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Veterinary Toxicology > Ethylene Glycol > Flashcards

Ethylene Glycol Flashcards

1
Q

What is ethylene glycol?

A

chemical found in most automotive radiator antifreeze products

  • not in all products: propylene glycol, methanol
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2
Q

What is the misconception about ethylene glycol’s taste?

A

its sweetness - manufacturers in the USA agreed to add bittering agent and its most common to see poisoning if no other water source is available, if a puppy chews through a container, or if a cat walks through a spill and grooms itself

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3
Q

How is ethylene glycol metabolized and excreted?

A

50% into toxic metabolites —> metabolic acidosis

50% unchanged in the urine

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4
Q

What causes the formation of crystals in ethylene glycol toxicity?

A

calcium in blood and urine combines with oxalic acid (metabolite) —> precipitates in kidney and contributes to renal failure

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5
Q

What are the 3 stages of ethylene glycol toxicity? What metabolites cause each?

A
  1. CNS - unmetabolized EG; ataxia, incoordination, inebriation, vomiting, PU/PD dehydration due thirst center stimulation
  2. ACIDOTIC - glycolic acid, oxalic acid; all systems affected; vomiting, depression, anorexia, tachypnea, arrhythmias, metabolic acidosis; many animals die at this stage
  3. RENAL FAILURE - oxalic acid, calcium oxalate; vomiting, anorexia, dehydration, abdominal pain
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6
Q

What is the most common way to diagnose ethylene glycol toxicity at the first stage? What do the biochemical profile, urinalysis, and Wood’s lamp test show?

A

(CNS STAGE)

ethylene glycol test kit - colorimetric assay to indicate the presence of EG in whole blood or serum

  • BIOCHEM: increased osmolarity, P may be elevated due to decreased GFR and phosphate rust inhibitors added to antifreeze
  • URINALYSIS: negative
  • WOOD’S LAMP: sodium fluorescein is sometimes present in antifreeze to detect leaks and causes the formation of fluorescent urine, vomit, or face/paws in UV light
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7
Q

What is required to get a positive test on the ethylene glycol test kit? What is unique about cats?

A

> 50 mg/dL

can ingest a lethal dose and never get a positive

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8
Q

What is the best test window for the ethylene glycol test kit? When are false negatives and positives achieved?

A

1-24 hours post exposure

  • FALSE NEGATIVE: test too early when not enough is absorbed or too late when all has been metabolized
  • FALSE POSITIVE: presence of compounds with similar structure, like propylene glycol, metaldehyde, sorbitol, or glycerol
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9
Q

Wood’s lamp:

A
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10
Q

What are the 2 principles of treatment for ethylene glycol toxicity?

A
  1. stop EG from going down its metabolic pathway to prevent the production of toxic acid metabolites
  2. force EG to be excreted unchanged in the urine, since it is less toxic and not nephrotoxic or acidotic
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11
Q

What are the 2 most common treatments for ethylene glycol toxicity?

A
  1. 4-methylpyrazole (fomepizole, Antizol-Vet) - inhibits alcohol dehydrogenase so EG cannot bind and be metabolized; 500-1000x affinity compared to ethanol
  2. ethanol - competitively inhibits ADH with 100x affinity compared to EG

use ONE, not both

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12
Q

What is the drug of choice for treating ethylene glycol toxicity in dogs?

A

4-methylpyrazole (fomepizole)

  • also effective in cats, but needs a much higher dose to inhibit ADH
  • must be administered within 5 hr in dogs and 3 hr in cats
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13
Q

Even though it is effective, why is 4-methylpyrazole (fomepizole) rarely used? What is commonly used instead?

A

manufacturer requested Antizol-Vet withdrawal because of low demand and expensive production

  • human-use fomepizole (Antizol)
  • compounded versions
  • ethanol (careful!)
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14
Q

What adverse effects are associated with 4-methylpyrazole (fomepizole)?

A

RARE - short-duration salivation and tremors + mild sedation in cats

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15
Q

Why is ethanol not commonly used to treat ethylene glycol toxicosis?

A

not as effective and much more toxic than fomepizole

  • very narrow margin of safety - amount needed to outcompete EG is very close to the lethal dose in dogs and cats
  • puts animals into a drunken stupor for 2-3 days
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16
Q

What sources of ethanol be used to treat ethylene glycol toxicity? What does proof mean? How is it administered?

A
  • medical grade from veterinary supplier (cheap in US, expensive in Canada)
  • 95% ethanol from liquor stores in US, 40% in Canada —> must be diluted to at least 20% before administration

constant rate infusion (no peaks and troughs = safer) or repeated boluses (less consistent inhibition of ADH)

17
Q

What adverse effects are associated with ethanol used to treat ethylene glycol toxicity?

A

MANY —> semi-comatose drunken state for the duration of treatment

  • CNS depression
  • respiratory depression
  • osmotic diuresis and dehydration
  • can easily progress to death —> intensive care is needed entirety of treatment
18
Q

What are 6 disadvantages to using ethanol to treat ethylene glycol toxicity?

A
  1. enhances many metabolic effects of EG
  2. CNS depressant*
  3. metabolized into acetaldehyde, which impairs glucose metabolism and is a cerebral irritant
  4. contributes to metabolic acidosis by enhancing the formation of lactic acid from pyruvate
  5. potentiates hypokalemia
  6. compounds the effects of EG-induced osmotic diuresis and serum hyperosmolality
19
Q

What do the ethylene glycol and Wood’s lamp test show at stage 2 of ethylene glycol toxicity?

A

(ACIDOTIC)

positive in most cases

positive - fluorescein

20
Q

What is seen on urinalysis by stage 2 of ethylene glycol toxicity?

A

(ACIDOTIC)

calcium oxalate crystalluria

  • monohydrate = picket fence, rods, dumbbells
  • dihydrate = square envelopes
21
Q

How is the ultrasound used to diagnose ethylene glycol toxicity by stage 2?

A

(ACIDOTIC)

precipitation of calcium oxalate crystals in the renal medullar and cortex, with a clear line between (halo effect) —> echogenicity increased

22
Q

How is the anion gap calculated? What is normal? How is it affected by ethylene glycol toxicity?

A

([Na + K]) - ([Cl + HCO3])

~8-19 mEq/L in dogs; 9-20 mEq/L in cats

elevated from 3 hr post-ingestion and the duration of the toxicosis due to the accumulation of acidic EG metabolites and the reduction of serum HCO3 (since it is used to buffer H+)

23
Q

Anion gap:

A
24
Q

How is the serum osmolarity/osmolality affected by ethylene glycol toxicosis? How is it measured? What is the normal value?

A

increases within 1 hr and remains high for more than 18 hr due to EG

osmometer = measures ALL osmotically active particles in serum, including EG and its metabolites

280-310 mOsm/L

25
Q

What is the osmolar gap? How is it calculated? What is the normal value? How is it affected by ethylene glycol toxicity?

A

difference between measured osmolarity and calculated osmolarity

[1.86(Na + K)] + (glucose/18) + (BUN/2.8) + 9 ~ 10 mOsm/L

increased to > 60 mOsm/L because EG and its metabolites are measured by the osmometer, but are not considered in the formula used to calculate osmolarity

26
Q

How can the serum ethylene glycol concentration be estimated if the osmolar gap is known?

A

multiply osmolar gap by 6.2 (MW, or 62/10)

27
Q

What should all values be converted into to calculate the osmolar gap? What units are used for electrolytes and glucose/urea?

A

[1.86(Na + K)] + (glucose/18) + (BUN/2.8) + 9

millimolar

  • electrolytes = mEq/L = mmol/L for monovalent ions
  • glucose/urea = mg/dL
28
Q

What is the difference between osmolarity and osmolality? How can osmolarity be calculated?

A

OSMOLARITY = millimoles of solute per liter of solution

OSMOLALITY = millimoles of solute per kilogram of solution

mOsm/L = (wt of substance (g/L)/MW) x number of species x 1000

29
Q

What treatment is used by stage 2 of ethylene glycol toxicity? How is it calculated?

A

too late to decontaminate —> correct acidosis and dehydration with bicarbonate fluids

bicarb replacement (mEq) = HCO3- deficit x 0.3 x BW

30
Q

Other than fluids, what antidote is used to treat stage 2 of ethylene glycol toxicity?

A

fomepizole - as long as unmetabolized EG is in the body

31
Q

What is seen on the biochemical profiles, urinalysis, ultrasound, and kidney palpation by stage 3 of ethylene glycol toxicity?

A

BIOCHEM: severe azotemia with elevated BUN and creatinine

UA: crystals seen, look like sludge

US: increased renal echogenicity with halo effect

PALP: very painful, swollen, stretched capsule

32
Q

What treatment is used for stage 3 of ethylene glycol toxicity?

A

RENAL FAILURE —> mostly supportive!

  • maintain or re-establish urine output with fluids, diuretics, or dopamine drip
  • peritoneal dialysis and hemodialysis (uncommon in vet med) for renal failure
  • too late for antidote, EG must be unmetabolized
33
Q

What does prognosis of ethylene glycol toxicity depend on? What is specifically indicative of poor prognosis?

A
  • dose ingested
  • rate of absorption —> slow when food is in GIT
  • time interval between exposure and treatment —> treat within 5 hr for dogs and 3 hr for cats

azotemic before treatment starts

Veterinary Toxicology (29 decks)

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