Friday, July 13, 2018

Dilemmas in Aid in Dying: Podcast with Bernie Lo

In this week's podcast we talked with Dr. Bernard Lo (Bernie as he is known).  Dr. Lo is President of the Greenwall Foundation, a foundation dedicated to improving Bioethics research nationally.  Prior to Greenwall, Dr. Lo was Professor of Medicine at UCSF and head of the Bioethics Program.  He still maintains a primary care practice at UCSF.

We talked with Bernie about several dilemmas in the area of physician aid in dying, with conversation jump started by his recent NEJM perspective on this topic.  Key areas we discuss include: (1) when ought providers raise the possibility of PAD with patients?  Are they obligated to do so with all seriously ill patients? (2) what do we call it when talking with patients - physician aid in dying? assisted suicide?  or descriptive terms?  (3) In an era of sharp increases in the cost of barbiturates, what are the ethical issues at stake when clinicians are trying new regimens to help patients die with little oversight?  (4) what are there responsibilities of physicians who do not prescribe, or work in systems where prescribing or evaluation are not allowed?  (4) does the current law discriminate against people with ALS who are physically unable to self-administer, or those with early stage dementia, who do not have less than 6 months left to live, and in the future will not be able to consent?

Eric, Lynn, and I were remarking afterward about how skillful and thoughtful of a speaker Bernie is - and how by talking with him we learn how to think through complex issues, and how to provide affirmation up front in response to a question (great question, I think you're right, you've hit on a key point).  He is a master discussant who treats this potentially explosive topic with measured thoughtfulness and care.


-by Alex Smith, @AlexSmithMD

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Eric: Welcome to the GeriPal Podcast. This is Eric Widera.

Alex: This is Alex Smith.

Lynn: And this is Lynn Flint.

Eric: And Alex, who is our special guest today?

Alex: Today, we have a very special guest. We have Bernie Lo, who is Professor Emeritus from UCSF, ran the bioethics program at UCSF for years, and now is President of the Greenwall Foundation, a foundation focused on bioethics research and development nationally. Welcome to the GeriPal Podcast, Bernie.

Bernie: Oh hey, delighted to be here with you today. Thanks for inviting me.

Eric: And we are gonna be talking with Bernie about his New England Journal of Medicine paper called, "Beyond Legalization: Dilemmas Physicians Confront Regarding Aid in Dying." But before we do that, we ask all of our guests, do you have a song for Alex to sing?

Bernie: Alex, if you could sing something from The Beatles? How about "Help?"

Alex: Help! Help, I need somebody! Perfect. [Singing]

Alex: All right, we got Eric to join in the end there.

Eric: Yeah, but I think I was away from the microphone.

Lynn: Yeah, I was just gonna say you were like a foot away.

Bernie: That was great.

Alex: Thank you, Bernie. Thank you so much. Thank you for joining this podcast. So who wants to ask the first question?

Eric: So, May 31st. 2018, opened the New England Journal, well I don't open New England Journals anymore, I actually get it as a table of contents. But I see an article from Bernie Lo about dilemmas physicians confront regarding aid in dying. Before we talk about this article, Bernie, maybe you can just describe a little bit how you got interested in this subject. Why aid in dying? Physician assisted-

Bernie: Well, my interest goes back a long time before legalization. One thing I wanna say is that patients thought about this, patients wanted to talk to doctors about aid in dying, and would actually request that the physicians help them way before it became legal. And even when it was illegal, and now would imagine in states where it's not legal, sometimes some physicians do agree to a patient's request. Sometimes we get so caught up with the legalization of discussions and controversies, that as physicians we sometimes lose sight of the idea that legalization doesn't resolve all the ethical dilemmas that when you've decided which way you're gonna vote on a referendum for example, and thought it out, that doesn't necessarily prepare you for some of the things that will come up in your practice from patients. And how you're gonna respond to those, I think is something that I wanted to write about.

Alex: And you've been in practice as a primary care physician in San Francisco for a long time.

Bernie: Long time.

Alex: Long time.

Bernie: Not quite as long as The Beatles, but...

Alex: And I wonder if you've seen changes in how the physician community has responded to this issue of aid in dying over time? Through the AIDS epidemic, and now with legalization. What have you seen historically here in California?

Bernie: Well I think you're right Alex, that there have been changes driven by both medical occurrences like the AIDS epidemic, and then clearly legalization. I think a lot of people have either changed their minds or become more open to differing points of view, and also I think what's changed clearly is that patients are now much more willing than some patients to talk about these issues and want to discuss them with physicians.

Alex: So I wanted to ask as we get into this issue of dilemmas physicians confront regarding aid in dying, about first you raised this point, and you alluded to it already. That often these requests are not explicit requests. So how should physicians, what clues should physicians be looking for from patients that may be requests for aid in dying that aren't explicit?

Bernie: I think it's like so many things in medicine, that some patients will ask what's on their mind explicitly, and others will get at it indirectly or sound out the doctor. One of the things that I've noticed myself is that people will ask a question about something they saw in the newspaper, or an event like the legalization, the signing of the California bill. Or they'll tell a story about a friend or a neighbor or even a conversation they had. It may just be a question on that level, or it may be a lead in to their wanting to talk about with regards to themselves, or I've actually seen it also with regard to a family member.

So I think doctors need to be open to some of the unspoken, the hidden, the deeper meanings that may or may not be present. Sometimes a question of how do you feel about something is just a question.

Lynn: And I actually have a question. I was seeing a patient this morning, believe it or not, I was doing a video palliative care consult with a woman in a nursing home who has an advanced cancer. And she, this was the third visit today. She was really down in the dumps. She was not feeling well, she was having a lot of challenges getting her symptoms addressed in the nursing home she's in. She's not on hospice at this point. And she talked about passively being fine if her life ended sooner and physician aid in dying of course went through my mind, but I didn't say it, I just explored. I explored, and she didn't bring it up, and I didn't bring it up, and the conversation went on. But it made me think about when do you bring it up when you're not even sure if it's on the person's mind?

Bernie: Well, I think you did the right thing, just to explore, and sometimes the things we do, just open ended questions and listening, being empathic, draws people out. Sometimes I actually will ask explicitly, "You mentioned something a couple of minutes ago that I wasn't quite sure how to interpret, or what you meant by it." And then ask the more direct question, "When you were talking about this, were you thinking about the possibility of taking a medication to end your life?"

It's almost in a way like asking people who are depressed about whether they have a thought about ending their lives by suicide, or being violent for that matter if they're having real anger problems. Sometimes patients will say, "Oh no, no. I would never do that. But I must say, I can understand why people could do that." And that's fine.

Eric: Well Bernie, that brings up an interesting analogy, because the old thinking around depression is if you bring up suicidality, like people are gonna get the idea of, "Oh, wait. I can commit suicide." Now we pretty much rooted out that idea, that it's actually important to bring up thoughts about suicide, and it doesn't actually make people think, "Oh, I wanna commit suicide."

Bernie: Never thought of that before.

Eric: So are we suggesting kind of the same thing here? Because I think a lot of providers think, "Oh, I don't wanna bring up physician aid in dying," because then they're gonna think, "Oh, this is a reasonable option because my provider's bringing it up." Is that something we should be worried about?

Bernie: It is something to think about, Eric. I totally agree. And I think a lot depends on how you say it, and how it comes across. I think if it's a question, is this something that you've been thinking about? Then that's very different than I want to make sure you understand that here's an option that you might want to consider. So I think it's the difference between, Lynn you used the term of exploring, seeing what the patient might've been thinking that they haven't yet articulated, and giving the impression that you're actually suggesting or recommending something.

Eric: Well that's interesting. Can we talk a little bit about the ethics of it?

Bernie: Yep.

Eric: Because if memory serves me correct, I think somebody was working on a bill in California about making sure that people knew all of their options including physician aid in dying. I think nothing happened with that, but is there a distinction between us exploring whether or not people have thought about this and actually mentioning it as an option for around end of life care.

Bernie: Okay, great question. Let me just first say going back, there are people who believe you shouldn't bring up hospice to patients unless they ask for it, because it might be interpreted as a subtle way of telling them, "Your time is up," given the misunderstandings about hospice. So Eric, I think you really put your finger on an important point regarding how does what the physician say get interpreted by the patient? And how do you frame things in a way that you make clear that you're informing people without really advocating anything?

So again, I like to use the ... maybe you guys, sorry you all, do this better than I do, sometimes just bringing up palliative care or hospice, I have a patient now I'm trying to go into hospice discussions with, and one of the family members is really concerned that hospice means giving up, that you're signing a death warrant. But I did want to make sure that it was one of the options, and so I framed it by saying I just wanna make sure you know all the options ranging from sending the patient to the emergency room or this will happen to trying to manage her at home to trying to bring in people that can help relieve her symptoms at home, then hospice is the best way to do it. And I backed off, because I knew there were concerns there.

This may not be something that you want to consider, at least at this time, but I just wanted to let you know, it's one of the options. So I think how you frame it rather than just saying there are five things we can do, and number five is. I think it's really in the context of the relationship that you have, and the goals of care, and what your sense of what the patient’s needs and concerns are.

Eric: Have you or would you ever do the same with physician aid in dying? Would you actually ever say, these are options, and physician aid in dying is another option?

Bernie: I probably wouldn't quite say it that way, but I think people frame it differently. I would say, and there's another approach, and there are some people who consider, think about, and ask for aid in dying, which means getting a prescription for a lethal dose of medicine that the patient takes when they think the time has come in their terminal illness.

Eric: All right, one last question from me, because I think Lynn has a question.

Bernie: Yeah, sure.

Eric: What words should I actually use? So you wrote in this physician aid in dying, there's physician assisted death, there's physician assisted suicide, there's death with dignity. How should I label this?

Bernie: Yeah, I...

Eric: Or does it matter?

Bernie: Well no. I think it does matter because people interpret terms in very different ways and react to things that may have actually been misunderstanding. So I think you've all been through the ... we call it palliative care now, because so many people have negative connotations about hospice. I tend not to use the phrase and just describe what it is. It's talking about and in some cases asking for and receiving a prescription for a dose of medicine that they can take to end their lives.

Eric: That's great. Taking away the label, the often meaningless label.

Lynn: Just saying what it is. That's what it is.

Eric: But we can't do that as doctors. We need to actually not even label it, but-

Alex: Come up with an acronym.

Eric: Like PAD.

Alex: Right, right.

Lynn: We need to give it a name that nobody will understand. [crosstalk 00:14:35] That's why they changed it to HEF PEF from whatever it was, heart CHF. Going back to my patient, another thing that felt like a dilemma to me in that particular scenario, was that I was thinking about, no matter what, my own personal position is on physician aid in dying or whatever we want to call it for the podcast, I had this fear of maybe this because I'm a palliative care doc, I was less afraid of the emotion that was gonna come, and more afraid of the just the sheer logistics of what I would do if this person said, "Yeah, that sounds like a really great option."

And then it got a little stuck in my head of, well am I withholding this information because it's logistically difficult and I don't exactly know how to do this, and I got a little tied up in my head.

Bernie: Those are really, really important questions. And hats off to you for recognizing and being honest with yourself. So the very first thing I think is, you said something regardless of your own position. And I think clearly, doctors will have strong ... many doctors will have strong feelings one way or the other supporting or opposing, and one of the things I wanted to try and put out there is the idea that regardless of which way you come down on would you sign the prescription, trying to ascertain what the patients concerns are, trying to address them in the best way you know how is in palliative care.

All that should be independent. Then you bring up another set of questions, which is really important and we don't really talk about much, which is the logistics. Particularly if in any institution you practice in unless you're in a solo or small group practice where all your colleagues think the same, institutional policies really come into play. And the logistics of how you actually prescribe, what you prescribe, what doses, what pharmacies will fill some of these prescriptions, what if the patient is of sound mind but not of sound body and can't go down to the pharmacy herself? Who can pick it up? If it's in an institution, if someone's in a nursing home, will the nursing home stock the drugs you want to prescribe? Or you can allow the practice to take place? So I think all those are important, pragmatic, practical issues. Well, I guess the question I would come down to is, should you not get the patient interested in a topic that just won't happen because of the institutional constraints?

Or, at least for some patients in nursing home, could friends or family be mobilized to help? For example, I don't know if you all are ... I know Alex and Eric, you're at the VA, I don't know if you are as well, but...

Lynn: Me too, yeah.

Bernie: Yeah, so if it's the VA nursing home, I'm sure they have policies, and they may be national policies.

Eric: Yeah, with federal, you can't use federal funds for physician assisted suicide or euthanasia, so there's a Congressional law that we can't actually bypass. But it doesn't mean that we can't talk to our patients. Explore their wishes around physician assisted dying, or connect them to potentially other resources without actually making referral. We can't make a referral. We can educate.

Bernie: You're forbidden from making a referral.

Eric: We're forbidden from using any federal funds and making formal referrals.

Lynn: But we could give them information.

Eric: And educate.

Lynn: And educate, yeah.

Bernie: So, but this now gets down to nitty gritty. Are you allowed to say here's the state website that explains all this?

Eric: That's in education. I would say yes, it's like we're educating. We're not using federal funds to help people with the process, but we're educating, just like we would educate people on any mental health condition or option.

Bernie: Could you give them a list of advocates?

Eric: Yeah, so this is great Bernie, because it's not like I'm on a national podcast that I'm gonna get in trouble for talking about. I would say again, anything that has to do with just around education, as long as I am not sending them out to another physician who would prescribe it, personally I feel very comfortable actually giving them resources around our state that they can connect to. Where you draw that line, I think is that ... we have clear guidance on what we can and can't do, again with federal funds. Where you draw that line of this is what I can do or can't do within a system like the VA where we can't do it, it's gray, right? But I feel, for me and teaching others, that it's really important not just to say, "Sorry, we don't do physician aid in dying, talk to somebody else." But to be very clear is, "Thank you for bringing this up. I'd really like ..." How did you start thinking about this? Where is this coming from? Why now? All these great questions like you and Lynn were talking about. Inquiry.

Alex: Exploring.

Eric: Exploring. And then potentially addressing some of the issues that come up, whether it be around loss of control, or depression, or pain.

Alex: Which is a point that you bring up Bernie, in your article in a couple of different areas. First, at the time of the initial question and exploring, you highly recommend making sure that you're treating all reversible sources of suffering, including comprehensive palliative care, noting that 46% of patients who have requested physician aid in dying change their minds. And then second, after somebody's written the prescription, that doesn't mean you stop treating sources of suffering, but in fact that you try to help this person find other reasons to live, and that many patients who obtained the prescription do not actually use it.

Bernie: Right. That's right. And what I try to say, and maybe it's worth repeating it, even physicians who are morally opposed to let's call it aid in dying, that's what the California law calls it. My argument is they should do that exploration, talking to people, and really doing the most intense, successful palliative care they can. Even though they and the patient know that there's a real difference of opinion with regard to the aid in dying. If I can double back, is that okay to go back?

Eric: Sure, absolutely.

Bernie: To the issue that Eric and Lynn, you were talking about. So I don't want to make this a VA centric or certainly not put either of you on the spot. But I think in any institution, institutional policies may or may not constrain what physicians can do or feel comfortable doing. And Eric you brought out the between what you're expressly told not to do, and what you're expressly told but is okay, there's a gray zone. And where in that gray zone will you be? I think it's really important for each of us to think that through so that hospices have different policies regarding participation in aid in dying. So institutions, like UCSF or hospital or clinic that you would work in.

So I think it's important to think this through, and I think in a lot of other contexts, we are not shy about referring people outside the system so that now my practice is UCSF, for a lot of reasons tend to refer everyone to UCSF specialists. But if that's not working out, then I will ... and particularly if the patient expresses real unhappiness with the way a couple of referrals have gone, I will refer outside the system and say, "Well, I don't know what your insurance covers. I don't know these people as well, there's a little problem getting the records back and forth, but either it's closer to your home or they can give you a different opinion." So I think feeling comfortable saying the way we do it within our system is not necessarily the only way to do it, and for a given patient they may want to at least think about if they want to, the option of going outside the system.

Alex: I wanted to come back to a topic that you raised before about the way you go about prescribing may differ within health systems and what you prescribe and formulations. If you're allowed to within that system. And as you note in here, barbiturates are one of the mainstays of physician aid in dying, and they've become really difficult to obtain and in some cases prohibitively expensive. And my understanding is that those who prescribe these medications frequently, the physician aid in dying medicines frequently, are actually in some ways they're trying to come up with creative new uses of existing medications to help their patients die quickly and without suffering.

And it raises, for me, I wonder if you see some issues here of the clinical and research ethics interface. I worry that there is very little to no oversight over these practitioners who are trying new formulations with patients. If we had say a cancer trial with some new drug, we would be up in arms if there was no oversight about was informed consent obtained. How much did they actually understand about this new treatment that you're trying and the potential risks and side effects, etc.? And on the other hand, I also feel for those providers, because there is no mechanism to support research in this area. There is no mechanism to provide oversight that I'm aware of, maybe you're aware of mechanisms, to provide a research infrastructure for these practitioners.

Bernie: Great questions. So let me try and distinguish between oversight and evidence. If you start with the assumption that barbiturates may be prohibitively expensive and very hard to get-

Eric: Wait. Before we talk about prohibitively expensive, we're looking at $5,000 to $6,000? Is that about right?

Bernie: Yeah.

Eric: So like three days in the ICU. Two days.

Alex: Right, but they're paying for this out of their pocket. Out of pocket costs. They're not paying for that ICU stay in almost all cases.

Bernie: So there's actually not very much evidence on the older regimens that included barbiturates. And it's the Dutch who have done this. They have collected the best evidence on what are the adverse effects, how often does it work? And just parenthetically, one of the main reasons that physician assisted suicide is not that common in the Netherlands, although it's legal, they use active euthanasia, because they've had documentation of really disturbing adverse events from oral ingesting of medicines.

So there are people who have been trying to devise regimens that are effective, that are tolerated, that are affordable, and presumably are safe. So it’s an evidence issue, and I would differ a little with you Alex, in that I'm not sure it's actual formal research that meets IRB approval and the like, but it's really innovative practice, but there needs to be a systematic collection of what works, what doesn't, what happened. So I think what I would like to see is the doctors that are doing this a lot, and hats off to those who do it, it's very hard work. It's emotionally grueling, it's time consuming. My impression is that patients and families really appreciate what they do, that they keep a register of what was prescribed, how it worked, any adverse effects, so that people can later on say, well in a consecutive series of people using regimen X, this is what happened, and if it gets modified to regimen Y, this is what happens.

But I think the idea that things are intuitively gonna work is good, but you need to see in practice like can people take all the pills? Will they keep them all down? Those are things that are real practical.

Alex: And there are some people who have terminal illnesses, illnesses that will eventually end their lives, who do not fit in to this physician aid in dying. For example, I think of people who have amyotrophic lateral sclerosis, right? ALS, a motor neuron disease who will not be able to take the pill themselves because they are not physically able to do it, though they are of sound mind.

Eric: And anybody with dementia who may not have the capacity.

Alex: And who's cognitively not able.

Lynn: I was gonna give an example, I spoke at an Alzheimer's Association conference last year, and I was asked to sit on a panel there and talk about physician aid in dying, and a few months ahead I said what's the point in this group? Nobody here can access it. And this was a community facing conference, so lots of caregivers and family members, and I have never sat on a panel with such anger and emotion at the idea that people couldn't access this on behalf of their loved ones. It's pretty fascinating.

Bernie: Yeah, the laws in California, Oregon, and the other seven states and the District of Columbia are pretty narrow. It's terminally ill patients who are competent, not depressed, all that. But if you allow it for those cases, you brought up examples where logically it makes sense to extend it. So the person with ALS, who is mentally clear, but physically unable to ingest the medicine. It seems to me that, logically, that doesn't seem to be either consistent or fair, and you can certainly think of ways of devising robotic assistance to place the pill in someone's mouth on a voice command or something, but it seems like a lot of trouble for the same effect.

Eric: Because we're kind of skirting around this physician aid in dying versus euthanasia issue, right?

Bernie: So the ALS example, I would say it's still done at the command or voluntary decision by the patient. They are saying the time has come, I want someone to put the pill in my mouth. Or put it in my feeding tube. The Alzheimer's is different, because there presumably the patient is no longer saying this is exactly the situation, I didn't want to be in. Now's the time to stop, we’ve all come and said goodbye, I love you, thank you. So it's someone else saying this is what the patient would have wanted in this situation. That one step removed from the direct request or decision by the patient leaves it a little bit shakier, but logically I can see why people in that audience in your panel at that meeting Lynn were saying, "This doesn't make any sense. This is exactly, by the time she is sick enough to be in a position that she dreaded, you're saying she can't take the medicine, we can't administer this."

Lynn: Yeah, so the other thing I was thinking about in terms of the ALS example, and actually in general, correct me if I'm wrong, but once people obtain a prescription it's there, in their home. And they may be in a hospice agency or have some sort of institutional support, but they may not, and so we don't exactly always know how this ends up being administered in the moment?

Bernie: No, we don't. And frankly that's one reason someone suggested that a physician or a hospice nurse should be present. There are a whole lot of reasons, but one is to make sure there is, at least in states like California that's a voluntary choice. Not someone else administering. And if it were ever to get to the point, in the Netherlands, doctors make house calls to carry out either physician assisted suicide or active euthanasia. And it's done by GPs usually, not necessarily by specialists, and they make it part of their job. And it does give some assurance that what was done was ethically appropriate. Although then, there were also some problems with what actually was done in some cases.

Eric: So Bernie, last question. Do you have guidance for clinicians who are listening right now? Maybe three things that we should be actively thinking about or doing to prepare us for these ethical dilemmas around physician aid in dying?

Bernie: Let me try. So first is to the extent possible, treat this like any other new intervention that you're likely to see in practice. Anticipate what might happen. Think about it, try and read about it to the extent you can, talk to your colleagues about it who have maybe had some experience. Because I think more than a new device or new medication, it's important to sort of think this through in advance. Because a couple of you had said when something comes up, you can almost feel like a clutch, what's going on here? What am I gonna do? So I think that's important.

Okay, so my second point is, this is hard. It should be hard. And I think we all need to appreciate that. For all the reasons we've talked about, it's complicated, there's a lot of uncertainty, it's a lot of individualization. And I think you have to be willing to say this is gonna take time, emotional energy, and a lot of digging into yourself to say how much time am I gonna spend on this, and what do I ultimately feel comfortable doing, and where would I draw the line saying I'll support my patient up to this but not farther than that.

And third I guess is a corollary almost of two. Talk to people about this. Your partner, your spouse, your practice partners. It's really important that you not think that you're the only one going through this, or you have to work this all out yourself because the people I've talked to and practice who have faced this, and tended to face it alone because if you're outside an institution, the whole pace of things is different, it's really grueling on people and it's almost like what's the hardest emotional sub specialty? Maybe pediatric oncology? That you need to be able to re equilibrate. But part of that is, patients or families who will tell you, "We so appreciate you talking about this." You're spending the time. You're taking this seriously, you're engaging on a not just no I won't or yes I will, but really could see you trying your hardest.

That's so important to families, to patients. And that is to compensation for all the hard work and energy we put in. I think the other thing I would want to say is that you want to try and apply the same critical thinking and evidence based medicine skills, and to admit when we really don't know. I would always say to people, "Every medicine has its adverse effects, and we don't know what all of them are. This may not work, there may be side effects." I've had people say they want to be in charge of how and when they die. I need to say we can't guarantee that, because we can't guarantee anything in medicine.

Eric: Well it's interesting though, it feels like this is even more of a black box. It's kind of hidden from sight, at least like with we have people who can see what's happening after insulin. We have people researching that, but this is doctors are often not there, it happens in people's homes, and there's very little follow up.

Bernie: That's right, and I think and I'm willing to say, just a consecutive case series would be useful with standardized information on each case. There's some of that that's done in the state of Oregon and Washington have the best annual reports. They'll talk about adverse effects, but they don't specify what the regimen was. And so you can't crosswalk it to drugs and dosages, which of course doesn't help.

Eric: Well Bernie, I really wanna thank you for joining us today.

Alex: Thank you so much, Bernie.

Lynn: Thank you.

Bernie: Yeah, no thank you for inviting me. Great questions, I enjoyed the back and forth.

Alex: Incredibly thoughtful responses.

Eric: Incredibly thoughtful. I always learn a ton just listening to you.

Alex: I know I always learn so much.

Eric: Before we end Alex, I wanna end this on a high note with maybe a little bit more of The Beatles.

Alex: Another verse of Help. [Singing]

Eric: Well I wanna thank all of our listeners too, for joining us on this GeriPal podcast. We look forward to our next podcast next week.

Alex: Thanks, Bernie.

Lynn: Thank you.

Bernie: Thanks Alex, and Eric, and Lynn. It was a pleasure.

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Tuesday, July 3, 2018

Geriatricizing the ICU

For today's GeriPal Podcast we talk with Drs. Nathan Brummel and Lauren Ferrante, both critical care physician-researchers, about integrating geriatrics principles in intensive care units.

This is a major issue.  Just think about the older patients you've seen in the ICU recently: older, frail, sick.  Now imagine the environment - beeping, monitors, lines (tethers), sedating medications, stress, open doors, lights everywhere, noisy air mattresses.  The environment alone is crying out for geriatricization!  (I think I just made up a word).

Nathan and Lauren wrote a terrific article about the topic, link below, and discuss the landscape of work to be done in this area on this podcast. 


-Alex Smith, @AlexSmithMD


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Eric: Welcome to the GeriPal podcast. This is Eric Widera.

Alex: This is Alex Smith.

Eric: And Alex, we have two guests with us. One's skyping in and one here in studio.

Alex: Let's start with the in-studio guest. We have Nathan Brummel who is a Pulmonary Critical Care Physician Researcher at Vanderbilt and is in town for the GeriPal podcast and also happens to be attending the American Delirium Society meeting which is in San Francisco.

Eric: Great. I was just there yesterday. Great meeting.

Nathan: It is. It is.

Alex: Welcome to GeriPal podcast Nathan.

Nathan: Thanks for having me.

Alex: We also have via Skype Lauren Ferrante who is a Pulmonary Critical Care Physician Researcher at Yale. Welcome to the GeriPal podcast Lauren.

Lauren: Thanks for having me.

Eric: Lauren, we ask all of our guests, do you have a song request for Alex?

Lauren: Yes. We wanted to sing a song about change and so we are requesting “Waiting on the World to Change” by John Mayer.

Alex: Alright.

Alex: We keep on waiting ... Wait, let's do that again. Eric, you've got to sing too.

Eric: I have to sing too?

Alex: Yeah. You've got to sing “waiting”.

Eric: Alright.

Alex: Yeah. We need it. We need the backup. Let me start again. [Singing]

Alex: Alright!

Eric: I can't believe you made me sing, Alex.

Alex: It's great. That song is actually about how you're waiting for others to change. Is that what you're advocating here when you're thinking about geriatricizing ICU's? Should we be waiting for them to change themselves? Is that the point?

Lauren: No. The whole point of the article is that we are advocating that the time for change is now.

Eric: Wait. What article are we talking about, Alex, here?

Alex: We should say that the topic of today is geriatricizing the ICU which is like critical care medicine. The title of the article is “Integrating Geriatric Principles Into Critical Care Medicine: The Time Is Now”. And this was in Annals of the American Thoracic Society recently May of this year. Nathan and Lauren were both authors on this. Eric, do you want to start us off with the discussion here?

Eric: Yeah, so we'll have a link to this article online on our GeriPal blog. We usually like to start off how did both of you get interested in this subject?

Nathan: Sure. It started about three years ago at the American Geriatric Society meeting. There's a medical sub specialty section and at that breakfast Lauren and I were sitting together, we're both pulmonary critical care and knew each other through that but were at the AGS meeting. All the other groups were getting up, the cardiology section, the oncology section and they were presenting all the great work they were doing. We both sort of looked at each other and said, “Why not us?” We need something like this in critical care.

From that rose a sort of discussion between Lauren and I. We then put together an application to become a working group in the American Thoracic Society, the largest international group of pulmonary critical care physicians. Over the last few years that's morphed into an interest group now so we have a larger group that's working to do these very things of integrate geriatrics and aging research into critical care medicine.

Alex: Lauren, anything to add to that about like why did you see this as necessary? It was certainly a need there. Anything from your clinical experience that sort of cries out for this area?

Lauren: Definitely. I think in the hospital and in the medical schools we all talk about integration but we still tend to function in silos even in the ICU where we have to manage every single organ system. Actually, the ICU is pretty good at interdisciplinary and multidisciplinary care but with the growing number of older adults in our country and this is something that's been talked about a lot including on this podcast. I think we really saw that it's time to integrate these principles and not just to be calling geriatrics consults all the time. That's one of the things we address in the article.

Although we're both researchers, really it was the clinical need for this and that kind of drove us to form this working group and to address all facets of integrating geriatrics into critical care research education and clinical practice.

Eric: When we talk about principles, what geriatric principles are we actually talking about here?

Lauren: We're talking about a number of things. One of the things that both Nate and I have worked on are vulnerability factors that are present to a greater extent among older adults than they are among younger patients. These include things like frailty, or multi-morbidity, or cognitive impairment, or disability. And, many older adults are coming into the ICU with these preexisting problems but when we're looking at the critically ill older adult patient, it's extremely rare for someone in the ICU to be thinking about that at the forefront of their mind. We tend to focus on things inherent to the critical illness itself so something like respiratory failure that's keeping them on the vent and we're not really thinking about what they're coming in with. That's just one example.

Where a geriatrician might be thinking first about the preexisting vulnerability factors that an older adult is coming into the hospital with and how those vulnerability factors might inform their outcomes or their acute illness. That's just one example of a principle or at least consideration that we think we need to integrate into our practice that really isn't being considered in real time in the ICU currently.

Nathan: Yeah and I think adding to that, the increased emphasis on outcomes after critical illness. We're seeing things that are classically considered geriatric syndromes like cognitive impairment, disability and frailty in even our younger survivors. There's an added component not only for the older adults but younger survivors who are suffering with classic geriatric syndromes.

Alex: Of the geriatric syndromes, what do you think is the most common in the ICU? The one that comes to mind for me, well, it was sort of primed for this, was delirium. Does that ring true to you or is there actually empirical evidence about what's most common?

Nathan: Yeah. We haven't studied specifically the types of geriatric syndromes but delirium being the most common affecting up to 80% of people that are on a mechanical ventilator.

Alex: Wow. Say that again.

Nathan: Up to 80% will have at least one day of delirium while they're in the ICU.

Alex: Wow. That's huge.

Nathan: That cuts across ages and comorbidities and all these other factors. The vulnerability factors plus the insult that critical illness is that brings those two together. I think the other one that’s ubiquitous is immobility.

Lauren: Yes definitely.

Nathan: Every single patient in the ICU is even though we're trying to get better at that, it's still quite common.

Alex: What sort of ... What do you think is, there are a couple of historical factors we start to get into this here a little bit. The ICU has changed over time, right? It used to be younger folks with reversible conditions, right? One of my mentees, Brian Block who I think both of you have met is writing a piece where he talks about how that ICU has really changed from being a place where young people with polio were on ventilators and now it's just replete with older adults, dementia often, other geriatric conditions. The demographics and the illnesses and conditions that are seen in the ICU have really changed over time.

Nathan: Right. That's a combination of things. One is that the population is aging but two is this is the population that's most likely to develop common reasons for ICU admissions, thinks like sepsis and pneumonia and respiratory failure. All of those track with age as well. I think another factor as well is it's not as socially acceptable to deny older adults ICU admission like it once was.

Alex: Lauren, from your perspective, thinking about the level of expertise and awareness of the importance of this issue within the American Thoracic Society, within critical care physicians nationwide or even globally, where do you think we're at? Is this a frontier area or do they recognize it's important they have a need? Do they already have some training? Or is this pretty new stuff to them?

Lauren: I think that there is increasing awareness of the need and if you look back even I think it was Derek Angus back in 2000 had looked at the epidemiology and the prevalence of older adults in the ICU. We mentioned that in our article. At the time, he found that more than half of patients in the ICU were older adults.

If you look at, this is not an official publication research project that I did, but if you look generally at the number of citations and interest in this area, it has been increasing since that time. And, in fact, there's decent interest in mid career senior folks and also in early career investigators in these specific issues. And the group that Nate described that we created in the American Thoracic Society has only grown and we keep getting additional interests from other ATS members. I just think that this is a really growing area and it is a frontier as far as incorporating these areas into practice. I think that we have seen a lot of progress in research, but we need to see the same amount of progress in clinical care and to continue the progress that we’ve made in research.

Eric: I'm just going to drill this down to practical issues of what we should be doing. There was a recent tweet that came out saying we have lots of tools for monitoring delirium in all age groups so what's your excuse for not monitoring brain dysfunction?

Alex: Are you saying moderating?

Eric: Monitoring.

Alex: Oh monitoring.

Eric: Did I mispronounce that? Oops. There was an ICU doctor who had a rhetorical question. Is it important to monitor something for where there is no obvious intervention to make it better? The cam ICU suggest hypoactive delirium? What's next?

Alex: Right. What do we do? We can detect it. What do we do about it? Interesting. Response?

Nathan: Yeah. I think it's important that, I agree with that statement that we don't have a drug that we can give which is what we all want. We want something quick and easy that we can give a patient. The problem or the difficult part about delirium is that you have to step back and stop and think about what might be causing it. The average ICU patient has upwards of 11 risk factors for developing delirium. Some of that is related to their underlying critical illness. We recently published a paper that looked at risk factors for delirium and we called them delirium subtypes and we identified a bunch of different like sepsis and hypoxemia and sedation was one of the ones that we looked at. We looked at the duration of each of those subtypes, each of those types of delirium. We found that each of them were related to long term cognitive impairment so delirium that people have in the ICU is related to their thinking and memory a year later.

What we found in that study was of all the causes, right, sepsis and hypoxemia, those don't tend to be reversible but sedative associated delirium was associated with long term cognition. That's a totally modifiable risk factor for delirium. It's not necessarily giving something, it's taking it away that may be helpful to patients. When you think of that, it's important because it's associated with outcomes but it's also you can look for new problems that you can potentially intervene on.

Alex: Lauren it sounds like you wanted to add to that.

Lauren: Yeah. One of the things, one of the areas where we really can improve in the ICU and many units are working towards this, is the prevention of delirium. Some of the steps that we mentioned in our article include implementing interventions that are already pretty standard on ACE units or Acute Care for Elders units. These include things we mentioned additions and subtractions from the physical environment. Some additions to the physical environment might include portable amplifying devices for hearing impaired patients.

Alex: Yes.

Lauren: Those devices are not standard right now in Intensive Care Units. I usually find myself looking for one whenever I'm on service even though we have a pretty aging conscious unit here at Yale. Then other things would be subtractions from the existing environment. We all know that there's a lot of sensory overload in the ICU and a lot of sleep disruption. Those things also predispose patients to delirium. I think we have a lot of work to do also in preventing ICU delirium in addition to treating it.

Eric: You did a nice job on your paper to break it down to things that we should be doing be doing now, things we should be thinking about short term in the next three years, and long term. Maybe we can briefly talk about each one of those. What should we be doing now to geriatricize ICU's?

Nathan: I think the first thing is to start paying attention to these syndromes like delirium and immobility and sensory impairment that are prevalent. Those are modifiable right now. Eyeglasses, hearing aids, getting people up out of bed are interventions that are effective and by the way those at least mobility has been shown to reduce delirium in the ICU. That's the only thing that we have to reduce delirium, two separate randomized control trials have shown that. The larger term or the more short term, the three to five years and five to ten year goals are things about educating more of the nuances of caring for older adults and treating geriatric syndromes in the ICU. Developing an educational curriculum, research, or research agenda, what gaps in knowledge do we have about caring for older adults? We actually submitted a proposal to review the literature and one of the comments we got back was well we all know there's nothing there.

Alex: There is no literature.

Nathan: That's our point.

Alex: Right. That's the point. Lauren, do you want to add to that?

Lauren: Yeah. In addition to training pulmonary and critical care fellows to really consider these geriatrics principles especially as they become attendings, I also like to think a lot about what can we do with the current practitioners in the ICU. I saw a recent paper, I was just trying to find it, I think it was out at the UAB group where they talk about virtual ACE units and where they're basically going around to different units and training the existing practitioners. I wonder if that might be a more practical model for early implementation.

Although we outline a number, I think one of the things we mention, just in service trainings, things like that. I think we can't lose sight of the fact that we have to train our current practitioners so that they're thinking about these concepts in real time.

The other thing that we mentioned for the future is we, and this is something Nate and I have talked about a lot is creating a network of aging intensivists researchers because one of the areas that we outline in the paper is that many clinical trials and studies in critical care medicine often exclude the oldest old or don't have critical numbers of older adults. We're hoping that our group which has a lot of critical care researchers in it will one day as we go from the K to the R phase will be able to have an aging intensivist network so that we can answer some questions about how to best treat older adults in the ICU.

Eric: Is there a reason for that lack of inclusion of oldest old into ICU research?

Nathan: From a practical perspective, it's not that the study exclusion criteria, say if you're over 85 or 90 you can't be in this study, it's that they exclude people with multiple comorbidities or cognitive impairment from their studies. They sort of de facto exclude older adults.

Lauren: Right.

Alex: Do you want to follow up on that Eric?

Eric: No. Go ahead.

Alex: It does seem like this is the bait and switch that often happens with clinical trials that they test it in a very select group of sort of healthier individuals in order to show efficacy but then they roll it out for people who have multi morbidity, dementia, functional impairment, real world oldest old type of patients and we have no idea whether it works in them or not. I love this idea of setting up a trials network to actually study this effectiveness in real world settings.

Lauren: And some of the, you know the demographics of the existing trials and near future trials may change now that the NIA’s mandating inclusion across the lifespan with that new policy which I think is going to be effective next year. But we still feel that there will be benefit to have this aging intensivist network. That's in the longer term plan.

Eric: Right. Is there, you've probably been to a lot of ICU's, is there a design element to ICU's to make it more age friendly?

Alex: Are you talking about architecture?

Eric: Yeah. Like the way ICU's are designed. I mean when we think about ACE units, it's not just mobile ACE units but physical ACE units. A lot of times we also think about the design of those ACE units. Is there room for family members to be there? Is there room to actually do things like get up out of bed, walk around. Is there light coming in from the outside? Are the bathrooms easily accessible? What are your thoughts about that?

Nathan: I don't know from a national perspective but at Vanderbilt about now gosh it's when I was a fellow so it's longer ago than I care to think about but when we opened a new critical care tower and that incorporated a lot of those things you just talked about. There's space for the family to stay with the patient there. There is a bathroom that's accessible. It's a very large open space compared with our old ICU which you had to be an acrobat to be able to maneuver around all the equipment and the bed and everything like that. There may have been a chair in the corner for family versus a pull out couch or something for them to sleep on. I think those are important things.

We know from the demographic data that the number of ICU beds, even though the number of hospital beds nationally is decreasing, the number of ICU beds is increasing. Whether that's conversion of existing hospital beds into ICU beds or construction of new ICU's but I think that's a very important point for hospital administrators and architects to keep in mind as they design these spaces to make them aging friendly.

Lauren: Yes. We also have a new unit at Yale so we also have, space is definitely not a problem, there are huge windows, lots of light. But there are some things inherent to the ICU that aren't contingent on space that I think we, probably every ICU in the country, could improve on. And that one big problem is noise and also sleep disruption. We have a group here at Yale that works on sleep in the ICU. They measure the noise of the ICU and especially in certain rooms, it's just because the monitors are outside in the hall it can be really, really disruptive to the patient and disorienting. You can see how that might predispose to delirium.

The other problem we still have in every ICU I think is a tethering problem. I often start talks that I give of a picture that I give of a patient in the ICU bed just so that the audience can really grasp what that looks like. There are telemetry wires, multiple lines, central lines, Foley catheters, sometimes CVVH and the tethering devices, despite our best attempts at early mobilization, they can still be problematic especially for older adult patients.

Alex: I think about our ICU, the monitors are in the room, there's always at least one monitor beeping and if it's not the monitor beeping, it's the IV beeping, the fluids are beeping. There's always a beep. There's at least one beep if not two beeps. The television is on. They've got the air bed. And the air beds these days, the best air beds are wonderful for your skin but the decibel level of the air bed is like off the charts. You can hardly, I feel like I'm on an airplane with all that background noise. You need noise canceling headphones. We tried to have a meeting with an ICU patient the other day. We could hardly hear anything and we don't have, we're not like 88 years old with hearing loss. I can imagine just such deliriogenic, just sort of setting for older adults.

Nathan: It's a harsh environment for sure, for sure.

Lauren: From a design issue, it should really not be that hard to have the alarms transmit outside or to the nurse somehow or on their mobile heart beat. All the practitioners in our units are now connected through iPhones. From a design standpoint, there's really no reason that that alarm should be going off next to the patient's head as opposed to on our personal device. Hopefully, we can break, maybe engineers need to start working on that.

Eric: Yeah. The medication pumps, those are the worst.

Lauren: Yes.

Eric: All around the hospital they just go off. They go off for about ten minutes before somebody can walk into the room and turn it off. I just know the little yellow silence button but that only lasts for like a minute.

Alex: Then you've got to push it again.

Lauren: Yes.

Eric: Is there anything else that you guys would like to talk about before we end?

Lauren: I have a question for both of you as geriatricians. You read our paper and you've seen that we think we need to integrate the principles of geriatrics into critical care medicine but we certainly want to keep our geriatric colleagues involved in the ICU. Do you think that this is a good idea integrating it? Do you think that it's problematic from a geriatrics consult standpoint or do you think we would work together on this type of initiative? How do you foresee it from your end?

Eric: I love your analogy or the idea of bringing in an ACE unit into the ICU because if you look at a lot of ACE units, they're not taking over care. They're often just focusing on key geriatric syndromes for those individuals making recommendations on that. They don't need to be heavily involved with every patient and sometimes it's just a quick touch point. I can imagine the same thing happening in the ICU. I think the challenge is how do you actually staff that in hospitals. But I think if we think about interprofessional teams and ACE units, it's a reasonable and attainable goal to actually get. You don't have to do full geriatric consults on every ICU patient but you just develop a system where you can have those, even those quick touchpoints.

Alex: I just add to that to say that I think Eric, you're in more touch with this data that I am. The number of fellows, geriatrics fellows, clinical geriatrics fellows has remained relatively flat.

Eric: It's been relatively flat.

Alex: For a period of time. And there are a lot of older geriatricians who are retiring or approaching retirement age. I guess my point is there's no way that there's enough of a workforce of geriatricians to meet the demand in the ICU's. And so the primary focus should be on primary geriatrics delivered by critical care physicians in the ICU and education of those physicians, changing the environment, education nurses and the whole interdisciplinary team.

Eric: Yeah. Part of me also thinks, I think we can harp a lot on that geriatric workforce issue and why things can't happen. In some ways, that's probably not where we want to start. We can make this change. The workforce is there. The workforce is there from a specialty geriatric standpoint. The workforce is there from a interprofessional geriatric standpoint. Again, if you're in most ACE units, it's not just the geriatrician. It is the nurse with geriatric expertise. It's the physical therapist. It's the pharmacist. It's a team of individuals. And it's also like you said making sure we are also educating great primary geriatric skills for ICU providers, again, not just physicians but the whole interprofessional teams. I do think the workforce is there. We can do this. It's just getting bright people eager people, like the people we have on this podcast to actually make that change, not waiting.

Alex: Right. Don't wait for the change.

Nathan: Be the change, be the change. I think you raise a very good point about that where Lauren and I and others around the country and around the world really are approaching this from a critical care perspective but I don't know that we've really engaged our geriatrics colleagues to say hey let's sit down and figure out what that primary geriatrics for the ICU really looks like and how do we train people in that. I think that's a very good point that you raise.

Alex: One of our listeners out there or many of our listeners out there, if listening right now and you're thinking to yourself “I want to get involved in this. I'm a geriatrician. I do a lot of consults in the ICU. I see the issues they're talking about. This all rings true.” Contact Nathan, contact Lauren. Get involved. We need geriatricians to have input on this issue.

Eric: I think there's a lot of great analogies. For instance like geriatric ED's, emergency departments. Learning lessons from the places where this has been implemented both delivering specialty geriatric care and also in like geriatric ED's, it's a lot about primary geriatric care from physicians and nurses and everybody that's involved and also design. Thinking about how we design these units whether ED's, ICU's, or hospitals.

Lauren: Absolutely and just to anyone who’s listening and is thinking I want to be involved, but I don't know when I'm ever going to see an intensivist and I'm not going to the ETF meeting, we do have a group in the American Geriatric Society called the Medical Subspecialties Section and these are exactly the issues that we work on. If you email me or look in the program at the next AGS meeting, you should contact us even though the section is called the Medical Subspecialty Section, we actually invite everyone to come. Surgical subspecialists, geriatricians and these are the issues that we want to be talking about and working on. Again, that's where this group started, the group that Nate and I formed was actually at that meeting.

Eric: Wonderful. Well I want to thank both of you for joining us at this GeriPal podcast.

Alex: Thank you Nathan. Thank you Lauren.

Nathan: Thank you Alex. Thank you Eric.

Lauren: Thank you.

Eric: And Alex, how about you end with a little bit more of that song.

Alex: [Singing]

Eric: No more waiting right, the change is now. I want to thank all of our listeners for joining us. We look forward to talking with you next week and thank you to our guests.

Lauren: Thanks for having us. This was fun.

Nathan: Thank you.

Alex: Thank you so much Lauren. Thanks Nathan. Appreciate it.

Read more »

Tuesday, June 26, 2018

Tramadon't: a podcast with David Juurlink about the dangers of Tramadol

Tramadol. Is it just a misunderstood opioid that is finally seeing its well deserved day in the sun, or is it, as our podcast guest David Juurlink put it, what would happen if "codeine and Prozac had a baby, and that baby grew into a sullen, unpredictable teenager who wore only black and sometimes kicked puppies and set fires"?

Well that's what we are going to be discussing today with none other than David Juurlink, an Internist and Clinical Pharmacologist at the University of Toronto who has written about Tramadon’t on both his twitter account and on the blog "Tox and Hound."

David walks us through the top reasons why we should question the rapid uptick in Tramadol prescriptions, including that its metabolism is hugely variable, so giving a dose of Tramadol is like giving venlafaxine and morphine in an unknown ratio.  It also is associated with increased risks of hypoglycemia, seizures, serotonin syndrome and all the other usual stuff with opioids (including dependence, addiction, and death).

So take a listen and comment below.   We'd love your thoughts on Tramadon't.

Listen to GeriPal Podcasts on:


Eric: Welcome to the GeriPal podcast. This is Eric Widera.

Alex: This is Alex Smith.

Eric: And Alex who do we have with us on our podcast?

Alex: Today we have Professor David Juurlink who is an Internist and Clinical Pharmacologist at the University of Toronto who has written about Tramadon’t.

Eric: Tramadon’t.

Alex: Tramado, Tramadon’t. Welcome to the GeriPal podcast.

David: How you doing?

Eric: Wonderful.

Alex: Good.

Eric: So before we go into Tramadon’t which sounds like maybe a new version of Tramadol, we always ask all of our guests to give Alex a song to play. Do you have a song for Alex?

David: Yeah, I'll pick, "You Can Close Your Eyes," by James Taylor.

Alex: Terrific. [Singing]

David: Very nice. I've heard James Taylor play that song about a dozen times live and I wouldn't pay money to see you but it was pretty good.

Alex: Yeah that was okay. I think I played it better at the memorial service we had recently. We had three part harmony because the accompanying vocals were terrific.

Eric: James Taylor has nothing on you, Alex.

Alex: Right. I think James Taylor might be the most requested artist on the GeriPal podcast and I don't know whether that says something about the type of people we have on the podcast or whether...

David: Older people.

Alex: Right.

David: I'm actually seeing him in Tanglewood this July. My wife is taking me there for a birthday gift so looking forward to it.

Alex: What a terrific venue.

David: Yeah.

Eric: So again, thanks for joining us on this podcast. I'd just like to start off is that you write for a blog and you're also on Twitter and I gotta ask the question, Tox and Hound, that's the Twitter handle here. What does that refer to?

David: So Tox and the Hound is a blog, just started up a few months ago, it's run primarily by Dan Rusyniak and Howard Geller, Toxicologists in New York. Did I say Geller, I meant Greller. Anyway there's a group of toxicologists in Canada and the US, I'm one of them, maybe a dozen or so of us and we just write on a variety of topics. We publish it every week on Monday and they're up to around 1,100 or so followers now and they've got a lot of people following, reading their stuff. We can just talk about whatever we want and my first post a few weeks ago was on Tramadol, but some very instructive posts up there.

Eric: And I also notice that on your Twitter page which is @ToxandHound there's actually a picture of the Hound from Game of Thrones. So is the Hound like a Games of Throne reference or is it..?

David: I think they were just looking for some catchy title and so for each of the people who post a blog we have pictures of our dogs. I guess that we're just dog people more than cat people. My dog happens to be wearing a wedding dress which is kinda funny.

Alex: I saw that.

David: It's all in good fun.

Alex: So let's get into talking about Tramadol here. I'm not sure how to lead in with this because there's so much to talk about in this post.

Eric: How about just start us off, like what got you interested out of all the drugs out there your first post is on Tramadol, like why Tramadol?

David: Well, that's a good question. I guess I've been thinking about Tramadol a lot for the better part of the last five years in part because it kinda burns me that in Canada, at least, and in fact it was this case in the US until a few years ago, in Canada it's not a controlled substance and that bothers me because it's perceived as somehow safer than things like Codeine or Morphine and what not. And I've had patients come under my care who have been on Tramadol and had problems with Tramadol and it is very clear from talking to them and their physicians, that it's scheduling in Canada which is no different than Atorvastatin or Glyburide. It's part of the reason why docs perceive it to be safer and there is just no case to be made that it's safer than traditional opioids. In the blog post I unpack it's pharmacology and my concerns about it but I guess the reason I singled it out was because I'm irritated by it's scheduling which by the way I think, I don't know if you have Australian followers, I think it's the same situation there, not a scheduled drug.

Alex: And in the US is it a scheduled drug?

David: I think it is. So I think, I wanna say 2014 or so it was added to schedule 4, I don't that makes since. I think Codeine is three but the fact is that just being a scheduled drug helps, I think, providers realize ... If you have an analgesic that's not scheduled and one that is scheduled, you're probably gonna to the one that's not scheduled if for no other reason than you perceive it to be somehow safer or devoid of some of the problems we encounter with traditional opioids. So that happened a couple of years ago in the US.

Eric: Yeah but we still see it here where people feel like Tramadol is a safer drug, that it doesn't have this same bad side effects.

Alex: I was taught this in my Palliative of Care Fellowship, it was like, "If we wanna spare them opioids maybe we should think about Tramadol." And then I started to teach my trainees when I was an attending the exact thing.

Eric: So we can all blame this on Alex.

Alex: That's right, I started this epidemic of Tramadol.

David: Yeah, so I think that comes in part from the fact that it is different because, and we could talk about this in a bit, but it does have these dual mechanisms of action and that's a fair claim but there are, I see it in Canada at least, I see pockets of prescribers in Ottawa and in London Ontario and few other parts of the province where there just seems to be a lot Tramadol use. I think it's just people emulating what their colleagues are doing or following the advice of a key opinion leader and it's not that it can't help some people, like really it can do that but it's pharmacology is not inherently rational and that's why I try to discourage it's use.

Eric: Well tell us a little bit about, what is the pharmacology here?

David: All right, so Tramadol itself, the drug Tramadol isn't much of an opioid. It's an SNRI, more or less like Venlafaxine. It's converted by the liver into an opioid. It's actually got several metabolites but there's a key one, goes by the handle M1 or O-Desmethyltramadol and that metabolite is an opioid. So you have Tramadol, the SNRI, and the metabolite, an opioid. And the first problem that arises is that the conversion of Tramadol to it's metabolite is effected by one of these CYP enzymes in the liver, CYP2D6. It's the same enzyme that turns codeine into morphine and I think most people appreciate now that codeine isn't an analgesic until it's turned into morphine and that conversion, the 2D6 enzyme based conversion varies tremendously from person to person. It's subject to a high degree of polymorphism and so depending where you're from, six or seven percent of people don't have any CYP2D6 and they won't turn codeine into morphine, they won't turn Tramadol into M1 and when you give somebody who's a slow 2D6, you give them Tramadol, you're giving them all SNRI and no opioids.

On the other end of the spectrum you get people with overactive CYP2D6, multiple copies of the gene. They're typically from the Middle East or from Eastern Africa where this is quite prevalent and they'll turn Tramadol into M1 like nobody’s business. And so all this is to say that when you give somebody Tramadol what you're really giving them is this, you're giving them like Venlafaxine and Morphine in an unknown ratio. In the individual patient level experiment that is analgesia this very kinetic issue introduces unnecessary noise.

Alex: So you have this terrific line in this post, "I like to think of Tramadol as what would happen if Codeine and Prozac had a baby and that baby grew into a sullen unpredictable teenager," sounds like my teenager, "who wore only black and sometimes kick puppies and set fires."

David: Yeah, I quite like that line. It came to me just before I submitted the post. It's a little bit of hyperbole but it's really just meant make people appreciate that there's a lot of complexity to this drug that I think isn't appreciated.

Alex: You just mentioned that there is a concentration of people who have more active or more copies of this particular gene or enzyme that metabolizes Tramadol into the active opioid in the Middle East and I think you also noted in your post that there appears to be more of an epidemic of Tramadol in that region of the world. I wonder if you could say more about use of Tramadol worldwide?

David: Yeah, so in India and I think also in China there are these generic companies that produce a massive amount of Tramadol and they ship it out to parts of the world where opioids are often quite hard to get. In fact you'll read quite a lot now about the lack of access that physicians have, especially for palliative care, in parts of the world that aren't especially affluent, like I think in Africa in particular and maybe in the Indian subcontinent it might be kind of hard to get your hands on Morphine for somebody at the end of life or some other opioid that we might not think twice about using. But Tramadol I think fills a void there and I don't think the ... So Tramadol's very heavily misused in the Middle East and throughout Africa. I don't think it's exclusively that the genetics of the population, that's gotta play a role, I think it's more just the sheer availability. I tweeted a thread maybe a year ago on Tramadol, a ten or eleven piece thread on the same stuff I unpacked on the blog and I overnight got about 200 followers from Nigeria. I think part of the reason it's such a problem in Africa is you just buy it, you don't need a prescription you just kinda get it from

anywhere and it sounds like they're huge swaths of the population in Africa and the Middle East that are physically dependent on and in many instances addicted to the stuff.

Eric: So, when I went through training, the idea of Tramadol was is that, oh it's great, you have your SNRI, your Venlafaxine, you have your opioid, you combine them together, it's two drugs for the price of one. You're hitting multiple receptors and maybe helps with neuropathic pain, maybe it helps with a Mu opioid. Isn't this great. It sounds like you're saying, maybe it's not so great.

David: Well yeah, no that's ... I mean there is truth to the fact that SRNI's can have analgesic effects because the dorsal horn of the spinal cord involves serotonin transmission and obviously opioids can. So the party line, "Tramadol's a good drug 'cause it has these dual mechanism of action," is superficially appealing but if you just leave it there you've missed the point that you really have no idea how much of these various components you're giving a person and you've got no assurances at all that you're giving the person any opioid. So it just seems to me if you wanna give somebody an opioid, give them an opioid and if you wanna give them an SNRI, give them an SNRI. But don't give them an SNRI that is converted in a highly unpredictable fashion to an opioid oh and, by the way, is encumbered by a whole bunch of other toxicities.

I make the same point, I gotta say, about Codeine too but we're all comfortable with Codeine, right? But the fact is when you give somebody 60 of Codeine you are giving that person an unknown amount of Morphine and it is inherently irrational. Tramadol is the same way except Tramadol's even worse because the parent compound has toxicities that Codeine doesn't really have.

Eric: So it sounds like it's a bad Mu opioid. Is Tramadol also a bad SRNI? Like how does it compare to effectiveness compared to let's say Venlafaxine?

David: Well no, it is an SNRI and if you happen to have the genetic machinery to turn it into M1, it is an opioid but the problem isn't that ... M1's a decent opioid and Tramadol is a decent inhibitor of the reuptake of Serotonin and Epinephrine. The problem is that the kinetics of the conversion just lends so much unpredictability to the experiment, that's the crux my concern with the drug.

Alex: Right, you would never give somebody ... Let's say you were giving somebody a mix of Acetaminophen and Oxycodone, right? And say, "I'm gonna prescribe you an unknown mix of these two drugs," right?

David: Yeah.

Alex: "Were just gonna give a mystery mix. Here you go. There might be a lot of Acetaminophen, there might be a lot of Oxycodone. I don't know which. We won't know, we'll just give it to you."

Eric: It's a surprise.

Alex: Let's see what happens. You would never do that, that just makes no sense.

David: Exactly. To be fair, I think that when you were taught or when you taught people that Tramadol was an effective therapy and I think I have to make this point, it is true that in some people Tramadol can do what we want but we don't know how the patient's gonna respond until we try it and given the high prevalence of the polymorphism to 2D6 and the other various ancillary toxicities, I think it's really hard to justify starting a patient on Tramadol when we have other options that are more predictable.

Eric: Are there other things we should worry about with Tramadol?

David: Oh yeah. So the kinetics is one thing, seizures is another and again, this is dose dependent and I think it primary reflects the parent compound Tramadol, might be more likely in people who are slow 2D6's or people who take more of it but seizures can occur, Serotonin toxicity can occur. I think this is actually pretty rare but there are some pretty compelling case reports of people who are on Citalopram and Tramadol and they have just obvious Serotonin toxicity happening within hours of starting one or the other drugs. The 2D6 thing is important for another reason. Let's just say, let's say that you're on Tramadol, you're taking a 150 a day and you're doing well and you're converting some of it into the M1 metabolite. If I came along and put you on a CYP2D6 inhibiting drug like Buprenorphine or Paroxetine or Haloperidol or Amiodarone, there's a long list of them, what I would effectively do is turn you into a poor metabolizer and so that would have the effect or at least in theory could trigger something that looks like opioid withdrawal. You've been getting a lot of M1 for who knows how long because you were turning Tramadol into M1 and I come along with a new drug that turns off 2D6 and suddenly you don't have any M1 and then you would be expected to display all the features of opioid withdrawal.

There are some other things, hypoglycemia, physical dependence is a huge issue. I did a tremendous anecdote of a guy I saw a while ago, he had a bad shoulder and he saw an orthopod who wanted to put him on Percocet and the guy said, "No thank you. I don't wanna be on opioids." So the orthopod said, "Well here's some Tramadol." So away he goes on Tramadol and does okay. About a year and half into it he wanted to come off of it and when he went from 150 down to 100 he was crippled with insomnia and he just tried and tried and could not manage to come down on the dose. He wasn't addicted but he was physically dependent and it took a major toll on his quality of life.

Eric: So can I ask about the hypoglycemia? So big study came out in JAMA IM in 2014 making this link between Tramadol and hypoglycemia even in non-diabetics. How does that work?

David: Good question. I wrote the accompanying commentary with Louis Nelson on that and we scratched our heads and we have no clue what the mechanism is. When you dig into the literature ... So first of all, I think it involves Tramadol the parent compound. There are similar reports, by the way, with Venlafaxine. If you look at the structures of Tramadol and Venlafaxine side by side, there's more than a passing resemblance but the literature on this is very, very thin and it seems to involve a combination of either increased peripheral glucose uptake or reduced hepatic gluconeogenesis but as soon as you say those things people's eyes start to glaze over and like I just don't know. Maybe one day I will, maybe someone will listen to this podcast and they'll tweet at me and educate me. I'm not sure but it happens, I think it's a rarity but it's one more reason, one more reason to be thinking twice and if you've got a patient on Tramadol who's seizing, is it the Tramadol or is it the sugar in their boots.

Alex: So let's bring it home, a bottom line for our clinical audience who are primarily practicing geriatricians, palliative care providers, doctors and nurses who are seeing older adults with multi-morbidity often on multiple medications, some with chronic pain or patients who are seriously ill nearing the end of their lives. In that context is there any role for Tramadol?

David: Different people will give you different answers. I think the answer is no and I'll summarize why I think that is. When you put a patient on an analgesic whether it's an opioid or an NSAID or acetaminophen or a cannabinoid or whatever, you aren't just trying to relieve pain, what you're trying to do, like all drugs have side effects and benefits, what you're trying to do is to afford the patient more benefits than harms and of course pain relief is part of the benefits as is improved function and quality of life and what not. But into that experiment, the unusual and highly unpredictable kinetics with Tramadol and all of these other side effects that accompany even standard doses, it introduces unnecessary noise and unnecessary toxicities. It's not that it can't work, it's that when you start it you are really rolling the dice and given that we have so many other alternatives that are less unpredictable it doesn't seem, to me, it doesn't seem sensible to roll those dice.

The only time I prescribe Tramadol is when I've got a patient who comes in on it and they are doing okay and I'm not gonna rock the boat by changing things but I would universally discourage my colleagues and my house staff from starting them.

Eric: So you wrote this post on the blog, you tweeted about it, did you get any hostile reactions from people who strongly disagree?

David: Oh yeah, yeah, of course. Whenever I'm ... I'm quite critical of opioids generally. I prescribe them at end of life all the time and I prescribe them for acute pain and I do prescribe them for chronic pain, although I do so differently than I did five years ago. Maybe we could talk about that on another podcast 'cause that's even a bigger deal. But when you criticize opioids or you criticize cannabinoids for that matter, this has happened to me on the cannabis front, you invariably encounter people who hold different opinions and most of the disagreement is, at least with Tramadol, is polite and it comes from other professionals but when I reduce it down to what the crux of the disagreement is, the disagreement is, "Well I've used it and it works." My point is that sure it can work but if you think about the drug’s pharmacology a little bit which you aren't really asking all that much 'cause it is a drug and we should think about the pharmacology of the drugs we prescribe, it does not make sense full stop. It's not that it can't help some people, it's not that it can't do what we're trying to do and afford more benefits than harms, it's just that the initiation of Tramadol is it's open season on your patient when it comes to side effects and benefits and that's kind of what it boils down to.

Alex: That's terrific. I wanna ask a somewhat tangential question. Your post on twitter, your tweet went crazy. That entire thread, there are multiple components of it that have been retweeted multiple, multiple times and picked up by a number of people.

David: This is thread on Tramadol?

Alex: Yeah, the thread on Tramadol, it's just incredible. We'll link to it in the podcast that accompanies this or the post that accompanies this podcast. But I wonder if you could say a little more about ... One of the things that Eric and I are often asked to give talks about is use of social media and medicine. Something about the role of Twitter in disseminating this message and how you decide to use this thread method of disseminating this message.

David: I didn't see that question coming but it's a good one. So like you guys, I publish things and I guess I could have got into Twitter maybe five or six years ago. It has pros and cons, it can be a bit of a time sink if you're not careful but it became apparent to me that, especially as you accrue followers, that it's a better way of reaching people. I can publish a paper, in fact I've written about Tramadol a couple of times and I'm sure that those publications have been read by somebody but I don't just want an extra pub net hit, I don't just want an extra line on my CV, what I care about ... I'm mid career now. What I care more about is influencing how people think about drugs and so I think that the reach of Twitter is just far greater than most journals. We even had a piece in New England maybe a year and a half ago on opioids and I had a Twitter thread about that that also got a lot of attention. I think it probably honestly got more reading than the actual publication in the journal.

So I think that the thread approach provided you don't overdo it, I see people who write these threads that go on for 30 or 40 or 50 different tweets that are all like together, it's a matter of personal taste, I find that a bit tiresome. This Tramadol thread I probably spent about three hours putting it together and yeah it did get, let me just see...

Eric: Three thousand retweets.

Alex: Three thousand retweets.

Eric: Two hundred and thirty four comments today.

David: I'm just looking at the analytics now. So the engagements, 555,000 impressions, 50,000 engagements. So I don't know how many people are gonna take stuff away from this but if they take nothing else ... Can I make some political comment?

Alex: Please.

David: Where was it? I think I ended up on my thread, I linked to a ... tweet number 13 I made the point, "Anyways those are some of the problems with Tramadol. Here's an analogy to simplify things." And then I linked to a tweet after I'd given a talk to a bunch of med students at the University of Toronto and this will probably get me in trouble with some of your listeners but I said that tweet was, "Just told 200 medical students Tramadol is the Donald Trump of pain medicine, dangerous, irrational and you're going to regret it." I can say that 'cause I don't work in the US, probably denied entry next time I try and come. But the whole point of it is that if some medical student out there or some resident or some faculty doesn't remember 2D6 and all that stuff, if they just remember that one little joke about Tramadol being unpredictable and irrational and dangerous, I've accomplished what I've wanted. Maybe somebody out there will choose not to prescribe it because of something I wrote on twitter a couple years ago.

Eric: Well I would love to say we want to have you, invite you to come in person to one of our podcasts but I think that's no longer an option 'cause you'll be denied at the border.

David: Yeah, I'm North of the border now.

Eric: They'll build a second border wall north of us now.

David: Well Canada's not paying for that I'm pretty sure.

Eric: Well before we end, is there anything else that you think we haven't talked about that you think is important to talk about?

David: No, nothing. I think we covered all the bases. I think we did importantly touch on ... I guess I should back up a little bit. You asked if I get any brush back. I have had a couple of unpleasant interactions with patients, not interactions that I've engaged in but people who've said, "Don't tell me that Tramadol can't work you pointy headed pharmacologist." There's no point debating those things but I think I do want to make clear that it's not that we shouldn't just be taking everyone's Tramadol away. It can sometimes help people and I think it's a point that needs to be made. My concern with it is that it's the initiation of it and the uncertainties that accompany that. There are all kinds of people who are on Tramadol and actually are doing okay, I think. Although that's a separate issue in and of itself because, and I guess this is the last point I'll make and it relates to all opioids and it's a dose dependent thing, I am convinced that there's a huge swath of the chronic pain population out there who are on opioids, on high doses, they're on maybe a 150 or 200 Tramadol or they're on 2 or 300 of Morphine equivalents of something else and they and their physicians are very often convinced of the benefit of the opioid therapy long term and I think that is at least partly obfuscated by the phenomenon of dependence and withdrawal.

If you say that to a patient, well how do you know? There's no data to suggest this, you've got this anecdote. You've been on 500 of Morphine equivalents for the last few years. How do you know that it's helping you? Well the answer is usually, without it I'm not doing very well. That is obviously withdrawal and the symptoms that accompany withdrawal have to be obfuscating the overall assessment of benefits versus harms and so that's happened with Tramadol, it's happened also happens a lot more with Fentanyl and Oxycodone.

Alex: Now often when we go after medication, there's often behind the medication there's often some other power, right? Big pharma making a lot of money, behind the scenes pulling the levers, pushing the medication. Is that true for Tramadol?

David: Yes. Tramadol, I don't quite have a handle on sales figures but it's a very popular drug in even Canada. Here's an example of exactly that phenomenon. In 2007 Health Canada announced that they were going to consider putting Tramadol on our schedules for controlled substances which it's pharmacology demand, there's no, we've talked about this, there is no reasonable basis to have it on the same schedule as Atorvastatin. When they made the announcement they were very quickly lobbied by Purdue Pharma and by I think Janssen and by a palliative care organization coincidentally that received funding from at least one of those companies. They decided, Health Canada in its wisdom decided not to schedule Tramadol and now 11 years later it's still not a scheduled substance, it's still being given to people by orthopedic surgeons or other physicians who don't view it as an opioid in part because of its classification. So that is one example of how lobbying on the part of industry or groups that are funded by industry influences what happens out in the real world. It's just one small example but companies are in business to make money. They make money by selling pills and it's understandable that they would oppose measures to curtail the use of the pill.

Eric: Well again, I wanna thank you for joining us today.

Alex: Thank you so much David.

Eric: I learned a ton.

David: My pleasure.

Alex: It was terrific and this was fun.

Eric: How about before we leave, Alex, you wanna finish off with a little bit more of that song?

Alex: I'll keep working on it and maybe someday it will be worth paying for.

David: You never know. Hey, thanks guys.

Alex: [Singing]

Thanks David.

Eric: Thanks David.

David: All right, thanks guys. That was fun.

Eric: Well thanks again for joining us and thank you to all our listeners. We look forward to talking with you next week.

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