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mg/kg over 24-48 h, and if seizures persist, followed by 2-3mg/kg every 12 h in dogs, and 1.5-2.5 mg/kg every 12 h in cats (see Chapter 13)Propofol1-4 mg/kg IV bolus or 0.1-0.6 mg/kg/min constant rate infusion titrated to effect or up to 6 mg/kg/h (see Chapter 24)Skeletal muscle relaxation (control of tremors)Methocarbamol DiazepamInitial dose 44-220 mg/kg IV given in small boluses of 30-40 mg/kg to effect, up to 330 mg/kg in 24 h in dogs and cats. Oral administration is also an option0.5 to 1.0 mg/kg IV to effect or PO, up to a maximum total dose of 20 mg in dogs and cats, up to three times in 24 hInduction of emesisApomorphine Xylazine0.04 mg/kg IV or 0.06 mg/kg SC or IM, in dogs 0.4 mg/kg, IM or SC, in catsPrevention of further absorption of toxinActivated charcoalSodium sulphate (40% solution)Sorbitol (70% solution)1-5 g/kg of activated charcoal solution or of powdered activated charcoal mixed with 50 to 200 ml of water to make a slurry250 mg/kg PO once to a maximum of 5 g in cats and 25 g in dogs1 to 2 ml/kg (0.7-1.4 g/kg) PO onceReduction of free and tissue levels of lipophilic agents20% lipid preparation for intravenous infusion1.5 ml/kg IV slow (over 2-15 min) bolus followed by a constant rate infusion of 0.25 ml/kg/min for 30 to 60 min. This may be repeated every 4 h as long as serum is not lipaemic but should be discontinued if a positive response is not seen after three treatments. Animals should be hospitalized and monitored until clinical signs have resolved and the serum is no longer lipaemic as signs of toxicity may return after the intravenous lipid emulsion has been metabolized

      Colonic lavage is indicated for toxins than may be absorbed from the colon when ingestion has occurred more than 4–6 h before presentation. Colonic lavage may be beneficial when performed earlier than 4 h post-ingestion of organophosphates and carbamates. Colonic lavage is performed by inserting a lubricated narrow non-rigid tube from the anus into the rectum and transverse colon and instillation of warm water under gravity flow. Animals with decreased consciousness should be endotracheally intubated during the procedure as colonic distension can stimulate emesis.

      Activated charcoal can be administered by stomach tube after gastric lavage or syringe-fed to animals that can swallow. Activated charcoal is indicated for adsorption of most toxins when the toxic substance is likely to still be present in the gastrointestinal tract, particularly with toxins with slow gastrointestinal release and adsorption or toxins undergoing enterohepatic recirculation. In these cases repeated dosing of activated charcoal (without sorbitol) 1–4 g/kg PO every 6–8 h for 24 h is indicated. Serum sodium should be closely monitored for patients receiving repeated charcoal doses due to potential of development of hypernatraemia. Constipation can be prevented by maintaining the animal well hydrated. Strong acids or alkalis, dissociable salts and metals, and alcohols are not adsorbed by activated charcoal. Activated charcoal is contraindicated in animals with high risk of aspiration pneumonia or hypernatraemia. Cathartics are often administered in association with activated charcoal to minimize toxin absorption by reducing intestinal transit time. Repeated dosing is not recommended due to the risk of osmotic diarrhoea and hyper-natraemia. Cathartics are contraindicated in dehydrated or hypovolaemic animals.

       Urinary excreted toxins

      With urinary excreted toxins, diuresis and/or modification of the urine pH can enhance toxin excretion (O’Brien, 1998). Urine acidification can be achieved by administering ammonium chloride, 100 mg/kg PO for dogs and 20 mg/ kg PO for cats. Ammonium chloride should not be used in acidotic animals and overuse may result in ammonia toxicosis. Urine alkalinization can be achieved by administering sodium bicarbonate at 0.5 to 2 mEq/kg IV every 4 h. Possible adverse effects of systemic pH modulation need to be considered. The acid-base status of the animal must be monitored.

       Intravenous lipid emulsion infusion

      Intravenous lipid emulsion (IVLE) (e.g. Intralipid) infusion has been increasingly used as antidotal treatment of toxicosis from various lipophilic agents (Fernandez et al., 2011; Gwaltney-Brant and Meadows, 2012; Kaplan and Whelan, 2012). IVLE is composed of neutral, medium to long-chain triglycerides derived from plant oils (e.g. soybean, safflower), egg phosphatides and glycerine, formulated primarily as a source of essential fatty acids for patients requiring parenteral nutrition (Gwaltney-Brant and Meadows, 2012). The exact mechanism of antidotal action of IVLE is unknown. The sequestration effect theory proposes that IVLE acts as pharmacological ‘sink’ for lipid soluble compounds decreasing their tissue availability and increasing their clearance (Kaplan and Whelan, 2012). IVLE expands the plasma lipid phase creating a discrete compartment that sequesters lipophilic agents and prevents them from reaching their sites of action. In addition, the expanded plasma lipid phase creates a concentration gradient that facilitates the passage of the lipophilic compounds from the interstitial space into the intravascular space. Potential adverse effects 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

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