Animal exposure to toxic substances is one of the common forms of emergencies presenting at a veterinary practice. The 2012 Annual Report of the American Association of Poison Control Centers (AAPCC) included 66,440 reports of non-human toxic exposures, of which 90.43% were dogs, and 8.49% were cats. In 2013, the American Society of Prevention of Cruelty to Animals (ASPCA) Poison Control Center handled approximately 180,000 possible toxin exposure cases. The top 10 exposures included prescription human medication, insecticides, over-the-counter human medication, household products, people food, veterinary products and medications, chocolate, rodenticides, plants, and lawn or garden products. Toxic exposures are predominantly through ingestion, though dermal, ocular, and inhalant contacts are some other forms seen. Many of these exposures require swift intervention, decontamination, and supportive care until the patient is no longer at risk of detrimental effects of the toxins.

At Home Intervention

First notice of an animal being exposed to a toxin is typically communicated through a phone call to the veterinary practice with the owner seeking advice. Advice given to the owner requires vital information to be collected swiftly and a judgment made on further treatment. Information on the species, breed, age, gender, and body weight should be obtained as one of the first pieces of information. Obtaining of the body weight from a recent visit and considering the likelihood of significant change (growth, disease), and owner estimates should be considered with the possibility of inaccuracy. Information regarding the toxin exposure including the type of potential toxin, amount exposed to, the degree of certainty of exposure, estimated amount of time since the exposure, and any information gained from poison control advice lines (if obtained) is valuable in making a judgment. One of the main purposes of the phone conversation is to establish whether there is a life-threatening problem occurring with the patient. The mentation and level of consciousness of the patient is an important indicator of stability. Animals with no impairment in cerebral perfusion and oxygen delivery will be alert and responsive to owner cues. The patient may be obtunded, having a slowed or decreased response to stimuli, indicating some compromise. If the patient is stuporous, or only responsive when providing noxious stimulus, this indicates even further compromise to brain function. If a patient is comatose, or unresponsive to any stimuli, the compromise is severe. Questions directed at determining respiratory effort should also be considered, as specific toxins of vomiting may lead to respiratory compromise. Patients with altered mentation and respiratory distress require immediate medical attention.

While appropriate medical treatment at the veterinary practice is advocated, at home intervention may be necessary if the trip to the veterinarian is expected to be longer than allowable time for interventions before the toxin takes effect (general allowable time is within one hour, though certain substances may be shorter or longer), and ingestion was witnessed or virtually certain. Induction of emesis at home may be warranted, though care should be taken to make sure no contraindications of emesis exist. Emesis should not be suggested in patients that have altered mentation, respiratory distress, compromise to normal protection of the airway (laryngeal or musculoskeletal disease), or ingested caustic substances. In the case of ingestion of caustic substances, dilution with large amounts of water or milk prior to heading to see the veterinarian is suggested.

In case inducing emesis at home is necessary, options include syrup of ipecac, table salt, and 3% hydrogen peroxide. Syrup of ipecac stimulates receptors in the stomach and the chemoreceptor trigger zone in the posterior medulla, inducing vomiting. However, side effects such as prolonged vomiting and diarrhoea, lethargy, fever, and irritability is seen in humans, cautioning use. Recommended dose is 1–2 mL per pound in dogs, and 3.3 mL per pound in cats, and it may be justifiable to use if there is no other option available to prevent gastric absorption (activated charcoal) and a delay in treatment is expected otherwise. Salt and hydrogen peroxide stimulate the central nervous system through neurons in the pharyngeal and gastric areas, causing nausea and emesis. Table salt, while may be recommended by some sources, can be very harmful by causing electrolyte disturbances (hypernatraemia) leading to life-threatening harm, and is not recommended. Hydrogen peroxide can cause mucosal erosion leading to gastrointestinal ulceration, and should be used with caution. One (1) mL per pound up to a maximum of 45 mL (3 tablespoons or 9 teaspoons) even in the largest dogs is the recommended dose.

If vomiting does not occur readily within 15 minutes, repeat doses of the above emetics may increase the chances of emesis occurring. However, the additional time required to administer the additional dose and wait for it to take effect may be counterproductive as it causes delays in medical intervention by the veterinarian. Instructing owners to induce emesis in a manner that is easy to collect the vomitus for examination by the veterinary staff is recommended. Once the attempt to induce emesis has been performed, the animal should be brought to a proper medical facility. Some toxins may induce seizures, tremors, hyperactivity, or altered mental states in the animal and precautions in preventing trauma to the patient and the owner during transport are important.

Medical Intervention at the Veterinary Facility

Medical attention to the patient presenting for intoxication should be directed at patient stabilization, control of neurologic or haemorrhagic symptoms, correction of any metabolic derangements, decontamination, and any supportive care needed.

Patient Stabilization

Patient stabilization includes assessment of the patient’s airway patency and ability to protect their airway. Neuromuscular paralysis or paresis, severe respiratory distress, and respiratory arrest is an indication for endotracheal intubation (anaesthesia may be required) to secure the airway. A cuffed endotracheal tube is recommended. If significant respiratory signs are present, monitoring of oxygenation and ventilation through pulse oximetry, capnography, or arterial blood gas analysis is helpful. If oxygenation or ventilation is seen to be inadequate, supplementation with oxygen or assistance in ventilation through manual or mechanical positive pressure ventilation (PPV) may be necessary. The degree of oxygen supplementation and PPV should be moderated to allow for normal oxygenation (SpO2 of 95–98% or PaO2 of 80–100 mm Hg), and slightly higher than normal PaCO2 (50–60 mm Hg). The higher CO2 level is permissible from an acid-base standpoint, and will also continue to stimulate the respiratory drive of the patient.

The patient’s cardiovascular status should also be assessed through the evaluation of forward perfusion parameters, including mentation, mucous membrane colour, capillary refill time, heart rate, pulse quality, and core to extremity temperature variance. The intravascular volume status of an intoxicated patient is variable depending on the symptoms and the time elapsed since exposure. Hypovolaemic or dehydrated patients will require fluid resuscitation and replacement of deficits. In the case of vitamin K antagonism, plasma would be a part of the treatment plan, and the patient may even require red cells if sufficient bleeding has occurred. Electrolyte abnormalities should be considered for the choice of fluids as well. Most electrolyte imbalances can be corrected with fluid therapy and supplementation. Toxins that produce cardiotoxic effects may alter cardiac rhythm and function. An ECG may be warranted for further evaluation. Drugs aimed at providing cardiovascular support may be required if fluid therapy alone is not adequate in supporting adequate cardiac output or cardiac dysfunction is present. Dobutamine is used as an inotropic agent intended to increase cardiac contractility. Dopamine, vasopressin, norepinephrine, are all vasopressors which can cause vasoconstriction creating better systemic vascular resistance and blood pressure. Epinephrine can be used as both an alpha- and beta-adrenergic agonist causing an increase in cardiac output and systemic vascular resistance. However, sympathomimetics (dopamine, norepinephrine, and epinephrine) are contraindicated in use with methylxanthine (caffeine, throbromine) toxicities, inducing severe cardiac arrhythmias. Toxins causing severe hypertension will benefit from the use of vasodilators such as hydralazine, amlodipine, and nitroprusside, causing reduction of systemic vascular resistance. Toxins altering oxygen carrying capacity through alteration of haemoglobin or red blood cell levels can cause significantly reduced oxygen delivery and tissue hypoxia. In the case of impaired haemoglobin function, oxygen supplementation, and in some cases transfusions are necessary. Reduced red cell mass will benefit from red cell transfusions.

As these immediately life-threatening factors are controlled, any neurologic symptoms brought on by the intoxication need to be treated. Many toxins cause seizures and muscle tremors when allowed to persist lead to hyperthermia and damage to vital tissues and organs, coagulopathies, and a multitude of sequelae leading to an animal’s demise. Anticonvulsants and muscle relaxants may be necessary to control these neurologic signs as decontamination takes place. Benzodiazepines such as diazepam and midazolam are commonly used anticonvulsants. Barbiturates such as pentobarbital and phenobarbital are also used, with alternatives such as levetiracetam being used more frequently. Propofol may be used to control muscle movement, though electrical activity within the brain may not cease with its use, and electroencephalography is required to determine cessation of seizure activity. Intoxication with tremorgenic toxins can be treated with muscle relaxants, with methocarbamol being the primary agent used.

Decontamination

Regardless of the toxin the animal is exposed to is, prevention of further exposure is necessary. Various methods of decontamination are employed depending on the route of exposure and elimination of the toxin.

Ocular exposure should be decontaminated through irritation with copious quantity of saline or water, to wash away and dilute out the toxin in question to prevent further exposure. Care should be taken to prevent prolonged application of direct pressure on the globe with pressurized fluids, accomplished by irrigating at an angle more parallel with the globe surface. Irrigation may be possible at home, though thorough treatment may require sedation or anaesthesia to accomplish it.

In the case of dermal exposure to toxins, care should be taken for the owner and medical personnel to protect themselves from exposure through second-hand contact through transportation or treatment. Toxic exposure can occur transdermally, or through ingestion as the animal tries to clean their body and ingestion should be prevented. For long-haired individuals, shaving the coat off may be a more effective and efficient way to remove contamination from the fur than to wash it off. Using a mild soap and detergent may be adequate to remove most toxic substances, though oily substances will require degreasing detergent used for strong hand cleaning or dish washing to eliminate. Care should be taken to prevent hypothermia in patients from the bathing. Dermal exposure to caustic chemicals requires special care. Copious flushing and gentle cleaning is necessary to prevent further traumatization while removing the toxin.

Most toxic exposures, however, are through the gastrointestinal tract by ingestion. The benefit of induction of emesis will depend on various factors. Similar to at home emesis, patients at risk of aspiration because of altered mentation, neurological dysfunction, or pre-existing conditions that prevent protection of the airway or ingested caustic substances should not have emesis induced. Otherwise, recovery of gastric contents are greater when emesis is induced closer to the time of ingestion (mean of 49% if induced within 11 to 30 minutes post ingestion). Emesis is worth inducing within 60 minutes from ingestion, with induction beyond more than 4 hours post ingestion having very little value.

Apomorphine, directly stimulating the chemoreceptor trigger zone, induces vomiting in animals. It is used primarily in dogs as it seems effective in swiftly inducing emesis. Apomorphine is given at 0.02 to 0.04 mg/kg IV or IM, or topically as a tablet in the subconjunctival sac. Vomiting typically occurs within minutes, with repeat doses having mixed results in inducing further emesis. If any negative side effects are seen, naloxone (0.01 to 0.04 mg/kg IV) may be used to reverse the opioid. Patients with metaldehyde toxicity can have CNS excitation through administration of apomorphine, and should have a different method utilized. Xylazine is an alpha-2 agonist sometimes used at 0.1 mg/kg IV in cats (and less commonly dogs) as an antiemetic, having limited reported success rates (∼60%). Other drug combinations such as rapid injections of cefazolin, hydromorphone and midazolam combinations, or dexmedetomidine in cats have been used with limited success.

Gastric lavage, the act of irrigating the stomach with water to dilute or wash out the toxin, may be considered in some cases. The patient is placed under anaesthesia, a cuffed endotracheal tube placed, and a gastric tube inserted into the stomach. The patient is placed at a slight decline (20 degrees) towards the head to prevent any gastric content to flow into the airway, though too much of a decline will reduce patient tidal volume by pressing on the diaphragm. Care should be taken to prevent overdistension of the stomach, and saline should be used in smaller patients to alleviate electrolyte losses through the lavage. External, manual manipulation of the stomach is performed to dislodge any toxins on the gastric mucosa. Copious amount and repeat lavaging is used. The amount of gastric content recovered through gastric lavages are variable and minimal compared to emesis (29–38% when performed within 15–20 minutes of ingestion and 8.6–13% if longer than 60 minutes), making advocating for this technique in the majority of cases difficult. Gastric lavages can be beneficial when the ingested material is prone to causing clumps or toxins that delay gastric emptying, which may stay in the stomach longer than typical material.

Whole bowel irrigation is a technique used to clear the intestines of their content by administration of a polyethylene glycol electrolyte solution through a nasogastric tube. This technique is indicated in patients that have ingested sustained-release or enteric coated forms of medication which require additional effort in eliminating the effects of. Studies show a 68.9% elimination rate in dogs. The rate of solution required for this technique is quite high, at 500 mL/h, and may require administration of an antiemetic or prokinetic to allow for administration without induction of emesis. A 50% reduced rate may be necessary to prevent vomiting. Whole bowel irrigation is contraindicated in patients with gastrointestinal compromise (perforation, ileus, haemorrhage), haemodynamic instability, uncontrolled vomiting, or unprotected airway. Effectiveness of activated charcoal therapy is also reduced through concurrent use of whole bowel irrigation.

Ion exchange compounds such as cholestryramine and activated charcoal are administered to bind the toxin, removing it from the absorbable pool. These compounds especially are useful in treatment for toxins that undergo enterohepatic recirculation. Enterohepatic recirculation is the process of chemicals being excreted out by the liver into the bile being reabsorbed the enterocytes back into the liver, prolonging systemic circulation of the chemical. Activated charcoal is very commonly used as an adsorbent, preventing absorption of the toxin. Activated charcoal reaches equilibrium with chemicals in the environment within 30 minutes, at which point some adsorption may occur. This is one of the reasons administration with a cathartic is advocated, to shorten gastrointestinal transit time. Recommended dosage of activated charcoal is 2 to 5 g/kg (refer to product label for accurate dosing). Charcoal has the disadvantage of not being able to adsorb ionized toxins, and preventing endoscopic viewing of intestinal contents (62 hours for intestines to clear up).

Cathartics, such as sorbitol, are commonly administered with, or included in activated charcoal solutions to shorten gastric transit time. Reduction of transit time allows for less time for absorption to occur, and promotes excretion. Osmotic cathartics will promote movement of water into the lumen of the intestines increasing the fluid volume of the bowel content. Osmotic cathartics can be saline based, made of sodium and magnesium containing solution leading to higher osmolarity, or saccharide based (sorbitol). Repeated doses of cathartics are dangerous, as they can cause vomiting, nausea, dehydration, and even hypotension due to fluid depletion. Cathartics are often not very effective when administered alone. Cathartics are often combined with activated charcoal to provide a synergistic effect.

Diuresis, or increased urination, can be induced through administration of intravenous fluids and diuretics, increasing elimination of the toxin through the urine. Diuretics such as furosemide and mannitol are frequently used. The strategy is most useful in toxins that show a high degree of renal excretion (bromide, lithium, amphetamine, phenobarbital, and salicylate), while benefits may not be seen as much with protein bound toxins. Care must be taken to prevent fluid overload and electrolyte abnormalities, as high-volume fluid administration can lead to hyponatraemia, hypokalaemia, pulmonary oedema, and cerebral oedema if not closely monitored. Patients that are anuric or oliguric whether from the toxin or pre-existing disease, are at higher risk of complications.

Ion trapping is a technique used to allow for further excretion of toxins through the urine by “trapping” the toxins in its ionic form to prevent reabsorption through the kidneys. Ionized molecules less readily diffuses through cellular membranes made of lipids. Trapping of weak acids and bases are easier to accomplish. Ion trapping is useful when the toxin is excreted predominantly through the urine, is a weak electrolyte, and is distributed to the extra-cellular space and non-protein bound. Ion trapping can be accomplished through acidifying the urine through administration of ammonium chloride or alkalinizing the urine by administration of sodium bicarbonate. Acidifying may be useful for treatment of amphetamines and phencyclidines. Ion trapping requires frequent monitoring of urine pH and blood pH to prevent detrimental acidosis or alkalosis, and may alter metabolism and excretion of other drugs.

Lipid emulsions, typically used for parenteral nutrition, have been more recently used for treatment of toxicities. Lipid emulsions consist of triglycerides and phospholipids, which can solubilize lipophilic chemicals (ivermectin, pyrethrins, permethrin, ionophores, marijuana) and make them unavailable for binding to the site of action. Each compound has a differing degree of lipophilic nature, which the effectiveness will depend on.

Physical removal of the source of the toxin through gastrotomy may be necessary if other options of decontamination are not expected to be fruitful. Iron tablets, for example, are known to adhere to the gastric mucosa and are difficult to remove without manually removing them. For some toxins, placement of a urinary catheter to keep the bladder empty is warranted for the prevention of reabsorption of metabolites across the bladder wall (methylxanthines, for example).

There are many considerations to be made in successful decontamination and recovery of a patient exposed to toxins. The appropriate method and giving the highest chance of success requires knowledge of options available and an understanding of the types and pharmacology of the toxins the patient is exposed to. We are often faced with situations where we do not know what the patient has been exposed to and are forced to treat based on suspicions due to symptoms seen, creating a level of difficulty in appropriate decontamination.