The Grim Reaper
Want to know what drug has caused the same number of American deaths as World War I? Want to know how to treat an overdose? Want to know what new adulterant in this drug is causing horrific non-healing wounds? Then stay tuned!
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 patients survive this podcast? It’s up to you and the choices you make. Our episode today is called the Grim Reaper. Want to know what drug has caused the same number of American deaths as World War I? Want to know how to treat an overdose? Want to know what new adulterant in this drug is causing horrific non-healing wounds? Then stay tuned!
Today’s episode starts on a sidewalk in Philadelphia. You’re walking down the street to meet a friend for dinner when you notice a man lying unmoving on the sidewalk. There’s a woman next to him leaning up against the steps to a brownstone. She’s awake, though she’s bent over at the waist and looks unstable, like she might fall over.
As you get closer, the woman drops to her knees and fumbles with her shopping bags. You can see her arms are covered in open wounds, some red and festering, others with a black eschar on top. Sort of black scabs. Two steps away, you stop to determine what to do. Should you should take a wide berth around this situation? Or stop to help? The woman shakes the man. He doesn’t respond.
This doesn’t look like a situation you should ignore. You squat down next to the man. The woman rummages again in her shopping bags. The man’s eyes are closed, he’s unconscious. You wait for the rise and fall of his chest. It barely moves, meaning he’s not breathing. He’s wearing a tank top, exposing the gruesome wounds on his arms. So, what you do here one the sidewalk in the middle of Philadelphia?
The first step, dial 911 to get some help. As you hang up the phone the woman finds what she was searching for. She manages to pull a white box out of her bag, fumbling it, dropping it to the ground. It reads Narcan (naloxone) nasal spray. By the time you glance down at the box and look back up, the woman slumps to one side, lethargic. She’s still breathing and not unconscious, but clearly high on something, and in no condition to help her friend.
Question number one in today’s interactive podcast. Give the unconscious man naloxone (brand-name Narcan)?
A. Yes, we have to do something.
B. No. We have no idea what’s happened to this guy.
Answer A. Give naloxone.
If you listened to episode five, then you know naloxone is the antidote for opioid overdoses. You also know it’s safe and effective. So much so, that the FDA just approved it for over-the-counter use. In addition, hospitals across the country prescribe it or give it out for free whenever possible, to patients suffering an opioid overdose or who have a substance use disorder.
So, it’s definitely not surprising in this day and age that a woman who almost certainly has a substance use disorder would also have the antidote. As always, when deciding about an intervention, we have to weight the risks against the benefits. Naloxone in and of itself essentially has no side effects. If you give it to someone who hasn’t had a drug overdose, nothing will happen, and no side effects are expected. The main risk in administering it is the risk of opioid withdrawal. Opioid withdrawal is not life-threatening. In contrast to alcohol and benzodiazepine withdrawal.
That said, we don’t give naloxone indiscriminately to every patient who presents to the emergency department with an altered mental status. In fact, guidelines based on research, recommend giving it only to patients whose respiratory rate is less than eight (in combination with a depressed mental status.) Why is this?
First a quick reminder about the opioid toxidrome. If you listened to episode 5, consider this a pop quiz. What is the classic triad of symptoms associated with opioid overdose? First, altered mental status, second, a depressed respiratory status, and third small pupils. A person who is unconscious but breathing normally, is unlikely to have overdosed on opioids. Thus, the recommendation to use naloxone only for patients specifically exhibiting slow and depressed breathing. Essentially you can’t have one without the other in a significant opioid overdose and if you don’t, naloxone probably won’t help.
The other risk of naloxone is causing withdrawal without waking the patient up. Picture this scenario. You have a patient who takes opioids every day, say for chronic pain. One day, they become suicidal and decide to overdose, not on opioids, but on something else. Benzodiazepines, Xanax, klonipin, valium, for example. If you give naloxone, you will put them into opioid withdrawal.
More on this in a second, first question number two. What are the symptoms of opioid withdrawal?
A. Vomiting and diarrhea
B. Yawning
C. Gooseflesh (piloerection)
D. Tearing (lacrimation)
E. All of the above
Answer: E. all of the above.
If you give naloxone to a patient who is a habitual user you can cause vomiting. If however, their altered mental status is from taking a benzodiazepine overdose, now you have a vomiting and a, still, unconscious person. You’ve accidentally caused more harm than good. They may aspirate the vomit into their lungs which is not good for their breathing. This is the reason, patients who benefited from naloxone, in the study I referenced above, were those with both a depressed mental status AND a low respiratory rate of less than 8 breaths per minute.
Back to our man on the sidewalk. His chest is barely moving, indicating impaired breathing and low respiratory rate. No need to stop and officially count for a whole minute to see if it’s less than 8.
You rip open the box and pull out the naloxone nasal spray. It has a nasal applicator like you might’ve seen on nasal steroids like Flonase or nasal medicines like Afrin. You stick it up his nose and press the button to administer the antidote.
While we wait to see if it works, let’s talk about drug contamination and adulteration. In the emergency department we used to treat heroin overdoses, and we used fentanyl to treat patients with pain. Patients say with broken bones, gunshot wounds or significant injuries after motor vehicle crashes.
Unfortunately, fentanyl has changed from a drug used by ER doctors, to a drug whose overdoses are treated by ER doctors. The pharmaceutical made its way into the illicit drug supply beginning in the late 1970s. In the 1990s and 2000s when I was a resident, we’d see a dramatic increase in heroin overdoses and deaths every summer. This was, in fact, due to fentanyl adulteration.
Now people are misusing fentanyl and fentanyl itself is adulterated with other compounds. Mortality rates from drug overdoses are soaring in the US and throughout the world, thanks to fentanyl. The reason I titled this episode the Grim Reaper is because of the following, terrible fact. I’m an ER doctor and a toxicologist, I take care of patients with overdoses regularly, and even I was shocked by this statistic. In 2001, about 20,000 Americans died from overdoses. Ten years later, in 2022, the number of deaths was greater than 100,000.
Question number 3. Which opioid kills the most Americans?
A. Oxycontin
B. Heroin
C. Fentanyl
You guessed it. The answer is C. Fentanyl
Seventy percent of drug overdose deaths, about 70,000 deaths, are caused by synthetic opioids. Pretty much meaning fentanyl. Almost 300 people per day die of fentanyl overdoses in the US alone. These numbers are horrifying. For comparison, 116,000 Americans died in World War I, during the whole war. Another comparison, about 400,000 Americans died in World War II. If overdose numbers continue on this trajectory, and there’s no evidence they’re declining, from 2020-2024 we could potentially see the same number of American deaths as we did from an entire massive world war. Insert brain exploding emoji here.
Fentanyl was created in a Belgian lab in 1959 by Paul Janssen. This is the reason toxicologists talk about opioids, not opiates. Opiate refers only to naturally occurring compounds like heroin, morphine, and codeine. Opioids includes the naturally occurring plus synthetic compounds.
Janssen’s goal was to create narcotics with a higher potency, faster onset, and lower side effect profile than morphine. Fentanyl met those criteria. It’s an important drug, and one I frequently use in the emergency department. It’s 50 to 100 times more potent than morphine. It’s fat-soluble, meaning it can cross the blood-brain barrier into the central nervous system quickly. To give an example of its potency, if I’m giving morphine, a standard dose is given in mg. A standard dose of fentanyl is given in micrograms, a dose one thousand times lower.
Fentanyl comes in many different formulations. All forms can and have been abused. The IV form is used in ERs and the operating room for acute pain. The initial stereotype of fentanyl abuse was the doctor found unconscious in the hospital bathroom with a needle still in their arm.
Fentanyl patches are used to treat chronic pain, in cancer patients, for example. People abuse the patches which contain a large volume of fentanyl, even after use. Children and pets have died after ingesting patches thrown in the trash after being worn for the standard three days. As much as 80% of fentanyl may remain inside after use. The original patch formulation contained a liquid formulation. This was easily misused, by withdrawing or drinking the liquid. The formulation was changed in an attempt to reduce abuse, with the fentanyl suspended in gel matrix. But this form has been abused also, chewed like gum called “chicklets” or boiled down and injected intravenously.
Fentanyl in pharmaceutical forms also comes in dissolving tablets, nasal sprays, and oral sprays. Surprisingly, it comes in lollipop form. Berry flavored.
I’ve always wondered why anyone would need a fentanyl lollipop, especially for a potent drug with abuse potential. While doing research for this episode, I came across an interesting anecdote in the medical literature about lollipop use in the military. According to one paper, the lollipop is placed inside the mouth and taped to the injured patient’s finger. Once the patient has gotten enough medicine to make them fall asleep, theoretically, their hand will relax, pulling the lollipop out of their mouth. While I’m very doubtful this is a safe or reliable method, in a low resource setting it’s an interesting way for patient to potentially titrate their own dose without being conscious.
Fentanyl’s gone from a sporadic ingredient in heroin, to being everywhere and in everything. It’s found counterfeit pills, fake Vicodins or Percocets. It’s in ecstasy or molly, cocaine, methamphetamine, and in counterfeit Xanax and Adderall pills. Now, fentanyl is often only ingredient in powders and pills. Illicit fentanyl is even put onto blotter paper, like LSD, and into eye drops and nasal sprays.
Essentially, no illicit drugs are safe from fentanyl adulteration and there’s is no way for users to know what they are getting. Fentanyl test strips exist and help in harm reduction. If the test is positive, fentanyl is present. However, a negative result can’t guarantee the drug contains no fentanyl. Think of a chocolate chip cookie. If fentanyl is the chips, you could easily test part of a pill or other drug without testing the part containing fentanyl.
Where does illicitly manufactured fentanyl come from? It’s sold on the dark web. Much is imported from manufacturers in China. However, Mexican cartels are increasingly manufacturing the drug themselves and smuggling it into the United States. Why fentanyl rather than heroin or something else?
It’s cheap to produce and as I’ve said, potent. Therefore, cutting it into heroin and pills increases profits and strengthens the opioid effect, making it sought after by users. It’s cheap to make from chemical precursors. Unlike heroin, it doesn’t take a whole field of poppies. No need to rely on the weather or to harvest the crops. Smaller volumes, mean it’s easier to conceal and therefore easier to smuggle.
So, back to the sidewalk and our patient. Up close, you can see suppurating wounds on his arms. One wound is so deep, muscle is exposed. On his other side, he’s missing half of two fingers. He’s barefoot, you can see wounds also on his legs.
All IV drug users are at risk of developing wounds and infections. Needles are often dirty, reused, and unsterilized. Typically, wounds form at the site or sites of injection. Not only are the needles not sterilized, but whatever the patient is injecting is not sterile either. Black tar heroin for example can contain bacteria including botulism. Drugs are far from pure, cut with things like talcum powder, baking soda and laundry detergent. Many substance users are experiencing homelessness, or living in locations where showering and cleanliness are difficult.
Could his wounds be from regular IV drug injection? Yes. But the extent and the severity of the wounds suggest adulteration with another substance. You may have heard about this in the news recently, a drug called Tranq, or Tranq dope. Tranq doesn’t respond to naloxone, because it’s not an opioid.
Question number four. Did we do the wrong thing by giving naloxone if he didn’t overdose on an opioid like heroin or fentanyl?
A. Yes, we did the wrong thing.
B. We did the right thing even if we do suspect Tranq.
Answer B. We did the right thing. If you didn’t administer naloxone, your patient stopped breathing and died.
What’s Tranq? Why do the wounds covering his body suggest exposure? Tranq, short for tranquilizer, is xylazine, a sedative hypnotic drug approved for veterinary use in animals only. It’s also called zombie, though it isn’t the only drug given this nickname. It used to be that fentanyl was the adulterant. Now fentanyl itself is adulterated with xylazine. According to the DEA it was found in 23% fentanyl powder and 7% fentanyl pills seized in 2022.
Where did it come from? What does it do?
It’s used in veterinary medicine as I said. It’s a sedative agent. It’s an alpha agonist, like a high blood pressure drug you may’ve heard of called clonidine. Also similar to an ingredient in eye drops referenced—incorrectly—in the movie the Wedding Crashers. See episode 1 for more on that. Xylazine mostly causes sedation, but can cause also a low blood pressure and a low heart rate. These are the reasons it was never approved for use in humans.
It's use as a drug of abuse was first described in Puerto Rico. It’s called—please excuse my Spanish-- anestestia de caballo (or horse anesthetic). In the US, it was reported in Philadelphia back in 2006. By 2020, 25% of overdose deaths in Philly were associated with xylazine.
As is typical with adulterants, the reason for inclusion is not always clear. Price is a consideration, xylazine is much cheaper than heroin, for example. One kilo of xylazine from China costs between $6-$20.
Users seem to have two opposing opinions. Some seek out Tranq, others wish they could avoid it. Some say it gives “legs” i.e. an increased rush and a longer high. Meaning fentanyl with xylazine is cheaper and longer lasting, requiring injection less frequently. Others fear the prolonged unconsciousness it causes and the associated risks of robbery and rape while unconscious.
For reasons unknown, xylazine seems to cause is terrible, non-healing wounds. It has some local anesthetic and numbing effects, like lidocaine. Because of this effect and to prevent new wounds, users often inject directly into open wounds. There are reports of users injecting even into arms that are necrotic and dying, and into wounds covered in maggots and flies.
Xylazine isn’t an opioid, meaning naloxone won’t reverse it. Why then did we do the right thing in administering naloxone to a man who’s probably taking xylazine? Essentially because it’s rarely alone, and most often mixed with heroin or fentanyl. Therefore, it is recommended to give naloxone in patients with an overdose. Concerning the risk of withdrawal after giving naloxone, we definitely don’t know what else he’s taking, I’d recommend giving enough naloxone for the patient to start breathing. No more, we don’t need to give a massive dose so he fully wakes up. As long as he’s breathing, it’s ok if he’s still sedated.
Xylazine has its own withdrawal syndrome. Users report it complicates stopping use of fentanyl and heroin. There aren’t specific medications to treat xylazine withdrawal. The symptoms are poorly defined, but include irritability, anxiety, and restlessness.
On the sidewalk, our patient starts breathing and opens his eyes, though he’s still sleepy. His companion slumps over unconscious, now not breathing herself. There’s no more naloxone. Luckily EMS arrives to help, giving her a dose as well. Overdoses have become so prevalent in parts of the US, public naloxone boxes are installed on telephone poles and newspaper boxes in an attempt to mitigate harm and save lives.
Both the Moscow Theater Crisis and the modern opioid crisis highlight fentanyl’s potency and its danger. Hopefully, you’ll never experience a gas attack, but given the prevalence of opioids, you may encounter or know someone struggling with an opioid use disorder.
What should you do if someone overdoses? If naloxone is available give it as we did with our patient. I’m thrilled about the approval of naloxone for over-the-counter use. It’s great news for harm reduction in substance users and will, I hope, prevent some deaths.
If you don’t have naloxone, try to keep the person awake. If you can’t, roll them on their side to reduce the risk of choking. If they stop breathing you can do mouth-to-mouth resuscitation or CPR if they lose their pulse.
Question number five. You can become poisoned from contact with fentanyl powder or pills. True or false?
A. True
B. False
Answer: False.
This myth is one of a toxicologist’s pet peeves. You cannot be poisoned by contact with fentanyl in powder or pill form. Let me say that again. You cannot be poisoned by contact with fentanyl in powder or pill form. It’s a myth that’s been falsely perpetuated by the news media.
Wait a minute you might be saying -- we just talked about inhaling fentanyl. The Moscow Theater Crisis is a completely different scenario. The Russians used the drug and its analogues in a specially formulated, aerosolized gas form. Weaponized fentanyl. They spent years developing and testing the gas. The weaponized form requires specialized chemical knowledge and specific preparation in a lab. The important point here, is that regular fentanyl powder can’t aerosolize spontaneously.
First responders, police officers, and other bystanders in contact with powdered or pill forms of fentanyl are NOT at risk for fentanyl toxicity. You may have seen videos of police officers collapsing after discovering fentanyl. While these symptoms are real to those experiencing them, they aren’t consistent with an overdose. In most cases, they are more consistent with anxiety or panic attacks. The American College of Medical Toxicologists released a position statement stating “the risk of clinically significant exposure to emergency responders is extremely low. To date, we have not seen reports … from incidental contact with opioids.”
Our patient in Philadelphia is fictional, as are all our cases, to protect the innocent. But it is based on real poisonings that have occurred, not periodically as is the case with our previous episodes, but daily in the United States.
The last question is also our Pop Culture Consult. Fentanyl is implicated in the deaths of which celebrity or celebrities?
A. Prince
B. Michael K. Williams
C. Tom Petty
D. Coolio
Post your answers on our Twitter poll @pickpoison1. I’ll post the answer in the next 24 hours.
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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.