Ethylene Glycol Toxicity and Related Alcohols

What are the physical characteristics of ethylene glycol?

Colorless, odorless, synthetic liquid; sweet to bittersweet taste.

How is ethylene glycol absorbed?

Rapidly absorbed in GI tract; limited dermal/respiratory absorption.

How quickly is ethylene glycol metabolized and excreted?

Metabolized by liver in 2-4 hours; excreted by kidneys within 48 hours.

What products may contain ethylene glycol?

Antifreeze, de-icing solutions, and some brake fluids/windshield-washer fluid.

Which species are susceptible to ethylene glycol toxicity?

All species susceptible.

When were bittering agents added to ethylene glycol products?

2012.

What percentage of ethylene glycol elimination occurs in the liver?

80%.

-20% remainder excreted unchanged by livers

What is stage 1 of ethylene glycol toxicosis?

• 0.5-12 hours

• inebriation- ataxia, hypersalivation, vomiting (GI irritation and stimulates CRTZ), PU/PD, hypothermia

What is stage 2 of ethylene glycol toxicosis?

• 12-24 hours

• quiet stage- clinical signs may appear to resolve, more in dogs

• tachycardia, tachypnea, dehydration may be seen

What is stage 3 of ethylene glycol toxicosis?

• 12-24 hours (cats)

• 36-72 hours (dogs)

• severe AKI - CaOx crystalluria

• severe anorexia, dehydration, oliguria, anuria, depression, lethargy, vomiting, coma, seizures

What diagnostic tests are used to evaluate suspected ethylene glycol toxicity?

EG tests, CBC, blood gas/biochemistry, and urinalysis.

When may an ethylene glycol test produce a false negative?

If testing after 24 hours of ingestion.

When may an ethylene glycol test produce a false positive?

Ingestion of products containing propylene glycol, isopropyl alcohol, sorbitol, mannitol, and others.

What are the limitations of ethylene glycol tests?

Limited availability; not routinely performed.

What CBC findings may occur with ethylene glycol toxicity?

• Mature neutrophilia

• lymphopenia

• increased PCV/TP

• apparent thrombocytopenia

• echinocytes

• limited utility

Why may PCV and total protein increase with ethylene glycol toxicity?

Dehydration.

What are blood gas (venous)/biochem findings in ethylene glycol toxicity?

• azotemia - grave prognosis

• hyperphosphatemia

• hyperkalemia

• hyperglycemia

• hypocalcemia

• decreased bicarbonate concentrations

• increased anion gap

• hypernatremia

What normal anion gap range does the lecture list for dogs and cats?

15-25 mEq/L.

How high may the anion gap become with ethylene glycol toxicity?

>40 mEq/L.

How does anion gap increase occur with ethylene glycol toxicity?

• secondary to glycolate and oxalate metabolites

• excess organic acids dissociate into H+ and A-

• bicarbonate binds to excess H+ leaving excess A- in the body

• results in metabolic acidosis

Why is the anion gap usually positive?

Unmeasured anions are more abundant than unmeasured cations.

How does the body compensate as bicarbonate decreases during metabolic acidosis?

CO2 decreases by hyperventilation.

How does increased intracellular calcium affect cardiac output during metabolic acidosis?

Decreased cardiac output.

How does movement of H+ into cells contribute to hyperkalemia?

It shifts K+ into the extracellular space, causing cardiac arrhythmia

How does acidosis affect the response to epinephrine and other vasopressors?

Reduces heart and blood vessel response to epinephrine and other vasopressors, causing hypotension and vasodilation.

What urinalysis findings may occur with ethylene glycol toxicity?

Isosthenuria, aciduria, hematuria, proteinuria, and glucosuria.

What cells, casts, and crystals may appear in urine with ethylene glycol toxicity?

Epithelial cells, casts, calcium oxalate monohydrate/some dihydrate crystals, and hippuric acid crystals.

What is one of the end products of ethylene glycol metabolism?

Oxalate

Why does ethylene glycol toxicity cause hypocalcemia?

Oxalate in the blood binds to Ca2+, resulting in calcium oxalate crystals in the kidneys and urine

How do calcium oxalate crystals damage the kidneys?

Cause acute tubular necrosis, resulting in urinary casts and severe azotemia.

What findings support a diagnosis of ethylene glycol toxicity?

• Exposure history

• physical exam findings

• clin path findings

  • increased AG/metabolic acidosis, azotemia, hypocalcemia, and CaOx crystalluria

• adjunct tests

What are differential diagnoses for ethylene glycol toxicity?

• Other toxic alcohols

• vitamin D toxicosis

• DKA

• mushrooms

• ivermectin

• NSAIDs

• CKD

What are the three main treatment goals for ethylene glycol toxicity?

• Decontaminate

• prevent metabolism to toxic metabolites

• provide supportive care

When may early emesis and gastric lavage be useful with ethylene glycol toxicity?

Within 1-2 hours post-ingestion

What is another name for fomepizole?

4-methylpyrazole, or 4-MP.

What is the antidote for EG toxicity?

Fomepizaole

-competitive inhibitor of alcohol dehydrogenase

What treatment window is fomepizole effective in dogs and cats?

• dogs: 8-12 hours

• cats: 3 hours

What dosing pattern is required for fomepizole?

Loading dose and repeat doses.

What side effects of fomepizole are listed in the lecture?

Anaphylaxis to second dose, CNS depression, tachypnea, hypersalivation, trembling, and osmotic diuresis.

How does ethanol treat ethylene glycol toxicity?

Competes for metabolism by alcohol dehydrogenase enzyme

-use clear, non-flavored, high concentration/proof alcohol

-alcohol proof is 2x the percentage of alcohol

what are the two different methods of using ethanol IV?

CRI and alternative

What adverse effects of ethanol treatment are listed?

CNS depression, ataxia, metabolic acidosis, hypoglycemia, bradycardia, hypoventilation, and hypothermia.

Supportive care for EG toxicity

• IVF therapy

• gastroprotectants

• anti-nausea/emetic meds

• monitor water intake and urine output

examples of other toxic alcohols: propylene glycol

• antifreeze, disinfectants, food coloring

• lactic acid

• stages 1-2, HB anemia

examples of other toxic alcohols: methanol

• paints, cleaners, perfumes

• formic acid- cumulative

• stages 1-2, retina toxicity

examples of other toxic alcohols: benzyl alcohol

• historic preservative

• benzoic and hippuric acids

• stages 1-2(3)

examples of other toxic alcohols: diethylene glycol

• brake fluid, ink, lacquers

• acetic acid

• stages 1-3

examples of other toxic alcohols: isopropanol

• rubbing alcohol

• acetone

• stages 1-2