ETHYLENE GLYCOL TOXICITY IN CATS

VetSuite Veterinarians
Critical Care & Emergency Medicine - Toxicology

Ethylene glycol toxicosis primarily occurs after ingestion of antifreeze. Although ethylene glycol itself is toxic, it is the metabolites of ethylene glycol that cause renal failure. Oxalic acid is the metabolite associated with renal failure. Unfortunately, many owners do not realize that their pet has consumed ethylene glycol and first become aware of the problem when the pet shows signs of renal failure such as loss of appetite, lethargy and vomiting. These signs may show up 2 to 5 days after ingestion. Treatment often is futile after severe kidney failure has developed.

DIAGNOSIS OF ETHYLENE GLYCOL TOXICITY

ETIOLOGY AND RISK FACTORS

• Causes - Potential sources of ethylene glycol in the environment include antifreeze (the most common source of ethylene glycol poisoning), air-conditioning coolants, brake fluid, heat exchange fluids from solar collectors and fluids used in color film processing. Cats that roam outside unsupervised are more likely to encounter ethylene glycol in antifreeze, which has been disposed of improperly. Cats may ingest antifreeze as they drink water from contaminated puddles.
  
  Despite a lower incidence of poisoning, cats are more susceptible to ethylene glycol poisoning than dogs. The minimum lethal dose for a cat is 1.5 milliliters of antifreeze per kilogram of body weight. Therefore, a teaspoonful can be lethal for a 7-pound cat.
• Risk factors
• Age - Any age cat can ingest ethylene glycol
• Breed/genetics - No known risk
• Sex - No known risk
• Geographic/environmental - Cats allowed to roam or those that have access to places where ethylene glycol products are stored are at a higher risk.
• Other medical disorders - Animals with underlying renal insufficiency are more susceptible to poisoning and require less ethylene glycol to induce fatal renal failure.

• Prevention - The mainstay of prevention is to keep containers of ethylene glycol tightly closed and out of the "reach" of pets. Owners should be instructed to clean up spills immediately and thoroughly. Antifreeze products are now on the market that do not contain ethylene glycol (Prestone LowTox®, Sierra®). Although these propylene glycol containing products are not associated with the renal failure of oxalic acid, they may cause the CNS depression of short chain alcohols and may induce oxidative damage to red cells.

HISTORY AND CLINICAL SIGNS

• Species affected - Dog and cat
• Presenting signs and historical problems - Animals that ingest potentially toxic doses of ethylene glycol first appear "drunk" (loss of proprioception, CNS depression), then acidotic and then have the GI signs of renal failure. Ethylene glycol may cause severe kidney failure with almost complete cessation of urine output. Ethylene glycol poisoning can be fatal if not treated within 3 hours after ingestion.
  
  The most common early symptoms of ethylene glycol poisoning are nausea, vomiting, lethargy and incoordination progressing to coma. Most cats are profoundly depressed and most do not show polydipsia as is common in dogs. The animal may act as if it is drunk. These signs develop within 30 minutes to 12 hours after ingestion of ethylene glycol depending on the amount ingested.

PHYSICAL EXAMINATION FINDINGS

• General
• Attitude - Mental status will vary from lethargic to comatose. Most cats are profoundly depressed.
• Body condition - The body condition is often normal.
• Vital signs - Depending on the stage of toxicity, the vitals signs may be normal. In later stages, the animal may be hypothermic with slow shallow respirations.
• Mucous membranes - In later stages of toxicity, the mucous membranes may be tacky due to dehydration.
• Hydration status - Many pets are dehydrated on presentation.
• Head and neck - Unremarkable
• Eyes - Unremarkable
• Oral cavity - Dehydration results in tacky mucous membranes. The remainder of the oral cavity is unremarkable.
• Thorax (cardio-pulmonary) - Usually unremarkable but in later stages (metabolic acidosis), the breath sounds are normal but the respirations may be slow and shallow.
• Abdomen (gastrointestinal/urinary) - The kidneys may be enlarged and painful, especially 12 to 14 hours after ingestion of ethylene glycol.
• Reproductive system - Unremarkable
• Lymph nodes - Unremarkable
• Integumentary system - Skin turgor may be significantly decreased, indicating dehydration.
• Neurologic examination - Mental status is often affected and many cats are profoundly depressed. Seizures may also occur, either due to very high levels of glycoaldehyde or from severe metabolic acidosis.
• Musculoskeletal examination - Unremarkable

DIAGNOSTIC STUDIES

• Special examination techniques
• An ethylene glycol blood test should be performed as soon after ingestion as possible. The test detects glycols and is much less sensitive to the metabolites. For this reason, the test is considered accurate only if performed within 6 to 12 hours of ingestion. In cats, false negatives are more likely than in dogs. The ethylene glycol test will be positive if a certain amount of ethylene glycol is present in the blood. Since cats only need 1.5 mls of ethylene glycol per kilogram to result in toxicity, there may not be enough ethylene glycol in the circulation to result in a positive test. Unfortunately, it also reacts to propylene glycol and glycerol so false positives are possible. Serum osmolality may be required if ethylene glycol toxicity is suspected but cannot be confirmed with the ethylene glycol test.
• Blood gas analysis is recommended to evaluate for the presence of severe acidosis.
• Clinical laboratory tests
• CBC - The hematocrit is often elevated due to dehydration. Stress leukogram (neutrophilia with left shift) is also common.
• Serum biochemical tests - Biochemical tests may indicate any of the following:
  ↑ Serum osmolality
  ↓ Calcium
  ↑ Creatinine
  ↑ Phosphorus
  ↓ Total carbon dioxide
  ↓ Bicarbonate
  ↓ Blood pH
  ↑ Glucose
  ↑ Potassium
  ↑ Total protein
  
  Abnormal kidney function tests can be observed if acute kidney failure has developed. Without treatment oliguric renal failure often occurs between 12 to 14 hours after ingestion of ethylene glycol. Anuria occurs 72 to 96 hours after ingestion depending on the amount of ethylene glycol ingested.
• Urinalysis - Urinalysis is recommended. Calcium oxalate crystals may help confirm the diagnosis of ethylene glycol intoxication but be aware that calcium oxalate crystals are found in the urine of normal animals. Finding these crystals in the urine is not diagnostic.
• Diagnostic imaging
• Radiographs (thoracic/abdominal) - An ultrasound and ultrasound-guided kidney biopsy may be performed for diagnosis if the pet is presented in kidney failure. The ultrasound examination typically shows very "bright" kidneys with ethylene glycol poisoning.
• Pathology
• Biopsy/histopathology - A biopsy may be performed to confirm the diagnosis of acute kidney failure due to ethylene glycol poisoning because of the extensive treatment required and the poor prognosis.

DIAGNOSIS AND PROGNOSIS

• Differential diagnosis - Ethylene glycol toxicity is a life-threatening condition. The symptoms of ethylene glycol poisoning however are not specific for this disorder. Other diseases may result in symptoms similar to those observed in ethylene glycol toxicity. Examples of some disorders that may have similar symptoms include:
• Garbage ingestion can cause vomiting, diarrhea and nervous system symptoms especially if the garbage contains mold.
• Acute pancreatitis also causes vomiting, severe lethargy and, rarely, nervous system symptoms.
• Severe gastroenteritis or intestinal tract obstruction can cause vomiting, lethargy, and progressive deterioration of the pet.
• Acute kidney failure may result from other types of toxins, trauma and infection.
• Recommended tests
• Ethylene glycol blood test
• Serum biochemical tests
• Urinalysis
• Serum Osmolality
• Summary of diagnostic criteria - If tested early, the ethylene glycol test may be positive. Serum osmolality will often reveal an increase osmolality. Serum biochemical tests may reveal renal failure, depending on the length of time from ingestion to blood draw.
• Prognosis - Therapy may be successful if the pet is presented to the veterinarian within three hours of ingestion of ethylene glycol and before kidney damage has occurred. With very aggressive treatment such pets may not develop kidney failure and may be discharged after a few days of intensive treatment.
  
  If kidney failure is already present the prognosis for recovery is grave. Treatment is difficult and hospitalization may extend for weeks. Most pets with severe acute kidney failure due to ethylene glycol poisoning die despite intensive treatment.

TREATMENT OF ETHYLENE GLYCOL TOXICITY

TREATMENT PRINCIPLES

The goal of treatment is to prevent additional absorption, prevent metabolite formation, and enhance excretion of ethylene glycol.

INITIAL/HOSPITAL THERAPY

• Prevent additional absorption:
• Induction of vomiting or gastric lavage is indicated if the pet is seen within a few hours of ethylene glycol ingestion.
• Activated charcoal can be administered via a stomach tube or by syringe to help prevent further absorption of ethylene glycol from the digestive tract. Whether or not this is effective is debatable.
• Prevent metabolism:
• Ethylene glycol is metabolized by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase. If ADH can be inhibited, or a substance given that has a higher affinity to ADH than ethylene glycol, ethylene glycol metabolism can be reduced. The two most commonly used drugs to prevent ethylene glycol metabolism are 4-methylpyrazole and ethanol. Unfortunately, 4-MP is not recommended in cats and ethanol must be used within 3 hours after ingestion for a positive outcome. Treatment requires at least 2 days.
• Twenty percent ethanol (ethyl alcohol) is the most commonly used in cats. There are two primary doses of ethanol, repeated doses and constant rate infusion. Both methods produce nervous system signs of drunkenness.
• For the repeated dose method, 20 percent ethanol is dosed at 5 ml/kg IV every 6 hours for 5 treatments. Then, 5 ml/kg is given IV every 8 hours for 4 more treatments.
• The constant rate infusion of 20 percent ethanol is dosed at 1.35 ml/kg/hour for 60 hours. Cats need higher concentrations administered for a longer time when compared to dogs.
• Treatment with sodium bicarbonate may be required if the pet has severe acidosis. If the pH is less than 7.2, consider treating with 6.2 mEq/kg every 4 to 6 hours.
• Thiamine may be administered as an adjunctive treatment.
• Enhance excretion:
• Fluids are administered intravenously to correct dehydration resulting from vomiting and to help prevent damage to the kidneys. Intravenous fluids often are continued 24 to 48 hours after treatment with ethanol has been completed.
• Furosemide and dopamine are used to attempt increasing urine production when kidney failure is present. Often it is impossible to increase urine production despite intensive treatment.
• Peritoneal dialysis and hemodialysis are available for animals that have developed severe kidney failure and are not producing urine despite intravenous fluid, furosemide and dopamine administration. This treatment is very expensive and is only available at selected specialty referral hospitals. Some animals with severe kidney failure due to ethylene glycol poisoning die despite dialysis support.
• Other:
• Metoclopramide and the antihistaminic drugs cimetidine, ranitidine, and famotidione are examples of drugs that may be used to treat the gastrointestinal complications of severe kidney failure such as vomiting and gastric hyperacidity, respectively.
• If hypocalcemia seizures occur, calcium gluconate (0.5 to 1.5 ml/kg) may be administered IV. If seizures and hypocalcemia continue, calcium gluconate can be administered at 5 to 15 mg/kg/hr as a constant rate infusion. This is not used to correct hypocalcemia but should only be used to control seizures. Attempting to correct hypocalcemia may precipitate the formation of calcium oxalate crystals.
• Phosphorus binding drugs such as aluminum hydroxide may be given to bind phosphorus in the digestive tract.
• Blood transfusions and intravenous nutritional support (total or partial parenteral nutrition) may be required from animals that survive yet have prolonged hospitalization times.

LONG-TERM/HOME THERAPY

Animals that survive and do not have renal insufficiency do not need any specific long-term treatment. Animals with lingering renal disease will need long-term therapy for chronic renal failure.

FOLLOW-UP CARE

After release from the hospital, periodic blood tests to determine renal function are recommended. Initially, recheck renal values 5 to 7 days after release. Based on results, additional tests may be necessary or the pet may just need to be monitored at home.