On this episode of the CMAJ Podcast, Dr. Catherine Varner, deputy editor of CMAJ, sits in for Dr. Blair Bigham and joins Dr. Mojola Omole to explore two articles published in the journal that highlight troubling findings concerning the treatment of opioid use disorder.
They begin with a study that revealed significant gaps in treatment for opioid overdose patients, where only 5.5% received opioid agonist therapy within a week of their hospital visit. This comes five years after the release of guidelines for opioid use disorder management in Canada, which recommended starting opioid agonist therapy, specifically Suboxone, in patients with opioid use disorder. One of the paper’s co-authors, Dr. Jessica Kent-Rice, a PGY5 resident in emergency medicine and toxicology fellow at the University of Toronto, dissects the complexities of treating opioid use disorder in the emergency department and makes a passionate plea for physicians to increase their prescriptions of these life-saving therapies.
Transitioning to the second article, the hosts examine the presence of xylazine, a veterinary sedative, in the illicit opioid supply. Dubbed the "zombie drug" due to its effects on people's skin and prolonged effects during overdose, xylazine is raising alarm bells among emergency physicians. However, the article's co-author, Dr. Peter Wu, an internist and clinical pharmacology and toxicology physician at the University Health Network in Toronto, advocates for a balanced response. He cautions against excessive concern, noting that treatment continues to revolve around providing supportive care.
Join us as we explore medical solutions that address the urgent need to change healthcare. Reach out to us about this or any episode you hear. Or tell us about something you'd like to hear on the leading Canadian medical podcast.
You can find Blair and Mojola on X @BlairBigham and @Drmojolaomole
X (in English): @CMAJ
X (en français): @JAMC
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Instagram: @CMAJ.ca
The CMAJ Podcast is produced by PodCraft Productions
On this episode of the CMAJ Podcast, Dr. Catherine Varner, deputy editor of CMAJ, sits in for Dr. Blair Bigham and joins Dr. Mojola Omole to explore two articles published in the journal that highlight troubling findings concerning the treatment of opioid use disorder.
They begin with a study that revealed significant gaps in treatment for opioid overdose patients, where only 5.5% received opioid agonist therapy within a week of their hospital visit. This comes five years after the release of guidelines for opioid use disorder management in Canada, which recommended starting opioid agonist therapy, specifically Suboxone, in patients with opioid use disorder. One of the paper’s co-authors, Dr. Jessica Kent-Rice, a PGY5 resident in emergency medicine and toxicology fellow at the University of Toronto, dissects the complexities of treating opioid use disorder in the emergency department and makes a passionate plea for physicians to increase their prescriptions of these life-saving therapies.
Transitioning to the second article, the hosts examine the presence of xylazine, a veterinary sedative, in the illicit opioid supply. Dubbed the "zombie drug" due to its effects on people's skin and prolonged effects during overdose, xylazine is raising alarm bells among emergency physicians. However, the article's co-author, Dr. Peter Wu, an internist and clinical pharmacology and toxicology physician at the University Health Network in Toronto, advocates for a balanced response. He cautions against excessive concern, noting that treatment continues to revolve around providing supportive care.
Join us as we explore medical solutions that address the urgent need to change healthcare. Reach out to us about this or any episode you hear. Or tell us about something you'd like to hear on the leading Canadian medical podcast.
You can find Blair and Mojola on X @BlairBigham and @Drmojolaomole
X (in English): @CMAJ
X (en français): @JAMC
Facebook
Instagram: @CMAJ.ca
The CMAJ Podcast is produced by PodCraft Productions
Dr. Catherine Varner:
I'm Catherine Varner, sitting in for Blair Bigham.
Dr. Mojola Omole:
And I'm Mojola Omole, this is the CMAJ Podcast. So, as you noticed or you hear, Blair's not with us today and we have Catherine. Thank you so much for joining us today, Catherine.
Dr. Catherine Varner:
Oh, thanks for having me. I'm one of the deputy editors of CMAJ, and I'm happy to be here although I'm not nearly as witty or as charming as Blair.
Dr. Mojola Omole:
But you're better looking, so that helps me because I get to look at a pretty face for the podcast recording. Today we're going to be looking at two articles recently published in CMAJ. The first one is a retrospective population-based study of hospital encounters for opioid toxicity among patients with opioid use disorder between January of 2013 and March 31st of 2020. And so, they were looking at hospital encounters for toxicity if patients were being dispensed opioid agonist therapy within a week of discharge.
Dr. Catherine Varner:
And our second article is a “Five-things-to-know…” article on xylazine and the illicit opioid supply. Xylazine is a veterinary medicine that is contaminating the illicit opioid drug supply that has also been dubbed a zombie drug for the effects that it has on people's skin. And also, the prolonged effects that it has on people when they are experiencing overdose. It's a very interesting article that I think will be of interest to clinicians who see this patient population.
Dr. Mojola Omole:
So, Catherine, as the assistant deputy editor of the CMAJ, you are involved in picking these articles. What was it about it for you that stood out, or why did you think that this is important for clinicians to know?
Dr. Catherine Varner:
I think first and foremost, given the opioid drug crisis, there was urgency to both of these articles. The research article, it shows us what we are doing in our clinical practice related to opioid agonist therapy and whether or not it's being used. And the findings of this research study really point out how we can care for patients better in the hospital setting.
And on the second article, the toxicologists approached CMAJ, the authors, and they said, "We see this new tranquilizer contaminating the opioid supply, and we think clinicians should be made aware of it.” It's not a new drug in veterinary medicine, but it's certainly not one that we're used to seeing in humans.
Dr. Mojola Omole:
This is fascinating. This is going to be a really great conversation we're going to have with these two authors. Let's get into it. Dr. Jessica Kent-Rice is the coauthor of the first paper we're going to discuss on this episode. It looked at how often opioid agonist therapy was initiated after hospital visits for opioid toxicity.
Dr. Kent-Rice is a PGY5 resident in emergency medicine and is a toxicology fellow at University of Toronto with a research interest in addictions. Jessica, thank you so much for joining us today.
Dr. Jessica Kent-Rice:
Oh, thanks for having me. Really great to meet you.
Dr. Mojola Omole:
So, you work in the emergency department, Catherine also works in the emergency department. The scale of opioid crisis for you is probably very clear, but physicians who don't necessarily work in there or just go in there like me, I come in to see an appendix and then I come out, what can you describe for us the scope of the opioid overdose crisis, and how do we communicate to our other physician colleagues how serious it is?
Dr. Jessica Kent-Rice:
Yeah, so that's a great question. From a scale of how serious the opioid overdose is, in general, we've got lots of data on the seriousness from a death perspective. In 2023, the most, I guess, recently published stats on opioid death was that 22 Canadians are dying every day from opioid overdoses, which is crazy. And what's more crazy is that two years ago it was 12 people per day. So, it's astronomically increased from an already very high and unacceptable level of patients dying from opioid overdoses.
From a specific emergency department lens, I've not had a shift where I haven't encountered someone with an opioid use disorder, with someone coming in either in withdrawal or after having had an opioid overdose. It is extremely common, and certainly, the amount of visits for opioid overdoses in the ED have also increased astronomically. I think I looked at a stat preparing for this talk, and it was 300% since 2016. Again, it's just crazy, yeah.
Dr. Mojola Omole:
Oh, wow. So, in 2018, Canada released this opioid use disorder management guideline. What did it recommend for people to treat them who are presenting to the hospital with opioid-related conditions?
Dr. Jessica Kent-Rice:
The bottom line of that guideline was that in patients with opioid use disorder, it was appropriate and recommended to start opioid agonist therapy. And the bottom line for me as an emergency physician was that in patients with an opioid use disorder, you should be starting Suboxone. So, the take home for me was if I'm seeing patients with an opioid use disorder, they may benefit and should be started on Suboxone.
Dr. Mojola Omole:
So, then you did the study to look at this, and going into the study, what did you expect to see?
Dr. Jessica Kent-Rice:
I think this is a perfect opportunity first, before I go into the study, to thank my amazing coauthors, and specifically the study lead, which was Dr. Tina Hu who was the brains behind the operation. I'm the ED representative on the paper. So, she had the main idea herself along with Dr. Tara Gomes who does a lot of research in this area.
But what we were expecting to see, I think, was knowing that the guidelines had been published.I think we were all hoping that we were going to see a slow but sustained increase in opioid agonist therapy prescriptions over the course of the time period of the study.
Dr. Mojola Omole:
What did you find instead?
Dr. Jessica Kent-Rice:
So, while it showed a small increase in the amount of opioid agonist therapy that is being prescribed, it was a disappointing increase in the amount of opioid agonist therapy that was prescribed. From going from 1.5% to 5.5%, so about a 5% increase over time. And we found that the 2018 guidelines had absolutely no impact on opioid agonist therapy prescribing.
Dr. Mojola Omole:
I guess for me it's interesting because if there is data showing a practice-changing guideline, for us in surgery, depending... I mainly work in breast, it usually gets adopted pretty quickly. And so, because it's, okay, well, now we know margins have to be two millimeters, we don't need more for DCIS. Why is it not being adopted by emergency physicians to prescribing these opioid agonist therapies?
Dr. Jessica Kent-Rice:
It's a great question and definitely multifactorial I would say. Unfortunately, what I think it boils down to, and there's also studies that have shown this. Specifically, there was a 2020 trial that was published in JAMA, and after that, there was a trial published in the Canadian Journal of Emergency Medicine about emergency physician barriers to prescribing Suboxone in the ED.
And I'll speak from that perspective because I can't speak for how and why inpatient hospital physicians or internal medicine physicians don't prescribe this other than what I can see from our data. But from an emergency perspective, which is where I'm most familiar with in the literature, these studies are showing that physicians don't feel comfortable prescribing these medications.
They don't feel knowledgeable to prescribe these medications, and they feel that they're not supported by their institutions to prescribe these medications. So, even though many recognize they're helpful, they feel that there are many barriers preventing them from prescribing the medications.
Dr. Mojola Omole:
So, your data showed that it's not that maybe patients aren't filling out the prescription, that it's actually that prescriptions are not being written for these.
Dr. Jessica Kent-Rice:
Unfortunately, that can't be said from the study design that we chose. While we did the best that we could to try and really target hospital prescriptions and ED prescriptions using the IC/ES database, we're not able to actually see a prescription until it's been filled at a pharmacy. So, that's one of the major limitations of the study is that we can't determine whether or not a prescription was in fact given and the patient just didn't fill it.
Now, there are individual hospital not published studies, abstracts talked about at conferences that have talked a little bit about this. But while that probably has some impact, there's probably a group of patients who don't fill their prescription, we can't speak to how much of a factor that that is. And the bottom line is there are physicians who are stating they're uncomfortable with prescribing these medications. I think we can do a lot to address that, and that's more what this paper comes in and talks about.
Dr. Catherine Varner:
And Jessica, when you say low, how low are you talking in terms of what percentage of patients who have experienced overdose are receiving a prescription for opioid agonist therapy?
Dr. Jessica Kent-Rice:
So, that was the main finding of this paper, which was that of all these patients who were either admitted to the hospital or presented to the emergency department after a non-fatal opioid overdose, only one in 18 people were started on opioid agonist therapy within the week, which is crazy.
Dr. Catherine Varner:
Wow.
Dr. Mojola Omole:
Wow.
Dr. Catherine Varner:
Do you think it's people like you who are not only emergency physicians but are also interested in this area, particularly, are making up that percent?
Dr. Jessica Kent-Rice:
You know what's interesting? While this wasn't a primary outcome of the study, we actually did look at, to the best that we could, who was prescribing the opioid agonist therapy in our study. And what we found was that it was actually more likely to be a middle-aged male physician who'd been practicing medicine for 10 years and had a generalist training background, so not exactly me.
Dr. Mojola Omole:
Interesting. What do you think the supports that emergency physicians need from their hospitals to feel more comfortable in prescribing drugs such as Suboxone?
Dr. Jessica Kent-Rice:
Yeah, so I think a lot of that comes from speculation based on what emergency physicians are saying they need to help them feel more confident and comfortable prescribing these medications. So, they're saying they don't feel knowledgeable to prescribe them. Certainly, in residency training programs, having opportunities to learn about opioid agonist therapy and knowing how to prescribe it, why to prescribe it, and how it works is one piece.
And then once you're actually starting as a staff physician, having opportunities at your hospital to gain continuing medical education credits or what have you to learn more and fill that knowledge gap as a staff. And then that's one piece, that's the knowledge and comfort piece perhaps.
But the other big thing is making sure... And this is more on a hospital or leadership level, trying to make your emergency department or hospital a safe and effective place to prescribe opioid agonist therapy. And what I mean by that is to prescribe... Medications to treat patients who've had an overdose are only one piece of the puzzle. So, when you're prescribing opioid agonist therapy, forget the speculated complications from prescribing that. You are wanting that person to come back in a few days to be linked up with treatment in addition to the opioid agonist therapy.
So, there's two pieces to that. One being that having, whether it's prepopulated order sets at your hospital or take-home options for patients to make it easy that this is your patient, this is the situation, so therefore, this is the dose, and this is when they need to come back. That takes care of the complicated prescribing piece.
But then also having your hospital provide you with the referral networks. Okay, you work at St. Michael's Hospital, so this is the rapid access addiction clinic here at St. Michael's, or here is another local rapid access addictions clinic so that we can provide patients with more options than just the hospital if they don't want to come back. But having those barriers taken away, I think, as is shown, would really increase prescribing.
Dr. Mojola Omole:
Is it complex to prescribe Suboxone?
Dr. Jessica Kent-Rice:
So, before I answer, I would like to preface that as emergency physicians and as all physicians, we do complicated things all the time. And there is some element of prescribing opioid agonist therapy, specifically Suboxone, that requires a little bit more nuance than, say giving a prescription for aspirin. But again, we learn how to do complicated things all the time.
Suboxone is a medication that's shown to reduce death in patients with opioid use disorder by 50%. That is crazy. Aspirin and the prevention of NSTEMIs in patients the numbers aren't even like that. So, bringing it back, we do complicated things all the time. Prescribing Suboxone shouldn't qualify as one of those things.
There are certainly nuances to prescribing Suboxone, and by that, I mean it's one of those medications that based on its pharmacology, it's a partial opioid agonist. So, rather than methadone or slow release or morphine, which is also a thing that we looked at in this study, which are full opioid agonists, there is a risk with Suboxone that you will precipitate opioid withdrawal in patients. And this is the last thing that you or the patient wants to experience.
Now, if there is a prepopulated order set or specific instructions or guidance on how to prescribe so that you avoid that precipitated withdrawal, that's the thing, that would be the key, and that's what people are afraid of. And then there's also... The other thing I'll say is that's a traditional Suboxone induction. There are also things like micro inductions of Suboxone for patients who don't necessarily want to stop using opioids or who aren't in withdrawal but want to go on Suboxone. So, it's all about knowing what tools you have in your toolkit and when to use them, and who to call if you need help.
Dr. Mojola Omole:
The question I was going to actually ask is that we know that using Suboxone decreases the mortality. Is it because it prevents them from using opioids that leads to overdose? Just wanted to make sure I got that clear.
Dr. Jessica Kent-Rice:
Yeah, so how Suboxone prevents death does it in a couple of ways. One, it provides patients with an opioid partial agonist in place of someone who may other be using street drugs like street fentanyl. So, therefore, they have a medication that is prescribed that is not exposed to contaminants, which it sounds like we're getting to with your next interview, like xylazine and dexmedetomidine and all of that, so there's that piece.
Because Suboxone is a opioid partial agonist, it doesn't fully agonize the opioid receptors, which means that it doesn't have as much potentiating effect of the respiratory depression. So, patients who take an opioid overdose, they die because they stop breathing because they've taken too much opioid. Whereas because Suboxone is a partial agonist, you have less of that effect happening. So, it prevents death in that way, I hope that made sense.
The other thing is having a patient, we see this with lots of interventions we do in the emergency department. When you're giving a prescription for patients for things like Clare Atzema's work with prescribing anticoagulation in the ED. If you are given a prescription in the ED, I don't know if patients are taking things more seriously, I don't have the answer for it. They're more likely to stay on that medication, so there's that piece too.
There's the pharmacology behind why Suboxone probably prevents death due to its partial agonist effects. There's probably some... I don't know what the right word is, is it psychosocial aspects that come into play as well? And we also know that, yeah, Suboxone reduces overdoses and deaths. It also keeps patients more engaged in treatments, which probably speaks to that psychosocial piece as well. And we have randomized control trials for that from the ED, so this isn't even just PGY5 opinion.
Dr. Catherine Varner:
Jessica, I'd love some pointers on this on how you make this easier in your practice because it seems easier in your practice than it does in mine. Because often what happens is that the patient will come in an overdose. The period of time that they're being monitored in the emergency department is often quite long, and they're not in a state where they can receive information in the initial assessment by the emergency department provider.
And so, what happens is they get handed over to another emergency department provider who doesn't know them in the way that the initial emergency department provider did, and then the patient is now awake, and they want to go home. They're ready to go home, and sometimes they don't want to wait for the second emergency department provider to come back and talk to them.
Or the ED physician that has been handed over all of the patients in the department and seeing all of the new patients doesn't have the time to come back and talk with them, that critical time to prescribe Suboxone? So, how do you make this easier in the ED setting?
Dr. Jessica Kent-Rice:
Honestly, Catherine, I wish I had a perfect answer for this, and I really don't because those are indeed the challenges of working in the emergency, especially overnight where you may be the only solo coverage emergency physician. I definitely have the benefit, being a resident and planning to work at an academic center, of being able to hold patients overnight and having that nine-to-five addictions medicine service that I know isn't available other places.
So, I get spoiled, because I have that service that I can consult. Over the weekend, it's tough. I try to remind myself that... For example, I've had a patient in AFib, new AFib, and I thought they would really benefit from being on anticoagulation, they met the criteria. I would not let them go home until we'd had that discussion.
And I think maybe reminding ourselves that patients who are coming into the emergency department after having an opioid overdose, in that week and month prior, they're at the highest risk of dying. Not even just having another opioid overdose, they may die, and they may never have an opportunity to speak to another provider again.
So, again, I don't have a great answer for how to manage that workload when you're overnight, you're managing the whole department and this person wants to go home or you may not know it other than just to be mindful of the stats and help however you can, I guess. I don't have a great answer.
Dr. Catherine Varner:
Wow, it's super helpful to hear that there are places that have addictions medicine providers that see patients in the emergency department. That to me is new and a novel concept that maybe a lot of emergency departments should be considering.
Dr. Mojola Omole:
Jessica, you're really passionate about this topic. What's driving that?
Dr. Jessica Kent-Rice:
I mean there's two things really. One is growing up in a smaller Northern Ontario rural place. There's a lot of mental illness and substance that goes often unaddressed due to lack of resources. So, I think growing up in that environment, I was already primed to want to do something about it. I thought at the time pathology might be the way to go about that, and then after working in the pathology field, you realize you're just seeing these cases after cases of people dying.
So, then in medical school, wanting to do something that's more action-oriented and coming in doing emergency medicine. I'm also a toxicology fellow doing some addiction stuff. I'm like, okay, now I'll actually be able to do something about it. And then here I am five years later with this study realizing that I'm not having as big of impact in this as I would like to think that I am. And again, speaking to why I'm passionate about this-
Dr. Catherine Varner:
You're having a huge impact, Jessica.
Dr. Jessica Kent-Rice:
You see these people every day, every shift, and it's just devastating. And to see people suffering, we all go into medicine. We want to help people, and this is something we see every shift. You want to do something about it.
Dr. Mojola Omole:
Great. So, thank you so much for joining us.
Dr. Jessica Kent-Rice:
Oh, thank you, guys.
Dr. Mojola Omole:
Dr. Kent-Rice is a PGY5 resident in emergency medicine, and a toxicology fellow at University of Toronto. Thank you.
Dr. Catherine Varner:
Our second article in CMAJ looked at a contaminant showing up with greater frequency in street drug samples tested across Canada. The practice paper “Xylazine in the illicit opioid supply” describes the effect of the veterinary sedative when it is mixed with fentanyl.
Dr. Peter Wu is the lead author of the article. He is an internist and clinical pharmacology and toxicology physician at University Health Network in Toronto. Peter, thanks for joining us.
Dr. Peter Wu:
Thanks for having me.
Dr. Catherine Varner:
So, we're curious about xylazine. We've heard about it in media articles, it's dubbed the zombie drug. Tell us, what is xylazine?
Dr. Peter Wu:
Xylazine is a primarily centrally acting alpha agonist, which really, by comparison, is similar to drugs like clonidine, which as physicians, we're a lot more familiar with because we have clinical indications for it. It's not exactly the same drug, but just to give some reference, it's helpful to think of it like that.
It is a veterinary medicine. There is no use in humans. There was some original data looking at its potential use for medical conditions in humans such as hypertension but was quickly taken away in terms of looking at its use because of excessive sedation and adverse effects from the medication. So, it's primarily a veterinary medicine sedative, and it's increasingly being found in illicit opioid samples, specifically most often in fentanyl.
Dr. Catherine Varner:
Can you tell us a bit about the effects of xylazine in someone who's used opioids, and how would you recognize it clinically?
Dr. Peter Wu:
Yeah, some of the things to think about with xylazine is if there is an additional sedative mixed with an already known intoxicant that can cause sedation, then some of the things that we would watch for is excessive sedation or an incomplete response to therapies that we know would work for opioids but not for xylazine. So, for example, naloxone.
In theory, some of the things to think about would be if patients presenting with a suspected opioid overdose have excessive sedation than one might expect with an opioid-only presentation, particularly after treatment with naloxone. If some of the CNS sedation persists despite respiratory reversal with naloxone, that's clues to think that perhaps there is something else going on, and that something else may be xylazine.
Other clues are really related to the other clinical features that have been associated with xylazine, particularly the necrotic wounds that have been seen. So, a patient presenting with those wounds, particularly if they are distant or not necessarily from injection sites, or not necessarily the typical wounds we see with injections, that would be another clue to suspect xylazine.
The final clinical scenario that may become more prevalent, which admittedly is still up for debate, and this is part of the emerging discussion with xylazine is withdrawal symptoms, and how that may be a little bit different than what we might expect with opioid syndromes.
And so, in general, when we manage patients with opioid intoxications, we're always very mindful of judicious and appropriate balanced doses of naloxone not to precipitate withdrawal. And of course, there are priorities in their management in terms of their airway and then their CNS effects. And then after those acute phases are over, is watching for withdrawal symptoms.
And when managing opioid withdrawal, there's obviously a little bit more experience in general, and practitioners do feel a bit more... It's still very difficult to manage, but in general, we do have other therapies that are opioid agonists that can help with withdrawal. And if it's particularly bad, we will reach for adjunct agents, which may include benzodiazepines or even clonidine.
So, the scenario then that might be different with xylazine, particularly if someone has been exposed to it chronically, is what if their withdrawal symptoms are primarily from the xylazine and less so from the opioids. Then similarly, in theory, then the typical treatments, for example, opioid agonist therapies that we would use for opioid withdrawal wouldn't be effective for xylazine.
And so, sometimes you may find that treating withdrawal symptoms may be refractory. That's still admittedly something that we're still teasing out and trying to understand how different this is in clinical practice.
Dr. Catherine Varner:
So, Peter, you just unloaded a lot of information there about xylazine, and I think, from my perspective at the bedside treating a patient with an opioid overdose, I want to know what do I need to know about this veterinary medicine right now when this patient is particularly sedated? More sedated than normal after giving naloxone, and potentially not responsive to naloxone? So, what should be going through my mind as an emergency physician about this drug that we're relatively unfamiliar with?
Dr. Peter Wu:
Yeah, I think that in the situation where your clinical impression is discordant with the expected results of therapy, so for example, if you're managing someone with a suspected opioid overdose, and they're either not responding to naloxone or only partially responding to naloxone, then what I would say for emergency physicians is that your thinking should be what it probably is anyways, and that's to expand your differential to see if you're missing something.
And that could obviously include non-toxic ideologies for their diagnosis, and I think providers do that anyways. But I think specific to xylazine, it may be worth having that as part of the differential to wonder if part of what is contributing to the clinical symptoms is due to xylazine.
And it's hard because some of these things that we say, for example, excess sedation is a rather subjective term. There's no scale to say this is 20% sedation versus 80%. And so, it really would come down to, as you mentioned, the clinical response to therapies. And so, if you encounter a situation where the naloxone is not working or is only working to an extent you think, well number one I think is have we given sufficient naloxone?
And as we know, now we titrate our doses and we get to a certain point where we're quite certain that we've addressed the opioid component. And then if there are persistent symptoms, then I think what should be going through one's head from a toxicology standpoint is, is there anything else contributing to the sedation?
And it may be xylazine, it may be other substances. It may be alcohol, it may be benzodiazepines, but what I would say is that the same way you would likely manage concomitant sedatives that you're more familiar with like benzodiazepines or concomitant ethanol use, in many ways the treatment is the same for xylazine. In that you wouldn't be reaching for specific antidotes, you might not even have antidotes, but you would simply be managing them with meticulous supportive care and being very mindful of their airways and protecting all of that and giving them time.
And I guess the biggest message is it's not that we want people to dismiss xylazine and not care about it, but we do simply want to help reassure that in many ways, the treatment of its effects are going to be what you're doing already, and not to feel like you're missing something.
And that was really a big part of why we wanted to get this paper out there, because it's a bit counterintuitive, but I guess the absence of very clear documentation may open the door to uncertainty and may distract providers that if they hear about a drug, they may start to get a little bit anxious in the clinical environment and start thinking that they're missing something. That they need to be looking for an antidote. Got to be rushing to the poison center to ask them for something when in fact, actually, no, you're doing all the right things anyway.
And it does give some reassurance to clinicians to say, no, that supportive care really is the right thing. Focusing on the opioid component with naloxone is still the right thing. And it seems a bit weird to say, but even if there's nothing else you need to do, that's still, I believe, really important to clinicians to have that certainty.
Dr. Catherine Varner:
So, we've heard a lot about xylazine in the media being implicated in clusters of overdoses. And so, do you think that the inclusion of xylazine as a substitute or a contaminant in the fentanyl supply, do you think it's making it more dangerous, the drug supply?
Dr. Peter Wu:
So, I think it's a hard question because the big challenge with that is none of this is regulated. We have no idea how much of this is substituted, is it a lot? We have no idea what the strength of the xylazine is. We have no idea what else is in there other than what we test for.
I think it's tempting at first to say that this is making everything more dangerous. That would be the gut reaction to this, but some of the data has not really shown necessarily that there is increased mortalities, but again, this data can often be skewed in that they're selecting for less severe cases.
There is a lot of nuanced discussion going on in the med tox community around this very question in the sense of is it truly more dangerous or are we causing concern for no reason. And I think that the answer has to be balanced. I think it's not responsible for us to simply dismiss the presence of a new compound, especially when we don't know if the next batch is going to be greater concentration, or we have no idea. We can't control for that, and so we can't assume that everything will remain the same, and so that the exposure risk is going to be the same.
Dr. Mojola Omole:
Do we know why they're adding it to the fentanyl? Does it have an addictive property? What's the rationale?
Dr. Peter Wu:
I think that's similar to other substances that are cut into illicit supplies like levamisole in cocaine or xylazine with fentanyl. It's hard to know, because we're not the actual suppliers, but I think part of it may relate to additional addictive properties. Some of it may relate to the overall cost. It may be cheaper to get xylazine as opposed to fentanyl or cocaine or whatever it is that they're trying to sell, and it's just diluting down their product. And that's often, as far as I understand, the reasons behind substances being cut into illicit drugs is usually for either cost purposes or potentially more addictive properties.
And so, I think the question about is it making it more dangerous? I get that it's unsatisfying, but it's hard to say a very clear answer. I think some of the other nuanced considerations, and again, this is largely theory but has been posed by some toxicologists that if you had a certain amount of fentanyl that if it was all completely fentanyl, we have a handle on how dangerous that could be. If 20% of it is now occupied by xylazine, does that make it more dangerous or less dangerous? Because you've actually taken away some of the fentanyl and replaced it with another substance.
But the counterargument to that is, is there a synergistic effect between two classes of medications? And so, I think it's largely a debate, and I think that's why people struggle to say with certainty that yes, this is making people die more or this is making people go to the ICU more because truthfully, we haven't seen that.
Dr. Mojola Omole:
So, overall, how concerned should we be that it's included in the illicit drug supply?
Dr. Peter Wu:
I think that right now the concern should be balanced. It should be medium. I don't think that people should be overreacting to this. I think it's a bit of a counterintuitive way to think about something, but I don't think this is headline-grabbing, appropriately so. I wouldn't want people to be overly alarmist about something that we're still learning what the clinical significance is.
And I think that's important both ways. I think it would be important not to over-call and cause over-anxiety to patients and the public. That doesn't mean that these aren't harmful substances. Of course, they are that's why we care about them. And I also don't think that it's helpful to over-alarm clinicians and making them think that they're dealing with a new and unparalleled substance.
I think what's more important is to ensure that clinicians are aware that it is contaminating the opioid supply to know what the potential symptoms could be, but ultimately, and most importantly, to recognize that at the end of the day, you know how to manage sedatives, and this is one of them. And that the priority is still, and this is actually equally important, is the opioid intoxicant principles.
Because that would be the worst-case scenario. We have a known lifesaving reversal agent for opioids, but to have delays in that administration because we've become distracted with something that ultimately is like, "Well, no, focus on the opioids. If there are persistent symptoms, it may be related to xylazine, it may be related to something else. It may be related to another non-toxic entity, but at the end of the day, the opioids first, we know how to treat that, focus on that. You're not missing anything, there's no other magic pill out there, and good supportive care is going to help you out 99% of the time.
Dr. Catherine Varner:
That's good to hear that we should just continue good supportive care, in the same way that we would normally in the setting of an opioid overdose. Thanks, Peter.
Dr. Peter Wu:
You're welcome.
Dr. Mojola Omole:
So, Catherine, as an emergency physician, what's your key takeaway from our discussions with both Dr. Kent-Rice and Dr. Wu?
Dr. Catherine Varner:
So, I think what comes to my mind is how important that discussion is at the end of a patient's stay in your emergency department, and how critical those conversations can be. Particularly, as they relate to opioid agonist therapy and having a conversation about a patient's interest in starting opioid agonist therapy, and then continuing opioid agonist therapy.
So often those are rushed conversations, but those are critical, and I think they are an opportunity to save a life. We so easily go back to the bedside of a patient who's had anaphylaxis, for instance, and make sure that they have an epinephrine prescription and a follow-up with their family doctor and allergist. I think we should think about an opioid overdose in the same way. And so, these articles make me realize that those conversations are just critical.
And the same takeaway about xylazine. Having a conversation with patients about the importance of naloxone, having naloxone with them. And also, not using alone such that they're not in a situation where they're so sedated that someone needs to call for help on their behalf.
Dr. Mojola Omole:
That's great. From listening to both discussions and your experience also as an emergency physician, what really stood out for me is that part of it is that I don't think our healthcare system in the emergency department is not designed to manage drug dependencies. Because we're just there to put out fires, take them to here, move them to here. And oftentimes, these are longer conversations, longer in-ED stays. And part of the problem is that we just don't create the space for that.
And then also I do also wonder if in all of us, there's a bit of a bias of not looking at opiate dependencies as a form of a medical disorder because we still view it as an addiction. Which an addiction is– this is you deciding to do something, versus you have hypertension, which is the same as you have a drug dependency. So, I do wonder if part of our approach to it is because we don't treat it the same way we would treat someone who comes in metabolic acidosis.
Dr. Catherine Varner:
Yeah, I think many light bulbs came on for me as an emergency department provider about how I can do a better job in my practice about caring for patients following an overdose. I think it should be a wake-up call for all of us.
Dr. Mojola Omole:
So, that's it for this episode of the CMAJ Podcast. If you like what you heard, please give us a five-star rating wherever you get podcasts. If six stars is available, please do that too. Share with your networks and leave a comment. This podcast is produced for CMAJ by PodCraft Productions. Thank you so much for listening and thank you so much for being with us today, Catherine.
Dr. Catherine Varner:
Thanks for letting me stand in for Blair. He'll be back on the next episode.
Dr. Mojola Omole:
It's been great. I'm Mojola Omole.
Dr. Catherine Varner:
And I'm Catherine Varner.
Dr. Mojola Omole:
Until next time, be well.