EM@3AM: Ethylene Glycol Toxicity

Author: Brit Long, MD (@long_brit, EM Attending Physician, San Antonio, TX) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

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A 37-year-old male presents with altered mental status. He has a history of recurrent alcohol intoxication, and his wife found him on the couch after he was working in the garage. She is concerned because he seems to be much more intoxicated than is usual. She also found spilled containers of antifreeze in the garage. He has no other medical problems.

Initial VS include T 37.2C, HR 114, BP 110/61, RR 26, SpO2 97% RA.

Exam reveals dry oral mucosa and altered mental status, as the patient is only alert and oriented to himself.  However, you don’t detect any focal neurologic deficits.

What could be going on with this patient? Is he just intoxicated?


AnswerEthylene Glycol Toxicity

  • Background: Ethylene glycol is a component of automobile coolants/antifreeze, deicing agent, solvents, and brake fluid. It typically tastes sweet, and the primary compound results in intoxication.
    • Toxic alcohols are metabolized into acids through normal alcohol metabolic pathways (alcohol dehydrogenase). Glycolic acid and oxalic acid, the metabolites of the breakdown of ethylene glycol, result in severe toxicity.
  • Pharmacology: After ingestion, peak serum concentration occurs within 4 hours, with elimination in 3 hours. The minimum lethal dose is 1-1.5 mL/kg, but this also depends on the specific concentration. Metabolites cause toxicity, but they are not responsible for the osmolal gap.
  • Features: Consist of several different stages.
    • 1: CNS
      • Occurs within 30 minutes and lasts 12 hours. Patients appear intoxicated with nausea/vomiting, slurring of speech, ataxia, stupor, coma, seizure.
    • 2: Cardiopulmonary
      • Occurs 12-24 hours after ingestion, with most deaths occurring within this stage.
      • Marked by hypertension, tachycardia, CHF, ARDS, hypoxia, hyperventilation (compensate for metabolic acidemia), hypocalcemia due to oxalate chelation, myositis, arrhythmia, organ failure.
    • 3: Renal
      • Occurs 24-72 hours after ingestion.
      • Flank pain, CVA tenderness, hematuria, proteinuria, oliguria, anuria.
  • Differential diagnosis: Other intoxication, sepsis, pulmonary abnormality, cardiovascular condition (CHF, MI), rhabdomyolysis, DKA/HHS, trauma.
  • Evaluations:
    • Electrolytes/chemistry: May see renal failure, low glucose (decreased caloric intake), and anion gap acidosis (typically not present immediately after exposure).
    • Serum osmolality: Gap > 50 is suggestive of toxic alcohol poisoning. Normal gap should not be used to rule out toxic alcohol ingestion. Only the parent alcohol functions to raise the osmolol gap.
      • Normal levels range from negative to positive values. High osmolar gaps may only be found immediately after ingestion.
    • Ethanol level should be obtained. If negative and patient appears intoxicated, think toxic alcohol. If ethanol level is positive, this can be protective against a toxic alcohol. Positive ethanol level does not rule out toxic alcohol.
    • CK may be elevated due to rhabdomyolysis.
    • VBG is needed to assess for acidosis (anion gap acidosis). Bicarbonate is often single digits.
    • Urinalysis may demonstrate hematuria, proteinuria, and pyuria.  Calcium oxalate crystals are late and only present in 50% of cases. Urinary fluorescence is not sensitive or specific.
    • Lactate
    • ECG: May show QT prolongation due to hypocalcemia.
    • Obtain acetaminophen and salicylate levels due to risk of coingestion and discern cause of anion gap acidosis.
    • Obtain toxic alcohol levels if able, but these are often not available.
  • Recognition:
    • Tachypnea without respiratory disease (compensation), not sobering as expected, seizure.
    • Anion gap metabolic acidosis, high osmolality (decreases with time), low ethanol in intoxicated patient, hypocalcemia and prolonged QT.
    • As osmolality decreases, acidosis worsens.
  • Management: Call poison control/toxicologist immediately. Treatment focuses on three goals.
    • Block toxic metabolites: Fomepizole is first line. Dosing is 15 mg/kg, then 10 mg/kg every 12 hours for 48 hours. May use ethanol to target BAL 100-150, but this is more difficult to titrate and risks hypoglycemia.
      • Indications for fomepizole or alcohol to block ADH: known ingestion without access to lab assessment, metabolic acidosis plus strong suspicion of ingestion, elevated ethylene glycol level, end organ dysfunction and suspicion of ingestion.
      • Cofactors should be replenished: folic acid 50 mg IV every 6 hours, thiamine 100 mg IV every 6 hours, pyridoxine 100 mg every 6 hours.
    • Correct acidosis: Bicarbonate infusion, targeting pH 7.2. This will require patient respiratory compensation to blow off CO2.
    • Eliminate toxic metabolites: Gastric decontamination is typically not recommended due to rapid gastric absorption. Dialysis may not be needed if fomepizole is started early after ingestion without acidosis or renal dysfunction. Consider dialysis with refractory metabolic acidosis, renal insufficiency (Cr elevation by 1 mg/dL or Cr > 3 mg/dL), worsening hemodynamic status, electrolyte abnormalities refractory to standard therapy, ethylene glycol level > 50 mg/dL (not definitive), glycolic acid level > 8 mmol/L.
  • Disposition: Patients require admission to a critical care unit.

Which of the following laboratory findings suggests ethylene glycol ingestion?

A. Anion gap 16 and pH 7.32 associated with vision changes

B. Lactate 0.9 mmol/L, pH 7.12, and creatinine 2.5 mg/dL

C. Osmol gap 20, anion gap 8, and ketonemia

D. pH 7.10, lactic acid 5.5 mmol/L, and anion gap 21

 

Answer: B

The toxic alcohols include ethanol, ethylene glycol, methanol, and isopropanol. Each alcoholic overdose has its own clinical characteristic. Markers of intoxication with ethylene glycol include high anion gap metabolic acidosis with an absence of significant lactate or ketone concentrations, calcium oxalate formation leading to acute renal failure. Therefore, lactate 0.9 mmol/L, pH 7.12, and creatinine 2.5 mg/dL would be characteristic of ethylene glycol poisoning; although, lactate can be slightly elevated (both falsely or truly), but not at levels that would explain the the significant acidosis. Sodium bicarbonate may be used for urine alkalinization to improve acidemia. Ethanol or fomepizole may be utilized for acute management in conjunction with a nephrology consultation. Hemodialysis is indicated for ethylene glycol levels > 25 mg/dL. Adjunctive therapy includes thiamine and pyridoxine every 4 to 6 hours.

Anion gap 16 and pH 7.32 (A) associated with vision changes characterizes acute methanol toxicity. This leads to high anion gap metabolic acidosis with “snow field” vision, blindness, or optic disc hyperemia or retinal edema on fundoscopy. Osmol gap 20, anion gap 8, and ketonemia (C) suggests acute isopropanol (isopropyl alcohol) poisoning, which leads to ketosis without acidosis, a normal anion gap, and an elevated osmol gap. A pH of 7.10, lactic acid 5.5 mmol/L, and anion gap 21 (D) is nonspecific and may represent metabolic acidosis from sources other than toxic ingestions, such as sepsis.

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FOAMed:

Emergency Medicine Cases – Minding the Gaps

emDOCS.net – The Unhappy Drunk

LITFL – Toxic Alcohol Ingestion

Sinai EM – What’s the gap?

Core EM – the basics

emDOCs.net-  Toxcard

FOAMCast – Alcohols

PulmCrit – Osmolar gap

 

References:

  1. Kraut JA, Mullins ME. Toxic Alcohols. N Engl J Med 2018; 378:270-280.
  2. Ng PCY, Long B, Davis WT, Sessions DJ, Kofyman A. Toxic alcohol diagnosis and management: an emergency medicine review. Internal and Emergency Medicine 2018;13(3):375-383.
  3. Wiener SW (2015) Toxic Alcohols. In: Hoffman RS, Howland M, Lewin NA et al (eds) Goldfrank’s toxicologic emergencies, 10th edn. McGraw-Hill, New York.
  4. Mégarbane B,Borron SW, Baud FJ. Current recommendations for treatment of severe toxic alcohol poisonings. Intensive Care Med. 2005 Feb;31(2):189-95. Epub 2004 Dec 31.

 

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