Patricia Ann Talcott,     Pullman, Washington

Organophosphate and Carbamate Insecticides

Organophosphate and carbamate insecticide poisonings are still one of the most commonly encountered toxicoses in small animals because of their widespread use on animals, around the house, and in agriculture (Hansen, 1995a,; Talcott, 2000). These insecticides may be used on animals intentionally or accidentally. Many exposures are accidental, caused by either inappropriate use by the applicator or accidental access to the product by the pet because of inappropriate storage or disposal. Many insecticide products are intended to be applied to the premises or other property, but some are components of pet products including shampoos, flea and tick collars, and insecticide dips.

These products are generally formulated with oily vehicles or solvents to increase contact time and enhance stability. Literally hundreds of formulations are marketed in the form of sprays, dips, shampoos, collars, foggers, or bombs. These marketed products are sometimes mixed with food items to intentionally or maliciously expose pets.

Hundreds of cholinesterase inhibitor insecticides are marketed in the United States. See Box 32-1 for a list of some of the more commonly used chemicals. The toxicity of these chemicals varies widely. Unfortunately, there are few well-established toxic or lethal doses for dogs or cats reported in the literature. Dermal or oral exposures are commonly encountered by dogs or cats. The inhalation route of exposure is more common in humans. Most of the organophosphate and carbamate insecticides are rapidly metabolized by hepatic enzymes; then both the parent compound and its metabolites are rapidly eliminated in the urine. However, a few lipophilic compounds have longer half-lives, giving them a greater potential to cause central nervous system effects.

Both the organophosphate and carbamate insecticides inhibit acetylcholinesterase (AChE) and pseudocholinesterase enzymes to varying degrees. AChE is responsible for breaking down acetylcholine released at cholinergic sites. Thus animals poisoned with cholinesterase inhibitors often exhibit a mixture of clinical signs as a result of overstimulation of the nicotinic receptors of the somatic nervous system (skeletal muscle), sympathetic and parasympathetic preganglionic junctions, all parasympathetic postganglionic junctions (including a few sympathetic postganglionic junctions), and some neurons within the central nervous system.

The onset of clinical signs can vary between a few minutes to several hours, depending on the dose, the route of exposure, and the specific chemical involved. Commonly reported muscarinic signs include excessive salivation, anorexia, emesis, diarrhea, excessive lacrimation, miosis or mydriasis, dyspnea, excessive urination, and bradycardia or tachycardia. The mnemonics SLUD (i.e., salivation, lacrimation, urination, defecation) and DUMBBELS (i.e., diarrhea, urination, miosis, bronchospasm, bradycardia, emesis, lacrimation, salivation) are often used in the classroom as a device to remember these clinical signs. Prominent nicotinic signs include ataxia, weakness, and muscle twitching. In acute high-dose oral exposures, seizures can occur within 10 to 20 minutes. It is important to note that not all signs are seen in every poisoning case.

Death is generally the result of respiratory failure and tissue hypoxia caused by excessive respiratory secretions, bronchoconstriction, paralysis of the respiratory muscles, and direct depression of the respiratory center in the medulla. Cats appear to be particularly sensitive to chlorpyrifos; anorexia, muscle weakness, ataxia, and depression are the predominant features. Exposure to these more lipophilic compounds has been referred to as the intermediate syndrome; additional clinical features may include muscle tremors, abnormal mentation, and abnormal posturing with hyperesthesia.

A clinical diagnosis of organophosphate or carbamate poisoning relies heavily on observing compatible clinical signs and a history of known exposure. Inhibition of whole blood, plasma, serum, retinal, or brain cholinesterase activity (at least 25% to 50% of normal) suggests an exposure to these compounds and toxicosis if the clinical signs are compatible. Cholinesterase testing can still be performed after the administration of atropine and may still be useful several days after pesticide exposure. Lack of inhibition cannot rule out exposure to carbamate compounds because of the reversibility of their binding to the cholinesterase enzyme. In addition, because of the acuteness in onset of signs and possible death and the lack of some compounds to readily traverse the blood-brain barrier, brain cholinesterase may be normal in the acutely poisoned patient. Lower red blood cell counts may also lower true AChE activity; this is one reason to check the packed cell volume before running the assay. Therefore cholinesterase testing should be regarded as a screening tool, and false negatives and positives may occur. Tissue analysis for the organophosphate or carbamate insecticide is primarily reserved for confirming an exposure following a postmortem examination. Stomach and intestinal contents and samples from the liver, kidney, fat, and skin (in cases of suspect dermal exposures) should be collected, individually bagged and labeled, and kept frozen during shipment to a laboratory.

Changes observed on a complete blood count, serum chemistry panel, and urinalysis are typically very nonspecific and highly variable. Pancreatitis accompanied by significant elevations in amylase and lipase has been reported following exposures to certain organophosphate insecticides.

Treatment should be aimed at preventing further absorption through aggressive decontamination procedures and controlling the muscarinic and nicotinic clinical signs. Many dermal exposures lead to subsequent oral exposures, particularly in cats; thus multiple decontamination procedures may be needed. In the asymptomatic orally exposed patient, emetics such as 3% hydrogen peroxide or apomorphine are generally recommended. Three percent hydrogen peroxide is dosed at 1 ml/lb or 2.2 ml/kg PO, with a total dose not exceeding 10 ml in the cat or 50 ml in the dog, regardless of body weight (however, this volume has been routinely exceeded in dogs, and I have observed few serious complications). It can be used shortly after feeding a small amount of food. If emesis is contraindicated, a gastric lavage can be performed after inducing light anesthesia, followed by the placement of a cuffed endotracheal tube to prevent aspiration.

Induction of emesis and gastric lavage should always be followed with the use of activated charcoal and a cathartic. Administration of multiple activated charcoal doses may be warranted; care should be taken to reduce the subsequent cathartic doses and monitor the patient for the rare occurrence of hypernatremia or hypermagnesemia. A mild detergent bath and thorough rinsing are recommended in cases of dermal exposure. In the topically exposed patient, particularly in cats, exposure may be both dermal and oral because of excessive grooming. In these cases both dermal and oral decontamination procedures may be beneficial.

Atropine sulfate is used to control the muscarinic signs (e.g., miosis, salivation, diarrhea, bradycardia, bronchoconstriction). The usual dosage range is 0.20 to 0.50 mg/kg (one fourth IV, the remainder SC or IM; some individuals administer the entire dosage IV). The dosage selected should be just enough to provide adequate atropinization, and atropine may be repeated at half the initial dose if signs return. Hypersalivation is often the most useful clinical sign for monitoring atropine therapy. Oxygen therapy with or without artificial respiration may be required until the patient is breathing normally on its own.

Seizures, muscle tremors, or agitation can be controlled with intravenous diazepam, methocarbamol, or phenobarbital. Pralidoxime chloride ([2-PAM]; 10 to 20 mg/kg IM or SC BID or TID) can help reduce muscle tremors resulting from nicotinic receptor stimulation by an organophosphate. A clinical effect should be observed within the first 3 to 4 days, and treatment should be continued as long as improvement is observed. 2-PAM has its best effect if administered within 24 hours of exposure; however, some benefits may occur, particularly in cases involving large toxin exposures, if given within 36 to 48 hours. Rapid intravenous injection may cause tachycardia, muscle rigidity, transient neuromuscular blockage, and laryngospasm. The use of oximes in cases of carbamate poisonings is somewhat controversial (particularly since the carbamate binding is reversible); one should weigh the benefits and risks of its use in each case. It is impossible to tell based on clinical signs alone whether the exposure was caused by an organophosphate or a carbamate insecticide.

Diphenhydramine use is also controversial in the treatment of organophosphate and carbamate poisonings; I do not recommend it. One suggested dose of diphenhydramine in dogs is 2 to 4 mg/kg orally every 6 to 8 hours. However, there have been reports of excessive sedation or excitement and anorexia when used in dogs and cats.

Good supportive and nursing care, including intravenous fluid therapy, adequate nutritional management, and maintenance of normal body temperature and electrolyte balance, should also be considered in the acutely poisoned patient. Chlorpyrifos poisoning in cats requires special attention; these cats often show signs of ataxia, anorexia, depression, and muscle tremors for several days or weeks after initial exposure.