Research Gaps in Acute Pain Management in People with Opioid Use Disorder: Results from a Systematic Review: IMPOWR-YOU webinar

Transcript

• 00:13And we're gonna be joined
• 00:15by,
• 00:17doctor Michelle Bernora,
• 00:19who is assistant professor
• 00:21of medicine at, Einstein School
• 00:23of Medicine,
• 00:25and doctor Melissa Weimer, who's
• 00:26an associate professor of medicine
• 00:29at Yale School of Medicine
• 00:30and also director of the
• 00:31Yale Addiction Medicine Consult Service.
• 00:34And,
• 00:35this work is,
• 00:37they're gonna be presenting their
• 00:38work
• 00:39that stems from a recently
• 00:41published,
• 00:42paper
• 00:43that I will share briefly
• 00:44in the chat.
• 00:46But the title of which
• 00:47is research gaps and acute
• 00:50pain management in people with
• 00:51opioid use disorder,
• 00:53results from a systematic review.
• 00:56And,
• 00:57I'm really pleased at the
• 00:59way this has turned out.
• 01:00And I think one of
• 01:01the
• 01:02take home messages,
• 01:03especially for all the junior
• 01:05investigators on on today is,
• 01:08the incredible amount of work
• 01:10there is for you all
• 01:11to do over the rest
• 01:12of your career.
• 01:14One of the things I
• 01:16like to highlight
• 01:17for,
• 01:18junior faculty is
• 01:20how beneficial doing a systematic
• 01:22review early on can be
• 01:24because,
• 01:25Michelle,
• 01:27at this point is now
• 01:28the world's expert,
• 01:30in this topic because she
• 01:31knows all of the literature.
• 01:33And, you know, that happened
• 01:35within a year or two.
• 01:37And then,
• 01:38she's also,
• 01:39you know, well aware of
• 01:41what are the unanswered questions
• 01:42in the field.
• 01:44And, she's got the rest
• 01:45of her
• 01:47career,
• 01:48sort of in her research,
• 01:50mapped out. So
• 01:52think about it as you
• 01:53think about ways when you
• 01:55start your career. But,
• 01:57without saying more,
• 01:59I will introduce both Michelle
• 02:01and Melissa. Thank you.
• 02:05Thanks, David.
• 02:06I'm just gonna say a
• 02:08few words, and then I'm
• 02:09gonna really hand it over
• 02:10to Michelle who's gonna lead
• 02:12us through the review.
• 02:14I will also say that
• 02:16systematic reviews are not always
• 02:18for the faint of heart.
• 02:20This,
• 02:22topic,
• 02:25idea started about,
• 02:28I'm embarrassed to say, but,
• 02:30probably about
• 02:32four and a half, five
• 02:33years ago.
• 02:35And it took me,
• 02:37a lot of time to
• 02:38figure out
• 02:39how to put it all
• 02:40together and,
• 02:42create the right team to
• 02:44work on this
• 02:46immensely important topic.
• 02:49So sometimes you have brilliant
• 02:50ideas, and it takes time
• 02:52to get the right people
• 02:53together. So,
• 02:55thankfully,
• 02:56Michelle
• 02:57was interested in taking this
• 02:59on and helping to lead
• 03:00it,
• 03:02And I think the product
• 03:04was,
• 03:05a
• 03:07wonderful yet very,
• 03:10time intensive process.
• 03:13So, anyway,
• 03:14excited for her to share
• 03:16our findings. And as David
• 03:18said, there's
• 03:20literally an open field here.
• 03:22You could essentially think of
• 03:24any potential question,
• 03:27and this topic in the
• 03:28hospital, out of the hospital,
• 03:30in so many different settings,
• 03:32and
• 03:33there's just so much potential
• 03:35research that can be done.
• 03:36So,
• 03:37excited to share that with
• 03:38you today.
• 03:42Thanks, Melissa.
• 03:45Yeah. As as David, mentioned,
• 03:47my name is Michelle.
• 03:49It's a pleasure to be
• 03:50here.
• 03:51I'm gonna share my slides
• 03:52in just a second. But
• 03:53before I start, I do
• 03:54wanna encourage people. As Melissa
• 03:57said, there are more gaps
• 03:59than knowledge in this research
• 04:00area, and so please don't
• 04:01hesitate.
• 04:03We've tried to make this
• 04:04kind of as tangible and
• 04:06useful of a talk for
• 04:07folks.
• 04:08But if anything comes up
• 04:10for you as,
• 04:11as we're speaking, just feel
• 04:13free to interject or drop
• 04:15it in the chat or
• 04:15whatnot,
• 04:16rather than waiting till the
• 04:17end.
• 04:19I think that that,
• 04:20yeah, that would be great.
• 04:24So let me just share
• 04:25my slides. Bear with me
• 04:26one second.
• 04:36I think I just have
• 04:37to switch.
• 04:45Okay.
• 04:46If I could just have
• 04:47a thumbs up or down,
• 04:48are you do you just
• 04:49see my slide full screen?
• 04:51Perfect. Okay. Great. Alright.
• 04:55So right. Right, so research
• 04:57gaps in acute pain management,
• 04:59in people with opioid use
• 05:00disorder results from a systematic
• 05:02review.
• 05:05So I have no disclosures.
• 05:06I'm not sure if that
• 05:07was necessary.
• 05:09We are
• 05:11planning to just describe the
• 05:13current evidence base for strategies
• 05:14to treat acute pain in
• 05:16people with OUD according to
• 05:17this recently published
• 05:19review that Melissa and I
• 05:20led. Identify
• 05:22specific evidence gaps regarding strategies
• 05:25to acute to treat acute
• 05:26pain in people with OUD.
• 05:28You'll see them interspersed throughout.
• 05:30And then, hopefully, you can
• 05:31walk away from this with,
• 05:32you know, at least one
• 05:33or two ideas for a
• 05:35research project to address current
• 05:37gaps,
• 05:38if not many more than
• 05:39that.
• 05:41Just by way of background,
• 05:43treating acute pain in people
• 05:44with OUD is surprisingly common
• 05:46and yet challenging to treat.
• 05:49A systematic review and meta
• 05:50analysis from last year found
• 05:52the pooled prevalence of current
• 05:53pain among people with OUD
• 05:55as sixty percent.
• 05:58Additionally, an estimated thirty percent
• 06:00thirty six, I'm sorry, percent
• 06:01of hospitalizations
• 06:02among people with OUD are
• 06:03for acutely painful conditions,
• 06:07such as injection related infections
• 06:10or trauma in addition to
• 06:11painful conditions common among all
• 06:13adults.
• 06:15And then pain can be
• 06:16challenging to treat in this
• 06:17population for a few reasons,
• 06:19including pain related sequelae from
• 06:21long term exposure to opioids,
• 06:23The fact that pain and
• 06:24withdrawal can often co occur
• 06:26and symptoms can be difficult
• 06:27to distinguish between the two.
• 06:29And then last because pharmacologic
• 06:31properties
• 06:32of the medications we use
• 06:33for opioid use disorder can
• 06:35affect the activity of pain
• 06:36medications and often need to
• 06:37be considered when you're coming
• 06:39up with a plan for
• 06:40your patient.
• 06:43Additionally,
• 06:44and important to not forget,
• 06:47when treating acute pain in
• 06:49people with OUD, it's important
• 06:50to consider the patient perspective
• 06:52and how,
• 06:53the care they receive impacts
• 06:55their overall well-being.
• 06:56Qualitative data shows us that
• 06:58people with OUD consistent
• 07:00consistently report experiencing stigma and
• 07:02perceived minimization of their pain
• 07:04in acute care settings
• 07:06and often avoid seeking medical
• 07:07care altogether for fear of
• 07:09mistreatment.
• 07:12This is a quote that
• 07:13I really like from, a
• 07:15study a few years back,
• 07:17in which,
• 07:18sorry, the study was for
• 07:20folks, undergoing bup initiations in
• 07:22the ED. But, you know,
• 07:24one participant said, I've had
• 07:25emergency room doctors tell me
• 07:26that I shouldn't be ashamed
• 07:28of myself, just ashamed,
• 07:30and belittled and mean to
• 07:31feel, you know, as though
• 07:32my pain is not real.
• 07:36And so with that,
• 07:39we,
• 07:41oh, I'm so sorry. Last
• 07:43last piece. Why should we
• 07:44care about treating acute pain
• 07:46in people with OUD? It's
• 07:48important to note there are
• 07:49multiple negative outcomes that are
• 07:50associated with on or undertreated
• 07:52acute pain for people with
• 07:54OUD,
• 07:55including poor engagement and retention,
• 07:57MOUD care,
• 08:00an increased likelihood of self
• 08:01directed discharge, which itself is
• 08:03associated with increased risk of
• 08:05incomplete antibiotic regimens,
• 08:08higher hospital readmission rates, morbidity,
• 08:10mortality, and health care related
• 08:12cost.
• 08:15Alright.
• 08:16And so with that, we
• 08:17sought to better understand the
• 08:19current evidence base by conducting
• 08:21a systematic review about acute
• 08:23pain management in people with
• 08:24OUD.
• 08:27Our key questions were, first,
• 08:29among adults with OUD, including
• 08:31those prescribed MOUD,
• 08:33what are the benefits and
• 08:35harms of opioid and non
• 08:36opioid interventions for acute pain?
• 08:38Secondly, among adults with OUD,
• 08:40including those prescribed MOUD,
• 08:42are interventions associated with OUD
• 08:45related outcomes,
• 08:46including withdrawal, return to use,
• 08:48or treatment initiation and retention?
• 08:51And then lastly, do the
• 08:52benefits and harms of acute
• 08:53pain interventions vary by use
• 08:55of MOUD before or during
• 08:57the acute pain episode?
• 09:03This was our PICO framing,
• 09:06understandably quite vague in the
• 09:07beginning. I won't talk you
• 09:08through all of it. I
• 09:09think it's somewhat self explanatory,
• 09:11most notably because the extent
• 09:12of available evidence at the
• 09:14time we start to, we
• 09:15set out to do the
• 09:16systematic review.
• 09:18We were just a bit
• 09:19uncertain,
• 09:20and so we we designed
• 09:22this intentionally quite broad.
• 09:29We evaluated,
• 09:31or we systematically,
• 09:34extracted,
• 09:35articles from any of these
• 09:36sources listed here that were
• 09:38published through July seventh of
• 09:39twenty twenty four,
• 09:41and use Citation Chaser,
• 09:43as of the date of
• 09:44our initial search, which was
• 09:45March sixteenth twenty twenty three.
• 09:51And this is our flow
• 09:52diagram. I'm not sure if
• 09:53you can
• 09:55see in detail, and it's
• 09:56not super important, but I
• 09:57do think worth noting
• 09:59that we started with almost
• 10:01twenty thousand records identified
• 10:03from online databases,
• 10:05and we ended up including
• 10:07only a hundred and fifteen
• 10:08studies. And part of that
• 10:09was because of the difficulty
• 10:10in
• 10:13in pulling,
• 10:13acute pain,
• 10:15interventions
• 10:17in, from, you know, online
• 10:19database source, sources.
• 10:26Included studies represented those evaluating
• 10:29a range of interventions
• 10:31highlighted there across multiple different
• 10:33patient populations,
• 10:34grouped by MOUD treatment status,
• 10:37and then across a number
• 10:38of different painful conditions and
• 10:40or settings.
• 10:41And importantly, in sorting through
• 10:43available evidence, we identified several
• 10:45research gaps, which we're gonna
• 10:47walk you through now.
• 10:50First in each domain, we'll
• 10:51talk you through what we
• 10:52did find, and then we'll
• 10:53highlight a notable gap or
• 10:55or notably what we did
• 10:56not find.
• 11:00To make this most useful,
• 11:01we'll organize this first by
• 11:04population,
• 11:05then by setting, and last
• 11:07by intervention. Oh, I'm sorry.
• 11:08It's intervention and setting, but
• 11:11by those three,
• 11:12domains,
• 11:16and we'll sprinkle the rest
• 11:17of it, and as it
• 11:19relates to outcome and and
• 11:20timing and and study design,
• 11:22throughout as it's relevant.
• 11:26So first,
• 11:27a number of notable gaps,
• 11:29emerged as it relates to
• 11:30the study population.
• 11:31We categorized our findings into
• 11:33various subpopulations
• 11:34based on OUD treatment status.
• 11:37So notably, people who are
• 11:38taking buprenorphine,
• 11:39people who are taking methadone,
• 11:42naltrexone,
• 11:43or who are actively using
• 11:45and not taking any medication
• 11:46for opioid use disorder.
• 11:48And so first,
• 11:51we can talk about people
• 11:53taking buprenorphine.
• 11:54So,
• 11:55the first intervention that became
• 11:57apparent in,
• 11:59our systematic review was, the
• 12:01continuation
• 12:02compared to discontinuation
• 12:04of people who are taking
• 12:05sublingual buprenorphine.
• 12:07We found twelve,
• 12:08controlled cohort studies with a
• 12:10total n of one thousand
• 12:11five hundred and twenty nine
• 12:12study participants,
• 12:15with a median baseline buprenorphine
• 12:17dose reported in included studies
• 12:19ranging from eight to sixteen
• 12:21milligrams.
• 12:23And then outcomes reported included
• 12:25pain severity,
• 12:26full agonist opioid analgesic use,
• 12:28opioid cravings, and buprenorphine treatment
• 12:30retention.
• 12:35Notably,
• 12:36no studies compared pain outcomes
• 12:38with buprenorphine
• 12:39continuation versus discontinuation
• 12:41in people taking doses greater
• 12:43than twenty four milligrams a
• 12:45day. It is possible that
• 12:47some cohorts included individual study
• 12:49participants on doses higher, but
• 12:52no study exclusively looked at
• 12:54groups with,
• 12:55twenty four or more milligrams
• 12:57per day of their baseline
• 12:58buprenorphine dose.
• 13:00Secondly, only two small studies
• 13:03compared OUD outcomes, so cravings,
• 13:05return to use, or treatment
• 13:07retention
• 13:08with buprenorphine,
• 13:09continuation compared to discontinuation of
• 13:11any dose.
• 13:13And so we thought that
• 13:14was,
• 13:15a notable,
• 13:16gap in the literature.
• 13:19Secondly,
• 13:21we did,
• 13:23look to see what the
• 13:23evidence base was around, making
• 13:26changes to someone's baseline sublingual
• 13:28buprenorphine dose and or frequency,
• 13:30and we found one case
• 13:32report.
• 13:33It described effective pain management
• 13:35resulting from a temporary increase
• 13:37of sublingual buprenorphine postoperatively
• 13:40from twenty four milligrams at
• 13:41baseline all the way to
• 13:42seventy two milligrams daily that
• 13:44was then tapered,
• 13:46post hospital discharge.
• 13:51Yeah.
• 13:53And so,
• 13:54the gap here is, that
• 13:56no studies compared pain or
• 13:58OUD outcomes associated with temporary
• 14:01dose or frequency
• 14:02changes to sublingual buprenorphine,
• 14:05for example, split in the
• 14:07same.
• 14:08I'll just add,
• 14:10sorry, going back that
• 14:12though we categorized
• 14:13case studies in our systematic
• 14:15review, we didn't
• 14:17include them in the decision
• 14:19making or our findings.
• 14:22So I think what's
• 14:23helpful about our systematic review
• 14:25is
• 14:26we,
• 14:28we tried to categorize all
• 14:30of the research,
• 14:32though,
• 14:33really, the systematic review was
• 14:34focused on controlled studies.
• 14:36However, in our appendix, you'll
• 14:38see
• 14:39I think there are about
• 14:41almost sixty case studies,
• 14:43that we did include, and
• 14:45that was important for
• 14:48some of the categories
• 14:50of patients who were, say,
• 14:52on extended release buprenorphine
• 14:53or extended release naltrexone or
• 14:55oral naltrexone because there weren't
• 14:57controlled studies on those populations.
• 15:00So,
• 15:01also, I think a helpful
• 15:03resource, if you're doing work
• 15:04in this area, would be
• 15:05look at our appendix because
• 15:07it's gonna show you,
• 15:08albeit not not high level
• 15:10of evidence, but it's gonna
• 15:12show you case reports that
• 15:13are out there for those
• 15:14particular
• 15:16modalities of treatment for OUD.
• 15:21Yeah. Thanks, Melissa. That's Michelle,
• 15:23can I can I just
• 15:24ask a clarifying question?
• 15:26Yeah. I think it's absolutely
• 15:27fascinating. So you in you
• 15:30included that case report of
• 15:31dose increase.
• 15:33I think it was a
• 15:33letter or a case report
• 15:35or something
• 15:36of buprenorphine to treat acute
• 15:37pain.
• 15:38I and that was back
• 15:40in two thousand seven. I
• 15:41remember it very well. Are
• 15:43you saying that nobody has
• 15:45systematically evaluated
• 15:47dose increases
• 15:48for QPIP?
• 15:49Not a single study. Wow.
• 15:51I know. Thank you. I
• 15:52know we were shocked as
• 15:53well.
• 15:54Also, interestingly,
• 15:56most of the
• 15:57perioperative
• 15:58management of buprenorphine,
• 16:01all of it has really
• 16:02looked at potential dose reductions
• 16:04or as Michelle
• 16:05mentioned,
• 16:09doses that don't go up
• 16:10to what we're typically using
• 16:12for patients now, which is
• 16:13twenty four or thirty two
• 16:14milligrams, or patients who are
• 16:16on extended release
• 16:17no.
• 16:19Excuse me. Extended release buprenorphine.
• 16:21So we really don't have
• 16:25rigorous
• 16:27research
• 16:28to support what I do
• 16:30in clinical practice, which is
• 16:32I don't reduce the dose
• 16:33of buprenorphine.
• 16:34I keep the dose of
• 16:35buprenorphine at twenty four milligrams
• 16:38for patients who are
• 16:40in the perioperative setting.
• 16:42Now could we do a
• 16:44retrospective
• 16:44cohort study? Yes. We certainly
• 16:46could. But that's an example
• 16:48of we need research like
• 16:50that, particularly in the,
• 16:53in the clinical setting. If
• 16:54you
• 16:56are practicing that way and
• 16:57you have a data source,
• 16:59like, that would be a
• 17:00great example of a study
• 17:01that you could potentially think
• 17:02about.
• 17:06It looks like Shelley said
• 17:08one of Jesse Merlin's EMPOWUR
• 17:10study will examine bup up
• 17:12to thirty two milligrams in
• 17:13split dosing. So data in
• 17:15a few years and chronic
• 17:16pain, not acute pain.
• 17:18So, yes. Right. Still still
• 17:20an open research question.
• 17:23Yeah. And I will add
• 17:24anecdotally. I think I think
• 17:26that you'll see this as
• 17:27as we go throughout. But,
• 17:29this is a an exciting
• 17:32clinical and research area in
• 17:33many ways because clinical practice
• 17:36somewhat precedes and and expert
• 17:37guidelines,
• 17:39somewhat precede the evidence here.
• 17:41Right?
• 17:42Which was actually the intention
• 17:43of my next slide, which
• 17:44I don't think I need
• 17:45to introduce to this audience,
• 17:47but worth noting that the
• 17:49idea of,
• 17:50split dosing or temporary increases
• 17:53is already,
• 17:55recommended in expert,
• 17:57guidance,
• 17:58and being done in clinical
• 17:59practice. So the fact that
• 18:01we only find it on
• 18:02a handful, in this case,
• 18:03one case report,
• 18:06I think is notable.
• 18:10Okay.
• 18:11Continuing on
• 18:14to Melissa's point, we also
• 18:16looked for any intervention in
• 18:18people taking a long acting
• 18:19injectable buprenorphine.
• 18:21And although I will note,
• 18:23that,
• 18:24we're seeing an increase in
• 18:26the number of publications
• 18:28on this topic, they
• 18:30are up until at least
• 18:32July seventh twenty twenty four
• 18:34limited to case reports and
• 18:35series.
• 18:36We found six in our
• 18:38systematic review, and I won't
• 18:39list them individually, but can
• 18:41just kind of summarize
• 18:43as a group they all
• 18:44describe,
• 18:45various effective
• 18:46multimodal analgesic strategies,
• 18:49many of which including included
• 18:51the use of full agonist
• 18:52opioid medications
• 18:54in people,
• 18:56taking long acting injectable buprenorphine
• 18:58for OUD.
• 19:00And so, again, the gap
• 19:02here being,
• 19:03no comparative studies have evaluated
• 19:05any acute pain intervention, including,
• 19:08adding on additional sublingual buprenorphine
• 19:10in this group,
• 19:11for people taking a long
• 19:13acting injectable buprenorphine for OUD.
• 19:19Okay.
• 19:20Moving on. Our next subpopulation
• 19:22being folks taking methadone for
• 19:24OUD,
• 19:27and
• 19:28the practice of continuing methadone
• 19:29versus discontinuing, I think, is
• 19:31perhaps
• 19:32less debated,
• 19:33in terms of clinical practice
• 19:35given the difference in the
• 19:36pharmacologic properties of the two
• 19:38medications.
• 19:39However,
• 19:40in this case as well,
• 19:41we found one controlled cohort
• 19:43study.
• 19:46This was a a study
• 19:47of twenty nine people on
• 19:49methadone for OUD who were
• 19:50hospitalized with acute pain,
• 19:52which found that the mean
• 19:53pain scores and cumulative morphine
• 19:55doses required during the hospital
• 19:58were similar between those who
• 19:59continued versus discontinued
• 20:01their usual methadone dose perioperatively.
• 20:05However, notable that more people
• 20:06who discontinued
• 20:07their methadone received NSAIDs and
• 20:10I beam ketamine,
• 20:11and,
• 20:12this study did not control
• 20:13for those differences.
• 20:15And so we we we
• 20:16weren't able to make any
• 20:17conclusions based on this for
• 20:19the systematic review.
• 20:24As it relates to changes
• 20:26in baseline methadone dose and
• 20:27or frequency, we did find
• 20:29one uncontrolled cohort study in
• 20:31one case series,
• 20:32addressing this practice. The observational
• 20:35study published in two thousand
• 20:36and eight,
• 20:37of sixty seven people on
• 20:38methadone average dose of eighty
• 20:40two milligrams
• 20:42hospitalized with acute pain reported
• 20:44that twelve percent had their
• 20:45daily dose of methadone increased
• 20:47during the stay, and premature
• 20:49discharge was more common among
• 20:50those who did not have
• 20:51their methadone dose increased compared
• 20:53to those who did. However,
• 20:55no explicit pain outcomes were
• 20:57compared between the two groups.
• 20:59And then the case series
• 21:00from two thousand one describes
• 21:01six people taking methadone for
• 21:03OUD with acute or subacute
• 21:05cancer related pain,
• 21:07and this just kinda describes
• 21:08how they were able to
• 21:09achieve pain control with increased
• 21:11doses and or frequencies ranging
• 21:13from every four to eight
• 21:14hours
• 21:15of oral methadone or the
• 21:17administration in one case of
• 21:19IV methadone.
• 21:24And so the gap here,
• 21:26no studies have compared pain
• 21:28or OUD outcomes associated with
• 21:30temporary increases in methadone dose
• 21:32and or frequency,
• 21:33I e split missing. So
• 21:35similar to in the case
• 21:36of buprenorphine.
• 21:42I just pulled in. I
• 21:43actually borrowed this table from
• 21:45I adapted it from a
• 21:46publication from, Dale Terasaki,
• 21:50And just highlighting the fact
• 21:52that,
• 21:52again, similar to to buprenorphine,
• 21:55this
• 21:56practice of, temporarily making changes
• 21:59to the methadone dose and
• 22:00or frequency
• 22:01is currently recommended by a
• 22:03number of expert organizations,
• 22:05and is already clinically in
• 22:06practice,
• 22:07or has been for many
• 22:08years.
• 22:13Okay.
• 22:16So now we'll talk a
• 22:17little bit about different interventions
• 22:19that we came across in
• 22:20the systematic
• 22:22review. And so to refresh
• 22:24everyone's memory, I'm talking about
• 22:26the far left, column.
• 22:30And we did in the
• 22:31systematic review make a few,
• 22:33conclusions with low strength of
• 22:35evidence,
• 22:37based on the presence of
• 22:38at least one randomized clinical
• 22:41trial with low,
• 22:43risk of bias,
• 22:45for interventions, which may improve
• 22:48pain outcomes in people with
• 22:49with opioid use disorder. And
• 22:51so I've listed those three
• 22:52here, and I'll go into
• 22:53a time a bit more
• 22:54detail for you.
• 22:55So first,
• 22:57p oclonidine.
• 22:58So this was a single
• 22:59RCT with a low risk
• 23:01of bias conducted among seventy,
• 23:04adults,
• 23:05in Iran with OUD actively
• 23:07using opium
• 23:08who presented to the ED
• 23:10for acute pain from an
• 23:11orthopedic fracture.
• 23:12Oriclclonidine
• 23:13at zero point two milligrams
• 23:15was found to decrease pain
• 23:17severity up to an hour,
• 23:20compared to placebo.
• 23:23And that's what we found
• 23:24for Keoclonidine.
• 23:26A single RCT with a
• 23:28low risk of bias,
• 23:29conducted among eighty seven, adults
• 23:32with OUD in Iran actively
• 23:34using opium again presented to
• 23:36the ED with acute traumatic
• 23:37or non traumatic limb or
• 23:39abdominal pain.
• 23:41This study found that the
• 23:43combination of I'm,
• 23:45Haldol with I'm midazolam and
• 23:47IV morphine
• 23:48can decrease pain severity up
• 23:50to six hours,
• 23:51compared to IV morphine alone.
• 23:55And then the third intervention,
• 23:57we found a single randomized
• 23:59clinical trial with a low
• 24:00risk of bias,
• 24:02conducted among a hundred and
• 24:03eighty adults with OUD actively
• 24:05using opium in Iran,
• 24:08reporting that IV lidocaine administered
• 24:11during general anesthesia,
• 24:13may decrease postoperative pain severity
• 24:16and full agonist opioid analgesic
• 24:18use compared,
• 24:20to IV ketamine or,
• 24:22placebo. It was a three
• 24:23arm study.
• 24:27So there are many gaps
• 24:28here. I've listed some of
• 24:29them. I'm sure this is
• 24:30not a complete list, But
• 24:32for all of these interventions,
• 24:33the optimal medication dosing and
• 24:35duration remains unclear.
• 24:37Their safety and efficacy in
• 24:38people taking a medication for
• 24:40OUD, notably all three trials
• 24:42I just mentioned, were conducted
• 24:43in people actively using opium.
• 24:46And then the optimal clinical
• 24:47setting or scenario,
• 24:50in terms of what,
• 24:51you know,
• 24:53right, PACU being one example.
• 24:55And then, none of these
• 24:57studies looked at OUD OUD
• 24:58related outcomes.
• 24:59And so that's a notable
• 25:00gap for every intervention
• 25:03listed here.
• 25:05We also came across some
• 25:07interventions
• 25:08with insufficient evidence,
• 25:10and so I've listed some
• 25:11of those here.
• 25:13IT,
• 25:14intra sorry. IT intrathecal,
• 25:17clonidine,
• 25:18IV dexmedetomidine.
• 25:20I always say that wrong.
• 25:22IV ketamine, and then various,
• 25:25phlebotomist opioid medications,
• 25:28and our conclusions regarding this
• 25:30group of interventions
• 25:32or these groups of interventions
• 25:34was largely that evidence was
• 25:35insufficient,
• 25:37to make any conclusions.
• 25:40Mostly, I should add, due
• 25:41to heterogeneity
• 25:42in either the study population,
• 25:45the comparator,
• 25:47or outcomes evaluated,
• 25:49among studies reporting on these
• 25:51interventions.
• 25:56I do wanna spend a
• 25:57minute touching on IV ketamine
• 25:58because I feel this is
• 25:59often,
• 26:00an intervention of interest.
• 26:04And so for for this,
• 26:06intervention in particular, we did
• 26:08find three RCTs,
• 26:10two observational studies, and ten
• 26:12case reports,
• 26:14just reporting on the use
• 26:15of IV ketamine for pain
• 26:17in people with OUD.
• 26:19All three RCTs
• 26:21were conducted,
• 26:23among predominantly male participants.
• 26:26Two included
• 26:27participants actively using opium, and
• 26:29one included participants,
• 26:32on methadone for OUD.
• 26:34Pain conditions,
• 26:36reported on included limb fractures
• 26:38and postoperative pain, and then
• 26:40all compared IV ketamine alone
• 26:42or with an IV phle
• 26:43agonist opioid compared to an
• 26:45IV phle agonist opioid alone,
• 26:48and findings were mixed.
• 26:52In general,
• 26:53there were reported improvements in
• 26:55pain severity up to twenty
• 26:57four hours following medication administration.
• 27:02I'm sorry. Reported improvements were
• 27:04similar or improved,
• 27:06among those who received IV
• 27:07ketamine compared to the IV
• 27:09phlebotomist opioid,
• 27:11that being either morphine or
• 27:12fentanyl.
• 27:14However, participants who received ketamine
• 27:16also reported higher rates of
• 27:18adverse events,
• 27:20and I've listed the ones
• 27:21specifically evaluated
• 27:23here. So diplopia, nystagmus, agitation,
• 27:25loss of consciousness,
• 27:27nausea, vomiting, or confusion.
• 27:35And so we ended up
• 27:36concluding from the systematic review
• 27:39that,
• 27:40the scenarios in which the
• 27:41benefits exceed the risks of
• 27:43ketamine are unclear.
• 27:46And so
• 27:48that's a notable
• 28:00gap. Okay.
• 28:01And then lastly,
• 28:03I did wanna spend a
• 28:04minute touching on full agonist
• 28:05opioid medications, and Melissa can
• 28:07attest to this as well
• 28:09as Leila. She's still,
• 28:11here and listening. But we
• 28:12had a really difficult time
• 28:13making sense of our full
• 28:15agonist opioid
• 28:16medication data,
• 28:19in terms of informing our
• 28:20our systematic review.
• 28:23And so
• 28:24I'm just gonna summarize a
• 28:26little bit.
• 28:27We found four randomized clinical
• 28:29trials, twenty five observational studies
• 28:32that described any oral or
• 28:34IV phle agonist opioid.
• 28:39Three RCTs and six studies
• 28:41described IV PCA,
• 28:43and then the settings,
• 28:44ranged from nonoperative to postoperative,
• 28:47but they were all hospital
• 28:48settings.
• 28:50Importantly, study designs
• 28:52varied as to whether the
• 28:54full agonist opioid was the
• 28:55intervention or the outcome.
• 28:58And notably, a lot of
• 28:59studies used full agonist opioid
• 29:03dosing or requirement
• 29:05as a proxy for pain
• 29:06severity,
• 29:07in terms of their evaluation
• 29:09of a different
• 29:10intervention.
• 29:11And so it was kind
• 29:12of a lot for us
• 29:13to make sense of.
• 29:19What I was able to
• 29:20do is to summarize the
• 29:22range of doses reported
• 29:23by setting,
• 29:25and then the n here
• 29:26you see on the left
• 29:27hand column is the number
• 29:28of studies,
• 29:30informing that range
• 29:32that you see in the
• 29:33right hand column.
• 29:35And so
• 29:39in nonoperative settings, the dosing
• 29:41dosing range from eighteen to
• 29:43seventeen morphine milligram equivalents per
• 29:46day of PO and IV
• 29:47full agonist opioids.
• 29:49In postoperative settings,
• 29:51twenty studies,
• 29:53provided a range from forty
• 29:55four to seven hundred ninety
• 29:57three
• 29:57morphine milligram equivalents per day
• 29:59of phalagonist opioids.
• 30:01Among two studies that reported
• 30:04the,
• 30:05phalagonist opioid dose,
• 30:08among people receiving PCAs only.
• 30:10The range was one fifty
• 30:11five to two eighty two
• 30:13MMEs per day.
• 30:14And then
• 30:16broken down by population, people
• 30:17taking methadone or people taking
• 30:19buprenorphine,
• 30:21People taking methadone, nine studies
• 30:23provided a range of five
• 30:24to six hundred eighty eight
• 30:26MMEs per day, and people
• 30:28taking buprenorphine,
• 30:29sixteen studies provided a range
• 30:31of eighteen
• 30:32to three hundred and eight
• 30:33MMEs per day.
• 30:37As you can note, the
• 30:38range is quite wide regardless
• 30:40of setting your population. And
• 30:41I think,
• 30:43when thinking about this, it's
• 30:44important to note that studies
• 30:45vary not only in the
• 30:47type of acute pain studied
• 30:48as well as the method
• 30:50they use to calculate the
• 30:51MME, as in whether or
• 30:53not they included the methadone
• 30:54or the buprenorphine
• 30:55respectively
• 30:56in their MME calculations,
• 30:58and that this precluded conclusions
• 31:00regarding,
• 31:02any type of summative conclusion
• 31:03we could make based on
• 31:04the data provided.
• 31:08Lastly, if we have enough
• 31:09time, it looks like we
• 31:10do.
• 31:11I wanted to make a
• 31:12quick note,
• 31:13about
• 31:14some studies directly compared the
• 31:16full agonist opioid dosing between
• 31:18people taking methadone and buprenorphine,
• 31:20and this was one of
• 31:21our questions when we set
• 31:22out for the systematic review.
• 31:25And for the most part,
• 31:27they found that full agonist
• 31:28opioid dosing generally did not
• 31:30differ between these two populations,
• 31:33with two exceptions in terms
• 31:35of observational studies.
• 31:37The first was a,
• 31:41a low risk of bias,
• 31:44comparative
• 31:45observational cohort study
• 31:47that looked at postoperative full
• 31:49agonist
• 31:50opioid use between a hundred
• 31:52and ninety five people on
• 31:53buprenorphine
• 31:54eighty percent for OUD
• 31:56and seven hundred and thirty
• 31:57three people on methadone for
• 31:59OUD.
• 32:00And they found that those
• 32:01taking buprenorphine had lower full
• 32:03agonist opioid use across multiple,
• 32:06I think over five different
• 32:07sensitivity
• 32:08analyses,
• 32:09and one in which they
• 32:10compared people with OUD taking
• 32:13buprenorphine
• 32:14specifically at doses greater than
• 32:15sixteen milligrams
• 32:17per day compared to people
• 32:19taking methadone
• 32:20with at least sixty milligrams
• 32:22per day,
• 32:23and then all of whom
• 32:24continued their baseline MOUD.
• 32:27The second study was,
• 32:30a bit older. I don't
• 32:31remember the year. I wanna
• 32:32say two thousand seven.
• 32:34Was an observational,
• 32:35cohort study of forty seven
• 32:37pregnant people taking methadone and
• 32:39ninety nine people taking bupendorfine
• 32:42for OUD who underwent cesarean
• 32:44section
• 32:45and reported that higher,
• 32:47baseline doses of methadone but
• 32:49not buprenorphine
• 32:50were associated with higher inpatient
• 32:52full agonist opioid use.
• 32:56And so
• 32:58primary gaps,
• 33:00again, there are many,
• 33:01but as it relates to
• 33:02full agonist opioid medications,
• 33:05we don't understand,
• 33:07or
• 33:08notable gaps, I guess you
• 33:10could say include which medications
• 33:12dosing and durations
• 33:13might be best for which,
• 33:15patient and clinical scenario.
• 33:17No studies have evaluated opioid
• 33:19use disorder outcomes associated with
• 33:22the administration of FOL against
• 33:23agonist opioid medications during acute
• 33:25pain. And very few studies
• 33:27compared the impact of full
• 33:28agonist opioid medications
• 33:30on pain or OUD outcomes
• 33:32between different MOUD groups except
• 33:34the two studies I mentioned.
• 33:45And then lastly,
• 33:47worth note,
• 33:49it's worth talking about setting.
• 33:50And so this was,
• 33:53a very fun figure that
• 33:55one of our coauthors made,
• 33:57breaking down the different interventions
• 34:00that we found in the
• 34:01systematic review,
• 34:03by setting,
• 34:05similar to an evidence map,
• 34:06I guess you could say.
• 34:08And it's worth noting. So,
• 34:10you you're seeing four quadrants.
• 34:12The top left is,
• 34:14interventions that looked at postoperative
• 34:16pain in hospital settings.
• 34:18Top right are the studies
• 34:19looking at post labor or
• 34:21post cesarean section pain in
• 34:22hospital settings.
• 34:24Bottom left, other acute pain
• 34:26in hospital or ED settings.
• 34:28And then lastly,
• 34:29a group looking specifically at
• 34:31orthopedic injuries in hospital or
• 34:33ED settings.
• 34:35And importantly,
• 34:37we did not find a
• 34:38single comparative study looking at
• 34:40any acute pain intervention in
• 34:42people with OUD in any
• 34:43outpatient setting.
• 34:45So every comparative study we
• 34:47included in the systematic review
• 34:49was conducted in hospital
• 34:52setting. Although we did not,
• 34:54I should mention, although we
• 34:55did not look specifically for
• 34:56hospital settings, our our our
• 34:58search criteria was to include
• 35:00all, and this is just
• 35:01what we found.
• 35:09And then I'll just close
• 35:10with,
• 35:11just perhaps an anecdote that
• 35:12when we set out to
• 35:13do the systematic review, we
• 35:15convened a group of expert
• 35:17clinicians and researchers in this
• 35:18area, and we did identify
• 35:20a number of research questions
• 35:22we thought might be helpful
• 35:23to answer with the systematic
• 35:25review. We ended up,
• 35:27structuring our key questions a
• 35:29bit differently, but I do
• 35:30think it's worth mentioning,
• 35:32that, you know, these are
• 35:33two notable questions I've pulled
• 35:35on the screen here that
• 35:36our expert group had thought
• 35:37it would be useful to,
• 35:40speak out evidence on, and
• 35:42we did not find anything.
• 35:46Right. So, for people with
• 35:49opioid use disorder who are
• 35:50not taking a medication,
• 35:52does,
• 35:53MOUD initiation
• 35:54provide effective analgesia
• 35:56during periods of acute pain?
• 35:58And then secondly,
• 36:00bit more broadly, how do
• 36:01acute pain management strategies impact
• 36:04OUD outcomes?
• 36:06And I think that's an
• 36:07important evidence gap.
• 36:12And so
• 36:13that rounds out the gaps
• 36:14that we had identified.
• 36:16I see a few chats
• 36:18look like they've come in,
• 36:18but I haven't been able
• 36:19to look at them. Yeah.
• 36:20No. No. No. No. Welcome
• 36:22questions. Great. Thank you, Michelle.
• 36:24Thank you, Melissa.
• 36:26I'll read some of the
• 36:27questions.
• 36:29Starting off early on,
• 36:32doctor Parker from the emergency
• 36:34department and ASAP. Is there
• 36:36any reported outcome data for
• 36:38use of new
• 36:39non opioid oral pain medications
• 36:43for patients with
• 36:44ongoing buprenorphine or methadone
• 36:47and the change of in
• 36:48pain?
• 36:54Non opioid
• 36:56oral pain medications.
• 36:58So please feel free to
• 37:00only read if you wanna
• 37:01clarify. Or
• 37:08I guess I was struck
• 37:09also many of your competitors.
• 37:11I think you included clonidine,
• 37:13aldol, ketamine.
• 37:14I didn't hear any nonsteroidals.
• 37:18No.
• 37:21Yes. I think that's right.
• 37:22Sorry. I had not previously
• 37:25thought of that as its
• 37:26own class of medication missing,
• 37:27but I think I think
• 37:28you are right.
• 37:30And I can tell
• 37:33you perhaps by pulling up
• 37:35this this is our table.
• 37:40Yep.
• 37:41That's single nodal.
• 37:43Yeah. I think there were
• 37:44there were some studies where
• 37:47NSAID or
• 37:48acetaminophen
• 37:49may have been combined with
• 37:50one of these other
• 37:52interventions, but not as a
• 37:54standalone intervention.
• 37:58Yes. I think that's right.
• 38:00Yeah. And,
• 38:01Bruce may be referring
• 38:04to, you know, the new
• 38:06new approved non opioid treatment,
• 38:09suzatrogine
• 38:12or Jordanavex.
• 38:13This is a non opioid,
• 38:16pain medication
• 38:17that was recently approved, but
• 38:19I imagine
• 38:20We did not recognize
• 38:22any. No. Yep.
• 38:25So,
• 38:26next question,
• 38:29from Adam Seidner. Was there
• 38:31anything in the review about
• 38:33adding
• 38:34digital therapeutics,
• 38:35virtual environments,
• 38:37or any nonpharmacologic
• 38:39interventions
• 38:39to the pharmacologic interventions?
• 38:42That's a great question.
• 38:45I apologize. I did not
• 38:46include that here. We came
• 38:47across one,
• 38:50and it was a
• 38:52oh, jeez. Melissa, please correct
• 38:54me if I'm wrong. It
• 38:54was a virtual reality
• 38:56administered. I think it was
• 38:58a mindfulness
• 38:59intervention,
• 39:00but administered using a VR
• 39:03headset,
• 39:04that they did a pre
• 39:06it was it was an
• 39:07observational cohort study with no,
• 39:10comparison group where they looked
• 39:12at this rollout on an
• 39:13orthopedic unit on a in
• 39:15hospital setting and then just
• 39:17kind of reported
• 39:18a bit about pain
• 39:20outcomes prior to rolling out
• 39:21this virtual reality intervention and
• 39:23then,
• 39:26post rollout.
• 39:27And they they did find
• 39:28that pain outcomes were improved
• 39:30after rolling out said,
• 39:32intervention, but that was the
• 39:34only one that we found
• 39:37in conducting
• 39:38this,
• 39:39right, this,
• 39:41systematic review. I think,
• 39:44yeah, that brings up another
• 39:45important
• 39:46point or thing to keep
• 39:48in mind. So
• 39:49we were really focused in
• 39:51this systematic review on opioid
• 39:53use disorder, not opioid dependence.
• 39:57So one of the challenges
• 39:58of this systematic review is
• 40:00within the literature,
• 40:02there's a conflation of the
• 40:03two that we found in
• 40:05many of the studies.
• 40:07So we really had to
• 40:08grapple with this idea of
• 40:11what is the population and
• 40:12clearly defining the population. So
• 40:15is this opioid dependence prescribed
• 40:17long term opioids versus someone
• 40:19with opioid use disorder?
• 40:21And there were actually times
• 40:23when
• 40:24some of these studies included
• 40:26both populations,
• 40:27and so then we had
• 40:28to decide if we would
• 40:29include the study that had
• 40:31both populations.
• 40:33And so we chose
• 40:35if there were enough people
• 40:36with OUD in the study,
• 40:39we we did choose to
• 40:41include some of those studies,
• 40:42but there were times where
• 40:43it was so unclear that
• 40:45we didn't include that study.
• 40:47So I think there are
• 40:48more studies
• 40:50looking at individuals
• 40:52who are prescribed long term
• 40:54opioids who may might meet
• 40:55that definition of opioid dependence
• 40:58on some of the nonpharmacologic
• 41:00interventions,
• 41:01but not specifically in this
• 41:03population of people with opioid
• 41:05use disorder.
• 41:11Thank you, Melissa. That's helpful
• 41:13and an important distinction.
• 41:15Patient Dow asked,
• 41:17how was the co occurrence
• 41:19of acute and chronic pain
• 41:20handled in the review?
• 41:21And, also, what share of
• 41:23the studies in the review
• 41:24were from the US?
• 41:29Two very good questions.
• 41:31So first, this is somewhat,
• 41:35similar to Melissa's prior answer,
• 41:37but we we notably did
• 41:39not include studies
• 41:41that,
• 41:42had, for example, buprenorphine
• 41:44prescribed for chronic pain without,
• 41:46explicit mention of opioid use
• 41:48disorder. And so we did
• 41:49focus the population
• 41:51on opioid use disorder
• 41:53with acute pain.
• 41:55Now
• 41:57the co occurrence
• 41:58of acute and chronic pain,
• 42:01I'm sure that was represented
• 42:03in our,
• 42:04in the studies that we
• 42:05included. But,
• 42:10yeah, I guess
• 42:14most of the outcomes I
• 42:16guess,
• 42:16to address your question, most
• 42:18of the outcomes, even the
• 42:19pain related outcomes were short
• 42:21term,
• 42:22and were focused specifically on
• 42:24a
• 42:25specific acute pain condition. We
• 42:27didn't break up our studies
• 42:29that way or the way
• 42:30we reported our findings because
• 42:31it was so
• 42:32heterogeneous,
• 42:34the largest perhaps subgroup being
• 42:36postoperative
• 42:37pain.
• 42:40So I I I would
• 42:42like to say that most
• 42:43of the pain outcomes we
• 42:44found and reported on were
• 42:47specifically
• 42:48for acute pain.
• 42:50However,
• 42:53is it likely acute on
• 42:55chronic pain,
• 42:56and is there a high
• 42:57prevalence of chronic pain in
• 42:59people with OUD? We know
• 43:00the answer to that is
• 43:01yes.
• 43:02And so
• 43:03I guess my assumption is
• 43:05that chronic pain is at
• 43:06play here, although we didn't
• 43:07specifically find a way to
• 43:09account for it in our
• 43:10presentation results.
• 43:13I would also add that
• 43:14you'll see here
• 43:16at the bottom
• 43:17the different types of pain
• 43:19that were included, and, notably,
• 43:21men most of these
• 43:25are surgical
• 43:26or post surgical or some
• 43:28type of injury.
• 43:30So there
• 43:31there was some acute nonsurgical
• 43:33pain, but that was definitely
• 43:35not
• 43:36the
• 43:38majority of these studies.
• 43:40So if you're thinking about
• 43:41individuals you're treating on a
• 43:43general medical unit who, say,
• 43:45have abdominal pain,
• 43:48or pancreatitis
• 43:49related pain, or, you know,
• 43:51some other sort of medically
• 43:53related pain condition,
• 43:56which probably fits more of
• 43:58that acute on chronic pain
• 44:00that we you're thinking of.
• 44:02There weren't many studies
• 44:04of those
• 44:05patients. So I think,
• 44:07you know,
• 44:08if somebody comes in with
• 44:10an acute fracture, we're really
• 44:11talking about acute pain. We're
• 44:13not talking about chronic pain.
• 44:16So I think that's another
• 44:17area of potential
• 44:21research would be for
• 44:23more of the medically related
• 44:25complex pain that we're seeing
• 44:27in
• 44:28generally,
• 44:29you know, general medicine
• 44:32settings.
• 44:33And I get I guess,
• 44:34Melissa, to that point, I,
• 44:35you know, I'm not seeing
• 44:36any
• 44:37reports
• 44:38of osteomyelitis
• 44:40or abscesses,
• 44:42you know,
• 44:43and it I think what
• 44:44I'm hearing is
• 44:46those types of things that
• 44:47you would presume would be
• 44:49common among people receiving
• 44:51MOUD
• 44:52have not been represented
• 44:54in the scientific literature as
• 44:56causing acute pain or being
• 44:58treated acutely.
• 45:00Not in large comparative
• 45:03well done studies with low
• 45:05risk of bias. Correct.
• 45:07Thank you.
• 45:08They're all really limited to
• 45:11case reports or case series.
• 45:14But, you know, the patients
• 45:16that we see
• 45:17in the hospital who have
• 45:19the osteo, who have the
• 45:20endocarditis, who have the
• 45:22spinal abscess,
• 45:24we don't have a great
• 45:26comparative
• 45:27study about how to best
• 45:29treat those individuals.
• 45:34Michelle, so you mentioned OUD
• 45:36outcomes, and I was just
• 45:37gonna challenge you a little
• 45:39bit. So what OUD outcomes
• 45:41would you
• 45:43be interested in looking at
• 45:45and and what time window?
• 45:48That's a great question.
• 45:49It was one of our
• 45:50main,
• 45:51like, conclusions from our systematic
• 45:54review, but I do
• 45:56welcome
• 45:57feedback.
• 45:59Some study did report on
• 46:00the presence of cravings,
• 46:02short term,
• 46:05mostly the randomized clinical trials
• 46:08among people not prescribed,
• 46:10MOUD, you see in the
• 46:11right hand column.
• 46:13But we did not we
• 46:14noted we sorry. We notably
• 46:16did not identify
• 46:19many at all studies looking
• 46:20at, either initiation or retention
• 46:23in MOUD
• 46:24treatment.
• 46:25I think there was one
• 46:27study that looked at buprenorphine
• 46:29discontinuation
• 46:30versus continuation at thirty day
• 46:32retention.
• 46:33But other than that, that
• 46:34was the only one that
• 46:35looked at retention post hospital
• 46:37discharge,
• 46:40return to use,
• 46:41or maybe patterns of use
• 46:45would be the two that
• 46:47I think were most notably
• 46:48missing.
• 46:51And,
• 46:52just to be clear, you're
• 46:54thinking of post discharge or
• 46:56post
• 46:56resolution of the painful
• 46:59Yes. Episode. Okay. Yes. I
• 47:02I think part of that's
• 47:03informed by a notable concern
• 47:05you see among clinicians to
• 47:06aggressively
• 47:07treat acute pain among people
• 47:09with OUD is worsening the
• 47:11OUD,
• 47:12either with return to use,
• 47:15among people,
• 47:17not currently using,
• 47:19or some other, negative outcome
• 47:21post the acute pain episode.
• 47:24Mhmm. And we did not
• 47:25find any studies specifically
• 47:27looking at those outcomes.
• 47:29And
• 47:30another I should say. Yeah.
• 47:32Another potential
• 47:34surrogate marker could be premature
• 47:36discharge,
• 47:38or and and a lot
• 47:40of the work that we've
• 47:42done through Empower has looked
• 47:44at patient satisfaction
• 47:46or or quality of life,
• 47:48like, how satisfied is the
• 47:49person with the pain the
• 47:50quality of pain care that
• 47:52they're receiving
• 47:54for an individual with opioid
• 47:56use disorder, and I think
• 47:57that's a notable
• 47:59gap that we don't we
• 48:00don't really know
• 48:02how people are doing
• 48:05in regard to pain specifically
• 48:07when they have a pain
• 48:09condition and OUD.
• 48:13Thank you.
• 48:15Shelly Sue asked, does the
• 48:16review tell us how well
• 48:18hospitals
• 48:19are maintaining people on MOUD
• 48:21versus removing them?
• 48:28Alyssa might be better equipped
• 48:30to answer this question than
• 48:31I, but,
• 48:32the review did not specifically
• 48:34address
• 48:37that. We did hope to
• 48:40look at that in terms
• 48:41of, when we separated our
• 48:43findings by MOUD management being,
• 48:46continuing, discontinuing, or altering someone's
• 48:49baseline MOUD when in acute
• 48:52pain and then other interventions.
• 48:56But I
• 48:57I think what you're getting
• 48:58at is if we have
• 48:59a sense for what the
• 49:00current standard of practice is
• 49:03using these studies as to
• 49:06how people are most often
• 49:07managed,
• 49:08when they come in, and
• 49:09I
• 49:10I don't think we got
• 49:11that answer.
• 49:15I would say as a
• 49:15group, most of the studies
• 49:18seem to be most interested
• 49:19in how do you
• 49:21successfully continue someone on their
• 49:24MOUD.
• 49:26Though there weren't many about
• 49:27initiation,
• 49:30it did seem to be
• 49:31a question that people are
• 49:32grappling with. There there weren't
• 49:35I don't remember any studies
• 49:37that talked about complete discontinuation
• 49:41of
• 49:42MOD.
• 49:44I think most people are
• 49:45grappling with how do we
• 49:47safely continue
• 49:48particularly the buprenorphine
• 49:50and still have good pain
• 49:51relief. And thankfully, many of
• 49:53the studies show that that's
• 49:54very possible to do and
• 49:56and consistent with current
• 49:58guidance, albeit,
• 50:00you know, we don't have
• 50:01a great evidence base for
• 50:03it. So I would say
• 50:04by and large, it seems
• 50:06like people are getting the
• 50:08message, though I still think
• 50:09there's a lot of misinformation
• 50:11out there
• 50:13about buprenorphine continuation
• 50:15and methadone continuation.
• 50:17I don't think anybody thinks
• 50:18you should discontinue methadone if
• 50:20somebody's been,
• 50:22stable on it, but
• 50:25you know, I don't make
• 50:26many assumptions like that anymore.
• 50:27Yeah. Though
• 50:29that's a good point. Unless
• 50:30I I guess I will
• 50:32argue
• 50:32in,
• 50:34as a, you know, as
• 50:35a result of our understanding
• 50:36what happens
• 50:37in our own state.
• 50:39I think it's probably very
• 50:41hyperlocal,
• 50:43decision. You can have two
• 50:44hospitals in the same city
• 50:46that have completely
• 50:48disparate protocols with respect to
• 50:51continuation versus,
• 50:53tapering or discontinuation.
• 50:55So I
• 50:57my I think the the
• 50:59short answer to Shelley is
• 51:00there's huge amount of practice
• 51:02variation
• 51:03that is very much institutionally
• 51:05determined, and, unfortunately,
• 51:07not as many patients are
• 51:08continued as we would expect
• 51:10around the country at large.
• 51:13Definitely.
• 51:13And this this will actually
• 51:15answer,
• 51:16the another question that patients
• 51:18had was how many of
• 51:20these studies were outside the
• 51:21US? I will say in
• 51:22the non US studies, it
• 51:24was very rare for those
• 51:25people to be started on
• 51:27any form of MOUD,
• 51:30and most of these individuals
• 51:31were treated
• 51:32The majority of them were
• 51:34in treated in Iran.
• 51:36There was one study in
• 51:37Egypt, I believe.
• 51:39That's right. And interestingly,
• 51:41almost a hundred percent of
• 51:43the people in the study
• 51:44were male.
• 51:46So a hundred percent men
• 51:47who used opium,
• 51:50not
• 51:51opioids, not heroin, not fentanyl,
• 51:53opium
• 51:54in Iran
• 51:56coming in with a traumatic
• 51:58injury.
• 52:00That was what the majority
• 52:01of those studies were. But
• 52:03those were all the studies
• 52:04that were actually looking at
• 52:05some of these non,
• 52:08opioid interventions, which is kind
• 52:10of interesting. So you do
• 52:11have to think about generalizability.
• 52:14The total number of those
• 52:15studies, there were maybe
• 52:18ten, Michelle.
• 52:21I think,
• 52:23the rest were from were
• 52:24from the US.
• 52:26That's right.
• 52:27Yeah. So
• 52:28interesting. And then because I
• 52:30know we're out of time.
• 52:31I saw Natalie's question about
• 52:34the benefits of regional blocks,
• 52:36on acute pain. And I
• 52:38think this is a really
• 52:39important question and something that
• 52:40I'm always advocating for our
• 52:42patients who
• 52:44have OUD. Because if you
• 52:45can,
• 52:46you know, block someone's foot
• 52:48who has osteo in their
• 52:49foot,
• 52:50you can really improve their,
• 52:52their pain, or at least
• 52:53we think you can improve
• 52:54their pain.
• 52:56Unfortunately,
• 52:56most of those studies, and
• 52:58this would be something that
• 52:59I would hope Natalie would
• 53:01want to study in the
• 53:02future,
• 53:04most of those studies were
• 53:05only looking at block duration.
• 53:09They weren't actually looking at
• 53:10pain outcomes.
• 53:12So we don't wanna just
• 53:13know how long did the
• 53:15block last. We wanna know
• 53:16how it helped the patient.
• 53:18And so
• 53:19though there are block studies,
• 53:22they were limited in the
• 53:23outcomes that we could look
• 53:24at.
• 53:25I would actually be happy
• 53:27to share some of those
• 53:27studies with anybody interested because,
• 53:30Tom Hickey was our anesthesia
• 53:32colleague
• 53:33on this
• 53:34review, and we we did
• 53:35have amongst the authors and
• 53:37then with the editorial team
• 53:38of the journal a bit
• 53:39of a debate about whether
• 53:41duration of block is a
• 53:43sufficiently pain related outcome to
• 53:46include in the study and
• 53:47report on.
• 53:48And we ended up concluding
• 53:50that if postoperative
• 53:52pain itself was measured and
• 53:54reported, that was sufficient. But
• 53:56if it was just duration
• 53:58of block, it was not.
• 53:59But we did find a
• 54:00number of studies, including about,
• 54:03lidocaine infusions intraoperatively,
• 54:06as they relate to postoperative,
• 54:08block, and perhaps you could
• 54:10transferably say pain,
• 54:12and I'd be happy to
• 54:13kinda dig those up and,
• 54:15share them with folks.
• 54:18Yeah. Shelley gets the last
• 54:20question. She says the MME
• 54:22levels across MOUDs
• 54:24seem to show that there
• 54:25isn't a direct relationship between
• 54:27MOUD type and MME
• 54:30slash pain control,
• 54:32assuming that the MMEs
• 54:34may not be calculated the
• 54:36same across studies.
• 54:39I love this comment, Shelley,
• 54:40I will say.
• 54:42I got down a whole
• 54:43rabbit hole with this and
• 54:45made tables on tables of
• 54:48looking at how each
• 54:50study calculated their MMEs. Did
• 54:51they include methadone? Did they
• 54:53include buprenorphine? Did they not?
• 54:55And it was honestly, it
• 54:57was so
• 54:58the the heterogeneity
• 54:59made it impossible
• 55:01to compare,
• 55:02in any meaningful way. And
• 55:04so the best we could
• 55:06do is just kinda report
• 55:07a range, and you can
• 55:08even see the range. I
• 55:08mean, the range in methadone,
• 55:10five to seven hundred
• 55:12MMEs per day,
• 55:14is quite a wide range.
• 55:16And so I I don't
• 55:17think there is data yet
• 55:18to support that it differs
• 55:21by MOUD.
• 55:22However,
• 55:23I
• 55:24am not confident
• 55:27that we can
• 55:28say we've sufficiently
• 55:30determined that there isn't. I
• 55:31think it's just that the
• 55:33the data is too
• 55:35heterogeneous
• 55:36at this time.
• 55:38And I I would be
• 55:39interested in a more rigorous,
• 55:41comparison.
• 55:44I don't know if you
• 55:45wanna add to that, Melissa.
• 55:47I would just say, though,
• 55:48right, we did find studies
• 55:50that
• 55:51that helped us rigorously answer
• 55:53this question.
• 55:55I would say in my
• 55:56clinical practice,
• 55:57interestingly,
• 55:58I am seeing individuals
• 56:00who are treating with methadone
• 56:02need much higher doses
• 56:05of full agonist
• 56:06than those who are are
• 56:08receiving buprenorphine.
• 56:09And I think some of
• 56:10that could be related
• 56:12to some of the hyperalgesia
• 56:13that we see with methadone
• 56:15and the need to overcome
• 56:17the
• 56:18blockade
• 56:19of methadone, which I think
• 56:20actually,
• 56:22strangely, is higher than with
• 56:24buprenorphine.
• 56:26And so,
• 56:28you know, we've been
• 56:29in our practice seeing individuals
• 56:32postoperatively,
• 56:34say, going through cardiac surgery,
• 56:36if they are treated with
• 56:37methadone, it's gonna be much,
• 56:39much harder to get their
• 56:40acute pain under control than
• 56:41if they are treated with
• 56:42buprenorphine.
• 56:44We're actually able to get
• 56:45their pain under control with,
• 56:48much fewer
• 56:49lower doses of opioids. So
• 56:52I think there's
• 56:53that is a huge open
• 56:55question that I think,
• 56:57would be great to to
• 56:59be able to have more
• 57:00rigorous study about.
• 57:02Wonderful. Thank you everybody for
• 57:03joining. Thank you, Michelle and
• 57:05Melissa.
• 57:07I think you all see
• 57:08that there's a research road
• 57:09map that has just been
• 57:11outlined for you. Emergency medicine,
• 57:14anesthesiology,
• 57:16hospitalist,
• 57:17addiction medicine.
• 57:19Go forth and,
• 57:21prosper.
• 57:22Thank you, everybody.