Common and Not So Common ToxicitiesCommon and Not So Common Toxicities Peter Lands, DVM Saint...

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.