Ethylene glycol poisoning: fomepizole first

AKImedium

A 22-year-old man is taken to the emergency department by his friend after accidental ingestion of an unknown fluid earlier that day. He complains of abdominal pain but has not experienced any nausea or vomiting. He has no past medical history and takes no medications. On examination, BP is 110/77 mm Hg, heart rate is 112/min, respiratory rate is 19/min, and oxygen saturation is 98% while breathing room air. He appears distressed and is alert to person and place but is unsure of the date. Physical examination reveals mild tenderness to palpation of the abdomen but is otherwise normal. Laboratory data: sodium 142 mEq/L (reference 136–145); potassium 3.8 mEq/L (3.5–5.0); chloride 106 mEq/L (98–106); total CO₂ 14 mEq/L (23–28); BUN 9 mg/dL (8–20); creatinine 0.7 mg/dL (0.7–1.3); glucose 81 mg/dL (70–99, fasting); osmolality 322 mOsm/kg H₂O (275–295). Shortly after arrival, the patient provides a urine sample, which shows blue-green fluorescence under a Wood's lamp. Which ONE of the following is the most appropriate next step in management?

  1. A.Ethanol IV
  2. B.Activated charcoal
  3. C.FomepizoleCorrect
  4. D.Hemodialysis

Explanation

The most appropriate next step in this patient with suspected ethylene glycol toxicity is the prompt administration of fomepizole. This patient has an elevated anion gap, an elevated osmolal gap, and fluorescent urine under a Wood's lamp, all of which strongly suggest ethylene glycol ingestion. Other evidence of ethylene glycol ingestion would be AKI and oxalate crystals in the urine. Antifreeze ingestion is a common cause of ethylene glycol toxicity. Sodium fluorescein is added to some commercial antifreeze preparations to aid in detecting automobile cooling system leaks and can produce the urinary fluorescence described in this patient. This patient has an anion gap metabolic acidosis with a calculated anion gap of 22. The osmolality can be calculated using the following equation: Calculated serum osmolality = 2 [Na⁺] + [BUN]/2.8 + [Glucose]/18 The calculated serum osmolality for this patient is 292 mOsm/kg H₂O, with a measured serum osmolality of 322 mOsm/kg H₂O, leading to an osmolal gap of 30 mOsm/kg H₂O. A normal osmolal gap is <10 mOsm/kg H₂O. Ingestion of ethylene glycol, methanol, and propylene glycol causes elevated osmolal gap due to their accumulation in the serum. As these compounds are metabolized to organic acids, the anion gap will rise. Isopropyl alcohol is associated with an elevated osmolal gap but a normal anion gap, as its metabolite is neutral acetone. In normal physiologic states, ingested ethanol is metabolized to acetaldehyde, a reaction catalyzed by the enzyme alcohol dehydrogenase. Aldehyde dehydrogenase then converts acetaldehyde into acetic acid. Alcohol dehydrogenase also plays a role in metabolizing the alcohols methanol and ethylene glycol into formaldehyde and glycoaldehyde, respectively. Glycoaldehyde is further oxidized to its final end products, which include the toxins glycolate and oxalate. Fomepizole is an alcohol dehydrogenase inhibitor used to attenuate the metabolism of toxic alcohols. It has a 500–1000 times greater affinity for alcohol dehydrogenase than ethanol and helps prevent the metabolism of ethylene glycol or methanol into their toxic byproducts. HD is effective in removing ethylene glycol and its toxic metabolites and is recommended in the setting of severe metabolic acidosis (pH <7.25), AKI, ethylene glycol level >50 mg/dL, or glycolate level >10 mg/dL. HD is generally continued until the ethylene glycol level is <20 mg/dL. Even in patients who require HD, fomepizole should be given first to prevent further damage while preparing for dialysis initiation. Activated charcoal is unlikely to be effective unless given in the first 30–60 minutes after ingestion. IV ethanol works by acting as a competitive inhibitor of alcohol dehydrogenase and can be used in low resource settings to prevent ethylene glycol metabolism if fomepizole is not available.

Why each option

A.
Intravenous ethanol also inhibits alcohol dehydrogenase but causes intoxication, hypoglycemia, and dosing difficulty; it is reserved for when fomepizole is unavailable.
B.
Toxic alcohols are absorbed within minutes and bind charcoal poorly, so charcoal hours after ingestion offers no benefit.
C.
Correct. Anion gap 22, osmolal gap 30, and fluorescent urine indicate ethylene glycol; fomepizole blocks alcohol dehydrogenase and prevents formation of glycolate and oxalate.
D.
Dialysis may be needed for severe acidosis, AKI, or high levels, but fomepizole is given first to stop toxic metabolite formation while dialysis is arranged.

Reference: Mégarbane B, Intensive Care Med 2005 (current recommendations for treatment of severe toxic alcohol poisonings); Ghannoum M, Crit Care 2023 (EXTRIP recommendations for ethylene glycol poisoning)

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