Lecture 14-15 Ethylene Glycol + Ethanol Mini Topic

What is the most common source of ethylene glycol?

antifreeze (94.6%)

What are less common sources of ethylene glycol?

radiator fluid, paints, lotions, heat exchange fluids, ice rink freezing equipment, snow globes (some up to 10%)

What is the most common source of ethylene glycol?

antifreeze (94.6%)

What are less common sources of ethylene glycol?

radiator fluid, paints, lotions, heat exchange fluids, ice rink freezing equipment, snow globes (some up to 10%)

True or False? Ethylene glycol has a sweet odor and is blue-green in color.

False. EG is colorless and odorless, but antifreeze may be sweet tasting and blue-green

Antifreeze, wiper fluids, boat anti-freeze may have other active ingredients other than EG like ___, ____, and ___.

propylene glycol, methanol, diethylene glycol

It is important to ask client for the ____ regarding antifreeze toxicity!

NAME

When you see CNS lethargy think of the ____.

little ol’s: ethylene glycol, methanol, ethanol, propylene glycol, isopropanol, xylitol, pentobarbital

___, ____, and ____ are RARE!

diethylene glycol, dipropylene glycol, glycol ethers

What species are susceptible to EG?

all species, particularly dogs and cat

What amount is required to cause EG toxicity in a dog and cat?

SMALL amounts

e.g. 40lb dog ~3-6 tbsp, 10lb cat 1.5 tsp

True or False? EG toxicity primarily occurs in the winter/cold seasons.

False. EG toxicity happens all year round because in addition to accidental exposures, malicious exposures.

Mortality rates with EG toxicity can be ____ because of what?

very high, due to difficulty in dx and narrow time frame to work in

In a study in dogs, within ___ hours of ingestion, save ___. In ___ hours of ingetion, save ___.

6 hrs, 100%

8 hrs, 75%

Ideally want to treat dogs within ___ hrs and in cats ___ hrs.

6-8 hrs

3 hrs

Why is it important to understand the pharmacodynamics of EG toxicity?

Determines criteria (clinical signs, pathological signs) you will use to establish a dx and guides treatment

With metabolism of EG the ___ and ___ will change over time.

clinical signs, clinical pathologic data

Absorption of EG in the GI is ___. Peak blood levels in ___ hrs makes ___ difficult, and has half-life of ___ hrs. By ___ hrs, all EG is metabolized or excreted.

rapid

1-4hrs

2-10hrs

16-24hrs

Metabolism of EG occurs in the ___ via a series of ___ reactions.

liver, oxidation

Describe the EG chart starting from ethylene glycol to glyoxylic acid

ethylene glycol — alcohol dehydrogenase —> glycoaldehyde —> glyoxal OR aldehyde dehydrogenase —> glycolic acid —lactate dehydrogenase—> glyoxylic acid

From glyoxylic acid, name its metabolites

glyoxylic acid breaks down to

• glycine+benzoic acid → hippuric acid

• oxalic acid → with calcium → calcium oxalate, monohydrate

• formic acid

What is the #1 rate limiting step of EG metabolism?

alcohol dehydrogenase (liver)

What is the #2 rate limiting step of EG metabolism?

lactate dehydrogenase

Glycoaldehyde is more/less toxic than EG, and has a short/long half life.

Glycolic acid has a short/long half life.

Glycoaldehyde: more toxic, short half life

Glycolic acid: long half life

What metabolites of EG metabolism causes CNS depression which may lead to coma/death if dose high enough?

ethylene glycol, glycoaldehyde, glycolic acid

Metabolites of EG, particularly glycolic acid, induces what?

severe metabolic acidosis and electrolyte abnormalities

Metabolites of EG in addition to metabolic acidosis can cause ___.

cytotoxicity to renal tubular cells

___ crystals from EG metabolism can cause what?

calcium oxalate monohydrate,

mechanical obstruction and cytotoxicity or acute oxalate nephrosis

True or False? Calcium oxalate monohydrate crystals in the urine indicate renal damage.

False. Crystals in urine indicate EXPOSURE to EG, not necessarily renal damage yet.

Clinical signs of EG toxicity will vary depending on what?

dose, time of presentation → where they are at in metabolism cycle!

What is the time frame of the stages of EG toxicity?

Stage 1: 1-3-12 hours, may overlap

Stage 2: 6-8-12 hours

Stage 3: 6-12 hours, up to 12-24 hours+

What are the clinical signs seen in Stage 1 of EG toxicity?

Within 1-3-12 hours: CNS depression, lethargy, vomiting, ataxia, PU/PD, death if severe CNS depression

Why do you see PU/PD in Stage 1 of EG toxicity?

PU - osmotic diuretic, PD - rise in serum osmolality stimulates thirst

What are the clinical signs seen in Stage 2 of EG toxicity?

Within 6-8-12 hours: metabolic acidosis, tachypnea, PU/PU, worsening or recovering slightly from CNS depression as EG and glycoaldehyde metabolized

What are the clinical signs seen in Stage 3 of EG toxicity?

Within 6-12 hours, to 12-24 hours: oliguric, anuric renal disease, renal failure, lethargy, vomiting, abdominal discomfort, anorexia, seizures (uncommon) retinal lesions

Abnormalities caused by EG in clinical pathology is ____ dependent. It is not ___, but ___ for ethylene glycol. Look for a ____ of ____.

time

specific, consistent

preponderance of evidenceA

Almost all clinical pathology for EG occurs in the first ____.

6-8 hours

What are the early clinical lab abnormalities with EG toxicity?

hyperosmolality/elevated osmolal gap, elevated anion gap, metabolic acidosis, calcium oxalate monohydrate crystalluria, hypocalcemia (in 50% of cases)

How do you calculate the anion gap?

(Na + K) - (HCO3 + Cl)

Elevated osmol gap of >__ is concern, >__ is significant.

10, 20

Elevated anion gap of >___ is signifcant.

25 mEq/L

Metabolic acidosis is relevant when pH <____

7.3

Acidosis will kill ___, but ___ can get extremely acidotic and can still survive.

cats, dogs

True or False? If the urine is negative for calcium oxalate monohydrate crystals, you can rule out EG exposure.

False. If negative, do not rule out as can be too early or too late when in stage 3!

True or False? Calcium oxalate monohydrate crystalluria indicates renal disease.

False. Crystalluria does not ALWAYS equate renal disease but is evidence of exposure.

What might you see on labwork if it has been >6-12 hours from EG exposure?

oliguric/anuric renal disease-failure in Stage 3, azotemia, hyperphosphatemia (from rust preservatives), hyperkalemia, hyperglycemia, isosthenuria, glucosuria, proteinuria, casts

___ can be present in all stages of EG.

isosthenuria

What is the acronym for the ddx of hypocalcemia?

PEACE PAIN

PEACE PAIN, ddx for hypocalcemia

Phosphate enema

Eclampsia

Albumin is low

Chronic renal disease

Ethylene glycol toxicity

Parathyroid deficiency

Acute pancreatitis

Intestinal malabsorption

Nutritional (deficiency in vitamin D)

Describe the gross lesions seen in EG toxicity

nonspecific - may see mouth ulcers from urea to ammonia

Describe the microscopic lesions seen with EG toxicity

proximal tubule degeneration and necrosis, birefringent calcium oxalate monohydrate crystals within renal tubules (brain, GIT vasculature)

True or False? EG is the only cause of renal oxalates.

False. Think EG first, then think soluble oxalate containing plants - Halogeton, e.g. Bovine kidney exposed to Cenchrus ciliaris

List the key diagnostic criteria for EG toxicity

• exposure history (within 6-8 hours in dogs, 1-3 in cats)

• clinical signs

• clinicopathological changes - comprehensive testing via CBC, Chen, UA, acid-base and interpret based on stage

• chemical analysis kits best used first 12 hours as screening, but can have false ±, screen blood/urine/serum/plasma for EG

• wood’s light, postmortem

A cheap test to see if there’s antifreeze is a suspect material:

see if it will freeze in the freezer

If a patient looks drugged, anesthetized, CNS depressed, think ___.

-ols = ethlyene glycol, ethanol, propylene glycol, methanol, xylitol, pentobarbital (and ivermectin, amitraz, mushrooms, marijuana, tranquilizers)

What is a halo sign?

seen in stage 3, increase renal cortical and medullary echogenicity

Treatment of EG toxicity depends on ___ and ___.

clinical presentation, stage

What treatments should be considered if in Stage 1 or Stage 2 of EG toxicity?

• fluid therapy to treat dehrydation. maintenance, promote excretion, support kidneys

• monitoring bw, calcium, acid-base, urine output continuously

• ethanol or fomepizole to stop metabolism of EG

____ is not commonly used because EG is rapidly absorbed.

decontamination (emesis, AC, cathartics, gastric lavage)

What is the monitoring protocol/timeline for EG toxicity?

Monitor bw, calcium, acid-base, urine output q3h x9h; for first 12h and 24h then daily for 3d; Ca checked q4-6h x24h

Why do you want to give ethanol to a EG patient?

competitive inhibitor of alcohol dehydrogenase, cheap and effective, few side effects e.g. ethanol stupor

Why do you want to give 4-methylpyrazole aka fomepizole to a EG patient?

direct inhibitor of alcohol dehydrogenase, fewer side effects and more effective than ethanol BUT more expesnive

What is the purpose of ethanol or fomepizole in treatment of EG?

preventing toxic metabolites, and allows EG to be excreted in urine unchanged

True or False? It is recommended to use ethanol and fomepizole in treating EG toxicity.

False. Don’t use if in stage 3 or when EG no longer around, and is not recommended to combine treatments

What are the core goals of EG treatment?

• correct acidosis

• correct hypocalcemia

  • get them to eat

Treat EG toxicity until what?

until normal renal values and normal acid-base data for 24 hours

What is the prognosis for each stage of EG toxicity?

1 and 2 - guarded

3 - poor, $$$, QOL, cannot predict full recovery

What are ddx for acute renal disease?

lily (cat), Vitis-tamarinds-cream of tartar, NSAIDs, aminoglycoside antibiotics, vitamin D, mushrooms, leptospirosis, ethylene glycol, paraquat

Which antifreeze products cause toxicities but without renal involvement?

propylene glycol, methanol

Which antifreeze products cause toxicities with a renal component but no crystalluria?

diethylene glycol, dipropylene glycol

Rank the #1-4 antifreeze sources.

1. ethylene glycol

2. propylene glycol

3. methanol

   1. diethylene glycol

Do pets like ethanol?

YES

How much is too much ethanol?

clinical signs seen at 1 mL/kg of 95% ethanol

When is the onset of clinical signs of ethanol?

within minutes to 1-2 hours, rapid absorption

What is a common source of ethanol toxicity?

fermented raw bread dough (yeast)

True or False? Baker’s yeast, brewer’s yeast, nutritional yeast, baking soda and powder are all sources of ethanol and CO2 problems in pets.

False. Only baker’s yeast (cake yeast, active dry yeast, instant dry yeast, rapid rise yeast, quick rise yeast) converts carbs to ethanol and CO2

Ingesting yeast is generally NOT a problem unless what?

dose is high and there is a source of carbs in stomach

What are signs of fermented raw bread dough ingestion?

ethanol depression, ataxia, urinary incontinence, vomiting, bloat from CO2

What are treatment options for ethanol toxicity?

• decontamination use with caution, emesis within 1 hour, NO AC

• manage hypothermia, CV function, respiratory depression, maintain airway

• monitor for hypoglycemia, hypokalemia, metabolic acidosis

• IV fluids to offset ethanol diuresis from affecting ADH

• Ice chips if alert and can swallow or cold water lavage with stomach tube

True or False? Surgical removal of bread dough blob is a common method of treatment to decompress the stomach.

False. It is rare to need surgery to remove the surgery if unsuccessful in decompression.

Drunken gummies and jello shots can be source of ___ and ___ poisoning in dogs!

ethanol, xylitol