Toxicology - Tidbits for treatment of common intoxications

Lisa Foster, BS, RVT, VTS (ECC) Internal Medicine/Oncology Technician Iowa State University Plan

• General management • Specific intoxications – NSAIDs • Human • Veterinary – Xylitol – Bromethalin rodenticide Decontamination

• Goal of decontamination – Eliminate and prevent absorption • Ocular – Flush medially to laterally for 20-30 minutes – At home flush 1st if corrosive/caustic agent • Saline • E-collar if possible – Recommend minimum ophtho database Decontamination

• Dermal – Prevent oral re-exposure • Grooming in cats – Bath with mild dish soap • No dishwasher detergent • Protect yourself from toxic agent – Gloves – After decontamination monitor for hypothermia Decontamination

• Emesis – Risk of aspiration all patients • Contraindications – Caustic – Sharp objects – Altered mentation – Inability to protect airway • If emesis is contraindicated – Gastric lavage GI Decontamination

• Only vomit 40-60% of stomach contents • Most effective within 1-2 hours post ingestion • Dogs – Apomorphine – 3% Hydrogen peroxide • Cats – Dexmedetomidine – Xylazine Apomorphine

• Acts directly on the chemoreceptor trigger zone • Dose: – 0.03-0.04 mg/kg IV – Repeat if necessary • Emesis occurs within 4-6 minutes • Rare side effect: CNS depression or respiratory depression – Naloxone • 0.01-0.04 mg/kg, IV, IM, or SQ • Will not reverse emetic • Counteract emesis effects with: – Maropitant 1 mg/kg IV/SQ – Ondansetron 0.1-1 mg/kg IV 3% Hydrogen Peroxide

• Acts as a gastric irritant • Dose: 1-2 mL/kg PO – Can be repeated – Do not exceed 50 mL • Emesis typically occurs in 5-10 minutes • At home – Carefully syringe • Tu r k e y b a s t e r • Works best if food is present • Risks – Esophagitis – Gastritis Dexmedetomidine

• Centrally mediated alpha2-adrenergic agonist • Dose: 5 mcg/kg IM – Can repeat dose if not too sedate • Emesis occurs within 5-10 minutes • Reversal • Atipamezole: same volume as dex., IM • Yohimbine: 0.1 mg/kg IM, SQ or IV slowly Xylazine

• Centrally mediated alpha2-adrenergic agonist • Dose: 0.4 mg/kg IM • Emesis occurs within 10-20 minutes – But not always effective • Often see CNS & respiratory depression – Reversal • Yohimbine: 0.1 mg/kg IM Remember

• Emesis can’t be induced in all species – Rabbits – Horses – Birds Gastric lavage • How to: – Anesthesia and intubation required – Measure stomach tube from nose to 13th rib – Empty contents – Lavage with large amounts of water • Until contents is clear • Give charcoal • Complications: – Aspiration – Esophageal/gastric injury Decontamination-Adsorption

• Activated charcoal (AC) – Oxidized carbon compounds – Draws substance to the surface and binds to them • Preventing absorption from the GI tract • Administration – Suspensions work best (toxiban) – Some will eat/drink • Does food affect efficacy? – Syringe feed – Orogastric/nasogastric tube Activated Charcoal

• Adsorbs many toxins – But not heavy metals, ethylene glycol, or xylitol • Dose is 1-3 g/kg PO – Dose repeatedly if enterohepatic recirculation • Cathartics (ex. Sorbitol) – Only use once; osmotically active – Increases GI motility Activated Charcoal

• Complications – Vomiting • Aspiration – Dehydration – Electrolyte abnormalities • Hypernatremia • Monitor with repeated dosing – Black/tarry stool-warn owners • Oral dosing contraindicated with reduced gag/ swallow reflex Intravenous lipid emulsion (ILE)

• Long chain triglycerides from plant oils – Soybean & safflower • Use sterile technique for ILE administration – Prevent bacterial contamination – Use within 24 hours • “Lipid Sink” – Lipids bind to toxin – Prevents toxic effects Intravenous lipid emulsion (ILE)

• 20% concentration • Initial bolus over a minute at 1.5 mL/kg • Constant rate infusion: 0.25 - 0.5 mL/kg/min for 30-60 minutes – Repeat up to every 6 hours as needed once lipemia clears • Useful for many toxins: – Local anesthetics (bupivacaine, lidocaine, etc.) – Baclofen – Ivermectin – Permethrin – Others... Intravenous lipid emulsion (ILE)

• Storage – Unopened room temperature – Shelf-life up to 2 years • Cons – Possible pancreatitis – Fat embolism Human NSAIDs

• (Advil®) • (Aleve®) Ibuprofen

• – Rapidly absorbed (30-90 minutes) – Plasma half life 2-2.5 hours – Rapid/complete absorption from GI – Highly protein bound • Albumin – Metabolized in liver • Extensive enterohepatic recirculation – Mainly excreted in urine Ibuprofen • Mechanism of Action (MOA) – Inhibit COX – Systems affected (dose dependent): • Gastrointestinal – Ulcerations/perforation • Kidneys – Acute kidney injury • Platelets – Primary coagulopathy • Central nervous system – Seizures/coma Ibuprofen • Toxicity – Cats are more sensitive – GI signs • 2-6 hours post ingestion • Dogs: ≥50-125 mg/kg – Renal signs • Develop as early as 12 hours post ingestion • Dogs: ≥175 mg/kg – CNS signs • Often seen within 1-2 hours of exposure • Dogs: ≥400 mg/kg Naproxen

• MOA & Pharmacokinetics – Half life: 74 hours • Toxicity – GI signs: 5-10mg/kg – Kidney injury: 20-25mg/kg Acute NSAID overdose

• Treatment – Emesis – Multiple doses of AC • Enterohepatic recirculation – Dose q 6-8 hours for 24 hours – Diuresis of 2x maintenance for at least 48 hours • Prevent AKI • Monitor chemistry values daily • Slow tapering – Cats treated more aggressively GI irritation & ulceration

• Treatment – GI protectants • 7-10 days or depending on severity of clinical signs • H2 blockers – Cimetidine, famotidine, or ranitidine • Proton pump inhibitors – Omeprazole, esomeprazole, or pantoprazole • Sucralfate • Nephrotoxic dose of NSAIDs • IVF – 2x maintenance for 48-96hrs • Dependent on dose & NSAID involved • Monitor renal function – On presentation and daily – For up to 3-5 days • Hemodialysis in severe cases Liver injury

• Can be seen with large overdoses – Idiosyncratic • Monitor liver values – ALT – Alk Phos • Monitor liver function • Liver protectants Neurological injury

• Severe intoxication • Treatment – Control seizures • Anticonvulsants – Respiratory support • Ventilator – Monitor for hypothermia NSAID overdose

• Prognosis – Variable depending on the dose and NSAID – Acute ingestion • Good – Severe signs • Fair to guarded Veterinary NSAIDs

• • (Rimadyl) • • Deracoxib (Deramaxx) • (Previcox) Veterinary NSAIDs • MOA – COX inhibition • Pharmacokinetics – Highly protein bound – Metabolized by liver • Enterohepatic recirculation – Meloxicam – Limited or suspected » Carprofen and ketoprofen – Excreted in feces Carprofen • MOA – Inhibits COX enzymes • Toxicity in cats – 4 mg/kg • Toxicity in dogs – GI signs • 20mg/kg – Acute kidney injury • 40mg/kg Veterinary NSAIDs • Toxicity in Dogs – Deracoxib • ≥10mg/kg showed GI signs • Doses up to 100mg/kg showed no renal damage – Firocoxib • 50mg/kg resulted in GI signs – Meloxicam • 5 times therapeutic dose – 0.1-0.5mg/kg resulted in some GI signs NSAIDs

• Clinical Signs – Decreased appetite – Vomiting/diarrhea – Dark/tarry stool – PU/PD – Lethargy – Seizure Veterinary NSAIDs • Treatment – Emesis – Activated charcoal • Multiple doses if enterohepatic recirculation – GI protectants • H2blocker – Famotidine: 0.5-1 mg/kg PO, IV, IM, SQ q 12-24hr • Proton pump inhibitor – Pantoprazole: 0.7-1 mg/kg IV q 12hrs – Omeprazole: 05-1 mg/kg PO q 12hrs – IVF – Misoprostol Veterinary NSAIDs

• Prognosis – Fair to good with acute & chronic ingestion – Oliguria or anuria • Guarded to poor prognosis Xylitol • Natural sugar alcohol • Used as a sugar substitute – Chewing gum & mints – Nicotine gum – Candy – Toothpaste – Baked goods – Peanut butter – Vitamins – Diet/diabetic food Xylitol

• MOA – Quickly absorbed in about 30 minutes – Direct stimulation of insulin from the pancreas • 80% is metabolized in the liver Xylitol

• Toxicity in dogs – Doses: • 50 mg/kg – Mild signs • 100 mg/kg – Hypoglycemia • 500 mg/kg – Hepatic injury Xylitol and cats

• Small study in 2018 • Gave xylitol at: – 100, 500, and 1000 mcg/kg • 100 & 500 showed no hypoglycemia • 1000 mcg/kg showed an ↑ of insulin • Safe for cats?

Xylitol

• Clinical Signs – Vomiting – Hypoglycemia • Weakness • Depression • Collapse • Ataxia • Tremors or seizures Xylitol treatment

• Emesis – Caution in patients with documented hypoglycemia • Activated Charcoal • Not effective Xylitol treatment

• Diagnostics – Baseline blood glucose – Electrolytes • Potassium – Liver values – evaluate for liver damage/ dysfunction Xylitol treatment

• Blood glucose checks – Q2hrs for the first 12hrs • Frequent meals • IVF – 12-24 hours – +/- dextrose • Liver protectants Xylitol

• Prognosis – Good • Lower doses ingested & decontamination – Guarded • Evidence of hepatic involvement Bromethalin

• New Environment Protection Agency – Ruling in 2008 – Stop the use of anticoagulant rodenticide • Purpose to reduce ecologic effects • Reduce risk to children, wildlife and pets • All products on the market follow guidelines by June 2011 Bromethalin

• MOA – Reduces ATP production • Impairs Na+ & K+ pump – Electrolyte imbalances » Fluid shift – Causes brain swelling and seizures/coma Bromethalin

• Pathophysiology – Absorbed in GI tract – Metabolized in liver • Metabolite is more potent than bromethalin – Wide distribution in body – Highest levels are found in fat and brain – is slow • Occurs in bile • Some enterohepatic recirculation Bromethalin

• Toxicity – Lethal dose for dogs is 1 mg/kg • Death reported as low as 0.36mg/kg – Cats lethal dose is 0.25mg/kg – Ingestion of lower doses • May delay signs for 2-7 days – Mild poisoning could have signs for up to 4-6 weeks Bromethalin

• Clinical signs – Acute onset of CNS signs • Excitation, muscle tremors, & seizures – Common • Anorexia • Progressive ataxia, paresis & hind limb paralysis • Abnormal PLR, forelimb extensor rigidity Bromethalin acute ingestion • Emesis & AC Symptomatic bromethalin ingestion

• Treatment is support – IVF – Electrolyte monitoring – ILE – Seizures • Anticonvulsants – Cerebral edema • Mannitol • Hypertonic saline Bromethalin Treatment

• Severe cases – Medical coma – Ventilation – Hypothermia • Prognosis – Very guarded once clinical signs develop – Grave if severe signs Helpful Resources

• Online – VIN – http://aspcapro.org/animal-poison-control-center – www.petpoisonhelpline.com • Phone – Case number to reference – Pet Poison ($59) • 855-764-7661 – ACPCA ($65) • (888) 426-4435 • Books – Blackwell’s Five-Minute Veterinary Consult