Dr. Maggie Lowenstein

Hey, before we get to the show, I wanted to remind you to check out our patreon@patreon.com curbsiders if you haven't signed up yet, sign up now to get ad free episodes, twice monthly, bonus episodes and a whole bunch of other cool stuff@patreon.com Curbsiders. The Curbsiders podcast is for entertainment, education

Dr. Carolyn Chan

and information purposes only and the topics discussed should not be used solely to

Sponsor/Advertisement Voice

diagnose, treat, cure or prevent any diseases or conditions. Furthermore, the views and statements expressed on this podcast are solely those of the

Dr. Carolyn Chan

host and should not be interpreted to

Sponsor/Advertisement Voice

reflect official policy or position of any

Dr. Carolyn Chan

entity aside from possibly cash like moral, hospital and affiliate outreach programs, if indeed there are any.

Dr. Maggie Lowenstein

In fact, there are none. Pretty much we aren't responsible if you screw up. You should always do your own homework and let us know when we're working.

Dr. Carolyn Chan

Sean, it's so good to see you.

Dr. Sean Cohen

It's good to see you too. Feels like it's been so long and I can't believe we someone has agreed to let us come back.

Dr. Carolyn Chan

I know. On that note, welcome back. This is actually going to be an episode from season five of the Curbsiders Addiction Medicine, our miniseries on substance use disorders. So we are actually going to give Paul and Matt a break this week from the Curbsiders Internal Medicine Podcast to really chat about how to care for patients with addiction. So I'm Carolyn Chan and I'm joined by my co host Dr. Sean Cohen. And on tonight's episode we'll discuss hospital addiction medicine 3.0. Yes folks, we have covered two other episodes on this that we encourage you to listen to with incredible Dr. Maggie Lowenstein. But before we get started with our episode, hey Sean, will you remind folks what what do we actually do on this on this miniseries?

Dr. Sean Cohen

I would love to Carolyn. We are the Addiction Med Podcast and we use expert interviews often with people we really idolize or follow on Google Scholar because every paper they publish is practice changing to demystify common addiction med topics, reduce stigma, inspire listeners to be fierce advocates for all people who use substances. As a reminder that most episodes are available for CME CRED through VCU Health CE for all health professionals at curbsiders.vcuhealth.org all you have to do is create an account and by listening to this episode specifically in completing the CME this can count towards your DEA 8 hour requirement on substance use disorders education.

Dr. Carolyn Chan

This podcast is brought to you by the American College of Academic Addiction Medicine. ACAM offers practical expert led education focused on caring for patients with substance use disorders in real world clinical settings. Learn more@acam.org and today we have a

Dr. Sean Cohen

really fantastic conversation with Dr. Maggie Lowenstein, who's an internist and addiction medicine specialist at the University of Pennsylvania in Philadelphia. She works in an integrated addiction medicine and primary care clinic and attends on Penn's inpatient Addiction Medicine consult services where she teaches a whole host of learners, fellows, residents and students. And her other hat is that she's a researcher that really looks into care delivery models to support patients with substance use disorders in hospital setting and during care transitions. And kind of in our Hospital Medicine 3.0 episode, she really goes through pearls about the more kind of complicated situations with continuing methadone in the hospital, both going through dose verifications. How do you manage missed methadone doses or acute prolongation, particularly in the setting of withdrawal? And then we really spend the bulk of our time going through a primer on management of metatomidine intoxication and withdrawal. And metatomidine is a new adulterant in the drug supply that's really super prevalent in Philly and kind of spreading throughout a lot of the United States. And it's a really great kind of overall guide to management and kind of when to think about it. And so after this episode you really become more precedent at managing withdrawal. You got it? No.

Dr. Carolyn Chan

We are so excited to have you here today, Maggie. This is the part of the show where we really want our guests to have the chance to get to know you. So do you mind giving us a one liner to describe yourself?

Dr. Maggie Lowenstein

Sure. So I am a 40 year old internal and addiction medicine doc. I'm also a wife, a mom of two kids, so a six year old daughter and a two year old son. And outside of work, mostly what I do is things that my kids like to do. So my daughter's really into musicals and my son is really into picking flowers and going to the park. And I'll spend a lot of time. I live in an old house in West Philadelphia, so I spent a lot of time fixing all the things that break and trying to make it a little bit better.

Dr. Sean Cohen

It sounds like a lot of fun and also very stressful.

Dr. Maggie Lowenstein

Depends on the day.

Dr. Carolyn Chan

What is your favorite musical that you've had to see this past year with your kids?

Dr. Maggie Lowenstein

Well, my daughter is really into the Sound of Music right now, which really holds up. So yeah, we've, I've watched that many times now in the last few months and we recently went to see the stage production so we've really, we've gone all in. But she was, she was locked in. She was really into. Was great.

Dr. Carolyn Chan

That's incredible. I said that I have a almost three year old and she also loves musicals and we took her to see the wizard of Oz and now she just runs around singing Ding Dong the Witch is dead everywhere. She like doesn't really know what that means. She just runs around and screams it and it's very adorable and slightly terrifying. I think they're strangers.

Dr. Sean Cohen

Imagine being a little surprised.

Dr. Carolyn Chan

And also they're probably like, you know, you let your 2 year old watch this movie. I'm like, well, it's not the most fun.

Dr. Sean Cohen

It's not very violent. Like it's a. I feel like it's three year old appropriate.

Dr. Maggie Lowenstein

Definitely.

Dr. Sean Cohen

Can you tell us, I feel like everybody's path and kind of how they got to addiction medicine and also kind of what kind of gives them the kind of drive to continue doing it is different. What, what like in addiction medicine, what drives you? Like, what's your favorite aspects of it?

Dr. Maggie Lowenstein

I would say I really love the patients and how you kind of get to know people very, you know, kind of deeply and intensely. I do both inpatient and outpatient work. So sometimes I'm meeting people in one setting and caring for them in another or vice versa. And I feel, you know, patients really connect with you and your, your kind of most authentic self and I, I really enjoy practicing medicine in that way. And you know, just being able to see people sort of through that journey is I think what one of my favorite aspects of the work.

Dr. Sean Cohen

I love that I, I every time like someone starts on a new rotation with us, I'm like, you can put your stethoscope away. We were just going to talk to people for a really long time. It's going to be awesome. And by the end of it, they're pretty into it.

Dr. Maggie Lowenstein

So yeah, patient. And I think patients are, they're like, I think they appreciate when you kind of bring yourself to work and you're just talking and kind of being who you are. And I think everyone develops their own style. But I think that's like a very fun part of the field is sort of figuring out what your style is and how, how you, how you make that work.

Dr. Carolyn Chan

Totally. And I think this is actually a great time to learn a little bit more about your style about talking and caring for patients. So Sean, do you mind actually kicking off today with a case from Cash Philly Branch to start?

Dr. Sean Cohen

Yeah, yeah, I would love to. So you're Working and called to admit. This 35 year old patient who is currently unhoused and is a woman with a history of severe opioid use disorder who reports that they're currently treated with methadone 100 milligrams, currently continuing to use about two bundles of fentanyl intravenously daily and also has a cocaine use disorder, is presenting with concern for injection associated cellulitis in their right forearm. On presentation to the eds, her vitals were notable for the fact that she's afebrile, tachycardic to 120 and hypertensive to around 160 over 95. She has large pupils and piloerection. The ED clinician starts vancomycin for concern for the cellulitis. They attempted but were unable to verify methadone dose. So they didn't give her any methadone and gave her Klondine 0.1 milligram which she not surprisingly not help very much. And they also completed an EKG which showed sinus rhythm and a mildly prolonged QTC of 510 with historical values that were all normal. So I think first steps is this is a patient you're taking care of with opioid use disorder who reports that they received methadone and opioid treatment program. So how do you confirm that? What are the steps to actually getting them their methadone?

Dr. Maggie Lowenstein

So yeah, it's sort of crazy that this is still the system that we have. But right now the typical practice at my hospital and I think in most places is that you need to try to reach out to the methadone clinic or otp. Usually that is a phone call, faxing of some sort of form giving permission to release records. And unsurprisingly that doesn't always work. But that's kind of the typical way right now is trying to reach out to somebody in the clinic and getting a sort of faxed or paper dose

Dr. Sean Cohen

confirmation and I mean I'll just say ours. Similarly in kind of our hospital, I don't actually we don't have to get papers. Thankfully most of the people do it over the phone.

Dr. Carolyn Chan

Okay.

Dr. Sean Cohen

But yeah, most OTPs, I guess in your experience is it easy to contact most OTPs or there is there a lot of work behind that?

Dr. Maggie Lowenstein

Yeah, it depends. So I know most OTPs are supposed to have kind of after hours coverage. I think there's some states that actually have laws about this but, or have hotlines. But the reality is this is pretty variable. So sometimes I know like in our setting we will Rely on some back channeling, you know, so and so has the number of this medical director and we can sort of make it work. But obviously that's not a great sort of system or policy issue. I think, you know, some places have more streamlined kind of relationships with OTPs or integrated electronic health records. That's not the case where I practice. But I'm hoping for other people's sake that it's a little bit better of a system where you are and let's

Dr. Carolyn Chan

say you do get in touch with a methadone clinic. So by chance, in the area where I practice, I'm often able to just call the clinic and then usually they'll say click 3 to verify a patient's dose. If you're a healthcare provider, in a very smooth voice, that makes me very optimistic. And today I'm lucky. Somebody picks up the phone and they're like, how can I help you? What type of information do you want from the methadone clinic? Are you just getting the milligrams? What is helpful for you as a clinician in the hospital?

Dr. Maggie Lowenstein

So I think the most important thing is really understanding, you know, what, what not only the milligrams, but sort of when the most recent dose was and if you have sort of other information about kind of recent attendance, I think those are the most helpful pieces. But I think the two most important things are what milligrams and when did they last receive it?

Dr. Sean Cohen

Yeah, yeah. I mean I think I focus on the same things and try to get a sense if you can, of like with attendance. Is there like is this their stable dose? Is this they're on a buildup because they've missed doses recently. Just so you're going to kind of get an idea of like where they are compared to normal. I guess like in situations where you can't contact the otp, I guess too, it's like, do you have any like other sneaky ways to confirm doses and if then nothing works, then what do you do?

Dr. Maggie Lowenstein

Yeah, so I mean one, one sneaky way sometimes, especially for patients who have take home doses, like or bottles, is to see if they've got a take home bottle that often will give you the dose and of that it was dispensed. You can ask patients or family members if they have those. That can be one sneaky way. I'm curious if you have others. Maybe I can learn something sometimes. I'll look and see if they have recent hospital admissions or other kind of healthcare touch points where we might have a methadone dose. That's been sort of documented and administered in some way. So maybe they had an outside ED visit where they were able to confirm the dose, something like that. And we can see that in our ehr. But if you can't confirm the dose, typically we don't want to just kind of leave the patient with the point one of clonidine. So we want to try to address their withdrawal as best we can, you know, and not like if we're not sure typically what that means is starting kind of our asking them what their most recent dose was and trying to start sort of on the more aggressive side of our initial methadone dosing. So maybe we do like 40 milligrams and then perhaps like four hours later another 10 or even another 10 and try to get them up as quickly as we can until we can get that dose confirmation. And then sometimes also supplementing that with short acting opioids. So that's sort of our typical practice. Ideally we get it as soon as possible to avoid, you know, delays in care, but if we're really in a bind, we'll, we'll, we'll do that.

Dr. Carolyn Chan

I totally agree. I feel like we do something very similar here with. If I always imagine like, hey, if this person was just walking in today to start methadone, well, honestly they would get somewhere between 30 and 50 milligrams no matter what. And I know you've been in the emergency department since 2am and that there's no possible way, right, that you could have gotten, you know, this methadone in any way, shape or form. So I think that's like helpful for folks to know that like, yeah, if somebody was just a new start we would be able to do this anyway. Sometimes do I look for other clues that just like are helpful, like is there urine, is there a methadone in their urine Drug screen. I think depending on the state you're into, like on my prescription drug monitoring program it will actually say in the corner if somebody is at an otp. So again, it's just sometimes another piece of information, I'm like, oh, all of this sort of aligns with, you know, what is what is being told to me and totally agree that using other flagonists as well can be really helpful on top if you're just like not sure.

Sponsor/Advertisement Voice

This episode is brought to you by Babbel. I recently traveled to Paris and this was my first trip out of the country. And I'm not going to lie to you, I have the bug now I would like to explore other countries in my head. I'm constantly planning my next trip. Maybe Italy, maybe Greece. But wherever it is, I'd like to at least have some of the fundamentals of the language down so that I can navigate without feeling terrified or completely at sea. And if you're traveling this summer, here's a real travel don't wait until you land to start learning the language. Instead, try babbel. Even just 10 minutes a day with Babbel can help you start having real conversations in as little as three weeks. Instead of memorizing random vocabulary, you're learning phrases you'd use ordering dinner, asking for directions, or talking with locals. What's cool about Babbel is it's built for real life. There are no vocab lists. There are no verb charts. But there is real conversation. Practice lessons are quick, practical, and built by more than 200 language experts. They have interactive dialogue, personalized reviews, even podcasts, all designed to get you speaking quickly and confidently. And unlike cramming before a trip, Babbel fits into your actual schedule. You can do it at a coffee break, during your commute, even a few minutes before bed. Babbel's award winning app has sold over 25 million subscriptions and is backed by a 14 day money back guarantee. If you've got summer travel coming up, now's the time to start so you can actually use what you learned on the trip. Right now, Babel's offering listeners up to 60% off. Go to babbel.com curb that's Babbel. B-A-B-B-E-L.com curb for up to 60% off. Rules and restrictions apply. This episode is brought to you by figs. Here at the Curbsiders, we are always talking about the latest medical breakthroughs. But if I'm being perfectly honest, there is one thing we weren't seeing any major advancements in, and that is medical scrubs. Back when I was a resident, the scrubs I used to wear were stiff and itchy and boxy. They definitely did not fit right. And then five years ago, I noticed a change in the scrubs landscape. I noticed that people started looking comfortable and actually good. And I thought, wait, scrubs can actually look good. Figs are made for all of us in healthcare. They are lightweight, breathable, antimicrobial and oh, they have pockets for your stethoscope, your pager, that parking ticket you forgot to validate all of it. Wado owns five pairs of figs and he says when he is in scrubs he doesn't wear anything else. I'm never quite sure what that means. I don't investigate it fully. But he likes Figs is the point that I'm trying to make here. And we here at the Curbsiders have teamed up with Figs and now Curbsiders listeners can get 15% off. Just go to wherefigs.com and use code FIGSRX. That's wherefigs.com and use Code FIGSRX for 15% off.

Dr. Sean Cohen

Worth also saying that. I mean, that's really cool that your PMP has a fact that they're at an OTP in it. I don't. Unless I've missed an update, our PMP has no records of methadone on it. And so, I mean, it's just worth knowing that that is not a way to say someone is not on methadone because it's not in the pmp. Because I see kind of both sides of the mistakes being made sometimes.

Dr. Maggie Lowenstein

And so, yeah, that makes sense. I think it does vary state by state. Ours doesn't have any methadone information either, but. Right. Kind of knowing your state's local regulation and context is really important here.

Dr. Carolyn Chan

And exactly to your point, too. It's still not right all the time. So they're like, yep, they're a patient here. I'm like, great, okay. It's. It's more. It's like one of those. It's helpful if it's there, and if it's not there, it's actually probably not that helpful. But if it is there, it's good to know. And it usually gives me a number to call, which is nice.

Dr. Maggie Lowenstein

That is helpful.

Dr. Carolyn Chan

So I'm curious, Maggie, too. Like, let's say our patient has come in and it turns out that they actually have missed some doses in their clinic. They've just been feeling really poorly, haven't been able to get to clinic on a daily basis. And how do you approach missed methadone doses? You know, let's say she's missed like 12 days in clinic. So it's been a little bit of time since she dosed.

Dr. Maggie Lowenstein

Yeah. So I think this is, again, going to vary a little bit by your institution and sort of.

Dr. Carolyn Chan

I'll just say that a lot of

Dr. Maggie Lowenstein

this is expert opinion, but there's not a lot of evidence for how quickly methadone can be restarted after missed doses, I think, especially in the context of ongoing use. So I think a lot of the older guidance that we often look to and that kind of health systems or OTPs look at is recommending dose reductions pretty quickly when people miss methadone doses. So if they miss more than, I don't know, like three days or so, starting to dose reduce by like 50% sometimes and then if they miss more than five days, starting to, you know, just basically restart them. And you know, there are real, there are real concerns with, you know, kind of miss dosing methadone. Right. Like it has a long half life and it takes many days to reach steady state. But obviously there's also a lot of risks associated with under treating withdrawal. You know, we want to keep people in the hospital, we want to keep them stable in their recovery. We don't want to sort of, you know, worsen ongoing use if that's still in the picture. And so, and we know a lot of these rules are based on kind of older data and guidance. So I think when I'm thinking about this decision, you know, I'm guided by a couple of things. You know, there's growing evidence, we were referring to this a little bit and just what we were saying, but there's more and more evidence for more rapid methadone up titrations in the hospital. So you know, I think if we are feeling like we need to dose reduce, we can still pretty confidently, you know, try to go back up as quickly as possible. So from an outpatient OTP setting, there's some data that suggests that maybe we don't need to be as conservative in restarting doses or as conservative with missed dosing as we typically have been. So there's a study from Colorado where one OTP incorporated a protocol that basically took into account like ongoing non prescribed opioid use when people missed methadone doses. And also looked at other sort of risk factors for potentially complications from methadone like you know, older age or concurrent benzo use or things like that. And in patients who missed doses but continued to use and didn't have a lot of these risk factors, they were much more aggressive in kind of maintaining or only slightly dose reducing patients. And most people did okay. So again, there's not like a perfect study that's going to exactly guide our practice. But I think some of the dose, like the way that I was initially taught to do dose reductions is probably more conservative. So you'll of course want to kind of think about your instit policies. But I think we can use some clinical judgment in not always completely reducing doses in the case of missed methadone, especially if people are having ongoing fentanyl use at the time or other opioid Use curious what your practice has been. I don't know. This has changed for us recently.

Dr. Sean Cohen

Yeah, I know. I think you laid it out pretty well of like you have to figure out how to balance this risk of potential risk of over sedation if they've lost tolerance versus the very also very real risk of opioid withdrawal leading to horrible outcomes like premature discharge in a patient that clearly needs to be hospitalized. And again hospital not a great place. So it takes people a lot of kind of activation energy to even get to the hospital when they know it's not going to be the best experience for them. And so I will say like we kind of do the similar to you of like we previously were practicing more conservatively and now have gotten much more proactive about increasing doses or not decreasing doses. I don't know that I have a, a hard cutoff on like how many days until I reduce the dose. It's definitely beyond three now if someone's reporting regular fentanyl use, doesn't have respiratory like high risk respiratory features, isn't elderly. But I think like really if you do have to dose reduce because they've missed like a week or something like that, thinking about lower grade dose reductions rather than like halving their dose or stopping it entirely and really leaning on the opioid withdrawal, maximizing opioid withdrawal treatment while you really rapidly get them back to their dose too.

Dr. Carolyn Chan

Yeah, I think I'm hearing the same thing across the board. So you guys look at three factors. I'm going to do my summary of it. So one, are they still using non prescribed fentanyl? I think that's a big thing. I think we're all just trying to make sure people have maintained opioid tolerance in some way because methadone is so potent and the metabolism is very variable with the liver and the sip, you know, enzymes and all the magic things that sip enzymes do. You'll look at also any, I presume also like any acute ongoing medical illness too. Like hey, are they all of a sudden on 6 liters of oxygen and do they have a huge spike in their lts and do they have acute hepatitis? You know like these things could really possibly impact how cautious we're doing as well as whether they're using alcohol, benzos and other things and then make an estimate. Our, I can say our OTP sort of has a protocol where basically if a patient is gone less than a week, they'll only reduce by 10% which I find is like not, you know, it's, it's Just kind of helpful. If people are like very unfamiliar with this. People are gone seven to 10 days will dose reduce by 15 to 20%. If they're gone by 10 to 14, 20 to 30, and if it's more than 14, 30 to 50. So we may not even be doing a full restart. But it's up to ultimately the clinician's judgment. In the clinical scenario, I find that if people are on higher doses of methadone, I'm more likely to do more of the higher end of dose reduction than if somebody's on just like 60 milligrams of methadone. I may say, I don't even know if I have to dose reduce you at all. So, man, I don't think we gave our listeners a great answer for this. I think we may have just confused them.

Dr. Sean Cohen

I mean, it's tough because I mean, as this whole episode we will talk about like the drug supply changes so quickly that it's hard for evidence to keep up. And so like you're really using your best clinical judgment, along with like pathophys and knowledge about pharmacology and stuff to try to do your best to treat the person in front of you. I mean, I appreciate, Carolyn, that you have hard numbers, at least that you gave compared to like a lot of hand waving that Maggie and I did. But yeah, I think it's like, I mean that's some of the, that's some of the difficulty in addiction med, but it's some of where you feel like you actually get to make an impact too is like you get to try to adapt your care to this rapidly changing drug supply to really help people that are experiencing it firsthand.

Dr. Maggie Lowenstein

But I think your point too, about the higher doses cutting more versus the lower doses, I think it's really, you know, one of the kind of mainstays of care or like, or kind of priorities within hospital based care is really trying to, to quickly and effectively manage acute withdrawal. Because we want to be able to keep people, you know, keep people in the hospital, manage their medical condition. So, you know, ideally we're kind of keeping them on doses that are not going to, you know, kind of increase their risk of acute withdrawal and really. And then again supplement if we do feel like for, you know, various clinical reasons we need to dose reduce patients, trying to keep them at a dose that's, or trying to add to the dose that they're on with things like short acting opioids to really quickly and effectively manage that withdrawal.

Dr. Carolyn Chan

Totally. And I feel like this has come up on other curbsider episodes, I think with Dr. Melissa Weimer, who, who always says, right, you can always give more. You can't give less in the hospital. You don't have to give it once a day. You could give some amount and see how they're doing four hours later when methadone at its peak, and then give more. And that is absolutely easier to do in the hospital and more feasible than outpatient. So.

Dr. Maggie Lowenstein

So that's a good point.

Dr. Carolyn Chan

I'm curious too, about this QTC prolongation. So again, our patient, as a friend of reminder, her qtc was like 5, 10. Is this something you may see in the setting of withdrawal and how do you think about methadone in the setting of kind of the spectrum of QTC prolongation that we can see?

Dr. Maggie Lowenstein

Yeah, so we can definitely, we definitely see prolonged QT when patients are in the hospital with acute withdrawal, probably for a number of reasons. It may be related to acute illness. It may be electrolyte derangements. They may be on other QT prolonging meds. So I think there's a lot of reasons why people might have those, and often those are, you know, sort of addressable or reversible. So I think one of the things I'll, you know, sort of, especially when it's kind of hovering around 500 as this patient is, but it's a little higher than that. You know, the 500 that we sort of often use as a cutoff, I think the first step is really just like repeating the ekg, you know, maybe fixing fixable things like giving them some K and some mag, you know, looking at their med list quickly. And are there, are there medications that are going to contribute to QT prolongation that are, you know, gonna, we don't really need and really trying to sort of correct those things. This is going to be another thing where it's expert opinion and there's not a hard cutoff. But I do think that, like, that 500 number is the number that I think we all kind of keep in our head and we don't want to get too much above that. But there's sort of risk benefit discussion. We can look at sort of see whether this is something that's been a pattern over time or it's sort of, you know, acutely changed and we most likely expect it to go back to normal and, you know, sort of use that to guide some of our decision making around, like, how much we're willing to continue versus not. Yeah. And then again, same thing I Think if people are still experiencing symptoms and we're worried and we want to, you know, not, not either increase as aggressively or we want to, you know, kind of wait for some of these things to correct, we can use short acting opioids to kind of help supplement. But ideally if a patient's on methadone we want to try to continue it. So I think that would be my first choice if we can kind of manage those other factors.

Dr. Sean Cohen

Yeah, I mean I'd also put in a hard pitch for like look like don't just trust the machine read on the qt. The machine reads are complete, are not often correct let's say. And so actually manually looking at, I'm not going to say print it out and get your calipers and stuff, but at least manually looking at it and being is this more than half and making sure there's entire papers written about which QT calculation to use that are honestly mostly beyond me but at least making sure it's accurate first. I practice the same way of if it's in the low 500s, don't press me on what low 500s means. But if it's in the low 500s and they're in withdrawal and they look terrible, I'm going to more like give them the benefit of the doubt, give them their methadone, maybe split it to twice a day and recheck EKGs and try to like fix the reversible things and hold the other non essential QT prolonging meds before making any shifts in care.

Dr. Maggie Lowenstein

I'm glad you brought up the manual thing. I totally meant to say that, but I definitely have seen a lot of wonky reads from machines. I was on consults last week and I had one that was reading at like 650 and when I did it it was like 475. So I think it was some weird thing going on. And you know that's a bit extreme. Usually it's not quite so different. But I do think it's worth at least you know, both eyeballing and then if it doesn't eyeball right, actually doing it yourself with one of the calculators.

Dr. Carolyn Chan

I informally use the squiggle test. If I look at it and I'm like, oh, there are too many squiggles on here. There's no way this read is right. Then maybe I'll try and bust out calipers where I'm just like, like I can barely tell where these end and start. I think same thing with as you guys, a lot of shared decision making because, you know, reducing, stopping methadone can have some pretty severe consequences as well, such as overdose and death. And I think that if, you know, there's no arrhythmia happening, nothing urgent to like, hey, you have some time. This patient's probably been this, on this dose. They've probably been living their life at this, you know, QT to kind of make decisions as to what you and the patient really think is the next best step. So let's say hypothetically we have a new ekg. It is real, you print it out, you do the, you actually do the whole caliper test and oh my gosh, their qtc is like 600 and you're like, wow, this is, this is a long qtc. This is one where we're, we're getting a little sweaty, getting a little anxious. How, how would you manage that? Would you stop the methadone entirely? And if you did, how would you sort of help manage their withdrawal?

Dr. Maggie Lowenstein

Yeah, it's one of those things where again, you can't give less as, as you wisely quoted earlier. So I do think if it's really that high, I am going to think about, you know, I holding the methadone for some period of time. I think, you know, going back to some of the basics of withdrawal management, it's really, I think most helpful for the patient to have some sort of long acting agonist. Methadone tends to be the most effective and the one that obviously could be continued outpatient if that's what the patient wants. We could think about buprenorphine and depending on sort of the situation, you know, we could potentially pivot. But I think, you know, if we're sort of buying some time, the patient has been on methadone, they're in acute withdrawal, but we really don't feel safe giving, giving methadone. I think some sort of combination of scheduled other full agonists. In our, in our context, we will often default to oxycodone, ER and ir and so we'll have some sort of long acting extended release and then the use, the immediate release scheduled so that we can kind of more rapidly up titrate. That definitely does not work as well as methadone and I wouldn't. And also isn't, you know, evidence based in the way that methadone is both for acute withdrawal and for longer term treatment. But I do think if you're in a bind sometimes we will use those things and then. Right. It's a process. Once the patient stabilized, it's the process of shared decision making around, like, what, what's our next step? Is, is methadone the best option for you long term or do we need to think about something else? But, you know, kind of using the, like some sort of full agonist scheduled so that we're really not having kind of constant like persistent withdrawal and then sometimes even IV full agonists as more of a rescue thing or kind of for ongoing withdrawal that's not managed with the oral. Curious what you guys do.

Dr. Carolyn Chan

We'll do something. We'll do something similar. I think the messy part that I always struggle with is, man, how do I switch methadone, which is just such a different opioid to oxycodone or morphine or anything else really. Any other opioid in theory could work. Do you have an approach to manage that? I think it's hard to be precise, but how do you get in the ballpark?

Dr. Maggie Lowenstein

Yeah, I think it's a tough one. I know. Again, kind of the starting doses that we'll often recommend in our context are like Oxy ER40Q8, Oxy IR20Q4, or sort of equivalent hydromorphone doses within an IV hydromorphone rescue. But for someone who is.

Dr. Sean Cohen

Is.

Dr. Maggie Lowenstein

Has a much higher use or higher opioid tolerance will likely start a bit higher than that. And again, if there's sort of risk factors for respiratory depression, they're medically ill and we're not sure what's going on. You know, we may dial that down a little bit, but I will say those typically are not adequate and we're having to kind of add to that pretty regularly. You just, as you said, it's hard to convert between methadone and some of these other things. It's. There's many things that I'm going to wave my hands that go into it, but. And so it's so often it's kind of guesswork. And I think that's really where like frequent reassessment and adjustment is critical because we don't want to just kind of put someone on a dose and then kind of come back in 24 hours and see if it worked. Like, that's a really critical period to kind of manage and stabilize patients. So, like, yeah, we're sort of putting out a starting dose and then we're pretty quickly adjusting.

Dr. Sean Cohen

Yeah, I mean, I. There is this one resource that I plug whenever I'm teaching of palliative care, fast facts number 75, which is like a palliative care resource for converting long term opioids to methadone and has all these ratios that are dependent on the number of MMEs. But it's worth saying it ranges from 1mg of methadone is 3MMEs, up to 1mg of methadone is 20MMEs. So the range is humongous. But I often use that as a starting point. If I'm really like, someone's on 150 of methadone, I can't give them anything. I use that as a starting point and kind of rapidly go up too. And I've found that the 1 to 3 never works. It's usually like you end up at like 1 to 10 or 1 to 15 or something when you get them stabilized.

Dr. Carolyn Chan

As a consultant, I'll do that. I'll use the similar, like, hey, here's what I think the range should be. And then I'll, and I will always get a message and they'll be like, this is a very broad range. This is a very wide range. I'm like, I know though, I'm sorry, it's somewhere between these two numbers. I like to give the range because it gives people permission to go up. I think people get scared about going up. And I say I wouldn't go past this number, which is very, very high. But it is probably, I feel very confident is somewhere between these two wide ranging numbers.

Dr. Maggie Lowenstein

Well, I think one thing that this always kind of reminds me and I feel like I'm teaching teams when I'm on consults is like how potent methadone and buprenorphine are because people are like, oh, 20 milligrams. But that's a lot of MME. And I think, um, you know, and methadone is also sort of a little bit magical. It has other properties besides the opioid receptor agonism that, you know, make it effective as, you know, we talked about, or you talked about it in the other episode. But yeah, I do think it's. We, we forget sometimes that these are really potent medications. And so sometimes people are really surprised by the doses of other opioids that, you know, we end up landing on in these situations. But I'll just emphasize, as you both did, that I think, I think this is always kind of like a distant third choice for your opiate withdrawal management. Because I think ideally starting with methadone or buprenorphine in situations where you can and it's appropriate and the patient's okay with that plan because those are just much more evidence based both for withdrawal and longer Term treatment. Yes.

Dr. Carolyn Chan

And on that note, a friendly reminder. You can use the other opioid agonists in the hospital. You cannot use them outpatient. So I think we all sort of view these as, like, these are temporizing measures till we sort out X, Y and Z.

Dr. Sean Cohen

Okay, so you get a repeat ekg. Thankfully, it's normalized for her. And you're able to call the methadone clinic. Someone answers and confirms with you that she's on 100 milligrams. She hasn't had any recent dose changes. So you give her 100 milligrams of methadone. You also start her on some PRN oxycodone, like you mentioned, at 20 milligrams every three hours. And then, like you also mentioned, frequent reassessment. Go back in a couple of hours. She's now a hospitalist border in the emergency department. Her piloerection and madriasis are gone, but she has persistent tachycardia, the hypertension really hasn't approved, and she's really profoundly nauseous and just says, like, I still feel horrible. She's still able to take oral medications that they're giving her to the ED despite her nausea, not actively vomiting yet. And so. So does that clinical picture ring any bells for you or make you worried about anything particularly?

Dr. Maggie Lowenstein

Yes. So we know that we are, I believe, in the Philadelphia branch of Cash, like, and we know that this is a patient who had pretty significant opioid withdrawal, now having kind of persistent symptoms after what we would consider pretty good management of opioid withdrawal with opioid agonists. So we need to start thinking about impact, impacts of novel adulterants and particularly Alpha 2 withdrawal. So we know that Alpha 2 agonists like xylazine and more recently, metatomidine can cause an acute withdrawal syndrome that has a lot of overlap with opioid withdrawal but isn't responsive to our traditional management. In the case of this patient I mentioned, xylazine is one that we had seen in Philly and many other places for a couple of years now, which had a less severe acute withdrawal syndrome. I think there's some debate as to kind of the extent of it, but now we're seeing in Philadelphia that that has largely been replaced by this new Alpha 2 agonist called metatomidine, which is detectable in the vast majority of our fentanyl supply and, you know, causes some of the things that we're seeing in this patient. So the persistent tachycardia, the hypertension, and the Profound nausea, all being kind of key parts of that clinical syndrome.

Sponsor/Advertisement Voice

This episode is brought to you by Freed. You know that sinking feeling when you check your phone system after a lunch break and see 15 missed calls and voicemails from patients? Every one of those is a person who couldn't reach your practice. Research shows clinics lose four to five new patients every month just from missed calls. At thousands of dollars per patient per year, that adds up fast. What if every single call got answered? Nights, weekends, lunch breaks. By technology that actually talks to your patients, not a phone tree that drives them crazy. That's Freed front desk. It's a conversational AI receptionist built by the same company that 26,000 clinicians already trust for AI charting and coding. It answers calls in over 90 languages, collects intake info, triages by urgency, and delivers everything to your team in one organized inbox. No missed calls, no voicemails, no hold music. Setup takes 30 minutes, and pricing starts at $149 a month. Try it free for seven days at GetFreed AI. That's Get Freed AI front desk.

Dr. Carolyn Chan

Can you tell us a little bit more about. You already alluded to that, like, Metatomidine is an alpha 2 agonist. What does that mean for clinical presentation? And why do I think it's in the opioid supply?

Dr. Maggie Lowenstein

Yes. So Alpha 2 agonists are. There's some common ones that we use in, like, clinical medicine for people, things like clonidine, dexmedetomidine infusions, guanfacine. So they're kind of pharmaceutical versions. There are a couple of different veterinary alpha agonists that are used as sedatives in kind of acute sedation for animals. So and they are potent and very selective alpha 2 receptor agonists. So metatomidine is one of those, and it's actually going back to some biochemistry. It's a racemic mixture of Levo metetomidine and dexmedetomidine. Which is. The dexmedetomidine part is something you're gonna be familiar with because we use it as a sedative for ICU patients as well. But. But basically all of these are sedatives, and then at very high doses can cause some things like pretty profound hypotension and bradycardia. But essentially, we think that they're probably added to the supply to kind of augment or potentially the effects of fentanyl or maybe to allow people to use a little bit less fentanyl. So it's kind of a different type of sedative that has sort of a different mechanism of action than the opioids in the supply. So, you know, I'm not like a drug supply chemist, but I think the idea is it kind of prolongs people's sedation or high. And, you know, that is viewed potentially as a positive thing in the market. But I think the reality is most people aren't necessarily aware that they're being exposed to this. And so they're not necessarily, you know, like, it's not necessarily something that's desired. It's just more. It's sort of present and they don't really have a choice about whether they're getting it a lot of the time.

Dr. Sean Cohen

Time.

Dr. Maggie Lowenstein

And I should say, too, that it's, you know, this. The idea that is that it's an adulterant. So it's something that's probably, we think, is deliberately added and kind of systematically added as opposed to like a contaminant where it's, you know, cut on a dirty table and something is in it. And, you know, we. We have potential complications from that. This is thought to be something that's like deliberately added again for these reasons of like, you know, potentially enhancing or adding to the effect of the drug that people are using.

Dr. Sean Cohen

So it sounds like it's just essentially an extra potent. It's kind of the sedative that's replaces Ilazine where you guys are. And I will say it's definitely creeping its way into where I practice as well and kind of taking over the opioid supply. It's not that anybody, at least in my experience, and I don't know that there's data. It's not anybody that's intentionally seeking out metatomidine itself. It's just that it is adulterating the opioid supply. And now we're seeing all these after effects and effects from it. Does it? I guess, like, I mean, we're afraid our patient has metatomine withdrawal, which we'll definitely focus on too. But is there a way that has impacted, like overdose presentations or intoxication at all that you guys are seeing?

Dr. Maggie Lowenstein

Yes. So there's a couple things. When people have used and they're intoxicated, we're seeing pretty profound hypotension and bradycardia as well as sedation. So, like I. And if I have patients who are kind of in active use coming into my clinic, people, it's not, not infrequent to see someone walking in with a heart rate in the 40s, which is pretty different than I think you know what we typically see in primary care or in outpatient settings. And so that's one kind of just big change. But also in terms of some of the overdose presentations, this was true to some extent with Xylazine, but I think even more so here. It's very sedating. And so people may not wake up when they receive naloxone in the same way that you might expect for somebody who's not using adulterated fentanyl. And you know, so they may resume breathing, but that sedation is, you know, still there. Sometimes, you know, we worry about people kind of, you know, being like using and then becoming really sedated and maybe having like weather related injury or heat, you know, whether it's cold or heat. So there's some, you know, again, it's, it's a little bit context dependent, but I think those, some of those, the presentation can look a little bit different when people or intoxicated with metatomidine.

Dr. Sean Cohen

And I think worth highlighting too is that, I mean, you mentioned that people don't wake up from the naloxone, but their breathing still improves. And so like naloxone's still effective for opioid overdose reversal, where respiratory depression and arrest are your concern, but it just doesn't wake people up.

Dr. Maggie Lowenstein

Yes. Yeah. And I've seen this be kind of talked about as like naloxone resistant fentanyl or whatever. And I think that's a really important message that that's not true. Like you can kind of reverse that respiratory depression. People will like, you know, have become apneic or you know, have a fatal overdose. They may just not appear, you know, the way that we might expect them to in kind of an acute opioid withdrawal and very awake if, when, you know, or at least maybe you gave too much Narcan in that case or too much naloxone in that case. But, you know, people don't necessarily wake up in the same way because they, the naloxone doesn't act on the, on the sedative part, but absolutely, it's still life saving. And that's one of the big teaching points that I think, I think needs to be made over and over again.

Dr. Carolyn Chan

Yeah. And I know right now I don't think we have a reversal agent approved for humans, at least for menatomidine, to my knowledge.

Dr. Maggie Lowenstein

No. Typically when people come in kind of with a presentation where they, you know, it's. I don't know if I'd call it an overdose, but they're intoxicated or we're concerned the treatment is supportive and I think because of the withdrawal syndrome we're about to get into, probably a reversal agent, clinically we might not want to use that because that could cause a whole host of other problems. So there's certainly not something kind of in routine clinical medicine that's available. I think there may be some theoretical chemicals out there that could be used, but not something that's kind of commercially available but probably wouldn't advise it because typically intoxication is self limited. Again, people kind of over time sleep it off and wake up and tend to tolerate, I think for chronic use people. So with some of these really low heart rates or low blood pressures have sort of compensated and are usually okay.

Dr. Carolyn Chan

And what is the typical course of metatomidine withdrawal? Like what symptoms do we see? What timeline does this occur across?

Dr. Maggie Lowenstein

Yeah, so this is based on, you know, some of my own clinical experience, some of what has been published on this, and you know, some of the limited data that's out there. But typically we're seeing symptoms within a couple of hours from last use. So like maybe like 4 to 6. So fairly short timeframe. That's when people sort of begin to see some things, maybe some anxiety, maybe some agitation. It tends to get worse within about six to 12 hours. So that's where you start to see more severe nausea, pretty really profound hypertension and tachycardia. And you know, again, some of the other things we might see are like tremor, even sort of a delirium or agitation. But I think it can be confusing on paper because a lot of these symptoms overlap with other withdrawal syndromes, especially opioid withdrawal. But what I have noticed, and I think a lot of others have described in the literature that exists, is that this is really out of proportion to a typical presentation for other acute withdrawal syndromes. So really high blood pressure, really fast heart rate. People have reported on complications like press or, you know, nstemmies, kind of complications of hypertensive emergencies and that, you know, these things don't respond to the usual therapies like opioid agonists. So I'm describing a little bit of like a, you know, when you see it kind of a situation. But I think for me, when this really clicked was when I saw, maybe like a year ago I saw a patient in the emergency room that I was consulted on who was on, you know, recently received a long acting injectable buprenorphine dose and had been stabilized on that, but was using on top of it and looked so sick, like Profound withdrawal syndromes, hypertension, tachycardia, nausea, vomiting. And we know if someone's on long acting injectable buprenorphine, their opioid receptors are quite saturated. And so this is probably pure Alpha 2 withdrawal. And so I think, you know, we really do see this as its own distinct syndrome that, you know, can is variable in its presentation but. And kind of severity, but definitely kind of of distinct from some of these other syndromes that we've seen in the past or typically see.

Dr. Sean Cohen

Yeah, I feel like the times I've seen it, it's like, I think what differentiated is like it's so rapidly progressive often for people of like they come in and they start having these kind of more often like a little bit subjective and then vital sign abnormalities and then they get really sick really quickly. And so it seems like a lot of it is like identification and proactive treatment early and having your kind of ears up that you are worried about this. And so what do you. When you're first getting worried, hopefully before they're super duper sick, how do you actually. And with the caveat of I know the data is very limited, but how do you start treating metatomidine withdrawal?

Dr. Maggie Lowenstein

Yeah, so I think like you said, the first kind of important thing is just having a high index of suspicion. And this really as a clinical diagnosis, like even in Philadelphia, where we see it a lot, we don't have sort of clinically available testing. So we're often sort of assuming that for people who are using street fentanyl in our city, because it's so prevalent in that supply, like people are being exposed to it. So I think having kind of a high index of suspicion and getting things started early is important. Definitely expert opinion here. I know our center has. Has developed some protocols that we're updating all the time. And I think we can put our link in the show notes. There's also a really good publication from Mike lynch and his team at Pittsburgh on sort of their expert opinion on how they're managing this, but they're actually all really similar. So I think the two kind of biggest pieces of this are aggressive treatment with pharmaceutical alpha agonists. So things like clonidine, guanfacine and sometimes dexmedetomidine. And I go into that a little bit more. And then also really aggressive antiemetics because that nausea and vomiting sometimes that's part of that rapid decompensation if people can no longer tolerate pos. And then you have very limited medication options. And then of course the other, the Sort of third part of this is treating concurrent opioid and other withdrawal syndromes. Because kind of the way that we're thinking about this clinically is, you know, this is kind of refractory symptoms after adequate opioid withdrawal treatment, so. Or at least reasonable opioid withdrawal treatment. So I think those are. That's kind of the rigor approach. I can kind of drill down a little bit on, like, how that looks specifically, because I know that our practice has changed a lot in the past couple of years, or not even years, sorry, in the last, like, year, so couple of months. But typically what we're doing is we're trying to start oral alpha 2 agonist, often multiple, quickly and ideally before people really start to decompensate. So when people have kind of normal vital signs, like, as soon as we feel like it's safe, you know, they're normotensive, they're not super bradycardic. We're starting clonidine doses often kind of 0.1 to 0.2 q 6 hours standing. And then we will pretty quickly up titrate two doses I had never seen before, like 0.6 q 6 hours standing at times. That's kind of been our max dose recently. We'll also add guanfacine scheduled, which is another alpha agonist that, you know, kind of acts slightly differently and will actually layer both of them on potentially if people are having additional symptoms. And some places also use clonidine patches to have kind of an alternative route of delivery. I'll say that the amount in a clonidine patch isn't that much, but sometimes, you know, it's longer lasting. And sometimes people. Some of the hospitals in our area will do, like, multiple at a time. So that's another option. And again, we're typically, like, scheduling those alpha 2, the clonidine in particular. And if we're adding guanfacine, we're scheduling that and then uptray treating relatively quickly as people's symptoms sort of progress. So, again, these are much higher doses than I had ever used before. But I think that's been our approach, and we've been able to, you know, I think anecdotally see some success with that. And then the other piece I talked about was the antiemetics, which is really important because, again, that nausea can really kind of kick off that nausea and vomiting can kind of kick off that cascade where people then can't take methadone, get electrolyte derangements. QT is long. Then you're in a big mess. And so we usually have one or more antiemetics as well. What has been found or the experience of a lot of people is that the one that I had kind of reached for, typically on Dansetron, just doesn't work as well. So usually we're using prochlorperazine or olanzapine are the two that we tend to reach for. And then anecdotally, I've also seen some benefit with promethazine, which has a little more histaminergic activity. So some of these other mechanisms of antiemetics besides the ondansetron, that I think we often default to. So that's kind of our basic approach here. Just to summarize, early aggressive and kind of up titrating alpha agonists orally, sometimes transdermally, and then again antiemetics, either scheduled or, you know, available to try to manage the nausea as well as we can. And then I can talk a little bit about refractory symptoms if you would like me to, but I will stop for a second.

Dr. Carolyn Chan

I would actually. I think these details are really helpful to our listeners. Curious what doses of guanfacine you're using. And again, titrating to are we going sort of above what we typically see? And also curious if you have found, like, tizanidine to be helpful at all in some of these patients.

Dr. Maggie Lowenstein

That's a good question. So guanfacine is not a drug I had really ever prescribed or administered before. But we're using doses of one, starting doses of 1 milligram, like three times a day, and then going up to 2 milligrams three times a day. We also do use tizanidine sometimes. I've seen people use all three of those. Often I've seen them stick with the clonidine and then guanfacine. Tizanidine can also be helpful and sometimes causes a little bit less hypotension than the others. So we'll reach for it, particularly if someone's got a little bit of soft blood pressure. But our first line is usually the clonidine and then adding guanfacin on and potentially tizanidine in cases where it's, it's like the blood pressure is a little softer or, you know, we, we aren't necessarily feeling comfortable just loading them up on the other ones.

Dr. Carolyn Chan

I'm curious too. Like, what, what are you titrating to? Is it a withdrawal score? Is it a blood pressure? Is it clinical judgment? Like, when I, when I think about putting somebody on clonidine 0.6 milligrams every six hours. Hours. You know, just curious where, where's, you know, what makes you decide to go that high or not?

Dr. Maggie Lowenstein

Yeah, so no, it is, it's, it's, it's interesting. It's like, like I said, this has evolved over time, and that was not to us. Those weren't doses we were using even six months ago. There are no validated scores for kind of Alpha 2 withdrawal that we're using kind of routinely clinically. So I would say I tend to look at two things. One, one is clinical staff and nursing is really comfortable and often assessing cow scores anyway. So we'll often kind of use the cows as at least kind of a general sense of how our control of multiple withdrawal syndromes is going. And a lot of this because of the overlap in symptoms, but also the prominent things like nausea, vomiting, tachycardia, that some of those things are included in cows, we can use it as a little bit of a benchmark. The other thing I often use is, is just thinking about heart rate, since that's something that's sort of easy to glance at. So I often think of sort of withdrawal control happening around a heart. Once heart rate is less than about 110, feel like maybe we're getting a handle on it. And often these, these, you know, doses are like that. Often we'll start these doses and even if someone kind of requires escalation, we'll continue these oral meds if they're tolerated so that it makes it easier to then de. Escalate. But yeah, obviously the other thing to note for people, because you're right that these are really high doses of meds that in other contexts could be very dangerous, is we want to make sure that we are, you know, not like putting hold parameters on them, not writing them, standing in, someone who's coming in with a heart rate of 50 and a blood pressure of, you know, 80 over 40, but also not waiting until people are really, really sick. And so trying to find that sweet spot where they, they're, you know, more normotensive, more, you know, their heart rate is, you know, not, not super low, but we're not really escalated yet. And I'm waving my hands because that is a little bit of a hard number to define. But typically we're kind of, we're starting them maybe earlier than I would. Just, you know, like once somebody's heart rate is sort of consistently above 60, for example, we might start a low dose and then kind of go up from the there, I think too Something

Dr. Carolyn Chan

that we haven't mentioned before, actually briefly, is like, your point of it, man, this is just entirely in your fentanyl supply in Philly. I encourage folks to reach out to their own local drug checking data to see what it looks like by you. And where I am, it has evolved rapidly in the past year. We went from around 20% to 70%. And we're really, we're. We're seeing it quite a bit more now. But. But if the prevalence is low in your supply, it may be a watch and wait. Right. And that's starting the higher doses of clonidine right away. So I think reach out to local harm reduction agencies, public health agencies. There's probably somebody in your neck of the woods that has your data, because I don't, I don't think it's at every state yet. To my knowledge. I think I saw last like 18, 19, 20 states. So it's not everywhere yet.

Dr. Maggie Lowenstein

I think that's a great point. And the other thing I'll say is that even in places like Philadelphia, where it is really kind of, you can pretty much assume that everyone is exposed if they're using the street fentanyl. Here, the presentation of this syndrome is really variable. Some patients do fine. I would say doses that I think of as much more standard for opioid withdrawal, maybe clonidine 0.1 or 0.2 scheduled or PRN and do fine. And I think that's probably, probably, you know, that when you look back at some of the literature on things like, you know, withdrawal syndromes from dexmedatomidine and ICU patients or, you know, rebound hypertension from clonidine, that we're all taught for our boards, not every patient gets those symptoms. And so I think that's, you know, extrapolating from that. We. It's. And sort of thinking my clinical experience, some patients really don't have this profound presentation that we've been describing. And so, so not just kind of knowing your local supply, but being sort of attuned to people's clinical trajectory. Like, people will tend to get sick faster, but a lot of people don't really need some of these heroic measures. And so it's worth just kind of having a high index of suspicion and starting some of these meds at lower doses, many of which, like clonidine, also treat opioid withdrawal, but also not starting everyone at the highest dose and walking away and, you know, not thinking about it anymore because a lot of patients actually, you know, still plenty of people do okay. But I do think that at least most people experience at least some more mild symptoms like the anxiety or that kind of edginess, but not necessarily the whole picture of all the autonomic instability.

Dr. Sean Cohen

I appreciate the point of like you have to tailor your approach to where you're working, what the drug supply is and also having a high index of suspicion if you're in the right place that has metatomatin supply. You mentioned that again the presentation is super variable. Do you have a sense or like I guess what is there a definition? Or like when do you consider someone refractory and needing step up care and do you have a sense of like how many people what or like a rough percent of people that do need more intensive care?

Dr. Maggie Lowenstein

Yeah. So I think again the measurement is really imprecise. But some of these same hall like sort of clinical scores or vital sign changes that I think I used to think about control. If you look at those, you know, if you're thinking about like somebody still having really significant tachycardia, like 1 teens, 120s, 130s, somebody whose hypertension is not responding to those med, to the oral meds, those are all people that you know, perhaps need to escalate to dexamenatomidine cows and then kind of alongside that cow scores tend to be remain high and not kind of go down. I think the other thing that often is the tipping point is if people start to have really severe nausea and vomiting that's either not responsive to the antiemetics we're giving or maybe we get behind and their QT gets really long and then we're feeling nervous about giving a lot of the antiemetics that we would otherwise be effective. And so that's another situation that just that really refractory nausea and vomiting that may be an indication for, for dexmedetomidine. And often that means ICU transfer at a lot of institutions, including my own. But we have, you know, looking at our own data, the rate and kind of number and rate of ICU admission and dexmedetomidine treatment for people with kind of in the metatomidine era has increased since we started detecting it. But right now about 30 to 40% of people end up on dexmedetomidine in my hospital. And you know again that for us means an ICU transfer. Some places have implemented this in like step down units. But you know that that is a little bit institution dependent. But just in terms of a ballpark of who really, you know, tends to be is refractory to some of these other options that's that's been our experience. And again, this is like in an area with really, you know, basically almost all the fentanyl has metatomidine. And we're talking about people coming to the hospital who are using really heavily. So we're essentially a pretty select sample. But yeah, but in terms of numbers and thinking about your own health system, that's our experience.

Dr. Carolyn Chan

So luckily for our patient, they did really well because we started them on all of these oral alpha 2 agonist medications. We got ahead of their vomiting using different agents. So I'm curious, what does the typical management look like after the acute withdrawal symptoms have subsided? Like how long are you tapering these medications over? How long does it typically take?

Dr. Maggie Lowenstein

Yeah, so we often see the worst of the acute withdrawal resolving within 72 hours, as I think, certainly when we think about how long people are on dexmedetomidine, it's usually about 48 to 72 hours. But in terms of how to de escalate beyond kind of turning off some of the IV infusions, this is even more expert opinion than the prior stuff because I think this is really something where our practice continues to evolve. I think again, going back to basics, we want to make sure someone's got an moud plan if that's in their wheelhouse and that we're managing the opioid withdrawal. We typically are going to wean antiemetics and try to get alpha ago agonist doses down to like a number that or a dose that many of us would feel more comfortable discharging people on. But I think initially we were doing pretty rapid tapers of clonidine and we weren't using guanficin and we were doing pretty rapid tapers of clonidine in the hospital and finding that for, you know, not insignificant number of patients, they were kind of having some reemergence of symptoms. Like I said, I see patients in both the hospital and clinic. And so I would have patients come in occasionally with like, you know, shortly after hospital discharge with like pretty bad tachycardia or hypertension. And more frequently it's not necessarily that, but just a lot more subjective kind of ongoing anxiety, edginess. People call it different things. And so I know our group has moved towards doing much slower tapers actually, if, if you can feasibly arrange for that. And that's going to depend on the comfort of the people you're handing off to and the ability to follow patients. But what I done and seen a lot of my colleagues do most recently is kind of get People down to a dose of clonidine, like 0.3 milligrams, maybe every eight hours, something like that. And then sending them home with a scheduled taper over the course of the next, say like three or four weeks if they're going to like rehab or a monitor facility or something, and then discharging them for if they're going to the community, trying to discharge them into outpatient follow up so someone can kind of assess them and help them, them think about the pace of the taper. And in my own experience I've seen that taper be, you know, sometimes just a couple weeks and sometimes patients really feel it and it, they, it feels like it works best for them to go even a few months out, like very slowly. But we have gotten them off of it. So I don't know the right answer. I think it's patient dependent. But our group has moved towards at least recommending some at discharge with either kind of a planned taper or sort of a touch point to reassess and kind of continue to prescribe and help patients get off of it eventually. But yeah, I think very much expert opinion there.

Dr. Sean Cohen

I appreciate the plug for not forgetting about the importance of meds for opioid use disorder too. And I guess like knowing that metatomidine is kind of throughout the fentanyl supply, like, how has that changed? I mean, a lot of our job, I think in the hospital and your job in the outpatient setting too, is like talking through harm reduction and how to keep people safe. And so how has that changed that conversation for you? Or like, what do you talk to patients about regarding metatomanine?

Dr. Maggie Lowenstein

Yeah, I mean, I think the first thing I try to talk to patients about is just helping them understand what they have gone through. It's really awful and traumatic for people as they, especially for the first time they're experiencing it. And people will say, I've never felt this bad in my life. And like, why, especially if, you know, they're, you're getting treatment with things like methadone or, you know, sort of, you know, other opioid agonists and you're like, why do I still feel so sick? So I think really helping them understand like what has happened and you know, really that they're, we're dealing with like two different substances and kind of, you know, just contextualizing that for them because it's really scary and traumatic and confusing for both patients and clinicians. But beyond that, I think, you know, a couple things I again, really always plug getting them on moud, if that's their goal. But you know, if kind of letting them know that they may still experience some withdrawal if they are on MOUD and continue to use is kind of part of that conversation as well, depending on, you know, what the patient's hoping to do. A couple other like more kind of specific harm reduction things. In our case, metatomidine is really so pervasive. It's things like testing strips or metatomidine test strips aren't super helpful because I think it's hard to get drugs without it. But that if you're in a region where it's more variable that those are available commercially. I think it's commercially or at least they exist. And I also talk to people about that it's a potent sedative. And so some of the things we talked about before, like being careful about heat related injury or cold related injury, if you're sort of using outside and then you become sedated. And then the most important thing we've already talked about but is worth talking about again is just the, you know, know that naloxone is still effective to reverse overdose and like don't, you know, don't let anybody tell you otherwise. It will reverse the, you know, the opioid part of the overdose. And that, that's really important for people to understand and still have at discharge. So those are, I think that's probably the bulk of it. But yeah, I think it's still kind of confusing for patients and really, again, really, really unpleasant and traumatic in some cases. And so I think kind of helping them to just understand what was going on. And you know, that's, that's a very important piece of this.

Dr. Carolyn Chan

And also curious, you know, thinking back to our patients, she's done really well this hospital stay. You know, we have now gotten her to a routine dose of clonidine, like 0.2 milligrams every six hours. Her cellulitis is improving. We're going to put her on oral antibiotics and we're getting ready to really think about her discharge plan planning. We really want to just try and set her up for as much success as possible with that transition. Do you have any tips or best practices as we help transition patients in the hospital who may have opioid use disorder or honestly any other substance use disorder. Right. To successfully helping them engage in sort of like outpatient treatment if that's what they desire?

Dr. Maggie Lowenstein

Yeah, yeah, no, I think that's really, really important. And you know, the big role of when people come to the hospital and have kind of gone through all this, we really want to help them kind of meet their goals afterwards. So I think the first thing is just really kind of spending a fair bit of time on making a clear transition plan, like figuring out what, what their follow up, you know, MOUD and other care is. And I think if, if at all possible, like kind of getting everything scheduled, getting everything lined up, communicating if possible with the outpatient. So if you adjust to methadone dose, making sure that's documented communicated with the OTP, if they're a new start of an MoUD, making sure they have an OTP intake or a buprenorphine follow up and a bridge, a prescription to get them to there. I think having some of the just things that are really probably good practice for a lot of patients, but trying to get meds to bed, making sure they have transportation lined up, making sure you've done the harm reduction teaching or the naloxone, you know, handing them the naloxone, all those kind of things. I think a couple, you know, specifically that with the Alpha 2 withdrawal, really trying to articulate a taper plan. I know in our area there's really variable comfort with kind of managing that as an outpatient. And I think especially a lot of places that aren't like, you know, traditionally doing like vital sign assessments, like behavioral health settings may not, you know, that this is new to them. So I think really kind of, of being clear about, you know, what, what dose you're discharging, what some of that follow up expectations are. And then I'm just like a really big fan of having many backup plans. And so I think if, you know, there's just so many ways that things can fall through here in this, you know, like the patient gets to the pharmacy and it's closed or they, you know, like their appointment is at the wrong place. You know, there's a million ways that things can go wrong. So I really, I think if at all possible having some sort of system in place that plans for these unexpected things, whether it's having a person who they can call or a bridge clinic or some sort of walk in situation and maybe the ED is your ultimate backup. But really talking through what might happen if things fall through, hoping that they don't, but really kind of empowering patients to advocate and follow up even if it doesn't work out as planned. So that's kind of my other. I always say to patients on discharge, I'm like, we're going to have like a great plan and then we're going to have, you know, a really great backup plan and maybe another backup plan just because I just again, I hate to see. I've seen too many things kind of fall through the cracks if we don't have that. And so yeah, I think that's really important.

Dr. Carolyn Chan

I love that. A minimum of three backup plan. Going to add it to my consult notes. A, B, C. Yeah.

Dr. Maggie Lowenstein

So like I'll say in our context, we have a kind of telehealth navigator team. So we'll give them their phone number and then there's also like a drop in option and so we'll kind of, you know, we'll kind of provide them with that information. So like that's, you know, one of many examples. It just depends on where you work. But if you have it, you know, use it, empower patients to use it.

Dr. Carolyn Chan

Great. Well, I think that this has been a wonderful episode. We've learned so much from you and um. Sean, anything else before we move to take home points?

Dr. Sean Cohen

No, I mean I think you. Yeah, I think you walked us through kind of a relatively complicated topic and a complicated hospitalization and get made. I mean, I feel even though I've been seeing this, more comfortable managing metamidine withdrawal after this and methadone. So I appreciate kind of all the tips and tricks.

Dr. Maggie Lowenstein

Yeah.

Dr. Carolyn Chan

Do you have any final take home points for our audience that you just want to re. Emphasize?

Dr. Maggie Lowenstein

Yeah, so I guess I'll say I think, you know, metatomidine withdrawal is something we're seeing a lot in Philly and people are seeing variably other places. So I think sort of kind of having a, having an index of suspicion, thinking that this, you know, keeping an eye out for patients who may be fitting this presentation and then when they do, remembering the kind of the mainstays are the opioid, you know, oud treatment, managing the opioid withdrawal and then also dosing, you know, aggressive dosing of alpha agonists and antiemetics. And then I think the other thing is, you know, staying tuned for how this is evolving over, you know, these. There's a lot of new data coming out. There's like protocols are changing. I know a couple of places that do this work a lot, including my own, have put some of our protocols online to be available publicly. There's some great papers that we'll put in the show notes. But I think really sort of as this evolves, kind of keeping, keeping an eye on it because it is something that we're learning more and more about every day.

Dr. Carolyn Chan

Awesome. And is there anything you want to plug, no pressure. If there's anything addiction related, non addiction related that you just want to share with our audience?

Dr. Maggie Lowenstein

I guess I will plug our Penn center for Addiction Medicine and Policy website which is one of the places that houses a lot of this information that I'm referring to. So we try to update again, Philadelphia is a place that we often unfortunately are one of the places that foresees a lot of the new adulterants or other kind of new drug supply changes. So we're often on the front lines seeing and trying to, you know, treat these things. And so we try to do a, we, we really make an effort to put as much as we can online and kind of keep, you know, so you can come to our website, see what we're doing now and then come again in a month or two and see how that has changed in the this case. But I think that can be a really helpful resource.

Dr. Sean Cohen

I will say I go to that website all the time. So.

Dr. Carolyn Chan

Oh good.

Dr. Sean Cohen

Even I looked up this morning.

Dr. Maggie Lowenstein

So yeah, I think again this, this paper that I have mentioned from Mike lynch at Pittsburgh is really helpful summary of a lot of this management. But I think there's not a lot else publicly available out there kind of with the details. And so as I would just, you know, again try to, there's a couple of resources, ours being one of them that you can look to.

Dr. Sean Cohen

Great.

Dr. Carolyn Chan

Well, thanks so much Maggie. We, we appreciate your time.

Dr. Maggie Lowenstein

Oh, thank you. It was a pleasure to be here.

Dr. Carolyn Chan

This has been another episode of our Curbsiders miniseries, the Curbsiders Addiction Medicine. Get your show notes@the curbsiders.com addiction but are you still hungry for. For more, join the Curbsiders Internal Medicine Patreon and get all episodes ad free twice monthly bonus episodes@patreon.com curbsiders. You can also find show notes@thecurbsiders.com and sign up for our mailing list to make sure our weekly show notes end up in your inbox.

Dr. Sean Cohen

We are committed to providing you with high value practice changing knowledge. To do that, we need your feedback. So please subscribe, rate and review the show on Apple Podcasts and contact contact us at curbsiders addiction med gmail.com A reminder that this and most episodes are available for CME credit for all healthcare professionals through VCU Health at curbsiders.vcuhealth.org and

Dr. Carolyn Chan

a very special thanks to ACAM, the American College of Academic Addiction Medicine. Learn more about their organization@acaam.org. and thank you so much to our writer, our producer for the episode, Dr. Sean Cohen Cohen, our editor, Dr. Pyle Roy, and our incredible infographics expert, Zoya Serrani. And honestly, the entire Curbsiders team. Our technical production is done by the team at Podpaste. Elizabeth Peroto does our social media. Jen Watto runs our Patreon. Chris the Troop and Troupe moderates the discord. Stuart Brigham composed the theme music. And with all that, honestly. Until next time, I am Dr. Carolyn Chan.

Dr. Sean Cohen

And I am Dr. Sean Cohen. Thank you all for joining us today and letting us bring you some addiction med pearls.

Dr. Maggie Lowenstein

How did you get your website to look like that? Mine's so basic. Thanks. I just used wix Harm Harmony. Sounds fancy. What's that? It's wix's AI website builder. You can just tell it what you want and it builds you a whole site. So it's like vibe coding a website? Exactly, but even better, because you can still click and edit anything by hand. You don't have to use prompts for everything. Oh, that's neat. Yeah. Try it for free@wix.com Harmony.