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Basics ⬇

Basics

Definition

Results primarily from ingesting substances containing ethylene glycol (e.g., antifreeze). Rarely from other products.

Pathophysiology

  • Ethylene glycol-rapidly absorbed from the gastrointestinal tract; food in the stomach delays absorption.
  • Toxicity-initially causes CNS depression, ataxia, gastrointestinal irritation, and polyuria or polydipsia; rapidly metabolized in the liver by alcohol dehydrogenase to glycoaldehyde, glycolic acid; glyoxalic acid, and oxalic acid; leads to severe metabolic acidosis and renal epithelial damage.
  • Minimum lethal dosage-cats, 1.4 mL/kg; dogs, 6.6 mL/kg.

Systems Affected

  • Gastrointestinal-irritated mucosa.
  • Nervous-inebriation from ethylene glycol and glycoaldehyde owing to inhibition of respiration, glucose metabolism, and serotonin metabolism and alteration of amine concentrations.
  • Renal/Urologic-initially, osmotic diuresis; later, metabolites, especially calcium oxalate monohydrate crystals, are directly cytotoxic to renal tubular epithelium, resulting in renal failure. The mechanism of toxicity is now thought to involve attachment of oxalate to cell plasma membrane, activation of enzyme activity, and production of free radicals and lipid peroxidation, leading to cell necrosis.

Incidence/Prevalence

  • Common in small animals.
  • Highest fatality rate of all poisons; fatality rates higher for cats than dogs.
  • Incidence similar in cats and dogs.

Geographic Distribution

Higher incidence in colder areas where antifreeze is more commonly used.

Signalment

Species

Dogs, cats, and many other species, including birds

Mean Age and Range

  • Any age susceptible (3 months–13 years)
  • Mean, 3 years

Signs

General Comments

  • Dose-dependent.
  • Almost always acute.
  • Caused by unmetabolized ethylene glycol and its toxic metabolites (frequently fatal).

Physical Examination Findings

  • Early-from 30 minutes to 12 hours post-ingestion in dogs; nausea and vomiting; mild to severe depression; ataxia and knuckling; muscle fasciculations; nystagmus; head tremors; decreased withdrawal reflexes and righting ability; polyuria and polydipsia.
  • Dogs-with increasing depression, patient drinks less but polyuria continues, resulting in dehydration; CNS signs abate transiently after approximately 12 hours, but recur later.
  • Cats-usually remain markedly depressed; do not exhibit polydipsia.
  • Oliguria (dogs, 36–72 hours; cats, 12–24 hours) and anuria (72–96 hours post-ingestion)-often develop if untreated.
  • May note severe hypothermia.
  • Severe lethargy or coma.
  • Seizures.
  • Anorexia.
  • Vomiting.
  • Oral ulcers.
  • Salivation.
  • Kidneys-often swollen and painful, particularly in cats.

Causes

Ingestion of ethylene glycol, the principal component (95%) of most antifreeze solutions.

Risk Factors

Access to ethylene glycol-widespread availability; somewhat pleasant taste; small minimum lethal dose; lack of public awareness of toxicity.

Diagnosis ⬆ ⬇

Diagnosis

Differential Diagnosis

  • Acute (30 minutes–12 hours post-ingestion)-ethanol, methanol, and marijuana toxicosis; ketoacidotic diabetes mellitus; pancreatitis; gastroenteritis.
  • Renal stage-acute renal failure by nephrotoxins (e.g., aminoglycoside antibiotics, amphotericin B, cancer chemotherapeutic drugs, ibuprofen, oxalate-containing plants such as philodendrons, plants of the lily family [cats], cyclosporin, grape and raisin toxicosis [causes hypercalcemia, unlike ethylene glycol toxicosis], and heavy metals); leptospirosis, tubulointerstitial nephritis; glomerular and vascular disease; renal ischemia (hypoperfusion).

CBC/Biochemistry/Urinalysis

  • PCV and total protein-often high owing to dehydration.
  • Stress leukogram-common.
  • High BUN and creatinine-dog, 36–48 hours post-ingestion; cat, 12 hours post-ingestion.
  • Hyperphosphatemia may occur transiently 3–6 hours post-ingestion, owing to phosphate rust inhibitors in the antifreeze; hyperphosphatemia is also seen with azotemia owing to decreased glomerular filtration.
  • Hyperkalemia if oliguric or anuric.
  • Hypocalcemia-occurs in approximately half of patients, owing to chelation of calcium by oxalic acid; clinical signs infrequently observed because of acidosis.
  • Hyperglycemia-occurs in approximately half of patients, owing to inhibition of glucose metabolism by aldehydes, increased epinephrine and endogenous corticosteroids, and uremia.
  • Isosthenuria-by 3 hours post-ingestion, owing to osmotic diuresis and serum hyperosmolality-induced polydipsia; continues in the later stages of toxicosis because of renal dysfunction.
  • Calcium oxalate crystalluria-consistent finding; as early as 3 hours post-ingestion in cats and 6 hours in dogs; monohydrate form is more common.
  • Urine-pH consistently decreases; inconsistent findings-hematuria; proteinuria; glucosuria; may note granular and cellular casts, WBCs, RBCs, and renal epithelial cells.

Other Laboratory Tests

Blood Gases

  • Metabolites cause severe metabolic acidosis.
  • Total CO2, plasma bicarbonate concentration, and blood pH-low by 3 hours post-ingestion; markedly low by 12 hours.
  • PCO2-decreases, owing to partial respiratory compensation.
  • Anion gap-increased by 3 hours post-ingestion; peaks at 6 hours post-ingestion; remains increased for approximately 48 hours (ethylene glycol metabolites are unmeasured anions. Glycolate, a metabolite of EG, can result in a false increase in plasma lactate, which could lead to the assumption that acidosis is due to increased lactate, rather than EG toxicosis.

Other

  • Serum osmolality and osmole gap-high by 1 hour post-ingestion, in parallel with serum ethylene glycol concentrations; dose-related; usually remain high for approximately 18 hours post-ingestion; ethylene glycol toxicosis most common cause of a high osmolal gap.
  • EG serum concentration-peaks 1–6 hours post-ingestion; usually not detectable in the serum or urine by 72 hours.
  • Commercial kits: PRN Pharmacol REACT EG measures concentrations at >50 mg/dL; estimate by multiplying the osmole gap by 6.2.
    • Test does not detect metabolites so must be used within the first few hours post-ingestion.
    • Results are available in 6 minutes but should not be read over 10 minutes.
    • Labeled for dogs and cats. Some cats may have toxicosis at levels below 50 mg/dL.
    • False-positive test results can be seen with propylene glycol, glycerol, mannitol, and sorbitol. Ethanol may combine with propylene glycol or glycerol to give a false positive.
  • Woods lamp examination of urine, face, paws, or vomitus may detect fluorescein that is sometimes added to antifreeze. This method is non-specific and may be unreliable.

Imaging

Ultrasonography-renal cortices may be hyperechoic as a result of crystals.

Diagnostic Procedures

  • Kidney biopsy-with anuria; confirm diagnosis.
  • Cytologic examination of kidney imprints-often diagnostic; numerous calcium oxalate crystals.

Pathologic Findings

  • Kidneys often swollen.
  • Post-mortem examination of kidney reveals the presence of calcium oxalate crystals in the tubules.

Treatment ⬆ ⬇

Treatment

Appropriate Health Care

  • Cats-usually inpatient.
  • Dogs-usually outpatient if <5 hours post-ingestion and treated with fomepizole; inpatient if >5 hours for intravenous fluids to correct dehydration, increase tissue perfusion, and promote diuresis.

Nursing Care

  • Goals-prevent absorption; increase excretion; prevent metabolism.
  • Induction of vomiting and gastric lavage with activated charcoal not recommended unless can be performed in first 30 minutes following ingestion due to the rapid absorption of ethylene glycol.
  • Intravenous fluids-correct dehydration, increase tissue perfusion, and promote diuresis; accompanied by bicarbonate given slowly intravenously to correct metabolic acidosis.
  • Monitor serial plasma bicarbonate concentrations-0.5 × body weight (kg) × (24 – plasma bicarbonate) = sodium bicarbonate needed (mEq).
  • Monitor urine pH in response to therapy.
  • Azotemia and oliguric renal failure (dogs)-most of the ethylene glycol has been metabolized; little benefit from inhibition of ADH; correct fluid, electrolyte, and acid-base disorders; establish diuresis; diuretics (particularly mannitol) may help; hemodialysis or peritoneal dialysis may be useful; may need extended treatment (several weeks) before renal function is re-established.

Surgical Considerations

Kidney transplantation-successfully employed in cats with ethylene glycol–induced renal failure.

Medications ⬆ ⬇

Medications

Drug(s) Of Choice

Dogs

Fomepizole (4-methyl pyrazole; Antizol-Vet)-effective and non-toxic liver ADH inhibitor; more expensive than ethanol but less intensive care required; 5% (50 mg/mL) at 20 mg/kg IV initially; then 15 mg/kg IV at 12 and 24 hours; then 5 mg/kg IV at 36 hours.

Cats

  • Fomepizole-cats must be given a higher dose of fomepizole than dogs; 125 mg/kg IV initially, then 31.25 mg/kg at 12, 24, and 36 hours.
  • Ethanol-use if fomepizole not available; 20% at 5 mL/kg diluted in fluids and given in an IV drip over 6 hours for 5 treatments; then over 8 hours for 4 more treatments.

Contraindications

Avoid drugs that cause CNS depression, including ethanol.

Precautions

  • Competitive substrates (alcohols, such as ethanol) contribute to CNS depression; monitor respiration.
  • Cats may become hypothermic; require heat.
  • Other pyrazoles-may be toxic to the marrow and liver; do not substitute for fomepizole.

Possible Interactions

  • Fomepizole-contributes slightly to CNS depression in cats; none in dogs.
  • Ethanol-contributes to CNS depression; further increases serum osmolality.

Alternative Drug(s)

  • Ethanol, propylene glycol, and 1,3-butanediol have-higher affinity for ADH than does ethylene glycol; effectively inhibit ethylene glycol metabolism; may cause CNS depression and increase serum osmolality; constant serum ethanol concentrations of 100 mg/dL will inhibit most ethylene glycol metabolism.
  • Ethanol treatment requires hospitalization, constant intravenous infusion (ethanol and fluids); continuous monitoring for respiratory and acid-base status.

Follow-Up ⬆ ⬇

Follow-Up

Patient Monitoring

BUN, creatinine, acid-base status, and urine output-monitored daily.

Prevention/Avoidance

  • Increasing client awareness of the toxicity-helps prevent exposure; earlier treatment of patients.
  • Use of antifreeze products (e.g., Sierra, Prestone LowTox) that contain propylene glycol, which is much less toxic.

Possible Complications

  • Without azotemia-usually no complications.
  • Urine concentrating ability-may be impaired with azotemia; may recover.

Expected Course and Prognosis

  • Untreated-oliguric renal failure (dogs, 36–72 hours; cats, 12–24 hours); anuria by 72–96 hours post-ingestion.
  • Dogs treated <5 hours post-ingestion-prognosis excellent with fomepizole treatment.
  • Dogs treated up to 8 hours post-ingestion-most recover.
  • Dogs treated up to 36 hours post-ingestion-may be of benefit to prevent metabolism of any remaining ethylene glycol.
  • Cats treated within 3 hours post-ingestion-prognosis good.
  • If a large quantity of EG is ingested, prognosis is poor, unless treated within 4 hours of ingestion.
  • Patients with azotemia and oliguric renal failure-prognosis poor; almost all of the ethylene glycol will have been metabolized.

Miscellaneous ⬆

Miscellaneous

Age-Related Factors

Patients <6 months of age with oliguric renal failure sometimes fully recover.

Synonyms

Antifreeze poisoning

Abbreviations

  • ADH = alcohol dehydrogenase
  • BUN = blood urea nitrogen
  • CNS = central nervous system
  • EG = ethylene glycol
  • PCV = packed cell volume
  • RBC = red blood cell
  • WBC = white blood cell

Suggested Reading

Connally HE, Thrall MA, Forney SD, et al. Safety and efficacy of 4-methylpyrazole as treatment for suspected or confirmed ethylene glycol intoxication in dogs: 107 cases (1983–1995). J Am Vet Med Assoc 1996, 209:1880–1883.

Connally HE, Thrall MA, Hamar DW. Safety and efficacy of high-dose fomepizole compared with ethanol as therapy for ethylene glycol intoxication in cats. J Vet Emerg Crit Care 2010, 20(2):191–206.

Tart KM, Powell LL. 4-Methylpyrazole as a treatment in naturally occurring ethylene glycol intoxication in cats. J Vet Emerg Crit Care 2011, 21(3):268–272.

Authors Mary Anna Thrall, Gary D. Osweiler, Gregory F. Grauer, Heather E. Connally, and Sharon M. Dial

Consulting Editor Lynn R. Hovda

Client Education Handout Available Online