Dr. Gussow is a voluntary attending physician at the John H. Stroger Hospital of Cook County in Chicago (formerly Cook County Hospital), an assistant professor of emergency medicine at Rush Medical College, and a consultant to the Illinois Poison Center. He is also the editor of his own blog, www.thepoisonreview.com. Follow him @poisonreview, and read his past columns at http://bit.ly/GussowToxRounds.
Calls to poison centers for exposures to nicotine-containing e-cigarette liquid have increased dramatically over the past few years, according to the Centers for Disease Control and Prevention. Exactly one call was made in September 2010, but poison centers handled 215 inquiries in February 2014 alone, an increase of 21,400 percent. (MMWR 2014;63:292; http://1.usa.gov/1isCh79.)
It might seem that these results should have been published in the American Journal of Duh! The e-cigarette phenomenon has grown so rapidly over the past few years that it would have been surprising if related calls to poison centers had not gone up so radically. Prefilled e-cigarettes have been available in the United States since 2007, but devices with tanks that can be refilled with liquid nicotine are a more recent arrival.
These sweet-smelling liquids come in fruit and candy flavors such as banana-strawberry and bubblegum, and there has been concern that toddlers might ingest them and develop significant nicotine toxicity. I am not aware of any cases involving serious toxicity from these products, and the CDC reported that the most common adverse effects were nausea, vomiting and eye irritation.
The popularity of inhaling vapor from these e-cigarettes or tanks — called “vaping” — is growing so fast that it seems a good time to examine some important questions about the potential toxicity of these products.
It is surprisingly difficult to get a reliable answer to the simple question of how much nicotine is in an e-cigarette refill. Supplies of e-cigarette liquid typically come in vials labeled as containing anywhere from 0 to 36 mg of nicotine. But does that figure represent the nicotine content per vial? I asked this question at several vape shops around Chicago, and the clueless clerks would claim that the number referred to the total amount of nicotine in the vial, which would be a remarkably low dose. What the figure actually represents is the nicotine content per milliliter of fluid. A 30 ml vial marked as 24 mg of nicotine would therefore contain a total dose of 720 mg of nicotine.
Many references claim that the lethal nicotine dose for an adult is 60 mg, approximately 1 mg/kg. Pharmacologist Bernd Mayer, PhD, questioned this figure, and traced its origin back to an unscientific 1906 paper, a source that itself referenced an even earlier anecdotal report in an 1856 textbook. (Arch Toxicol 2014;88:5.) Many observations since then suggest that the lethal dose must be much higher than 60 mg. Dr. Mayer estimated that “more than [500 mg] of oral nicotine is required to kill an adult.” Extrapolating to the pediatric population, this would mean that about 70 mg would be lethal for a 10 kg toddler. A vial of even 12 mg/ml of liquid nicotine would contain considerably more than enough to kill a child.
Nicotinic receptors are present throughout the central and peripheral nervous systems. Nicotine causes initial stimulation of these cholinergic receptors, followed by blockade and paralysis. Low-dose exposure causes nausea, tremor, and tachycardia. Higher doses can cause typical manifestations of cholinergic syndrome: hypersalivation, vomiting, diaphoresis, and diarrhea. Severe exposure can progress to fasciculations, arrhythmias, seizures, respiratory paralysis, and apnea. Nicotine is also an irritant, which explains why eye pain was one of the most common adverse effects listed in the MMWR report.
I purchased several e-cigarette refills and performed a taste text to see if young children might find the taste of nicotine liquids attractive. I put a micro drop on my finger and licked it. A grape-flavored preparation called “Grapeful Dead” (24 mg) had an unpleasant aroma of rotting fruit and burning tires. It had these same qualities on the palate, plus a cayenne-like sting at the back of the throat from the nicotine. I cannot imagine a child being attracted to this.
A preparation labeled “Coffee” (18 mg), on the other hand, had a distinct mocha latte nose with strong characteristics of sweet caramel, toffee, and molasses on the tongue. The burn at the end was less than the grape flavor, probably because of the lower nicotine concentration. I could definitely imagine a child ingesting this. In fact, I almost went back for seconds.
Even a small amount of product can contain a lethal dose of nicotine, so all children with reported exposures should be referred to a health care facility for observation. Nicotine is rapidly absorbed, and children who remain asymptomatic after six hours of observation can be discharged. Those with manifestations of nicotine toxicity — other than perhaps nausea or mild self-limited vomiting — should be admitted. Parents should be advised of the potential danger these products represent and the need to keep them out of the reach of children.
The Food and Drug Administration is proposing regulations for e-cigarettes and nicotine refills. Right now the industry is completely uncontrolled, and there is no assurance that the products do not contain harmful additives or that the listed concentrations of nicotine are accurate. And no current regulations require that containers be childproof.
The attractive packaging, sweet candy and fruit flavors, and readily opened containers make these nicotine liquids scary products. All such episodes should be approached carefully, and assumed to have medically significant toxicity until proven otherwise.
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