ACMT Toxicology Visual Pearl: Clutching your Perles

4. Widened QRS

Background [1-4]

Benzonatate (Tessalon Perles®) was approved in 1958 as an anti-tussive for patients older than 10 years old. It is available in 100 or 200 mg capsules, with a noted maximum daily dose of 600 mg/day. The yellow/gold liquid-filled spherical capsules can be mistaken for candy, particularly by children, leading to devastating inadvertent toxicity. The FDA has issued warnings for children below the age of ten after multiple accidental ingestions were reported. A single “perle” is thought to be enough to cause mortality in young children, primarily due to its potent voltage-gated sodium channel inhibition properties, which may result in widened QRS intervals and arrhythmia.

How does benzonatate work? [1]

• Benzonatate is used as an oral antitussive through its purported ability to anesthetize the vagal stretch receptors located in the respiratory passages, lungs, and pleura
• It is structurally similar to procaine and tetracaine, two local anesthetics (LA)
• Similar to LAs, benzonatate is a potent voltage-gated sodium channel inhibitor, which can lead to toxicity, primarily in the cardiovascular system and central nervous system

How does benzonatate toxicity present? [1-5]

• Symptom onset is rapid after overdose, often occurring within 15-30 minutes
• Breaking or chewing on the capsules can cause oropharyngeal numbness, choking, aspiration, bronchospasm, or laryngospasm
• Neurologic symptoms: encephalopathy, agitation, seizures, coma
• Cardiovascular: hypotension, tachycardia, ventricular dysrhythmias (V-tach, V-fib), PEA, or asystole
• Unfortunately, this ingestion can be rapidly fatal, particularly after intentional ingestion

How do you manage benzonatate toxicity? [1,4,6]

• Activated charcoal and whole bowel irrigation are typically not recommended due to the rapid absorption & onset of action
• Supportive care, ABCs
• Cardiopulmonary monitoring, frequent EKGs, and sodium bicarbonate boluses for widened QRS
• Continuous monitoring of neurologic status; benzodiazepines for seizures
• IV lipid emulsion 20% – no specific studies of use in benzonatate; however, it may be beneficial in cardiovascular collapse, given the structure and toxicity of benzonatate being like local anesthetics
  • <70 kg
    • Bolus: 1.5 mL/kg over 2-3 minutes
    • Infusion: 0.25 mL/kg/min (consider using pump if <40 kg)
  • >70 kg
    • Bolus: 100 mL over 2-3 minutes
    • Infusion: 250 mL over 15-20 minutes
  • If the patient remains unstable, repeat the bolus, double the infusion
• In severe/refractory cases, ECMO can be considered, although the literature is limited

Bedside “Perles”

• Benzonatate is highly toxic to children, and a single “perle” can result in mortality
• Rapid onset of symptoms and severe clinical effects may occur following ingestion
• Can mimic local anesthetic systemic toxicity with concerning features of hypotension, tachyarrhythmias, cardiac arrest, encephalopathy, seizures, coma, and even death
• Treatment aims at supportive care, managing ABCs, benzodiazepines for seizures, sodium bicarbonate for widened QRS, and in severe cases, IV lipid emulsion and ECMO can be considered