II. Pathophysiology

  1. Ethylene Glycol found in antifreeze and de-icer
    1. Rapid absorption from Stomach and Small Intestine
  2. Toxicity results at doses >1.0 ml/kg
    1. Ethylene Glycol causes CNS depression (Alcohol-like)
    2. Ethylene Glycol is metabolized to Glycolic Acid 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 Oxalic Acid which is toxic (see below)
    3. Glycolic Acid (metabolite) effects
      1. Metabolic Acidosis
      2. Renal Failure
    4. Oxalic acid (metabolite) effects
      1. Calcium oxalate crystal deposition

III. Symptoms and Signs

  1. Stage I: CNS Effects (peak 6-12 hours after ingestion)
    1. Confusion
    2. Ataxia
    3. Slurred speech
    4. Hallucinations
  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
  3. Renal Effects (ensue within 24 to 72 hours)
    1. Oliguria or Anuria (Acute Renal Failure)

IV. 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. Metabolic Acidosis with increased 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
  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)

VI. Management: Antidotes

  1. Approach
    1. Combine with Vitamin Supplementation (Vitamin B6, Thiamine) as below to shunt metabolism to non-toxic agents
    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

VII. 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. Fomepizole not available and serum level >50 mg/dl
    1. Serum level does not otherwise indicate Dialysis

VIII. 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
    1. Syrup of Ipecac is not effective
    2. Gastric Lavage is not effective
    3. Activated Charcoal is not effective

IX. Prognosis

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

X. References

  1. Nordt and Swadron in Herbert (2013) EM:Rap 13(12): 3
  2. Leiken (1995) Poisoning and Toxicology, p. 925-6
  3. Barceloux (1999) J Toxicol Clin Toxicol 37:537-60 [PubMed]
  4. Scalley (2002) Am Fam Physician 66(5):807-12 [PubMed]

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Ontology: ethylene glycol (C0015083)

Definition (MSH) A colorless, odorless, viscous dihydroxy alcohol. It has a sweet taste, but is poisonous if ingested. Ethylene glycol is the most important glycol commercially available and is manufactured on a large scale in the United States. It is used as an antifreeze and coolant, in hydraulic fluids, and in the manufacture of low-freezing dynamites and resins.
Definition (CSP) viscous dihydroxy alcohol solvent with a sweetish acrid taste; poisonous if ingested; used as an antifreeze and coolant, in hydraulic fluids, and in the manufacture of low-freezing dynamites and resins.
Concepts Hazardous or Poisonous Substance (T131) , Organic Chemical (T109)
MSH D019855
SnomedCT 81886002
LNC LP14106-6, MTHU004290
English ethylene glycol, 1,2 Ethanediol, 1,2-Ethanediol, 2 Hydroxyethanol, 2-Hydroxyethanol, Ethylene Glycol, Glycol, Ethylene, Glycol, Monoethylene, Monoethylene Glycol, Ethylene Glycol [Chemical/Ingredient], ETHYLENE GLYCOL, Ethylene glycol, Ethanediol, Ethylene glycol (substance)
Swedish Etylenglykol
Czech ethylenglykol
Finnish Etyleeniglykoli
French 1,2-Dihydroxyéthane, Éthane-1,2-diol, Glycol 1,2-éthanediol, Glycol éthylique, Éthylèneglycol, Éthylène glycol
Japanese ジヒドロキシエタン, エチレングリコール, エタンジオール, 1,2-エタンジオール
Polish Glikol etylenowy
Portuguese Glicol de Etileno, Etileno Glicol, Etilenoglicol
Spanish etilenglicol (sustancia), etilenglicol, Glicol de Etileno
German Ethylenglycol
Italian Glicol etilenico

Ontology: Antifreeze (C0598248)

Concepts Substance (T167)
SnomedCT 311922005
English Antifreeze, antifreeze, Antifreeze (substance)
Spanish anticongelante (sustancia), anticongelante