Discussion

Nicotine poisoning is well described in the pediatric population, and even small oral doses may result in toxic effects. There has been a dramatic increase in nicotine poisoning related to the use of e-cigarettes over the past year, with a reported increase of 300% in exposure to highly concentrated liquid nicotine in the United States.Reference Miller ¹ Of calls to poison control centers in the United States, e-cigarettes now comprise 42% of the nicotine-related calls.Reference Chatham-Stephens, Law and Taylor ² Despite there being no recent deaths from nicotine ingestion, reports of less serious cases of accidental poisonings, especially among young children, are rapidly increasing.Reference Richtel ³ Nicotine is readily absorbed through mucous membranes, skin, the gastrointestinal tract (GI), and respiratory alveoli. Numerous studies have investigated nicotine toxicity in infants and toddlers. The source of this nicotine is usually tobacco products and, more recently, nicotine replacement products such as gum and patches. Connolly and colleagues found that over 70% of such ingestions involve infants, and that smokeless tobacco products were the second most commonly ingested after cigarettes.Reference Connolly, Richter and Aleguas ⁴ With the more frequent use of novel products such as e-cigarettes, concerns have arisen surrounding liquid nicotine (Figures 1 and 2). It has been reported that e-liquids are much more dangerous than tobacco, as the liquid is absorbed more quickly, even if in a dilute concentration.Reference Richtel ³ As there are no regulations regarding child-proof bottling or packaging, it appears that there may be potential for unintentional ingestion of these colorfully and appealingly packaged products by children.

Figure 1 Example of a nicotine liquid bottle.

Figure 2 Example of a delivery device for liquid nicotine.

Nicotine is a plant derivative that functions as a nicotinic acetylcholine receptor agonist in the autonomic ganglia, adrenal medulla, neuromuscular junction and brain. Nicotine thus increases the levels of several neurotransmitters, including acetylcholine, beta-endorphin, dopamine, norepinephrine, and serotonin. It is metabolized in the liver by cytochrome P450 and has a half-life of one to two hours. ⁵

The toxic effects of nicotine result from overstimulation of the nicotinic receptors. This often results in inhibition of receptor action following initial stimulatory effects. The toxic dose depends on whether or not the patient is habituated to the effects of nicotine, but in a child it may be as low as 1 to 4 mg orally. A lethal dose has not been established, but it is estimated that an oral dose of 40 to 60 mg may be fatal. Reports indicate that ingestion of one to three cigarette butts can cause adverse effects in children, and a cigarette butt is estimated to have 4 to 5 mg of nicotine (Table 1). Signs and symptoms of ingestion appear to be dose-related. One study found that children ingesting 0.5 mg/kg of nicotine remained asymptomatic, while 0.8 mg/kg resulted in mild symptoms and 1.4 to 1.9 mg/kg resulted in severe toxicity. ⁵

Table 1 Concentrations of nicotine in various products

The Canadian Pharmacists Association report that <1 mg/kg can be a lethal dose in adults, and an even lower dose may pose the same risk in children. ⁶ Standard textbooks and safety sheets typically cite a lethal dose for adults as between 30 to 60 mg (LD50 of 0.8 mg/kg). After several detailed reviews, Mayer has argued that a careful estimate suggests that a lower limit causing fatal outcomes is 0.5 to 1 g/kg of ingested nicotine, corresponding to an LD50 of 6.5 to 13 mg/kg.Reference Mayer ⁷ In the case we report, if our patient ingested the entire bottle of liquid nicotine, she would have consumed approximately 1.4 grams of nicotine, or 107 mg/kg, an amount over 50 times the dose reported to result in severe toxicity.

The toxic effects are dose-dependent. Symptoms of mild to moderate toxicity may include nausea, vomiting, dizziness, headache, tremor, diaphoresis, tachycardia, pallor, and hypertension. Of these, the most commonly seen symptoms are GI upset with nausea and vomiting, as well as pallor, diaphoresis, and mental confusion. ^{5 , 6} The commonly seen initial vomiting can help to reduce absorption and is usually self-limited; treatment with anti-emetics is not recommended, but maintaining adequate hydration in the form of intravenous fluids may be necessary in severe cases. The onset of symptoms is usually within two hours, with the exception of delayed-release products such as patches. ⁵

Overstimulation of the nicotinic receptors can cause receptor inhibition after the initial stimulatory effects. More severe toxicity can result in seizures, confusion, weakness, bradycardia, hypotension, and respiratory muscle paralysis. ^{5 ,} Reference Singer and Janz ^{8 ,} Reference Oberst and McIntyre ⁹ Initial hypertension, tachycardia, and tachypnea can be followed by hypotension, bradycardia, and bradypnea.

The treatment of nicotine toxicity is primarily symptomatic and supportive. ^{5 ,} Reference Woolf, Burkhart and Caraccio ¹⁰ In cases of dermal exposure to a nicotine solution such as the one in this case report, contaminated clothing should be removed and affected areas should be washed thoroughly with mild soap and copious amounts of cold water to reduce absorption. Activated charcoal is recommended if patients present shortly after ingestion, owing to the possibility of nicotine-induced seizures, provided the risks do not outweigh the anticipated benefits. ⁶ If a patient is vomiting, seizing, or has a decreased level of consciousness, there is a risk of pulmonary aspiration with charcoal administration. Enhanced elimination techniques, such as multiple-dose charcoal or dialysis, are theoretically useful, but have not been described owing to the rarity of life- threatening toxicity. ⁵ Supportive treatment is directed toward the specific presenting complaint. For example, hypotension should initially be treated with intravenous fluid boluses to avoid cardiovascular collapse, seizures should initially be treated with benzodiazepines, atropine can be administered for excessive bronchial secretions or diarrhea, and respiratory support should be provided for bradypnea.

Recently, electronic cigarettes and nicotine liquid cartridges have been marketed and have become widely available in Canada. Most are shaped to appear like real cigarettes, often with a glow at the tip, and produce a vapor that resembles smoke. The liquid mixture may contain varying amounts of nicotine, propylene glycol, and other chemicals, and is vaporized in the e-cigarette by a battery-powered delivery system. ¹¹ Some websites even allow denser concentrations of nicotine (up to 72 mg/mL) for heavy smokers.

Our report prompts the consideration of a number of key points (Table 2). Currently, Health Canada advises Canadians to not purchase or use electronic smoking products, as they have not been fully evaluated for safety, quality, and efficacy, and may pose unknown health risks. Health Canada also explicitly states that nicotine cartridges and electronic smoking products should be kept out of reach of children at all times, both because they are a choking hazard and because they present a risk for nicotine poisoning. However, there are no laws regulating the sale of these products, and they can readily be found over-the-counter in convenience stores as well as through Internet purchase. ¹¹ As there is currently a disconnect between the legality and regulation of e-cigarette nicotine products and their availability to the general population, children are at particular risk, as such products are not child-proofed and under the protection of Health Canada.

Table 2 Liquid nicotine exposure

We suspect that many parents are unaware that e-cigarette nicotine liquid is toxic. The American Association of Poison Control Centers recommends always protecting skin when handling e-liquid products, following disposal instructions on the label, and always keeping e-cigarettes and liquid nicotine locked and out of reach of children.Reference Picard ¹² It is imperative to educate the public on the serious risks these liquids pose to the pediatric population. If a child has been exposed to an e-cigarette or liquid nicotine, the local poison control center should immediately be contacted for management advice.