Common and Not So Common

Toxicities

Peter Lands, DVM

Saint Francis Veterinary Center

Summary

Decontamination

Specific Toxicities• Acetaminophen

• Rodenticide

• Chocolate

• Grape/Raisin

• Pyrethrin

• Lily

• Marijuana

• Xylitol

Take Away Points

●Treatments

●Monitoring

●Clinical Signs/Presentation

Decontamination

●Emptying the GI tract to reduce toxin exposure or increase

elimination.

●4 Methods

–Emesis

–Gastric Lavage

–Enemas

–Activated Charcoal

Induction of Emesis

●Performed if recent toxin

exposure (2-4 hours)

●Do NOT perform if ingestion of

caustic substance

–Cleaning agent, petroleum

products, or detergents

●Do NOT induce if patient is

comatose, dyspneic, or

obtunded

Induction of Emesis - Dogs

●Hydrogen Peroxide – 1 tablespoon/20 lbs

–Can be repeated

–No more than 3 tablespoons per dose

●Apomorphine – 0.03mg/kg IV or 0.25mg/kg

subconjunctival

Induction of Emesis - Cat

●Xylazine – 0.44mg/kg IM

–Takes about 30 minutes

–Can reverse with yohimbine 0.1 mg/kg IV

●Dexdomitor - 10mcg/kg IM or SQ

Gastric Lavage

●Performed in patients where emesis is contraindicated

–Ingestion of caustic material

–Increased risk of aspiration

–Actively seizuring

●General anesthesia with properly inflated ETT

●Measure stomach tube to last rib and mark

●Pass the tube into the stomach

●Check to ensure it is properly in the stomach

●Infuse large amounts of warm water

Enema

●Used to clear toxins from lower GI tact

●Helps prevent enterohepatic recycling by

increasing GI transit time

Activated Charcoal

●Binds charged molecules in the GI tract

●Do NOT mix with food, will become inactive

●Toxiban – 6-10ml/kg

●UAA – 1-3ml/kg

●Repeat dose 4-6 hours for toxins with enterohepatic

recycling

●Start oral medications at least 2 hours after

administration

Toxiban Caveats

●Patients may have black feces for 24-48 hours

●Toxiban will cause positive on ethylene glycol

tests

●Very Messy!!!

●Acetaminophen

●Amphetamines

●Anthelmintics

●Antibiotics

●Aspirin

●Atropine

●Barbiturates

●Camphor

●Cantharides

●Carbamazepine

●Carbamates

●Chlordane

●Chloroquine

●Chlorpheniramine

●Cocaine

●Diazepam

●2,4-D (dichlorophenoxy acetic acid)

●Digitalis

●Digitoxin

●Ethylene glycol

●Fungicides

●Hexachlorophene

●Ipecac

●Isoniazid

●Malathion

●Mefenamic acid

●Meprobamate

Activated Charcoal

●Methylene blue

●Methyl salicylate

●Morphine

●Muscarine

●Narcotics

●Nicotine

●Nortriptyline

●Organic iodine

●Organic metal compounds

●Organochlorine insecticides

●Organophosphorus insecticides

●Parathion

●Phenobarbitol

●Phenothiazine

●Phenylbutazone

●Phenylpropanolamine

●hydrochloride

●Phenytoin

●Quinacrine hydrochloride

●Quinidine

●Quinine

●Rodenticides

●Salicylamide

●Salicylates

●Strychnine

●Sulfonamides

●Theophylline

●Tricyclic antidepressants

Acetaminophen (Tylenol)

Acetaminophen

●One of the most commonly seen toxicities

●Generally given by owner or sought out by patients

●Available in many strengths

–80mg, 325mg, 500mg, ect.

●Toxic dose:

–Cat – 10mg/kg

–Dog – 150-200mg/kg

Mechanism of Action

●Absorbed via GI tract

●Poorly protein bound

●Primarily metabolized by the liver

●Eliminated by two major pathways:

–Glucuronidation

–Sulfation

●If pathways are deficient or saturated an alternative pathway

converts to NAPQI

Mechanism of Action

●NAPQI is a free radical

●Damages hemoglobin, RBCs, and kidney cells

●Binds to hepatocytes causing injury and death

●Causes oxidative stress to RBCs

Clinical Signs

●Seen within 1-4 hours of ingestion

●General signs

–Anorexia, salivation, dyspnea, hypothermia,

depression, weakness

●Chocolate colored mucus membranes, blood, and

urine

●Facial and forelimb edema – mechanism unknown

Clinical Signs

Diagnosis

●Based on history

●PE findings

●Methemoglobinemia - Co-oximetry

●Heinz bodies

●Elevated liver enzymes

●Metabolic acidosis

●Compare drop of patients blood to normal blood on

white paper

Treatment●Decontamination

–Emesis – within first 2 hours

–Activated charcoal

●Oxygen therapy

●N-acetylcystine (Mucomyst) = antidote

–Binds NAPQI and serves as glutathione precursor

–Dose – 140mg/kg IV or PO, then 70mg/kg q6h for 7 treatments

–Dilute to a 5% solution with D5W

●Blood transfusions

●Vitamin C – 30mg/kg PO or SQ QID

Prognosis

●Cats – guarded to poor if not treated within 24 hours

●Poor prognostic indicators

–Progressive methemoglobin concentrations

–Methemoglobin concentrations >50%

–Rising liver enzymes

●Resolution of signs from methemoglobinemia within 72 hours

Rodenticide Toxicosis

●3 Common Rodenticides:

–Anticoagulants

–Bromethalin

–Cholecalciferol

●Different rodenticides require different treatments

History

●Sweet-clover (dicoumarol) poisoning in cattle led to

development of anticoagulants

●Cattle suffered from internal bleeding

●Dicoumarol tested as rodenticide

●First generation (Warfarin) created in 1940-50s

●Second generation (brodifacoum, difethialone,

difenacoum, bromadiolone)

–More palatable, more effective, faster, longer acting

Anticoagulant

Pathophysiology

●Interfere with production of clotting factors

–Produced in the liver

–II,VII, IX, X

●Anticoagulants inhibit Vitamin K1 Epoxide Reductase

●Leads to depletion of active Vitamin K1

●Halts the production of active clotting factors

Clinical Signs

●Takes 36-72 hours for depletion of clotting

factors and clinical signs

●Hemorrhage

●Dyspnea, coughing, lethargy, hemoptysis

●Cavity bleeds are common (chest, abdomen,

joints, ect.)

●Can bleed into brain or spinal cord

Diagnosis

●History

●Elongated PT

●CBC – anemia, thrombocytopenia,

hypoproteinemia

Treatment

●Decontamination

●Activated Charcoal

●Vitamin K1 – 3-5 mg/kg PO divided over BID

–Short acting anticoagulants (warfarin and pindone) treat for 14 days

–Bromadiolone treat for 21 days

–All others treat for 28 days

●If Asymptomatic have 2 options

–1: Begin treatment with K1

–2: Monitor PT

●Baseline then repeat in 48-72 hours

Treatment

●Symptomatic Patients – Treat symptomatically

–Oxygen therapy

–Blood transfusion (whole blood or plasma +/-

pRBC)

–Hospitalize until PT WNL

Prognosis

●Depends on severity of toxicity

Bromethalin

●Neurotoxin

●Inhibits mitochondrial energy (ATP) production in the

brain

●Absorbed from GI tract

●Plasma levels peak within 4 hours

●Metabolized by the liver

●Undergoes enterohepatic recirculation

●Slow excretion through bile

Clinical Signs

●Presents as 2 different syndromes

●1: High dose can cause a “convulsant syndrome”

–Hyperesthesia, hyperexcitability, tremors,

seizures, circling, vocalization, mild/severe CNS

depression, hyperthermia, death

–Signs occur 4-18 hours after ingestion

Clinical Signs

●2: Low dose can cause a “paralytic syndrome”

–Signs may take 1-7 days to develop and progress over 1-

2 weeks

–Ataxia, CNS depression, hind limb paresis

–GP deficits, UMN signs, loss of nocioception

–May become comatose

Diagnosis

●Based on clinical signs and history

●Green colored feces

●BW is unremarkable

Treatment

●Decontamination

●Activated charcoal – q8h

–Monitor Na levels

●Fluid therapy

●Symptomatic treatment

–Seizure – mannitol, anticonvulsants

Prognosis

●Good if decontamination is successful

●If neurologic signs present prognosis is poor to

grave

Cholecalciferol

●Cholecalciferol=Vitamin D3

●Toxicity increased serum calcium and phosphorus

●Increases intestinal absorption of Ca and transfer of

Ca and P from bone to plasma

●Prolonged increased plasma levels result in tissue

mineralization

●Renal mineralization leads to AKI and failure

●Decreased functioning of GI tract, skeletal, and

cardiac muscles, blood vessels, and ligaments

Clinical Signs

●Vomiting, lethargy, muscle weakness, anorexia,

depression

●Acute renal failure can occur within 24-72 hours

–PU/PD

Diagnosis

●May notice bait in stool

●Chemistry – HyperPHOS, HyperCA (total and

ionized), HyperBUN, HyperCREAT,

●UA – Isosthenuria

●Radiology – may show mineralization of soft tissue

in symptomatic animals

●25-hydroxycholecalciferol -15x above normal

●PTH – low, iCa - high

Treatment - Asymptomatic

●Decontamination

●Activated Charcoal – repeated doses

●Cholestyramine in dogs – 0.3-1g/kg PO TID for 4

days

Treatment - Symptomatic

●Treatment aimed at correcting hypercalcemia

●Rehydration with NaCl

●Loop diuretics when rehydrated

–Furosemide enhances Ca excretion from kidneys

●Glucocorticoids

–Suppresses bone resorption of Ca

●Phosphate binders – for HyperPHOS

●Pamidronate – 1.3-2 mg/kg, diluted in saline IV over 2-hours

–Lowers Ca in 24-48 hours

May repeat dose in 5-7 days

Chocolate Toxicity

●Contains caffeine and theobromine

●Caffeine is found in coffee, tea, chocolate, colas, ect.

●Theobromine is found in chocolate, cocoa beans, cocoa

bean mulch, colas, and tea

●Common around holidays

–Halloween, Christmas, V-Day, Easter

Toxicity

●Central nervous system stimulant

●Absorbed from the GI tract and undergoes enterohepatic

circulation

●Half-life of caffeine – 4.5 hours

●Half life of theobromine – 17.5 hours

●Many chocolate products contain high fat and cause GI

upset and/or pancreatitis

●Unsweetened baker's chocolate > semisweet chocolate >

milk chocolate > white chocolate

Clinical Signs

●Restlessness and hyperactivity → tremors and

seizures

●Vomiting and diarrhea

●PU/PD

●Rapid heart rate

Diagnostics

●Based on history and clinical signs

●Online Chocolate Toxicity Calculator or Poison

Control Hotline

●Comorbidities possible

●No definitive test

Treatment

●Decontamination

–Emesis

–Activated charcoal q4-6h up to 72 hours

●Intravenous fluids

●Anti-emetics – Cerenia, Anzemet

●Gastric protectants – Protonix, Pepcid

●Frequent walks - q4h

●Symptomatic care – Tachycardia – B-Blocker

(esmolol/propranolol/metoprolol)

Prognosis

●Most cases recovery in 24-48 hours

●Guarded prognosis if large amounts are ingested

or if patient exhibiting severe signs

Grape/Raisin Toxicity

●First identified in 1989

●Unsure of causative agent

●Studies on type of grape, seed/seedless, region

of US, brand, ect.

Grapes/Raisin Toxicity

●Toxic dose – 0.41-1.9 oz/kg

●Lowest documented dose

–0.7 oz/kg grapes

–0.11 oz/kg raisins

Clinical Signs

●GI and Renal signs

●Vomiting

●ARF within 18-36 hours

–Oliguria, Anuria

–Dehydration

–Depression

–Abdominal pain

Clinical Presentation

●Recently ingested = NORMAL

●Vomiting and Diarrhea

●Lethargy

●Anorexia

●Ataxia, trembling

●PU/PD progressing to oliguria or anuria

Diagnostics

●History!

●CBC/CHEM/UA

–Azotemia

–HyperPHOS

–HyperALT/ALKP

–Isosthenuria

–Hyper/Hypo K

Diagnostics

●Abdominal Ultrasound

–Enlarged Kidneys

–Hyperechoic renal cortices

–Decreased corticomedullary distinction

●Blood Pressure - Hypertensive

Differential Diagnosis

●Leptospirosis

●Ethylene Glycol Toxicity

●NSAID Toxicity

●Addisonian Crisis

Treatment●Decontamination

–Emesis

–Activated Charcoal q4-6h

●Antiemetic

●Antacid

●Phosphate Binders

–Aluminum hydroxide at 30-100 mg/kg/day PO with meal

●Antihypertensives

–Amlodipine at 0.5mg/kg PO q12-24h

Treatment

●If no Clinical Signs

●Intravenous fluids at 90-120 ml/kg/day for at least

48 hours

●If BUN/Creat WNL 3 days after ingestion, likely

no adverse consequences

Treatment

●If Clinical Signs

–Intravenous fluids at 90-180 ml/kg/day for at least 48-72 hours

–Monitor BUN/Creat

–If Oliguric/Anuric

●Mannitol at 0.5-1 g/kg IV over 20 minutes q8h

●Furosemide at 2-6 mg/kg IV or CRI at 0.25-1 mg/kg/min

●Dopamine CRI at 1-3 ug/kg/min IV

–DIALYSIS

Monitoring

●BUN/Creat and Phos q24h

●E-lytes q24h or sooner if severe changes

●Weigh q12-24h

Prognosis

●Great if:

–Early onset of therapy

–Continued normal urine output

–Eating

–Response to therapy

●Poor/Guarded if:

–Delayed onset of therapy

–Decreased/absent urine output

–Ataxia or weakness

Pyrethrins

●Commonly used in flea/tick preventatives

●Available as dips, powders/dusts, sprays, collars,

gels, aerosol bombs, ect.

Diagnosis

●Based on:

–History

●Topical most common

●Dog treatment on cat

–Clinical signs

–Exclusion of other differentials

●Blood work WNL

Clinical Signs

●Seen within minutes to hours

●May be delayed up to 72 hours

Clinical Signs●Mild/Moderately Affected Cats:

–Hypersalivation

–Mild tremors

–Hyperexcitability or depression

–GI signs (vomiting, diarrhea)

●Severely Affected Cats:

–Disorientation

–Hyperthermia

–Muscle fasiculations

–Generalized tremors

–Seizures

Clinical Signs

VIDEO

Treatment

●Decontamination

–Topical

●Bathe in warm water with lipophilic soap

–Oral

●Induce emesis

●Activated charcoal

Treatment

●Methocarbamol IV

–40-50 mg/kg IV BOLUS, then CRI at 10mg/kg/hour

–May give additional bolus if needed

–Do not exceed 330mg/kg/day

●Diazepam/Midazolam IV

–0.5mg/kg IV as needed

●Propofol IV

–4mg/kg IV to effect or 1.5-19mg/kg/hr CRI

●Intravenous Lipid Emulsions (ILE)

Prognosis

●Excellent if treated fast and aggressively

●Most pets leave the hospital in 24-96 hours

Lily Toxicity

Lily Toxicity

●Easter Lily

●Tiger Lily

●Rubrum Lily

●Stargazer Lily

●Japanese Show Lily

●Day Lily

Lily Toxicity

●Toxic to CATS

●Causes Renal Failure

●ALL parts are considered toxic

Presenting Complaint

●Lily Ingestion

●Vomiting

●Lethargy

●Anorexia

●PU/PD

●Common around Easter (March and April)

Diagnostics

●CBC – WNL

●CHEM

–Azotemia

–Hyperkalemia

–Hyperphosphatemia

●Urinalysis

–Isosthenuria

–Glucosuria in absence of hyperglycemia

–Urinary Casts

Treatment

●Decontamination

–Emesis

–Activated Charcoal q4-6h

●Fluid Therapy

–120ml/kg/day

–At least 48 hours

–Monitor body weight BID-TID

Alternative Treatment

●If Oliguric (<2ml/kg/hr)

–Furosemide 2mg/kg IV

–If oliguric in 1 hour, give 4mg/kg IV

–If oliguric in 1 hour, give 6mg/kg IV

●Hyperkalemia

–Bicarbonate (0.5-2 mEq/kg) IV

–Glucose (1-2ml/kg of 50% dextrose diluted) IV

Alternative Treatment

●Peritoneal Dialysis

●Hemodialysis

●Renal Transplant

Supportive Treatment

●Antiemetic

●Antacid

●Phosphate Binders

●Pain medication

Monitoring

●Weights

●BUN and Creat

●Phosphorus

●Potassium

Prognosis

●Good if:

–Able to produce urine

–Able to concentrate urine

–Decreasing azotemia

–Appetite

●Poor if:

–Anuric

–Isosthenuria

–Increasing azotemia

–anorexia

Marijuana Toxicity

●Main toxic principle is 9-tetrahydrocannabinol (THC)

●Intoxication after ingestion of marijuana leaves,

baked products, smoke inhalation

●Lethal dose – 3g/kg

Diagnosis

●History

●Clinical Signs

●Urine Test

Clinical Signs

●Occur within 30-90 minutes after ingestion

●Neurologic

–Depression, ataxia, tremors, seizures, mydriasis,

disorientation, hyperesthesia, bradycardia,

hypersalivation, weakness, hypothermia, urinary

incontinence

●GI - Vomiting

Treatment

●Decontamination

–Emesis

–Activated Charcoal q8h for 24 hours

●Intravenous Fluids

●Hospitalization for 24-72 hours

●Diazepam at 0.25-0.5 mg/kg IV as needed for agitation

and/or seizures

Prognosis

●Great

●Most recovery completely in 24-72 hours

Xylitol

Xylitol

●Manufactured sweetener in sugar-free candy and

gum, baked good, beverages, cereals, and

toothpaste

●Toxic to DOGS

●Toxic dose

–>0.1 g/kg causes hypoglycemia

–>0.5 g/kg causes hepatotoxicity

Xylitol

●Peak plasma levels in 30 minutes, may be delayed

●Increased insulin levels in Dogs by 2.5-7x (also rabbits, baboons,

cows, and goats)

●Causes severe hypoglycemia

●Hepatotoxic:

–Idiosyncratic reaction

–Liver enzyme elevation

–Hepatic necrosis

Clinical Signs

●Vomiting

●Hypoglycemia:

–Usually within 30-90 minutes

–May be delayed for up to 12-48 hours

–Altered mentation, dullness, weakness, recumbency, ataxia, seizures

●Hyperglycemia secondary to somogyi

●Icteric

●Petechiae/Ecchymosis

Diagnostics

●Hypoglycemia

●Hypokalemia – intracelluar shift

●HyperALT

●HyperTBILI

●HypoPLT

●Prolonged PT/PTT

Treatment

●Decontamination

–Emesis

–Activated Charcoal – does not bind xylitol but is still recommended

●Monitor BG q2h for at least 12 hours

●Monitor K/Phos q4-6h

●Monitor Liver enzymes q24-72h

●If 0.1-0.5 g/kg ingested

–Hypoglycemia 0.5cc/kg 50% Dextrose IV, then 2.5%-5% CRI

Treatment

●If >0.5 g/kg ingested

–0.5cc/kg 50% Dextrose IV, then 2.5%-5% CRI

●Liver protectants and antioxidants

–N-acetylcysteine

–S-adenosylmethionine

–Vitamin E

●Coagulopathies treated with FFP

Prognosis

●Good if develop uncomplicated hypoglycemia

●Guarded to poor if develop hepatotoxicosis and

liver failure

QUESTIONS?

Work Cited

●Common Rodenticide Toxicoses in Small

Animals. DeClementi, Ca and Sobczak, Br. Vet

Clin Small Animal 42 (2012) 349-360.

●VIN -

●Grape and Raisin Toxicity in Dogs. Savigny,

Michelle and Macintire, Douoglass. Standards of

Care (2007) Volume 9.1.

●Lily Toxicoses in Cats. Jill Richardson. Standards

of Care (2002) Volume 4.4.