Approach to Suspected Toxicities in Small Animals Part 2

This part goes over the different toxins mentioned in this lecture, and how they effect the body

PARACETAMOL

How is this toxic to animals, and why are cats more susceptible to paracetamol toxicity?

Paracetamol is metabolized in the liver

• Broken down into NON-toxic metabolites via the sulphation and glucoronidation pathways

• This is why Paracetamol is non-toxic to a point in dogs; able to metabolize it well enough

Cats LACK the glucoronidation pathway!!!

• Sulphation pathway then becomes overwhelmed, and the remaining Paracetamol is then OXIDIZED into TOXIC metabolites

  • NAPQI metabolites

• NAPQI metabolites are initially deactivated by the glutathione that’s present in the liver, but once THOSE become overwhelmed, the NAPQI metabolites cause:

  • Oxidative damage to RBCs

  • Hepatic cell injury / death

In Paracetamol toxicity, will overall see hepatocellular necrosis, methemoblobin formation, and Heinz body anemia

• Random: dry eye in dogs

What are the clinical signs of Paracetamol toxicity at <24 hours post ingestion? (6)

1) Cyanosis / muddy brown mucus membranes

2) Tachycardia, tachypnea

3) Lethargy

4) Facial or paw edema

5) Vomiting

6) Anemia

What are the clinical signs of Paracetamol toxicity at >24 hours post ingestion? (5)

1) Liver failure

2) Icterus

3) Seizures / coma

4) Renal failure (RARELY)

5) Hematuria / hemaglobinuria

At what dose of Paracetamol ingested would you treat a dog for paracetamol toxicity? What about a cat?

Cat → ANY DOSE

Dog → anything greater than 50-100 mg/kg

What is the ANTIDOTE for Paracetamol toxicity

N-acetylecysteine (Parvolex)

• Acts as a glutathione precursor, binding to NAPQI metabolites and inactivating them

• Dilute, and give slow over IV every 6 hours for 7 doses

What are some other things that you would do for treatement of paracetamol toxicity? (Remember, some of these would really depend on the circumstances of the case…)

1) Emetics - depends on timing

2) Adsorbents

Get them on IV fluids for sure and give O2 if needed

• If super advanced, may need blood transfusion

METALDEHYDE

What is it, and how toxic is it?

Slug killer

• HIGHLY TOXIC

• Treat for even the smallest of doses ( >2mg/kg)

• Any dose extremely toxic

What are the early signs of metaldehyde toxicity? What will it progress to?

Early signs:

• Vomiting

• Diarrhea

• Hypersalavation

Soon after: “Shake and Bake”

• TREMORS AND SEIZURES

• Hyperasthesia - extreme sensitivity to touch and other stimuli

• Hyperthermia

• Mydriasis - excessive dilation of the pupil

Death will then occur due to respiratory arrest and multiple organ dysfunction

How should you treat a metaldehyde toxicity? Think of how quickly it sets in…

• Not likely emesis, as it is rapid onset and neurological signs develop quickly 

• Activated charcoal can help + enema to flush out the intestines and prevent further absorption 

• Should also focus on seizure control:

  • Benzodiazepines 

  • Propofol 

  • Methocarbamol - muscle relaxant 

• IVFT

• Manual cooling

• O2

Slow recovery over 24 hours; 15% of cases even with treatment can be fatal 

Unfortunately no antidotes

ANTICOAGULANT RODENTICIDES

How are they toxic to animals? What is their mechanism of action?

Slowly absorbed, with a long plasma half life 

Mechanism - Work by blocking Vitamin K activation, which is needed to produce clotting factors II, VII, IX, and X

• Leads to a defect in secondary hemostasis and causes coagulopathy (takes 1-5 days to reach this stage, depending on dose)

After 3-5 days post-ingestion, what clinical signs would you see after a rodenticide poisoning? (8 overall; think of what could be affected if your blood can’t clot)

1) Lethargy

2) Body cavity hemorrhaging

3) Dyspnea / cough

4) Hemoabdomen

5) Epistaxis - nose bleed

6) Melaena / hematemesis - blood in stool / vomit

7) Joint pain

8) Anemia

** image shows blood seeping into the lungs

What is the main method to definitively diagnose a rodenticide poisoning?

Prolonged Prothrombin Time (PPT) - do this first (from 36hr post ingestion)

Can then do:

• Prolonged APTT (from 72 hr post)

• Check the platelets; are they normal or decreased?

• Check PIVKA levels

  • Proteins induced by Vit K antagonism

• Blood panel for anemia

What is the ANTIDOTE for a rodenticide poisoning?

VITAMIN K1

How would you treat for an anticoagulant rodenticide poisoning in an ASYMPTOMATIC animal?

• Most cases will be asymptomatic, but you should treat if a patient gets 10% of the LD50 for the rodenticide 

• Treat with emesis and activated charcoal and, if it calls for it, the ANTIDOTE -> Vitamin K1

  • Sometimes you shouldn’t start with Vitamin K1, as rodenticides have a long half life and can still be in the body if not flushed out.  So, do emesis and activated charcoal first, check PPT 48hr and 72hrs post ingestion, then treat with Vitamin K1 if initial attempt was unsuccessful 

How would you treat a rodenticide poisoning in a SYMPTOMATIC animal?

No point in emesis or charcoal, poison has already taken effect

ABSOLUTELY VIT K1 TREATMENT

• May need O2 supplementation

• TRANSFUSION ideal if bad enough; specifically plasma, ± RBCs

ETHYLENE GLYCOL (anti-freeze)

How is ethylene glycol toxic to animals?

• Very poor prognosis; rapidly absorbed, can be fatal at 1mL/kg in cats and > 4mL/kg in dogs 

• Is metabolized in the liver by alcohol dehydrogenase; metabolites are toxic 

  • Glycoaldehyde -> CNS effects 

  • Glycolic acid -> metabolic acidosis 

  • Oxalate -> binds to calcium (CaOx), leads to hypocalcemia and is deposited in the renal tubules, leading to acute kidney injury 

What are the signs of anti-freeze poisoning in the first 12 hours? (4)

** Think about the order of the toxic metabolites and when they are made… and which what effects which body system…

Neurological signs

• Ataxia

• Twitching

• Seizures

• Vomiting

After 24 hours?

Cardiopulmonary signs

• Tachypnea

• Tachycardia

• Metabolic acidosis

• Pulmonary edema

• Shock

After 24 hours?

Acute Kidney Injury

• Swollen / painful kidneys

• Vomiting

• Anorexia

• Oral ulceration

• Oliguria / anuria

How would you diagnose an anti-freeze poisoning within the first 12 hours?

• Patient would be in metabolic acidosis

• Calcium oxalate crystals present in urine (CaOX crystalluria)

• Isosthenuria (UPG = 1.008-1.012)

How would you diagnose anti-freeze poisoning AFTER 24 hours?

Blood panel!! Will show:

• Azotemia (once that is present = grave prognosis)

• Hyperphosphatemia

• Hyperkalemia

• HypOcalcemia

• Hyperglycemia

All indicative of Acute Kidney Injury

What would a urinalysis show > 12 hours POST anti-freeze poisoning?

• Reduced USG (isosthenuria)

• Glycosuria

• Hematuria

• Proteinuria

• Clacium oxalate crystals (see image)

• Cellular casts (from cell death)

• pH <6.5

What is the ANTIDOTE for ethylene glycol poisoning?

ETHANOL

• Blocks alcohol dehydrogenase from metabolizing anti-freeze… allows ethylene glycol to pass through the kidneys unchanged

  • Only effective < 3 hrs post ingestion in CATS

  • Effective < 8 hrs post ingestion for DOGS

******** ONCE KIDNEY INJURY IS PRESENT, ETHANOL WILL MAKE IT WORSE ********

What is the dosage for an IV treatment of ethanol?

• 5% solution as a constant rate infusion at a rate of 5 ml/kg/hour OR

• 5 ml/kg body weight 20% ethanol in saline IV every 6 hours for 5 doses then every 8 hours for 4 doses.

How would you make a 20% dilution of ethanol from 40% vodka? What about a 5% dilution?

To make a 20% solution:

• dilute an equal volume of vodka with IV fluids such as lactated Ringer's or saline (e.g. 500 ml with 500 ml). An in-line filter should be used for the IV.

To make a 5% solution:

• add 125 ml of vodka to 875 ml of IV fluid lactated Ringer's or saline, that is remove about 125 ml from the bag and replace with vodka. An in-line filter should be used for the IV.

What are the side effects to treating anti-freeze poisoning with ethanol? (4)

• CNS depression

• Bradycardia

• Hypoventilation

• Hypothermia

THEOBROMINE (chocoloate)

What are the signs of theobromine poisoning at a 20 mg/kg dose? 40 mg/kg? 60 mg/kg?

20 mg/kg chocolate consumption causes:

• GI sins

• Hyperactivity (energetic; like being given caffiene)

• Panting

• Shaking

40 mg/kg chocolate consumption causes:

• Cardiotoxicity

• Tachycardia

• Arrhythmias

60 mg/kg chocolate consumption causes:

• Seizures

What kind of chocolate has the MOST theobromine content? After how much chocolate consumption would you treat?

DARK CHOCOLATE → ~ 5.3 mg/g theobromine content

**** Treat if patient eats > 3.5 g/kg of dark chocolate

• Reduces as it gets lighter

• White chocolate is negligible

For milk chocolate → 1.4 mg/g theobromine content

**** treat if patient eats > 14 g/kg of milk chocolate

**** Most accurate to calculate theobromine content from total cocoa solids

• Theobromine content in mg/g = cocoa % x 0.16

  • Ex: for 75% dark chocolate = 12 mg/g (75 × 0.16)

What are the general treatments for a mild theobromine poisoning?

1) Emesis - depends on timing of consumption

2) Charcoal

3) IVFT if needed

4) Urinary catheter

• Theobromine is absorbed through the bladder, so getting them to urinate as frequently as possible is best

  • Can be controlled via catheter

How would you treat a more advanced theobromine poisoning (w/ neurological signs or arrhythmia)?

Seizure control (from most effective to least)

• Benzodiazepines

• Phenobarbitone

• Leviteracetam

• Propofol

Arrhythmias

• Supraventricular tachycardia

  • Beta blocker

• Ventricular tachycardia

  • Lidocaine

Of course this would be on top of the general treatments (IVFT, catheter, etc.)

XYLITOL

How is xylitol toxic to animals? At what dose of xylitol consumption should you begin treatment?

RAPID absoption and onset of symptoms

• Hypoglycemia

  • Due to insulin spike caused by xylitol

  • Reported at > 100 mg/kg ; see within the first 30 mins

• Hepatic necrosis

  • Reported at > 500 mg/kg

  • Signs delayed by up to 72 hrs

  • Causes coagulopathy

Treat with even the smallest dose ( > 50mg/kg, which is one piece of sugar free gum)

How would you treat an animal with xylitol poisoning? What if they become hypoglycemic or had received a hepatotoxic dose?

General treatments:

• Emesis? Remember, rapid absorption

• Monitor BG levels

• IVFT

If hypoglycemic…

• Dextrose CRI

• Frequent, small meals

• Monitor K and Phos.

If ingested a hepatotoxic dose…

• Liver protectants

• Monitor ALT, TBIL, and clotting times

• Transfusions?

• Vitamin K supplementation?

RAISINS / GRAPES

What is the “toxic component” in grapes and raisins? Is it toxic for every animal? What can it cause?

Is an IDIOSYNCRATIC reaction in ~ 10% of dogs; most don’t react, but some are more susceptible

Toxic component: Tartaric acid

Can cause:

• GI signs early on (V/D, abd pain)

• AKI from 24-72hr

How would you treat a raisin/grape poisoning?

Emesis!! Useful even up to 6hrs post ingestion

• ± charcoal

MONITOR

• Establish bloods → urea, creat, lytes (+ phos and Ca)

• Check urine

Then continue to monitor as outpatient

• Establish bloods baseline, then recheck q 24hrs for 72 hrs

*** START IVFT if creat. INCREASES > 26.4 umol/L