is used in the manufacturing of resins, plasticizers, and synthetic fibers and waxes.

TOXIC DOSE

One or two sips or gulps can produce potentially toxic ethylene glycol levels in children and adults.

PATHOPHYSIOLOGY

• Ethylene glycol is metabolized by alcohol dehydrogenase to toxic organic acids, which produce an increased anion gap metabolic acidosis.
• The metabolite oxalic acid combines with calcium to form calcium oxalate crystals, which can be deposited in the renal tubules and cause renal damage.

EPIDEMIOLOGY

• Poisoning is uncommon.
• Death occurs in patients who do not receive medical care.

CAUSES

• Poisoning most commonly occurs after the accidental ingestion of antifreeze or attempted suicide.
• The possibility of child abuse or neglect should be considered if the patient is less than 1 year of age; suicide attempt should be considered if the patient is more than 6 years of age.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• TOXIC DOSE
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY
• CAUSES

DIFFERENTIAL DIAGNOSIS

• Toxic causes of an increased anion gap metabolic acidosis include methanol, salicylates, and alcoholic ketoacidosis, as well as lactic acidosis from any source.
• Nontoxic causes include diabetic ketoacidosis as well as lactic acidosis from any source.

SIGNS AND SYMPTOMS

• Inebriation may develop initially.
• Over several hours, an anion gap metabolic acidosis may develop, followed over 24 to 72 hours by progressively worsening renal injury.

Vital Signs

Tachypnea, tachycardia, and hypotension may occur in serious poisoning.

Cardiovascular

• Hypocalcemia with QT prolongation is possible in severe poisoning.
• Myocarditis occurs rarely.

Pulmonary

Pulmonary edema occurs rarely.

Gastrointestinal

• Nausea and vomiting are common.
• Pancreatitis and gastritis may occur.

Renal

Acute renal failure 24 to 72 hours after ingestion is common in patients without prompt treatment.

Fluids and Electrolytes

• Anion gap metabolic acidosis appears over several hours.
• Hypocalcemia can occur due to formation of calcium oxalate.

Musculoskeletal

Myalgia with elevated levels of creatine kinase may occur.

Neurologic

• CNS depression, ataxia, and slurred speech are common and resemble symptoms of ethanol toxicity.
• Seizures occur rarely.

PROCEDURES AND LABORATORY TESTS

Essential Tests

• Serum ethylene glycol level
  • Levels should be obtained in all patients with a history of ingestion.
    • A level of over 20 mg/dl is an indication for fomepizole or ethanol infusion.
    • A level of over 50 mg/dl is an indication for hemodialysis.
• Serum electrolytes, BUN, creatinine
  • As metabolism occurs, an increased anion gap metabolic acidosis will develop.
  • The absence of a gap soon after ingestion does not exclude toxicity because the patient may not have metabolized enough to develop acidosis.
  • Acidosis is an indication for fomepizole or ethanol infusion and hemodialysis.
• Urinalysis with microscopic examination
  • The presence of calcium oxalate crystals with a history of ingestion or metabolic acidosis is strong evidence of poisoning.
  • The absence of crystals does not exclude the diagnosis.
  • Patients often have proteinuria and hematuria.

Recommended Tests

• Measured serum osmolality, using freezing point depression method
  • Serum osmolality is not a substitute for an ethylene glycol level.
  • If a delay is expected before an ethylene glycol level can be obtained, serum osmolality can be used as a screening test to rule in (but not to rule out) the possibility of ethylene glycol poisoning.
  • An elevated osmolal gap suggests the presence of an unmeasured solute such as ethylene glycol.
  • Osmolal gap is calculated as follows:

    Osmolal gap = (calculated serum osmolality)- (measured osmolality)

  • The cause of a gap greater than 15 mEq/l must be determined.
  • The patient should be treated with ethanol infusion until the cause is determined.
  • The measured osmolality is determined by the laboratory.
  • The calculated osmolality is determined as follows:2 × [Na (mEq/L)] + [BUN (mg/dl)/2.8]+ [glucose (mg/dl)/18]
  • Drugs and disorders that may alter these laboratory results include acetone, ethanol, isopropyl alcohol, mannitol, methanol, propylene glycol, renal failure, lactic acidosis, and alcoholic ketoacidosis.
• Arterial blood gases should be measured in patients with a low serum bicarbonate to assess acidosis.
• Serum ionized calcium should be followed closely after significant ingestion.
• ECG and cardiac monitoring should be performed to detect dysrhythmias and effects of hypocalcemia.
• Blood ethanol concentration
  • Ethanol will delay the onset of symptoms and sequelae of ethylene glycol toxicity.
  • Patients on ethanol infusions should have ethanol levels followed hourly until stable for 4 hours, then every 4 hours.
• Serum acetaminophen and aspirin levels are used in overdose setting to detect occult ingestion.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • Vital Signs
  • Cardiovascular
  • Pulmonary
  • Gastrointestinal
  • Renal
  • Fluids and Electrolytes
  • Musculoskeletal
  • Neurologic
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests

• Focus treatment on supportive care, control of airway, and treatment with fomepizole or ethanol and hemodialysis as indicated.
• Dose and time of exposure should be determined for all substances involved.
• Consultation with a toxicologist and nephrologist should be considered early in symptomatic patients.

DIRECTING PATIENT COURSE

The health-care professional should call the poison control center when:

• Acidosis, renal failure, or other serious effects are present.
• Toxic effects are not consistent with ethylene glycol toxicity.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

The patient should be referred to a health-care facility when:

• Attempted suicide or homicide is possible.
• Patient or caregiver seems unreliable.
• Any signs of toxicity develop.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

Admission Considerations

Inpatient treatment is warranted when patient has altered mental status, acidosis, ethylene glycol levels over 20 mg/dl, or renal injury.

DECONTAMINATION

In Hospital

• Nasogastric aspiration using a nasogastric tube within the first 30 to 60 minutes following a large ingestion may be beneficial.
• If there is concern for a coingestant, then gastric lavage with a large-bore orogastric tube may be indicated.
• If the presence of a coingestant is suspected, then one dose of activated charcoal (1-2 g/kg) should be administered without a cathartic.

ANTIDOTES

Fomepizole

Fomepizole is the preferred agent for treatment.

• Indications
  • History of possible ethylene glycol ingestion and evidence of toxicity (increased anion gap, metabolic acidosis, hematuria, proteinuria) or increased osmolal gap
  • Serum ethylene glycol level above 20 mg/dl
• Contraindications
  • History of documented allergic response to fomepizole
• Method of administration
  • Loading dose for adult or pediatric patient is 15 mg/kg intravenously.
  • Maintenance dose for all age groups is 10 mg/kg every 12 hours for four doses and then 15 mg/kg every 12 hours until ethylene glycol level is less than 20 mg/dl.
  • Each dose is diluted in 100 ml normal saline or D5W and infused over 30 minutes.
  • For further details (e.g., use during hemodialysis), see SECTION III, Fomepizole chapter.

Ethanol

10% solution in D5W.

• Indications
  • Ethanol treatment is recommended if fomepizole is not available.
  • Ethylene glycol level more than 20 mg/dl
  • If levels are not immediately available, therapy should be instituted if there is:
    • A reliable history of significant ingestion
    • Unexplained anion gap acidosis
    • Unexplained osmolar gap
• Contraindications. Preexisting ethanol level more than 100 mg/dl obviates need for the ethanol loading dose.
• Method of administration.
  • Consult SECTION III, Ethanol chapter, for details of administration.
    • Loading dose is 10 cc/kg of a 10% ethanol solution infused intravenously over 1 hour.
    • Maintenance dose is 1.0 to 2.0 ml/kg/hr of 10% ethanol solution.

ADJUNCTIVE TREATMENT

Pyridoxine and thiamine have been proposed to hasten elimination of toxic ethylene glycol metabolites. Because the safety margin is large, they may be administered at the discretion of the treating physician. Indications for use have not been established.

• Pyridoxine
  • Adult dose is 50 to 100 mg administered intravenously every 6 hours until ethylene glycol level is undetectable.
  • Pediatric dose is 1 to 2 mg/kg administered intravenously every 6 hours until ethylene glycol level is undetectable.
• Thiamine
  • Adult dose is 100 mg administered intravenously over 5 minutes every 6 hours until ethylene glycol level is undetectable.
  • Pediatric dose is 50 mg administered intravenously over 5 minutes every 6 hours until ethylene glycol level is undetectable.
• Sodium bicarbonate should not be routinely administered, but may be used as a temporizing measure for life-threatening acidosis and acidemia prior to hemodialysis.
• Hemodialysis is recommended for a serum ethylene glycol level of more than 50 mg/dl (and should be considered for levels in the 25 to 50 mg/dl range) or if signs of end-organ injury are apparent (increased anion gap acidosis, renal failure, or mental status changes).

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • In Hospital
• ANTIDOTES
  • Fomepizole
  • Ethanol
• ADJUNCTIVE TREATMENT

PATIENT MONITORING

• Serum electrolytes and arterial blood gases should be monitored every 2 to 4 hours until acidosis begins to resolve.
• Serum ethylene glycol concentrations should be monitored until they are below 10 mg/dl.
• If hemodialysis is performed, fomepizole or ethanol administration should be continued until a postdialysis ethylene glycol concentration is known to be less than 20 mg/dl.
• When ethanol is administered, blood ethanol concentrations should be monitored every hour and the infusion rate should be adjusted to maintain a concentration of 100 to 130 mg/dl.
• Serum glucose concentrations should also be monitored every 1 to 2 hours, especially in children (ethanol may cause hypoglycemia).

EXPECTED COURSE AND PROGNOSIS

• Toxicity may take several hours to develop.
• Peak toxicity usually occurs within 24 hours.
• Patients with renal injury may suffer residual renal dysfunction.

DISCHARGE CRITERIA AND INSTRUCTIONS

• From the emergency department. Asymptomatic patients with undetectable serum ethylene glycol levels and no anion gap metabolic acidosis may be discharged after psychiatric evaluation, if needed.
• From the hospital. Patient may be discharged with serum ethylene glycol level less than 20 mg/dl, normal anion gap, and stable renal function, following psychiatric clearance, if needed.

Section Outline:

• PATIENT MONITORING
• EXPECTED COURSE AND PROGNOSIS
• DISCHARGE CRITERIA AND INSTRUCTIONS

DIAGNOSIS

• Ethylene glycol toxicity cannot be ruled out by a normal osmolal gap or absence of an anion gap metabolic acidosis.
• Patients with potentially toxic ethylene glycol levels may be asymptomatic initially.
• Serum ethylene glycol levels must be measured in all patients with a history of ingestion.

TREATMENT

• If an endotracheal intubation is performed, the increased minute ventilation (compensation for acidosis) that was present before intubation should be maintained.
• Blood ethanol levels should be monitored closely and maintained at 100 to 130 mg/dl.

Section Outline:

• DIAGNOSIS
• TREATMENT

Toxic effect of alcohol.

See Also: SECTION II, Osmolar Gap; SECTION III, Ethanol, Fomepizole (Antizol), Pyridoxine, and Thiamine chapters.

RECOMMENDED READING

Baud FJ, Galliot M, Astier A, et al. Treatment of ethylene glycol poisoning with intravenous 4-methylpyrazole. N Engl J Med 1988;319:97-100.

Author: Edwin K. Kuffner

Reviewer: Luke Yip