Ethylene Glycol Toxicity Treatment & Management

Guidelines on the medical management of ethylene glycol poisoning are available from the Agency for Toxic Substances and Disease Registry. These include recommendations on prehospital, emergency department, and critical care treatment, and on management of industrial accidents with multiple casualties. ^[1]

Initial emergency department treatment includes infusion of crystalloids to enhance renal clearance of the toxic metabolites. Ethyl alcohol (ethanol) has traditionally been used for antidotal treatment, but it has largely been supplanted by fomepizole in the United States.

 In centers where fomepizole is available, patients who present early and are without acidosis clinically well can be treated with fomepizole and hemodialysis on a regular floor. Any patients who are ill and acidotic or who present to centers where ethanol is used instead of fomepizole should be treated in an intensive care unit (ICU) or other setting with cardiac monitoring and close nursing care. Patients who present to a facility without those capabilities should be transferred to a facility where hemodialysis and an ICU are available.

 

 

Emergency medical services should do the following:

• Ascertain as much specific information regarding the identity of the ingested substance as possible.
• If possible, obtain the bottle or container that held the ingested substance. Interviewing persons present at the site of the ingestion may be helpful in this regard.
• Obtain intravenous access and administer crystalloid infusions.
• Monitor cardiac function and determine blood dextrose level.
• Airway management is a priority because of the risk of aspiration.

 

Rapidly evaluate patients who present with signs, symptoms, or history of toxic alcohol ingestion; determine serum osmolal gap. The prehospital (EMS) personnel often can provide important details regarding the identity of the chemical(s) involved and the clinical characteristics of the patient.

Considerations in emergency department (ED) care include the following:

• Many patients with ethylene glycol ingestions are extremely obtunded and are at high risk of aspiration; endotracheal intubation may need to be considered.

• Obtain intravenous access and laboratory specimens.

• Activated charcoal and nasogastric lavage have no role in toxic alcohol poisoning; typically the alcohols will be absorbed too quickly for either of these modalities to have any efficacy.

• Measure levels of electrolytes, calcium, and magnesium, especially in patients with alcoholism because alcohol is a cofactor in oxalate metabolism. Obtain a ethylene glycol serum concentration if you have access to this at your institution or locally.

• Administer crystalloids at 250-500 mL/h IV initially to enhance renal clearance of the toxin and to limit deposition of oxalates in the renal cortices.

• Administer bicarbonate to correct severe acidosis (pH level ≤7.2); this of course should be done in conjunction with addressing the underlying cause of the acidosis.

• Pyridoxine and thiamine are cofactors in ethylene glycol metabolism that promote production of nontoxic metabolites, and are safe adjuncts with no significant disadvantages.They may be administered parenterally.

• Place symptomatic patients in a monitored setting.

• An electrocardiogram may be useful to detect arrhythmias that may result from hypocalcemia. With low serum calcium, the QT interval may also be prolonged.

• Foley catheterization may be considered for patients with altered mental status, to monitor urinary output and to allow serial examination of urine for crystals or fluorescence.

• If ethylene glycol poisoning is suspected, begin antidotal therapy empirically while awaiting confirmation. This is performed with either fomepizole (4-MP) or ethanol. The latter is usually administered intravenously but may be administered orally in remote settings where emergency hospital care is not immediately available. In the United States, contemporary treatment of this poisoning is most commonly done with fomepizole alone.

Treatment of patients with suspected ethylene glycol intoxication has traditionally been indicated in any of the following three circumstances. First, the plasma concentration of ethylene glycol is 25 mg/dL or more. Second, the patient has a definite history of recent ethylene glycol ingestion (especially if the osmolal gap is 10 mOsm/L or more, though patients with potentially toxic ethylene glycol ingestions may have an apparently normal osmolar gap; see Workup/Laboratory Studies). Third, a history or suspicion of ethylene glycol intoxication and the presence of at least two of the following ^[13] :

• Arterial pH less than 7.3
• Serum bicarbonate level less than 20 mg/dL
• Osmol gap greater than 10 mOsm/L
• Oxalate crystals in the urine

However these criteria may be too conservative; if there is clinical concern or if laboratory testing will take an extended amount of time to return it is advisable to initiate therapy earlier. A review of 121 ethylene glycol poisoning cases found that patients who did not receive an antidote (ethanol and/or fomepizole) until more than 6 hours had passed had higher odds of dying or having prolonged renal insufficiency (odds ratio 3.34). ^[14]

Fomepizole

Fomepizole (Antizol) is a convenient antidotal therapy for treatment of ethylene glycol or methanol intoxication. Fomepizole received US Food and Drug Administration (FDA) approval for use in ethylene glycol intoxication in December 1997, and it appears to have largely supplanted ethanol as the antidote of choice in toxic alcohol exposures in the US. ^[15] Fomepizole is administered with a loading dose and twice-daily intravenous dosing. ^[16]

Fomepizole is equally efficacious for the treatment of methanol intoxication but does not cause any alteration in mental status, hypoglycemia, or respiratory depression.

Fomepizole is advantageous because it does not depress the patient's mental status or airway and needs to be administered only every 12 hours. The main drawback of fomepizole is the cost, which can total thousands of dollars. Because this agent is so expensive, clinicians should check its availability at their institution and discuss the plan for use of this antidote, especially for empiric treatment of cases in which the cause of acidosis is unknown.

The availability of timely results of laboratory tests can be a problem. Weigh the benefits, risks, and costs of each therapeutic intervention at the treating institution.

Ethanol

If fomepizole is not used, oral or parenteral ethanol loading is less commonly used as a temporizing measure while awaiting test results. A loading dose of ethanol is administered based on body weight, followed by infusion to maintain a serum level of approximately 100 mg/dL.

Carefully calculate the loading dose and administration of ethanol antidote to prevent excessive administration. Overly aggressive ethanol administration has reportedly caused cases of apnea that required intubation and mechanical ventilation, so serum ethanol concentrations must be checked regularly and the infusion rate adjusted to prevent over- or undertreatment. When administering ethanol, determine glucose levels by fingerstick collection at regular intervals and confirm with laboratory analysis, as hypoglycemia is occasionally associated with ethanol therapy. Other potential adverse effects include hyponatremia, sclerosis of veins, and intoxication (which can be particularly distressing in pediatric patients).

Any patient receiving intravenous ethanol therapy requires ICU monitoring.

Hemodialysis

Hemodialysis is used to treat metabolic acidosis or to prevent renal insufficiency.

Early in the intoxication, the toxin is present as the parent compound, ethylene glycol. As time passes, toxic metabolites accumulate and the patient develops metabolic acidosis. Eventually, oxalate is deposited in the kidney and elsewhere; renal insufficiency may ensue. Once any of these manifestations occurs, antidotal therapy alone (used to block alcohol dehydrogenase with ethanol or fomepizole) is insufficient to treat the poisoning.

Alcohol dehydrogenase–blocking therapy must be accompanied by dialysis to remove the metabolites in these cases. Consulting a nephrologist early in the intoxication is prudent to facilitate the timely initiation of dialysis to these patients. Delays may result in renal failure or other severe complications.

Traditional dialysis indications include the following ^[17] :

• pH < 7.25
• Acute kidney injury
• Ethylene glycol serum concentration >50 mg/dL
• Serum glycolic acid >8 mmol/L

Some clinicians have suggested that effective blockade of alcohol dehydrogenase may permit the treatment of ethylene glycol intoxication without dialysis. In one case report, ^[18] a patient with an initial ethylene glycol level of 700 mg/dL was treated aggressively with fomepizole and was able to avoid dialysis. However, because of the cost of fomepizole and the safety of hemodialysis, the threshold for this approach should be carefully considered on the basis of the clinical setting.

It is highly recommended to include the regional poison center (or a toxicologist) in the management of these patients. The telephone number for certified poison centers anywhere in the United States and Puerto Rico is 1-800-222-1222.

If dialysis is considered, consult a nephrologist as early as possible to allow timely treatment of patients with toxic metabolite accumulation. Antidotal therapy is inadequate by itself in these circumstances, and dialysis should be performed as soon as possible.