Out of This World
Want to know what substance has been used at parties since 1799 and is still popular on sites like TikTok? Why it’s used as much as 600 times per day and where you can find it in the grocery store?
This is the Pick Your Poison podcast. I’m your host Dr. JP and I’m here to share my passion for poisons in this interactive show. Will our patient survive this podcast? It’s up to you and the choices you make. Our episode today is called Out of This World.
Want to know what substance has been used at parties since 1799 and is still popular on sites like TikTok? Why it’s used as much as 600 times per day and where you can find it in the grocery store? Listen to find out!
Today's episode starts with a text from one of your residents asking you to see a friend of her’s. He’s a 22-year-old man with difficulty walking. He’s currently in the emergency department, she texts she’ll meet you there shortly because he only agreed to go if she promised to walk his dog first.
His chart reports the following vital signs temperature 98.0 F (36.6 C), heart rate 90 beats per minute, respiratory rate 18 breaths per minute, oxygen saturation 100% on room air and blood pressure 120/80. In other words, completely unremarkable. Entering the room, he’s sitting on the stretcher, fully dressed. This is a serious pet peeve of mine, because you can't do a thorough physical exam unless the patient is undressed, in a gown. His gown is at the bottom of the bed, under his shoes which are also still on.
You decide to talk to him first, take the history, then ask him, again, to get undressed after you step out. He says he's been having difficulty walking for weeks. His legs are weak and his balance is off, causing several falls over the past few days. He denies significant traumatic injuries from the falls. Also, his hands and feet are numb.
He denies fever and chills along with current or recent upper respiratory infections. The rest of the history is unremarkable, he denies all other symptoms, including past medical history and medicines. He doesn't smoke, reports occasional alcohol, and denies illicit drug use. He doesn’t work, he’s still a student. You ask him to get undressed so you can examine him. Back at your computer, you order some basic lab work and a head CT.
When you return to the room, he’s still completely dressed. He looks at you, embarrassed, saying he can't unbutton his shirt. He says his girlfriend helped him dress this morning. So we have an otherwise healthy 20 year old man who can’t get undressed? What is happening here?
You ask him to try to see what the problem is. His fumbles with a button, but his fingers don’t grasp it and he can’t move them in a particular direction. He’s still sitting on the stretcher, his torso is moving back and forth, involuntarily. This is truncal ataxia, neurologically it goes along with and contributes to gait instability.
You help him get undressed and into the gown. On exam, he has diminished sensation in his hands and feet. He can move his legs, but they are weak. He has the strength of a 90-year-old, not a 20-year-old. The findings are worse in the legs than the hands. You have him stand up, grasping his arm so he doesn’t fall, and ask him to take a few steps to check his gait. He lurches forward and almost falls with the first step. You grab him and help him back to bed.
Well, this is not looking good. What could be causing this?
Common things like strokes or intracranial hemorrhage, bleeding in the brain, cause unilateral symptoms, just on one side. Most people would order a head CT, just in case, tho it’s likely low yield here. An MRI might be more helpful, but will take longer to get.
The numbness in his hands and feet is in a stocking glove distribution, a classic description of peripheral neuropathy, caused by local nerve damage. It’s very common, you may be suffering from it yourself or know someone who has it. It's caused by things like diabetes, chemotherapy and alcohol misuse. Peripheral neuropathy by definition means affecting peripheral nerves. In contrast, ataxia is caused by a problem with the central nervous system, meaning the brain and spinal cord. So peripheral neuropathy, while present, isn’t causing his balance problems. Also, it doesn’t cause significant leg weakness like this either, so we need to look further.
You’ve probably heard of Gillian-Barre syndrome, a disease occurring after infections, or very rarely vaccines. It’s ascending weakness beginning in the feet and rising to the head. He’s had symptoms for weeks, if it was Guillain-Barre, the truth is he’d already be dead.
ER doctors always worry about cauda equina syndrome, resulting from compression of nerves in the back. The spinal cord ends in the cauda equina, becoming a series of nerves running from the back all the way down to the toes. Compression here causes weakness in the legs, sensory loss in the groin, and bowel and bladder incontinence, ie peeing or pooping on yourself. The compression happens from things like cancer and infection. He denies incontinence and, Again, we wouldn’t see a central problem like ataxia.
Bottom line, this sounds like a problem for neurology. His results come back. As expected, his head CT is normal. There is an interesting finding on his labs. He has anemia, meaning a low blood count. Nothing dangerously low, to suggest bleeding, but low for a 20-year-old man. Anemia is very, very common, especially in women. We most often see iron deficiency anemia, causing small red blood cells. Our patients red blood cells are macrocytic, or large. Not as common and often associated with alcohol use and vitamin deficiencies. In fact, the patient’s symptoms look a lot like pernicious anemia, a disease caused by a specific vitamin deficiency.
Question #1. What vitamin deficiency causes macrocytic, large, red blood cells and pernicious anemia?
a. Vitamin A
b. Vitamin B12
c. vitamin C
d Vitamin D
Answer: B. B12 deficiency causes macrocytic anemia. Pernicious anemia is a hereditary problem resulting in inability to absorb B12. vitamin A deficiency is extremely rare, causing night vision difficulties, and ultimately blindness. Vitamin C deficiency is scurvy. and vitamin D deficiency leads to osteoporosis.
Can we test for it? We can send a B12 level. I would send one, but it will take days to come back. It might not be helpful, more on this in a minute. His symptoms are classic, so I’d continue down this path.
How do you get B12 deficiency? Pernicious anemia is a hereditary but it’s more often acquired. Vegan diets may result in deficiency from not eating enough B12. Gastrointestinal problems like Cron’s disease or a surgical removal of the bowel can cause malabsorption. Heavy alcohol use results in B12 deficiency. Age is also a risk factor for decreased absorption.
The patient confirms he’s not a vegan, has never had surgery and again denies more than a drink or two per week.
Question #2. What drug of abuse is notorious for causing symptoms of B12 deficiency?
A. mdma or ecstasy
B. Cocaine
C. Fentanyl
D. nitrous oxide, or whippets
The answer: is D nitric oxide sometimes called whippets or more recently know as galaxy gas. Nevermind about calling neurology, at least not for help with the diagnosis.
You ask him if he’s using nitrous oxide. His eyes widen in surprise. After several moments of silence, he nods yes. Reluctantly, he says he’s been inhaling galaxy gas several times per day, saying he’s been very stressed from the demands of school. Inhaling the gas makes him feel more relaxed.
Wait a minute did I hear you say? During the history the patient denied illicit drugs! And now you’re telling me this is due to drug use? Yes, patients very often aren’t forthcoming about substance use, but in this case it’s our mistake. Nitrous oxide is legal and therefore not illicit. So, he told us the truth. In medical school we’re all taught to use extremely specific language. For example, if you ask a patient “What brings you to the ED today?” you’ll often hear my car or the ambulance.
What is nitrous oxide, where do you get it and what does it do?
First, let me clarify a few points to clear up any confusion. A lot of different substances are abused as inhalants. We've talked previously about the largest category, hydrocarbons, found in spray paint and keyboard cleaners, for example. Listen to the Deadly breath equals sudden death episode for more about this type of exposure.
Nitrous oxide is also used by inhalation, but is a different compound, with different toxicity. This drug, is unfortunately, everywhere and easy to come by. It’s legal, and in your local bodega or grocery store.
Question #3. Where do you find it?
A. Whipped cream chargers
B. Olive oil spray
C. Hairspray
D. Spray kitchen cleaners
Answer: A. Whipped cream chargers
Nitrous oxide is the propellant from the whipped cream machine chargers that you might use in your house or see at a restaurant, thus the name whippets. It’s found in small cartridges or larger canisters. Often the gas is put into a balloon, for slower inhalation, like with whippets. IT can be inhaled directly from the canister. Galaxy gas is the brand name of larger canisters, many flavored, which for some reason became popular on social media, leading to newer slang calling nitrous oxide Galaxy Gas.
Users report a calm, relaxed state with feelings of euphoria. They can feel dreamy and detached. It’s been called an “Atmosphere of Heaven”. Unwanted side effects include dizziness nausea and vomiting. Hallucinations are possible.
What’s the toxicity of nitrous oxide? We have to separate acute from chronic exposure. Acutely, there is a risk of overdose and death, but it’s rare. The gas itself has a short half-life and symptoms last only for a few minutes. If a person stays connected to nitrous oxide for more than a few minutes, then oxygen is displaced from the lungs leading to hypoxia and death. This risk is higher when patients intentionally asphyxiate themselves by placing it into a bag over their head.
There are tragic cases associated with driving while intoxicated. A woman killed a teenager in her car after taking nitrous oxide while driving, losing consciousness and crashing the vehicle.
Nitrous oxide is easiest to obtain in these smaller canisters, but it does come in large canisters, like oxygen tanks. Why? Because we use it in medicine, especially dentists. The effects range from mild euphoria and reduced anxiety to complete anesthesia. This difference has to do with the concentration – usually it’s mixed with oxygen with a low concentration of nitrous to prevent hypoxia and death, as well as the length of exposure. At a dental visit, generally the patient stays awake, but is calmer and less anxious. You might see this at a party where people are using whippets. Someone uses the tank to fill up balloons with nitrous oxide which other partygoer’s inhale.
This brings us to another potential issue, frostbite and burns. The tanks and cartridges become extremely cold as the gas is released. Patients can get severe burns and frostbite from holding the cylinders. Oral burns are reported after inhaling directly from cartridges. The burns are often seen in a surprising location, inside the thighs. Why? Because the person filling balloons holds the nitrous tank between their thighs. The burns look mild initially but then develop into more severe ulceration and even gangrene in the days following.
So if you go to the dentist should you say no thanks to nitrous to avoid weakness and paralysis? No. Our patient didn’t develop these severe complications from one use at the dentist, or even inhaling whippets at a party. These effects are due to problems with B12 caused by chronic exposure and very frequent exposure to the gas over weeks and usually months.
It's chronic exposure with frequent use that causes the real problems. Interestingly enough, we don't know exactly how nitrous oxide works. Not the mechanism of its anesthetic effects or the mechanism of chronic toxicity. It's believed that nitrous oxide interferes with an enzyme called methionine synthase, resulting in B12 inactivation in the body and symptoms of B12 deficiency. Like B12 deficiency, chronic nitrous abuse causes subacute combined degeneration in the spinal cord. Our patient has the classic symptoms of this including a combined sensory motor problems with numbness and tingling, weakness and ataxia. While I would send the B12 level as I said earlier, some patients do have low levels, but others have normal levels so it’s not always helpful.
The history of nitrous oxide use is really fascinating, including its other name, laughing gas. It was discovered in the 1700s and became extremely popular, not for medical use but for recreational use. In 1799, Humphry Davy a chemist, researching treatments for tuberculosis popularized nitrous oxide after taking it himself, reportedly laughing and screaming and leaping around the laboratory.
He then conducted parties at his house with laughing gas inhaled from a green silk bag, asking users to record their experience. Samuel Coleridge the poet said it was “like returning from a walk in the snow into a warm room”. Davy developed an addiction, using it 3-4x per day and eventually constructing an “air-tight breathing box” in which he nearly died several times. Eventually he stopped, was knighted and had a lauded career.
Wealthy British people continued holding laughing gas parties well into the 1800s. In the United States, nitrous oxide was used in theater performances. Patrons were called to the stage, given laughing gas and then entertained the audience with their ridiculous behavior.
In modern times, nitrous oxide was popular in the 1960s and '70s along with psychedelics, and at raves and dance parties in the 1990s and 2000s. More recently, as I said nitrous oxide brand name galaxy gas is popularized on social media. Abuse is particularly common amongst teenagers and people in their early 20s, partly because it is legal and easy to obtain. It doesn’t show up on drug tests. In fact, it’s difficult to test for, period including postmortem, because it has a very short half-life.
Your resident bursts into the patient’s room with a box under her arm. It clanks loudly as she thrusts it toward you, obviously arriving at the same conclusion you have. The box is filled with twenty or thirty canisters of nitrous oxide intended as chargers for whipped cream machines.
Entering his apartment to walk his dog, she discovered the entire floor covered in empty canisters. Think this is a fictional exaggeration? It isn’t. I’ve had patients with similar apartments. There are reports in the medical literature of patients using as many as 600 canisters per day if you can believe it. How is there even that much time in a day? In addition to the neurological problems our patient has, chronic use can also cause psychiatric changes including mood disturbances and psychotic episodes.
Question #4. How do we treat nitrous oxide toxicity in our patient?
a. Antibiotics
b. Oxygen
c. B12
D. N-acetylcysteine or NAC
The answer: choice C. B12 supplementation.
It does help treat toxicity. The most important thing, of course, is stopping the nitrous exposure and use. Antibiotics won’t help and acetylcysteine is the antidote for acetaminophen toxicity. If you said oxygen and were thinking of acute toxicity, then I’ll give you credit. Certainly, if a patient was hypoxic after an acute exposure, oxygen would be the treatment, but it won’t help our patient. His breathing and oxygen are normal.
If he stops using and takes B12 will he get better? He should, many patients do, though it’s not a guarantee. Some people are paralyzed permanently after severe chronic nitrous oxide use. The dose and route of B12 supplementation is not well studied, but it should be given in high doses orally or as intramuscular injections. Also, methionine supplementation is recommended. If you remember, methionine synthase is the enzyme implicated in toxicity, so extra methionine might also help and there’s little down side to giving it. Given the severity of his symptoms, you’d probably admit him to the hospital, though the symptoms will take time to improve regardless of admission or discharge. Alternatively, he could be referred to a neurologist as an outpatient for ongoing care. This is a fictional case, as are all our cases, to protect the innocent. But it is based on real poisonings.
Because of its recent popularity in the US and Europe. I should say, one study in the UK reported nitrous oxide was the most popular drug after cannabis amongst 16–24-year-olds. Regulations have been passed to try to reduce the risk. For example in New York City, you need to be 21 to purchase nitrous canisters and cylinders. Some countries in Europe have limited the number of canisters purchased at one time, because they might be sold in boxes of 300. Nobody needs that much whipped cream, not even a restaurant.
Remember nitrous oxide N2O is different than nitric oxide NO, a signaling molecule found inside our cells and the target of some drugs like Viagra.
The last question is today's pop culture consult. Which artist has been associated with nitrous oxide use?
A. Drake
B. Lady Gaga
C. The Chemical Brothers
D. Kanye West
Follow the Twitter and Instagram feeds both @pickpoison1 and you’ll see the answer when I post it. Remember, never try anything on this podcast at home or anywhere else.
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While I’m a real doctor this podcast is fictional, meant for entertainment and educational purposes, not medical advice. If you have a medical problem, please see your primary care practitioner. Thank you. Until next time, take care and stay safe.