jen loewen, dvm, dacvecc

Approach to oral toxins

JEN LOEWEN, DVM, DACVECC

ASSISTANT PROFESSOR, WESTERN COLLEGE OF VETERINARY MEDICINE

Overview

General Approach to Intoxications

Specific Intoxications

Objectives

Describe and implement general treatment of

toxicities

List some specific antidotes

List resources for toxicities

Terminology

Poison / toxicant:

A solid, liquid, or gas that can interfere with homeostasis of an organism or life processes of its cells by its own inherent properties.

Toxin:

Poison that originates from a biological source (AKA biotoxin)

Toxic:

Used to describe the effects of a toxicant (i.e. the “toxic” effects of substance X)

Toxicosis:

The syndrome of adverse effects that result from exposure to a toxicant. Interchangeably used with poisoning and intoxication.

Small Animal Toxicology (Peterson)

General Approach to

Intoxications

Goals

Gather information about exposure and patient

Learn about the toxin

Decontamination

Provide toxin antidote when possible

Decrease toxin absorption

Enhance toxin elimination

General supportive therapy

Ultimate goal: inhibit or minimize further toxicant absorption

and to promote excretion or elimination of the toxicant

from the body

General Approach to

Intoxications: Historical info

Known or suspected intoxication:

Information about toxin

Active ingredient

Route of exposure

How much was ingested?

When was the toxin ingested?

Patient information

Body weight

Clinical signs noted since ingestion

Pre-existing disease/illness

Current medical therapy or supplements administered

***Ask client to bring remainder of package/label***

General Approach to

Intoxications

Other helpful questions

Learn more about patient’s environment

Access to garage, neighbor’s yard, farmland, etc.

Patient examination

Triage examination: ABCs (+ N)

Full physical examination

Learn about the toxin

Important information

Toxic dose

Mechanism of action

Is emesis safe/indicated?

Is there an antidote?

Treatment / Prognosis

References

ASPCA pet poison- (888) 426-4435

Pet poison hotline- (855) 764-7661

*fees apply

Specific therapy:

Is there a known antidote?

Types of antidotes

Direct reaction with toxicant

Chelation of heavy metal ions

Interaction with the toxicant’s receptor

Naloxone = μ-opioid receptor antagonist

Alter metabolism

Inhibition of metabolic pathway

4-MP inhibits alcohol dehydrogenase

Provide alternative substrate for enzymes

Ethanol competes w/ ethylene glycol for alcohol dehydrogenase

Small Animal Toxicology, Ch 24

Examples of known antidotes

Toxicant Antidote

Acetaminophen N-Acetylcysteine

Anticoagulant Rodenticides Vitamin K1

Benzodiazepines Flumazenil

Cadmium, Iron, Lead Chelation (D-penicillamine)

Digitalis Digoxin immune Fab

Ethylene glycol4-methylpyrazole (4-MP),

ethanol

Organophosphates /

Carbamates

2-Pralidoxime (2-PAM),

atropine

Opiods (morphine,

hydromorphone, fentanyl,

heroin)

Naloxone

Small Animal Toxicology, Ch 24

Decontamination

Considerations

Route of exposure

Dermal

Ocular

GI

Respiratory

Risks/benefits of decontamination procedure

Decontamination

Dermal Exposure

Lipophilic toxicants, surfactants are more readily absorbed

Standard method: rinse with water or bathe patient with mild

dish soap.

**Caution: may cause patient distress, use care with obtunded

patients, prevent hypothermia, avoid human exposure

Ocular Exposure

Copious ocular irrigation with tepid tap water, saline, or distilled

water.

Flush laterally (avoid contamination of other eye)

***Caution: Contact lens solutions may cause further irritation

SACCM, Ch 77

Decontamination

Gastrointestinal Exposure

Emetics

Gastric Lavage

Whole Bowel Irrigation

SACCM, Ch 77

GI Decontamination

Emetics

Encouraged

Emesis

Encouraged

Immediately after toxin ingestion

Within 1-2 hours of toxin ingestion

In the alert patient

Product known to last in stomach for prolonged period

Contraindicated

Caustic products

Petroleum products, Acid/alkali

Altered mentation

Risk of aspiration

Toxins that increase risks of aspiration: gasoline, kerosene, motor oil

Laryngeal paralysis, megaesophagus

etc.

Toxins rapidly absorbed:

acetaminophen

SACCM, Ch 77

Only allows retrieval of a fraction of gastric contents

GI Decontamination

Emetics

Centrally Acting (CRTZ)

Apomorphine

Opiate, stimulates dopamine receptors

***Emetic of choice in dogs***, unreliable in cats

Dose: 0.03 mg/kg IV or 0.04 mg/kg IM → can repeat

dose also subconjunctival administration

Side Effects: Protracted vomiting, restlessness,

excitement, CNS depression.

Naloxone to reverse SE (not emesis)

SACCM, Ch 77

GI Decontamination

Emetics

Centrally Acting (CRTZ)

Xylazine

α-2 agonist

***Often used in cats, unreliable in dogs

0.44 mg/kg IM or SQ.

Reverse with yohimbine (0.25 -0.5 mg/kg IM) following emesis

Side Effects: Sedation, bradycardia, arrhythmias, muscle

tremors

α-2 agonists contraindicated in animals with structural heart

disease

SACCM, Ch 77

GI Decontamination

Emetics

SACCM, Ch 77

Xylazine (0.36-0.64 mg/kg IM): 9/21 (43%)

Dexmed (6-18 mcg/kg IM): 15/26 (58%)

Equal effects

Xylazine (0.4-0.5 mg/kg): 11/25 cats

Dexmedetomidine (0.96-10 mcg/kg IM ): 13/16

Hydromorphone (1 mg/kg SQ) – 9/12 vomited

Dexmedetomidine (7 mcg/kg IM)- 7/12 vomited

GI Decontamination

Emetics

Local Irritants

3% Hydrogen Peroxide

1-2 ml/kg PO (max dose 50-150 ml/large dog

Repeat once if ineffective

May result in persistent vomiting/gastritis

In cats: anecdotally 25% develop severe hemorrhagic gastroenteritis

Others (NOT RECOMMENDED)

Dishwashing liquid

Table salt

Stimulation of gag reflex

SACCM, Ch 77

GI Decontamination

Gastric Lavage

Administration and evacuation of liquid through orogastric tube

Encouraged

Within 1-2 hours of toxin ingestion

Depressed mental state/loss of gag (vs emesis)

Contraindicated

Ingestion of hydrocarbons or corrosive substances

In patients with risk of hemorrhage/GI perforation

More than 2h after ingestion

SACCM, Ch 77

GI Decontamination

Gastric Lavage

Procedure

Anesthetize and intubate patient with cuffed ETT

Position patient with head slightly lower than thorax

Premeasure large bore gastric tube from nose to last rib

Lubricate tube and gently pass down esophagus into stomach to marked distance.

Check positioning

Aspirate gastric contents

Insufflate with air while ausculting stomach

Abdominal radiograph to confirm placement if unsure

Lavage with 5-10ml/kg of warm water or saline

Allow to drain from tube via gravity, then repeat until fluid is clear

Kink off tube prior to removal

SACCM, Ch 77

GI Decontamination

Gastric Lavage

Toxin Recovery

Mean recovery of 29-38% of toxin within 15-20

minutes of ingestion.

8.6-13% recovery after 60 minutes have elapsed.

Risks

Aspiration pneumonia (ETT is critical!)

Injury to/perforation of esophagus/stomach

SACCM, Ch 77

GI Decontamination

Whole Bowel Irrigation

Procedure

Administration of large amounts of balanced polyethylene glycol

electrolyte solution through NE tube until bowel movements resemble

fluid administered.

Human Med: Used for ingestion of sustained release or enteric coated toxins

Encouraged

?? Unknown utility in veterinary patients

Improved removal of paraquat in dogs (experimental intoxication)

Contraindicated

GI hemorrhage, obstruction, compromised airway, intractable

vomiting, hemodynamic instability

Complications in humans: nausesa, vomiting, cramping, bloating

SACCM, Ch 77, Mizutani 1992

Decrease Toxin Absorption:

Adsorbents

Activated Charcoal

Does not absorb every toxin

Factors: temperature, solubility of toxin,

ionization of toxin, pH, presence of other

gastric contents

Not effective for: alcohols, ferrous sulfate,

xylitol, caustic alkalis, nitrates, petroleum

products, mineral acids

SACCM, Ch 77

Decrease Toxin Absorption:

Adsorbents

Activated Charcoal

Dose = 1 to 4 grams/kg PO (recc 1-2 gm/kg)

Offer PO, mix with food.

Syringe feed (carefully!!)

Orogastric tube (anesthetized, intubated)

Most effective soon after ingestion.

First dose w/ sorbitol…

Risks: Aspiration

Unprotected airway, seizures patient, too sedate

Hypernatremia

SACCM, Ch 77

Abstract presentation

15 mg/kg of oral carprofen

2 g/kg activated charcoal (AC) 30 minutes after carprofen administration

Apomorphine-induced emesis at 30 minutes followed by 2 g/kg activated charcoal (EAC) administration at 60 minutes,

No treatment (control group).

activated charcoal alone is as effective as emesis followed by activated charcoal in dogs following carprofen overdose in this model

120 mg/kg of carprofen PO

a single 2 g/kg activated charcoal administration 1 hour following carprofen ingestion (AC)

2 g/kg activated charcoal with 3.84 g/kg sorbitol 1 hour following carprofen ingestion (ACS);

2 g/kg activated charcoal 1 hour after carprofen ingestion and repeated every 6 hours for a total of 4 doses (MD)

no treatment (control)

AC and ACS with are as effective as MD in reducing serum carprofen concentrations following experimental overdose in dog

Food with charcoal?

Food decreased adsorptive capacity

Unlikely to be clinically significant (but study invitro)

Decrease Toxin Absorption

Reduce enterohepatic recirculation

Repeated activated charcoal administration

WITHOUT sorbitol

Urinary bladder wall reabsorption

Urinary catheter placement or frequent walks

Methylxanthines and metabolites

SACCM, Ch 77, Sm Anim Toxicol p850

Enhance Toxin Elimination

Enhance GI Elimination: Cathartics

Accelerate expulsion of toxins from the GI tract

Saccharide (i.e. sorbitol)

Commonly available in some activated charcoal

preparations

Use Caution:

May cause dehydration, hypernatremia

Saline cathartics: Mg, phosphate may be absorbed

Caution in animals with renal disease, CHF, dehydration

SACCM, Ch 77

Enhance Toxin Elimination

Enhance Renal Excretion

IV fluids to promote diuresis

For renally excreted toxins

Risk of volume overload

Alter urine pH

i.e. ascorbic acid

Some products may cause systemic acidosis/alkalosis

Hemodialysis

An additional option for toxin removal

ethylene glycol

$$$, limited availabilitySACCM, Ch 77

Lipid rescue therapy

Intralipid 20% ($30/250 ml)

Mechanism of action:

???

Improved myocardial performance?

Lipid sink?

Dose?

1.5 ml/kg bolus over 1-3 min followed by 0.25-0.5 ml/kg/min x 30-60 min

Can repeat as long as serum is no longer lipemic

Potential complications

Minimal reported, no safety studies

Bacterial contamination (aseptic technique

required)

Hypersensitivity reaction

Pancreatitis?

ARDS

Pulmonary lipid emboli

General Supportive Therapy

IV Fluids

Antiemetics

Sedation, etc

Monitoring

ECG, TPR, BP, Mentation

Specific Toxicants

ADME

Absorption

Distribution

Metabolism

Excretion

Mechanism of Action/Toxicity

Diagnosis

Treatment

Hot off the press

Has it finally been solved??

Is it Tartaric acid?

Maybe???

Letter to the editor is lowest quality of evidence

Posses a hypothesis that we need to further investigate

Ethylene Glycol

Minimum lethal dose:

Dogs: 4.4 to 6.6 ml/kg Cats: 1.5 ml/kg

Mortality rate 59-70% in dogs, likely worse in cats.

A/D:

Rapidly absorbed after PO exposure→ distributed to all body tissues

Peak blood level at 3h, high concentration until ~12h, may be

undetectable by 48h

M/E:

Primarily metabolized in the liver

Alcohol dehydrogenase*

Variable amt excreted unchanged in urine

SACCM Ch 78, Sm Anim Toxicol Ch 45, Image: fixacar.net

SACCM Ch 78

Ethylene Glycol

Systemic Effects

Stage 1 (30 min – 12h):

CNS Depression

Due to glycoaldehyde, EG, hyperosmolality, metabolic acidosis

Depression, ataxia, somnolence, seizure, coma

CNS signs may improve ~12h after intoxication

GI Signs: Vomiting

Direct gastric mucosal irritation

CRTZ (increased serum osmolality)

PU/PD

Osmotic diuresis

SACCM Ch 78, Sm Anim Toxicol Ch 45

Ethylene Glycol

Systemic Effects

Stage 2 (12-24h):

CNS Depression Improves

Dogs appear improved/recovered

Cats remain depressed

Dehydration, tachycardia, tachypnea


Ethylene Glycol

Systemic Effects

Stage 3

Acute Renal Failure

24-72h after ingestion in dogs

Earlier (12-24h) in cats

Mechanism of acute tubular necrosis

Incompletely understood

Calcium oxalate crystal deposition in renal tubules

Direct renal tubular epithelial cytotoxicity

Frequently oliguric/anuric, 72-96h post-ingestion


Ethylene Glycol

Diagnostic Tests

CBC – +/- echinocytes, usually unremarkable

Serum Chemistry

Early:

Metabolic acidosis (↓HCO3-)

Elevated anion gap

Glycolic acid and other acid metabolite accumulation

+/- Hyperphosphatemia

Phosphate rust inhibitors

Late:

Renal failure:

Azotemia, hyperphosphatemia

Hyperkalemia (with oliguria, anuria)

Hypocalcemia (50% of cases)

Chelation of calcium by oxalic acid


( ( Na+ + K + ) – ( Cl - + HCO3- ) )

Ethylene Glycol

Diagnostic Tests

Urinalysis

Isosthenuria (within 3h)

Osmotic diuresis → renal dysfunction

Calcium oxalate monohydrate crystalluria

As early as 3-6h

Other findings may include:

Hematuria, proteinuria, glucosuria, casts


Ethylene Glycol

Diagnostic Tests

Confirmatory Tests

Ethylene Glycol Test Kit

Estimates blood levels ≥50 mg/dl

Cats can suffer intoxication below this level

False positive (propylene glycol, glycerol)

Activated charcoal, diazepam, semimoist diets

SACCM Ch 78, Sm Anim Toxicol Ch 45, Image: prnpharmacal.com/egtkit

Osm

+

2.8

Ethylene Glycol

Diagnostic Tests

Other supportive tests/procedures

Examination of patient with Wood’s Lamp

Fluorescein present on face, paws, in urine (up to 6h)

Also assess vomitus

Abdominal Ultrasound

“Halo sign”

Hyperechoic cortical/medullary regions with hypoechoic

corticomedullary junction and central medullary tissue

Supportive, not pathognomonic

SACCM Ch 78, Sm Anim Toxicol Ch 45, Image: prnpharmacal.com/egtkit

Ethylene Glycol

Treatment

Emesis (within 2h of ingestion)

(Activated charcoal = questionable benefit)

Competitive Inhibition of Alcohol Dehydrogenase

Ethanol (IV bolus or CRI)

CNS Depression, hyperosmolality, osmotic diuresis

4-Methylpyrazole (4-MP)

Higher dose (6x) required in cats

ADH has greater affinity for 4-MP > ethanol

Safer than ethanol


Ethylene Glycol

Treatment

Supportive Therapy

IV Fluids

Tx (if necessary) for metabolic acidosis, hypocalcemia

Antiemetics

Hemodialysis

Prognosis

Variable/good if treated (EtOH/4-MP) within 8h

Grave prognosis: anuric acute renal failure

20% with hemodialysis


Acetaminophen

Toxic Dose

Dogs: 200-600 mg/kg (as low as 75-100 mg/kg)

Cats: 50-100 mg/kg (as low as 10 mg/kg)

A/D

Rapidly absorbed after PO exposure

Peak blood levels in 30-60 minutes

M/E under NORMAL Conditions (at low doses)

90% undergoes hepatic metabolism - conjugation with:

Sulfate

Glucuronide

5% excreted unchanged in urine

5% metabolized to NAPQI (N-acetyl-p-benzoquinoneimine, TOXIC)

Normally conjugated with glutathione → nontoxic cysteine/mercapturicacid conjugates

SACCM Ch 79, Sm Anim Toxicol Ch 28, Image: amazon.com

Non-toxic metabolites

Acetaminophen

Metabolism

Image: sailingsimplicity.com/non-toxic-lifestyle-choices/

Acetaminophen

Low Dose

SulfationGlucoronidati

oncP450

Unchanged

in Urine

GS

H

Acetaminophen

TOXIC Dose

= NAPQI

Cats: low levels of glucoronyl

transferase

Acetaminophen

Systemic Effects

NAPQI

Reactive Oxygen Species

Binds to cellular proteins → oxidative injury

Cats

Methemoglobinemia, Hz bodies, Hemolytic Anemia

Feline RBC more susceptible (Hb contains 8 sulfhydryl groups)

Brown mucous membranes, respiratory distress, face/paw edema, depression, hypothermia, vomiting

Hepatotoxicity at higher doses and in males

Dogs

Hepatocellular Injury/Necrosis

Secondary vomiting, diarrhea, HE

Methemoglobinemia at higher doses

SACCM Ch 79, Sm Anim Toxicol Ch 28, Image: amazon.com, illustratedmedicine.blogspot.com/2010/09/methemoglobinemia.html

Fe2+→ Fe3+

Ferrous Ferric

Acetaminophen

Diagnostic Tests

Minimum Database

Brown tinge to whole blood (MetHb)

+/- Heinz bodies, hemolytic anemia (anemia, Hb-emia,

Hb-uria, ↑Tbili)

↑ALT, AST

↓Hepatic function (↓BUN, albumin, cholesterol)

Confirmatory Tests

Measurement of acetaminophen conc (?)

Co-oximetry (measure % methemoglobin)

SACCM Ch 79, Sm Anim Toxicol (Peterson) Ch 28, Sm Anim Toxicol (Osweiler), Image: amazon.com

Acetaminophen

Treatment

Decontamination:

Emesis, activated charcoal x 1 dose (recent exposure)

Additional doses AC not indicated, may bind antidote

Antidote

N-acetylcysteine

Increased synthesis/availability of GSH (precursor)

Direct binding/detoxification of NAPQI

Supplies substrate for sulfation (↑% nontoxic metabolites)

140 mg/kg IV loading, 70 mg/kg IV or PO q6h x 72h.

Side effects: nausea, vomiting, anaphylaxis (if PO given IV)

SACCM Ch 79, Sm Anim Toxicol (Peterson) Ch 28, Sm Anim Toxicol (Osweiler ), Image: amazon.com

Acetaminophen

Treatment

Adjunctive Therapy

Ascorbic acid (vitamin C)

30 mg/kg PO q6h x 6. → To reduce methemoglobin to hemoglobin

SAMe

Important for PL and glutathione production

Cats: protective against development of erythrocyte oxidative injury.

Cimetidine

Inhibitor of cP450, reduce metabolism to NAPQI

Methylene blue

MB + NAC had little advantage vs NAC

Worsen Hz body anemia

SACCM Ch 79, Sm Anim Toxicol (Peterson) Ch 28, Sm Anim Toxicol (Osweiler), Image: amazon.com

Rodenticides

Three Main Categories

Anticoagulant

Cholecalciferol

Bromethalin

Also..

Phosphide

Strychnine

Image: http://blommi.com

Anticoagulant Rodenticides

Examples:

Brodifacoum

Bromadiolone

Diphacinone

Chlorophacinone

Warfarin

NOT Bromethalin

SACCM Ch 82


LD50 and T1/2 varies by chemical

Categorized by generation

First Generation: 4-6 days

Second Generation: 2-4 weeks

Absorption:

Peak plasma conc in minutes to 1h after exposure

Clinical signs: ≥36h after ingestion

SACCM Ch 82, Peterson Sm Anim Toxicol


Mechanism of Toxicity

Vitamin K1 is required for synthesis of clotting factors:

Factors must be able to bind Ca++ to be activated

Dicarboxylic acid groups on clotting factors

Initial synthesis – single carboxylic acid group

Vitamin K1 required for addition of second carboxylic acid group

(post-translational modification)




Do these rodenticides remove Vitamin K1

from the body?

MOA: Inhibition of Vitamin K Epoxide Reductase

SACCM Ch 82



Coagulopathy:

1) Depletion of active Vitamin K1

2) Depletion of clotting factors

T1/2 of clotting factors

Which coagulation test becomes abnormal first?

Coag factors reduced by 24-64h after exposure

Bleeding generally does not occur until 3-5d after

ingestion


VII 6.2h

IX 13.9h

X 16.5h

Extrinsic

Intrinsic

Common


Systemic Effects No clinical signs (if acute presentation)

Hemorrhage

Anemia, tachycardia, tachypnea, hypotension, lethargy

Dyspnea, other specific signs of bleeding

What are typical sites of hemorrhage? Body cavities

Hemothorax

Hemoabdomen

Hemopericardium

Hemarthrosis

Other

Hematuria, hemoptysis, hematomas,etc.

SACCM Ch 82, , Peterson Sm Anim Toxicol


Diagnostic Tests

MDB: Anemia, hypoproteinemia, thrombocytopenia

(consumption)

Coag testing: Prolongation of PT > PTT/ACT

PIVKA (send-out)

Detects inactive precursor proteins to II, VII, IX, X, C/S.

Abnormal results are not specific to anticoagulant rodenticides

Anticoagulant rodenticide screen (3-5d for results)

Generally not necessary, proves exposure



Approach to Treatment

1) Acute ingestion, asymptomatic, no previous exposure

Emesis, activated charcoal (repeated dosing)

Vitamin K1 PO

Or recheck PT at 24-36h, 96h after exposure and Rx if ↑

2) Acute ingestion, asymptomatic, possible previous exposure

Check PT. If not prolonged, treat same as above

If prolonged, avoid emesis +/- charcoal.

Administer Vitamin K1 (PO if eating) and monitor overnight for

bleeding

Ensure availability of plasma if needed




3) Symptomatic (bleeding) patient

Emesis / Activated Charcoal Contraindicated

Plasma Transfusion

+/- pRBC (or whole blood)

Other Supportive Care

Thoracocentesis (If symptomatic)

IV Fluids

Vitamin K1

No direct effect on coagulation

Requires 6-12h for clinically significant synthesis of new clotting factors

Still MUST be administered

PO at any point when the animal is eating (well absorbed)

SQ if not eating. NOT IV – risk of anaphylaxis,




Plasma

Can use: FFP, FP, Cryo-poor Plasma, FWB

How much?

To replace 1/3 of clotting factors? (15 ml/kg FFP)

6-10 ml/kg of plasma, 12-20 ml/kg FWB?

Every patient is different – assess efficacy / recheck PT




Vitamin K1

Dose:

2.5 mg/kg – 5 mg/kg PO daily (can be divided)

Duration of Vitamin K1 therapy

1st vs 2nd generation (1 wk or 2-4 wk)

Conservative approach: 4wk if toxin unknown

Recheck PT 48h after discontinuation of Vit K1

Other notes

Check patient environment for source of re-exposure

Prognosis: Good with appropriate supportive care


Other Rodenticides

Cholecalciferol (Vitamin D3)

Severe hypercalcemia, hyperphosphatemia, ARF

Bromethalin

Uncoupling of oxidative-phosphorylation and decrease

in ATP production

Cerebral edema, ↑ ICP, CNS Depression, ataxia,

tremors.

SACCM Ch 82, Sm Anim Toxicol (Osweiler)

Other Rodenticides

Zinc Phosphide

Creates phosphine gas with exposure to gastric acid → free radicals, oxidative damage.

Vomiting, myocardial damage (arrhythmias, ↓ contractility), pulmonary edema, pleural effusion, metHb, Hz bodies, ataxia, seizures, increased ALT, AST, Tbili, etc,

Gas produced smells like rotten fish, acetylene, garlic

Strychnine

Prevents uptake of glycine at inhibitory synapses of Renshawcells in CNS → dis-inhibition (excitatory) effect.

Hyperextension of limbs, muscle (extensor) rigidity, seizures,

respiratory arrest.

SACCM Ch 82, Sm Anim Toxicol (Osweiler)

References

Bonagura JD, Twedt DC. 2009. Kirk’s Current Veterinary Therapy XIV. St Louis: Saunders Elsevier.

Mizutani et al. 1992. Efficacy of whole bowel irrigation using solutions with or without adsorbent in the removal of paraquat in dogs. Hum ExpToxicol 11(6):495-504.

Mount et al. 2003. Use of a test for proteins induced by vitamin K absence or antagonism in diagnosis of anticoagulant poisoning in dogs: 325 cases (1987–1997). J Amer Vet Med Assoc 222(2): 194-8.

Osweiler GD, et al. 2011. Blackwell’s five-minute veterinary consult clinical companion: Small animal toxicology. Ames, IA: Wiley-Blackwell.

Peterson ME, Talcott PA. 2006. Small Animal Toxicology, 2nd Edition. St. Louis: Saunders Elsevier.

Silverstein DC, Hopper K. 2009. Small Animal Critical Care Medicine. St. Louis: Saunders Elsevier.

jen loewen, dvm, dacvecc

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