21 Oct 2019
Lotfi El Bahri describes the case of a German shepherd dog that presents after having ingested some insecticide.
Lotfi El Bahri
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Image: © Kateryna / Adobe Stock
You are presented with a two-year-old male German shepherd dog weighing 28kg at your emergency veterinary clinic.
The dog’s owner found him ingesting some quantity of bluish colour powder in an open box of insecticide – the label of which listed the active ingredient as methomyl 4%. The owner has noted vomiting, drooling, frequent urination and diarrhoea.
Methomyl belongs to the family of the N-methylcarbamate (ester of carbamic acid) used as broad-spectrum insecticide in home gardening, fly baits, rodenticide and field crops (for example, vegetables and fruits). Carbamate toxicosis is the most common class of pesticides involved in animal poisoning in Europe. The majority of toxicities are accidental, but malicious poisoning can occur.
It can cause high acute oral toxicity. The oral median lethal dose (LD50) is 17mg/kg in male rats. In humans, the lethal dose is estimated to be 12mg/kg to 15mg/kg. Methomyl is considered to be highly toxic to mammals, fish and aquatic invertebrates.
Carbamate insecticides inhibit the enzyme acetylcholinesterase (AChE) that hydrolyses acetylcholine – a neurotransmitter that mediates the transmission of nerve impulses. Inhibition of AChE leads to the accumulation of excessive acetylcholine.
The accumulated acetylcholine excessively stimulates cholinergic receptors – muscarinic receptors located in the smooth muscle of glands, intestinal tract, cardiac muscle, the eye and in the CNS; nicotinic receptors located at the neuromuscular junctions of striated muscle; and the ganglionic synapses of autonomic ganglia. However, this inhibition of AChE is reversible (AChE is decarbamylated rapidly) – the enzyme retakes its normal function within several hours.
Based on oral studies, the half-life for methomyl-induced inhibition of erythrocyte AChE activity in humans is 1.6 hours. In addition, the enzyme-inhibitor complex does not undergo the process of ageing as it does with organophosphate insecticides.
The clinical signs appear within 30 minutes to 2 hours after ingestion. The muscarinic signs – the first to manifest – are very pronounced. They are:
CNS signs (being lipid soluble, methomyl crosses the blood-brain barrier) include:
Or
Death is due to respiratory failure. Acute pancreatitis is a serious complication (activation of pancreatic secretions by carbamates, escaping into the interstitial and peripancreatic tissue) within a few days after the acute period. In humans, children with carbamate exposures often present with predominantly nicotinic and CNS symptoms.
Methomyl poisoning is a medical emergency, patients may die minutes after ingestion. Pralidoxime (pyridine-2-aldoxime methyl chloride or 2-PAM), the antidote for organophosphate poisoning, which regenerates AchE that has been inactivated by phosphorylation, should not be used to treat carbamate poisoning (cholinesterase inhibition is reversible and short-lived). In the case of some carbamates (for example, carbaryl and carbofuran), pralidoxime may accentuate the toxicity.
Atropine (sulfate) – an anticholinergic agent – competitively blocks the action of acetylcholine at muscarinic receptors is the specific treatment. The dosage is 0.2mg/kg to 0.5mg/kg: give a quarter of the dose IV initially, then wait 15 minutes to observe the effects and administer the remainder SC. The dosage may be repeated every four to six hours as needed, until signs of atropinization are present (drying of secretions, increased heart rate).
Atropine therapy is usually required for less than 24 hours. Atropine reverses muscarinic effects, but not nicotinic effects. Atropine will not counteract muscle tremors, weakness or paralysis. Due to the shorter duration of effects of carbamates (as esters, carbamates are rapidly metabolised by hydrolysis and more than 80% is excreted within 24 hours), overtreatment with atropine should be avoided because atropine toxicosis (anticholinergic symptoms: tachycardia, mydriasis) can occur.
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. This is contraindicated in patients with severe liver disease, however.
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.
Barbiturates are contraindicated (depress respiration and aggravate toxicity of carbamates). In cases of refractory seizures, 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). Attention to airway, breathing and circulation are paramount. Intubate affected animals and provide artificial respiration with O2 during convulsions. ECG and continuous cardiac monitoring should be performed.
Emesis should be induced only if the animal is asymptomatic. Administer apomorphine 0.03mg/kg IV, or 0.04mg/kg IM or 0.025mg tablet crushed and dissolved in physiological saline. Instil in the conjunctival sac and rinse with water after emesis has occurred. Alternatively, use xylazine (1.1mg/kg SC or IM).
To prevent further absorption of methomyl from the intestinal tract, use activated charcoal (AC; 1g/kg to 4g/kg) mixed with water to make a 20% slurry (1g/5 ml water) via a nasogastric tube as soon as possible post-ingestion, and after the airway is secured. AC admitted orally is contraindicated in convulsing or comatose animals. Maintain the patient on IV-balanced crystalloid fluids, such as lactated Ringer’s solution 40ml/kg/hour to 90ml/kg/hour.
Administer a laxative, lactulose: 1ml/4,5kg orally, three times daily, then adjust as needed, producing enhance intestinal transit (atropine slows intestinal motility) and rapid elimination of the adsorbed methomyl via the faeces.
IV lipid emulsion therapy is indicated, because methomyl is lipid soluble (log P values of 1, 24). 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 at 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. A vasopressor may be administered if severe hypotension (dopamine: 1micrograms/kg/min to 3micrograms/kg/min CRI).
Enhanced elimination is not recommended (volume of distribution of methomyl is very large). Drugs such as aminoglycoside antibiotics they have neuromuscular blocking properties are contraindicated. Phenothiazines (for example, acepromazine) are not recommended, as the seizure threshold may be lowered. Intermediate syndrome and delayed peripheral neuropathy do not occur with carbamate pesticides. The patient can be discharged home once clinical signs have resolved.
