II. Pathophysiology
- Ethylene Glycol found in antifreeze (e.g. radiator fluid) and de-icer
- Rapid absorption from Stomach and Small Intestine
- Toxicity results at doses >1.0 ml/kg (only 2-3 ounces for an adult)
- Ethylene Glycol causes CNS depression (Alcohol-like)
- Ethylene Glycol is metabolized to Glycolaldehyde via Alcohol dehydrogenase and then by 3 pathways
- Two pathways are non-toxic and rely on Cofactors Pyridoxine (Vitamin B6) and Thiamine
- Remaining pathway is to Glycolate and Oxalic Acid which are toxic (see below)
- Glycolic Acid or Glycolate effects (metabolite of glycoaldehyde via aldehyde dehydrogenase)
- Oxalic acid effects (metabolite of glycolate via oxidation)
- Calcium oxalate crystal deposition
- Nephrotoxicity
III. Causes: Ethylene Glycol Sources
- Antifreeze
- Cosmetics
- Films
- Paints
- Solvents
- Plastic
- Ballpoint pens
- Stamp Pad Ink
- Brake Fluid
- Mix of glycol ethers and diethylene glycol
- Hemolysis risk due to glycol ethers, in addition to Ethylene Glycol effects (described on this page)
- (2024) Crit Dec Emerg Med 38(7): 33
IV. Pharmacokinetics
- Rapid absorption after ingestion
- Bioavailability 90%
- Half-Life: 17 hours (in normal Renal Function)
V. Findings: Symptoms and Signs
- Stage I: CNS Effects (peak 6-12 hours after ingestion)
- Stage II: Cardiopulmonary Effects (onset 12-36 hours)
- Renal Effects (ensue within 24 to 72 hours)
VI. Labs
- Initial labs
- Arterial Blood Gas or Venous Blood Gas
- Chemistry panel
- Serum Osmolality
- Urinalysis
- Lab findings suggestive of Ethylene Glycol ingestion
- Serum Osmolar Gap increased (especially if >10 mOsm/kg H2O)
- Osmolar Gap x6 approximates Ethylene Glycol level
- Serum Osmolality increases 16 mmol/L for every 100 mg/dl serum Methanol
- Low Test Sensitivity
- Metabolic Acidosis with High Anion Gap
- Hypocalcemia
- Serum lactate increased
- Calcium oxalate crystals seen on urine microscopy
- Needle-shaped monohydrate form or
- Envelope-shaped dihydrate form
- Acute Kidney Injury
- Onset >24 hours after ingestion
- Increased Serum Creatinine
- Proteinuria
- Hematuria
- Serum Osmolar Gap increased (especially if >10 mOsm/kg H2O)
- Other tests to consider
- Serum Ethylene Glycol test
- Specific, but expensive and not readily available
- Does not predict prognosis
- Level >20 mg/dl indicates antidote below
- Woods lamp exam of urine (not typically helpful)
- Antifreeze contains Fluorescein
- Toxicologists do not recommend this
- Low Test Sensitivity
- Pediatric urine will fluoresce normally (in absence of Ethylene Glycol)
- Serum Ethylene Glycol test
VII. Differential Diagnosis
VIII. Management: Antidotes
- Approach
- Combine with Vitamin Supplementation (Vitamin B6, Thiamine) as below to shunt metabolism to non-toxic metabolites
- Consider Hemodialysis (see below) as definitive management in severe ingestions
- Indications
- Serum Ethylene Glycol level >20 mg/dl or
- Suspected Ethylene Glycol intake and 2 or more:
- Arterial pH <7.3
- Serum bicarbonate <20 meq/L
- Follow serially
- Osmolal Gap >10 mOsm/kg H2O (although normal baseline osmolality varies considerably)
- Levels above 20 mOsm/kg are definitive
- Calcium oxalate crystals in urine
- Mechanism
- Blocks Alcohol dehydrogenase
- Prevents metabolite (Glycolic Acid) formation
- Agents
- Fomepizole (Antizol)
- Preferred agent specific for Alcohol dehydrogenase
- Increases half life from 3 to 20 hours
- Load: 15 mg/kg
- Next: 10 mg/kg q12 hours for 4 doses
- Maintenance: 15 mg/kg q12 hours
- End point: Ethylene Glycol <20 mg/dl
- Ethanol (not typically used in U.S.)
- Alternative if Fomepizole not available
- Requires blood alchohol level 100 to 150 mg/dl
- Dose: 10% Ethanol diluted in 5% dextrose
- Load: 8-10 ml/kg over 30 minutes
- Maintenance: 1.4 to 2.0 ml/kg/hour
- Fomepizole (Antizol)
IX. Management: Hemodialysis Indications
- Deteriorating condition despite maximal support (serious end-organ toxicity)
- Metabolic Acidosis with serum pH <7.25
- Acute Renal Failure refractory to other measures
- Serum Electrolyte imbalance refractory
- Altered Mental Status
- Fomepizole not available and Ethylene Glycol serum level >50 mg/dl
- Serum level does not otherwise indicate Dialysis
X. Management: Other measures
-
Vitamin Supplementation to shunt Ethylene Glycol metabolism to less toxic metabolites
- Pyridoxine Supplementation
- Thiamine 0.25-0.5 mg/kg up to 100 mg PO or IV daily
-
Sodium Bicarbonate
- Benefits
- Corrects Metabolic Acidosis
- Inhibits Calcium oxalate crystal deposition
- Increases Glycolic Acid excretion
- Technique
- Keep Urine pH >7.0
- Benefits
- Unhelpful measures: Gastric Decontamination (due to rapid absorption)
- Gastric Lavage is not effective
- Activated Charcoal is not effective
- Syrup of Ipecac is not effective (and never indicated in U.S.)
- Disposition
- Admit all patients requiring antidote or Hemodialysis
- Discharge at 4-6 hours after ingestion if normal serum bicarbonate and normal osmol gap
XI. Prognosis
- Fatal if severe case (large ingestion) not treated within 24-36 hours
XII. References
- Leiken (1995) Poisoning and Toxicology, p. 925-6
- Nordt and Swadron in Herbert (2013) EM:Rap 13(12): 3
- Rodriguez (2022) Crit Dec Emerg Med 36(4): 26-31
- Tomaszewski (2019) Crit Dec Emerg Med 33(6):28
- Barceloux (1999) J Toxicol Clin Toxicol 37:537-60 [PubMed]
- Scalley (2002) Am Fam Physician 66(5):807-12 [PubMed]
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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 |
Russian | ETILENGLIKOL', ЭТИЛЕНГЛИКОЛЬ |
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: Ethylene glycol poisoning (disorder) (C0413194)
Concepts | Injury or Poisoning (T037) |
SnomedCT | 426692001, 7759006 |
English | Antifreeze caus toxic effect, Antifreeze causing toxic effect, Ethylene glycol poisoning, Ethylene glycol poisoning (disorder), ethylene glycol poisoning, ethylene glycol toxicity, anti-freeze poisoning, anti freeze poisoning |
Spanish | intoxicación por etilenglicol, intoxicación por etilenglicol (trastorno), intoxicación por anticongelante |
Ontology: Antifreeze (C0598248)
Concepts | Substance (T167) |
SnomedCT | 311922005 |
English | Antifreeze, antifreeze, Antifreeze (substance) |
Spanish | anticongelante (sustancia), anticongelante |
Ontology: Poisoning by antifreeze containing ethylene glycol (C3671905)
Concepts | Injury or Poisoning (T037) |
SnomedCT | 282391000009104 |
English | Ethylene glycol antifreeze intoxication, Poisoning by antifreeze containing ethylene glycol (disorder), Poisoning by antifreeze containing ethylene glycol |