10 May 2021
Lotfi El Bahri, DVM, MSc, PhD, lookins at a case of poisoning in a male Chihuahua in this Case Notes article.
Lotfi El Bahri
Job Title
Image: © mirzamlk / Adobe Stock
You are presented with a two-year-old male Chihuahua weighing 3.5kg at your emergency veterinary clinic.
The dog’s owner found him ingesting a large quantity of open jar “over-the-counter (OTC) medication” for the treatment of arthritis – the label of which listed the active ingredient as camphor 10% The owner has noted significant vomiting, diarrhoea and muscle tremors.
What is the toxic dose and mechanism of toxicity of camphor?
Structurally, camphor is a bicyclic monoterpene ketone produced naturally by the camphor tree (Cinnamomum camphora) and synthesised from turpentine. It is a solid, white, translucent crystal with a characteristic, strong, penetrating, aromatic odour.
Camphor is a common ingredient found in hundreds of OTC medications in various forms (liquid, cream, ointment), widely used in humans topically for the treatment of relief of muscles and joints pain, muscle stiffness, backache, sprains and coughs due to cold sores. Camphor is also used to control clothes moths.
Camphor has moderate-to-high acute oral toxicity. The lethal dose in dogs is reported to be between 9g and 14g. Cats may be more sensitive than dogs because of their low capacity of glucuronide conjugation (in dogs, camphor is oxidised in the liver to campherols – 3-hydroxycamphor and 5-hydroxycamphor – which are then conjugated with glucuronic acid).
Lipid soluble, camphor is readily absorbed from the skin. It should never be applied dermally to dogs or cats due to risks of poisoning.
In humans, severe toxicity with convulsions is estimated to occur at approximately 34mg/kg. The oral median lethal dose in mice is 1,310mg/kg.
In 1983, the US Food and Drug Administration set a limit of 11% allowable camphor in OTC products and totally banned products labelled as camphorated oil, camphor liniment and camphorated liniment.
The easy availability of camphor in various forms puts pets at high risk of poisoning. Camphor is not known to be palatable to dogs. However, poisoning can occur when a dog accidentally ingests a large amount of camphor as it chews on a tube of ointment or cream containing it.
As a rubefacient/counterirritant agent, camphor is irritating to the mucous membranes, skin and eyes.
Camphor has a rapidity of toxic action. The main target organ of exposure is the CNS, with alterations in brain cell functions. Camphor is a CNS stimulant – a result from excitation of the cerebral cortex cells. It causes neurotoxic effects (seizures). Camphor also exhibits cardiotoxicity (cardiac disturbances) and vascular collapse. Hepatic and renal damage can occur.
What are the main clinical features of camphor poisoning in dogs?
Camphor poisoning has a rapid onset of clinical signs, within 30 to 60 minutes after ingestion. They are:
Death is due to respiratory failure.
Toxic effects of camphor poisoning may persist far beyond a 24 to 48-hour window and require attention from the practitioner.
Laboratory values indicate metabolic acidosis (lactate dehydrogenase) and elevations in hepatic enzyme tests (alanine aminotransferase and aspartate aminotransferase). In humans, an ECG shows cardiac conduction disturbances: widening of QRS complex and prolonged corrected QT (QTc) interval. Abnormal QTc interval prolongation should be considered as an increased risk of sudden cardiac death.
2D echo images reveal features of acute myocarditis. An electroencephalogram (EEG) shows diffuse neuronal disturbances with excessive slow activity in the bianterior and bicentral areas of the brain. Postmortem lesions include damage in the brain (neuronal degeneration in the hippocampus and frontal cortex), liver (enlarged, friable, histologically irregular fat deposits) and kidney (swelling of the proximal tubules).
How should camphor poisoning in dogs be managed?
Camphor poisoning is a time-critical, life-threatening emergency. No specific antidote exists. Treatment is largely supportive.
An IV catheter should be placed. To control seizures, diazepam (0.5mg/kg to 2mg/kg IV bolus) should be administered and repeated if necessary within 20 minutes (serum half-life in dogs is 2.5 hours to 3.2 hours) up to three times in a 24-hour period, or 1mg/kg to 2mg/kg rectally. Do not give diazepam IM (contraindicated in patients with severe liver disease).
Alternatively, administer lorazepam (long-acting benzodiazepine 0.2mg/kg IV bolus, because of its high affinity for benzodiazepine receptors in the CNS) or midazolam 0.2mg/kg to 0.4mg/kg IV may be repeated once. When IV access is not available, midazolam can be administered by IM because it is rapidly absorbed by this route.
If seizures persist or recur, administer phenobarbital (2mg/kg to 5mg/kg IV bolus), which can be repeated at 20-minute intervals, up to two times. Do not use in patients with significant liver disease, though.
Alternatively, administer propofol (3mg/kg to 6mg/kg IV initial bolus) followed by 0.1mg/kg/min to 0.6mg/kg/min constant rate infusion (CRI).
Alternatively, 2% to 2.5% concentrations of isoflurane alone with oxygen can be used. For maintenance, use 1.5% to 1.8% concentrations of isoflurane in oxygen.
Attention to airway, breathing and circulation are paramount. Intubate affected animals and provide artificial respiration with O2 during seizures. ECG, EEG, hepatic and renal function, and blood pressure should be monitored.
Correction of lactic acidosis (normal values in dogs: pH less than 7.33; standardised base excess less than -4mmol/L) by sodium bicarbonate 8.4% solution: 1ml/lb to 2.5ml/lb bodyweight CRI depending on the severity of the acidosis, over a four-hour period.
To correct dehydration (for example, vomiting, diarrhoea), IV fluids should be used. Lactated Ringer’s solution should be avoided in patients with hepatic insufficiency (hyperlactataemia can occur as a result of impaired metabolism of lactate by the liver).
The induction of emesis is contraindicated (stimulates seizures).
Oral activated charcoal is also contraindicated (camphor is rapidly absorbed). However, it could be considered if other ingredients (for example, salicylate) exist in the product that are effectively adsorbed by activated charcoal.
Antiemetics may be required. Maropitant citrate injectable solution is given in dogs: 1mg/kg SC, once a day, for up to five consecutive days.
N-acetylcysteine (NAC) may be effective for preventing hepatic injury. NAC should be given at an initial dose of 140mg/kg IV bolus and then 70mg/kg every six hours for seven treatments. The NAC solution should be diluted to a 5% concentration with 5% dextrose. Each dose is infused over 30 to 60 minutes through a peripheral IV catheter using an inline 0.2µm Millipore filter.
A vasopressor may be administered if severe hypotension (dopamine: 1µg/kg/min to 3µg/kg/min CRI).
IV lipid emulsion therapy is indicated because camphor is high lipid soluble (log P values of 3.04). The following dosage recommended for dogs is adapted from human literature. Administration of an initial IV lipid emulsion (ILE) 20% IV bolus 1.5ml/kg over one minute, followed by a CRI of 0.25ml/kg/min for the next 30 minutes to 60 minutes.
In non-responsive patients, additional intermittent bolus can be given IV slowly, up to 7ml/kg.
If clinical signs do not improve after 24 hours, discontinue ILE. ILE 20% preparations are isotonic and can be given by a peripheral vein or in a central catheter using aseptic techniques to prevent bacterial contamination risk.
Enhanced elimination is not recommended (volume of distribution of camphor is large). The patient can be discharged once clinical signs have resolved.
Owners should be advised to keep camphor-containing products out of the reach of pets.
The lethal concentration 50 after 96 hours bioassay in zebrafish (Brachydanio rerio) is 50mg/L. An estimate bioconcentration factor of 38 suggests the potential for bioconcentration of camphor in aquatic organisms is moderate (rapid photodegradation). Therefore, the camphor residues are not expected to be at concentrations that would pose a risk concern for environment.
