Ethylene Glycol Poisoning

Aka: Ethylene Glycol Poisoning, Ingestion of Ethylene Glycol, Ethylene Glycol Antifreeze Ingestion, Ethylene Glycol, Ethylene Alcohol, Ethylene Dihydrate, Glycol Alcohol, Monoethylene Glycol, Antifreeze Fluid, De-icing solution

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II. Pathophysiology

  1. Ethylene Glycol found in antifreeze (e.g. radiator fluid) and de-icer
    1. Rapid absorption from Stomach and Small Intestine
  2. Toxicity results at doses >1.0 ml/kg (only 2-3 ounces for an adult)
    1. Ethylene Glycol causes CNS depression (Alcohol-like)
    2. Ethylene Glycol is metabolized to Glycolaldehyde via Alcohol dehydrogenase and then by 3 pathways
      1. Two pathways are non-toxic and rely on Cofactors Pyridoxine (Vitamin B6) and Thiamine
      2. Remaining pathway is to Glycolate and Oxalic Acid which are toxic (see below)
    3. Glycolic Acid or Glycolate effects (metabolite of glycoaldehyde via aldehyde dehydrogenase)
      1. Metabolic Acidosis
      2. Renal Failure
    4. Oxalic acid effects (metabolite of glycolate via oxidation)
      1. Calcium oxalate crystal deposition
      2. Nephrotoxicity

III. Causes: Ethylene Glycol Sources

  1. Antifreeze
  2. Cosmetics
  3. Films
  4. Paints
  5. Solvents
  6. Brake Fluid
  7. Plastic
  8. Ballpoint pens
  9. Stamp Pad Ink

IV. Pharmacokinetics

  1. Rapid absorption after ingestion
  2. Bioavailability 90%
  3. Half-Life: 17 hours (in normal Renal Function)

V. Findings: Symptoms and Signs

  1. Stage I: CNS Effects (peak 6-12 hours after ingestion)
    1. Confusion
    2. Ataxia
    3. Slurred speech
    4. Hallucinations
    5. Nystagmus
    6. Headaches
    7. Lethargy to Coma
    8. Seizures
  2. Stage II: Cardiopulmonary Effects (onset 12-36 hours)
    1. Nausea or Vomiting
    2. Hyperventilation
    3. Muscle Tetany or Seizures (Hypocalcemia)
    4. Hypertension
    5. Tachycardia
    6. Tachypnea
    7. Cyanosis
    8. Pulmonary Edema
    9. Hypotension
  3. Renal Effects (ensue within 24 to 72 hours)
    1. Oliguria or Anuria (Acute Renal Failure)
    2. Abdominal Pain
    3. Flank Pain

VI. Labs

  1. Initial labs
    1. Arterial Blood Gas
    2. Chemistry panel
    3. Serum Osmolality
    4. Urinalysis
  2. Lab findings suggestive of Ethylene Glycol ingestion
    1. Serum Osmolar Gap increased (especially if >10 mOsm/kg H2O)
      1. Osmolar Gap x6 approximates Ethylene Glycol level
      2. Serum Osmolality increases 16 mmol/L for every 100 mg/dl serum Methanol
      3. Low Test Sensitivity
    2. Metabolic Acidosis with High Anion Gap
    3. Hypocalcemia
    4. Serum lactate increased
    5. Calcium oxalate crystals seen on urine microscopy
      1. Needle-shaped monohydrate form or
      2. Envelope-shaped dihydrate form
    6. Acute Kidney Injury
      1. Onset >24 hours after ingestion
      2. Increased Serum Creatinine
      3. Proteinuria
      4. Hematuria
  3. Other tests to consider
    1. Serum Ethylene Glycol test
      1. Specific, but expensive and not readily available
      2. Does not predict prognosis
      3. Level >20 mg/dl indicates antidote below
    2. Woods lamp exam of urine (not typically helpful)
      1. Antifreeze contains Fluorescein
      2. Toxicologists do not recommend this
        1. Low Test Sensitivity
        2. Pediatric urine will fluoresce normally (in absence of Ethylene Glycol)

VII. Differential Diagnosis

  1. See Metabolic Acidosis with Anion Gap
  2. See Poisoning
  3. See Poisoning Causes
  4. Methanol Poisoning
  5. Sepsis

VIII. Management: Antidotes

  1. Approach
    1. Combine with Vitamin Supplementation (Vitamin B6, Thiamine) as below to shunt metabolism to non-toxic metabolites
    2. Consider Hemodialysis (see below) as definitive management in severe ingestions
  2. Indications
    1. Serum Ethylene Glycol level >20 mg/dl or
    2. Suspected Ethylene Glycol intake and 2 or more:
      1. Arterial pH <7.3
      2. Serum bicarbonate <20 meq/L
        1. Follow serially
      3. Osmolal Gap >10 mOsm/kg H2O (although normal baseline osmolality varies considerably)
        1. Levels above 20 mOsm/kg are definitive
      4. Calcium oxalate crystals in urine
  3. Mechanism
    1. Blocks Alcohol dehydrogenase
    2. Prevents metabolite (Glycolic Acid) formation
  4. Agents
    1. Fomepizole (Antizol)
      1. Preferred agent specific for Alcohol dehydrogenase
      2. Increases half life from 3 to 20 hours
      3. Load: 15 mg/kg
      4. Next: 10 mg/kg q12 hours for 4 doses
      5. Maintenance: 15 mg/kg q12 hours
      6. End point: Ethylene Glycol <20 mg/dl
    2. Ethanol (not typically used in U.S.)
      1. Alternative if Fomepizole not available
      2. Requires blood alchohol level 100 to 150 mg/dl
      3. Dose: 10% Ethanol diluted in 5% dextrose
        1. Load: 8-10 ml/kg over 30 minutes
        2. Maintenance: 1.4 to 2.0 ml/kg/hour

IX. Management: Hemodialysis Indications

  1. Deteriorating condition despite maximal support (serious end-organ toxicity)
  2. Metabolic Acidosis with serum pH <7.25
  3. Acute Renal Failure refractory to other measures
  4. Serum Electrolyte imbalance refractory
  5. Altered Mental Status
  6. Fomepizole not available and Ethylene Glycol serum level >50 mg/dl
    1. Serum level does not otherwise indicate Dialysis

X. Management: Other measures

  1. Vitamin Supplementation to shunt Ethylene Glycol metabolism to less toxic metabolites
    1. Pyridoxine Supplementation
    2. Thiamine 0.25-0.5 mg/kg up to 100 mg PO or IV daily
  2. Sodium Bicarbonate
    1. Benefits
      1. Corrects Metabolic Acidosis
      2. Inhibits Calcium oxalate crystal deposition
      3. Increases Glycolic Acid excretion
    2. Technique
      1. Keep Urine pH >7.0
  3. Unhelpful measures: Gastric Decontamination (due to rapid absorption)
    1. Gastric Lavage is not effective
    2. Activated Charcoal is not effective
    3. Syrup of Ipecac is not effective (and never indicated in U.S.)
  4. Disposition
    1. Admit all patients requiring antidote or Hemodialysis
    2. Discharge at 4-6 hours after ingestion if normal serum bicarbonate and normal osmol gap

XI. Prognosis

  1. Fatal if severe case not treated within 24-36 hours

XII. References

  1. Leiken (1995) Poisoning and Toxicology, p. 925-6
  2. Nordt and Swadron in Herbert (2013) EM:Rap 13(12): 3
  3. Rodriguez (2022) Crit Dec Emerg Med 36(4): 26-31
  4. Tomaszewski (2019) Crit Dec Emerg Med 33(6):28
  5. Barceloux (1999) J Toxicol Clin Toxicol 37:537-60 [PubMed]
  6. Scalley (2002) Am Fam Physician 66(5):807-12 [PubMed]

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