Alarming Surge in Liquid Nicotine Toxicity in Kids

This discussion was recorded on August 17, 2023. This transcript has been edited for clarity.

Robert D. Glatter, MD: Hi. I'm Dr Robert Glatter, medical advisor for Medscape Emergency Medicine. Joining me today is Dr Ryan Marino, an emergency physician, medical toxicologist, and addiction medicine specialist at Case Western Reserve University School of Medicine.

Welcome, Dr Marino. It's really a pleasure to have you join us.

Ryan Marino, MD: Hi, Dr Glatter. Thanks for having me.

Glatter: Today's topic is the toxicity of liquid nicotine, and it's something that's been very important, especially since the CDC put out a report several months ago looking at the cumulative exposure from 2022 in the mid-year toward 2023 and the number of exposures — there were nearly 7000. The thing that caught my eye was that almost 90% of these exposures were in children under the age of 5, which to me was a significant wakeup call. I know that the proportion of children exposed to liquid nicotine has been increasing, but this is something that seems like a real public health concern, if not an emergency. I wanted to get your take on this report.

Marino: This was a report based on poison center calls. There are a couple of things to mention here. We've seen exposures to nicotine and calls to poison centers about nicotine increasing steadily over the past number of years. This is a pretty significant increase year-on-year, and it correlates to the liquid nicotine and vape market that we're seeing in this country.

One thing that I do want to mention about these data is that because these are poison center data, people have to call this in and it's self-reported, so it's probably an undercounting and underestimate of actual nicotine exposures. The real number is probably going to be even higher than what we're seeing here.

Nicotine Toxicity – Signs and Symptoms

Glatter: What are the signs and symptoms that a child has a significant exposure? What are the things you look for? What's the history? How do you approach a pediatric patient?

Marino: The most important thing is if someone reports that they think their child was exposed to nicotine, that's going to be the best clue because the symptoms can be nonspecific. Early on, you can get pretty mild symptoms. The most common presenting symptoms that you would see, especially in the emergency department, are going to be gastrointestinal symptoms, including nausea, vomiting, and diarrhea. You can get a sympathomimetic-looking picture like adrenergic stimulation with tachycardia, hypertension, diaphoresis, and those kind of things. We really worry because this can progress to things like bradycardia, hypotension, depressed level of consciousness, and even coma and respiratory failure. Kids can get respiratory paralysis from nicotine poisoning on the far end of the spectrum.

Glatter: With the liquid nicotine vial itself, you may ask a parent, "How much do you think your child might have been exposed to?" What's a quick way that you estimate this in a child who vomited once and looks okay clinically? What determines whether you observe that child for another 4-6 hours? How are you determining the degree of exposure in terms of milligrams of nicotine?

Marino: That's a good question and it can be really tough. I don't know that there is necessarily a good answer in terms of the exact dose and a correlation to symptoms. This is something that is still debated in the literature, but we tend to think, for a small child or toddler, ingestion of one cigarette would merit observation for at least several hours. A cigarette can contain probably 12 mg of nicotine. The liquid nicotine in vaporizer products, refill cartridges, and those kinds of things can have up to 20 mg/mL nicotine.

Very small amounts can contain significantly more than even an ingestion of a cigarette, which we used to teach. The unregulated products can have even more than that and can be more concentrated, and that's something that is not seen infrequently. That does make it more concerning with this liquid nicotine exposure. Anyone who's symptomatic, I think, has kind of bought themselves at least a several-hour observation in the emergency department, with 6 hours probably being the general cutoff. Certainly, there is a low threshold to admit for significant symptoms or any signs of progression.

The one good thing about nicotine — which maybe is not really a good thing — is that it is rapidly absorbed and should have pretty rapid onset of effects after ingestion. It's not like you would be expecting significant delay in your presentation or progression of symptoms. Again, because it is very rapidly absorbed, there's not really much time to intervene before it can get into the body.

Nicotine Absorption vs Inhalation

Glatter: That raises a question, too, in terms of gastrointestinal vs inhalational absorption. If a child puts his mouth on a device and takes a few puffs, how concerned are you in that scenario vs a child who actually ingests liquid nicotine?

Marino: The inhalation is definitely less concerning. Not to say that it isn't a concern or that you can't have significant toxicity, especially in little kids, but that would be a lower risk for toxicity and you would usually get a lower potency or lower dose exposure that way; whereas ingestion of the liquid, because it is so concentrated and is so rapidly absorbed from the stomach, is a much bigger risk. Usually, these are going to be flavored to taste good. Those little bottles of refill nicotine liquid can contain quite large doses of nicotine, and a small child might just ingest the whole thing.

Dermal Exposures to Liquid Nicotine

Glatter: I wanted to ask you also about dermal exposures. Certainly, it's a concern with farmers who are in the tobacco fields. For children who get a hold of liquid nicotine, it spills on their hands and they rub their face and so forth. How much concern should parents and caregivers have about that aspect? Maybe you can talk about absorption through the dermal route.

Marino: Unlike many other substances, nicotine is very readily, rapidly, and completely absorbed through the skin. Certainly, this is historically described in tobacco farmers — green tobacco sickness — where they would get significant toxicity just from harvesting the leaves and getting the liquid from the plants on their skin.

When it comes to the concentrated nicotine fluid, this is much higher doses of nicotine and much smaller amounts of liquid, so this is definitely something that is a concern. Adults can get toxic effects from skin exposure. Although I haven't personally seen any children with this, I have to imagine that this is a concern for children because they're much smaller in size and they have much larger skin area, so any exposure to that kind of dose of nicotine, which would be very quickly and rapidly absorbed, could be a big risk. I think parents should also keep in mind that even if it just gets on their skin, it's worth calling poison control and keeping a close eye on them.

Glatter: How soon would you expect to see symptoms after a significant dermal exposure relative to, say, an ingestion?

Marino: It would probably be a little slower than an ingestion but still would be within 1-2 hours where you would expect to have some symptoms. In this case, if you give poison control a call, they can tell you what symptoms to watch for, and they can check back with you and maybe keep you out of the emergency department. Certainly, within 2-6 hours, you should have symptoms from any exposure, including dermal.

'Fancy' Packaging and Other Enticements

Glatter: Another point you're bringing up here is how children are enticed by this, including the marketing and especially the flavors, packaging, and the colors. It grabs you and it grabs children more so, in the sense that they want to pick it up and put it in their mouth. Often they spill it, but they'll get some amount ingested or maybe even inhaled if it's a vaping device.

In terms of legislation and child-resistant packaging, 2016 saw the advent of legislation by Congress, but it wasn't complete. It didn't really speak to the devices themselves. It talked about packaging and legislating packaging, but it didn't go quite far enough. I want to get your comments on that.

Marino: Packaging and safety are definitely beyond my area of expertise. In terms of things that we've seen, when you do have less secure packaging and more child-friendly, colorful, enticing things — adults also like those things, don't get me wrong; that's how you sell a product — that does lead to more exposures. We've seen this in the edible THC market where, if you have edibles that look like regular candies or are brightly colored or have cartoons on them, you have more children eating those than if you have just nondescript, white packaging.

The best thing would be for these to be in out-of-reach, secure locations, but the packaging definitely does make a difference. This is something that has been borne out over and over in the literature. Any way that we can minimize the risk to children is definitely worth looking into, going forward, from a legal perspective.

Glatter: In terms of safety, if parents would lock up their vape liquids and their devices, that might go even further. I think this is something that any caregiver or parent needs to keep in mind when there are children in the home.

Marino: Even if it's not just the parent or caregivers, given the popularity of vapes and these different vape products that are on the market now, knowing that these are going to be around, even if you're in public, there's a good chance that someone could have it sitting out on a table at a restaurant.

We see these things like the Elf Bars, which are very brightly colored. Single-use vapes like that have less of a risk for the liquid being an exposure or anything getting out of them other than inhalation. Still, that is something that's going to entice children. These are things that I see when I am out in public as well.

Treating Nicotine Toxicity in Children

Glatter: When you're looking at a child, in terms of sensitivity of symptoms, would you say that vomiting is the most sensitive or even specific way to note that there's been significant exposure, assuming no other symptoms have occurred, especially, for example, a seizure?

Marino: In terms of presentation, without having some sort of reported history of vomiting, I would have a hard time convincing myself that a significant nicotine exposure had occurred. Certainly, a large-volume exposure may progress more rapidly, but usually there would be at least some report of vomiting or gastrointestinal symptoms prior to coming to the emergency department, if not on presentation.

Glatter: In a sicker patient, who comes in post ingestion with altered mental status and then gets bradycardic, their airway may be at risk. Say they require intubation; is there any role for charcoal or gastric lavage based on presentation in terms of severity?

Marino: That's a great question. I don't know that this is a 100% definitive answer, but given that the nicotine liquid formulations are usually so quickly absorbed, there probably isn't much of a role beyond supportive care; especially if you're concerned about mental status or airway issues and any vomiting, charcoal would probably be contraindicated in most of those situations.

Glatter: Essentially, supportive care and airway management would be front and center in any patient that we approach. Are there any other considerations, any nuances or pearls that you can give us in caring for children who are suspected of an exposure?

Marino: The main thing beyond supportive care is knowing that this is something that can progress rapidly. It's something that is very rapidly and readily absorbed. A child who is well-appearing, appears very stimulated, or has hyperadrenergic vital signs early on can progress to the opposite with coma, shock, and more concerning features. It is acting on your acetylcholine receptors. Just remember that cholinergic toxicity is something that we worry about often.

We don't see organophosphate poisoning in the United States anymore, but everyone remembers, from the killer bees incident, this is a poisoning that is a big problem. Nicotine can progress to very much the same kind of features, so just remember that it's nothing to sneeze at.

Glatter: Is there any role for atropine or even pralidoxime in terms of management of the critically ill child that's poisoned?

Marino: Certainly, in terms of treatment of bradycardia and hypotension, reaching for atropine is reasonable, and also if you have any concern about secretions, although you wouldn't necessarily see the same kind of bronchorrhea from nicotine poisoning as you would expect from organophosphates. Atropine, in terms of hemodynamic support, is a reasonable choice.

Glatter: Do you feel that that other organizations, especially emergency medicine organizations, need to pick up the ball and shout louder about this public health danger?

Marino: I definitely agree with that. This is something that most people are not aware of. Even with the popularity of vapes and the prevalence of nicotine products, which seems to be increasing, as well as the dramatic increase in exposures, for the most part, I think people who use these products and people who have small children are unaware that this is a significant risk and how risky those concentrated nicotine fluids can be.

Metal Exposure from Vapes

Glatter: There has been some concern about the metals, especially in first-generation vapes, in terms of the metal coil having some leaching of chemicals, including nickel, cadmium, zinc, manganese, and chromium — really dangerous, potentially carcinogenic chemicals other than, say, acetaldehyde, formaldehyde, and so forth.

How much of a concern should parents have on inhalational exposure or even a liquid nicotine exposure in a vape pen?

Marino: The metal concern is significant. This is probably going to be a bigger issue for people who are using these chronically. The inhalational exposure is the most concerning route of exposure for most of those substances that you listed, and certainly, things like manganese and cadmium cause pretty profound and very difficult-to-treat forms of toxicity.

Anyone who's using any of these older products or unregulated vapes from international markets should be aware of that. It's probably less of a risk than the nicotine to children who get a couple of puffs by accident, but it's definitely also something to keep in mind because it is a concern and we want to minimize that. There's no "safe" amount of those toxic metals that I would want anyone exposed to.

Glatter: Do you feel that convection-based vaping devices, as opposed to conduction-based, might have a role in mitigating some of the dangers in this regard?

Marino: Yes. That is something the market has been trying to regulate and improve on. Again, the fact that older and different products are still out there, and can be obtained from other places as well, is something that is concerning.

Glatter: This has been great information. I appreciate you sharing this with our audience. Thank you for your time and your expertise. It's quite an honor to have you join us. Thank you again, Dr Marino.

Marino: Thanks for having me.

Robert D. Glatter, MD, is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. He is a medical advisor for Medscape and hosts the Hot Topics in EM series.

Ryan Marino, MD, is a medical toxicologist, emergency physician, and addiction medicine specialist at University Hospitals Cleveland Medical Center and an assistant professor in the departments of emergency medicine and psychiatry at Case Western Reserve University School of Medicine. He recently started University Hospital's medical toxicology division as well as its emergency department addiction services and emergency addiction bridge clinic at Cleveland Medical Center.

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