Drops, Ointments, Gels, and Patches: The Dangers of Topical Medications

The anxiety of caring for a child in imminent peril may cause even an experienced clinician to forget to ask important questions about ingestions and exposures that can be critical to the patient’s management. Though emergency physicians (EPs) routinely ask about household medications when obtaining a history from family members, they occasionally gloss over a detail of utmost importance: topical medications.

The use of topical medications is extremely prevalent in the United States, in turn resulting in accidental ingestion—particularly in the pediatric population. In 2015, there were 56,455 calls to US Poison Control Centers for pediatric (children ≤5 years) exposures to topical preparations.¹ Topical drug-delivery-system formulations include drops, ointments, gels, and patches. Intentional and unintentional misuse or overdose of any of these formulations can cause toxicity. Unintentional overdose of these drugs can occur secondary to exploratory ingestions, therapeutic errors, or medication overuse due to the perception of safety associated with topical preparations.

Drops

Topical liquid medications such as ophthalmic and otologic drops can be fatal when ingested or used inappropriately. The following sections review commonly used prescription and nonprescription formulations, associated toxicological manifestations, and appropriate management.

Ophthalmic Drops

A common class of ophthalmic drops includes imidazoline-derived agents such as tetrahydrozoline (eg, Opti-Clear, Visine). Tetrahydrozoline hydrochloride is an agonist of alpha-1, alpha-2, and imidazoline receptors.^2-4 Stimulation of alpha-1and imidazoline receptors impede sympathetic output, leading to bradycardia and hypotension. Imidazoline derivatives can mimic clonidine toxicity, with miosis, lethargy, diminished bowel sounds, respiratory depression, and apnea.²

Treatment. Management of overdose of imidazoline agents depends greatly on the patient’s presentation and is largely supportive. Overdoses of these agents and clonidine are similar: Patients can be extremely somnolent, but may transiently improve when a painful stimulus is applied. Activated charcoal may be useful for recent ingestions,³ but it should only be considered in patients whose airway is patent or protected. Intravenous fluids are indicated if the patient is hypotensive. Atropine may be considered for symptomatic bradycardia,³ and transcutaneous pacing should be considered if the patient is hemodynamically unstable. Intubation may be required if there is concern for airway compromise, though such compromise is a rare occurrence in ophthalmic ingestion of imidazoline-derived agents.

Although not well studied due to a lack of data, some sources recommend naloxone administration, given the similarities of imidazoline agents to clonidine in the overdose scenario.^3,4 Although the optimal dose is unknown, high doses of naloxone (ie, pediatric patients, 0.4 mg, followed by 2 mg, then 10 mg, if no response) are typically required and should be considered in symptomatic patients after an ingestion. After successful supportive management, most patients continue to do well during their hospital course and have a full recovery.

Methyl Salicylate

Methyl salicylate (oil of wintergreen) is a common ingredient in muscular pain-relieving creams and ointments that can have devastating consequences in overdose. Significant toxicity from these compounds is rare, as large exposures are needed to reach a toxic threshold. However, oil of wintergreen is also available as a liquid preparation with 98% methyl salicylate.⁵ At this concentration, 1 teaspoon (5 mL) is roughly equivalent to 7 g of acetylsalicylate,⁵ and this amount of oil of wintergreen is severely toxic and may be lethal to a child. Because it is a liquid, oil of wintergreen is more rapidly absorbed than creams and ointments and can cause rapid toxicity in small quantities.

Methyl salicylate overdose initially causes stimulation of the brain’s respiratory center, which leads to a respiratory alkalosis. Uncoupling of oxidative phosphorylation later causes an anion gap metabolic acidosis. The combination of these two processes leads to a mixed acid-base disturbance. Common signs and symptoms of toxicity include tinnitus, hyperpnea, tachypnea, hyperthermia, nausea, vomiting, multisystem organ dysfunction, altered mental status, and death.

Treatment. Supportive care is critically important. Clinicians must be sure the patient’s airway is patent, particularly in those with altered sensorium or in patients who are becoming fatigued secondary to work of breathing. Extreme caution should be used when intubating these patients, as the patient’s respiratory rate (RR) must be matched if placed on a ventilator. If the RR is too low, the patient will become increasingly acidotic and may become hemodynamically unstable. Activated charcoal should be considered if the patient is mentating well or if the airway is protected.^5,6 Adequate fluid resuscitation is essential.

Serum alkalinization is critical in helping to prevent central nervous system (CNS) toxicity. Urinary alkalinization with sodium bicarbonate will augment the salicylate excretion rate and may also help correct the patient’s acidemia.

Current guidelines recommend hemodialysis in asymptomatic patients whose serum salicylate concentration is greater than 100 mg/dL, or in patients with consequential findings, such as altered mental status.⁷

In infants with severe salicylate toxicity, exchange transfusion can be considered, given the limitations of hemodialysis at this age.⁸ Clinical outcomes are generally good if managed appropriately, though oil of wintergreen ingestion can be fatal.