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Toxicity, Ethylene Glycol: Treatment & Medication
Updated: Aug 21, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Prehospital Care
- 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.
- Evidence-based guidelines on out-of-hospital management of ethylene glycol poisoning are available from the American Association of Poison Control Centers.4
Emergency Department Care
Rapidly evaluate patients who present with signs, symptoms, or history of toxic alcohol ingestion; determine serum osmolal gap.
- Obtain intravenous access and laboratory specimens.
- Measure levels of electrolytes, calcium, and magnesium, especially in patients with alcoholism because alcohol is a cofactor in oxalate metabolism.
- 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).
- Pyridoxine and thiamine are cofactors in ethylene glycol metabolism and should be administered parenterally.
- Place symptomatic patients in a monitored setting.
- An ECG may be useful in patients with arrhythmias that may result from hypocalcemia.
- Foley catheterization is usually indicated for patients with altered mental status to monitor urinary output and to allow serial examination of urine for crystals or fluorescence.
- If the serum osmolal gap is not zero, begin antidotal therapy empirically while awaiting confirmation. This is performed with either fomepizole (4-MP) or ethyl alcohol. The latter is usually administered intravenously but may be administered orally in remote settings where emergency hospital care is not immediately available.
- Treatment of patients with suspected ethylene glycol intoxication is indicated in any of the following 3 circumstances5 :
- The plasma level of ethylene glycol is 20 mg/dL or more.
- The history of recent ethylene glycol ingestion is definite, and the osmolal gap is 10 mOsm/L or more.
- A history or suspicion of ethylene glycol intoxication and at least 2 of the following are present:
- Arterial pH level is less than 7.3.
- Serum bicarbonate level is less than 20 mg/dL.
- Osmol gap is greater than 10 mOsm/L.
- Urinary oxalate crystals are present.
- Fomepizole (4-MP [Antizol]) is a convenient antidotal therapy for treatment of ethylene glycol or methanol intoxication. Many emergency departments have adopted routine use of this agent for cases of suspected toxic alcohol poisoning.6 Fomepizole is administered with a loading dose and twice-daily intravenous dosing.7
- 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.
- Fomepizole is equally efficacious for the treatment of methanol intoxication but does not cause any alteration in mental status, hypoglycemia, or respiratory depression.
- Fomepizole received US Food and Drug Administration (FDA) approval in December 1997.
- The availability of timely results of laboratory tests can be a problem. Weigh the benefits, risks, and costs of each therapeutical intervention at the treating institution.
- If fomepizole is not used, oral or parenteral ethanol loading can be initiated 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.
- When administering ethanol, determine glucose levels by fingerstick collection at regular intervals and confirm with laboratory analysis to detect the hypoglycemia occasionally associated with ethanol therapy.
- Most patients with ethylene glycol toxicity require monitoring in an ICU setting.8
- Hemodialysis is used to treat metabolic acidosis or to prevent renal insufficiency.9
- 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 4-MP) 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.
- Some clinicians have suggested that effective blockade of alcohol dehydrogenase may permit the treatment of ethylene glycol intoxication without dialysis. This has not yet been demonstrated clinically.10
Consultations
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. Consult a poison control center or a medical toxicologist for assistance in management options.
Medication
If the osmolal gap is not zero, begin antidotal therapy empirically while awaiting confirmation.
Antidotes
Avoid overdosing or underdosing of ethanol by frequently monitoring blood ethanol levels.
Ethanol
Goal is to maintain blood ethanol levels 100-150 mg/dL. This completely saturates ADH. May be administered PO or IV. Measuring initial blood level is important; if >100 mg/dL, loading dose may be unnecessary and patient can be started on maintenance dose.
Frequent monitoring of blood alcohol concentrations is important. Adjust dose to reduce methanol levels to <20 mg/dL.
Adult
IV loading dose: 7.6-10 mL/kg IV of 10% ethanol (V/V) in dextrose 5% in water over 30 min to achieve blood ETOH concentration of 100-130 mg/dL (21.7-28.2 mmol/L)
Oral loading dose: 0.8-1 mL/kg PO of 95% ethanol in 6 oz of orange juice over 30 min
Average maintenance doses (PO/IV): 0.15 mL/kg/h PO of 95% ETOH; 1.4 mL/kg/h IV of a 10% solution
Pediatric
Administer as in adults; titrate dosing to maintain BAL of 100-150 mg/dL
May increase toxicity of benzodiazepines and result in death
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Watch for hypoglycemia, especially in children; adjust dosing during hemodialysis; extreme caution if patient has ingested other CNS depressants; IV may cause thrombophlebitis; PO may cause severe gastritis
Fomepizole (Antizol)
Antidote with better safety profile than ethanol. Easier to dose and administer. In contrast to ethanol, 4-MP levels do not need to be monitored during therapy. The biggest drawback is the cost of the antidote; however, compare the additional expenses of fomepizole with the high degree of required vigilance, occasional treatment failure, and complications seen with ethanol.
Begin fomepizole treatment immediately upon suspicion of EG ingestion based on patient history or anion gap metabolic acidosis, increased osmolar gap, oxalate crystals in urine, or documented serum methanol level.
Adult
Loading dose: 15 mg/kg IV over 30 min
Maintenance dose: 15 mg/kg IV q12h until patient is asymptomatic with a normal pH level and the EG level is <20 mg/dL
Pediatric
Not established; suggested dose is proportional to body weight, as in adults
PO doses (10-20 mg/kg) have been shown to reduce rate of ethanol elimination by 40% in healthy volunteers; ethanol has been shown to decrease rate of fomepizole elimination by 50%
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Do not administer as bolus; caution with breastfeeding because no information exists on excretion of medication in breast milk; caution in patients with renal impairment; dosage interval needs to be adjusted during hemodialysis
Nutrients
Pyridoxine enhances metabolism of glyoxylate to glycine. Thiamine catalyzes metabolism of glyoxylate from glycolic acid.
Pyridoxine (Nestrex)
Water-soluble vitamin B-complex, which is a cofactor in conversion of GA to nonoxalate compounds. Involved in synthesis of GABA within CNS.
Adult
100 mg IV qid for 2 d
Pediatric
1-2 mg/kg IV in first 24 h of treatment
May decrease levodopa, phenytoin, and phenobarbital serum levels
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
>200 mg/d may precipitate withdrawal effects when medication is discontinued
Thiamine (Thiamilate)
Vitamin B-1 is water-soluble and used in many cellular functions that involve energy formation and use. Promotes conversion of glyoxylate to a nontoxic metabolite, alpha-hydroxy-beta-ketoadipate.
Adult
50 mg IV qid for 2 d
Pediatric
0.25-0.50 mg/kg IV on first day of therapy
None reported
Documented hypersensitivity
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Some early reports suggest that IV administration is associated with deleterious effects on cardiovascular function (eg, hypotension), but subsequent studies have not supported this; sensitivity reactions can occur (intradermal test-dose recommended in suspected sensitivity); fatalities have resulted from IV use; sudden onset or worsening of Wernicke encephalopathy, following glucose administration, may occur in patients with thiamine deficiency; administer before or together with dextrose-containing fluids in patients with suspected thiamine deficiency
More on Toxicity, Ethylene Glycol |
| Overview: Toxicity, Ethylene Glycol |
| Differential Diagnoses & Workup: Toxicity, Ethylene Glycol |
 Treatment & Medication: Toxicity, Ethylene Glycol |
| Follow-up: Toxicity, Ethylene Glycol |
| References |
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References
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Further Reading
Keywords
ethylene glycol toxicity, EG, EG toxicity, EG poisoning, radiator fluid, antifreeze, glycolic acid, GA, ethylene glycol poisoning, radiator fluid ingestion, accidental ingestion, ethanol, fomepizole, alcohol toxicity, ethylene glycol intoxication, calcium oxalate crystals, acidosis, glycoaldehyde, ethylene glycol ingestion
