Information for vets
Permethrin toxicity remains one of the most common causes of poisoning in cats worldwide.
Poisoning usually results from cat exposure to concentrated permethrin-containing spot-on products designed for use in dogs.
In the veterinary literature, permethrin poisoning in cats has been reported in many countries, including:
The following is extracted from an article by Tobias Grave and Amanda Boag (Feline toxicological emergencies: When to suspect and what to do) published in the Journal of Feline Medicine and Surgery (2010, Volume 12, pages 849–860):
Pyrethrin toxicity - from JFMS 2010 (Grave & Boag)
Pyrethrins and pyrethroids are insecticides that are sold for the treatment of flea and tick infestation. Pyrethrins are natural substances extracted from Chrysanthemum species; the term pyrethroid describes similar, synthetically manufactured molecules produced with the aim of increasing the photostability of this group of drugs. Although it might be expected that pyrethrins would be relatively safe to use for ectoparasite control, given the differences between mammals and insects, cats are frequently presented as an emergency to the veterinary practitioner showing clinical signs after pyrethrin exposure.
Between 1988 and 2006, the Veterinary Poisons Information Service in the UK received 1306 enquiries relating to permethrin exposure. Of those enquiries, 49.8% related to spot-on formulations, of which 80.9% involved cats . Intoxication frequently follows inappropriate application of spot-on formulations intended for use in dogs, and some cats may even be affected by close contact with dogs treated with a spot-on formulation .
The toxic dose for pyrethrin and pyrethroids is currently unknown, but based on cases reported to the Animal Poison Control Center (APCC) in the USA, 1 ml of 45% permethrin applied dermally to a 4.5 kg cat can result in life-threatening toxicosis . In the UK, spot-on preparations for dogs can contain up to 74.4% permethrin .
Why are cats susceptible to permethrin poisoning?
There are a number of reasons why cats may be particularly susceptible to intoxication with pyrethrins and pyrethroids. Their relatively high surface area to weight ratio means that, with topical application, smaller individuals tend to receive higher doses on a mg/kg basis. Furthermore, pyrethroids are excreted following either oxidation or glucuronidation and the reduced capacity for glucuronidation in the cat can contribute to the accumulation of metabolites and a less efficient detoxification process . Finally, other substances added to the formulation might utilise the capacity of detoxification enzymes, further prolonging exposure.
Mechanism of toxicity
After application of a spot-on emulsion, the lipophilic pyrethroids are quickly absorbed through the skin into the systemic circulation. Their absorption is also rapid after oral intake and even inhalation. Pyrethroids principally affect the peripheral and central nervous system. They reversibly alter the function of sodium channels within the axon in such a way that it prolongs their conductance and leads to repetitive firing of the nerve fibre. This effect is enhanced by low temperatures. Due to their lipophilic properties, pyrethrins pass easily through the blood-brain barrier and can induce CNS signs, including seizures. There is evidence of accumulation of pyrethroids within neural tissue even when blood levels are low.
Clinical signs and diagnosis
Clinical signs are normally noticed immediately after exposure, but can be delayed for up to 72 h. In mild intoxications, paraesthesia induced by direct contact with the substance may result in paw flicking, ear twitching and uncontrolled contractions of the cutaneous trunk muscles. Grooming of a contaminated body area can result in hypersalivation and vomiting. Severe muscle tremors, seizures and/or depression are normally seen only in severe intoxications. In one study , the most common clinical signs were:
- Tremors/muscle fasciculations (86%)
- Twitches (41%)
- Hyperaesthesia (41%)
- Seizures (33%)
- Pyrexia (29%)
- Ptyalism (24%)
- Ataxia (24%)
- Mydriasis (19%) and
- Temporary blindness (12%)
Laboratory detection of pyrethrins/pyrethroids is not readily available and haematology, biochemistry and other findings might be normal. One of the principal differential diagnoses is organophosphate/carbamate toxicosis. Where available, measurement of cholinesterase levels may be helpful in distinguishing between the two groups of toxins — with levels being unremarkable in pyrethrin/pyrethroid toxicity and most likely decreased in organophosphate toxicity.
Treatment and prognosis
Dermal decontamination should be instituted at the earliest possible opportunity. Bathing of the patient is generally indicated and the use of a hand- or dishwashing detergent might enhance the cleaning process .
Hypothermia may potentiate the effect of pyrethroids on ion-channel activity and, therefore, bathing the patient with cold water and/or prolonged sedation should be avoided. Conversely, bathing in water that is too warm might enhance resorption through the skin due to hyperaemia and should also be avoided. The patient should be actively dried and, if transport to a veterinary facility is delayed, owners can be advised to wrap it in a warm towel.
Valentine  showed a potential positive effect of activated charcoal even after dermal exposure. This may be due to the existence of some enterohepatic recirculation of the toxic agent. The risk of administering activated charcoal to these patients must, however, be carefully weighed against the potential benefit.
Once clinical signs are present, treatment should focus on control of the muscle tremors and/or seizures. Benzodiazepines are typically insufficient to control signs in severe intoxications, and may also be responsible for paradoxical exacerbation of neurological signs . Methocarbamol (Robaxin-V; Fort Dodge) is a peripherally acting muscle relaxant that is recommended for control of severe muscle tremors. Its use is limited by lack of availability of the intravenous preparation outside the USA. Where available it may be administered as multiple boluses or a continuous rate infusion; the recommended dose is 55–220 mg/kg IV and doses should not exceed 330 mg/kg/day.
Where methocarbamol is not available, or where it is suspected that the animal has seizures as well as muscle tremors, a constant rate infusion of propofol (0.1–0.4 mg/kg/min) may be used. The duration of propofol infusion in cats should ideally be limited to approximately 12 h due to its ability to induce red cell oxidative injury in this species. Phenobarbital is another drug that may be used; however, it should be noted that, even when given intravenously, its onset of action is in the order of 20–30 mins, making it less useful for control in the patient with acute seizures. Pentobarbitone may be used but its current lack of availability in a sterile form is a limitation. Whatever drug is chosen, it is not usually necessary to eliminate all muscle activity and an appropriate balance between an improvement in clinical signs and potential side effects of the sedative drug must be sought.
In the face of hypersalivation, the use of atropine is often considered but is not recommended as it may produce further CNS stimulation. A potential positive benefit of atropine administration is helping to distinguish between suspected pyrethroid and carbamate intoxication. (Low doses of atropine should not alleviate any signs in the carbamate-intoxicated patient.)
For mildly affected cases the prognosis is good and there are unlikely to be any long term effects. For more severely affected cases, survival rates can also be good but only if patients receive early aggressive management and continuous supportive care; unfortunately, some will be euthanased or die due to the severity of their signs. If prolonged seizure activity cannot be suppressed, irreversible brain damage can occur, but with successful treatment, long term clinical signs seem to be absent .
Typically recovery takes approximately 2–3 days, but there is a wide range between individual cases (3 h to 7 days) . As successful treatment may require intensive support, with all the associated expense, clearly the problem is best avoided where possible. Educating owners as to the potential severity of signs that can follow exposure of cats to some canine flea products is an important part of achieving this goal.
- Volmer P, Khan S. Warning against use of some permethrin products in cats. J Am Vet Med Assoc 1998; 213: 800–1
- Sutton NM, Bates N, Campbell A. Clinical effects and outcome of feline permethrin spot-on poisonings reported to the Veterinary Poisons Information Service (VPIS), London. J Feline Med Surg 2007; 9: 335–39
- Martin A, Campbell A. Permethrin toxicity in cats. Vet Rec 2000; 147: 639
- Peterson M, Talcott P Hansen S. Pyrethrins and pyrethroids. In: Peterson M, Talcott P, eds. Small animal toxicology. 2nd edn. St Louis: Saunders Elsevier, 2006: 1004.
- Whittem T. Pyrethrin and pyrethroid insecticide intoxication in cats. Compend Contin Educ Pract Vet 1995; 17: 489–92
- Boland LA, Angles JM. Feline permethrin toxicity: retrospective study of 42 cases. J Feline Med Surg 2010; 12: 61-71
- Valentine W. Toxicology of selected pesticides, drugs, and chemicals. Pyrethrin and pyrethroid insecticides. Vet Clin North Am Small Anim Pract 1990; 20: 375–82
- Richardson JA. Permethrin spot-on toxicoses in cats. J Vet Emerg Crit Care 2000; 10: 103–6.
Access to reference papers
To facilitate dissemination of information, SAGE (the publisher of the Journal of Feline Medicine and Surgery) and ISFM have made three published papers on permethrin toxicity in cats freely available:
- Malik et al (2010) Permethrin spot-on intoxication of cats - Literature review and survey of veterinary practitioners in Australia
- Boland & Angles (2010) Feline permethrin toxicity: retrospective study of 42 cases
- Sutton et al (2007) Clinical effects and outcome of feline permethrin spot-on poisonings reported to the Veterinary Poisons Information Service (VPIS), London
Summary of treatment recommendations:
Data from Boland & Angles (2010) JFMS 12:61–71
1. Dermal decontamination
- Bathe the cat in lukewarm water using a mild detergent to remove any remaining product from the coat and skin. Dry the cat and avoid hypothermia which could exacerbate clinical signs.
2. Manage muscle tremors
- Methocarbamol - if available this can be effective. Dose at 55–200 mg/kg IV; can be repeated up to three times a day, but total daily dose should not exceed 330 mg/kg. If injectable methocarbamol is not available, tablets may be used – crushed and given via nasogastric intubation or per-rectum (same dose)
- Benzodiazepines - drugs such as diazepam (0.25 mg/kg IV PRN) or midazolam (0.3 mg/kg IV/IM PRN) may be effective in controlling mild tremors. Care is needed though as paradoxical exacerbation of signs has sometimes been reported with their use.
3. Manage seizures (or severe refractory muscle tremors)
- Propofol – anaesthesia using a bolus (4–6 mg/kg IV) followed by a constant rate infusion (0.05–0.3 mg/kg/min)
- Phenobarbitone – can be given as a bolus (2–4 mg/kg IV), and can be repeated every 2 hours to a maximum of 20 mg/kg/day. A constant rate infusion could be considered.
4. Supportive therapy
- Maintain body temperature
- Intravenous fluids (e.g., 1.5 x maintenance rates)
- Ocular lubrication
- Bladder expression or catheterisation
- Quiet darkened environment
- Ensure patent airway – intubate if necessary
Intravenous lipid emulsion (IVLE) therapy
Recently, IVLE therapy has been proposed as supportive treatment for management of intoxications with lipophilic drugs, such as permethrin, in dogs and cats. A few reports have emerged of their use in cats with permethrin poisoning and initial results are encouraging. The exact mechanism of action is uncertain but it is thought that the lipid infusion helps draw the drug away from the tissues and thus lessens toxic effects.
Optimum products and dose rates have not been determined but rapid improvements have been reported with:
- 20% Intralipid (Fresenius Kabi) – has been used in cats with permethrin toxicity with typical doses of 10–15 ml/kg given as an infusion over 30–120 minutes and repeated daily if needed.
- 20% ClinOleic (Baxter Healthcare) – has been used with an initial bolus of 2 ml/kg followed by 16 ml/kg given over 4 hours with the protocol repeated daily if needed.
- Kuo K, Odunayo A. Adjunctive therapy with intravenous lipid emulsion and methocarbamol for permethrin toxicity in 2 cats. J Vet Emerg Crit Care 2013; 23: 436–441
- Haworth MD, Smart L. Use of intravenous lipid therapy in three cases of feline permethrin toxicosis. J Vet Emerg Crit Care 2012; 22: 697–702
- Brückner M, Schwedes CS. Successful treatment of permethrin toxicosis in two cats with an intravenous lipid administration. Tierarztl Prax Ausg K Kleintiere Heimtiere 2012; 40: 129–134