All of the above clinical signs are not necessarily seen in every case and variability depends on toxicant type, dosage, formulation, route of exposure, poisoned species and stage of intoxication. Cats are generally more susceptible to AChE inhibitors than dogs. Death from either organophosphates or carbamates is associated with respiratory dysfunction resulting from respiratory tract secretions, bronchiolar constriction, intercostal and diaphragm muscle paralysis and CNS-mediated respiratory paralysis.
The intermediate and chronic (also named organophosphate-induced delayed neuropathy) syndromes are characterized by generalized neuromuscular weakness. The reader is referred to other textbooks for further information on these syndromes that are not characterized by seizures.
Diagnosis
Clinical diagnosis is based on history of ingestion, clinical presentation and improvement or resolution of muscarinic signs after atropine administration. If the diagnosis is uncertain, a test dose of atropine (0.02 mg/kg IV) can be administered after evaluating the baseline heart rate. If the heart rate increases, the pupils dilate and hypersalivation stops in 10–15 min, the animal is unlikely to have organophosphate or carbamate intoxication as it takes approximately 10 times this test dose to resolve clinical signs caused by these compounds.
Laboratory findings of heparinized whole blood cholinesterase (ChE) activity reduced by 50% of normal (based on the normal range for that laboratory) suggest exposure, whereas ChE activity less than 25% of normal indicates toxicosis in animals with characteristic clinical signs (Wismer, 2012). ChE activity of heparinized whole blood is a combination of true AChE activity of RBCs and pseudo-ChE activity of serum. Packed cell volume should be checked on blood samples for AChE testing as anaemia can result in decreased AChE activity. Blood should be kept refrigerated to prevent the loss of enzyme activity. ChE activity can remain decreased for 6 to 8 weeks following organophosphate exposure, whereas it may be normal in animals with carbamate intoxication. Carbamates bind reversibly with AChE in the body and they may also dissociate from AChE or pseudo-ChE in a blood tube or other specimen during transit. Stomach content, vomitus, hair, or suspected baits can be submitted to the laboratory for an organophosphate or carbamate residue screen.
Management
Treatment includes administration of atropine (0.2 to 0.4 mg/kg, one-fourth of the initial dose slowly IV and the rest IM or SQ) to counteract the muscarinic signs, decontamination and prevention of further toxin adsorption (Table 4.1), skeletal muscle relaxants (Table 4.1), AEMs (see Table 4.1 and Chapters 12 and 24) and supportive care. Dramatic cessation of para-sympathetic signs is usually observed within 3 to 5 min after administration of atropine IV. Repeated administration of atropine, IV, IM or SC, at one-half of the initial dose is often required, especially in cats with organophosphate toxicity. Glycopyrrolate (0.01–0.02 mg/ kg IV) may also be used to control the muscarinic signs. Cardiac activity should be monitored. In animals with dermal exposure, decontamination is performed by bathing with a mild hand-dishwashing detergent and water. The individuals bathing the animals should wear protective gloves and aprons. In animals with oral exposure, decontamination is performed by induction of emesis (in asymptomatic animals) or gastric lavage and administration of activated charcoal with a saline cathartic or sorbitol (Table 4.1). Fluid therapy should be performed to correct possible dehydration, electrolyte imbalances and acidosis. Endotracheal intubation and ventilation may be necessary in cases of respiratory paralysis.
Pralidoxime chloride (2-PAM) is an AChE-reactivating oxime that acts specifically on the organophosphate-enzyme complex and counteracts the nicotinic cholinergic signs (Clemmons, 1990). Administration of 2-PAM should begin within 24 to 48 h of organophosphate intoxication as after this time the toxic compounds are irreversibly bound to AChE. The recommended dose is 10–20 mg/kg slowly IV with fluids over 30 min; or IM or SC. If nicotinic signs persist, the same dose can be repeated every 8–12 h, for 24 to 48 h. 2-PAM should be discontinued after three or four treatments if there is no response or nicotinic signs worsen. 2-PAM produces better results when atropine has already been administered; the atropine dose can be reduced when 2-PAM is used. Signs of muscle weakness and fasciculations usually disappear within 30 min. 2-PAM is not beneficial in treating carbamate toxicosis. If it is uncertain whether the toxicant is an organophosphate or a carbamate, 2-PAM should be used unless it is likely that the toxi-cant is carbaryl, in which case 2-PAM may be harmful. Administration of diphenhydramine (1 to 4 mg/kg PO every 8 h) has been recommended by one author to counteract the nicotinic signs 24 to 48 h after intoxication and to prevent signs of subacute intoxication (Clemmons et al., 1984; Clemmons, 1990). However, its use is controversial and other authors consider diphenhydramine contraindicated in animals with organophosphate and carbamate intoxication (Ellenhorn et al., 1997).
Prognosis
Prognosis depends on the dose and duration of exposure to the insecticide and promptness of adequate treatment (Blodgett, 2006). Generally, prognosis is considered good unless the animal shows signs of respiratory dysfunction or seizures (Wismer and Means, 2012).
Chlorinated hydrocarbons
Overview
Chlorinated hydrocarbons, also named organochlorines, have been used for prevention and control of insect infestations around farms, homes and on animals from the 1950s through the 1970s. Chlorinated hydrocarbons include endrin, aldrin, dieldrin, heptachlor, lindane, DDT and endosulfane. Most of these insecticides have been banned because of accumulating tissue residues and environmental persistence. Contaminated soils or leakage from old dump sites are possible sources of exposure for wildlife and domestic carnivores. The most likely source of exposure in dogs and cats is old stockpiles of insecticides and improper waste disposal. In addition, a few of these compounds may still be legal for ectoparasite control in dogs in certain countries. Exposure in dogs and cats may occur by ingestion, inhalation (less likely), or cutaneous absorption when the insecticide is applied topically and accidentally overdosed (Raisbeck, 2006).
Mechanism of action
The mechanism of action of most chlorinated hydrocarbons is poorly understood and they are considered to be nonspecific stimulants of the central nervous system (Hatch, 1988). Persistent opening of neuronal sodium channels and GABA inhibition are possible mechanisms.
Clinical presentation
Clinical diagnosis is based on history of exposure and clinical presentation. Clinical signs include hypersensitivity, nervousness, muscle tremors, spastic gait, ataxia, mydriasis, salivation, vomiting and severe generalized tonic-clonic seizures, which may be precipitated by external stimuli and may last for 2–3 days. Hyperthermia occurs as a result of the seizures. Death may occur within minutes or hours or after several days.
Diagnosis
Confirming the diagnosis is quite difficult as chlorinated hydrocarbon residues may be found in blood or tissue of normal animals due their persistence in tissues (particularly fat) (Raisbeck, 2006). Tissue samples should be submitted in glass or metal containers
