of IVLE infusions include: interference with lipophilic medications (i.e. methocarbamol, diazepam, phenobarbitone, propofol) administered for symptomatic or supportive care; pancreatitis due to persistent lipaemia; and hypersensitivity due to IVLE components (Gwaltney-Brant and Meadows, 2012). Based on growing number of case reports in veterinary medicine, IVLE infusion shows promise in the management of toxicosis from a variety of lipophilic agents, including macrocyclic lactones and pyrethrin compounds (Pritchard, 2010; Clarke et al., 2011; Haworth and Smart, 2012; Epstein and Hollingsworth, 2013). More studies are needed to determine optimum time of initiation, dosing regimens and margin of safety of IVLE as antidotal treatment for different lipid soluble toxicities. Treatment protocols are likely to be affected by the degree of lipid solubility and half-life of the toxin. The protocol recommended in Table 4.1 is based on the human literature and veterinary case reports. Care must be taken to use aseptic technique when handling and administering any lipid emulsions as they can promote bacterial growth (Kaplan and Whelan, 2012).
Insecticides
Pyrethrin and pyrethroid (permethrin)
Overview
Pyrethrins are natural insecticides obtained from Chrysanthemum cinerariaefolium, while pyrethroids (e.g. permethrin and fenvalerate) are synthetic analogues of pyrethrins classified as type I (no alpha-cyano-3-phenoxybenzyl group) or type II (with alpha-cyano-3-phenoxybenzyl group) (Hansen, 2006; Wismer and Means, 2012). Etofenprox is a nonester pyrethroid-like insecticide. Permethrin toxicosis is one of the most commonly reported poisonings in the USA and the UK in small animals. Pyrethrins and pyrethroids can be absorbed dermally, orally (e.g. grooming in cats) and via inhalation. Many pyrethrin and pyrethroid formulations are registered for topical use on dogs and/or cats (as spot-on, flea collars, medicated shampoo) and in the household for flea and tick control. Generally, most products registered for use on dogs and cats are safe when used according to label directions in healthy pets. Cats are more sensitive than most other species to pyrethrins and pyrethroids probably due to deficiencies in glucoronyl transferase resulting in slower hepatic metabolism of these compounds. Intoxication results from administration to cats of products labelled for use on dogs, overdose or repeated over-application (Hansen, 2006). Secondary exposure may occur in cats that are in contact with dogs or treated environments. Pyrethrins and pyrethroids are highly lipophilic and rapidly distribute to adipose tissue and the central and peripheral nervous system (Wismer and Means, 2012).
Mechanism of action
Type I and II pyrethroid and pyrethrin compounds can slow both opening and closure of voltage-gated sodium channels, causing prolonged neuronal depolarization or repetitive discharges of motor and sensory nerve fibres. Type II pyrethroids also inhibit binding of GABA to the GABAA receptor, which prevents influx of chloride. This causes further membrane depolarization, blockade of action potential and failure of membrane repolarization.
Clinical presentation
Clinical signs of toxicosis may occur within 3 to 72 h of exposure and include muscle fasciculations and tremors, hypersalivation, ataxia, vomiting, diarrhoea, obtundation, mydriasis, hyperexcitability, hyperactivity, paresthesia, hyperesthesia, seizures and dyspnoea. Type I pyrethroids tend to cause tremors and seizures, whereas type II pyrethroids cause depolarizing conduction blocks with weakness and paralysis (Wismer and Means, 2012). Death may occur but is uncommon.
Diagnosis
Clinical diagnosis is based on history of exposure and clinical presentation. The pet-owners should be specifically questioned on recent ectoparasite treatment either directly on the affected animal or other pets in the house.
Management
Treatment is symptomatic and supportive, including dermal decontamination by bathing with a mild hand-dishwashing detergent and water (in case of dermal exposure to spot-on preparations), methocarbamol (Table 4.1), AEMs (see Table 4.1 and Chapters 12 and 24), fluid therapy and oxygenation (if necessary). Activated charcoal (Table 4.1) can be used in case of oral exposure. The use of intravenous lipid emulsion (Table 4.1) as adjunctive treatment to reduce tissue concentrations of permethrin has produced encouraging results in cats with permethrin toxicosis (Haworth and Smart, 2012; Kuo and Odunayo 2013).
Paresthesia to spot-on preparations may be treated by rubbing vitamin E, corn or olive oil on the application area (Wismer and Means, 2012).
Prognosis
Clinical signs generally resolve within 72 h following appropriate treatment (Hansen, 2006). However, recovery may take a week or longer in some cases. Delayed treatment and generalized seizures are associated with a less favourable prognosis and increased probability of death. Mortality rates vary between 5% and 45% in cats.
Organophosphates and carbamates
Overview
Organophosphates (chlorpyrifos, diazinon, dichlorvos, fenthion) and carbamates (aldicarb, methomyl, carbofuran, carbaryl) are widely used for insect and nematode control in dogs and cats and for insect control in the household and garden. They are available as sprays, pour-ons, oral anthelminthics, baits, collars, dips, dusts and granules (Wismer and Means, 2012). Exposure commonly results from accidental cutaneous overdose or ingestion (Dorman and Fikes, 1993). Organophosphate toxicity may result in acute (<7 h), intermediate (7–96 h) and delayed (1–4 weeks) syndromes.
Mechanism of action
Organophosphates are irreversible inhibitors of acetylcholine esterase (AChE) and recovery depends upon synthesis of new AChE. Carbamates are reversible inhibitors of AChE with restoration of AChE activity when the carbamate insecticide and enzyme separate. Organophosphate and carbamate intoxication results in accumulation of the neuro-transmitter acetylcholine in the synaptic cleft and activation of muscarinic, nicotinic and CNS cholinergic synapses.
Clinical presentation
Clinical signs of acute organophosphate toxicity develop within minutes to hours depending on dose, route and toxicity of the compound and include:
• Muscarinic signs (associated with parasympathetic stimulation) such as hypersalivation, lacrimation, urination, increased gastrointestinal motility, defecation, bradycardia, dyspnoea and miosis;
• Nicotinic signs (associated with skeletal muscle stimulation) such as muscle fasciculations and tremors, which may result in a rigid stance and gait, and eventually weakness and paralysis;
• CNS signs including anxiety, restlessness, hyperactivity, obtundation to coma and generalized seizures.
