[SPEAKER_01]: Hello and welcome back to ACRAC.
[SPEAKER_01]: I'm Jed Wolpa and I am thrilled to have a fabulous guest for a fabulous topic today.
[SPEAKER_01]: We are going to talk about buprenorphin, something that is just really on everyone's minds these days.
[SPEAKER_01]: And I have with me Dr. Tom Hickey, Tom earned his medical degree from Harvard Medical School.
[SPEAKER_01]: and completed anesthesia residency at Brigham and Women's Hospital.
[SPEAKER_01]: He joined the Yale faculty in 2015 and he's a full-time staff at the West Haven VA Hospital.
[SPEAKER_01]: He's board certified in both anesthesiology and addiction medicine and his research interest focus on the overlap between addiction and acute pain management.
[SPEAKER_01]: So he is really the perfect person to have this discussion and I'm thrilled to have him here Tom.
[SPEAKER_01]: Thanks so much for coming on the show.
[SPEAKER_01]: The light is to be with you.
[SPEAKER_01]: So I read a little bit there, but tell us a little more about you.
[SPEAKER_01]: How do you get where you are?
[SPEAKER_01]: What does your career look like and how do you get interested in view of an orphan?
[SPEAKER_00]: Yeah, great question.
[SPEAKER_00]: So I think anybody who is co-resident with me at the Brigham shout out to the Brigham.
[SPEAKER_00]: Probably knows I had kind of a natural affinity for pain management.
[SPEAKER_00]: And I always had this feeling like, well, there's got to be a better way to handle these patients with chronic pain with chronic opioids.
[SPEAKER_00]: I feel like we just keep screwing this off every time.
[SPEAKER_00]: Like an ambulance or a case becomes like a five-day painful admission.
[SPEAKER_00]: You evolve in there, and there's no easy way to do it.
[SPEAKER_00]: But I think there was an inclination, and when I got to my current job at Yale and in the Connecticut D.A.
[SPEAKER_00]: healthcare system, and these are my views by the way, not the governments.
[SPEAKER_00]: It was actually a case cancellation, so something we all lived through if we've been in practice over say a decade or so, and it was a case cancellation because a patient who's on,
[SPEAKER_00]: buprenorphin for opioid use disorder, so most of us think suboxone, which is the buprenorphin eloxone combination product, and the guy had woken up that day like every day, taken as 16 or 24 milligrams of buprenorphin, and came in for his elective hip surgery, which he looked forward to for months, probably a lot of planning went to it, and the anesthesiologist very reasonably at the time said, sorry sir, really can't do it because we were too dang nervous about your pain management.
[SPEAKER_00]: So that was then, right, this probably about eight years ago.
[SPEAKER_00]: And that was, by the way, what we learned at the Brigham when I graduated in 2015, it was just the best practice.
[SPEAKER_00]: And more, more background on that later, I think, I'm sure we'll get into it.
[SPEAKER_00]: But at that point, the surgeon said to me, listen, Tom, like, I don't care what we do with this drug, but what we're doing ain't working, right?
[SPEAKER_00]: It just ain't working for anybody.
[SPEAKER_00]: So I partnered with an addiction psychiatrist, and honestly I don't even know if I knew there was such a thing as addiction psychiatrist at the time.
[SPEAKER_00]: And together we partnered and developed a very operative management strategy to try to really formalize our approach to these patients.
[SPEAKER_00]: So that got me interested in addiction medicine.
[SPEAKER_00]: And lo and behold, there was this pathway to addiction medicine through the ABPM, a practice pathway.
[SPEAKER_00]: and you just have to justify you practice addiction medicine and I would put it to the anesthesia audience every day you think about a careful anesthetic plan for your patient really you're practicing some addiction medicine.
[SPEAKER_00]: And the more I learned about bupromorphin in particular the more interested I became in particular getting to know what I think is largely forgotten literature for acute pain management.
[SPEAKER_00]: I thought man it was a good option in the 70s, good option in the 80s, good option in the 90s and it's a good option in 2026.
[SPEAKER_00]: So that's that's kind of the story, Jen.
[SPEAKER_01]: very cool yeah and I'll tell you I think so my my sister-in-law shout-out duty runs in addiction medicine fellowship and it's really just a fascinating field and incredibly applicable these days and she gets applicants from all different fields and so if folks are interested I think that's a really neat thing to think about as a way to take your career.
[SPEAKER_01]: So let's talk about buprenorphin specifically.
[SPEAKER_01]: Give me a little background on it.
[SPEAKER_01]: Tell me about the drug.
[SPEAKER_01]: Where did it come from?
[SPEAKER_01]: Obviously it's been around a while, but I think it's maybe entering people's minds in a way it hasn't before.
[SPEAKER_01]: What makes it unique?
[SPEAKER_00]: It's a great question, too.
[SPEAKER_00]: And I would recommend to the readers.
[SPEAKER_00]: Ask Google right now for a speech that a British chemist gave his name is John Lewis.
[SPEAKER_00]: So Dr. Lewis, he gave it before the college on problems of drug dependence.
[SPEAKER_00]: And he called it, Jed, in pursuit of the Holy Grail.
[SPEAKER_00]: So I know people out there like Hickie's, a Homer, for Beep and Orphan.
[SPEAKER_00]: I'm not the only crazy one out there if that's the case.
[SPEAKER_00]: This guy, John Lewis, and his colleagues, they were tasked in the 60s.
[SPEAKER_00]: would try to find an opioid and actually at the time it was to find an opioid that replaced an over the counter aspirin coding product, which is weird to think about an over the counter opioid, but that's what they were tasked to do.
[SPEAKER_00]: And that team of chemists thought
[SPEAKER_00]: Well, we know opioids are enormously complicated.
[SPEAKER_00]: There's a bazillion downstream effects, most of which are bad, right?
[SPEAKER_00]: Unless you're treating like diarrhea or tickipnea, they're bad.
[SPEAKER_00]: Basically, we just want the analgesia and nothing else, basically.
[SPEAKER_00]: So they thought, well, we know there's this full partial dichotomy and people's mind about opioids.
[SPEAKER_00]: They said, well, why don't we try to find the one that's the most full franalgesia and the most partial for everything else?
[SPEAKER_00]: And I think in Bupin orphan, they felt like they found that.
[SPEAKER_00]: Not perfect.
[SPEAKER_00]: Not perfect by any means, but that's what they thought.
[SPEAKER_00]: And that's what they're testing, of course, then, and animals really bore out.
[SPEAKER_00]: More on tested humans to come.
[SPEAKER_00]: Now, what was it about people in orphan, I think, that made it so a really fascinating pharmacology?
[SPEAKER_00]: So I promise you, Jed, this will be quick and clinically focused to the readers, though, the listeners don't put me on two X and start like unloading the dishwasher.
[SPEAKER_00]: But basically,
[SPEAKER_00]: There's some aspects in which it's very fascinating.
[SPEAKER_00]: Highly lipophilic, more so than anything you or I give on a day-to-day basis, fentanyl methadone, it's more lipophilic, which I think results in a getting into the brain, getting into the spinal cord quickly.
[SPEAKER_00]: We all learn that in pharmacology, a rapid onset, even when you give it under the tongue or against the cheek, it has a very rapid onset.
[SPEAKER_00]: So that's one thing.
[SPEAKER_00]: a very high affinity, second only to sufen to the one when Connelly's opioids are tested, affinity for the Murie sector.
[SPEAKER_00]: That aspect, together with a long dwell time, which is kind of a niche pharmacologic aspect, or topic I don't think many of us learn about, but those two things together give it a long duration of action.
[SPEAKER_00]: So for opioid use disorder, we're talking days for analgesia, like eight, nine hours, which I think better matches pain relief to pain, and that's something certainly fentanyl doesn't do.
[SPEAKER_00]: even though we use that like water.
[SPEAKER_00]: Me too.
[SPEAKER_00]: I'm guilty of that as well.
[SPEAKER_00]: So the next topic gets kind of the safety.
[SPEAKER_00]: So I think there's two key things.
[SPEAKER_00]: One is this intrinsic efficacy, which is usually described as low to intermediate.
[SPEAKER_00]: What does that mean to most people?
[SPEAKER_00]: That means it's partial.
[SPEAKER_00]: So that has contributed to this historical classification as a partial agonist.
[SPEAKER_00]: As opposed to the so-called full agonist, we always use.
[SPEAKER_00]: We always reach for morphine, hydro morphone,
[SPEAKER_00]: So that's one thing.
[SPEAKER_00]: The others this bi- agonist profile, which I admit to the listeners is kind of a nerdy niche topic as well.
[SPEAKER_00]: But basically you get more of the good less of the bad.
[SPEAKER_00]: More of the good less of the bad.
[SPEAKER_00]: More of the G protein coupled response less of the beta-rest and response.
[SPEAKER_00]: So more analgesia and less tolerance and receptor internalization, GI in respiratory ill effects.
[SPEAKER_00]: So those two things, the partial agonists and the bias agonist profile, then to its safety.
[SPEAKER_00]: And we'll talk more about that.
[SPEAKER_00]: I'm sure we talk about respiratory depression in particular.
[SPEAKER_00]: The other thing I think the listeners might be waiting for is me to talk about Kappa and Delta antagonism.
[SPEAKER_00]: It's a thing.
[SPEAKER_00]: I don't know, I can't sit here and you know, put a flag in the ground about how important they are in our clinical day-to-day.
[SPEAKER_00]: as well as pharmacologically active metabolites.
[SPEAKER_00]: So in every spec, like we learned about methadone and how methadone has these multimodal aspects, who proffin, you could say the same about.
[SPEAKER_00]: If nothing else, it's kind of cool to think about.
[SPEAKER_00]: a hepatic metabolism via P450 system, safe and renal failures, one aspect that's maybe in the ICU world might be especially advantageous.
[SPEAKER_00]: And then I think the last thing I'll say on sort of this pharmacologic background is that the government looked at it and said this is a scheduled 3-drug.
[SPEAKER_00]: Okay, what's that mean?
[SPEAKER_00]: Well, it means they thought that it's moderate to low risk of physiologic and physical, a psychological and physical dependence.
[SPEAKER_00]: And one other thing that,
[SPEAKER_00]: I get a blank stare sometimes for anesthesia people because you know I think we sometimes say God give people veins so we could put drugs in them right where IV people it's way we think it's what we do but there's a lot of formulations that I think are really advantageous especially when you get a patient beyond the pack you even in the pack you for that matter where really best practices are to avoid IV opioids so there's trans dermal
[SPEAKER_00]: Some people may have seen more and more of their patients on trans-dermal and buckle formulations.
[SPEAKER_00]: These would be for chronic pain management, where they have a labeled indication.
[SPEAKER_00]: Sub-lingual, which is ubiquitous, appropriate use disorder.
[SPEAKER_00]: Also, long-acting injectables for opioid use disorder.
[SPEAKER_00]: This would be sublocate, the monthly, and Brick's Adi, which has variable dosing intervals.
[SPEAKER_00]: I even was reading some papers from Japan and discovered there's a rectal repository, you know.
[SPEAKER_00]: Yeah, interesting.
[SPEAKER_00]: So, I would just suggest to the audience that these four relations provide some interesting flexibility opportunities to study, it may have been since our intern year, which we contemplated a sublingual drug, like NTG or something like that.
[SPEAKER_00]: But tell on you, it's not hard.
[SPEAKER_00]: Once you do the buckle once, you may become a believer.
[SPEAKER_01]: Okay, very interesting, and any NMDA receptor, a factor, no.
[SPEAKER_00]: Not that I'm aware of, I think when people talk about, say, anti-hyperal jizic effects, they usually kind of weigh their hands and talk about capo and delta antagonism.
[SPEAKER_00]: But the more you learn about this drug, the less it seems to, you know, so I wouldn't, I wouldn't rule it out entirely.
[SPEAKER_00]: But yeah, that's like a methadone, right?
[SPEAKER_00]: You think going to be a antagonism, maybe some sodium channel action and, yeah, right.
[SPEAKER_01]: Okay.
[SPEAKER_01]: Very interesting.
[SPEAKER_01]: So you mentioned safety before and obviously one thing we think about ubiquitously when we think about opiates is respiratory depression.
[SPEAKER_01]: And I think that people think about buprenorphine is having a ceiling, in other words, not causing as much respiratory depression as other opioids like Fendell delighted.
[SPEAKER_01]: What do we know about that?
[SPEAKER_01]: Is it safer?
[SPEAKER_00]: I think so, I think what we know is that there is that ceiling effect and I'll describe some studies.
[SPEAKER_00]: I would just put some table stakes out there, which is that we continue to use a lot of opioids in our patients despite really valiant efforts, I think, by us, by surgeons, by nursing, to really reduce their use.
[SPEAKER_00]: So we've done good job at that, but still we reach for opioids.
[SPEAKER_00]: People in our fin, as I'll describe, has important safety advantages, but still in opioids, still should be treated like an opioids, it's not a cure all.
[SPEAKER_00]: You should think about CDC prescribing guidelines, lowest effective dose, at least amount of time, and all that stuff that we've been beaten over the head with for good reason, and always multimodal analgesia.
[SPEAKER_00]: But I think in this way, we could think people orphan as a harm reduction.
[SPEAKER_00]: So why do I say that?
[SPEAKER_00]: Bottom line up front.
[SPEAKER_00]: It's relatively hard to compare to what we're reaching for every day to harm our patients with deep breaths.
[SPEAKER_00]: Respiratory depression would be the first abuse potential would be the second.
[SPEAKER_00]: So from a respiratory depression point of view, it's out there.
[SPEAKER_00]: It's almost always out there in combination when it's really a harm to patients.
[SPEAKER_00]: It's out there in combination with another CNS depressive.
[SPEAKER_00]: Benzo's being the most notable.
[SPEAKER_00]: If you look at studies involving respiratory depression as a primary outcome, you put off in really shy and it's very impressive.
[SPEAKER_00]: So the one that's usually looked at first is by DeHon.
[SPEAKER_00]: He's published a lot on this, 2006, and it was a double blind placebo control trial where basically volunteers got fentanyl.
[SPEAKER_00]: No surprise to anybody, above like three mics per kilo, they get it unstable, and then acne.
[SPEAKER_00]: I mean, they're getting a sternal rub saying, Jed, Jed, you know, deep breath.
[SPEAKER_00]: People are often on the other hand.
[SPEAKER_00]: the fentanyl goes to the x-axis.
[SPEAKER_00]: The buprenorphine goes to about 50%.
[SPEAKER_00]: That's what they found, increasing doses of buprenorphine that by about two to four microperquilo, and that's where the ceiling effect concept comes in.
[SPEAKER_00]: This is a good ceiling effect.
[SPEAKER_00]: A couple other studies worth mentioning that look at the different formulation.
[SPEAKER_00]: So Webster, at all 2020, they recruit volunteers who are
[SPEAKER_00]: had experienced with opioids, but were deemed non-opioid dependent by a negative urine toxin and eloxone challenge.
[SPEAKER_00]: And then they slug them with increasing doses of the buckle formulation, up to 900 mics.
[SPEAKER_00]: So the maximum available dose, and guess what?
[SPEAKER_00]: Indistinguishable from placebo.
[SPEAKER_00]: We'll rest in the rest.
[SPEAKER_00]: For respiratory depression.
[SPEAKER_00]: Exactly.
[SPEAKER_00]: So again, primary outcome when respiratory outcomes are the primary outcome.
[SPEAKER_00]: Now, similar study design and oldy but a good elite author was Walsh 1994, up to 32 milligrams.
[SPEAKER_00]: And again, same population, not opioid-dependent volunteers.
[SPEAKER_00]: That's a mega dose.
[SPEAKER_00]: Even in the fentanyl era, 32 milligrams of buber orphan is a heavy dose.
[SPEAKER_00]: And these guys, guess what their respiratory depression, their breaths per minute decrease by four.
[SPEAKER_00]: Wow, four breaths per minute.
[SPEAKER_00]: I mean, a 32 milligrams sublingual dose.
[SPEAKER_00]: That's pretty impressive.
[SPEAKER_00]: Now, this is experimental study.
[SPEAKER_00]: There's not all the variability of the OR, polypharmacy, and blowing off the CVO, and everything else.
[SPEAKER_00]: There's one other worth mention.
[SPEAKER_00]: And...
[SPEAKER_00]: It gets to the protective effect we could see in Buprofen.
[SPEAKER_00]: And this is by Moss at all.
[SPEAKER_00]: It's kind of a Balzy study, I think, 2022, where they basically did background Buprofen infusions in patients.
[SPEAKER_00]: They got an opioid tolerance group, an opioid native group.
[SPEAKER_00]: They give them background Buprofen infusions, and then they slug them with doses of fentanyl, big doses.
[SPEAKER_00]: Meanwhile, there's placebo infusions.
[SPEAKER_00]: Up to like 800 mics or so, a fentanyl.
[SPEAKER_00]: 50% reduction in fentanyl induced respiratory depression in the Buprofen.
[SPEAKER_00]: So you can imagine a scenario where you get that buprenorphine on board of patient.
[SPEAKER_00]: It's a, you can look at it kind of as a foundational opioid.
[SPEAKER_00]: And the other one's on top of it, maybe you see less respiratory depression.
[SPEAKER_00]: I'm theorizing that because these are of course experimental studies.
[SPEAKER_00]: We just don't know.
[SPEAKER_00]: Well, the next big category of use potential.
[SPEAKER_00]: So you can absolutely find non-prescription use of buprenorphine.
[SPEAKER_00]: It's certainly a thing, but it seems comparatively less compared to these other usual opioids,
[SPEAKER_00]: So a large study lead author was Bach, 2016 to 2020, found only 1% of 1600 persons who are surveyed use buprenorphin in a non-prescription way.
[SPEAKER_00]: So I think it's comparatively less.
[SPEAKER_00]: And I think that's reinforced by some early studies that looked at the positive negative reinforcement, something I think it was at your...
[SPEAKER_00]: cousin, or did you say was the program director?
[SPEAKER_00]: My sister-in-law, yeah.
[SPEAKER_00]: Fist-in-law.
[SPEAKER_00]: So it's kind of the jargon that we learned, but maybe we forget, like the addiction starts with the positive reinforcement.
[SPEAKER_00]: It's there to some extent.
[SPEAKER_00]: People can recognize it's an opioid.
[SPEAKER_00]: There's some euphoria, but less.
[SPEAKER_00]: But I think where it shines and what really drives the disasters of addiction.
[SPEAKER_00]: is the negative stuff.
[SPEAKER_00]: Keeps you coming, results in the compulsive use in the craving, the bad stuff, the horrible withdrawal, and that's much milder with DuPrenorphine.
[SPEAKER_00]: So it makes sense that there'd be less of this non-prescription use.
[SPEAKER_00]: Now just kind of rounding out the topic, there is the possibility
[SPEAKER_00]: that you'd need big doses of nooxone.
[SPEAKER_00]: So if you're going to a situation where you have to reduce, I'm sorry, treat buprenorphine induced respiratory pressure.
[SPEAKER_00]: Grab a ton of nooxone bios.
[SPEAKER_00]: It's not going to be one, it might be 10.
[SPEAKER_00]: So two to four milligrams an experimental study by Van Dorpittal to reverse buprenorphine induced respiratory pressure.
[SPEAKER_00]: But I would hasten to add.
[SPEAKER_00]: They were treating a 40% reduction in minivanolation.
[SPEAKER_00]: I mean, it will work.
[SPEAKER_00]: It takes a lot more in that particular case, 40% reduction of manipulation, probably, you know, Dr. Wolpo is not treating that and pack you or ignore ICU.
[SPEAKER_00]: But it's experimental study, and it provided that useful information that you got to go to the mattresses with the lock zone if you're really worried about it.
[SPEAKER_01]: And then, let me ask you about that because,
[SPEAKER_01]: So let's say that you reverse it, uh, I would imagine the half life of an aloxone is shorter than the half life of the buprenorphine.
[SPEAKER_01]: So do you need to put them then on a, if you want to maintain that reversal, you have to put them on an infusion, I would imagine or keep reducing.
[SPEAKER_00]: At the very minimum, I'm in a closely monitored environment and have all that stuff at the bedside ready to go, I would think, okay.
[SPEAKER_00]: I haven't run into that situation yet.
[SPEAKER_00]: And we've been using a lot of B.P.N.R.F.N.
[SPEAKER_00]: The last thing I'd say is just of interest, people can check this out, that B.P.N.R.F.N is actually a good research.
[SPEAKER_00]: So it's multiple studies of shown.
[SPEAKER_00]: It's comparable to the lock center of our soap you'd do stress-betray depression.
[SPEAKER_00]: As for all the other things we worry about with opioids, buprenorphin will be a culprit.
[SPEAKER_00]: Now, as you're vomiting, dizziness headache, probably less parietas, but otherwise for common adverse effects, you'll see them.
[SPEAKER_00]: And you just, you gotta do the preemption just like we would normally do with morphine, hydromorphone, whatever.
[SPEAKER_01]: Okay, Faba.
[SPEAKER_01]: So you said that one of the uses is to, you know, treat pain while reducing abuse potential because this is not a drug that seems to be used in a abuse in a way that would lead to abuse or to dependence or addiction, but in fact also is used to treat opioid use disorder.
[SPEAKER_01]: So how are we likely to encounter buponorphine in our clinical practice?
[SPEAKER_01]: Is it going to be patients who have opioid use disorder and are on buponorphine for that?
[SPEAKER_00]: Yeah, so buber orphan is the most prescribed medication broke your abuse disorder in the U.S. And people out there listening should just realize that this is a disease that's under-treated.
[SPEAKER_00]: So it's good if we see more of our patients on buber orphan for opioid disorder.
[SPEAKER_00]: That means they're getting treatment for life-threatening disease.
[SPEAKER_00]: Most of the studies that look at outcomes in opioid use disorder mortality find that if your treatment with buber orphan or methadone's like a 50% reduction of mentality, mortality, scusy.
[SPEAKER_00]: And more ability, of course, all the downstream stuff from good treatment, including like HID and have to see all that stuff decreases to with effective treatment.
[SPEAKER_00]: Sublingual is by far the commonest formulation prescribed, appropriate use to sorter, and in general there's
[SPEAKER_00]: a ton of different ways to approach induction in patients.
[SPEAKER_00]: The literature is all over the place.
[SPEAKER_00]: Most of them, though, are successful.
[SPEAKER_00]: And they all result in basically titrating up you for an orphan until patients feel some normal.
[SPEAKER_00]: The cravings are eliminated.
[SPEAKER_00]: The compulsive uses reduced to eliminated.
[SPEAKER_00]: They get some normal back in their lives.
[SPEAKER_00]: And that usually is about 16 to 32 milligrams.
[SPEAKER_00]: And I think it helps to just think about the CNS and the muereceptor for a second.
[SPEAKER_00]: at these big doses, so a lead author Greenwald and colleagues did some fascinating studies, but they took patients who were maintained on buprenorphine, say a 16-millimeter dose, and then four hours later they go to a pet scanner, they get injected with tagged car fentanyl, which is obviously going to hunt mirrored septors.
[SPEAKER_00]: And if they're there, it'll bind them and they'll light up at the pet scan.
[SPEAKER_00]: So after a 16-millimeter dose, it's like over 80% or 80% ish of mirrored septors are occupied, which is what that patient needs
[SPEAKER_00]: We'll talk more about it when we talk about pain, probably next in terms of how little and tiny the doses are for pain, but that's kind of the background for opioid use disorder treatment.
[SPEAKER_01]: And I want to make sure I understand what you just described.
[SPEAKER_01]: So they get the dose of buprenorphine and then the tagged car fentanyl is what role is that playing?
[SPEAKER_01]: What is that doing?
[SPEAKER_00]: That's just taking that.
[SPEAKER_00]: I mean, I don't know the radiology exactly, but it's taking that.
[SPEAKER_00]: isotope or whatever's actually going to show up on the pet scanner and it's going to grab onto some part of the brain where there's a mirror separator.
[SPEAKER_00]: And that way when they image the patient, they can see how much of the brain essentially lit up with the car fentanyl, well, the tagged car fentanyl.
[SPEAKER_00]: And they can make an estimate of the mirror receptors that are available.
[SPEAKER_00]: Their neat studies with beautiful pictures of the brain if you're into that kind of thing.
[SPEAKER_00]: And another thing that Greenwald and colleagues did is they correlated, simple, like, how the patients feeling to the unreceptor availability slash occupancy, they're in burst out of sleep, and found like, are you feeling or experiencing cravings?
[SPEAKER_00]: No, I'm not.
[SPEAKER_00]: Well, that's because 80% of your unreceptors are available.
[SPEAKER_00]: Well, maybe a 20% you're starting to really experience some, some craving and so on.
[SPEAKER_00]: So that's, that's the study.
[SPEAKER_01]: So the, when you say 80% were available, that means that the
[SPEAKER_01]: binding by the car fentanyl to 80% of them.
[SPEAKER_00]: Yeah, after a 16-millogram dose, 80% were occupied by buprenorphine.
[SPEAKER_00]: Okay.
[SPEAKER_00]: On available to the car fentanyl.
[SPEAKER_00]: Thank you for clarifying.
[SPEAKER_00]: So it just shows you there's not a big receptor reserve there for us to use other opioids.
[SPEAKER_01]: Yeah, and so that, so what you're saying is the craving and and need for opiate comes from unbound mu receptors.
[SPEAKER_01]: And so if you bind them with you Boopin' Orphan, then that you're not going to have that craving.
[SPEAKER_01]: And it sounds like 16 milligrams was enough to reduce that craving.
[SPEAKER_00]: 16 milligrams is usually about where people end up.
[SPEAKER_00]: It's a that or more, some less, but that or more, especially in the fentanyl era, where higher doses have been required to get people under control.
[SPEAKER_01]: Okay.
[SPEAKER_01]: Really fascinating.
[SPEAKER_01]: So what about for chronic pain?
[SPEAKER_01]: I think we're seeing more patients on bupone orphan for chronic pain, is that evidence-based?
[SPEAKER_00]: The evidence-based at pain is sometimes not the greatest.
[SPEAKER_00]: I think we can acknowledge and chronic pain is hard to treat.
[SPEAKER_00]: I also think that opioids are not recommended for chronic non-cancer pain.
[SPEAKER_00]: So let's just stipulate that.
[SPEAKER_00]: So I think the evidence-based for treating a patient with chronic non-cancer pain with any opioid including buprenorphine is not great.
[SPEAKER_00]: It could be opposite, right?
[SPEAKER_00]: Yeah.
[SPEAKER_00]: But in this setting,
[SPEAKER_00]: where that's face it, patients are still on opioids for chronic pain.
[SPEAKER_00]: Bupin orphan is increasingly recommended.
[SPEAKER_00]: So probably the,
[SPEAKER_00]: biggest recommendation I'm aware at least was by lead author Sandbrink and what they did is say VADOD you should think about this.
[SPEAKER_00]: It wasn't a super strong recommendation but it was the first of its kind that said we recommend considering buprenorphine for patients requiring daily opioids for the manager of their chronic pain why for the reasons that we mentioned less euforogenic effects and safer from a respiratory depression point of view.
[SPEAKER_00]: So I think in contrast
[SPEAKER_00]: at a OUD type dose.
[SPEAKER_00]: These doses are teeny.
[SPEAKER_00]: So starting dose in an opioid, naive patients say for Bucca, the buckle formulation is like 75 micrograms.
[SPEAKER_00]: So divide 32 milligrams by 75 micrograms.
[SPEAKER_00]: It's like potentially in the hundreds of times the dose for the opioid use disorder.
[SPEAKER_00]: So buckle, common for this, increasingly common, that was approved in 2015.
[SPEAKER_00]: So it's still kind of in catch on mode.
[SPEAKER_00]: Transdermal, I think, was approved for chronic pain in 2010.
[SPEAKER_00]: So you may see that to butreans.
[SPEAKER_00]: If you see those doses, they're very small, they're most likely for chronic pain management.
[SPEAKER_01]: And I guess I should have asked.
[SPEAKER_01]: We're talking about vehicles, trans-dermal.
[SPEAKER_01]: So this must not have oral bio-availability, is that right?
[SPEAKER_00]: A great question.
[SPEAKER_00]: It less than 10% oral bio-availability.
[SPEAKER_00]: OK, exactly.
[SPEAKER_00]: Sublink was about 30.
[SPEAKER_00]: Buckles about 55.
[SPEAKER_00]: Trans-dermals, if you read about it, it's 15.
[SPEAKER_00]: But it's all factored into the 10-bikes per hour, 20-bikes per hour.
[SPEAKER_01]: So you're actually getting, when they say 10-bikes per hour, that's how much it's getting into your intravenous system.
[SPEAKER_01]: Yes, sir.
[SPEAKER_01]: All right, so, have a very operatively, so, you know, this is a huge change since I trained, that we're seeing patients come for surgery on bupon orphan.
[SPEAKER_01]: I don't think I saw one patient during my residency on bupon orphan and now it's not uncommon at all.
[SPEAKER_01]: What is the best current practice for treating patients when they come to us for surgery who are on bupon orphan at home?
[SPEAKER_00]: This has really been a big change as the anecdotes suggested.
[SPEAKER_00]: So 10 years is not that long in medicine, right?
[SPEAKER_00]: 10 years ago, we were saying he should stop this drug for like three days.
[SPEAKER_00]: It was a well-intentioned practice because we were nervous about being the effectively treat patients pain.
[SPEAKER_00]: But in practice, what that old dog may did,
[SPEAKER_00]: was to create an opioid debt, maybe not withdrawal out and out with straw because we already said it's a milder syndrome, but you're basically taking creating an opioid debt, let's say, an opioid-tolerant patient who's going under a scalpel, and not only that, you're removing this life-saving medication, it creates a lot of anxiety, not just the patient, but the patient's family, and the prescriber, prescribers didn't like it, and I don't know if you ever remember this scenario, but sometimes we would be
[SPEAKER_00]: asking the prescriber to prescribe like oxycodone for a couple of days, which is kind of nuts and retrospect when the patient could have had an oxycodone addiction.
[SPEAKER_00]: So it wasn't great, even though I would just say it's well-intentioned, but thankfully retrospective data is just started to pile up a lot of it's safe from obstetrics where we knew that those women should stay on the buprenorphine throughout their pregnancy.
[SPEAKER_00]: And that data was just showing fairly clearly, even though it was retrospective that
[SPEAKER_00]: So, for the patients in whom it was withheld, for usually 72 hours, they were just requiring more analgesics and they had worse pain scores, as well as so you put that restrictive data together with what we know, which is that disruptions and OUD treatment can be really life-threatening.
[SPEAKER_00]: And the period operative setting is a real risk factor for that.
[SPEAKER_00]: Um, the, it led to a real paradigm shift over 10 years or so to just continue the but now you might say like, someone's on buprenorphine, is there a doshoot worry about?
[SPEAKER_00]: Is there, you know, any adjustments that need to be made and there the verdict is just not in yet I think with perspective data.
[SPEAKER_00]: There are some big health health care centers.
[SPEAKER_00]: The VA's recommendations include,
[SPEAKER_00]: include at least contemplating a dose reduction.
[SPEAKER_00]: Last I check my general Brigham, same thing.
[SPEAKER_00]: And the idea there would be if you reduce the dose little, it just gives you a little more flexibility.
[SPEAKER_00]: If you reduce the dose from 24 to say 16, maybe now you have some more, you know, opioid receptor reserve that you could treat the way you normally treat pain.
[SPEAKER_00]: I don't think there's a good evidence to support that.
[SPEAKER_00]: But I think the idea being would you keep enough people on our phone board to continue that, hope you'd just sort of treatment.
[SPEAKER_00]: And then you could,
[SPEAKER_00]: give some other opioids.
[SPEAKER_00]: Is the right answer to give more beef than orphan?
[SPEAKER_00]: Maybe, we just don't know.
[SPEAKER_00]: I could tell you when I talked to anesthesiologists and surgeons, they're more comfortable with the dose reduction idea.
[SPEAKER_00]: When I talk to addiction medicine audiences, like your sister-in-law, it's like, oh, heck, no.
[SPEAKER_00]: Let's not do that.
[SPEAKER_00]: Yeah, that's interesting.
[SPEAKER_00]: So it is kind of interesting.
[SPEAKER_00]: So I hope the easiest thing would be if the perspective trials just say, keep under the usual dose, and that's it.
[SPEAKER_00]: That'd be nice to see, because it'd be simple for everybody, we just don't know.
[SPEAKER_01]: Yeah, and this, this really comes down to the question of, is this a good way of treating acute pain or not, right?
[SPEAKER_01]: If it is, then maybe the more the better, and if not, then maybe we need to reduce the dose and have other options.
[SPEAKER_01]: So what do we think about that?
[SPEAKER_01]: Should we be thinking about Pupernorfer and as a frontline opiate in our day-to-day anesthesia practice?
[SPEAKER_01]: Is there evidence for that?
[SPEAKER_01]: What do you recommend?
[SPEAKER_01]: Stay with us.
[SPEAKER_01]: We'll be right back.
[SPEAKER_01]: All right, and we're back.
[SPEAKER_00]: Yeah, I think there's good evidence to support this for acute pain management.
[SPEAKER_00]: That's what you mean.
[SPEAKER_00]: Yeah, for patients just coming to your operating room for neighborhood placement, opioid naive, should we be thinking about buprenorphine?
[SPEAKER_00]: I'd say yes.
[SPEAKER_00]: So I just would stipulate for the audience that, again, despite our best efforts for still reaching for a lot of opioids, you probably know this literature as well as I do, patients come in for inpatient surgery over 90% are getting opioids.
[SPEAKER_00]: discharge after common surgery, 50% are getting discharge of opioids.
[SPEAKER_00]: A significant number, most studies say around 6% are taking six months later.
[SPEAKER_00]: Yeah, with significant harms to the system, to the patient, to the family, et cetera.
[SPEAKER_00]: So, like I kind of set at the onset, I was reading all these old studies.
[SPEAKER_00]: I mean, some of them really old,
[SPEAKER_00]: and has a scene being compared, you know, to be profan.
[SPEAKER_00]: So some old studies, and every time I looked at it, I might say, dang, who profanves doing good?
[SPEAKER_00]: Like, it looks impressive.
[SPEAKER_00]: And along came a systematic review meta-analysis in BJAA 2018 by Lead Offer White, and what they did is compared who profanves in just a morphine.
[SPEAKER_00]: It was acute pain in a hospital setting, but not all adults.
[SPEAKER_00]: Some of it was like renal colic ED kind of thing, so not all parry operatives.
[SPEAKER_00]: And their big conclusion was that buprenorphine was just as good as morphine, the granddaddy of opioids for acute pain management.
[SPEAKER_00]: But they didn't really put a lot of highlight on a p-value that was 0.07.
[SPEAKER_00]: And I was like, dang, that's interesting, right?
[SPEAKER_00]: So what I did was put together a team that really does this kind of thing, because I hadn't.
[SPEAKER_00]: And we did a meta-analysis that we published in Rappham earlier this year.
[SPEAKER_00]: And that included, and that looked at any study through time that looked at buprenorphin versus any comparator opioid.
[SPEAKER_00]: Just in adults, I don't do feeds to VA. And only perioperative.
[SPEAKER_00]: So kind of our patients, really.
[SPEAKER_00]: And an anesthesiologist, patients.
[SPEAKER_00]: And for the pain intensity outcome, we had almost 2,600 participants, so their data contributed to that and it showed to be profit significantly reduced pain intensity, the adz ratio for needing rescue analgesie was statistically significantly reduced, the duration of analgesie was eight and a half hours, and the average dose was about 750 micrograms, sublingual equivalent, which would be, like, 0.200 bikes, IV or so, something in that ballpark.
[SPEAKER_00]: Um, and, you know, just to show the audience, it's not completely crazy.
[SPEAKER_00]: Hickey idea, NYSORA put out a coverage of it pretty quickly.
[SPEAKER_00]: And their quote was, uh, should be considered as a first-line opioid analgesic for acute post-operate pain.
[SPEAKER_00]: It's used may reduce opioid-related harm.
[SPEAKER_00]: I think it's going to get some press and pain medicine news soon and anesthesiology news.
[SPEAKER_00]: So it's out there.
[SPEAKER_00]: I should mention regional, you know, there's a ton of papers, a shocking number of papers that have looked at it for as an adjuncted regional to local anesthetic.
[SPEAKER_00]: And I'll just quote from Vitor, who is lead author of a big review in 2023, which just said Buprofen is the most robust scientific efficacy.
[SPEAKER_00]: So it's out there.
[SPEAKER_00]: If you basically, the idea would be just as more of a prolongation of the sensory block than really any of their opioid, no big surprise because it's a long duration.
[SPEAKER_00]: Press it next.
[SPEAKER_00]: You get kind of a similar prolongation of duration and guess what more people in the Buprofen group throw up because it's an opioid and the other one's not.
[SPEAKER_00]: Right, but uh, but that's that's kind of the idea with it.
[SPEAKER_00]: We've really started to establish a program.
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[SPEAKER_01]: Alright, and now let's get back to that plan for how to incorporate bupon orphan.
[SPEAKER_00]: I think the first step, if you're thinking about using buprenorphin, is to think what does my patient need it.
[SPEAKER_00]: If a patient's eye can need opioids, it doesn't make any sense to use buprenorphin.
[SPEAKER_00]: But if you think they're going to need opioids after surgery, then because the surgical factors, patient factors, you can consider it.
[SPEAKER_00]: Obviously, multimodal two, obviously, anti-emesis like you normally would, not only because it's an opioid, but you want your first repetitions with anything new to be kind of reassuring to you and reassuring to the patient, reassuring to the pack you.
[SPEAKER_00]: If you have IV,
[SPEAKER_00]: As we said, we kind of, our Ivy type people, so the recommended dose for, um,
[SPEAKER_00]: Acute pain management, per the label is 300 micrograms.
[SPEAKER_00]: We got it.
[SPEAKER_00]: The VA had to be put off into the national formula in April of the last year, and we got pretty easily got IVB put off in on our shelves, and it comes in a pretty handy 300 mic per CC unit dose.
[SPEAKER_00]: In my practice, if I think a patient's older frail, I'll just give half of that.
[SPEAKER_00]: a little bit can go a long way.
[SPEAKER_00]: But in general, I'd say, you know, I give it pre-op once it's kind of green light to take the patient back to the room, give half of it.
[SPEAKER_00]: It's recommended to give us a slow bowl of, so whatever that means over a minute or two.
[SPEAKER_00]: And then maybe when we get into the operating room, give the other 150 mics.
[SPEAKER_00]: If you're relying on the opioid to really keep the blood pressure below 200 as you're doing the nasty, laryngoscopy intubation.
[SPEAKER_00]: You might not have it all there.
[SPEAKER_00]: It might not be really achieving that purpose exactly, yet, because that's the reason a lot of us give opioids.
[SPEAKER_00]: So you might want to have some vegetable handy if you're really worried about that.
[SPEAKER_00]: Impact you, our order sets, have 300 mics, IV.
[SPEAKER_00]: They have 150 mics if you're kind of worried about froudteer, elderly patient.
[SPEAKER_00]: If you don't have IV and prefer buckle, we really kind of pioneered a buckle pathway because we just didn't have IV.
[SPEAKER_00]: So it kind of necessitated an alternate formulation.
[SPEAKER_00]: And there, there's a lot of doses.
[SPEAKER_00]: It's a nice thing about the buckle.
[SPEAKER_00]: We went with 450 because, like we said, with bioavailability, it's about the same as the 300-mic IV dose.
[SPEAKER_00]: You could air toward lower dose, say 300 bikes in elderly frail patients.
[SPEAKER_00]: You can read dose it and pack you.
[SPEAKER_00]: You can give it early in the anesthetic.
[SPEAKER_00]: Basically, all of a patient needs a some moist mucosa.
[SPEAKER_00]: Just, tell them, just stick it on and leave it.
[SPEAKER_00]: I, my old chief here gave a lot of buckel buprenorphine to thoracic patients.
[SPEAKER_00]: That was kind of one of the first populations we started to use it in, and he was sometimes putting it in physician-laterally double loop big ass double lumen tube, you know, still stick it on there.
[SPEAKER_00]: The, some of the first adopters really, the first believers were actually the packing nurses because they were seeing such a difference.
[SPEAKER_00]: Transdermal.
[SPEAKER_00]: There's some really advocates out there for transdermal.
[SPEAKER_00]: I've never never used it for this purpose, but you kind of can see that if your patient is near-never placement, thoracic surgery, kind of patient is going to probably take it around the clock opioids for at least a few days.
[SPEAKER_00]: It's a week long patch, so it's designed to to to to to the last a week.
[SPEAKER_00]: So I think establishing a program with your surgeons, with your pharmacies, a good idea, especially if it's off-labeled use, like it would be for the buckle.
[SPEAKER_00]: We went with a twice daily inpatient dosing for these thoracic patients and knee replacements for pragmatic reasons.
[SPEAKER_00]: We just said surgeon do whatever the heck you want in the background.
[SPEAKER_00]: your usual order set just go ahead and we'll just order this buckleby Bernarfin and we publish results with some retrospective cohorts and it's all retrospective so take it for what it's worth but in general there was a signal that there was a decrease in in opioids in pain and the
[SPEAKER_00]: The VA has since published national guidelines, recommending DuProfen, at least consideration of DuProfen for acute pain management, including these alternate formulations.
[SPEAKER_00]: So since that, it's clinical judgment.
[SPEAKER_00]: We can use DuProfen.
[SPEAKER_00]: in any patient we think would benefit from it.
[SPEAKER_00]: And we've had some patients go through the whole parioperative period after near replacement, thoracic surgery where that's it.
[SPEAKER_00]: No oxycodone, no fentanone, no hydromorphone.
[SPEAKER_00]: And they go home on a little reduced dose of buckled buberorphin, like 300 mics, twice daily, PRN.
[SPEAKER_00]: So, yeah, and you can, the listener can ask Google that National Guideline from the VA will pop right up.
[SPEAKER_00]: And, and yeah.
[SPEAKER_00]: I'd love to talk more about this.
[SPEAKER_00]: This is kind of the center of my passion project with the Beprofen, but that's kind of the overview of what we've been doing.
[SPEAKER_01]: Yeah, very cool.
[SPEAKER_01]: So this reminds me a lot of methadone.
[SPEAKER_01]: I'm a big methadone fan for Perry operative use.
[SPEAKER_01]: And it is often referred to as an opioid sparing opioid, right?
[SPEAKER_01]: And I think this is what sounds like you're the way you're using Beprofen as well.
[SPEAKER_01]: It's at any thought on the,
[SPEAKER_01]: I'm doubt there's a study, you know, comparing them head-to-head, but any thought on methadone versus Bupin orphan for acute pain management, and I'm very operively.
[SPEAKER_00]: Great question.
[SPEAKER_00]: I love this question.
[SPEAKER_00]: It'd be like a heavyweight fight to see the two paired up.
[SPEAKER_00]: The only thing I could find is like a poster from like the 70s that compared to most energy after you'll like it.
[SPEAKER_00]: It's like a...
[SPEAKER_00]: It I don't think it ever turned into a full manuscript, but people are from one that one that round one of the interesting now instead of doing like a pro con I mean, I think both is the answer I like new method on for all the reasons you describe I think we're beautiful orphan shines and we had Evan Karrish from Duke come to give a grand round I thought it was super compelling.
[SPEAKER_00]: Yep.
[SPEAKER_00]: I love his work.
[SPEAKER_00]: I think that I thought I buy into this opioid sparing opioid idea
[SPEAKER_00]: Um, but let's say, you know, Jed Wolpa wants to create a program in Methodon at your institution and you want to continue it.
[SPEAKER_00]: You want to give it that second dose.
[SPEAKER_00]: Well, okay.
[SPEAKER_00]: All right.
[SPEAKER_00]: And pack you 2.5 milligrams or so.
[SPEAKER_00]: Nobody's going to be breathing down your neck and now you say, well, let's give another dose on the floor.
[SPEAKER_00]: Oh, let's do another.
[SPEAKER_00]: Is it going to happen?
[SPEAKER_00]: I doubt it.
[SPEAKER_00]: Because people have concerns about methadone safety, the variable pharmacology, metabolism, the dose stacking, the full agonist stuff, the QTC, which I know we could, you and I could be quite comfortable, it's not going to be a problem for a lot of good reason, but still, there to be a lot of other people who think it's a problem, who would probably interfere with your plans.
[SPEAKER_00]: So I think that's where buprofen shines.
[SPEAKER_00]: is that you get a lot of the same opioid sparing opioid effect largely just because it's long duration, but then you can continue it.
[SPEAKER_00]: So you can keep your lead, you know, use a sports metaphor, keep your lead, and
[SPEAKER_00]: Hopefully you get some of that long term opioid sparing in fact you see with methadone, but if a patient needs to go home with opioids for a while, they can go home with buprenorphin.
[SPEAKER_00]: I just think that's kind of the, from just a pragmatic standpoint, where buprenorphin would shine in that contest.
[SPEAKER_00]: That said, I think methadone's great.
[SPEAKER_00]: I love it when the residents come over and are pumped to give patients methadone.
[SPEAKER_00]: It's a kind of off-topic here when we're talking about buprenorphine, but I love carriages paper and like the dose finding for ambulatory surgery.
[SPEAKER_00]: And I just kind of would hear to that, you know, 10, 20 milligrams, you know, a little bit more in emergence, maybe a little bit more in pack you and man they sale, right?
[SPEAKER_00]: That is sale.
[SPEAKER_00]: They do a great, and I think you'd see the same honestly, if you try, try buprenorphine for size.
[SPEAKER_01]: Yeah, I love that.
[SPEAKER_01]: I love the idea of a single dose of methadone with induction and then pack you and even floor and maybe home with buprenorphin.
[SPEAKER_01]: That sounds like it could be the perfect combination.
[SPEAKER_01]: It's an interesting idea.
[SPEAKER_01]: Yeah.
[SPEAKER_01]: a lot of opportunities for research for the listeners I can't wait fabulous all right well you know we commonly take care of patients who are already on opioids that are not human often right so patients come in on oxycodone or maybe methadone that they take at home for maybe opioid use disorder how does human often fit in for those patients
[SPEAKER_00]: Yeah, great question.
[SPEAKER_00]: Common clinical scenario, these patients are difficult.
[SPEAKER_00]: And I think the first step is just saying, these patients are difficult.
[SPEAKER_00]: They're probably going to be difficult.
[SPEAKER_00]: They might surprise you.
[SPEAKER_00]: But some degree of tolerance is almost by definition.
[SPEAKER_00]: Some degree of hyperl GZO, we're not exactly sure how clinically relevant that is, but it probably plays some small role.
[SPEAKER_00]: Some degree of dependence, so if they stop taking the opioid, or we don't know they're on the opioid, with drawoff and hurts, like it's experiences pain.
[SPEAKER_00]: Then you take a history patient with a history of addiction, maybe they're on methadone, or people are offering for that.
[SPEAKER_00]: That adds another layer of complexity to management.
[SPEAKER_00]: Guess what they usually have comorbid chronic pain.
[SPEAKER_00]: Guess what they usually have anxiety.
[SPEAKER_00]: They maybe mood disorder, maybe insomnia.
[SPEAKER_00]: All these things if you look at the best paper you're aware of for risk factors to probably control pain.
[SPEAKER_00]: It's like ding ding ding ding ding ding ding ding ding ding ding.
[SPEAKER_00]: So it's challenging.
[SPEAKER_00]: So I think you tell yourself that and you'd be feel a little bit better about the situation, I think.
[SPEAKER_00]: Unfortunately, there's just credit evidence to go by, credit high level evidence.
[SPEAKER_00]: I was lucky to be part of a team, lead off their Bonara, Enlistment Journal Medicine, 2025 review that looked at just pain management strategies, didn't know there's similar paper that was published shortly thereafter.
[SPEAKER_00]: And man, there's just...
[SPEAKER_00]: you find like some small study from Iran looking at like some odd medicine intricately and there's some insect come out.
[SPEAKER_00]: There's just not a lot out there to support any particular intervention or other.
[SPEAKER_00]: So what do I do?
[SPEAKER_00]: Kitchen sink.
[SPEAKER_00]: I mean it's probably the same as you would do.
[SPEAKER_00]: Give them the kitchen sink and hope for the best.
[SPEAKER_00]: So that's expectation setting up front.
[SPEAKER_00]: Regional if you can do it.
[SPEAKER_00]: I mean regional is really a secret weapon for these cases if you can do it.
[SPEAKER_00]: Maybe continuous regional.
[SPEAKER_00]: one thing that I think a pain service would deliver is comfort with just aggressively titrating opioids.
[SPEAKER_00]: Just gotta remember, they're gonna get their baseline.
[SPEAKER_00]: So I could do anything for their pain.
[SPEAKER_00]: then it's some studies, 20% more, 30% more, 50% more, 100% more.
[SPEAKER_00]: You just kind of don't know.
[SPEAKER_00]: As long as you're doing all the adjuncts already, what else do you got?
[SPEAKER_00]: I mean, you're just going to try trade opioids aggressively.
[SPEAKER_00]: Obviously multimodal analgesia.
[SPEAKER_00]: I think non-pharmaceutical logic stuff is something that we usually fall short time, honestly, as anesthesiologists, and we could do better.
[SPEAKER_00]: So if you really have a pain service, especially a multidisciplinary one,
[SPEAKER_00]: even the cryotherapy, tens, PT, distraction techniques.
[SPEAKER_00]: A lot of the, we did a paper we did on pharmacological and non-pharmacological interventions.
[SPEAKER_00]: They tell you, most of the studies go down now are non-pharmacological.
[SPEAKER_00]: It's like yoga and stuff like that.
[SPEAKER_00]: I think a lot of people, there might be some eye rolling, but...
[SPEAKER_00]: Hey, that's powerful stuff, distraction from your pain is powerful stuff as well as just getting on your feet after surgery and multi-disciplinary team if you can at all do it if that's present in your hospital and you're setting do it.
[SPEAKER_00]: I think for the patients who are on methadone or be open.
[SPEAKER_00]: I mean, we kind of already touched on the main theme, the lowest hang fruit, keep it going, keep the methadone going, take the whole dose on the day of splitting the dose, meaning if you're on 24 milligrams, a buprenorphine splitting it in 888.
[SPEAKER_00]: There's some people that promote that.
[SPEAKER_00]: Maybe a part of it's just giving patient.
[SPEAKER_00]: more you say here's another payment here's another payment i don't know um there's a little bit of a difference opinion on whether that really improves outcomes but it's something you could consider um giving one will on the other you kind of mentioned it a little bit when you're just thinking about like a pain study and hope you had negative patients i don't really know where that fits in and i've seen much on that
[SPEAKER_00]: discharge planning's key in those patients.
[SPEAKER_00]: You really got to link them up.
[SPEAKER_00]: You're not probably usually an anesthesia thing, but if you're on a transitional pain service or something, that's key, obviously, to get them in touch with their prescriber.
[SPEAKER_00]: One just,
[SPEAKER_00]: It's like a, you might call it a reach goal for somebody out there who's motivated, you know, smoking cessation, there's some literature when people come in, they're motivated, man.
[SPEAKER_00]: They want that near place, they've been thinking about it for years.
[SPEAKER_00]: They lost 10 pounds for it, you know, they stopped drinking six pack, now it's a couple of beers a night, whatever, they're making this progress.
[SPEAKER_00]: It might be an opportunity for that patient who has untreated OUD, who has problematic prescription opioid use.
[SPEAKER_00]: Maybe this is a time you could actually rotate a patient to bug.
[SPEAKER_00]: Now, I think your average person out there is like, Jesus, I got enough on my plate, man.
[SPEAKER_00]: Hickie shut up.
[SPEAKER_00]: We got enough going on.
[SPEAKER_00]: And it's obviously not the couch at home.
[SPEAKER_00]: There's physiologic challenges, psychological challenges, pharmacologic challenges going on.
[SPEAKER_00]: It's a more complicated milieu.
[SPEAKER_00]: But I'll say, it's an interesting opportunity.
[SPEAKER_00]: And I think what might make people believe is that you just see pain outcomes might be better.
[SPEAKER_00]: And longer-term outcomes like pain interference function, all that stuff might be better if you're on a buprenorphine as opposed to some of these other opioids.
[SPEAKER_01]: Interesting.
[SPEAKER_01]: So yeah.
[SPEAKER_01]: My question is, you mentioned earlier that buprenorphine might even be an effective reversal agent for opioid overdose.
[SPEAKER_01]: So are we is there any danger in a patient let's say who's on it just a huge amount of opiate at home who comes in they they took their most recent dose in pre-op you know they've got it all on board if you give them let's say you're a fan of of doing your your plan is I'm gonna do buprenorphin as my primary analgesic if you give them a big dose of buprenorphin is there any risk of reversing the opiate they already have on board?
[SPEAKER_00]: I think it's a great question and I do think there's some risk.
[SPEAKER_00]: bad scenario would be patient comes in, you come in, and you just tell me, no, I don't take any opioids, but turns out you take like 200 MME a day.
[SPEAKER_00]: And then I give you me an orphan now.
[SPEAKER_00]: I doubt it would have a big impact that because we're talking about 300 micrograms.
[SPEAKER_00]: But if I, I'm sure in that scenario, if I gave you a, like a 12 milligrams of lingo or 16 million, then yeah, you'd probably be hurting.
[SPEAKER_00]: You'd probably be hurtin'.
[SPEAKER_00]: I think what we've learned from opioid use disorder treatment when it comes to this precipitation of withdrawal, it's a question I get a lot, is that those patients are taking astronomical fentanyl doses, just unbelievable fentanyl doses.
[SPEAKER_00]: And they come into an ED setting and ED is really led on this, rotations to buprawrfin.
[SPEAKER_00]: and they give them, they give them big doses of buber orphan, often just right away.
[SPEAKER_00]: It's not the old school, traditional road induction, where you wait until the patients in a withdrawal, you start with teeny dose, you tie trade up over time.
[SPEAKER_00]: These eedy docs are just going big.
[SPEAKER_00]: They're like, here's 12 milligrams.
[SPEAKER_00]: Here's another, you know, just keep going.
[SPEAKER_00]: And they do, they do well.
[SPEAKER_00]: And that's scenario.
[SPEAKER_00]: So could you conceivably, yes?
[SPEAKER_00]: You could, I think it's probably not what, I probably wouldn't reach for Buprofen and that patient is on high dose opioids at home, unless we really had a thoughtful approach to really rotate to it.
[SPEAKER_00]: When in the perioperative care, I don't know.
[SPEAKER_00]: It's really interesting topic.
[SPEAKER_00]: I think we should explore it as a field,
[SPEAKER_00]: But yeah, theoretically, there'd be that risk.
[SPEAKER_00]: But I do think what I mentioned from opioid disorder experiences that the likelihood of it happening at a 450-mic buckled dose, 300-mic buckled dose, or one of these small IV doses would be pretty darn small.
[SPEAKER_01]: OK, well, that's great to know.
[SPEAKER_01]: So I think much like methadone, there are a lot of misconceptions or even myths out there about buprenorphine.
[SPEAKER_01]: I know there are a lot about methadone.
[SPEAKER_01]: I try to address them all the time.
[SPEAKER_01]: Those address some of the you brought some of them already, but maybe just to kind of bring them all into one place.
[SPEAKER_01]: What are some common misconceptions about buprenorphine that may be preventing people from wanting to use it and how can we try to set them straight?
[SPEAKER_00]: Yeah, great question.
[SPEAKER_00]: I think Bethel is a really app comparison here.
[SPEAKER_00]: I think in particular, buprenorphine may even be a little bit worse in anesthesiologists because you had generations who basically trained to be in fear of the drug.
[SPEAKER_00]: Right.
[SPEAKER_00]: I mean, that's kind of the nature of our old practice was really to be kind of inferior to the drug.
[SPEAKER_00]: So when we hear Staboxa and we kind of a little shiver goes down our spine.
[SPEAKER_00]: So there's that.
[SPEAKER_00]: So there's certainly a knowledge gap that needs to be made up.
[SPEAKER_00]: But as far as sort of myths to bust, the partial agonist one comes up.
[SPEAKER_00]: Like if I'm taking care of you and pack you and I say, well, I got a partial pain medicine or a full, you know, you're going to be pretty sure which one you want.
[SPEAKER_00]: But we know from you, but often that's not partial and
[SPEAKER_00]: Right?
[SPEAKER_00]: It's not partial analgesia.
[SPEAKER_00]: It's very full in that effect.
[SPEAKER_00]: And actually, most of what comes downstream of the muricepter, you want to be partial as we said.
[SPEAKER_00]: So there's that myth.
[SPEAKER_00]: I don't think that historical categorization is really helped the drug.
[SPEAKER_00]: ceiling effect, so I think that came up a couple times, but people say, well, there's a ceiling effect for analgesia, right?
[SPEAKER_00]: And, you know, I would point unto another DeHon paper.
[SPEAKER_00]: I mentioned him earlier in the context of respiratory depression, but he had a BJA paper, also 2006, and the title was,
[SPEAKER_00]: But not in analgesia, so the title kind of says it all, across the doses they studied, which is up to, I think, twice the recommended IV pain dose.
[SPEAKER_00]: So I don't think ceiling effect for analgesia is something we should be concerned about.
[SPEAKER_00]: I often get this idea, well, forgive me, but in Arfen, can we give other opioids?
[SPEAKER_00]: So that's kind of a little myth to the bust.
[SPEAKER_00]: The answer is sure, you can.
[SPEAKER_00]: You could also give more people an orphan.
[SPEAKER_00]: Again, when we talked about this kind of esoteric topic of the miricepter availability, I just bring that up this sort of conceptual framework that if I'm occupying 10% of jet will pose miricepters, I mean, that means there's 90% still there, like available.
[SPEAKER_00]: So giving oxycodone on top of some buprenorphin is fine, we don't really know.
[SPEAKER_00]: I think that some of good experimental trials will be really neat to see whether there's an additive effect when you combine buprenorphin with usual care opioids.
[SPEAKER_00]: So that's another one.
[SPEAKER_00]: We talked about precipitation with straw comes up a lot.
[SPEAKER_00]: Do we need to taper?
[SPEAKER_00]: That's one that comes up.
[SPEAKER_00]: Surgeons in particular ask that because we're not in the usual practice of discharging patient's home on oxycodone.
[SPEAKER_00]: I think based on what we know about the withdrawal syndrome being pretty mild as well as being long acting and kind of auto tapering this wouldn't be a problem and often I'll just ask the audience when this question comes up like what do you do with oxycodone?
[SPEAKER_00]: Do you tap your tapering oxycodone routinely?
[SPEAKER_00]: I think the answer would be what you talking about no right well there you go needing IV for pain
[SPEAKER_00]: I think some people just think, boy, I, acute pain, man, we need IV medications.
[SPEAKER_00]: And really, Buprofen compares surprisingly well across the number of post-op pain, but also ED, we're talking renal colleague, break through cancer pain, bone fractures, so emergency medicine type pain.
[SPEAKER_00]: And sub-bling will beuprofen compares, it's most studies to say, as
[SPEAKER_00]: based on the equivalent pain outcomes, when you're just putting a milligrams sublingual bup under the tongue, compared to IMRIV method morphine, which I think is counter-induitive in our brains, but that's what the study show.
[SPEAKER_00]: And part of it's that lipophilicity and some of those pharmacological features.
[SPEAKER_01]: very cool.
[SPEAKER_01]: All right, well, those are all really important things to address and if people have those concerns, oh, I can't use this because there's only so much NLGZ I can get, right?
[SPEAKER_01]: Good to put that to rest.
[SPEAKER_01]: Let's talk about future reactions.
[SPEAKER_01]: This is an exciting medication.
[SPEAKER_01]: We're using it in new ways.
[SPEAKER_01]: It's got a lot of benefits that you've gone over.
[SPEAKER_01]: What do you see as big next steps for buponorphin?
[SPEAKER_01]: Where we might use it?
[SPEAKER_01]: How we might use it?
[SPEAKER_01]: What's going to come down the road?
[SPEAKER_00]: I think a big, a big contemporary study with contemporary drugs within a multi-model, analgesia pathway, looking at usual care, opioids versus spupin orphan, and then I think you're obligated to look at the pain intensity and pack you, pain intensity on the floor, opioid consumption.
[SPEAKER_00]: But I think the money shot is three months later, six months later.
[SPEAKER_00]: That's where I would theorize, based on what we know, just the theory, that
[SPEAKER_00]: If six percent of patients are still taking actually go to them six months after their surgery, what would it be with buprenorphine based on everything we know?
[SPEAKER_00]: What if it's five?
[SPEAKER_00]: Well, that's big.
[SPEAKER_00]: What if it's four?
[SPEAKER_00]: That's bigger.
[SPEAKER_00]: So I think there'd be a reduction in patients who are around opioids per cent.
[SPEAKER_00]: Would some of the patients be on buprenorphine six months later?
[SPEAKER_00]: Yes.
[SPEAKER_00]: I think we could stipulate that that will be a thing that happens.
[SPEAKER_00]: But would there be a reduction in persistent post-up opioid use?
[SPEAKER_00]: I think that's reasonable.
[SPEAKER_00]: I think that's very reasonable, and that's you to have to accompany that with some of those sophisticated pain, pain interference.
[SPEAKER_00]: You know, satisfaction, which is kind of an amalgam pain score that we should think probably more about as a profession.
[SPEAKER_00]: I think those outcomes is what we really need when it comes to be profit.
[SPEAKER_00]: You know, next steps, the lowest thing through it, as we've said, is to continue the bup and there's still a lot of practice variation across the country on this, believe it or not.
[SPEAKER_00]: I think you're setting ICU.
[SPEAKER_00]: I've been touched with some intensivists over at Yale, trying to get their head about thinking about buprenorphine and the ICU setting.
[SPEAKER_00]: I think based on the safety features, the respiratory component, the long duration.
[SPEAKER_00]: I think it's just an interesting thing to integrate into some ICU pain management.
[SPEAKER_00]: And people hurt in the ICU.
[SPEAKER_00]: There's a lot of pain in the ICU.
[SPEAKER_00]: And so I'm trauma similarly when I I've looked at trauma recently.
[SPEAKER_00]: Boy, all the post up opioid stuff is like is worse
[SPEAKER_00]: I mean, you know this, because that's part of your business.
[SPEAKER_00]: That part of my usual business.
[SPEAKER_00]: But trauma opioid outcomes and pain outcomes are worse than just straight surgery, partly because they all, a lot of them get surgery.
[SPEAKER_00]: So that's interesting.
[SPEAKER_00]: I think emergency medicine is another interesting frontier for this, and there's some people that stand for it.
[SPEAKER_00]: I'll shout them out, Jonathan Lee, Terry A. Heron, and published a number of interesting papers from Stanford, where they're using really small IV doses of buber orphan.
[SPEAKER_00]: We're talking like 100 mics.
[SPEAKER_00]: and they're getting really good pain outcomes and in typical garden variety, emergency medicine, encounters.
[SPEAKER_00]: DOD, so anybody from DOD listening, you know, you can figure my email address, call me.
[SPEAKER_00]: I think this idea, if the listeners have never opened one of these buckled buprenorphine, it's like a scope patch.
[SPEAKER_00]: It's like a scope patch, basically.
[SPEAKER_00]: If you think about it, we've all used scope patches, right?
[SPEAKER_00]: It's almost the same size, it's the same container.
[SPEAKER_00]: Everybody, every frontline medic has scissors.
[SPEAKER_00]: That's it.
[SPEAKER_00]: You just, you don't need a needle.
[SPEAKER_00]: You don't need glass.
[SPEAKER_00]: You don't need a refrigerator.
[SPEAKER_00]: You could put,
[SPEAKER_00]: hundreds you wouldn't need them, but you could put a hundred of these in your pocket and you wouldn't even notice it.
[SPEAKER_00]: So, and then to have something that causes less respiratory depression, probably less cognitive impairment, and less eight and a half hours is compatible with everything else they're using, which is basically and say acetaminophen, maybe ketamine, and then morphine historically was the other battlefield analgesic.
[SPEAKER_00]: I think it's kind of a cool to think about how it might fit into that scenario.
[SPEAKER_00]: I mean, there's some stuff that I've mentioned only because if you're trying to make a case to surgeons on this, they might be more into into this, which is that some there's some immunological stuff that's fascinating about it, most of this comes from animal studies, but if I injure mice,
[SPEAKER_00]: And then I give them buprenorphine versus like placebo.
[SPEAKER_00]: The healing is better.
[SPEAKER_00]: The buprenorphine group is like really?
[SPEAKER_00]: I said, I didn't make any sense.
[SPEAKER_00]: So that stuff is, of course, mice, I don't take that study too seriously.
[SPEAKER_00]: But it's something you could get some interest to certain audiences if you think about maybe there'd be some wound healing benefits for buprenorphine versus usual care opioids.
[SPEAKER_00]: That's super stretch.
[SPEAKER_00]: So I don't want to, you know.
[SPEAKER_00]: go too hard into that category.
[SPEAKER_00]: I think that's the stuff I'm kind of keen to see.
[SPEAKER_01]: Very cool.
[SPEAKER_01]: Well, Tom, this has been such an interesting talk and I learned a ton.
[SPEAKER_01]: I just think this is going to be really interesting to see where it goes.
[SPEAKER_01]: Hopefully more people will start using this.
[SPEAKER_01]: It sounds like there's just so many great uses in our world for it.
[SPEAKER_01]: So exciting to see what comes down the road.
[SPEAKER_01]: Let's turn to the portion of our show where we make random recommendations.
[SPEAKER_01]: What would you recommend the audience check out for fun?
[SPEAKER_00]: I got an author recommendation, a book author recommendation.
[SPEAKER_00]: You know the name Peter Heller, a sound familiar.
[SPEAKER_00]: So this Peter Heller writes really interesting books where there's a lot of outdoors, also just interesting characters, and the plots are kind of all over there, like there's...
[SPEAKER_00]: You know, a couple of high school buddies that just always do an annual canoe trip, and all the sun, the forest is on fire, and there's murder everywhere, and stuff like that.
[SPEAKER_00]: There's some post-apocalyptic ones, the one I'm reading now is called The Orchard, but I think I'd recommend dogstyers.
[SPEAKER_00]: So if somebody wants to start into the Peter Heller world, I think I'd call it Kormek McCarthy, launch me into Peter Heller.
[SPEAKER_00]: If you have an affinity for one, you probably have an affinity for this one.
[SPEAKER_00]: Dog stars is freaking awesome.
[SPEAKER_00]: Check out Dog stars first.
[SPEAKER_00]: The Dog stars, Peter Heller, you should do it.
[SPEAKER_00]: Very cool.
[SPEAKER_01]: I love new books and authors, so I will put it on the list.
[SPEAKER_01]: I am going to recommend, I'm sure people know the author, Michael Pollan, and he has a new book out called A World of Peers, a Journey into Consciousness.
[SPEAKER_01]: Now, I haven't read the book yet, but I've listened to Ezra Klein's interview with Michael Pollan about the book.
[SPEAKER_01]: And it's really interesting.
[SPEAKER_01]: So if you don't want to read the whole book, listen to the interview, I just find this so fascinating, this idea that consciousness is something we don't really understand, and maybe it's in our brain, or maybe our brain is just a receiver for something that's out there, and it's filtering it, and there's just so many interesting theories, and ways to think about this.
[SPEAKER_01]: And if you've read other things by Michael Pollan, he
[SPEAKER_01]: the previous book was about psychedelics and so that also plays a role here and thinking about how psychedelics help elucidate the role and meaning of consciousness.
[SPEAKER_01]: So really interesting and you can get a taste forward in Ezra Klein's interview with him.
[SPEAKER_01]: We'll put a link to it in the show notes.
[SPEAKER_01]: All right, Tom.
[SPEAKER_01]: This has been great.
[SPEAKER_01]: Thanks so much for coming on the show.
[SPEAKER_01]: That's yours all by.
[SPEAKER_01]: All right, hopefully you got as much out of that as I did.
[SPEAKER_01]: That was really fantastic.
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[SPEAKER_01]: That is it for today for the Accract Podcast.
[SPEAKER_01]: I'm Jed Wolpa.
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[SPEAKER_01]: Remember what you're doing out there every day is really important and valued.