Adulteration
What to know what drug of abuse is called rhino tranq? What adulterant found in fentanyl is also used as a medicine in the ED and ICU? And can cause life-threatening withdrawal?
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 Adulteration. What to know what drug of abuse is called rhino tranq? What adulterant found in fentanyl is also used as a medicine in the ED and ICU? And can cause life-threatening withdrawal? Listen to find out!
Today's episode starts in the emergency department. You’re walking down the hall to see a patient with fever, when the resident waves you down outside of room three, asking for help. The patient is a thirty-year-old woman with a fentanyl overdose. He’s given her a dose of naloxone. She hasn’t woken up. Also, he notes she has a low heart rate.
In the room, the patient is unresponsive with the following vital signs. Temperature 98.5 or 36.9 Celsius, heart rate 45 bpm, blood pressure 120/80, respiratory rate 7 breaths per minute and oxygen saturation 94% on room air.
You do a quick physical exam. As expected, she has pinpoint pupils. Her breathing is slow, but her breaths seem adequate, not the shallow breathing of a serious opioid overdose. Her heart rate is normal, her skin exam is unremarkable.
The nurse holds up a syringe saying “More naloxone?"
You look at the resident for a response. Instead, he looks at you uncertainly.
“How much did you already give?”
He answers, “0.4 mg IV.”
“Anything change after?” you ask.
“She didn’t wake up, obviously,” he says. “But her pulse ox is better, it was in the 80s. And now she’s breathing which she wasn’t before.”
Question #1. Give another dose of naloxone?
A. Yes
B. No
Answer: A yes. The nurse administers another IV dose. Naloxone is an amazing drug. One of the best things is watching it work right in front of you. Sometimes, A patient goes from blue and near death to awake in seconds.
You watch the woman closely, waiting for a response, but not much happens. On the monitor, her heart rate is 40 and her respiratory rate 10. Her pulse ox is 96%. The nurse draws up another dose of naloxone.
Question #2. Give a third dose?
A. Yes
B. No
Answer: B no. If you gave another dose, uh oh, you just put your patient into withdrawal. And now she’s unconscious, but vomiting. Meaning she’ll choke on the vomit. Not giving this last dose is the difference between management by a toxicologist or experienced ER doctor versus care by those less experienced.
What do I mean and how do I know? On TV if you give naloxone, you jab the patient with a dose and they miraculously wake up, back to normal. Real life is not this easy. There's no single, correct dose. Patients need different doses depending on how much fentanyl they took, their opioid tolerance, etc, none of which we know standing at the beside in the ED. Starting low and titrating up is the best approach.
But she didn’t wake up did I hear you say? True, that brings us to question #3. If you listened to the Grim Reaper episode, you know the answer to this. Which of the following is the best measure to guide naloxone dosing?
A. Respiratory rate
B. Mental status
C. Heart rate
D. Blood pressure
Answer: A. Respiratory rate. We have data showing little benefit, and potential harm, from giving naloxone if the patient’s respiratory rate is above 8. Why are respirations better than mental status? Remember naloxone only reveres opioid overdoses. Tons of things cause a depressed mental status. It’s a huge list, most don’t directly affect your breathing. Also, you can’t have a significant opioid overdose without depressed breathing. So, if your breathing is normal, 8 or above, your altered mental status isn’t from an opioid overdose. Additionally, this helps us avoid the main complication of naloxone administration, precipitating withdrawal. We want to avoid at all costs someone with an altered mental status who is now vomiting, and aspirating, or choking on it.
So back to our patient. Her respiratory rate after the first dose of naloxone was slow, so the second dose was a good idea. Now? If you give another dose, you risk putting her into withdrawal. Time to stop while your ahead, even if she’s not awake.
“What about her heart rate,” the resident asks. Good question. It’s low, but she has a normal blood pressure, and good pulses, so she’s perfusing fine for now. Bradycardia isn’t typical of fentanyl or most opioids with the exception of methadone an opioid used to treat chronic pain and opioid use disorders. Odd, but not especially concerning.
You tell the resident to monitor it for now, along with her respiratory rate to make sure she doesn’t require additional doses of a naloxone. An hour later, he updates you, saying she’s lethargic, but awake and reports taking several doses of fentanyl. Her heart rate is still low, her EKG shows sinus bradycardia, meaning it’s slow, but without heart block or other pathology. She’s not symptomatic and he thinks she can be discharged once she’s more awake.
Wrapping up at the end of your shift, you notice she’s still on the list. The resident hasn’t discharged her despite the fact she’s been in the ED now almost 12 hours. You’re about to question him about it when he rushes into the doctor’s station saying her blood pressure shot up to 200/100 and her heart rate to the 150s. Now, she’s complaining of chest pain.
Well, this is a curveball. Anyone who works in the ED knows these only happen at the end of a shift when you’re trying to wrap things up. You need to finish your notes and you still have to go up to the ICU to check in on a consult from a few days ago.
He’s repeated her EKG, now showing the exact opposite of her prior EKG, sinus tachycardia, a fast rate, but no arrythmia. He sent a troponin; the lab test we use to check for cardiac ischemia or heart attacks.
What the heck is happening? Her current diagnosis is? That’s Question number 4.
A. cocaine overdose.
B. hypertensive emergency.
C. serotonin syndrome
D. Aspirin overdose
The answer is B. This is a hypertensive emergency. Which is a real and dangerous diagnosis, but doesn’t tell us a darn thing about what’s actually happening with our patient. If you said cocaine, it’s a great thought. It does cause hypertension, tachycardia and hypertensive emergencies. But she’s in the Emergency department, did I hear you say? Let me tell you that doesn’t stop patients from substance use. The resident says she’s not sweating which we’d expect with a sympathomimetic toxidrome. The nurse confirms she hasn’t gotten out of bed and can’t reach her belongings. So I like it, but unlikely here. Aspirin doesn’t fit. She doesn’t have a fever, which we’d expect with serotonin syndrome, see the previous episodes for more.
What exactly is a hypertensive emergency? High blood pressure with signs of end organ damage. Meaning the kidneys, brain or heart. Renal failure, stroke or heart attack caused by the high pressure. Yes, this is the diagnosis, but why is she having a hypertensive emergency at all? It’s common in patients with hypertension. Which she doesn’t have. Sometimes patients have undiagnosed hypertension, ie they haven’t seen a doctor for years, and present this way. But her blood pressure was fine when she arrived, so again, not likely.
You have no idea why this is happening, but it’s clear you need to intervene before she gets worse. We don’t know if this chest pain is really a heart attack, or just a warning sign. The treatment? Antihypertensives to lower her blood pressure. There are lots of different options and different protocols.
The resident wants to start with labetalol, a good choice, it’s b-blocker with some alpha blocking properties, and when given IV works quickly. He gives her several doses. It doesn’t help. And, her heart rate stays fast. First of all, this doesn’t fit with hypertensive emergency, second regardless of the cause labetalol should’ve lowered the rate. And remember when she came in she was bradycardic. Why? None of this really makes sense.
The resident wants to try a different drug, esmolol because it can be given as a drip. You agree, tell him to start it and crank it up, while you run to the ICU for a few minutes.
The ICU team is rounding on a patient you consulted on several days ago, admitted after a seizure and intracranial hemorrhage from methamphetamine use. He was intubated in the ED and started on a dexmedetomidine drip, brand name Precedex in the US, for sedation. Currently he’s moving around and agitated. Clearly, they stopped the sedation.
“Planning to extubate him?” you ask the attending. Patients have to be awake and breathing on their own so you can stop the ventilator and pull the breathing tube out. The monitor shows a heart rate of 140 and a blood pressure to 190/95.
“We were,” she says. “Now we have an issue.”
“Another seizure?” you ask. He looks very twitchy, like he’s about to have one.
“No. Dexmedetomidine withdrawal.” She says.
The ICU loves dexmedetomidine because it causes sedation without depressing the respiratory drive. It’s a very interesting drug with a mechanism like clonidine, the blood pressure medicine and tetrahydrozoline, the ingredient in eye drops to reduce redness. It's an alpha two agonist, binding to alpha two receptors in the brain and central nervous system, inhibiting the release of norepinephrine. Less norepi, equals less fight or flight effects, meaning a lower heart rate, lower blood pressure and sedation. It’s therefore easy to guess the side effects of dexmedetomidine, low blood pressure and low heart rate.
Clonidine withdrawal is pretty well known, if stopped abruptly, patients experience tachycardia and hypertension. Same with ICU patients when dexmedetomidine is stopped. In fact, about 35 to 45% of patients experience withdrawal, typically after 4 to 5 days of exposure. The intensivist tells the nurse to restart dexmedetomidine with a plan to taper if off slowly this time.
Back in the ED, the resident hasn’t made any progress with your patient’s blood pressure. Now she’s having nausea and vomiting. He’s given her ondansetron or Zofran and metoclopramide. Those aren’t helping either. Is he a terrible resident? No, he’s doing the right things, this is a difficult case.
Good thing you went to the ICU, because now you have an idea about what’s happening. The patient insists she only took fentanyl. As any listener of this podcast knows, drugs are never pure and contain all sorts of contaminants. Xylazine, or tranq, we talked about before. Fentanyl itself used to be a contaminate in heroin.
The patient was bradycardic when she arrived, now 12 hours later is hypertensive and tachycardic. Could this be withdrawal from an alpha 2 blocker in the fentanyl? Clonidine can be found in opioids, but I have to say I’ve never heard of it causing an issue. And another thing, our patient never had a low blood pressure. Clonidine is an antihypertensive, low blood pressure is what it does best. We’re getting closer, but I don’t think we’re there yet. Either way, we can’t identify fentanyl contaminants at the bedside. If we send blood, or drugs, for analysis it will take weeks for the result.
“Let’s try a dose of clonidine and see what happens.” You suggest.
The resident frowns. “I thought clonidine was contraindicated in hypertensive emergency.”
“Excellent point.” Clonidine can cause transient blood pressure elevation before it lowers the pressure. It’s short, and not usually significant, but not great in a true HTN crisis.
“Also, she can’t take PO,” he says, due to the ongoing vomiting. Clonidine can’t be given IV in the US, it’s only a pill or patch form. The patch will take too long to work and you can’t titrate them.
Now that you are thinking about alpha2 blockers, it’s reminded you of a poster you saw at a conference a few weeks ago from toxicologists in Philadelphia.
It's time to pick your poison. This is a super tough one, so no shame if you guess wrong. Question 5. It’s time to Pick Your Poison. Is the adulterant in our patient’s fentanyl?
A. xylazine.
B. Medetomidine
C. Lidocaine
Answer: B medetomidine.
Lidocaine is a local anesthetic ie numbing medicine. It’s a common adulterant. It doesn't affect heart rate or blood pressure. We discussed xylazine causing an epidemic of horrific wounds. If you want to hear more about it, listen to the Grim Reaper episode.
Now this is where things take an interesting turn. Xylazine is also an alpha two blocker, it definitely causes sedation. It theoretically causes hypotension and bradycardia, but we don’t see much in patients using contaminated fentanyl. Our patient doesn’t have any wounds. This isn’t xylazine. It’s medetomidine, which you guessed it is like the dexmedetomidine or Precedex your ICU patient is getting.
In fact, they have the same chemical structure. What’s the difference? Medetomidine is a racemic mixture of two stereoisomers, dexmedetomidine and levomedetomidine. Stereoisomers are when two compounds have the same chemical structure, but are mirror images of each other. Like your left and your right hand, 5 fingers, same shape, mirror opposites in orientation. Medetomidine is use in veterinary medicine. In humans, levomedetomidine isn’t biologically active, so we only use dexmedetomidine or precedex.
It’s a relatively new adulterant. First seen in fentanyl in Baltimore in 2022, but really described in Philadelphia after outbreaks in 2024. Medetomidine doesn’t cause the horrific wounds xylazine does. Sounds great…. Well. Maybe, maybe not.
First what happens when you take fentanyl adulterated with medetomidine. You guessed it, bradycardia. Just like our patient had when she arrived. Sedation. That’s why her breathing improved with naloxone, but she didn’t wake up. Medetomidine, like xylazine, isn’t reversed with naloxone. And surprisingly it's not associated with hypotension which we'd expect.
Patients taking medetomidine contaminated fentanyl are noted to have heart rates in the 40s, but it’s not a serious problem. In several series of patients, no one passed out or required a pacemaker. The symptoms resolved spontaneously, on average in 3.5 hours. Essentially patients are fine and back to normal after ED observation.
Why wasn’t our patient fine? Because that’s not the end of the story. The second issue seems to be worse than exposure, and that’s withdrawal. A quick word to remember the opioid withdrawal syndrome. Patients feel terrible, jittery and anxious, with body aches and nonstop vomiting and diarrhea. That said, it’s not life-threatening like alcohol or benzodiazepine overdose. Patients receive treatment in outpatient settings. It's extremely rare to admit a patient to the hospital for opioid withdrawal. I’ve only done so once or twice in my entire career and in those cases, for specific and unusual issues.
Medetomidine withdrawal, however, is a whole separate issue, much like dexmedetomidine withdrawal syndrome seen in the ICU. Like alcohol withdrawal, it can be life-threatening.
Why? Like all alpha-2 agonists, withdrawal causes hypertension and tachycardia. Medetomidine withdrawal is causing, not just that, but true hypertensive emergencies with serious complications, like heart attacks, mostly NSTEMIs where the diagnosis is made with an elevated troponin rather than ST elevation on the EKG. PRES syndrome, or posterior reversible encephalopathy syndrome the neurologic sequalae high blood pressure in the brain causing headaches, altered mental status, visual disturbances leading to vison loss and seizures. It’s diagnosed on MRI, and as the name suggests is reversible if treated promptly by lowering the BP.
OK, so as I’ve alluded to true hypertensive emergencies, not just isolated high blood pressure by the way, but true end organ damage requires immediate treatment. Which we’ve thus far failed to do with our patient despite trying several different meds. It’s been an hour. Her troponin result is back. It’s very elevated at 300, so she is having a heart attack, an NSTEMI. You call the intensivist who recommends a trial of dexmedetomidine and says she’ll be down shortly to see the patient and help. She sends the intern to collect extra blood to send to an outside lab for analysis.
You start the medicine and wait. Holding your breath to see if it works. Medetomidine is sometimes called rhino tranq. After the 2024 outbreak in Philly, it’s been found across the US, in Canada and the UK.
In Philadelphia they've been monitoring the situation closely. Prior to 2024, almost all of fentanyl specimens tested contained xylazine. In May 2024, 29% of fentanyl specimens contained medetomidine and six months later it was 87%. Wounds and wound care visits are down thanks to less exposure to xylazine, but patients are requiring hospitalization for medetomidine withdrawal. Xylazine does cause withdrawal, mostly restlessness, jitteriness and agitation. It causes some mild elevation in heart rate and blood pressure, but it serious issues, other than the wounds, are rare. What’s the difference? Likely the potency. Medetomidine is 100 to 200 times more potent than xylazine at alpha two receptors.
So, medetomidine withdrawal is associated with tachycardia, hypertension, tremor, sweating, and for some reason really, really intractable vomiting. Meaning you can’t stop and antiemetics, or anti-nausea agents don’t work. Myoclonus, or twitching, and a waxing and waning mental status. One thing worth noting, is that the withdrawal syndrome can be very abrupt and has a very rapid progression. Onset can occur within just a few hours after stopping. It generally peaks around 18 to 36 hours.
How common is the problem of life-threatening withdrawal? No one knows for sure, some of the numbers published are shocking. In one series 91% of patients required ICU admission and 25% were intubated.
Your resident returns to the doctor’s station, this time with a smile on his face. The dexmedetomidine is working. Her blood pressure is now in the 180s. Her vomiting is improving.
Patients with medetomidine withdrawal require aggressive treatment regimens. For example, clonidine patches and pills at the same time or multiple different alpha 2 agonist together. Olanzapine, an antipsychotic is used for vomiting as patients seem to have a better response than usual medicines. Of course, you need to treat for opioid withdrawal as well. It's bad enough to have withdrawal from one substance imagine having it from two at the same time.
You admit the patient to the ICU. The team titrates up the dexmedetomidine drip up until she improves, then gently tapers it down. She gets aspirin and other meds for the NSTEMI. A cardiac catheterization shows no blocked arteries, meaning it’s all from demand ischemia due to strain on the heart from the high blood pressure. She's treated with buprenorphine for opioid withdrawal. After two days, she is much improved and discharged for outpatient treatment.
This is a fictional case, as are all our cases, to protect the innocent. But it is based on real poisonings. I really wish everyone could see lab analysis of drugs of abuse, or what’s in the blood of patient’s taking them. The amount of things other than the drug itself is astounding, whether you’re talking about MDMA, cocaine and fentanyl or something else. Things like lidocaine and other numbing medicines, caffeine, acetaminophen or paracetamol, phenacetin, an old anti-inflammatory we don't use due to multi organ side effects, lead, veterinary medicines, deworming agents. And that’s just to name a few. When you take unregulated drugs, bottom line, you have no idea what you’re gonna get and what other problems it could cause. We will definitely have more episodes on this in the future. It could be a whole series, frankly.
Last question in today’s podcast. Drug sniffing dogs can become poisoned by fentanyl.
A.True
B. False
Follow the Twitter and Instagram feeds both @pickpoison1 for the answer. 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. Until next time, take care and stay safe.