likely to provide a diagnosis. The dimethoxy derivative of strychnine, brucine (2,3-dimethoxystrychnidin-10-one), may be detected in serum.
Management
Treatment includes decontamination (induction of emesis in asymptomatic animals or gastric lavage followed by activated charcoal and cathartic administration in animals showing clinical signs of intoxication) (Table 4.1), promoting toxin excretion, controlling the tetany and seizures (Table 4.1, see Chapters 12 and 24), convective whole body cooling, adequate oxygenation (Murphy, 2002) and supportive care. Sedation or general anaesthesia for 24–72 h may be required. Forced diuresis with 5% mannitol in isotonic saline and acidification of the urine will enhance urinary elimination of strychnine. Animals with respiratory failure should be administered oxygen and if needed intubated and ventilated. Non-anesthetized animals should be kept in a dimly lit, quiet area and all forms of sensory stimulation should be minimized.
Prognosis
Prognosis is fair to guarded, depending on the amount of toxin ingested and promptness of treatment. If the animal survives the first 24 h post-toxin ingestion, prognosis for complete recovery is good.
Bromethalin
Overview
Bromethalin is a rodenticide that is sometimes implicated in accidental or malicious poisonings of small animals. It is available in pelleted forms such as place packs, blocks or bars of bait and baited worms (DeClementi and Sobczak, 2012). Exposure mainly occurs by ingestion of bromethalin bites. Secondary (or relay) poisoning may occasionally occur by ingestion of bromethalin-poisoned rodents. Bromethalin is readily absorbed from the gastrointestinal tract and reaches peak plasma levels within several hours after ingestion. It is highly lipophilic and therefore reaches high concentration in the brain.
Mechanism of action
Bromethalin and its active metabolite, desmethyl bromethalin, uncouple oxidative phosphorylation resulting in decreased cellular adenosine tri-phosphate (ATP) concentrations and reduced activity of ATP-dependent sodium and potassium ion channel pumps. This produces an increase in intracellular sodium concentrations, intracellular movement of water and consequent cerebral oedema, vacuolization of myelin and increased intracranial pressure.
Clinical presentation
Onset and type or clinical signs are dose-dependent. Dogs ingesting 2.5 to 5 mg/kg of bromethalin develop clinical signs in 1 to 4 days (Murphy, 2002), whereas dogs ingesting more than 5 mg/kg of bromethalin may develop clinical signs within 2–24 h after ingestion. Low doses (e.g. 2.5 mg/kg in dogs) result in pelvic limb ataxia and/or paresis/paralysis with extensor rigidity and obtunded mental status. High doses (e.g. 5 to 6.5 mg/kg in dogs) produce hyperexcitability, tremors, focal motor and generalized seizures, hyperthermia, obtunded mental status, which can progress to stupor, coma, decerebrate posture and death secondary to respiratory arrest (Dorman et al., 1990a, b). Cats ingesting 0.54 mg/kg develop signs (including ataxia, focal motor seizures, vocalization, obtunded mental status and stupor) 2 to 7 days after exposure (Dorman et al., 1990c). Most recently clinical signs and death have been reported following exposure to bromethalin doses as low as 0.46 mg/kg in dogs and 0.24 mg/kg in cats (DeClementi and Sobczak, 2012).
Diagnosis
The ante-mortem diagnosis is most often made based on the history of bait ingestion (stools may have a green discoloration) and the development of clinical signs. Definitive diagnosis can be reached only post-mortem by detecting bromethalin or its metabolites in kidney, liver, fat or brain samples using gas chromatography with electron capture (Dorman et al., 1990a, b). Samples should be submitted frozen and protected from light.
Management
There is no antidote to bromethalin. Treatment involves decontamination and prevention of further toxin adsorption (induction of emesis or gastric lavage followed by repeated administration of activated charcoal and administration of a cathartic with the initial dose of activated charcoal) (Table 4.1), AEMs (see Table 4.1 and Chapters 12 and 24) in seizuring animals, methocarbamol or diazepam in animals with excessive tremors (Table 4.1), and supportive care. The repeated and prolonged administration of activated charcoal (1–5 g/kg every 6–8 h for up to 2–4 days in animals ingesting high dosage of bromethalin) is indicated due to the enterohepatic recirculation of bromethalin. Cerebral oedema can be treated with mannitol. Serum sodium levels should be closely monitored due to the potential for hypernatraemia of repeated administration of activated charcoal as well as mannitol.
Prognosis
Prognosis is fair with prompt and prolonged treatment in animals with mild clinical signs. Animals with obtundation and ataxia may recover over a period of 2 to 4 weeks. Prognosis is guarded in animals with severe neurological signs such as tremors, seizures, coma or paralysis.
Zinc phosphide
Overview
As with other rodenticides, zinc phosphide poisoning can be accidental or malicious in small animals. Secondary (or relay) poisoning has been reported in dogs feeding on the dead rodents and other animals poisoned by zinc phosphide. When zinc phosphide reaches the stomach, on exposure to moisture and an acidic environment, it hydrolyses to phosphine gas which is rapidly absorbed across the gastric mucosa and distributed systemically where it exerts its toxic effect (Proudfoot, 2009).
Mechanism of action
The corrosive action of zinc phosphide accounts for the early, acute and generally haemorrhagic emetic effect on the gastric mucosa. The systemic toxicity of zinc phosphide is caused by phosphine. Postulated mechanisms of action of phosphine include inhibition of cytochrome C oxidase with mitochondrial dysfunction and interruption of cellular respiration, inhibition of serum acetyl cholinesterase activity resulting in cholinergic overdrive and formation of reactive oxygen species (ROS) with resultant oxidative stress, damage to cell lipids, proteins and nucleic acids and cell death (Proudfoot, 2009).
Clinical presentation
Clinical signs occur within 15 min to 4 h after ingestion (but may be delayed by 12 to 18 h) and include vomiting (often with frank or dark blood clots), aimless pacing or running, vocalization, anxiety, discomfort, generalized muscle fasciculations, tremors, exaggerated response to external stimuli and tonic-clonic or tonic seizures. In addition, the production of phosphine gas within the stomach may lead to gastric
