“Shake and Bake” – metaldehyde toxicity in a dog

RyAN PHIlIPS, BVSc

Poisoning of companion animals are commonplace in general practice. often the clinical signs seen may not guide the clinician to any specific treatment option, and as a result a generic approach to toxin decontamination is taken (tinson and Cook 2020). Since the toxin ingested is often not known, management and prognosis can be hard to define for the client.

many toxins affect the central nervous system with clinical signs ranging from mild ataxia to severe status epilepticus. metaldehyde (the active ingredient in a variety of slug and snail bait products), is a toxin that can cause severe neurological signs. together, these signs are often termed ‘shake and bake syndrome’ due to severe seizure and tremor-like activity and severe hyperthermia (Castle et al. 2017). this case report will describe the management and outcome of a case of metaldehyde toxicity in a dog, and some potential novel approaches to the treatment of this toxicity in a general practice setting.

A 2-year-old, neutered male Husky, weighing 40 kg, was presented for status epilepticus, severe muscle fasciculations and hypersalivation. Approximately 2 hours before arriving to the clinic, the owners believed the dog had eaten some type of toxin from their garage. up until the incident the patient had no previous health concerns.

the dog was carried into the treatment room and was able to hold himself in sternal recumbency. He was panting but thoracic auscultation was difficult due to the severe muscular fasciculations throughout his body. His pulse rate was 160, pulse quality was good, mucous membranes were pale pink and his capillary refill time was under one second. His rectal temperature was 39.5°C. the neurological exam revealed: bilateral miosis, the absence bilaterally of pupillary light reflexes, palpebral and menace responses. the patient also exhibited severe body tremors and hypersalivation, which transitioned to lateral recumbency and status epilepticus within 15 minutes of presentation. muscle fasciculations were observed over the entire body but were particularly severe in the hindlimbs and facial muscles. tremors worsened when loud noises or any part of his body were touched indicating hyperaesthesia, this soon disappeared once the status epilepticus developed.

Contact: Ryanp@vet111.co.nz

the clinical findings were not specific for any particular toxin. As a result, a generic approach to treatment was undertaken to try and decontaminate the toxin from the dog. Clinical signs such as tremors, hypersalivation, hyperaesthesia and seizures were consistent with metaldehyde toxicity, whereas other clinical signs such as constricted pupils and the multiple cranial nerve deficits were not. other differentials considered were organophosphate insecticide ingestion and trauma (teichmann-Knorrn et al. 2020).

Intravenous catheters were placed in both cephalic veins. Blood samples for a complete blood count and baseline biochemistry panel were taken, the results of which showed no significant changes. urinalysis was not conducted. to begin controlling the seizure activity, 1 mg/kg diazepam (Pamlin; Ceva Animal Health NZ, Auckland, NZ) was administered through one I/V access point. the other I/V access point was used to administer 0.9% sodium chloride (Baxter, Sydney Australia) at 5mL/kg/hour. I/V fluid therapy helps to maintain perfusion, correct acid-base abnormalities caused by many toxicities, and promote diuresis and thus excretion the toxin (if the toxin is metabolised and excreted via the kidneys). A second dose of diazepam was given 30–40 minutes later. However, the response was limited as the dog continued to seizure. It was then decided to induce general anaesthesia with I/V 3 mg/kg alfaxalone (Alfaxan; Jurox, Rutherford, Australia), intubate the patient and maintain anaesthesia with 1–2% isoflurane. the patient was kept at stage 3, plane 2 of anaesthesia for approximately 1 hour. A veterinary nurse was present to monitor the anaesthesia at all times. During this time, I/V 0.5mg/kg metoclopramide (metoclopramide; Pfizer, Auckland, NZ) was started along with 1 mg/kg maropitant (Cerenia; Zoetis, Auckland, NZ), to promote gastrointestinal motility and prevent aspiration once the patient was awake.

During this time, the patient also underwent gastric lavage. this was accomplished by pre-measuring a large bore gastric tube to the last rib, to determine the maximum length of insertion. once the tube was inserted, 10 cycles of 1–2 L of warm water was fed through the tube via gravity, and then emptied by creating a siphon. A considerable amount of small green pellets was retrieved which were later identified as slug bait. this was confirmed by the owner finding a box of slug bait in his garage that looked two-thirds eaten. the active ingredient of the bait was metaldehyde. During the gastric lavage, large amounts of the slug bait passed out along with faeces as the patient developed severe diarrhoea. once clear fluid began to be siphoned out of the stomach, 2.5 g/kg of activated charcoal (Carbosorb X; Phebra, Sydney, Australia) was fed through the gastric tube, followed by 500 mL of warm water. Before removal of the gastric tube, air was blown into the tube, it was then kinked and removed in one smooth motion. this allowed any remaining fluid and activated charcoal to enter the stomach and prevented fluid leaking out of the tube as it was removed.

the patient remained anaesthetised for another 40 minutes with his head slightly lower than his body to promote any additional fluid to drain out. During recovery, the endotracheal tube remained in place with the cuff inflated until the patient started to wake up. the patient was then recovered in a dark room in lateral recumbency, with the head elevated to reduce the risk of aspiration. the eyes were covered, and cotton balls placed in his ears to reduce noise and light triggering hyperaesthesia. After the anaesthetic recovery, the patient’s tremors were difficult to manage. multiple I/V boluses of alfaxalone were used with no significant long-lasting resolution. three low I/V doses (0.005 mg/kg) of medetomidine (Domitor; Zoetis NZ) were later administered. this was partially successful as the tremors seemed to reduce in severity. As the third dose of medetomidine began to wear off, the patient began to regain his palpebral reflex and showed improvements in pupillary light reflex. Approximately, 12 hours after admission the patient relapsed back to severe tremors, status epilepticus, and hyperthermia with a rectal temperature of 41°C. Active cooling was instituted with air conditioning and wet towels placed over the patient. this was stopped when the rectal temperature reached 39.5°C. At the same time a constant rate infusion (CRI) of 0.015 mg/kg/minute propofol (Aquafol; Ceva Animal Health) was begun (alfaxalone was not continued due to a stock shortage). As there were no syringe infusion sets available to allow easy administration of the CRI, an empty 0.9% sodium chloride bag was used and the propofol was diluted appropriately with 0.9% sodium chloride. An ordinary drip pump was then used to administer the CRI at the desired rate which was titrated to effect. the remaining I/V line was used to administer 0.9% sodium chloride at maintenance rates with additional fluids to account for losses due to diarrhoea.

the propofol CRI significantly reduced the seizure activity. the patient remained on the CRI for 6–7 hours, which during the morning was slowly reduced and titrated to effect. As the CRI was reduced over the day, the patient’s palpebral reflex, pupillary light reflex and consciousness began to improve. At the same time, there was no longer evidence of slug bait pellets in the faeces. there was also indication that the activated charcoal had fully passed through the digestive system as it was now seen in the patient’s faeces. the patient was rotated every 2–3 hours and approximately 24 hours after admission, began to lift his head, eat, and drink. there were still mild muscle fasciculations and tremors, but the patient was conscious and no longer in status epilepticus.

three days after admission the patient was walking, eating, drinking and toileting normally. He was discharged later that day with no notable clinical abnormalities. Serum biochemistry parameters measured at 24 and 72 hours showed decreasing alkaline phosphatase activities (which had not been particularly high to begin with). Activity of alanine aminotransferase was just above normal 24 and 72 hours after ingestion. No other significant changes to serum biochemistry were noted. Administration of activated charcoal, metoclopramide, omeprazole, and oral diazepam were continued for 1 week after admission to promote further decontamination, protect mucosal surfaces and reduce any minor muscular fasciculations.

metaldehyde is a pesticide that is commonly used to kill garden slugs and snails. unfortunately, metaldehyde is attractive to mammals due to its taste and is the second most common toxin ingested by dogs after chocolate (Castle

et al. 2017). metaldehyde intoxication has been aptly named ‘shake and bake syndrome’ as acute signs of seizure-like activity and hyperthermia are often seen (Bates et al. 2012). the exact mechanism for toxicity in mammals is not fully understood, but there is some speculation that metaldehyde may undergo gastric hydrolysis to form acetaldehyde which later disrupts the neurotransmitters gamma-aminobutyric acid (GABA), noradrenalin and serotonin (Bates et al. 2012; Bergamini et al. 2020). Disruption to the GABA system, which is the main inhibitory neurotransmitter in the nervous system, results in the convulsive clinical signs seen (Bates et al. 2012). As a result of the increased muscular and seizure activity hyperthermia develops (Yas-Natan et al. 2007). the biochemical findings seen in metaldehyde toxicity vary. In a retrospective study, Yas-Natan et al. (2007) describes that seizure activity can result in direct thermal damage to cells causing rhabdomyolysis, as a result, increases in biochemical parameters are most commonly muscular in origin rather than hepatic or renal. Yas-Natan et al. (2007) describes the main biochemical changes include increases in the activities of creatinine kinase, lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase. In this case only alanine aminotransferase was increased, as the other parameters were not available to test. Increases in alkaline phosphatase could also be attributable to hepatobiliary damage, which is commonly seen 24–72 hours after exposure (Bates et al. 2012). once again, this was not seen, as the alkaline phosphatase activity decreased over the duration of treatment. these variable biochemical changes highlight their non-specificity for metaldehyde toxicity. Conducting a repeatable and reliable neurological exam can be difficult especially if the patient is in status epilepticus. the cranial nerve deficits seen were not typical of metaldehyde toxicity. Bilateral miosis, and absence bilaterally of pupillary light reflexes, palpebral reflexes and menace response suggested a forebrain neurolocalisation (Asokan et al. 2019). An important differential considered which include these cranial nerve deficits was organophosphate toxicity (Asokan et al. 2019). this was considered less likely as the dog and owner were not residing on a farm where these chemicals are commonly found. macKay (2004) also describes that trauma can cause injury to the fore or midbrain which produces similar cranial nerve deficits but once again there was no evidence or history of trauma.

there are varying survival rates and LD50 ranges for metaldehyde intoxication described in veterinary literature. Survival rates from metaldehyde toxicity range from 60–80%, depending on how early and aggressively treatment was initiated (Bates et al. 2012; Bergamini et al. 2020; teichmann-Knorrn et al. 2020; Yas-Natan et al. 2007). the LD50 of metaldehyde stated in the literature ranges from 100–1000 mg/ kg which suggests that some animals may be more severely affected than others (Castle et al. 2017; Yas-Natan et al. 2007). I estimate that this patient ingested approximately two-thirds of the box of pellets equating to 4000 mg of metaldehyde, which at 100 mg/ kg placed him at the lower end of the LD50 range. It can be hard to determine how much metaldehyde an animal has consumed, and often there are differing concentrations of metaldehyde products available. unpublished data from the Animal Poison Control Centre suggests that veterinary assessment should be sought if the animal has ingested 2mg/ kg or more of the toxin (Dolder 2003). Due to its variable LD50, and differing concentrations of metaldehyde products any amount ingested should prompt veterinary intervention.

Decontamination of metaldehyde

treatment of poisoned animals does not hugely vary between toxins and is based on supportive and symptomatic therapy. the main goal of metaldehyde decontamination is removal of the toxin from the animal’s body and control of the clinical signs. If the patient is conscious and only recently ingested the toxin, inducing emesis, with a product such as apomorphine, is a logical first step (tinson and Cook 2020). However, in this case the patient had overt neurological signs which contraindicates induction of emesis due to the risk of aspiration. Enhancing the rate of elimination of toxins can be accomplished in multiple ways. Firstly, diuresis may be promoted with high I/V fluid rates. Lee (2018) discusses that forced diuresis is more beneficial for toxins that are metabolised and excreted by the kidneys. metaldehyde is not known to be highly excreted by the kidneys; Booze and oehme (1986), found that less than 1% of metaldehyde is excreted into the urine of dogs. Fluid diuresis was still instituted in this case as the initial cause for the toxicity was not known. Along with this, maintaining perfusion initiates resolution of acid-base abnormalities, as a majority of patients with metaldehyde toxicity develop metabolic acidosis (Dolder 2003). Fluid rates were gradually reduced to maintenance rates plus any additional losses due to the patient’s diarrhoea. Secondly, promoting gastric emptying and increasing the transition of contents through the gastrointestinal tract, using prokinetics like metoclopramide, will reduce absorption of systemic toxins (Lee 2018). the use of maropitant as a prokinetic has been studied, and there is no clear evidence that it exerts these effects or increases gastric emptying (Schmitz et al. 2016). In this case it was used primarily to prevent nausea and vomiting once the patient had recovered. Additionally, warm water enemas can be utilised while the patient is sedated or under anaesthesia to further promote decontamination (Bergamini et al. 2020). In this case, warm water enemas were not used, as the patient was readily producing large volumes of diarrhoea containing significant amounts of metaldehyde pellets. Lastly, gastric lavage can aid in the removal of large quantities of the toxin before they are digested and absorbed by the body. Conducting a gastric lavage is not a benign procedure and can carry risks. the biggest risk is aspiration which can have flow on effects such as hypoxemia and pneumonia (Lee 2018). the author goes on to discuss that in human poisoning

cases, gastric lavage has poor rates of recovery of the toxin (29–38%), with higher rates when intervention occurs earlier. In veterinary medicine, robust data on the success of gastric lavage is lacking, as most patients present to the clinic on average an hour after ingesting the toxin, and this can reduce success rates (Bates et al. 2012; Lee 2018). In this case, the benefits outweighed the risks as a significant amount of toxin was ingested and retrieving any amount had the potential to be beneficial for the patient. the risk of aspiration was reduced by ensuring selection of an appropriate size of endotracheal tube, adequate inflation of the endotracheal tube cuff, lowering the head, and using medications such as metoclopramide and maropitant to reduce the risk of aspiration during anaesthetic recovery. Following gastric lavage, the patient received activated charcoal (AC). Lee (2018) describes that AC has the ability to bind certain toxins and thereby decrease systemic absorption. the use of AC in human poisoning cases has recently sparked debate. A position paper published by the American Academy of Clinical toxicology and the European Association of Poisons Centres and Clinical toxicologists advised against its use as it has not shown to improve clinical outcome in humans (Chyka et al. 2005). However, the use of AC is still advocated for by many in veterinary medicine (Bergamini et al. 2020; Chyka et al. 2005; Lee 2018). A study conducted on rats by Shintani et al. (1999), showed that intestinal absorption of metaldehyde was reduced by up to 45% when orally administered AC was given early when compared to the control group. Because binding of AC to toxins is also reversible, the addition of a cathartic, such as sorbitol, is advised to enhance faecal expulsion whilst the toxin is still bound to the AC (Lee 2018; tinson and Cook 2020). the AC used in this case did not include a cathartic because the patient was already displaying signs of advanced gastrointestinal motility. management of seizures

management of refractory seizures (also known as status epilepticus; SE) is crucial for providing a favourable outcome in cases of metaldehyde toxicity. Being able to control seizure activity reduces energy demands of muscle cells, limits further neurological damage and helps maintain normothermia (marios et al. 2021). Currently, the recommended first line therapy for seizures are the benzodiazepines (Charalambous et al. 2021). often these may fail and the need for a CRI of an injectable anaesthetic is required (Gommeren et al. 2010; Heidenreich et al. 2016). In this case, a propofol CRI was used with great success. there have been limited studies that compare propofol and alfaxalone in the treatment of status epilepticus. there is some evidence that giving alfaxalone can result in increased myotonic and myoclonic movements in the recovery phase, which in a patient with status epilepticus is not ideal, and its effect on a seizure focus has not fully been studied (Jiménez et al. 2012; metea et al. 2018). Because of this and stock issues, propofol was used instead of alfaxalone for the remaining management of the case. Even though there was no access to a syringe infusion set, simple calculations allowed the use of a standard drip pump to administer the drug. Additionally, Heidenreich et al. (2016) found that at low doses, medetomidine may have neuroprotective properties and cause cerebral vasoconstriction which reduces the development of cerebral oedema, a common sequelae of status epilepticus. Although there was a poor response to controlling the status epilepticus with low dose medetomidine boluses, Heidenreich et al. (2016) suggests that its use as a CRI along with propofol may have propofol sparing effects and may reduce the side effects commonly seen with propofol. these include hypoventilation leading to hypercapnia and eventually brain oedema. the use of a low dose medetomidine CRI along with a propofol CRI should be considered if there is access to a syringe infusion set as this combination may improve patient outcomes. Recommended dose rates vary from 0.5–1 µg /kg/hour (Bergamini et al. 2020; Gioeni et al. 2020; Heidenreich et al. 2016).

Novel treatment options for metaldehyde toxicity, such as intravenous lipid emulsions (ILE) and haemodialysis, have been reported to have good success rates (Kopke and Yozova 2020; Lee 2018; Lelescu et al. 2017; Spray 2016; teichmann-Knorrn et al. 2020). ILE therapy is still being investigated for its efficacy in the treatment of metaldehyde toxicity, as its use is currently debatable. ILE therapy is likely more readily available in general practice, well described in human literature, and therefore will be focussed on here.

the use of ILE has been hypothesised to reduce metaldehyde tissue concentration as this toxin is lipid soluble (Lelescu et al. 2017). Although the exact mechanism is unknown, it is theorised that a ‘lipid sink’ is created where the toxin is drawn out of the tissue into an extended lipid phase where it can no longer exert its pharmacological action (Spray 2016). Lelescu et al. (2017) describe a case of metaldehyde toxicosis that was unresponsive after 8 hours of treatment with anti-epileptic medications and a propofol CRI. A 20% ILE bolus followed by an ILE CRI were then administered via a peripheral catheter. Within 1 hour of beginning this therapy, the authors noted that pulse and respiratory rates began to normalise, and SE was abolished. Another case report (Kopke and Yozova 2020) described resolution of seizure activity caused by presumptive permethrin toxicosis using similar doses and routes of administration of 20% ILE.

Although there are only a few case reports for the use of ILE in veterinary medicine, further research is needed in this field. the use of ILE is something to consider as it is relatively safe. Potential adverse effects include bacterial infection from contaminated product, hypersensitivity reactions, and fat overload syndromes (such as pancreatitis, icterus, and haemolysis).

the clinician should also advise the client that this treatment is off-label, and have judged that the benefits outweigh the risks before administering the product. Varying dose rates are proposed for 20% ILE products, however a loading dose of 1.5 mL/kg over 10–15 minutes, followed by a CRI at 0.25 mL/kg/minute is frequently reported (Kopke and Yozova 2020; Lelescu et al. 2017; Spray 2016).

the management of patients with toxin ingestion requires quick action by both the client and clinician. It is both a large commitment financially for the client and also involves intensive monitoring by the clinician. Clients and clinicians should always be prepared for both successes and relapses during treatment period. Clear communication between the clinician and client plays a vital role in toxicity case management. treatment almost always involves a multimodal approach to decontamination of the toxin for a successful outcome. It is not necessary to have complex monitoring equipment or extensive medications to have a successful result. It is the combination of having a basic understanding of the available medications in general practice, along with the confidence in performing decontamination procedures that will allow the patient, client, and clinician to have a successful outcome.

Special thanks to the nursing staff and Dr. Finja Philips from the Veterinary Centre, Waimate, for their help managing this case.

Harmon M. Organophosphate intoxication in 2 dogs from ingestion of cattle ear tags. Journal of Veterinary

Emergency and Critical Care 29, 424–430, https://doi.org/https://doi.org/10.1111/ vec.12855, 2019

Suspected metaldehyde slug bait poisoning in dogs: A retrospective analysis of cases reported to the

Veterinary Poisons Information Service.

Veterinary Record 171, 324, 2012

Magagnoli I, Giunti M. Conventional treatment of a metaldehyde-intoxicated cat with additional use of low-dose intravenous lipid emulsion. Journal of

Feline Medicine and Surgery Open Reports 6, doi:10.1177/2055116920940177, 2020 Booze TF, Oehme FW. An investigation of metaldehyde and acetaldehyde toxicities in dogs. Fundamental and Applied

Toxicology 6, 440–6, 1986

Review of the molluscicide metaldehyde in the environment. Environmental

Science: Water Research & Technology 3, 415–28, 2017

Bhatti SFM. First-line management of canine status epilepticus at home and in hospital-opportunities and limitations of the various administration routes of benzodiazepines. BMC Veterinary

Research 17, 1–19, 2021

Vale JA. Position paper: Single-dose activated charcoal. Clinical Toxicology 43, 61–87, 2005 Dolder LK. metaldehyde toxicosis.

Veterinary Medicine 98, 213–215, 2003

Rabbogliatti V, Ravasio G. ketaminedexmedetomidine combination and controlled mild hypothermia for the treatment of long-lasting and superrefractory status epilepticus in 3 dogs suffering from idiopathic epilepsy.

Journal of Veterinary Emergency and

Critical Care 30, 455–60, 2020

Hamaide A, Daminet S. Outcome from status epilepticus after portosystemic shunt attenuation in 3 dogs treated with propofol and phenobarbital. Journal of

Veterinary Emergency and Critical Care 20, 346–51, 2010

Successful treatment of refractory seizures with phenobarbital, propofol, and medetomidine following congenital portosystemic shunt ligation in a dog.

Journal of Veterinary Emergency and

Critical Care 26, 831–6, 2016 Jiménez CP, Mathis A, Mora SS,

Brodbelt D, Alibhai H. evaluation of the quality of the recovery after administration of propofol or alfaxalone for induction of anaesthesia in dogs anaesthetized for magnetic resonance imaging. Veterinary Anaesthesia and

Analgesia 39, 151–9, 2012 Kopke MA, Yozova ID. management of presumptive canine permethrin toxicosis using intravenous lipid emulsion as an adjunctive therapy. Veterinary

Record Case Reports 8, DOI:10.1136/ vetreccr-2019-001041, 2020 Lee JA. Decontamination and toxicological

Analyses of the Poisoned Patient. In:

Textbook of Small Animal Emergency

Medicine. Pp 819–30, 2018

M, Neagu AM, Nagy AL. Successful treatment of metaldehyde toxicosis with intravenous lipid emulsion in a dog. Acta

Veterinaria Brno 86, 379–83, 2017 MacKay RJ. Brain injury after head trauma: pathophysiology, diagnosis, and treatment. Veterinary Clinics of North

America: Equine Practice 20, 199-216, https://doi.org/https://doi.org/10.1016/j. cveq.2003.11.006, 2004

Sofie FMB. First-line management of canine status epilepticus at home and in hospital-opportunities and limitations of the various administration routes of benzodiazepines. BMC Veterinary

Research 17, 1–19, 2021

Characterization of alfaxalone-induced seizures in dogs upon emergence from anesthesia. Journal of Pharmacological and

Toxicological Methods 93, 135, https:// doi.org/https://doi.org/10.1016/j. vascn.2018.01.451, 2018

K, Neiger R. effects of the neurokinin-1 antagonist maropitant on canine gastric emptying assessed by radioscintigraphy and breath test. Tierarztl Prax Ausg K

Kleintiere Heimtiere 44, 163–169, 2016 Shintani S, Goto K, Endo Y, Iwamoto C,

Ohata K. Adsorption effects of activated charcoal on metaldehyde toxicity in rats.

Veterinary and Human Toxicology 41, 15–8, 1999 Spray JW. Review of intravenous lipid emulsion therapy. Journal of Infusion

Nursing 39, 377–80, 2016

Doerfelt R. Retrospective evaluation of the use of hemodialysis in dogs with suspected metaldehyde poisoning (2012–2017): 11 cases. Journal of Veterinary

Emergency and Critical Care 30, 194–201, 2020 Tinson E, Cook S. Supporting the intoxicated patient: toxicants affecting the neurological and cardiovascular systems. In Practice 42, 27–38, 2020 Yas-Natan E, Segev G, Aroch I. Clinical, neurological and clinicopathological signs, treatment and outcome of metaldehyde intoxication in 18 dogs.

Journal of Small Animal Practice 48, 438–43, 2007 l