Camphor

Camphor is an aromatic terpene ketone, originally distilled from the bark of the camphor tree and now synthesized from turpentine oil. It is a common ingredient in some topical and vaporized medications intended to treat musculoskeletal pain or symptoms of common flu-like illnesses (Table 158.1). Camphor is marketed as an analgesic, an antipruritic, and an antitussive, and it is also found in older formulations of mothballs.

Table 158.1 Common Camphor-Containing Products

The exact mechanism by which camphor produces toxicity is unknown, although the cyclic ketone of its hydroaromatic terpene group is hypothesized to be a neurotoxin. Camphor is highly lipophilic, resulting in rapid movement across cell membranes and a large volume of distribution. Its metabolites are stored in fat deposits and are cleared over a prolonged period of time, which may be responsible for the delayed onset of seizures associated with camphor toxicity.² Camphor may also cause gastrointestinal toxicity from its direct effect on mucosal surfaces.

Doses between 750 and 1500 mg, and doses as low as 500 mg in some case reports, are associated with seizures and death.² For this reason, the U.S. Food and Drug Administration ruled in 1982 that products could not contain more than 11% camphor. However, some commercially available formulations contain 500 mg in 1 teaspoonful of product. In addition, a case series of pediatric seizures attributed to camphor toxicity highlights the role that camphor still plays in some ethnic and cultural practices. Illegally sold, high-concentration camphor products pose a risk in these populations.³

Salicylates

Salicylates are present in numerous over-the-counter products and are marketed as analgesics, antipyretics, and antiinflammatory agents (Table 158.2). Several Asian herbal remedies sold as topical treatments for musculoskeletal pain also contain salicylates.

Table 158.2 Common Salicylate-Containing Products

Oil of wintergreen represents a specific concern in the pediatric population because of its extremely high concentration. One teaspoon of 98% oil of wintergreen contains 7000 mg of methylsalicylate, equivalent to 86 baby aspirin, a potentially lethal dose for children weighing less than 23 kg. This product has a pleasing aroma, thus rendering it particularly vulnerable to accidental ingestion. A review of pediatric salicylate poisonings found that all published cases of life-threatening toxicity or death resulted from oil of wintergreen or Asian herbal oil ingestions.⁴

Salicylate toxicity is caused both by direct stimulation of the central nervous system (CNS) respiratory center, resulting in hyperventilation and respiratory alkalosis, and by uncoupling of oxidative phosphorylation, which results in anion gap metabolic acidosis. Pulmonary and cerebral edema is hypothesized to result from increased capillary permeability. Impaired glucose metabolism can lead to hyperglycemia or hypoglycemia. Doses greater than 150 mg/kg are potentially toxic in children, and serious toxicity is seen in the range of 300 to 500 mg/kg.

Topical Anesthetics

Topical anesthetics are found in various pain-relieving products ranging from teething gels to hemorrhoid creams (Table 158.3). Amide anesthetics, which include lidocaine and dibucaine, work by blocking voltage-gated sodium channels and preventing action potential propagation. In toxic doses, these agents can cause CNS hyperstimulation secondary to central blocking of inhibitory pathways that can progress to seizures, respiratory depression, and coma. Amides can also cause cardiac toxicity because of their antiarrhythmic properties, but this is most frequently seen in intravenous, rather than oral, exposures.⁵

Table 158.3 Common Anesthetic-Containing Products

Benzocaine is an ester anesthetic whose metabolites can cause methemoglobinemia in toxic doses. Methemoglobin is formed by oxidation of iron from the ferrous (Fe²⁺) to the ferric (Fe³⁺) state within the hemoglobin molecule. This process causes a leftward shift in the hemoglobin-oxygen dissociation curve and decreases hemoglobin’s oxygen carrying capacity. Patients less than 6 months old have a relative deficiency of methemoglobin reductase and may be more susceptible to toxicity.⁵

Prilocaine is an amide compound that has been shown to cause methemoglobinemia as its primary toxicity in overdose.⁵ Both prilocaine and lidocaine are components in EMLA cream, so this particular cream can cause either CNS toxicity or methemoglobinemia in overdose.

A literature review found published cases of seizures resulting after single ingestions of 5 to 25 mL of viscous lidocaine by children 2 years of age or younger.⁵ Although dibucaine is less commonly prescribed than lidocaine, it is 10 times more potent, and ingestion of 2 to 3 teaspoons has caused death secondary to cardiopulmonary arrest.⁶ Published reports of benzocaine-induced toxicity vary; cyanosis secondary to methemoglobinemia may result from oral doses in the range of 15 to 40 mg/kg, although the development of methemoglobinemia may be idiosyncratic, rather than dose related.