Stage 3—Oliguric renal failure
This stage can be seen as early as 12 hours, especially in cats, but generally within 24-72 hours following exposure. Clinical
signs may include azotemia, depression, anorexia, vomiting, abdominal pain, oral ulcers, and oliguria progressing to anuria.
Laboratory findings may include low urine specific gravity, glucosuria and calcium oxalate crystals may be visualized in the
urine (absence of crystalluria does NOT rule out the possibility of EG toxicosis). Seizures are possible.
Clinical pathologic abnormalities include increased osmolal gap and anion gap, hyperglycemia, hyperkalemia, decreased blood
pH, and hypocalcemia. BUN and creatinine become elevated but usually not before 12 hours post exposure; therefore BUN and
creatinine are of minimal benefit in diagnosing early exposures.
Diagnosis is based on history, clinical signs, and confirmatory laboratory testing. In dogs, the PRN ethylene glycol test
kit can be an invaluable aid to determine whether an exposure is significant enough to warrant treatment. It is important
to remember that some forms of activated charcoal and most diazepam injectable products contain propylene glycol that may
interfere with the interpretation of the test. For this reason blood for testing should be taken prior to administration of
propylene glycol-containing activated charcoal (check the label) or diazepam. Other products that may cause false positives
for the test are glycerol, sorbitol, mannitol, metaldehyde, formaldehyde and Bailey's Irish cream liqueur. Other alcohols
such as ethanol, methanol or isopropanol will not interfere with the test. It is generally recommended that the test be run
an hour or more following ingestion, as this is when blood levels should be sufficient to get reliable test results. The test
will detect blood levels of 50 mg/dL or more. Cats are much more sensitive to ethylene glycol and may show signs at levels
well below the PRN test kit's level of detection. So for cats, while a positive test result is significant, a negative test
result does not rule out the potential for toxicosis.
A newer ethylene glycol test has recently been put on the market. This test, produced by Kacey, Inc. uses a test strip onto
which a drop of plasma is deposited and a color change indicates whether the sample contains ethylene glycol. Advantages to
this test include ease of use, short time to finish (8 minutes), and separate indicator pads for cats (measuring > 20 mg/dL)
and dogs (measuring >50 mg/gL). The increased sensitivity of this test makes it a reasonable test to use in cats. Disadvantages
of the test as it currently exists include false positive with the same agents that give a false positive on the PRN test
(see above) as well as false positive with any alcohol (methanol, ethanol, etc). Also since the color change involves green
dyes, people with red-green color blindness might not be able to distinguish color changes.
Other means of diagnosing ethylene glycol exposure in pets include having levels run at a human hospital on a STAT basis.
Many human hospitals are willing to do this, although sometimes it takes talking to the laboratory technician rather than
a receptionist. Levels of 50 mg/dl (or 5 μg/ml, be sure to check the units reported) or greater in dogs would be considered
significant. In cats, any level above zero should be considered significant, as toxic blood levels have not been determined.
Measuring anion gap (>25 mEq/L) or serum osmolality (> 20 mOsm/kg) may assist in diagnosing ethylene glycol toxicosis. Observation,
via Wood's lamp, of fluorescence in urine, stomach contents or on paws/muzzle may suggest exposure (fluorescein dye is added
to automotive antifreeze to help in detecting radiator leaks).
Treatment of ethylene glycol toxicosis must be timely and aggressive. Failure to institute appropriate therapy within the
first several hours may result in irreversible renal damage or death of the animal. For recent (within 45 minutes) exposures
and asymptomatic animals, induce vomiting or perform gastric lavage; because food in the stomach may slow absorption, emesis
or lavage may be of benefit up to 1 hour in animals that have recently eaten. The use of activated charcoal is somewhat controversial,
as aliphatic alcohols are not thought to be well adsorbed by charcoal, but many clinicians routinely use activated charcoal
in ethylene glycol exposures. Based on exposure history and/or diagnostic test results, the use of either fomepizole or ethanol
infusion (see below) may be indicated.
Symptomatic animals should be stabilized as needed. Seizures can be controlled with diazepam or barbiturates, but care must
be taken to minimize any further CNS depression. Intravenous fluids are the cornerstone of treatment, especially in symptomatic
animals. High infusion rates of crystalloids are necessary to correct dehydration and hypoperfusion; fluid ins and outs should
be monitored to avoid fluid overload and possibly pulmonary edema. Treatment of acidosis and renal failure may be required.
Oliguric or anuric animals may require peritoneal dialysis.
Intravenous ethanol and, more recently fomepizole (4-MP, 4-methylpyrazole, Antizol-Vet™), have been used successfully in the
management of ethylene glycol toxicosis in animals and man. The primary goal of using these compounds is to delay the breakdown
of ethylene glycol to its more toxic metabolites, allowing the parent compound to be excreted in the urine unchanged. Best
results with either of these treatments require initiation of treatment as soon as possible following ingestion, preferably
within the first 6-8 hours.
Ethanol has the advantages of being inexpensive and readily available, but it has some serious drawbacks, including worsening
of metabolic acidosis and CNS depression, making evaluation of the degree of ethylene glycol toxicosis difficult. Additionally,
ethanol treatments are time-intensive and require constant patient monitoring because of the severe side effects. Ethanol
can be used in both cats and dogs. The preferred treatment regime would be to administer 8.6 ml/kg (600 mg/kg) of a 7% (70
mg/ml) ethanol solution and then maintain at 1.43 ml/kg/hr (100 mg/kg/hour), up to 200 mg/kg/hr as a constant rate infusion.
The animal must be constantly monitored and the dosage adjusted to prevent severe respiratory depression and acidosis. The
other method of ethylene glycol treatment would be to make a 20% ethanol solution. Dogs are given 5.5 ml/kg every 4 hours
for 5 treatments then every 6 hours for 4 treatments. Cats are given 5.0 ml/kg every 6 hours for 5 treatments, then every
8 hours for 4 treatments.
Fomepizole will not cause hyperosmolality or metabolic acidosis. In contrast to ethanol, which is administered every 4 hours
or as a constant-rate infusion, fomepizole is administered every 12 hours for 36 hours. The initial dosage in dogs is 20 mg/kg
(slow IV over 15-30 minutes), then 15mg/kg (slow IV) at 12 and 24 hours, and then 5mg/kg is given at 36 hours. Fomepizole
is not expected to cause sedation in dogs. The main drawbacks with fomepizole are the cost of the medication and the fact
that fomepizole is only useful in cats if given within 3 hours of exposure. In cats, the dosage is 125 mg/kg initially, followed
by 31.25 mg/kg at 12, 24 and 36 hours. This protocol is based on a study on three cats. Sedation is expected with this protocol
Treatment should be continued until the patient is clinically normal and has had at least 24 hours with normal renal function
and acid base parameters. Alternatively, for dogs, a negative ethylene glycol test indicates that ethanol/fomepizole treatment
may be discontinued (although other treatment may need to be continued for any residual renal impairment). The prognosis for
recovery depends on degree of exposure, length of time between exposure and treatment, and aggressiveness of treatment. Surviving
animals may fully recover or may have residual renal insufficiency requiring lifetime maintenance. The presence of oliguria/anuria
indicates a grave prognosis.