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The Case: Metaldehyde Intoxication

Clinician's Brief

Toxicology

|August 2013|Web-Exclusive

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Two dogs from a single household were presented with tremors after they had together ingested a 3-pound bag of molluscicide (snail bait). Both dogs had been immediately seen by another veterinarian. Apomorphine was administered but no vomiting was elicited. After administering methocarbamol, the primary veterinarian transferred the dogs to a referral facility. One dog went into cardiac arrest and died immediately after transfer.

Related Article: Decontaminating the Poisoned Patient

History & Physical Examination

The surviving patient, a 6-year-old spayed female border collie, had a history of gagging 2 weeks prior to presentation, which resolved. No other medical history was reported. The dog was quiet, alert, and responsive. Hydration status was within normal limits. She was ambulatory on all limbs and exhibited mild diffuse tremors, most often involving the head and face.

  • Weight: 19.5 kg
  • Temperature: 102.5⁰F
  • Heart rate: 164 bpm; no heart murmur, regular rhythm 
  • Pulses: Strong and synchronous, with no deficits 
  • Lung sounds: Normal
  • Respiratory rate: Panting
  • Mucous membranes: Injected
  • Capillary refill time: <2 sec

Related Article: Metaldehyde: Slug Bait Toxicosis

Diagnostics

Blood analysis

  • Sodium: 150.5 mEq/L (range, 139–154)
  • Potassium: 4.05 mEq/L (range, 3.6–5.5)
  • Chloride: 123.6 mEq/L (range, 102–120)
  • Ionized calcium: 1.22 mmol/L (range, 1.16–1.34)
  • Magnesium: 0.71 mEq/L  (range, 1.5–2.5)
  • Glucose: 93 mg/dL (range, 70–138)
  • Lactate: 1.2 mmol/L (range, 0.6–2.9)
  • Blood urea nitrogen: 17 mg/dL (range, 6–31)
  • Creatinine: 1.1 mg/dL (range, 0.5–1.6)
  • Hematocrit: 53% (range, 36%–60%)
  • Total protein: 6.4 g/dL (range, 5.0–7.4)
  • Albumin: 2.6 g/dL (range, 2.7–4.4)
  • Alanine aminotransferase: <10 IU/L (range, 12–118)
  • Alkaline phosphatase: 64 IU/L (range, 5–131) 

Treatment

  • Methocarbamol: 44 mg/kg IV, totaling 360 mg/kg overnight, with continued but decreased mild tremors mostly involving the head
  • Lactated Ringer’s solution: 10 mL/kg bolus IV; then at 60 mL/hr IV
  • Activated charcoal: 50 mL PO orally
  • Activated charcoal with sorbitol: 120 mL, enema

Gastric lavage was initially discussed with the owner, who declined due to risk of aspiration with anesthesia.

Clinical Progression

At 4 hours after presentation, the patient exhibited a brief episode of neck and thoracic limb extension, presumably seizure activity.

  • Midazolam: 0.2 mg/kg IV (seizure resolved)
  • Body temperature: ~99⁰–100⁰F (despite persistent but mild tremors)

At 6 hours, the tremors worsened in severity.

  • Propofol: 1 mg/kg bolus IV; then 0.1 mg/kg/min CRI; then increased to 0.2 mg/kg/min CRI
  • Mannitol: 10 g IV once

Patient appeared more sedate. Tremors persisted, but at decreased intensity.
 
At 9 hours, the patient exhibited a modest generalized seizure despite treatment with propofol. Bilateral miosis was identified on neurologic examination. A soft cough had developed, prompting concern about aspiration pneumonia. At 12 hours, a mild fever (103.2⁰F) had developed.

DAY 2

Treatment (~ 10–12 hours after presentation)

  • Phenobarbital: 130 mg IV (to decrease amount of propofol required for intubation and to abolish tremors)
  • Propofol: 3 mg/kg IV bolus (prior to intubation with 8.5 mm endotracheal tube); then 0.1–0.6 mg/kg/min IV (to maintain light plane of anesthesia)
  • Methocarbamol: 44 mg/kg IV q2–4h (as needed for break-through tremors)
  • Enrofloxacin: 10 mg/kg IV q24h (for possible aspiration pneumonia)
  • Lactated Ringer’s solution: Increased to 90 mL/hr IV (to compensate for diuresis caused by mannitol)


Clinical Progression
The pupils remained miotic, but the fever resolved.

  • Mannitol 10 g IV once (for possible cerebral edema from tremors/seizures overnight). At 17 hours after presentation, the propofol CRI was tapered, after which the dog was tremor-free for 30 minutes. An hour later, she was sternal, breathing comfortably, and ate 2 tablespoons of a highly digestible low-fat diet.
  • Methocarbamol: q6h overnight

DAY 3

Clinical Progression
There was no further evidence of tremors overnight. The patient was discharged 36 hours after presentation without any medications. Pupils were normal-sized at recheck. 


The Generalist’s Opinion

Barak Benaryeh, DVM, DABVP

The main improvement that could have been made in this case was in the initial management. With this particular toxin, decontamination is critical––the earlier, the better.  

Protocol for Induction of Emesis
Rapid decontamination is the most effective and critical step in most cases of ingestion of a toxic compound. It can be achieved either by inducing vomiting or through gastric lavage. That the apomorphine failed to induce its desired effect in this case is unfortunate. Apomorphine is the most commonly used emetic in veterinary practice. We do not know the dose or by what route it was administered in this case. If used properly, apomorphine is generally very effective: It is not effective when given orally, as it undergoes first-pass hepatic metabolism. It can be administered via the conjunctival sac or through injection. A standard tablet is 6 mg or the drug can be compounded for injection. There are some issues with keeping compounded substances for general hospital use, so check your state board for appropriate guidelines. For conjunctival administration, a tablet (or fraction of a tablet based on patient size) is placed in the conjunctival sac and then rinsed out as soon as vomiting starts. Injection dose varies based on route (SC or IV), but both routes are acceptable and effective.

Other Treatments
In this case gastric lavage would have been an option given that neither dog had vomited. This treatment was offered but only once the dogs were presented to the referral facility, after some time had passed. Vomiting will empty 40% to 60% of the stomach contents. While gastric lavage is not more effective, it can be used in patients in which emesis induction has failed. A dose of methocarbamol was given prior to referral. Methocarbamol was a good choice to combat the oncoming muscle tremors. In addition, it would have been a good idea to administer an adsorbent such as activated charcoal.

Additional Monitoring
Once at the referral facility, the level of care was clearly very good. On presentation the dog had a low magnesium level of 0.71 (range, 1.5–2.5). There are many causes for hypomagnesemia, with opinions varying as to the significance of this finding and whether and how aggressively it should be treated. There is some thought that magnesium supplementation may be of benefit in critical cases; thus, it could have been a consideration in this case. Another option would have been to follow up on the low magnesium by rechecking it prior to discharge.  

In summation, severe cases of metaldehyde ingestion require 24-hour care; referral to a specialty facility is the appropriate step to take. A more aggressive approach early in this case would likely have helped reduce the severity of clinical signs for both these dogs.

Barak Benaryeh, DVM, DABVP, is the owner of Spicewood Springs Animal Hospital. He graduated from University of California–Davis School of Veterinary Medicine in 1997 and completed an internship in Small Animal Medicine, Surgery, and Emergency at University of Pennsylvania. Dr. Benaryeh has also taught practical coursework to first-year veterinary students and was a primary veterinary surgeon for the Helping Hands Program, which trains assistance monkeys for quadriplegic people. Dr. Benaryeh is certified by the American Board of Veterinary Practitioners in Canine and Feline Practice.

Suggested Reading
Effective decontamination techniques. Wismer T (ASPCA Animal Poison Control Center, Urbana, IL). Wild West Vet Conf Proc, 2009.

Suspected metaldehyde toxicoses in dogs: 92 reports (January 1999–May 2001). Richardson JA, Welch SL, Gwaltney-Brant SM, Huffman JD (ASPCA Animal Poison Control Center, Urbana, IL). ACVIM Proc, 2002.


The Specialist’s Opinion

Justine A. Lee, DVM, DACVECC, DABT, VetGirl, St. Paul, Minnesota

There are several take-home points regarding the management of this case. While the outcome of one dog was successful, the other dog’s death likely could have been avoided. While human medicine has moved away from the use of decontamination (eg, emesis induction, gastric lavage, administration of activated charcoal, etc), in veterinary medicine, decontamination is still considered the mainstay therapy in the poisoned patient. However, the appropriate indications and contraindications must be considered prior to decontamination. Inducing emesis in a patient that is already displaying clinical signs is contraindicated, as the toxicant has already been absorbed. As both dogs were presented with tremors, emesis induction should not have been performed. While the cause of death is unknown in the second dog, it may have been related to emesis induction from such developments as acute severe aspiration pneumonia or worsening hypoglycemia from tremors. Rather than attempting to induce emesis, immediate stabilization of the patients, with a focus on the ABCDs (airway, breathing, circulation, dysfunction) should have been––and should always be––the first step. Intravenous access with catheter placement and administration of a parenteral muscle relaxant (eg, 40–100 mg/kg methocarbamol IV, slow to effect) should have been initiated to stop the tremors.

These patients were candidates for gastric lavage. In general, gastric lavage should be performed

  • if the patient has clinical signs and is suspected to have toxicant remaining in the stomach
  • if the toxicant has a narrow margin of safety, as with macrocyclic lactones (ivermectin), baclofen, calcium channel blockers, metaldehyde, etc
  • when a dose approaching the LD50 has been ingested.

In this case, advanced diagnostics and therapeutics could have been performed once the patient(s) was stabilized. This would potentially include abdominal radiographs to look for the presence of radiopaque metaldehyde pellets in the stomach, followed by gastric lavage under anesthesia (with an inflated endotracheal tube to prevent secondary aspiration).

The second part of decontamination is administration of activated charcoal (AC). In the dog that initially survived, the oral administration of AC should have been carefully weighed, as the dog was experiencing tremors and at risk for aspiration. If gastric lavage was performed, AC could have been given afterward via the orogastric tube. Dose depends on the brand of charcoal, but in this case it appears to have been too low; charcoal should be administered at 1–5 g/kg (typically 10–20 mL/kg of ToxiBan). When administering AC, typically the first dose should contain sorbitol, a cathartic. Also, the use of rectal AC is controversial, and likely to be of limited benefit. Instead, a prokinetic (eg, metoclopramide) or warm water enemas to enhance fecal elimination could have been considered (depending on results of abdominal radiographs).

While urine specific gravity was not ascertained, the packed cell volume and elevated creatinine are consistent with hemoconcentration, and the use of a more aggressive fluid rate was likely warranted (eg, with an end goal of achieving hemodilution—packed cell volume: 35%/total solids: 5 g/dL. To counter hypernatremia that can rarely result from administering AC, aggressive IV fluids can be instituted. This measure was also indicated because  the dog was excessively sedate and thus at risk for dehydration from lack of oral intake. Finally, while metaldehyde is not renally excreted (therefore, aggressive fluids do not increase excretion or elimination), persistent tremors can result in myoglobinuria and put the patient at risk for acute kidney injury (albeit rarely).

While personal preference applies when it comes to selection of anticonvulsants, I generally do not advocate use of propofol as a primary anticonvulsant. Barbiturates (eg, 4–20 mg/kg phenobarbital IV, to effect) are generally considered to be more effective and result in less respiratory apnea. Likewise, midazolam is considered to be an ultra-short acting benzodiazepine, so the use of diazepam, if available, would have been preferred. More important, higher doses of methocarbamol could have been considered; in my clinical experience, the maximum published dose of 330 mg/kg/day can be exceeded safely when needed to control tremors. In this case, earlier use of phenobarbital rather than propofol should have been considered.

The use of mannitol may have been unnecessary in this patient. As the dog was probably anesthetized from the propofol, it would be difficult to assess neurologic function. Unless the dog was showing more significant clinical signs of cerebral edema (eg, anisocoria, Cushing’s reflex, etc), I would not advocate the use of mannitol. It likely contributed to the dog’s dehydration and is rarely necessary if tremors and seizures are well controlled with other drugs.

Finally, in a coughing, febrile patient at risk for aspiration pneumonia from either excessive sedation, aspiration during emesis induction, aspiration of AC, or other such factors, chest radiographs are warranted to evaluate for lung pathology. Appropriate antibiotic therapy is warranted but only if radiographic evidence of aspiration pneumonia is detected.

Treatment of the poisoned patient requires aggressive, appropriate decontamination and supportive care addressing clinical signs. General categories of supportive treatment include fluid therapy, gastrointestinal support (eg, antiemetics), anticonvulsants (eg, phenobarbital, diazepam), and monitoring (eg, head elevation at 15⁰–30⁰, blood pressure, ECG, and pulse oximetry monitoring). With aggressive supportive care, the prognosis for the poisoned patient is often excellent.

JUSTINE A. LEE, DVM, DACVECC, DABT, is the CEO and founder of VetGirl, a subscription-based podcast service offering RACE-approved continuing education (CE). Dr. Lee graduated from Cornell University and completed her internship at Angell. She also completed an emergency fellowship and residency at University of Pennsylvania. Dr. Lee is double-boarded in both emergency critical care and toxicology. In 2011, she was named the NAVC Conference Small Animal Speaker of the Year, and she is passionate about delivering clinically relevant CE.

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

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