Deadly Breath = Sudden Death
Do you know what toxin abused by teenagers causes sudden cardiac death? How fear can kill you? Listen to find out!
Will our patient survive this podcast? It’s up to you and the choices you make.
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. Our episode today is called Deadly Breath = Sudden Death.
Do you know what toxin abused by teenagers causes sudden cardiac death? What seemingly benign event can trigger cardiac arrest in a patient without any other symptoms? Then stay tuned!
Today’s episode starts in the emergency department. The ambulance doors bang open and the medics run in with a cardiac arrest in progress. You look down at the small form on the stretcher and your heart drops. Every ER doctor’s worst nightmare, a pediatric code. The thirteen-year-olds frame is so small, her chest is barely visible underneath the hands of the medic doing CPR. Behind the stretcher, a woman is screaming. The patient’s mother.
You transfer the teenager to the ER stretcher while hooking her up to the monitor and defibrillator pads. The medics say they administered a dose of epinephrine enroute. The monitor starts beeping like crazy because her heart rate is in the 200s. It shows an arrhythmia racing across the screen. Ventricular fibrillation. If you listened to prior episodes, you know this is a lethal arrythmia. What’s the next step?
A. Get more history. Talk to the mother about what happened.
B. Do a physical examination
C. Defibrillate her with an electrical shock
D. Give naloxone (Narcan)
The answer C. Defibrillation.
There is no time for history taking at this moment. I’d love a physical exam, and we will do what we can during the code, but there’s no time to stop and wait for either. We need to address the v. fib.
You tell the nurse to charge the defibrillator. Once it’s ready, she says clear. Everyone steps back as the patient’s small body jerks with the electrical shock. The mother continues to scream the child’s name. You have a few seconds of uncertainty about allowing the mother to stay in the room. In general, I believe the family should be in the room during a cardiac arrest, if they want to be present. It might be a relative’s last moments. And they should see the life-saving measures the team is taking to try to revive the patient. In pediatric cases, this is especially true. But it can’t be easy for this woman to see her lifeless teenager getting shocked. The nurse restarts CPR.
You have two minutes until the next decision in the pediatric cardiac arrest algorithm. You ask the medic what happened.
“Found down in the bathroom,” he says. “As Mom walked in, the child collapsed. When we arrived, the patient was in pulseless v. fib.” In other words, a cardiac arrest. “No past medical history,” he continues. “No complaints prior to the collapse.” Meaning she was well until she wasn’t.
What’s happened to this little girl? Ventricular fibrillation is a very dangerous but not uncommon problem in the emergency department. However, we typically see it in older patients with a history of heart disease. Not in otherwise healthy pediatric patients. It can be seen in children born with abnormal hearts, congenital heart disease, but those diagnoses are made in childhood. You’ve probably heard about sudden death occurring in young athletes, due to hypertrophic cardiomyopathy or HOCM. Wolff-Parkison White and congenital long QT syndrome are diseases predisposing patients to arrythmias and can present in the teen years.
This is a toxicology podcast not a pediatric cardiology podcast so let’s jump to the toxicologic causes of ventricular fibrillation. There are a lot of medicines and poisons to consider. Anticholinergics, like diphenhydramine brand name Benadryl can cause it. Antipsychotics and other psychiatric medicines. Cocaine, methamphetamine and other sympathomimetics. Aconitine and digoxin (Episodes 1 and 3 for more). Medicines for autoimmune disease like quinidine and its derivative hydroxychloroquine. Box jellyfish envenomation.
I could give you list of hundreds of medicines and drugs that can potentially cause v. fib. Sometimes our job in the ER and as a toxicologist is to expand the differential diagnosis list to consider as many things as possible. In this case we need to narrow it down.
She certainly didn’t get envenomated by a jellyfish in the bathroom. She might have taken an overdose, maybe on a family member’s medications. Not uncommon in a suicidal teenager. The one factor that really stands out to me in this case is the fact that she was fine until the moment she collapsed. Most of the medicines we listed above, and most toxins on the list causing v. fib, cause other symptoms first. If she took a diphenhydramine overdose, she’d be very sleepy or sedated. Same with most psych meds. If she was using cocaine or meth, she’d have been agitated or jittery.
Mom is finally able to answer a few questions. She says her daughter came home from school, had a snack and was fine. The patient was in the bathroom for a long time. When mom opened the door, the teenager was standing at the sink with a bottle of computer keyboard cleaner, like Dust Off in her hand. She dropped the bottle, then collapsed.
I’d classify this presentation as not just as a v. fib arrest, but as sudden cardiac death like I mentioned earlier. She dropped suddenly without any prodrome of other symptoms. What medicines can cause sudden death? Quinidine and hydroxychloroquine, used for disease like lupus and rheumatoid arthritis, cause what used to be called quinidine syncope, really v. fib. Methadone, an opioid can cause it. These aren’t commonly used drugs, and aren’t easy for a teenager to access. You ask mom if anyone is prescribed these meds at home. She shakes her head; she’s never heard of them.
Your two minutes are up, you pause for rhythm and pulse check. Still no pulse, still in v. fib, so you administer another shock. The nurse holds up a syringe of epinephrine, waiting for you to nod yes to give it. Question 2. Give the epinephrine?
A. Yes
B. No
The answer? I’ll be honest here, I don’t know because neither choice is a good answer. Epi is part of every cardiac arrest algorithm. Our patient is clearly still in cardiac arrest. Why even consider not giving it? Because we’ve just gotten a clue about the potential cause of this v. fib.
In real life, you’d have to decide on the spot. Fortunately, this is fiction. So, let’s talk about the cause first, then come back to this very thorny question. What’s the clue? The answer really? The bottle of computer keyboard cleaner, otherwise known as compressed gas cleaner. I’m sure you’ve seen this stuff, probably used it. It sprays air to get embedded dirt and crumbs out of your keyboard. The patient wasn’t cleaning her computer in the bathroom. She was sniffing or inhaling the gas inside the cannister to get high. This is Sudden Sniffing Death Syndrome.
Let’s take one more step back to first talk about inhalant abuse. Then we’ll come back to how it causes sudden death and how to treat it so we can answer question 2.
Inhalants encompass a wide variety of compounds. They’ve been misused by people around the world from North America, South America to Africa and Asia. The most common age group misusing inhalants are 12–17-year-olds, younger than average compared to other drugs of abuse. There are several reasons for this, likely due in large part to the fact that they are cheaper and easier to access than other illicit drugs. For this reason, inhalant abuse is associated with marginalized and impoverished patients. In many countries, inhalants are associated with homeless, street kids, sadly.
There are two large categories of substances misused via inhalation. Classic inhalants which are hydrocarbons. This is what we are discussing today. The other category are things like nitrous oxide, poppers and whippets. These cause different symptoms, not sudden sniffing death, and I’ll get to their toxicity in a future episode.
Classic inhalants, hydrocarbons, as I said, are abused because of their euphoric and dissociative effects. There are more than a thousand basic household products that can be used as inhalants. Let me give you a few examples. Toluene which is in paint thinners and rubber cement. Butane, lighter fluid, is also found in hairspray and room fresheners. Propane from fuel for gas grills is similarly in hairspray and room fresheners. Fluorocarbons are found in compressed gas keyboard cleaners. Acetone in nail polish remover. Even regular gas, like from your car, can be inhaled.
Hydrocarbons dissolve easily in fat, meaning that they can quickly cross the blood brain barrier, so onset of intoxication is quick, typically within minutes. It doesn’t last long, usually resolving within an hour or two. They cause a number of different effects ranging from euphoria to sedation, dizziness, gait unsteadiness. I could give you a long list of symptoms, or sum it up more succinctly with a comparison to another hydrocarbon intoxication with which we are all familiar. Ethanol, or alcohol is a hydrocarbon. Animal studies show low doses of hydrocarbons cause motor excitation and high doses cause sedation and motor impairment. Very much like alcohol.
That’s what they use. How do they do it? There are different methods with different names. Sniffing is sniffing the fumes directly from the container. Spraying means the inhalant is sprayed directly into the mouth or nose. Bagging is when the fumes are placed inside a bag and then inhaled from there. Huffing is soaking a rag with the compound, then holding the rag up to the face and nose. Dusting is a slang term for computer cleaner abuse. Gladding, referring to air fresheners involves sniffing or spraying directly into the user’s face.
Many effects are life-threatening. First, inhalants cause seizures and comas. Asphyxiation can happen via several methods. First asphyxiation within the lungs, as some inhalants are heavier than oxygen causing oxygen displacement. Not good. Comatose people can lose their airway if for example their head falls forward. Also, people have died after falling asleep with the rag or bag over their face. Accidents due to intoxication are not uncommon, like motor vehicle accidents and falls. Despite the myriad of dangerous side effects from inhalant abuse, shockingly more than one third of users believe inhalant use causes only slight or no risk.
And back to Sudden Sniffing Death Syndrome. One study reported that 22% of first-time users of inhalants suffered from sudden sniffing death. While I doubt it’s really that common, it is an eye-opening statistic. Side note – while the symptoms of inhalant use are similar to alcohol, ingesting alcohol doesn’t lead to sudden sniffing death.
What happed to our little girl is a classic scenario. A person sniffs or huffs, maybe notices some effects, but remains awake and alert. Then an authority figure like a parent, a teacher or police officer, shows up and the patient has a sudden collapse into cardiac arrest. How is this possible and what exactly occurs?
This is a fascinating topic about which I could do an entire hour-long podcast. I have done hour long talks, with slides detailing heart cells, ion channels and electrical impulses. It’s possible you may not be as excited as I am about ion flows and cell voltages. So I’ll sum it up into two main steps.
The first step is myocardial sensitization. The myocardium refers to cells inside the heart and sensitization occurs during or shortly after the time of inhalant exposure. In order for the heart to squeeze and pump normally, an electrical impulse is conducted from the atria, to the top of the ventricles then downward. This allows squeezing in a controlled fashion, to eject blood for circulation to the rest of the body. Depolarization causes the cells to contract, repolarization allows them to rest and reset, to be ready for the next impulse. Inhalants interfere with ion channels, especially potassium channels. This results in cells becoming disorganized, with some ready to conduct an impulse, and others not ready. Myocardial sensitization can be reflected on the EKG by a prolonged QT segment.
This is a problem in and of itself. In the case of sudden sniffing death, a second insult triggers an impulse which is then conducted by the disorganized heart cells. I mentioned a parent, teacher, or police officer. What do they have to do with cardiac conduction? Their presence can cause step number two, catecholamine release. Catecholamines are things like epinephrine, i.e., adrenaline. Adrenaline is released when you’re startled or scared to prepare your body for a flight or fight response. Catecholamines are the catalyst, starting an impulse which is conducted by the
disorganized heart cells. Some are contracting while others are still resting. This disorganization becomes ventricular fibrillation. The heart is fibrillating, rather than squeezing, meaning little or no blood is ejected from the heart. No circulation means no oxygen and no pulse.
Back to our patient. She’s in the bathroom, inhaling keyboard cleaner. The hydrocarbon has sensitized her myocardium, but she and her heart are fine. For the moment, until the door opens, she’s terrified at being caught, and her body releases epinephrine. This jumpstarts ventricular fibrillation, leading to her sudden cardiac arrest.
Bringing us back to the nurse holding the vial of epinephrine and question 2. We just said her cardiac arrest was caused in part by epinephrine. Do you really want to give more?
On the one hand, epi is a part of every cardiac arrest algorithm and this patient is clearly in cardiac arrest. If you don’t give it, you could be faulted for not adhering to basic guidelines, both ethically and legally. Do you want to withhold standard treatment from a pediatric patient in cardiac arrest?
On the other hand, this is sudden sniffing death and catecholamines, specifically, epinephrine triggered this problem. Do you want to give more?? There are no guidelines for sudden sniffing death, no studies directing our treatment options. The general expert consensus is to try to avoid catecholamines if possible. Which doesn’t help us answer question 2 at all.
What would I do? I’d hedge my bets, hold on epi for a few minutes and try some other medicines instead. I’d continue the electrical shocks. I’d give amiodarone, an anti-dysrhythmic we routinely use for v. fib. I’d try a beta-blocker, specifically esmolol. Beta-blockers are antihypertensives like metoprolol, which you may have heard of. They aren’t given in cardiac arrest as they reduce the ejection fraction, how much the heart squeezes. But beta-blockers are in many ways the opposite of catecholamines, working to slow the heart rate and lower the blood pressure. Esmolol is an IV preparation that’s easy to titrate.
Our patient receives several more rounds of electrical shocks. We give amiodarone and crank up the esmolol. To your huge relief, the v. fib stops and she gets a pulse back. We’ve achieved ROSC, the outcome you want in every pediatric cardiac arrest, in every single arrest, the return of spontaneous circulation.
Now that she’s stabilized, we can do a through physical exam, as well as additional work up like labs and a chest x-ray. The labs are to check her calcium and potassium. The xray to check for pneumonitis, lung inflammation due to hydrocarbon exposure.
There aren’t many physical exam findings associated with inhalants. I once had a patient in the emergency department whose beard was colored silver. Not silver like the hair color but silver like the paint color. He was huffing paint from the paper bag with resulting deposition in his beard. Interestingly, metallic paints are preferred by inhalant abusers. I believe this is because the heavier metal pigments require more hydrocarbon propellants in the spray paint canister.
You might see irritation around the nose and mouth, called perioral eczema. You can also see cracked dry lips and skin, called defatting dermatitis. Hydrocarbons can dissolve or breakdown normal subcutaneous fat.
Another physical exam finding is muscle weakness. It can be so severe, it may result even in paralysis. So far, we’ve discussed hydrocarbon inhalants as a category with similar effects. Specific compounds can have specific side effects, so let me highlight some of them now.
Muscle weakness is not a side effect of all inhalants, but specifically related to toluene exposure. Toluene is one of the most commonly abused especially outside the US, because it’s cheap and ubiquitous. It causes profound muscle weakness by causing dangerously low potassium levels. Muscles need potassium to contract and if the potassium is too low, they are unable to do so. This is typically seen in chronic users as it takes some time for the levels to drop. Toluene has several other specific effects. It can cause severe acidosis and renal failure.
Methylene chloride, found in paint stripper, can cause carbon monoxide poisoning. This is a fascinating compound because it’s metabolized in the liver to CO. Meaning the person gets carbon monoxide poisoning from the inside out, several hours later.
Butane in lighter fluid and propane can cause freezing burns with prolonged exposure. It’s not likely in an awake person, but a person who’s intoxicated and or falls asleep with a rag on their face dan develop serious burns.
What about our patient? Is she at risk for these complications? No. Computer cleaners usually contain difluroethane. It does have a few unique and extremely rare side effects. Fluoride binds calcium, and in a few cases death resulted from low calcium levels. Bone deformities occur from too much fluoride exposure. Both require long-term use.
Inhalant use in pregnancy causes miscarriages and something called the fetal solvent syndrome, similar to fetal alcohol syndrome.
Which brings us to long-term, irreversible consequences in chronic users. Neurocognitive sequelae cause dementia, psychiatric disease, memory loss, and hallucinations. Patients can have changes in speech and gait, as well as loss of hearing and smell.
Toluene leukoencephalopathy is one of the better described diseases. Toluene causes degeneration of white matter in the brain. It causes parts of the brain to atrophy and shrink. It thins the corpus callosum, the area responsible for communication between the right and left hemispheres. And it essentially dissolves the protective myelin sheath covering nerve cells.
I mentioned earlier that adolescents misuse inhalants because they are cheap and easy to obtain. In addition, some interesting studies have shown adolescent brains may be more susceptible to their effects. Inhalants, like other drugs of abuse, including cocaine and opioids, cause a reward and reinforcement feedback loop using dopamine. Same as all addictive behaviors. But interestingly with inhalants, the reward pathway varies with age of exposure and seems to be stronger in adolescents. Also, the adolescent brain seems to be at increased risk for dementia and neurocognitive changes.
Some manufactures taken steps to reduce misuse of their products. In the Philippines, “Rugby boys” is a term referring to homeless children who abuse toluene containing rubber cement sold under the brand name Rugby. The manufacturer changed the formulation from toluene to xylene in the hopes that it would be less toxic. In addition, added a bittering agent, in this case mustard oil, as a deterrent.
Question 3. There’s a test to confirm our patient was using inhalants. True or false?
A. True
B. False
The answer. False.
As with so much in toxicology, there’s no clinically useful test for this group of compounds. While some tests exist, they are run only in specialty labs and not widely available.
Inhalant misuse has a long and interesting history, beginning with laughing gas parties in UK in the 1800s to modern times. Inhalants are referenced in both music and movies. Today’s pop culture consult is about the death of singer and actor Aaron Carter. He had some pop hits in the 90s and was the younger brother of one of the Backstreet Boys. His death in 2022, after drowning in a bathtub, was ruled an accident by the medical examiner. Xanax, a benzodiazepine and difluroethane were found in his body.
Our patient survives the cardiac arrest and Sudden Sniffing Death Syndrome. She wakes up in the ICU and is fine, with no sign of brain damage. Surviving sudden cardiac death is very rare, the odds are always against the patient, regardless of the cause. This is a fictional case, as are all our cases, to protect the innocent. But it is based on real poisonings and a rare few have survived sudden sniffing death.
This brings us to question 4, the last in this episode. Which of the following musicians sang about inhalant abuse?
A. Elton John
B. The beastie boys
C. Nirvana
D. The Ramones
E. All of the above.
Post your answers on our Twitter feed @pickpoison1. I’ll post the answer in the next 24 hours. Remember, never try anything on this podcast at home or anywhere else.
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