Common Toxins in the Veterinary ER

7/9/2019

Sarah K. Rice BA, CVT

Principles Veterinary team approach Top 10 toxins of 2018

Exposures Triage Exposure Goals Management Goals Nursing considerations Triage Management Nursing considerations

▪ 4 routes of exposure: ▪ Ingestion ▪ Inhalation ▪ Injection PRINCIPLES OF ▪ Topical (mm, skin, eyes)

TOXICOLOGY ▪ Goals of veterinary intervention: limit absorption, progression of toxicity

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▪ TIME! Limit suggestion of home tx during phone triage

▪ Prevent further exposure ▪ Instruct owners to protect themselves ▪ Topical or inhaled toxin ▪ Protective gear- gloves, mask, etc.

▪ Bathe if stable, topical exposure ▪ Handling of patients displaying abnormal behavior ▪ Collect packaging (ingredient info) if available ▪ Collect post exposure eliminations ▪ +/- contact poison control

Primary Evaluation • mentation • A, B, C • Presenting complaint • Intervention & stabilization • Intubation, positive pressure ventilation, anti-convulsant administration, oxygen, CPR, IV catheter placement Secondary Evaluation • Detailed history and Physical Exam • Diagnostic sampling, continued monitoring

▪ Most pertinent: history, patient clinical signs, responses to treatment

▪ Often difficult to identify cause of clinical signs if unknown toxin exposure ▪ Specific chemical analysis and laboratory findings ▪ Illegal drug identification ▪ Ethylene glycol ▪ Toxin levels (lead, zinc, specific substances)

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Decontamination procedures

Controlling clinical signs

Anticdote if available

Patient monitoring

Repeated treatments when necessary

Follow up monitoring/post hospitalization care

▪ Prevent initial or continued absorption of a toxin ▪ Procedure dependent on route of exposure ▪ Dermal- bathe with mild dishwashing detergent (Dawn) ▪ Protective equipment for care team ▪ Ocular ▪ - flush with 0.9% NaCl or warm water x 15-30 min. ▪ Ingestions- ▪ Emetics- gastrointestinal emptying ▪ Apomorphine IV DECONTAMINATION ▪ Xylazine IV in cats, yohimbine or atipamizole ▪ Hydromorphone, morphine IV or SQ PROCEDURES ▪ Hydrogen peroxide PO ▪ Contraindications-corrosives, strong acids/bases, dyspnea, comatose/severe mental depression, hypoxia, lack gag reflex ▪ Emetics not recommended in rodents or rabbits ▪ Gastric lavage +/- enema administration ▪ Dilution techniques ▪ Activated charcoal ▪ +/-Cathartic (sorbitol) ▪ Poor efficacy for metals, small molecule intoxications

▪ Emetics ▪ Most effective shortly after toxin ingestion ▪ Food present in stomach

▪ Removal of stomach contents to remove toxin prior to digestion/absorption ▪ 40-60% stomach contents ▪ Emesis ▪ Two mechanisms of action: ▪ Stimulation of dopamine receptors in chemoreceptor trigger zone (Apomorphine) ▪ Gastric irritation (H202)

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▪ Many toxins lack anticdote

▪ Observation in hospital

▪ Supportive care ▪ Liver metabolism, kidney excretion ▪ IV fluid tx: replace fluid losses, maintain UOP 2-4ml/kg/hr ▪ Analgesia

▪ Anti-convulsant therapy

▪ Intravenous lipid therapy- fat soluble toxins ▪ Lipid emulsion- bolus dose (1.5-4 ml/kg IV) followed by CRI (0.25ml/kg/min) x 30-60 min

▪ Therapeutic plasma exchange, hemodialysis

▪ Mechanical ventilation

▪ Activated charcoal ▪ Apomorphine ▪ Atipamezole ▪ Atropine Sulfate ▪ Calcium EDTA COMMON MEDS ▪ Calcitonin ▪ Ethanol USED IN ▪ Fomepizole (4-MP) ▪ Flumazenil TOXICOLOGICAL ▪ Hydrogen Peroxide ▪ Naloxone EMERGENCIES ▪ N-acetylcysteine ▪ Pralidoxime (2-PAM) ▪ Vitamin K1 ▪ Yohimbine

▪ Respiratory status ▪ Oxygenation and ventilation ▪ fatigue

▪ Cardiovascular status ▪ ECG ▪ Blood pressure ▪ mm/CRT

▪ Renal status ▪ GI status ▪ v/d

▪ Coagulopathy ▪ Neurological/mentation status

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▪ Continuous monitoring in hospital when indicated ▪ Significant technician role- not just initial triage!!

▪ Repeated assessment ▪ Vital signs ▪ Mentation

▪ Repeated treatment ▪ Reversal agent administration ▪ Anticonvulsants +/- escalated control efforts CONTROLLING ▪ Intralipid administration (exception: serum lipemia, dose range) CLINICAL SIGNS ▪ New clinical signs secondary to toxin exposure ▪ Potential for altered tx plan/nursing considerations ▪ Ex: Dermal injury development, aspiration pneumonia, cardiac arrhythmia, electrolyte derangements, ventilatory/oxygenation status

Legal Landscape Agricultural Population Socioeconomic Environmental implications production status factors pharmaceuticals weather

• Dogs > Cats • 365 days a year, 24 hours a day • 888.426.4436 • Consultation with toxicologist, associated fee • 2018- 213, 773 cases evaluated

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▪ OTC Medications ▪ RX medicationss ▪ Food items & additives COMMON ▪ Chocolate ▪ Veterinary products TOXINS… ▪ Household items TOP 10 ▪ Rodenticide exposure ▪ Insecticide exposure ▪ Plants ▪ Garden products

▪ Non-Steroidal Anti-Inflammatory Drug (NSAID) ▪ Acetaminophen (Tylenol)

NSAID Acetaminophin

▪ Ibuprofen, naproxen ▪ Methemoglobinemia in cats ▪ Cats >susceptibility than dogs ▪ Carprofen, meloxicam, deracoxib ▪ Both species: oxidative and liver cell ▪ Toxic doses & clinical signs: damage ▪ 20-125mg/kg: v/d, abd pain ▪ Anticipate peak LE elevation at 72 hrs ▪ >125mg/kg: hematemesis, melena, AKI ▪ Dyspnea, cyanosis, dark brownish MM, edema ▪ 400-500mg/kg: CNS signs, acidosis ▪ KCS ▪ Tx: Decontamination, AC q6-8 hrs, GI protectants, diuresis ▪ Tx: decontamination, AC multiple doses, ▪ +/- barbituates if seizures ▪ IV fluids, gi & hepatic protectants ▪ Hemodyalisis ▪ N-acetylecysteine (PO or IV) ▪ Improves excretion, separate from AC ▪ 5% solution: 140mg/kg, then 70mg/kg q 6 hours for 7+ doses

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▪ Anti-Depressants ▪ Opioids ▪ Adderall 2. PRESCRIPTION ▪ Cardiac medications MEDICATIONS ▪ Antithrombotics ▪ Antihypertensives ▪ Bronchodilators

▪ Example: ALBUTEROL inhaler ▪ Tachycardia ▪ hypokalemia ▪ hyperexcitable ▪ pupil dilation ▪ Tremors, restlessness, ataxia ▪ hypertension ▪ vomiting ▪ Panting

4 groups: MAOIs, TCAs, SSRIs,atypical ▪ Adjust levels of serotonin, norepinephrine, dopamine, epinepherine ▪ Varying clinical signs: depression, restlessness, arrhythmia, respiratory depression, death, ataxia, seizures ▪ SEROTONIN SYNDROME ▪ Mentation changes, neuromuscular abnormalities, autonomic instability, ataxia, tremors/seizures ▪ Thermoregulation center → hyperthermia ▪ Tx: decontamination, AC, supportive care, ▪ Cyproheptadine: serotonin receptor antagonist ▪ Dog: 1.1mg/kg, cat: 2-4mg/kg q 4-6hr ▪ Propranolol: serotonin receptor antagonist, tx hypertension, tachycardia ▪ Phenothiazines (humans)- caution with hypotensive patient

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▪ Grapes & Raisins ▪ Allium species ▪ Xylitol 3. FOODS/FOOD ▪ Salt ADDITIVES ▪ Unbaked bread dough ▪ High fat substances ▪ bones

Xylitol Salts ▪ GI irritant, often cause emesis ▪ Vomiting, ataxia, collapse, seizures ▪ V, polydypsia, hypernatremia ▪ Potential liver failure: coagulopathy, increase ALT, tbili ▪ Salt toxicosis: ataxia, CNS sighs dehydration/overhydration, protracted v+ ▪ Hypoglycemia, Hypokalemia, hypophosphatemia ▪ Tx: decontamination, supportive care ▪ Electrolyte balance restoration with ▪ Dogs: insulin release up to 6x greater than diuresis: decrease slowly to avoid cerebral equal dose of glucose == rapid drop in BG edema ▪ GI tract absorption ▪ Max 8-12mEq/L/24hrs decrease ▪ Onset clinical signs 30 min-12 hrs post ▪ Mannitol, furosemide ingestion ▪ Ex: homemade play-doh ▪ toxic dose 0.1g/kg; hepatotoxic >0.5g/kg ▪ 2c. Flour, 1 c. salt, ½ c. H20 ▪ gum= 0.3g, 1cup granulated xylitol= 190g ▪ Toxic dose 2g NaCl/kg ▪ Tx: +/- emesis, baseline labwork, IV fluids ▪ 10lb dog: ¾ tsp of dough w/dextrose, liver protectants, antioxidants

Methylxanthines: caffeine & theobromine

-caffeinated soda, chocolate, cocoa beans, teas -Chocolate: theobromine toxicity ≥ 100mg/kg (dogs & cats) -Milk chocolate=45-60mg/oz -Semisweet (dark)=130-185 mg/oz -Baking choc (unsweet)= 400-450mg/oz Clinical signs: increased muscular contractility 4. CHOCOLATE -vomiting, diarrhea, hyperactivity, restlessness, ataxia, muscle tremors, ventricular cardiac arrhythmias -tx: decontamination (emesis, gastric lavage, AC), IV fluid therapy, anticonvulsants, ECG and BP monitoring -urinary catheter with closed collection: methylxanthines reabsorb via bladder - antiemetics, GI protectants for ongoing v/d - possible tx up to 72 hrs

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▪ Prescription medications ▪ oral, ocular, dermal, injectable ▪ adverse reactions, administration/dosing errors ▪ Topical Flea/Tick Medications 5. VETERINARY ▪ Permethrins, Pyrethrins PRODUCTS ▪ Flea tick collars ▪ Avermectin ▪ Organophosphates

▪ (see insecticides) ▪ Labeled for flea & tick control ▪ Indicated for dogs ▪ Toxic to cats via direct or secondary exposure; low toxicity in most mammals ▪ Available formulations: as spot-on application alone or in combination with other compounds, topical and premise sprays

▪ https://youtu.be/BifuRgxIYwU

• Topical toxin exposure

• Dermal decontamination: bathe

• Supportive care • Hyperthermia control • Dehydration • Nutrition • Anti-tremorgenic, anticonvulsant • Flea control recommendations & home care advice

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▪ Ethylene Glycol/Antifreeze ▪ Zinc ▪ Lead ▪ Bleach/cleaning products ▪ Nonionic, anionic, cationic detergents detergents 6. HOUSEHOLD ▪ Glues GOODS ▪ Mothballs ▪ Phthalates ▪ Batteries ▪ Kerosene ▪ Tobacco/nicotine

Ethylene Glycol Zinc

▪ Antifreeze, de-icers, solvents, brake fluid, ▪ Metals, pennies after 1983 condensers ▪ Toxic dose: 0.7-1g/kg ▪ Toxic dose: 4ml/kg (dog), 1.5ml/kg (cat) ▪ Labs: inflammatory leukogram, anemia ▪ Liver metabolism→calcium oxalate crystal (regenerative), spherocytes, hemoglobinuria →AKI, severe metabolic acidosis (renal tubule damage) ▪ Increased serum Zinc levels ▪ Stage 1: 0-12 hrs, neurologic changes

▪ Stage 2: 12-72 hrs, worsening of AKI signs to ▪ Acute hemolysis oliguric renal failure ▪ Clinical signs: anorexia, v/d, CNS depression, pale mm, icterus ▪ In house tests: false results ▪ Tx: FB decontamination (ex lap or endoscopy), ▪ TX: immediate decontamination, aggressive IV supportive care fluid tx, Fomepazole (4-MP), 30% ethanol ▪ Concern for DIC, renal failure ▪ hemodialysis ▪ Anemia – blood product administration ▪ Chelation therapy 29

▪ Expandable Glues: Gorilla Glue ▪ Vomiting, retching, abdominal pain & distention, excessive drooling, pawing at face ▪ Tx: Supportive care, anti-emetics, IV fluid replacement therapy ▪ Large ingestion requires gastrotomy followed by analgesia & surgical recovery

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▪ Anticoagulant Rodenticides ▪ Bromethalin 7. RODENTICIDES ▪ Zinc-Phosphide ▪ Cholecalciferol

Anticoagulant Rodenticides Bromethalin ▪ For use against warfarin resistant rodents ▪ Inhibit Vit K dependent coagulation factors from activation (II, VII, IX, X) ▪ Cerebral edema, increased intracranial ▪ Prothrombin time tests this pathway (elevation) pressure ▪ 2nd generation products worse > duration of ▪ Clinical signs: action than 1st, lower toxic dose ▪ High dose: muscle tremors, seizures, ▪ Clinical signs (3-7d. Post exposure): bleeding hyperexcitability, hyperthermia into body cavities (lethargy, resp distress) ▪ Low dose: ataxia, paresis/paralysis, CNS ▪ Tx: decontamination +/- AC, PO Vit K (with depression food) ▪ +/- transfusion FWB, FFP ▪ Tx: aggressive decontamination w/gastric ▪ Supportive care (thoracocentesis, etc) lavage, AC x 48 hrs, control of seizures, ▪ PT baseline, 48, 72 hrs, and 48 hrs post Vit K supportive care (O2, IV fluids) tx ▪ Cerebral edema mgmt: mannitol, head ▪ Vit K x 14 days (1st gen) or 30 days (2nd gen) elevation, avoid jugular vein pressure, ▪ Normocapnia ▪ Poor prognosis with severe signs 32

▪ Carbamates ▪ Organophosphates ▪ Permethrins 8. INSECTICIDES ▪ Pyrethrins ▪ Ivermectin

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Permethrins Ivermectin

▪ Uses livestock, companion pets, agriculture, home gardens ▪ Broad spectrum anti-parasitic, endo and ecto-parasite tx; small and large animal treatment formulations ▪ Permethrins: OTC spray, dust, gel, dip, shampoo, topical tx ▪ OTC ▪ Pyrethroids: synthetic permethrin, increased potency and toxicity ▪ Toxic dose: dogs 2.5mg/kg, cats 1.3mg/kg (varies due to individual sensitivity) ▪ Cats more profoundly affected than dogs, primary or ▪ Enterohepatic circulation secondary exposure ▪ Increased sensitivity with high flea burden ▪ Clinical signs: ataxia, agitation, disorientation, ▪ Rapid absorption mydriasis, acute blindness, bradycardia; seizure, ▪ Clinical signs: hyperesthesia, generalized twitching coma (tail, skin, ears), tremors and seizures ▪ Potential for rolonged signs (3-5 days), less if ▪ Tx: decontamination, AC aggressive care ▪ seizure control (avoid benzodiazepines) ▪ Tx: decontamination (dish detergent bath), ▪ Phenobarbital, propofol temperature regulation, muscle relaxers (methocarbomol) ▪ IV lipid therapy ▪ IV fluid support ▪ Mechanical ventilation (severe aspiration ▪ IV lipid therapy peneumonia, hypoventilation) ▪ AC not beneficial 34

▪ Lilies-Easter, Tiger ▪ Rhododendrons, Azaleas ▪ Sago Palm 9. PLANTS ▪ Oleander, Foxglove, Lily of the Valley ▪ Philodendron ▪ Aloe ▪ Castor Bean Plant

Sago palm Lillies

▪ Tropical, subtropical, decorative ▪ Easter, stargazer, Asiatic, tiger, rubrum, environments Japanese (all parts of plant) ▪ All parts of plant are toxic, seeds have ▪ Renal tubular injury, AKI, death in cats highest concentration of toxin ▪ Initial clinical signs: v, lethargy, anorexia ▪ Clinical signs: v/d, depression, LE elevation ▪ 24-72 hrs post ingestion: pu/pd, azotemia, ▪ Liver damage with encephalopathy, hyperphosphatemia coagulopathy ▪ Tx: decontamination, AC, aggressive fluid ▪ Tx: aggressive decontamination, multiple dialysis, +/- peritoneal dialysis AC doses, supportive care with IV fluid tx, liver protectants ▪ Prognosis dependent on extent of liver damage

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▪ Fertilizers ▪ Tremorgenic mycotoxins 10. GARDEN ▪ Metaldehyde PRODUCTS ▪ Insecticides/rodenticides ▪ Strychnine

Tremorgenic Mycotoxins Metaldyhyde ▪ Fungal metabolism ▪ Snail/slug bait ▪ Moldy garbage, foods, compost, grains ▪ Highly palatable, acetaldehyde odor ▪ Primarily canine ingestions ▪ Toxic dose: 100mg/kg ▪ Enterohepatic recirculation ▪ Clinical Signs: CNS signs--seizures, ▪ Labs: lactate accumulation, increased hypersalivation, incoofdination, muscle creatnine, AST, dehydration markers fasciculations, metabolic acidosis, tachycardia ▪ Hyperthermia, hyperesthesia, ▪ Clinical signs: onset 30min-3 hrs ▪ Progression to respiratory failure, liver ▪ Early: vomiting, panting, weakness, damage hyperexcitability, muscle tremors, rigidity ▪ Later: opisthotonos, seizures, nystagmus, ▪ Tx: decontamination, supportive care, control of recumbency hyperthermia ▪ Muscle activity results in hyperthermia, metabolic ▪ Good prognosis with tx changes, dehydration, rhabdomyolosis ▪ Tx: decontamination (emesis or gastric lavage), multiple AC doses, anticonvulsants, muscle relaxants, IV fluid therapy ▪ early decontamination= good prognosis 38