Ethylene glycol (EG) toxicity is a life-threatening emergency that is particularly devastating in cats due to their extreme sensitivity to this compound.
Overview and Clinical Importance
Ethylene glycol (EG) toxicity is a life-threatening emergency that is particularly devastating in cats due to their extreme sensitivity to this compound. Ethylene glycol is a colorless, odorless, sweet-tasting liquid found in antifreeze (up to 95% concentration), engine coolants, hydraulic brake fluids, and various household products. Cats are the most susceptible domestic species, with a minimum lethal dose of only 1.4 mL/kg of undiluted ethylene glycol–less than a teaspoon can be fatal to an average cat. This is compared to 4.4-6.6 mL/kg in dogs. The sweet taste makes it palatable to animals, and cats may also be exposed through cutaneous absorption during grooming after walking through spilled antifreeze.
The toxicity of ethylene glycol lies not in the parent compound itself, but in its toxic metabolites formed through hepatic metabolism via alcohol dehydrogenase (ADH). These metabolites cause severe metabolic acidosis and irreversible acute kidney injury through calcium oxalate crystal deposition in the renal tubules. Feline mortality rates may reach 97% without early intervention, making rapid diagnosis and treatment critical for survival.
High-YieldFor the NAVLE, remember that cats are MORE sensitive than dogs to ethylene glycol (minimum lethal dose 1.4 mL/kg vs 4.4-6.6 mL/kg in dogs), and treatment must begin within 3 HOURS of ingestion in cats to be effective, compared to 8-12 hours in dogs.
| Metabolite |
Enzyme |
Clinical Significance |
| Ethylene Glycol |
Parent compound |
Causes CNS depression (alcohol-like), increases serum osmolality |
| Glycoaldehyde |
Alcohol dehydrogenase (ADH) |
First toxic metabolite; contributes to early CNS depression |
| Glycolic Acid |
Aldehyde dehydrogenase |
PRIMARY cause of metabolic acidosis; accumulates due to slow conversion to glyoxylic acid |
| Glyoxylic Acid |
Glycolate oxidase |
Rapidly metabolized; nephrotoxic |
| Oxalic Acid |
Multiple pathways |
Binds calcium forming calcium oxalate crystals; causes hypocalcemia and renal tubular damage |
Pathophysiology and Metabolism
Ethylene Glycol Metabolism
Ethylene glycol itself has relatively low toxicity. The severe clinical effects result from its hepatic metabolism through a series of oxidation reactions. Understanding this metabolic pathway is essential for both diagnosis and treatment.
Metabolic Pathway
NAVLE TipThe key to treatment is blocking ALCOHOL DEHYDROGENASE (ADH), the rate-limiting enzyme. Both fomepizole and ethanol work by preventing EG metabolism to toxic metabolites. Treatment must occur BEFORE significant metabolism has occurred.
Mechanism of Renal Injury
Calcium oxalate crystal formation is the hallmark of ethylene glycol toxicity. Oxalic acid binds with serum calcium, causing ionized hypocalcemia. The resulting calcium oxalate is excreted via glomerular filtration. As the filtrate becomes concentrated in the renal tubules and pH decreases, calcium oxalate crystals precipitate within the tubular lumens and epithelial cells, causing direct cytotoxicity and acute tubular necrosis.
| Phase/Timing |
Clinical Signs |
Pathophysiology |
| Phase I
(0.5-12 hours) |
CNS/GI Phase:
Vomiting, ataxia, depression, stupor, knuckling, decreased proprioception, hypothermia, polydipsia (RARE in cats), polyuria |
Unmetabolized EG causes alcohol-like intoxication; GI irritation; osmotic diuresis |
| Phase II
(12-24 hours in cats) |
Cardiopulmonary Phase:
Tachycardia, tachypnea, pulmonary edema, transient clinical improvement followed by deterioration |
Severe metabolic acidosis from glycolic acid accumulation; cardiopulmonary compensation |
| Phase III
(12-24+ hours in cats) |
Renal Phase:
Oliguria progressing to anuria, azotemia, enlarged/painful kidneys, oral ulcers, salivation, anorexia, lethargy, seizures, coma, death |
Calcium oxalate crystal deposition in renal tubules; acute tubular necrosis; irreversible AKI |
Clinical Presentation: Three Phases
Clinical signs of ethylene glycol toxicosis progress through three distinct phases. In cats, the clinical course is more rapid than in dogs, and phases may overlap significantly.
High-YieldUnlike dogs, CATS DO NOT typically show polydipsia as a clinical sign. The absence of polydipsia should NOT rule out EG toxicity in feline patients. Additionally, note that Phase II and III occur EARLIER in cats (12-24 hours) compared to dogs (36-72 hours for Phase III).
| Test |
Finding |
Clinical Significance |
| Anion Gap |
INCREASED (greater than 25 mEq/L) |
Due to glycolic acid accumulation; develops within 1-3 hours of ingestion |
| Osmolal Gap |
INCREASED (greater than 10 mOsm/kg) |
Due to unmetabolized EG; present early but normalizes as EG is metabolized |
| Blood pH |
DECREASED (less than 7.3) |
Metabolic acidosis; severe acidosis indicates poor prognosis |
| Bicarbonate |
DECREASED (less than 12 mEq/L) |
Consumed buffering metabolic acids; indicates severity of acidosis |
| Ionized Calcium |
DECREASED (hypocalcemia) |
Calcium bound by oxalate; present in more than 50% of cats; may cause cardiac arrhythmias |
| BUN/Creatinine |
INCREASED (azotemia) |
Indicates acute kidney injury; azotemia at presentation is a GRAVE prognostic indicator |
| Glucose |
Variable (often INCREASED) |
Hyperglycemia common; hypoglycemia may occur during ethanol treatment |
Diagnosis
Diagnosis of ethylene glycol toxicity is based on history of exposure (if known), clinical signs, and characteristic laboratory findings. A high index of suspicion is critical, especially in cats presenting with acute neurologic signs or acute kidney injury of unknown cause.
Laboratory Findings
Urinalysis Findings
Calcium oxalate crystalluria is a hallmark finding but may appear as early as 3 hours post-ingestion in cats (6 hours in dogs). Two crystal types may be observed:
Additional urinalysis findings: Isosthenuria or minimally concentrated urine, acidic pH (less than 6), proteinuria, hematuria, glycosuria, and albuminuria.
Ethylene Glycol Testing
Point-of-care EG test kits can detect blood EG levels within 30 minutes of ingestion. However, these tests have a detection limit of greater than 50 mg/dL, which is problematic for cats. Cats can be intoxicated with levels as low as 20 mg/dL–meaning an exposed cat may have a FALSE NEGATIVE result. Test within 1-10 hours post-ingestion. Cross-reactivity with propylene glycol and glycerol may cause false positives.
NAVLE TipA NEGATIVE EG test kit result in a cat does NOT rule out EG toxicity due to the high detection limit relative to the feline toxic threshold. Treatment should be initiated based on clinical suspicion if consistent findings are present.
Wood's Lamp Examination
Some antifreeze formulations contain fluorescein, which may cause urine or vomitus to fluoresce under UV light. This finding is NOT RELIABLE for diagnosis, as not all antifreeze products contain fluorescein, and false positives can occur.
| Crystal Type |
Morphology |
Significance |
| Calcium Oxalate Monohydrate (Whewellite) |
Picket-fence, spindle, dumbbell, or hemp seed-shaped; flat elongated hexagons |
MORE SPECIFIC for EG toxicity; not seen in normal urine; birefringent under polarized light |
| Calcium Oxalate Dihydrate (Weddellite) |
Envelope or octahedral shape; square with crossed lines |
Less specific; can be seen in normal urine or with hypercalciuria; common storage artifact |
Treatment
Treatment goals are to: (1) prevent further absorption, (2) prevent metabolism to toxic metabolites by inhibiting alcohol dehydrogenase, (3) enhance excretion, and (4) provide supportive care. TIME IS CRITICAL–in cats, treatment must be initiated within 3 hours of ingestion to be effective.
Decontamination
Due to rapid GI absorption (peak levels 1-4 hours), decontamination is only useful within 1-2 hours of ingestion. Emesis induction or gastric lavage may be attempted if no neurologic signs are present. Activated charcoal is NOT effective for ethylene glycol as aliphatic alcohols are poorly adsorbed.
Antidote Therapy: ADH Inhibitors
High-YieldCats require HIGHER doses of fomepizole than dogs (125 mg/kg vs 20 mg/kg) because feline alcohol dehydrogenase is less effectively inhibited by fomepizole. This is EXTRA-LABEL use in cats.
Supportive Care
Memory Aid
"CATS ARE SWEET but EG is NOT"
- Crystalluria (calcium oxalate) - appears within 3 hours
- Acidosis (high anion gap metabolic)
- Three hours is treatment window
- Sensitivity is HIGHER than dogs (1.4 mL/kg lethal)
- SWEET taste attracts animals; 97% mortality without treatment
Fomepizole Dosing: "125, then quarter at 12s"
125 mg/kg initial, then 31.25 mg/kg (approximately 1/4 of initial) at 12, 24, and 36 hours
| Antidote |
Feline Dosage |
Notes |
| Fomepizole (4-MP) |
Loading: 125 mg/kg IV
Maintenance: 31.25 mg/kg IV at 12, 24, and 36 hours |
PREFERRED in cats; higher dose than dogs (feline ADH less effectively inhibited); mild sedation may occur; effective if started within 3 hours |
| Ethanol (20%) |
Bolus: 5 mL/kg IV q6h x 5 doses
Then: 5 mL/kg IV q8h x 4 doses |
Alternative if fomepizole unavailable; causes CNS depression, hypoglycemia; requires intensive monitoring; dilute in IV fluids |
| Ethanol (30% CRI) |
Bolus: 1.3 mL/kg IV
CRI: 0.42 mL/kg/hr x 48 hours |
Alternative CRI protocol; easier monitoring; maintain target blood ethanol 100-150 mg/dL |
Prognosis
Prognosis depends on the amount ingested, time to treatment, and presence of azotemia at presentation. Feline mortality rates approach 97% without treatment. Even with aggressive therapy, outcomes are often poor if treatment is delayed.
NAVLE TipOnce oliguric or anuric AKI has developed, inhibition of alcohol dehydrogenase is of little benefit because almost all EG has already been metabolized to toxic metabolites. At this stage, only hemodialysis or renal transplantation can be considered, and prognosis is grave.
| Intervention |
Details |
| IV Fluid Therapy |
Aggressive fluid diuresis with isotonic alkalinizing crystalloids (LRS); correct dehydration; maintain urine output; reassess fluid rates frequently |
| Sodium Bicarbonate |
For severe acidosis (pH less than 7.2, HCO3 less than 12 mEq/L); slow IV administration; monitor bicarbonate q4-6h; target urine pH 7.0-7.5 |
| Calcium Gluconate 10% |
CATS: 94-140 mg/kg (0.94-1.4 mL/kg) IV over 20-30 minutes; continuous ECG monitoring during administration; NOT routine–only if symptomatic hypocalcemia |
| Dextrose Supplementation |
2.5-5% dextrose in IV fluids; monitor blood glucose q4-6h; especially important during ethanol therapy |
| Urine Output Monitoring |
Place indwelling urinary catheter; oliguria = 0.5-1 mL/kg/hr; anuria = less than 0.5 mL/kg/hr; both indicate poor prognosis |
| Hemodialysis |
Removes EG and metabolites; limited availability; ideally initiated before AKI develops; consider for severe cases |
Gross and Histopathologic Findings
Post-mortem findings in cats with ethylene glycol toxicosis are characteristic and aid in confirming the diagnosis.
- Kidneys: Enlarged, pale, swollen; may have streaky cortical pallor; painful on palpation in live animals
- Renal histopathology: Acute tubular necrosis with calcium oxalate crystals in tubular lumens and epithelial cells; crystals appear birefringent under polarized light
- Other findings: Pulmonary edema, hemorrhagic gastroenteritis; calcium oxalate crystal deposition may occur in cerebral blood vessel walls
| Good Prognosis |
Poor Prognosis |
| Treatment within 3 hours
No azotemia at presentation
Urine output maintained
Minimal crystalluria |
Treatment delayed beyond 3 hours
Azotemia at presentation
Oliguria or anuria
Severe crystalluria
Severe acidosis |