Toxins - the general approach and common examples

• The unknown toxin -presentation

  May only present once clinical signs are occurring i.e. the owner has not seen the exposure.

  OR

  Known ingestion/exposure to something with unknown effects. This is much easier to deal with and follows several basic principles:

  • Decontamination
  • Assessment of effects
  • Treatment of symptoms.
• Unknown toxin - consider how a toxin is likely to be absorbed

  Eaten and therefor absorbed either across mucous membranes (rapid - e.g. alcohol) or absorbed across the intestinal mucosa often transiting the stomach (slower).

  Absorbed via skin exposure e.g. spot-on products (quick).

  • Some toxins not absorbed, but groomed and ingested.
  • Dog dose of some flea spot-ons in a cat.

  Absorbed via inhalation (rare)

  Many compounds are not inherently toxic until they have been metabolised e.g. by the liver.
• Unknown toxin absorbed via eating - mucous membrane absorption

  Mucous membrane absorption is rapid

  Gastric transit - induce emesis or gastric decontamination.

  • Window of opportunity 2-8 hours in dogs, 2-12 hours in cats.
  • Apomorphine - licensed in dogs (very effective).
  • Alpha-2 agonists e.g. xylazine, medetomidine - not licensed but can be used in cats (moderately effective).

  Avoid neurologically compromised patients e.g. obtunded due to aspiration risk.

  Avoid caustic substances “home remedies” e.g. hydrogen peroxide and causing oesophagitis and potential major complications.
• Unknown toxin absorbed via eating - intestinal absorption

  Can try to reduce intestinal transit time with laxatives but this will likely cause fluid and electrolyte losses unnecessarily.

  Adsorbants - activated charcoal

  • Doesn‘t work for all toxins
  • Bound carbon-toxin -> defaecated.
• Unknown toxin absorption - skin exposure

  Decontamination is now surface based.

  Washing the skin is primarily performed with water.

  Can apply activated charcoal topically before washing off

  Lipid soluble toxins can be easily removed with soap -e.g. fairly liquid.
• Unknown toxin absorption - inhalation

  Very rare, but realistically decontamination for your patient is not possible.

  Wear appropriate PPE.
• Unknown toxin absorption - metabolised

  Once toxins are in the bloodstream, we still have the opportunity to prevent them being metabolised.

  The simplest approach is fluid therapy:

  • Increase GFR and promote renal excretion.
  • Increased organ perfusion and transit of compounds.

  Lipid infusion:

  • Works well for lipid soluble compounds.
• unknown toxin - assessment

  Nuero - seizures, ataxia, sedation.

  Cardiovascular - arrythmias, tachycardia, bradycardia, hypotension, hypertension.

  Gastrointestinal - vomiting and diarrhoea

  Renal - azotaemia, inappropriate USG.

  Hepatic - jaundice, elevations in ALT, ALP and bile acids.

  Haemotological:

  • Clotting - prothrombin time, activated partial thromboplastin time.
  • Anaemia - PCV, HCT.

  Cardiovascular - ECG
• Treatment for unknown toxins - neuro

  Seizure control

  Diazepam IV x 3

  Levetiracetam, phenobarbital IV.

  Propofol CRI
• Treatment for unknown toxins - hepatic damage

  Supportive in nature.

  SAMe, Ursodeoxycholic acid, Silybin (milk thistle).
• Treatment for unknown toxins - acute kidney injury

  IVFT +/- diuretics depending on urine output.

  Dialysis.
• Treatment for unknown toxins - cardiovascular and respiratory

  Anti-arrythmics (e.g. lidocaine, amiodarone), beta-blockers (e.g. propranolol), parasympathetic (e.g. atropine).

  Blood pressure management - fluid therapy, vasopressor (e.g. nor-adrenaline) or anti-hyperintensive (e.g. amlodipine)

  Oxygen therapy.
• Treatment for unknown toxins - gastrointestinal

  Vomiting - may not want to stop in the acute phase.

  Irretractable vomiting - anti-emetic (e.g. maropitant, metoclopramide, ondansetron) and fluid therapy.

  Diarrhoea - fluid therapy, gastro-intestinal diet.
• Treatment for unknown toxins - haematological

  Clotting - vitamin K1, plasma

  Anaemia - packed red blood cells/ whole blood.
• Known toxins - presentation and signs of ibuprofen/ NSAIDs

  COX inhibitors - reducing prostaglandin production.

  PGE2 and PGI2 play important roles in:

  • Maintaining afferent renal blood flow.
  • Maintaining GI mucous productions, mucosal blood flow and cell turnover.

  Clinical signs - haemorrhagic vomiting/ diarrhoea, AKI.
• Known toxins - specific treatment for ibuprofen/NSAIDs

  H2 blockers - ranitidine/cimetidine.

  Proton pump inhibitor - omeprazole

  Prostaglandin analogue - misoprostol (not in the pregnant patient).

  Intralipid infusion.
• Known toxins - presentation and signs of aspirin


  Very similar to other NSAIDs but mau have greater inhibition of Thromoxane in addition to prostaglandin inhibition.

  Thromboxane (TXA2) it’s important for platelet function.

  Clinical signs:

  • Thrombocytopathy - bleeding e.g. prolonged BMBT
  • Other NSAID associated.
• Known toxins - clinical signs of paracetamol

  Brown mucous membranes (methemoglobin)

  Jaundice, abdominal pain, lethargy, vomiting (direct hepatic damage).

  AKI

  Signs of hypoxia to tissues - Brady or tachy arrhythmias, peripheral oedema (especially the neck in dogs), respiratory distress.

  Diagnostic clue - brown blood.
• Known toxins - treatment of paracetamol

  N-acetyl cysteine - glutathione precursor which binds the toxic metabolites.

  H2 receptor antagonists (e.g. ranitidine) may reduce CP450 oxidation.

  Ascorbic acid (vit C) may reduce methaemoglobin to haemoglobin.

  Liver support - SAMe, UDA, Silybin.

  AKI support - IVFT

  GI support.
• Known toxins - Chocolate clinical signs

  Hyperactivity - important to ask owners about.

  Vomiting/ diarrhoea.

  Arrythmias (usually tachy) with VPCs, tachypnoea.

  Seizures

  Coma

  Death
• Known toxins - chocolate treatment

  As per system with some specifics.

  • Entero-hepatic recycling - so charcoal every 4-6 hours.
  • Severe cases may need intubations, and urinary catheterisation.
• Known toxins - xylitol presentation

  This is a sugar alcohol, that mimics glucose but without a calorific contribution. Commonly a result of dogs eating chewing gums, can be found in other things, including some peanut butters.

  Stimulates insulin release and hepatotoxic:

  • Prolonged hypoglycaemia - 12-48 hours.
  • Liver failure - within 72 hours
  • Weakness, collapse, seizures, coma, death.
  • Jaundice.
• Known toxins - xylitol specific treatment

  Hepato-protectants - sAME, UDA, Silybin.

  Glucose supplementation

  • Oral vs IV
  • Bolus vs CRI
  • Try to avoid causing further insulin spikes.
• Known toxins - pyrethroids presentation

  Found in insecticides such as “raid” and ant powders, as well as some ‘old school’ flea products.

  Cats are particularly susceptible as they lack the enzyme glucuronyl transferase required for the glucuronidation pathway.

  Primarily act on neural axons (sodium channel).

  • Ataxia, tremors, disorientation and seizures.
  • Dyspnoea and respiratory arrest.
  • Hypersalivation and vomiting
  • Uncontrolled seizure h can cause rhabdomyyolysis and subsequent AKI.
• Known toxins - pyrethroids treatment

  General principles, but decontamination may involve the skin e.g. flea products.

  Intralipid is excellent - permethrin is highly lipophillic.
• Known toxins - cleaning products

  Many house hold cleaning products contain either strong acids or alkalis, as a result they are all toxic.

  Damage is primarily die to surface contact, in the case of ingestion this will the mucosa, particularly oral, oesophageal and gastric.

  Clinical signs;

  • Oral pain.
  • Dysphagia
  • Regurgitation
  • Vomiting

  Gastric decontamination is dangerous - risk of worsening oesophagitis.
• Known toxins - ethylene glycol

  Anti-freeze is sweet tasting and similar in structure to alcohol. This means it’s tasty and rapidly absorbed.

  Ethylene glycol is metabolised into glycoaldehyde, glycolic acid and oxalic acid.

  Glycoaldehyde is neurotoxic, glycolic acid produces a severe acidosis and oxalic acid binds calcium leading to calcium oxalate crystal formation in several organs.
• Known toxins - ethylene glycol diagnosis

  Increased osmalarity die to EG <1 hour; not often available in first opinion.

  Acid/base analysis - profound normochloraemic metabolic acidosis.

  Hypocalcaemia (ionised preferably).

  Renal damage - azotaemia, Hyperkalemia.
• Known toxins - ethylene glycol treatment

  Be realistic with owners.

  Slowing the production of toxic metabolites is key - alcohol dehydrogenase.

  • Medical ethanol (20%).
  • Vodka diluted with saline (20%)
  • 2-3 days - formulary has guidelines
  • Dialysis has improved outcomes - referral.
• Known toxins - Warfarin presentation

  Inhibit vitamin K epoxide reductase - i.e. they inhibit vitamin K synthesis. Vitamin K is important in production of clotting factors II, VII, IX and X - coagulopathy 36-72 hours post ingestion.

  Diagnosis

  • PT prolongation initially (factor VII has the shortest shelf life).
  • aPTT prolongation follows.
  • Cavitatory (large) bleeds - e.g. haemothorax.
  • Petechiae are unlikely to be present.
• Known toxins - warfarin treatment

  Vit K1 injectable initially, followed by oral - up to 8 weeks.

  Fresh frozen plasma transfusion in severe cases - clotting factors.
• Known toxins - raisins/grapes/sultanas/currants presentation

  Toxic substance is not known - Tartaric acid has been implicated but the jury is still out.

  Resultantly there is no known toxic dose - so any exposure should be considered serious. However retrospective reviews have highlighted a low degree of AKI developing after exposure - its difficult to gauge how worried we should actually be as a result.

  Clinical sign - AKI
• Known toxins - raisins/grapes/sultanas/currants treatments

  General principles; including recommendation of IVFT for 48-72 hours in non-azotaemic animals.

  Dialysis has improved outcomes where AKI is confirmed.
• Known toxins - recreational drugs cocaine

  Hyperactuve, hyperthermia, tachyarrythmias, vomiting, ataxia, seizures.

  Treatment:

  • General principles
  • Don’t forget hyperthermia
• Known toxins - recreational drugs marijuana

  Vomiting, ‘paranoia’, ataxia, depression, coma, urinary incontinence.

  Treatment:

  • General principles
  • Urinary catheter
  • Intralipid
  • Anxiolytics.
• Known toxins - recreational drugs opiates (e.g. heroin)

  Depression, lethargy, vomiting, constipation, hypoventilation

  Treatment:

  • General principles
  • Reverse with naloxone
  • Consider ventilating short term.
• Known toxins - recreational drugs ketamine

  Ataxia, hallucinations, aggression, cataplexy (K-hole) and loss of patent airway.

  Treatment:

  • General principles and consider intubation.
• Known toxins - lilies presentation

  Toxic substance not known (probably a steroidal glycoalkaloid).

  Cats are very sensitive - minimal can lead to AKI.

  Dogs are less sensitive - usually just GI signs.

  Any part of the plant is toxic - including the stamen and pollen - which cats will play with because they are ‘floppy’.
• Known toxins - lilies Treatment

  Treatment is as per AKI, and dialysis has improved outcomes.

  Consider the exposure though, particularly pollen.

  Decontamination should slo involve clipping/ washing paws and around the mouth to prevent further exposure through grooming.
• Known toxins - onions, garlic, leeks and chives

  Large quantities need to be eaten for toxicity to develop, cats may be more sensitive.

  Sulphur containing compounds which can cause:

  • Haemolysis
  • Heinz-body aneami

  Clinical signs:

  • Vomiting and diarrhoea
  • Tachycardia, tachypnoea, pale mucous membranes (anaemia).

  Treatment:

  • General principles, in severe cases consider a transfusion.