Reviewed by: Exam Review Panel

Vignette: A 16-year-old female adolescent (weight 55 kg) presents to the emergency department 90 minutes after ingesting 5–8 oz of antifreeze, according to patient report. She appears drowsy and “drunk.” She is conscious and alert, has not vomited, and is not experiencing nausea or abdominal pain.

Medical History: One previous overdose with promethazine 1 year ago; no diagnosis of depression, but a history of recent sexual assault leading to feelings of guilt and sadness

Social History: Has used cocaine and MDMA one time; marijuana use occasionally for 3 months, last use 2 months ago

Current Medications: None

Allergies: PCN (rash/hives/airway edema)

Vital Signs: Temperature 36.8°C, heart rate 96 beats/minute, respiratory rate 29 breaths/minute, blood pressure 124/80 mm Hg, Spo₂ (oxygen saturation) 97% on room air

Laboratory Values: WBC 9.9 × 10³ cells/mm³ (SI 9.9 × 10⁹ cells/L); Hgb 12.9 g/dL (SI 129 g/L); Hct 39% (SI 0.39); Plt 316,000/mm³; Na 135 mEq/L (SI 135 mmol/L); K 3.8 mEq/L (SI 3.8 mmol/L); Cl 107 mEq/L (SI 107 mmol/L); HCO₃ 19 mEq/L (SI 19 mmol/L); glucose 104 mg/dL (SI 5.8 mmol/L); calcium 9.4 mg/dL (SI 2.4 mmol/L); SCr 0.7 mg/dL (SI 63 micromoles/L); serum urea nitrogen 12 mg/dL (SI 4.3 mmol/L); capillary blood gas pH 7.37; Pco₂ 32 mm Hg; Po₂ 68 mm Hg/HCO₃ 19 mEq/L; base excess -6 mEq/L

Urine toxicology screen negative for amphetamines, barbiturates, cannabinoids, cocaine, PCP, benzodiazepines; ethanol undetectable; acetaminophen and salicylate undetectable; measured serum osmolality 307 mOsm/kg; calculated serum osmolality 280 mOsm/kg; urinalysis WNL except for a few calcium oxalate crystals present

Procedure Data: ECG – normal sinus rhythm

Other Data: Physical Examination:

CNS – alert, depressed mood, GCS 15, CN II–XII intact

GI – WNL

Skin – no rash, normal skin turgor, healing scars on left forearm and right upper thigh

Musculoskeletal – WNL

CV – RRR, no murmur, CR 2 seconds

Question 1 – 100 Points

Which patient information is most specific for ethylene glycol poisoning?

1. Calcium oxalate crystals present in urine
2. Elevated anion gap
3. Elevated osmolal gap
4. Metabolic acidosis

Answer: 1.      Calcium oxalate crystals present in urine

Rationale: Of the toxic alcohols, ethylene glycol is the one that would produce calcium oxalate in the urine. In this case, the anion gap is not elevated. Metabolic acidosis is present but mild, though this is not a very specific result of ethylene glycol poisoning. The same is true of an elevated osmolal gap, though it is present here (307 – 280 = 27; reference range 10–20 mOsm/kg). In addition, even in poisoned patients, the osmolal gap is not elevated. Thus, Answer 1 is best.

Citation: Kraut JA, Mullins ME. Toxic alcohols. N Engl J Med 2018;378:270-80.

Question 2 – 200 points

Which statement accurately describes the importance of a blood ethanol laboratory value?

1. Absence of ethanol would increase the risk of calcium oxalate crystal development.
2. Absence of ethanol would increase the risk of liver toxicity.
3. Presence of ethanol would delay the onset of CNS depression.
4. Presence of ethanol would delay the onset of elevated anion gap.

Answer: 4.      Presence of ethanol would delay the onset of elevated anion gap

Rationale: Elevated anion gap typically develops as the metabolism of the toxic alcohol progresses (in this case, ethylene glycol). Ethanol will compete for metabolism with alcohol dehydrogenase, which will slow the metabolism of ethylene glycol. Thus, Answer 4 is correct. Ethanol would of course contribute to CNS depression. Absence of ethanol would not affect calcium oxalate production or liver toxicity.

Citation: Kraut JA, Mullins ME. Toxic alcohols. N Engl J Med 2018;378:270-80.

Question 3 – 200 points

Which end organ is most likely to show evidence of injury after an ethylene glycol overdose?

1. Eye
2. Heart
3. Liver
4. Kidney

Answer: 4       Kidney

Rationale: Ethylene glycol would primarily cause kidney damage. Methanol can result in blurry vision (snow vision), whereas ethylene glycol is not associated with that. Heart and liver toxicity would be more of an indirect problem, depending on the severity of the overdose.

Citation: Kraut JA, Mullins ME. Toxic alcohols. N Engl J Med 2018;378:270-80.

Question 4 – 300 points

Which intervention would be most appropriate initially?

1. Gastric lavage
2. Hemodialysis
3. Intravenous fluid administration
4. Whole bowel irrigation

Answer: 3.      Intravenous fluid administration

Rationale: Ethylene glycol is absorbed very rapidly, so any GI decontamination would be ineffective. Hemodialysis is not indicated at this time because there is little evidence of acute kidney injury at this point, and even though no ethylene glycol serum concentration is available, patient status would indicate that it is not above the 50-mg/dL threshold. Thus, intravenous fluid administration, perhaps with acetate or base, is the best initial intervention.

Citation: Kraut JA, Mullins ME. Toxic alcohols. N Engl J Med 2018;378:270-80.

Question 5 – 300 points

After the initial intervention, which definitive therapy is most appropriate?

1. Ethanol infusion
2. Folic acid
3. Fomepizole
4. Supportive care

Answer: 3.      Fomepizole

Rationale: Unfortunately, in many hospitals, serum ethylene glycol or methanol concentrations are not obtainable. Thus, in this patient, history, examination, and laboratory analysis (oxalic acid in urine, elevated osmolal gap) provide enough evidence of a potentially significant exposure to warrant antidote therapy. Thus, supportive care is probably not enough. Folic acid, not ethylene glycol, is an additive therapy for methanol ingestion. The favored antidote is fomepizole. It has a high affinity for alcohol dehydrogenase, which will prevent metabolism of ethylene glycol to its toxic metabolites. Advantages to fomepizole compared with ethanol include association with lower mortality, fewer adverse events, and no need for intensive care during therapy; also, although fomepizole was very costly in the past, generic versions are significantly less expensive.

Citation: Kraut JA, Mullins ME. Toxic alcohols. N Engl J Med 2018;378:270-80.