Agency for Toxic Substances and Disease Registry
Case Studies in Environmental Medicine (CSEM) 

Ethylene Glycol and Propylene Glycol Toxicity
How Should Patients Exposed to Ethylene Glycol Be Treated?

Learning Objectives

Upon completion of this section, you should be able to

• identify the primary treatment strategy for managing ethylene glycol poisoning cases.

Introduction

Treatment should not be delayed pending results of ethylene glycol serum levels if the patient’s condition or history suggests such poisoning. Treatment advice can be obtained from a regional poison control center or medical toxicologist.

First Steps

Initial management of suspected poisoning

• includes basic life support
• may require intubation and mechanical ventilation

Prevent Absorption

When the ingestion is recent, take steps to prevent ethylene glycol absorption.

• Induced emesis or gastric lavage may be useful if
  • ingestion occurred within 2 hours
  • the patient has a normal level of consciousness
• Activated charcoal adsorbs ethylene glycol poorly and is probably not effective in this setting (Goldfrank LR 1998).

Specific Treatment

Specific treatment for ethylene glycol poisoning includes

• sodium bicarbonate to correct the metabolic acidosis as indicated,
• ethanol or fomepizole (Antizol) to competitively inhibit metabolism of ethylene glycol to its more toxic metabolites, and
• hemodialysis, if indicated, to remove ethylene glycol and glycolic acid. (Stokes and Aueron 1980; Gabow, Clay et al. 1986; Cheng, Beysolow et al. 1987; Malmlund, Berg et al. 1991; Jacobsen and McMartin 1997; Moreau, Kerns et al. 1998; Bey, Walter et al. 2002)

This treatment strategy is effective in most cases, but renal failure and death can occur if treatment is delayed.

^*The goal of ethanol therapy is to maintain the blood ethanol level between 100 and 150 mg/dL.

^†mg/kg: milligrams per kilogram; mg/kg/hr: milligrams per kilogram per hour.

^‡In 5% dextrose in distilled water (D5W) per kilogram body weight.

Adapted from Hall 1992.

Monitor the Patient

Prolonged administration of ethanol can cause hypoglycemia, particularly in children; therefore, blood glucose should be monitored closely throughout treatment. The hypoglycemia that develops in adults is often overlooked because the impairment of mental status is attributed to the ethanol.

Calculate the Dose

• Infuse the loading dose and the maintenance dose over the first hour of therapy. Begin the lower maintenance dose during the second hour.
• The patient’s actual drinking habits determine the appropriate dose. If those drinking habits cannot be determined, it is best to use the doses for the category of “social drinker.”
• Adjust doses to achieve a blood ethanol level between 100 and 150 mg/dl, although levels as low as 70 mg/dL have almost completely inhibited ethylene glycol metabolism in some patients (Jacobsen, Ostby et al. 1982).

To prepare 1 L of 10% ethanol in 5% dextrose in distilled water (D5W) for intravenous infusion, perform either of the following steps

• Remove 100 ml of fluid from 1 L of D5W and replace with 100 ml of absolute ethanol, or
• Remove 50 ml of fluid from 1 L of commercially available 5% ethanol in D5W solution and replace with 50 ml of absolute ethanol.

Monitor the Dose

Monitor blood ethanol and serum glucose levels at the end of the loading dose and hourly until the maintenance dose is adjusted. Both should then be monitored 2-3 times daily, along with blood glucose. More frequent monitoring is required during dialysis.

Most ethylene glycol (93.75%) is eliminated over 4 half-lives (prolonged to 17 hours with therapy). Therefore, most ethylene glycol should be out of the body within 68 hours (2.83 days). Ethanol therapy should be continued for 3 days if ethylene glycol levels are not available, or until the following conditions are met (Burkhart and Kulig 1990):

• ethylene glycol level <20 mg/dL
• resolution of the acidosis (normal ABGs, pH)
• resolved clinical findings (CNS)

Fomepizole Treatment Guidelines

Fomepizole (Antizol) was approved by the FDA in December 1997 for use as an ADH antagonist in treatment of ethylene glycol poisoning. The following criteria (Barceloux, Krenzelok et al. 1999) were developed by the American Academy of Clinical Toxicology for using fomepizole rather than ethanol:

• ingestion of multiple substances, resulting in depressed level of consciousness
• altered consciousness
• lack of adequate intensive care staffing or laboratory support to monitor ethanol administration
• relative contraindications to ethanol
• critically ill patient with an anion-gap metabolic acidosis of unknown origin and potential exposure to ethylene glycol
• patients with active hepatic disease

The manufacturer recommends a loading dose of 15 mg/kg infused intravenously over 30 minutes, followed by doses of 10 mg /kg every 12 hours for 4 doses, then 15 mg/kg every 12 hours until ethylene glycol levels are below 20 mg/dl (Meditext 2004). The dosage must be adjusted during dialysis.

Advantages of Fomepizole Treatment

This therapy may obviate the need for hemodialysis in the absence of both renal insufficiency and significant metabolic acidosis (Harry, Turcant et al. 1994; Harry, Jobard et al. 1998; Borron, Megarbane et al. 1999; Watson 2000; Brent 2001; Battistella 2002; Druteika, Zed et al. 2002). In addition, in comparison with ethanol, fomepizole

• is easier to use clinically and requires less monitoring
• has a slower rate of elimination
• has a longer duration of action
• has a reasonable dosing schedule
• has less potential for adverse effects
• is easier to administer
• results in shorter hospital stays,
• has more predictable and prolonged results
• does not cause CNS depression or hypoglycemia

Disadvantages of Ethanol Treatment

The disadvantages of ethanol are that it

• requires continuous administration and frequent monitoring of serum ethanol and glucose levels
• can cause CNS depression and hypoglycemia
• poses problems in patient care, such as drunkenness

Although ethanol costs much less, the savings may be offset by additional costs for

• monitoring the patient
• lab tests
• hemodialysis for some patients

Hemodialysis

Hemodialysis should be considered under these conditions (Ford M 1991; Hall AH 1992):

• serum ethylene glycol levels exceed 30 mg/dL
• severe upset in blood pH (pH <7.25) or fluid/electrolyte disturbances persist despite decontamination and ethanol or fomepizole therapy
• vital signs continue to deteriorate despite intensive supportive treatment, or
• renal failure develops

However, the decision to add hemodialysis in the treatment of ethylene glycol poisoning on the basis of plasma ethylene glycol concentrations is still debatable (Battistella 2002). A recent study suggested glycolic acid >8 mmol/L as a criterion for the initiation of hemodialysis in ethylene glycol ingestion (Porter, Rutter et al. 2001). Hemodialysis should be continued until

• acidosis is controlled
• serum ethylene glycol level falls below 20 mg/dL

At that level, ethanol or fomepizole therapy can also be discontinued. In contrast, a recent report described successful clinical management of pediatric ethylene glycol poisoning cases without hemodialysis (Caravati, Heileson et al. 2004).

Vitamin Treatment

Thiamine and pyridoxine are two water-soluble B-complex vitamins that act as metabolic cofactors in the metabolism of ethylene glycol. They

• promote the transformation of glyoxylic acid to nontoxic metabolites
• may decrease the formation of oxalate

Both should be administered intravenously [in dosages of 100 mg daily until intoxication is resolved (Davis, Bramwell et al. 1997; Jacobsen and McMartin 1997)] to patients who have ethylene glycol toxicity. Alcoholics who are nutritionally deprived may need more thiamine. If the vitamins are administered before dialysis, the dose should be repeated after dialysis because they are highly water-soluble and are likely to be removed by the procedure.

Magnesium may help prevent deposition of calcium oxalate in the urine (Meditext 2004).

Key Points

• Correction of metabolic acidosis is an important part of treatment in ethylene glycol poisoning.
• Specific treatments for ethylene glycol poisoning are ethanol or fomepizole therapy and hemodialysis.

Progress Check