Holiday toxins Introduc$on’

12/19/15

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Holiday toxins

Jus$ne A. Lee, DVM, DACVECC, DABT CEO, VETgirl [email protected]

Garret Pach$nger, VMD, DACVECC COO, VETgirl [email protected]

Garret Pach$nger, VMD, DACVECC

COO, VETgirl

Introduc$on

Jus$ne A. Lee, DVM,

DACVECC, DABT

CEO, VETgirl

Introduc$on Conflict of Interest Disclosure

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Call in from Smart Phone! Goals of the lecture

•  Review of common holiday toxicants! – Mechanism of ac$on

– Clinical signs – How to treat!

CHOCOLATE

Chocolate •  Naturally occurring alkaloids from the Theobrema cacao

plant

•  Methylated xanthines: –  Theobromine –  Caffeine

•  Associated with all the holidays! –  Easter –  Halloween –  Christmas

Chocolate

•  Chocolate bezoar – Slow absorption! – OK to induce emesis even hours out

•  Very long T½: 17 hours " treat until clinical signs resolve (typically 1-2 days; up to 3-4 days)

Chocolate: Toxic doses •  Methylxanthines (theobromine + caffeine) = toxic! •  It’s the dose that makes the poison…

Product Theobromine Caffeine

White chocolate 0.25 mg/oz 0.85 mg/oz

Milk chocolate 44-‐60 mg/oz 6 mg/oz

Dark semisweet 135 mg/oz 20 mg/oz

Unsweetened baker’s chocolate

390-‐450 mg/oz 47 mg/oz

Dry cacoa powder 400-‐737 mg/oz 70 mg/oz

Craft EM, Powell LL., 5 MVC

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Great free ASPCA APCC resources!

•  h`p://aspcapro.org/freebies •  Free app!

•  When do you see signs? (Theobromine) –  Mild signs (agitation, vomiting, diarrhea): 20 mg/kg –  Moderate signs (tachycardia, hypertension): 40-50 mg/kg –  Severe signs (tremors, seizures): 60 mg/kg

•  Clinical signs: –  GI: Vomiting, diarrhea, hypersalivation –  CARDIAC: tachycardia, VPCs, SVTs, hypertension –  CNS: hyperactivity, tremors, seizures –  MISC: polyuria, hyperthermia

Chocolate

Craft EM, Powell LL., 5 MVC

Decision to hospitalize?

•  Based on $me since inges$on

•  Based on emesis produc$on

•  Based on pet owner ($$)

•  Based on presence of clinical signs

Chocolate: Treatment •  Decontamination:

–  Delayed emesis –  Multiple doses of activated

charcoal (AC) –  Anti-emetic therapy or pro-

kinetics

•  Supportive –  IV fluids + frequent walks –  No need for UCS –  Sedation –  Temperature monitoring –  Anti-convulsant therapy

•  If HR or BP > 180 bpm " sedate! –  Acepromazine –  More acepromazine –  Butorphanol

•  Monitoring: –  Beta-blocker therapy (if HR >

180) –  ECG monitoring

Grapes and raisins •  Discovered 2001

–  Red, green, seedless, seeded –  Grape seed extract OK? –  Sources: trail mix, grape juice, etc. –  Baking process?

•  Eubig et al and VIN: –  Grapes: 0.7 oz/kg –  Raisins: 0.11oz/kg

•  More than a handful? –  Idiosyncratic?

Grapes and Raisins

•  Clinical signs: –  Anorexia –  Vomiting –  Diarrhea –  Kidney pain –  Azotemia –  Oliguria (0.5-1 ml/kg/hr) –  Anuria (< 0.5 ml/kg hr)

•  Azotemic? R/O nephrotoxicants: –  Grapes/raisins/currants –  NSAIDs –  Ethylene glycol

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So how aggressive do we treat Vitus spp.? •  Decontamination

–  Delayed emesis induction ok! –  Activated charcoal + sorbitol X 1

•  Anti-emetics

•  Aggressive IV fluids X 24-48 hours –  PCV/TS 35%/5 mg/dL –  UOP?

•  Monitoring clinicopathologic tests

•  Gastric protectants if azotemic

So how aggressive do we treat Vitus spp.?

•  Treat it like it was your dog

•  50% “unaffected”

Harper, 3 yo black lab, 30 kgs •  PC: ingested 12 oz. raisins 3 days prior – o unaware of toxicity

–  Vomiting, loose stool, anorexia, depression X 24 hours

•  PMHX: healthy

•  Went to RDVM: –  CBC/CHEM:

•  BUN: 180 mg/dL •  Creatinine 5.4 mg/dL " referred

•  Presentation: –  T: 100.2°F, HR 80, RR 16 –  5% dry –  Mild abdominal and renal pain, no palpable bladder

Harper •  Diagnostics:

–  Venous blood gas –  Catheterize, empty bladder, quantitate urine, pull UA,

CULTURE •  FAST U/S – no bladder seen •  10 mls

•  Treatment –  Bolused 1 liter LRS IV once

•  Post-bolus, small bladder seen on FAST U/S –  Blood pressure 170/100 mmHg (MAP 150 mmHg) –  Gastrointestinal protectants

•  Famotidine 0.5 mg/g IV q. 24 •  Aluminum hydroxide 10 mls PO q. 8 •  Sucralfate 1 gram PO q. 8

–  Ampicillin 22 mg/kg IV q. 8

Harper •  Treatment:

–  Antihypertensives: •  Enalapril 0.5 mg/kg PO SID •  Hydralazine 0.5 mg/kg PO BID

–  Anti-emetics: •  Maropitant 1 mg/kg SC SID

–  Blood pressure monitoring –  UOP monitoring (UCS)

Day 2 229 11

Day 3 300 14.7

Day 4 >300 18

Day 5 >300 22

Day 8 32 0.8

200-300 ml/hr

100 ml/hr

50 ml/hr

20 ml/hr; bolused 1 L

400 ml/hr

BUN mg/dL Creat mg/dL UOP Fluid rate PCV TS kg

35 5

30 4

30 4

34 6

27 4

Oliguric

Oliguric

Oliguric

Anuric

13 ml/kg/hr

33

33

35

31

31

ALCOHOL

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Common sources of alcohol

•  Ethyl alcohol (ethanol) –  Liqueurs – Wine –  Beer –  Eggnog!

•  Other sources: – Unbaked bread dough –  Baked goods soaked with alcohol –  Chocolate candies with liqueurs

Alcohol: Clinical signs

•  Ataxia •  Drunkenness •  Altered menta$on •  Seda$on •  Bradycardia •  Hypoven$la$on •  Tremors/seizures •  Vomi$ng

Alcohols

•  Clinicopathologic tes$ng: – Hypoglycemia

– Metabolic acidosis

•  Treatment: – Too late for decontamina$on?

– NO charcoal! – Symptoma$c suppor$ve care

Unbaked bread dough

•  Yeast!

•  Products: –  Pizza dough –  Starter kits – Roll products

•  Timing: – Holiday toxin

Unbaked bread dough •  Stomach = oven

•  CO2 and ethanol gas

•  Clinical signs: – GI: hypersalivation, retching, bloat, abdominal

distension, GDV, abdominal pain – Ethanol toxicosis: ataxia, blindness, bradycardia,

vocalization, hypoglycemia, m. acidosis

Treatment: Unbaked bread dough •  Decontamination if ASX

– ACC X1? Meh – Cold water lavage

•  IV fluids •  Anti-emetics •  Dextrose monitoring and supplementation •  Thermoregulation •  Surgery?

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CAFFEINE

Caffeine

•  Biggest cause of fatalities in poisoned patients

•  Commonly found in high concentration: – Coffee bean sources – Tea – Diet pills – Herbal products (guarana) – Caffeine stimulant tablets

Caffeine: Toxic doses

•  > 15 mg/kg: Agitation •  > 25 mg/kg: Moderate signs •  > 50 mg/kg: Cardiotoxic •  140 mg/kg: LD50 (for dogs) •  80-150 mg/kg: LD50 (for cats)

Caffeine

•  See clinical signs within 30 minutes –  Similar signs to theobromine – Often too late for decontamination?

•  Short half-life! 4.5 hours

•  Signs resolve within 12-36 hours

•  Same treatment as theobromine

Caffeine •  Blood pressure and ECG monitoring

•  Fluid therapy

•  Sedation (if hypertensive, tachycardiac)

•  Beta-blocker therapy

•  Anti-convulsant therapy

Macadamia nuts •  Macadamia intergrifolia or tetraphylla tree

•  Most common unknown toxicant

•  Unknown MOA – Affects neurotransmitters, neuromuscular

junctions, muscle fibers?

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Macadamia nuts •  Clinical signs seen in 12 hours, resolve in

24-48 hours

•  Toxic dose: 0.7-2 g/kg or 1 nut/kg body weight

Macadamia nuts •  Clinical signs:

– CNS: weakness, ataxia, tremoring, recumbent – GI: vomiting, colic, pancreatitis – MS/NEURO: lameness, hind limb weakness, joint pain

•  Blood work: – #cPL – #WBC, – #ALK PHOS – #triglycerides

Macadamia nuts: Treatment

•  If toxic dose ingested, decontamination: –  Emesis – ACC X1

•  Anti-emetic therapy

•  Symptomatic supportive care

•  Monitor for pancreatitis!

Poinsesas: Euphorbia pulcherrima

•  Don’t propagate the myth!

•  Milky sap (latex) " mild irritant

•  Irritant to: –  Gastrointes$nal tract –  Dermal

–  Ocular

Christmas Cactus: Schlumbergera bridgesii

•  General GI irritant

American Mistletoe: Phoradendron flavescens

•  Considered toxic due to toxicants: –  Toxalbumin

–  Lec$ns –  Phoratoxins

•  Toxicosis: – GI (e.g., vomi$ng, diarrhea)

–  CARDIAC (e.g., collapse, bradycardia, hypotension)

–  CNS (e.g., hallucinogenic, erra$c behavior)

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Glo jewelry •  OK to monitor at home!

•  Flush out mouth

•  Offender: dibutyl phthalate (DBP) – Oily, bitter liquid!

•  Treatment: – Any dermal exposure? –  Flush mouth –  Bath with liquid dish soap

De-icing salts

•  Mildly toxic

•  Typically high concentra$ons of NaCl, CaCl, MgCl, KCl

De-icing salts: Clinical signs

•  Gastrointestinal: – Hypersalivation – Anorexia – Vomiting – Diarrhea

•  Dermal irritation

•  Electrolyte abnormalities

De-icing salts: Treatment

•  Decontamination – NO activated charcoal

•  IV fluids –  0.45% saline + 2.5% dextrose

•  Anti-emetics

•  Electrolyte monitoring

ETHYLENE GLYCOL

Ethylene glycol (EG)

•  Not common but deadly

•  Sources: – Radiator coolant – Windshield deicer agents – Motor oils – Hydraulic brake fluid – Developing solu$ons – Paints – Solvents

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Ethylene glycol (EG)

•  Dose makes the poison!

•  Narrow margin of safety

•  Toxic dose: –  Cats: 1.4 ml/kg – Dogs: 4.4 ml/kg

–  LD50 dogs: 4.2-‐6.6 mL/kg –  LD50 cats: 1.5 mL/kg

•  Metabolites " CaOx crystalluria " AKI

Ethylene glycol (EG): Clinical signs

•  Stage 1 (30 min-‐12 hours): ataxia, hypersaliva$on, vomi$ng, pu/pd

•  Stage 2 (12-‐24 hours): Resolu$on, tachycardia, tachypnea, dehydra$on

•  Stage 3 (36-‐72 hours, dogs; 12-‐24 hours, cats): Azotemia, coma, AKI

Ethylene glycol (EG): Diagnosis •  Venous blood gas

– Metabolic acidosis (pH < 7.35, low HCO3, -‐BE) – ↑osmolality, anion gap & osmolar gap – May see hypocalcemia or hyperglycemia (50%)

•  Urinalysis –  CaOx crystalluria (as early as 3-‐8 hours) post-‐inges$on

Ethylene Glycol: Clinicopathologic Findings

•  EG test –  + in first 24 hours –  Ideally: human quan$ta$ve test

•  Veterinary test kits & cats –  False +: sorbitol, alcohol, propylene glycol, mannitol

Ethylene glycol (EG): Treatment

•  Decontamina$on? –  < 1 hour: emesis? –  NO ac$vated charcoal!


•  ANTIDOTE: inhibit EG conversion to dangerous metabolites (alcohol dehydrogenase) –  Must be started ASAP! –  Dogs: < 8-‐12 hours –  Cats: < 3 hours

•  Choices for an$dotes –  4-‐MP (fomepizole) –  Ethanol

Ethylene glycol: Treatment

•  Ideally 4-‐MP

•  Alterna$vely: ethanol –  Readily available but…

•  CNS depression •  Serum hyperosmolality

•  Osmo$c diuresis

•  Metabolic acidosis

•  Hypoglycemia

•  Gastrointes$nal signs (e.g., significant vomi$ng " aspira$on)

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Ethylene Glycol: 4-MP

•  Dogs –  20 mg/kg IV –  15 mg/kg IV @12,24,36 hours

•  Cats –  125 mg/kg slow IV loading dose –  31.25 mg/kg @ 12, 24, 36 hours

•  In cats treated @ 3 hours w/ 4-‐mp 100% survival –  ethanol 25% survival

•  In cats treated @ 4 hours w/ 4-‐mp 0% survival –  ethanol 0% survival

–  Once azotemic " grave prognosis

Connally et al. JVECC2010

BUT HOW DO I MAKE ALCOHOL CRI’S?

Ethylene Glycol: Treatment •  Go buy some concentrated alcohol (ethanol, ETOH)

–  Proof = ½ the alcohol content –  100 proof grain alcohol = 50% ETOH –  190 proof vodka = 95% ETOH –  Clear stuff only!

•  Make a 7% ethanol solu$on from 80 proof Vodka

•  C1 x V1 = C2 x V2 –  C1 = .40 (40%) –  C2 = .07 (.07%) –  V2 = 1000 mls –  .40 (X) = .07 * 1000 –  X = 175 mls

Ethylene Glycol: Treatment •  C1 x V1 = C2 x V2

–  .40 (X) = .07 * 1000 –  X = 175 mls

•  Next steps? –  Remove 175ml from a 1L bag of saline

–  Add 175 ml of a 80 proof vodka •  190 proof: remove 74 ml from a 1L bag of saline

•  Add 74 ml of the grain alcohol " 7% ETOH solu$on

•  DOSE: Loading dose of 8.6 ml/kg (7% ETOH) slow IV –  CRI of 1.43 ml/kg/hr

Addi$onal treatment

•  Nursing care •  Venous blood gas/renal panel/blood glucose •  An$-‐eme$cs

•  Fluid therapy •  UOP monitoring

•  Suppor$ve care

Ethylene glycol (EG): Prognosis

•  Prognosis is grave if… – Cats: > 3 hours – Dogs: > 12 hours – No hemodialysis or CRRT available – Already azotemic

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HUMAN MEDICATIONS

•  Analgesic and an$pyre$c

•  OTC pain relievers (Tylenol) and a wide variety of cold, flu, and allergy medicines.

•  Cats are very suscep$ble to acetaminophen toxicity – Lack glucuronyl transferase; cannot metabolize via glucuronida$on

Acetaminophen

•  Toxicity – Cats: 10 -‐ 60 mg/kg – Dogs: 100 -‐ 150 mg/kg

Acetaminophen •  Signs occur 1-‐2 hours afer inges$on

•  Early signs: anorexia, saliva$on, vomi$ng, facial and paw edema with lacrima$on and pruritus

•  Later / progressive signs: depression, methemoglobinemia, Heinz body anemia, hemoglobinemia, hemoglobinuria

Clinical signs in cats

•  Develop later than with cats

•  Hemolysis and icterus develop in 2-‐7 days of toxicity

•  Cyanosis with higher doses develops within 4-‐12 hours due to methemoglobinemia and anemia

•  Depression, anorexia, vomi$ng, abdominal pain, with progression to liver failure

•  Methemoglobinemia, hemoglobinemia, and hemoglobinuria in large doses (> 200 mg/kg)

Clinical signs in dogs: •  Diagnosis

– Cats: •  Methemoglobinemia •  Heinz body forma$on

– Dogs •  Elevated liver enzymes (ALT, AST)

Acetaminophen

•  Treatment – Decontamina$on:

•  Emesis: if recent inges$on < 15 minutes •  Gastric lavage? •  A/C (with cathar$c) afer lavage/emesis

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•  IV fluids at 1.5-‐2.5X maintenance to maintain perfusion

•  If severe metabolic acidosis (pH < 7.1), can consider sodium bicarbonate

Acetaminophen: Treatment •  Treatment

–  SAM-‐E (Denosyl®) •  Increases hepa$c glutathione levels •  Dose: 40 mg/kg PO to load, then 18 mg/kg every 24 hours X 30 days un$l liver enzymes resume to normal levels (ACVIM 2010)

–  Ascorbic Acid: •  Reduce methemoglobin to hemoglobin. Dose: 20-‐30 mg/kg PO, SQ, or IV every 6 hours x 3 days

–  Cime$dine: No longer recommended for cats and dogs!

Acetaminophen

•  N-‐acetylcysteine (NAC): – Should be given within first 8-‐12 hours

•  Mucomyst® -‐ can be given IV – Fitered using a 0.22 micron filter – Dilute appropriately

•  Mucomyst® orally – Dilute the 10 or 20% solu$on with a 5% Dextrose Solu$on (D5W) to a final concentra$on of 5%

Acetaminophen: Antidote Antidepressants

•  Most common type: SSRIs

•  Selective serotonin re-uptake inhibitors (SSRIs)

•  Tricyclic antidepressants

•  Other drugs affecting norepinephrine or serotonin

SSRIs: How do they work? •  Inhibit the reuptake of serotonin at the presynaptic membrane

•  More serotonin " more serotonin syndrome!

Permission granted Dr. Joe Stirt from http://www.bookofjoe.com/2005/03/07/

Amphetamines • Recognize! • Ritalin or Concerta (methylphenidate) • Vyvanse (lisdexamfetamine) • Adderall (dextroamphetamine /amphetamine) • D-amphetamine (Dexedrine)

•  Similar to crystal meth!

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What are amphetamines used for?

• #1 ADD/ADHD – College kids

•  Illegal purposes (street drug) • Narcolepsy • Obesity (weight loss)

Amphetamines: How do these drugs work?

•  Sympathomimetics!

•  Similar to norepinephrine " stimulate alpha and beta-adrenergic receptors

• CS: Overstimulation!

Clinical signs from SSRI & amphetamines

•  CARDIAC: hypertension, tachycardiac

•  CNS: sedation or agitation, mydriasis, ear flicking, vocalization, tremors, head bobbing, seizures

•  GI: drooling, vomiting, diarrhea

•  RESP: panting (to blow off heat)

•  MISC: Hyperthermia secondary to tremors

•  How do we treat it? Same as SSRIs!

Do we decontaminate? •  Is it asymptomatic?

•  Rapid onset of clinical signs

•  Should you have the pet owner do it? (NO) – Best done in clinic once TPR is assessed –  If asymptomatic –  If recent ingestion (< 1 hour)

Should we give charcoal?

•  If ASX " one dose of activated charcoal + cathartic (ACC)

•  If extra letters behind brand name (e.g., XR, ER, SR, etc.), give multiple doses of AC –  No sorbitol with additional doses

Treatment •  IV fluids:

–  Aids in enhanced urinary elimination •  Amphetamines only

–  Keeps them cool if hyperthermic –  Minimizes risk of myoglobinuria damage

•  Hyperthermia: –  Stop the tremoring " sedatives/methobarbamol –  Provide cooling measures if > 40.5ºC/105ºF –  Stop cooling measures if 39.7ºC/103.5ºF

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Treatment Monitoring:

–  Check TPR " monitor blood pressure and ECG –  When do we care? > 180 bpm /180 mmHg

Anxiolytics: –  If anxious, tachycardiac, hypertensive " –  Acepromazine

•  0.05-0.1 mg/kg IV, IM, or SQ, titrated to effect •  Plumbs: Do not “exceed 3 mg total”

Treatment •  Tachycardia (HR > 170-180 bpm):

–  Check stat BP •  Typically hypertensive with SSRI/ADD medications "

– Anxiolytics (more acepromazine) – Anxiolytics (more acepromazine + butorphanol?)

•  Still tachycardiac? – Beta-blocker (propranolol 0.02-0.06 mg/kg IV)

•  Tremors: – Methocarbamol 44-‐220 mg/kg IV or PO q. 6-‐8 –  Ideally IV –  “Do not exceed 330 mg/kg/day” ☺ –  Rectal absorp$on?

Treatment: • Serotonin syndrome

– Serotonin antagonist " cyproheptadine

– Consider PO or rectal administra$on

– Dogs: 1.1 mg/kg q. 6-‐8-‐12 hours – Cats: 2-‐4 mg total q. 6-‐8-‐12 hours

•  Seizures: –  Stop the seizure!

•  Phenobarbital 4-16 mg/kg IV or PO PRN, titrated to effect •  Diazepam 0.25-0.5 mg/kg IV PRN, titrated to effect

•  Sugar-free, natural sweetener

•  Found in everything! –  Sugar free gums, candies, mints –  Chewable multivitamins –  Baked goods –  Mouthwashes –  Toothpastes –  Anything “sugar-free” –  Peanut butter

Xylitol

Xylitol

•  Variable amounts in everything –  2 mg -1 gm/piece of gum is average

•  How toxic is it? –  > 0.1 g/kg " hypoglycemia –  > 0.5 g/kg " acute hepatic necrosis

•  Clinical signs: –  Signs of hypoglycemia: weakness, collapse, vomiting, ataxia (< 1 hour) –  Liver injury (days later)

How do we treat xylitol toxicosis?

•  STAT blood glucose (BG) + chemistry –  Is the patient hypoglycemic? –  Treat if BG < 60 mg/dL

•  1 mL/kg 50% dextrose IV diluted 1:3

•  Decontamination –  Delayed emesis induction if asymptomatic! –  No need for activated charcoal!

•  Treatment: –  BG monitoring with dextrose CRI in IVF –  SAM-e –  Baseline chemistry q. 24 hours X 2 days

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•  Pets ofen ingest baèries when chewing up: – Remote controls – Toys – Calculators – Watches

•  Chewed = alkaline gel is released

Batteries •  Most baèries are alkaline

•  Chewed: – Oral pain – Hypersaliva$on – Anorexia – Oral inflamma$on or ulcera$on – Dysphagia –  Vomi$ng – Abdominal pain – Melena.

•  Because of their size, baèries can also result in GI obstruc$on.

Batteries

•  If swallowed whole –  Radiographs –  Iden$fy the loca$on of the baèry

•  Endoscopy or surgery

•  Prognosis may be good to guarded, depending on if the baèry was chewed or ruptured and the presence, severity, and loca$on of any chemical burns.

Batteries Call for advice!

•  Beware of holiday poisons!

•  Save your faxes!

•  VIN

•  Call ASPCA Animal Poison Control Center – Chocolate wheel! – Free app!

#CPRwheel

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Check out our 2015 upcoming VETgirl appearances!

Dr. Jus$ne Lee •  NAVC, Jan 2016 •  IVS, Fiji, Feb 2016 •  WVC, March 2016 •  AAHA, March 2016 •  AVMA, July 2016

Dr. Garret Pach$nger •  NAVC, Jan 2016 •  WVC, March 2016

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Holiday toxins Introduc$on’