Basic principles, diagnosis and management of toxic exposures (Proceedings)

Oral exposure to toxicants among small animals (pets) is the most common. Biological activities are graded, and, are based on toxicants reaching their sites of action (effectors) in biological system at a sufficient concentration and duration. Intensity of a biological effect is dose related. Basic pharmacokinetic/toxicokinetic principles of toxicants become essential in addressing toxicity.

Toxicant concentrations at effector sites are based on absorption, distribution, metabolism, and excretion of individual toxicants.

This presentation addresses prevention, patient stabilization, diagnostic measures, diagnosis and management of toxic exposures.

     Toxicology is the study of adverse effects of poisons (toxins, toxicants, xenobiotics) on living organisms.

          "All substances are poisons; there is none which is not poison. The right dose differentiates a poison from a remedy"

               Philippus Aureolus Theophrastus Bombastus Von Hohenheim-Paracelcus 1493-1541

Prevention

Educating clients and animal handlers alike on the need to control the animals' environment (reduce risk of exposure to toxicants) is a must.

Initial evaluation

All cases of reported possible toxicant (s) exposures should be regarded as, and handled as an emergency. Assuming toxicity from limited initial information received from clients without a complete case work-up is wrong. Most often, animals are presented to the veterinarian already showing clinical signs.

Check for and treat all life threatening conditions – airway, breathing, temperature, hemorrhaging, cardiovascular, state of consciousness etc. Prior to administering any medication, collect specimens (un-clotted/clotted blood, vomitus, stomach contents etc.) for later analysis.

Stabilization

The important thing is to first stabilize the patient (treat the patient not the toxin). A complete history, thorough physical examination, collecting and analyzing the appropriate specimens, interpreting analytical results, and, evaluating all relevant facets in the case at hand, determines patient management with possible diagnoses, a workable effective treatment plan (subjected to modifications as new information permits) should be in place.

General Approaches to Treatment/Management of Poison Cases

     Prevents Further Toxin Exposure and Absorption

          • Decontamination

          • Ocular exposure – Flush eyes with tepid water or Saline solution for 20-30 minutes.

          • Dermal Exposure – Repeated baths in warm water with mild liquid dishwashing detergent (Dawn is frequently recommended)

          • Oral Exposure – Dilution (milk or water), induce emesis, gastric lavage, endoscopic and/or surgical intervention, adsorbent, and/or cathartics and/or enemas).

Approaches

Prevent Further Toxin Absorption; Promote removal of absorbed toxin; Administered appropriate antidotal therapy, and Supportive Therapy

Prevent Further Toxin Absorption

Emetics

Primarily in dogs and cats (Ferrets and Potbelly pigs - but not horses, rodents, birds and rabbits). Early (2-3h) post ingestion of toxins. Could be later with time released toxicants.

Effectively remove 40-60% of stomach contents. Contraindicated (Acid/Alkali, corrosive toxins, petroleum distillates).Hazardous for animals who have already vomited exhibiting coma, seizures, of lacking glottis control.

Apomorphine (drug choice in dogs)

Stimulated dopamine receptors in chemoreceptor trigger zone.

Can produce CNS depression and occasional convulsions. Safe dose not established for cats. IV @ 0.04 mg/kg (immediate effect; last 1-2 minutes); IM @ 0.04 mg/kg (vomits in 4-5 minutes and which can be protracted). Conjunctival sac @ 0.25 mg/kg.

Xylazine – Rompun (in cats not in dogs)

CNS and respiratory depression, bradycardia, hypotension possible (treat with Yohimbine 0.5mg/kg IV. IM or SubQ @ 4.4 mg.kg (emesis in 5mins)

3% Hydrogen peroxide – most suitable (available/effective/inexpensive)

Causes vomit from gastric irritation. P.O @ 1-2 ml/kg q5-10 min. if necessary (not to exceed 50ml/dog and potbelly pigs, or 10ml in cats and ferrets. Vomits within 10-15 min. post treatment.

Syrup of Ipecac (Efficacy questionable; Cardiotoxic? possible)

PO @ 1-2 ml/kg (dogs); 3.3 ml/kg (cats); followed by 1-3 cups of water. Effective only 50% of time, could be a long latent period (20 minutes or so), and becomes inactivated when given at same time with activated charcoal. Caution: repeat once only when initial dose was at the lower level.

Table salt - (Ineffective; causes hypernatremia and CNS dysfunction)

Liquid dishwasher, powdered mustard - (Ineffective)

Gastric lavage: In cases of unconscious and/or anesthetized animals, lower their heads respective to their chest, and with a cuffed endo-tracheal tube in place, insert stomach tube (nose to xiphoid cartilage), and lavage with activated charcoal solution: 4-10 ml/kg (agitate and remove) – initial washings saved (freezing) for toxin analysis. Continue washing (10-15 times) until removed solution is clear.

Adsorbants

Activated charcoal of vegetable origin via stomach tubing of a solution (1g activated charcoal in 3-5 ml water) @ a dose of 2-8 g/kg. (Toxiban). Follow-up (30-40 min. later) with saline cathartic (sodium sulfate) or mineral oil (prevents treatment-induced constipation). Repeated doses may be necessary in cases where toxicants (marijuana, ibuprofen and digoxin) undergo enterohepatic recirculation.

Bentonite (clay) – Paraquat poisoning, Mycotoxins (Aflatoxicosis)

Ion exchange resins - Trap toxin (s) by binding toxin to carrier and/or inhibiting systems promoting toxin absorption (cholestyramine or colestid binding to lipoproteins and/or bile acids) thus limiting gastrointestinal absorption, the carrier-toxin (s) excreted in the feces (interrupts enterohepatic recirculation): Poisonings induced by some pesticides, anticoagulants, E. coli heat stable enterotoxin, digitalis, etc.

Cathartics: Sodium Sulfate (Glaubers salt) P.O @ 250-500 mg/kg as a 20% solution (small animals). Magnesium sulfate (Epsom salt) – less effective with possible CNS depression, and freeing up toxin from activated charcoal.

Mineral oil – Contraindicated with fat-soluble toxins (organo-chlorine toxicity) and in cases with gastrointestinal irritation. Careful not to deposit in lungs (aspiration pneumonia). Dose @ 5-15 ml (dogs); 2-6 ml (cats); 1-3 liters (large animals).

Enhanced Removal of Absorbed Toxin(s)

Promote diuresis (contraindicated for anuric animals). Toxicant of significant plasma concentration. Forced diuresis in association with certain complications - Pulmonary edema, cerebral edema, metabolic acidosis or alkalosis, electrolyte imbalances (e.g., hyponatremia, hypokalemia), or cardiac arrhythmias.

Mannitol (IV 2g/kg/h of a 20% solution – first hour, then 5% mannitol solution @10 ml/kg/h). Should not be given in anuric, cardiac decompensation, pulmonary congestion or edema, dehydrated or intracranial hemorrhage patients. Furosemide – IV/IM @ 4 mg/kg q6-8h

Altered Urine pH (Ion Trapping)

Acidify urine (ammonium chloride) thus enhancing excretion of bases (amphetamine, phencyclidine, quinine, and strychnine etc. Contraindicated in myoglobinuria, ammonia toxicity, liver and/or kidney insufficiency.Dogs @ 100 mg/kg P.O q12h; Cats @ 20 mg/kg PO q12h.

Alkaline urine (sodium bicarbonate) thus enhancing excretion of acids (salicylates, ethylene glycol, phenobarbital, 2,4-D herbicide). Dogs and cats @ 50 mg/kg PO q8-12h or 1-2 mEq/kg q3-4h IV – Slow infusion.

Peritoneal Dialysis or Hemodialysis (Anuric Animals Primarily)

Altered Metabolism

Alcohol dehydrogenase inhibition in ethylene glycol toxicity.Mixed function oxidase enzyme activity induction in organo-chlorine pesticide toxicity.

Administration of Specific Antidotes

Antidotes are agents with specific action against the activity or effect of toxicants in the living organism, administered post exposure to a toxicant and most often, when clinical responses are observed.

Examples of common Antidotes and Toxicants

Supportive Therapy

Maintain normal body temperature (treat hypothermia/hypothermia); Control CNS activity (treat depression, hyperactivity); Cardiovascular and respiratory support.

Poison Diagnosis

A diagnosis of poisoning may be based on: history of exposure to a possible poison, demonstration of an adverse effect compatible with the poison, and confirmation of exposure and absorption of the poison by chemical analysis

Minimum Data base - necessary

Routine laboratory testing is recommended for all suspected life-threatening intoxications: Complete blood count (CBC), Serum electrolytes, Serum glucose; BUN; creatinine, calcium, liver enzyme determinations; and a urinalysis. Others - Coagulation panel, Electrocardiography, Radiographs

Should the cause of death be attributed to toxicity (Forensic), an extensive investigation needs to be done.

Collect tissues for histologic and toxicologic examination,

     10% buffered formalin

     Fresh frozen

          Submission often pending histologic findings

               Urine (10 mL) – drugs and pesticides

               Kidney (2 to 10 g) – heavy metals

               Liver (2 to 10 g) – best single tissue, mineral or organic chemical

               Vomitus, stomach/crop and intestinal contents (2 to 10 g)

               Suspected injection site (1 g)

               Brain (hemisphere or whole brain)

               Fat (2 to 10 g) - fat-soluble chemicals

               Bedding (100-g)

               Feed (100 g) and water (1 L)

               Whole blood (1 ml) or serum – lead (RBC))

Accredited Laboratory Methods

Can look for thousands of chemical compounds with a high degree of specificity and sensitivity

     Screening tools include:

          • Gas chromatography–mass spectrometry (GC/MS)

          • Inductively coupled argon plasma emission spectroscopy (ICPAES)

          • Inductively coupled plasma mass spectrometry (ICP/MS)