Chapters Transcript Symptom Management in Chronic Liver Disease Dr. Shah shares strategies and tactics for symptom management for patients with chronic liver disease. So our next speaker is Doctor Parth Shaw. He completed his medical degree at Saint Louis University School of Medicine. He then went to California to complete his residency in internal medicine at Cedars-Sinai Medical Center in Los Angeles. Angeles. After that, he moved back to Saint Louis to complete his fellowships in gastroenterology and transplant hepatology at Washington University School of Medicine, where he's currently assistant professor of medicine with the division of Gastroenterology and hepatology. He specializes in palliative care and hepatology, cirrhosis, liver transplantation, alcohol related liver disease, metabolic liver disease, autoimmune liver disease, viral hepatitis, liver cancer, and he sees patients at Barnes Jewish Hospital and Barnes Jewish West County Hospital. So, He's going to talk to us today about symptom management and chronic liver disease. So I will let you have the floor. Thank you very much. Thank you for that introduction. Uh, thank you for having me here. Uh, so, um, I, I do have a very, very special interest in palliative hepatology. It's, it's kind of a made up term, but it's, it's really focusing on the symptoms that these, uh, chronic liver disease patients have. I think we, we often get lost in the weeds of, OK, the patient has end-stage. Liver disease? Are they a transplant candidate or not? And then it kind of just stops there, you know, we get our answer and then we don't really kind of think about the patient anymore. Um, but I think you guys all in the audience know better than most is you get those messages, those phone calls, is what are you going to do about my abdominal pain? I have this cramping, I have, I can't sleep, well, you know, I have nausea, this and that. The whole point of this talk is, is to basically say that there are options, um, and we as, as trans hepatologists should be doing a better job, obviously, of, of addressing these things. Um, but I wanted to share this with you guys just to basically say, you know, there are safe ways of treating all of their symptoms. There's ways of, of, of bringing them up. Um, and obviously, this can always be done, you know, in, in joint collaboration with the hepatologist that's following them. But obviously very relevant for you guys, uh, who, who get these calls all the time. So, uh, just a couple of things, you know, I'm gonna obviously, um, kind of look at this in a more of a palliative care mind mind frame, um, because obviously, everyone here is, you know, is performing palliative care in one way or the other, if you think about it. Obviously, it's not specialty primary care, it's more primary palliative care where we're just talking to patients about symptoms, not even really related to just liver disease, obviously. Um, but we're gonna talk about, you know, how it pertains to chronic liver disease. I'll talk about some of the tools that I use, um, because a lot of this comes down to illness understanding and disease expectations. And when we don't communicate that with our patients, there's a lot of issues. And I think the, the number one thing, for example, is treating hepatic encephalopathy. Uh, we'll obviously go through that as well. And then, of course, we're gonna talk about all the symptoms that, that we usually hear about and how to safely treat them. And then at the end, if there's time, I'll talk about a uh new program that I just started, um, that's inpatient currently at that Big Barnes. Um, and I mentioned it because the, the hope is that eventually it will become an outpatient program as well, where all I would do is I would be talking to patients with chronic liver disease and their symptoms. So it could be a resource available to you, hopefully soon. Um, so starting out with palliative care, obviously, we all know what palliative care is. I love the idea of it because it's also, it's multidisciplinary. We're looking at different facets of a patient's life, and we're just talking about quality of life. We're improving it. So it doesn't matter if a patient is on the transplant list, it doesn't matter if they've been declined, it doesn't matter if they've been accepted for transplant. They're allowed to have Symptoms and they will have symptoms. And the, I think the reality of the situation is we often dangle transplant as, oh, this is going to cure everything. But in reality, for those who have seen patients after transplant, there are so many issues after transplant that still persist. Um, there's, there's a lot of issues, both psychosocial, physical, there's still a lot of issues that have to be addressed. And then, and, and I think that's why this is very, very important at any phase in, in a patient's, you know, life and, and disease stage, do they have symptoms. And so the fundamental principles of palliative care is really focusing on these three bullet points here where you're talking about symptoms and pain, you're talking about depression and anxiety, which is very seldomly addressed, and of course, caregiver bur burden as well. So why does it matter? Well, liver disease is progressive. Uh, so that means most of the times, 9 times out of 10, it's only gonna get worse, even if the patient stops drinking, even if their hep C is cured. Usually, you know, we're not gonna have regression of fibrosis to the point where they're completely normal again. Usually they're gonna eventually decompensate and have issues in the future. So what that means is more symptoms, that means more hospitalizations. And unfortunately, you know, this type of care where it's symptom focused, is, is often very lately, you know, it's given very late in a, in a, in a disease course. And so by the time it's provided, it's usually end of life when we're talking hospice, we're talking death in the hospital, in the ICU which intubated on a bunch of pressers, becomes a lot more resource intensive and invasive. Um, and then it ends up, you know, patients end up suffering. In the long run, and instead of families as well. So, the, the few studies that have looked at liver disease and integrating outpatient palliative care, they've basically shown that there's a reduced resource use, reduced readmission rate, decreased length of stay when they did come into the hospital, just because everyone knew what their goals of care were. They knew the expectations of their disease, they knew, you know, what to look out for, and they had, they had appropriate expectations as well. Um, of course, the, the, the focus was always on Symptoms and quality of life, and that improved. Everyone came to a consensus of the goals of care much earlier, and that meant that if comfort-focused care was needed at some point, it was actually given earlier, where hospice, sure, you may not be able to avoid hospice, but hospice at home is very different than hospice in the hospital, where we call it hospice, but really it's comfort-focused care. We palliatively extubate them, we stop the pressures, and they die within 4 hours. Uh, those are two very different scenarios. I really like uh these next couple of slides because it shows, you know, in on the X axis, you have time, Y, you have functional status. It's, it shows what, what usually happens is, you know, patients are walking around with compensated cirrhosis for, for years, and then all of a sudden, there's some kind of decompensating event, variceal bleeding. Societies, jaundice, fatigue, and there's this huge shock of diagnosis. They had no idea what to expect, and all of a sudden they're taking new medications. They have a very big delay in illness understanding, and we're just trying to treat the symptom that has shown up, and we're just trying to get them to kind of understand, OK, what is ascites? This is what we have to do. As time goes on, their functional status worsens, they get more emotional distress, caregivers start to burn out because they don't know what to expect. And then of course, financial distress because there's so many hospitalizations, length of stay, patients are getting weaker, they're getting sicker, and then at the very end, it's. Their death or liver transplant. And like I already alluded to, not everyone is a candidate for liver transplant. Very seldom, you know, even if we do 160 transplants a year, we turn away so many more than that. And so, the reality is, is, is this is often too much too late. And this is how we usually try to intervene as patients, as the time goes on, as patients get worse and worse, this is usually how, how we think about things is like they, they develop a symptom, we treat it, we try to help them cope when it's a little bit too late. We, we provide caregiver support when it's too late, and then at the end, we do advanced care planning, which really doesn't make sense, because at that point, it's really they're just looking at death, and that's not really true advanced care planning. So what should we really be doing? It should look something like this. Obviously, it's not always possible to, you know, do everything at once. But, but one of the things I do for, for my inpatient program, for my clinic patients is when I meet them for the first time, we talk about everything. Obviously, time is always, you know, the, the, the, the scarcity, obviously, but, you know, what the as best as you can, you know, I try to talk to them about what their disease means, why They have cirrhosis, what to expect, what are the different symptoms. And I also set expectations. So in a patient who's drinking actively, I will never tell them, you are a transplant candidate, or, oh, maybe you will be. I will tell them straight up that you need sobriety. You need to prove that you can remain sober, that you need to be able to follow a complex medical regimen. I will also always involve their caregivers as well, because as we all know, you know, Liver disease, along with others, uh, it, it requires very good caregiver support. How is a patient going to know that they're developing hepatic encephalopathy if they're, you know, if they're confused already, you know, and how do they know that they're supposed to take more lactulose? How do they know to count their bowel movements? You know, we need caregivers for that. We need caregivers to take them to the labs to make sure that they're, they're tolerating their diuretics, for example, or to know if they're starting to have melana, they need to take them to the emergency room. Um, so all of that is extremely important and it's, it's important to do it upfront. What ends up happening, and I think you guys in the audience can kind of attest to this is, is patients will complain about all these things, you know, the first line is, is all the the most common, you know, symptoms that patients will complain about. Um, a lot of things, and obviously, sometimes it's way too much to discuss in just one appointment, and it, it kind of needs to be brought up, but these are very, very common, and I think are worth addressing because it plays into quality of life. Um, the other issue is, like I mentioned, because it's a progressive disease, they become more frail, more sarcopenic. They have ascites, so they can't eat as much, they're more nauseous, they're taking lactulose, so they have a lot of gas bloat. And then that leads, it's a vicious cycle that leads to eating less, being more sedentary, then they lose more muscle mass, and then they're too weak, they get an infection and they end up in the ICU and then there's no option from there. So what we end up seeing is that patients and family members try to do what's right for them. So they'll go online, they'll try to get a bunch of supplements, you know, liver toxs, and they, but they don't really understand how poor their health truly is. They don't really understand what the MELD score is. They don't realize that even though their, their, their liver is scarred and they have a high MELD, it affects their ability to tolerate surgeries as well. Um, and they have a hard time coming to terms that they have to get an ultrasound every 6 months. They need an EGD every couple of years, depending on what, what is found for some varices. They have to know NSAIDs are no longer allowed, but you can take Tylenol up to 2 g, you know, so there's all these different changes, and essentially patients get very, very overwhelmed, and you can already imagine if they have hepatic encephalopathy, how is it reasonable to expect that they're going to be able to understand all of this. And so, um, when the the flip side of it is that the caregivers are also, you know, a critical aspect of palliative care and being able to deliver this care for, for the patients. Um, but there's a lot of emotional tension there. And, and the reality is, is caregivers, you know, I call them caregivers, but in reality, you know, we've all been there. We're, we're we're taking care of a family member, we don't think of ourselves as a caregiver. We think of them, this is just what we do, right? We're, we're, it's our family. And so they end up taking on a lot more stress and not really utilizing the resources that may be. Available to them or even asking or even, you know, watching out for their own health. Um, but a lot of it also has to do with just lack of information, um, and, and just not knowing what to look out for, not knowing what their loved one's diagnosis is, what the treatment options are. So they're unable to plan for the future, and, and they're and they are very hesitant towards the idea of palliative care, even though palliative care means you can get treatment plus Focus on symptoms because I think everyone thinks palliative care equals hospice equals death. And so there's a, there's a lot of misinformation or lack of information out there, and I, and I just say this because I highlight the point that, you know, we all, you know, especially on the hepatology side, we need to do a better job of letting, you know, educating patients and their caregivers and making sure that their caregivers are involved in these conversations. So how can we do that? Obviously, communication is, is key. Um, I personally, I really highlight the expectations. So I think, you know, one of the things I do this with is, is liver disease causes pain in different ways, and we're going to go through that in a little bit more detail later. But when I talk to patients, you know, and they say, OK, my pain is an 8 out of 10. You know, I never promised that their pain is going to be a 0 out of 10, but I also say it straight up that, hey, you know what, your pain's an 8 out of 10. The goal is to kind of get you more functional again. It, it means maybe we're aiming for a 5 out of 10 instead, and, and it's going to help you be able to eat better or be able to move around or participate in, in, in physical therapy, for example. Uh, so it's very goal centered, um, and it's, it's setting expectations. And for the same, on the same token, you know, letting them know if they're not a transplant. And I let them know right away because it would be unfair of us to dangle that option in front of them when that's really not a reality and patients can't really plan accordingly. It changes, you know, their lifestyle, their, their quality of life as well. Um, and it changes what options they have available for them as well. Um, and of course, these discussions are, are difficult to have sometimes, but, but discussing, you know, the, the common symptoms is always beneficial and just letting them know that, you know, they will be addressed over time. So what are some, some tools that I like to use? Now, obviously, I think you guys are probably familiar with the majority of these. I think the big fear of using them, not just in hepatology clinic, but just in any clinic in general, is when you give a patient with chronic illness, multiple chronic illnesses, these, these surveys, they're going to say yes to everything. It's gonna be a pan-positive review of systems. When we look at the Edmonton symptom. scale, you're going to get a 10 out of 10 on every single one, and you're not, you're no better off than where you were before. So you might as well not use them. I think that is kind of the, the, uh, the, the census that, that, that I, that I gain. Um, so I, I would say that, you know, use what works best for you. Um, I have my own way of doing it. I highlighted the last one, because that's one of the tools I like to use the best. Um, but I, I kind of also have a, uh, uh, my own way of kind of going through the common liver related symptoms, but all of these are great. All of these kind of ask about chronic liver disease, symptoms, quality of life, um, and I think it's important, and of course, asking caregivers as well, you know, how they're doing, how they're coping with as well, because if they're not doing well, the patient is not going to be doing well as well. Um, so, yeah, I'm not gonna obviously go through all of these, but these are just different variations of the same thing, trying to get what symptoms, what's distressing them. Um, obviously you can imagine that you don't want to look at a paper that has X's all across it, and you don't know where to start. Um, one of the things I do do when I do see that is obviously talk about what's the thing that's bothering them the most, and often they'll say everything is, but then you, as you talk to them, you can kind of figure out what's the common denominator. So if someone is saying they're not sleeping well, they can't breathe at night, they can't eat at, they can't eat during the day, they're very nauseous, well then ascites is probably the common denominator there, and then you should focus on that. Um, so this is, this is the tool I wanted to spend a little bit more time on now. Honestly, this could be applied to any disease process. I specifically like this because I write it down for all my patients, and I hand it to them. And I find that having patients, you know, giving them something to refer to is very, very helpful. Um, I don't use medical jargon when I do this best case, worst case scenario, and what, and I don't use statistics, I focus on quality of life as well, and how that's going to be addressed during these three phases. So, so really, it's, it's basically, you know, what's your best case scenario, what's your worst case scenario, and then what's the most likely. Um, so, so for example, for a patient who is, who is about to be listed for transplant, you know, the best case is they don't have to wait very long. Uh, the worst case is, is that they get too sick and then they have to be removed from the transplant. Now that might seem very like silly to, to bring up, but you would be Surprised at how many patients that that actually happens to, and they, and, and the patients in the family say, well, how does that make sense? I'm sick because of my liver disease. How can I be too sick for the liver transplants? Well, it's a very real thing and it happens a lot more frequently than we think. That we have to delist someone because they're, they're way too sick, they're in the ICU, multiple pressors, or they develop a comorbidity that makes them not a candidate for surgery. And so, if we don't mention it like this, how do they know that that's not an outcome? Now, obviously that doesn't make it any easier necessarily when we have to tell the patients that, but at least it's in the back of their mind that, hey, I was warned that this could happen. And then, of course, talking about the most likely, this is where it's really important to, you know, set expectations. Um, you don't want to promise anything you can't. Um, and so the most likely is, hey, you know what, you're going to probably get listed, but that doesn't mean that all your problems are going to end. You probably will be hospitalized for a hepatic encephalopathy in the interim. You're probably going to need rehab, you're probably going to have a new baseline of everything, and you're going to have to adjust to that. Um, and along the way, you can, you can kind of sprinkle in whatever symptoms they're talking about, always making sure to mention that we're going to be addressing that. Um, and so I really like this, and this is what I do for my inpatient, uh, program as well as we go through this, we document this way, I give it to the patients, their caregivers, they can basically, you know, review it at any point in time. And so, uh, let's kind of move then into, uh, the, the symptoms that, that we always hear about, um, from, from liver disease. So when, when they kind of survey, obviously, these are all over the place, a wide ranges here, but when they survey, uh, chronic liver disease patients, you know, pain, shortness of breath, muscle cramps, sleep issues, Social, psychological issues, and then sexual dysfunction. These are the most common issues that, that always get reported. And I will say a lot of these are undertreated as well. And like I said, sometimes we get lost in the idea of, is this patient a transplant candidate or not, and we kind of forget that, you know what, they're still going home and they're going to have all these symptoms. So I start with psychosocial, uh, distress, um, because it's probably the most prevalent. Um, definitely, definitely, at least 30% of patients with cirrhosis have some form of either depression or anxiety. It's got to be much higher than that, and rarely do, do we ever treat it properly. Um, and, and the, the thing that's really important about this is a lot of, a lot of patients that we're seeing, especially the younger population who are Coming with alcohol-related liver disease, they're drinking to treat something. A lot of times it's depression, anxiety. Sometimes, yes, it's pain, but it, it would be unfair of us to expect them to remain sober if we're not treating their underlying symptom that that they're using alcohol for. So the, the most important thing, and, and I guess I'll take a step back to the common theme that you're going to hear me say as we go through all these treatment options for any kind of medication. Just start low and go slow. That's gonna be the kind of the theme of the next several slides. Um, so for example, depression, anxiety can be treated very safely in cirrhosis. Um, we don't, we, it, it, even if, if someone has decompensated cirrhosis, they can safely tolerate it. Usually, we have them on 50% of their dose, and they tolerate it just fine. Now, of course, just like any patient, just like any medication, we should still be talking to these patients about the side effects. Effects. Obviously with SSRIs, SNRIs, there's certain side effects we have to look out for. We don't want to make their encephalopathy worse, but we have to also let them know, and of course, their caregivers, what to look out for. Um, so, so it's, it's just worth noting that we can definitely treat it, and a lot of the way I do it is I try using treatments that can, that can do multiple things. So for example, the first medication I reach for is Usually Zoloft. The reason being is because a lot of these patients also have pruritus, and Zoloft will treat pruritus from liver disease, and it will also help them with their depression as well. Same thing with hydroxyzine. A lot of patients end up saying that it ended up helping their anxiety along with their itching. Um, now, now that we're using Coreg a lot more for varices rather than propranolol, we're not using the propranolol as much for like the symptoms from, uh, uh, anxiety, but that Used to be another, another option as well. Um, the other important thing is we have to rule out other mimics. A lot of these patients, especially those who, who, uh, have alcohol abuse in their history, are vitamin deficient, and they can mimic encephalopathy and dementia as well. Um, and, and it's very easy to, to, to kind of screen for these, you know, it's a very common vitamin deficiencies that we can check for in labs, or you can just empirically treat. There's no problem with that as well. But I use both SNRIs and SSRI's. Oh, the other thing that I really like is for our patients with chronic pain, duloxetine can obviously help with, with more than one thing. It can help with pain, can help with depression as well. Um, so once again, you can start low and then just up titrate slowly as needed, um, and they, they often very well tolerate it, and they respond very well to it. The one thing that we don't talk about or maybe don't realize as much is with this psychosocial distress, a lot of it does come in the realm of transplant. So there are patients who they're on the transplant list and their lives are out of their hands. They really feel, feel a lot of fear because they don't know when they're going to get that phone call. They also don't know, am I going to get too sick for transplant? Am I gonna lose my window? So there's huge, huge, you know, depression and depression and anxiety in, in that pre-transplant phase on the waitlist. And that doesn't stop. And, you know, even after transplant, there's the concern that, you know, if we've transplanted them for cholangiocarcinoma or metastatic colorectal mess or liver cancer, what, what if it comes back? And that unfortunately it does happen, you know, that's they have that anxiety because we talk about it, right? You know, we have to give them the appropriate expectations that it's not 0%, but it's the greatest chance of cure that we can give them. Um, with our young patients, the recurrence of PSC is a huge thing. Recurrence of autoimmune hepatitis is, is another possibility. So there's a lot of fear and anxiety with that as well. Um, and there's a lot of caregiver depression and anxiety as well, because there's a lot of shifts, even though we say, oh yeah, you know what, the transplant is great, you're not going to have to take lactulose anymore. Well, you're on a lot of new medications that you really can't miss anyways. Uh, so, even though, even though you may be on less medications, you're still on just as. Important medications for their health. And so caregivers have a hard time, you know, making sure they take their medications at the right time, knowing what to look out for, um, knowing when to take them to labs, those kind of things. There's more appointments in the beginning. So there's a lot of caregiver burnout that we, we see. And that's why one of the most important parts of our transplant evaluation is a caregiver assessment, because if they don't have a caregiver, then we can't transplant them because we know that's not going to end well. And then of course, there's the, the, uh, distress when a patient is removed from the waitlist because they have improved health. And this does happen, maybe not as frequently, but there's a patient who maybe, you know, was drinking and then they stopped drinking, and then all of a sudden their meld is now 10. Well, that kind of puts them in a weird limbo and they get Very frustrated because they're clearly not sick enough for transplant, but at the same time, they're definitely not living a normal life. So they feel very frustrated and, and they kind of feel like they're being penalized for getting better. Um, they don't know what's gonna happen next. Are they gonna get sick again or what's their, you know, is this their new normal for the rest of their life? Um, do they have to take medications for the rest of their life? So there's a lot of adjustment with that as well. And so along that same route, you know, other than obviously prescribing and addressing, you know, the depression, anxiety with, with the patients themselves, always asking, you know, obviously caregiver, uh, burnout, asking, asking and making sure that caregivers are doing OK. Uh, like I mentioned before, they always think we and they. Always think of, of, of, of themselves as loved ones rather than caregivers. Um, and, and studies that have looked at caregivers and poor outcomes, the consistency is if the patient has a history of hepatic encephalopathy or alcohol use, or recurrent admissions, and then obviously younger dependents at home. It just does not end well. You know, there's the both for, for both the patient and the caregiver. There's a higher mortality in both, um, higher burnout in both, um, and, and it, it's just very important and something we do not address. There are obviously caregiver surveys that we could do, but sometimes it's as simple as just asking them a couple of questions and taking just a a couple of Seconds to, to address that. Um, sometimes, you know, all it takes is also a referral to a social worker, maybe to just talk to them about resources that they could use. Um, but a lot of it is just information too. A lot of it is just making sure that when you're talking to the patients, that their caregivers are present, whether on the phone or in person, so that they can hear what you're saying, because it really is a. Team effort when taking care of patients with chronic liver disease. Um, and there's a lot of cultural influences. There's a lot of things you don't realize until you start to kind of go down that path. Um, so once again, it would be wrong of us if a patient says, I don't receive blood products. Well, how can we talk about liver transplant then there's no such thing as a bloodless liver transplant. Well, at least I watch you, there isn't. Um, I know that a few institutions do it, but, um, If that's the case, then we should not be telling them that we, we should not be hiding things from them. We should be very upfront with them and say, you know what, maybe Washu is not the right place for you, especially if you need a transplant, you need to go elsewhere, um, and that needs to be taken into account. The only way we're going to find out is if we're having these conversations. And there, you know, I actually pulled this picture off Facebook, you know, there's, there's a lot of great groups out there as well, um, for specifically caregivers in, in the transplant realm, um, where they can kind of get help on, you know, what changes have to be made. Um, our transplant team does send out YouTube videos as well and, and information about what life looks like, but You know, that's just the tip of the iceberg. There's a lot of things that are not addressed in there as well. A lot of things that kind of come up on the fly that, that they have a hard time s uh uh struggle, they, they struggle with. And so these support groups are, are great. Um, and what we can do is obviously provide guidance as much as possible, um, and make sure that the caregivers take time for themselves as well. So one of the biggest things, if not the biggest things that we hear about, um, from our patients with end-stage liver disease is pain. There's different types of pain, you know, there's no susceptive pain, um, then there's obviously neuropathic pain. Most of the times, the pain that we, we hear about is usually from ascites causing really bad abdominal distention and the stretch of the nerves, and then, of course, the stretch of the glisten's cap. Capsule in the of the liver when there's acute hepatitis, then there's splenomegaly. There's a lot of nerves that are getting irritated in that, in that regards. So we always say, and, and of course, these patients always have comorbidities. Now that MASH is basically taking over in the United States, all these patients have diabetes, all of them usually have some form of neuropathy as well from long-standing diabetes. So that plays a role as well. So, NSAIDs are completely contraindicated. Um, not only will they harm the liver, but they will push the patient into basically HRS AKI, um, and then kind of go downhill from there. But 2 g of Tylenol daily is perfectly fine. Um, what I was, and, and actually a lot of the guidelines say Tylenol with tramadol should be first line for visceral pain. Um, I think tramadol is underutilized. Um, obviously, kind of think of it as kind of like an opioid in a way, and, and yes, it may have some kind of addicting qualities to it compared to Tylenol, for example, but it is certainly much safer than opioids, um, uh, certainly much safer than the patient having, coming to the hospital with IV Dilaudid every, you know, so few weeks. But, but I will say that in my inpatient program, I actually don't treat pain with tramadol or opioids. I usually do topicals. Uh, diclofenac is fine. There's, there's a very, very, very, very little systemic absorption to the point where it's never been proven to harm the liver. Capsaicin, I try not to use, although it's an option. I know it helps, uh, with joint pains. Uh, patients often, you know, they forget to wear gloves or whatever, they end up itching their eye or something, and then, There ends up being more of a mess, and so I just kind of stick with lidocaine patches, whether over the counter or the prescription ones, and then diclofenac gel, you know, Voltaren, Tiger Balm, all those, all, all those kind of work the same way. So on top of that, we'll do the Tylenol. On top of that, I will do gabapentin or pregabalin. Once again, the theme of this is start low, go slow. The gabapentin, uh, you know, you can go up to like 800 mg daily. Obviously, if they have kidney disease, that's gonna kind of be the, the rate limiting step there because, because of the excretion, but If they start to get, you know, sleepy with it, well, then just tell them to take it at nighttime, or have them do 300, 300, and then 900 at nighttime. That way they can sleep better at nighttime. Same thing with pregabalin. I really, really like the muscle relaxers as well, not just limited to baclofen and Flexeril, but methocarbamol, tizanidine. All those are safe. Once again, you start low and you go slow. Obviously, watch out for their kidney function and make sure that you're not giving too much in that regards, but if one doesn't work, you can always switch to the next. The nice thing about it is they're taking it throughout the day. So, so ideally, they're, they're having some sort of Um, uh, symptom relief throughout the day as well. And as I had mentioned before, duloxetine, I really like that for both treating, you know, uh, pain, but also for treating depression, and I usually do these together. So in patients who have really bad pain, you know, young alcoholic hepatitis, they're not a transplant candidate, uh, even if they were, you know, I've put them on a little bit of Tylenol, um, I'd put them on gabapentin, I'd put them on a muscle relaxant, and then I'd put them on a TCA plus or minuses. SNRI. So all of these can be given together. Obviously, if one of them ends up causing the patient to be dizzy, lightheaded, um, or their encephalopathy starts to get worse, obviously, you got to stop that one and you got to do the other. So I wouldn't recommend throwing everything at once. I would do it in a very stepwise progression and maximize one before you start another. These patients are obviously have an increased pill burden to begin with. They often will forget to take their medications, but I just, Mention all these options because I usually treat pain without opioids. Um, and it's usually pretty successful. Once again, it's never gonna get it down to 0%. But as long as the patient's aware of that, in my, in my, you know, uh, practice thus far, I haven't had issues with that. Um, obviously, easier said than done, you know, sometimes patients, that's all they want to talk about. Um, but, but I think you can help them feel a little bit more reassured that there's a lot of different options here. And of course, treating the underlying cause. So, like I mentioned, one of the most common causes of abdominal pain is when you've got everything, all the nerves stretched from ascites. Um, so, so obviously making sure that we're aggressively treating that. Diuretics, in the end of the day, if someone is getting weekly paracentesis, diuretics are really not gonna do anything for them. We just need to aggressively do the paracentesis. Um, and, and there's no problem with doing it once a week. The patients that get it twice a week, we just have to watch their kidney function, make sure that we don't push them into hepatorenal syndrome. Obviously, tips is a great, great resource resource when, when it's appropriate. It obviously has its own contraindications, so it's not for everyone. But I think we should be thinking about that for patients who have ascites, um, who, who just seem very, very miserable from that, but are just not quite transplant candidates. Same thing for peritoneal drains. This is kind of a controversial thought here, but we usually obviously save peritoneal drains for our patients who are on hospice. But, but the reality is, is there are other patients who would benefit from peritoneal drains. I have placed a peritoneal drain for many patients who are elderly individuals who whose platelets are in the single digits. Every time they get a paracentesis, they end up bleeding into the cavity. Well, it doesn't make sense then for us to keep on doing that. They end up in the ICU, they need blood transfusion, they need embolization. In certain cases, it's OK to put a peritoneal drain. Obviously, this should be discussed and, and the risks and benefits should be discussed with the patient, with all the other providers and make sure we're on the same team. But here's the, the concern is always, OK, you put an external drain in, it's going to get infected. Well, we've had everyone, everyone in, in our hepatology division has had expertise with that, where we get a patient with a peritoneal drain that's infected. Well, what do we do? We just treat them with antibiotics and Pull the drain, and we say we tried. Um, obviously, it could be worse, you know, patients, especially older patients, they could become, go into septic shock and die from that. But I would say that if the patient understands the risk of it getting infected and them not recovering because of their underlying liver dysfunction, then I think that's their right to make that decision, and we could offer that to them. Um, there's, there's a new thing called Alpha pump, you know, we don't do them at WashU. I don't know any surgeons that have, uh, necessarily been trained or signed on to do it. But it may, it's, it's, it's recently been kind of approved in the United States, it's available. The idea is it's a subcutaneous pump that basically pushes ascites into the bladder. Now, a lot of these patients already have incontinence, whether from the lactulose or from the diuretics. I can only imagine this is going to make it worse, um, but this is something that maybe in the future, this, this could be more, more of a, an option for patients who are not a transplant candidate, who are not a TIPS candidate, and we don't necessarily want to go down the peritoneal drain portion. The other thing worth mentioning for peritoneal drains, which also apply to pleurrax drains for the lungs, is you do need good caregiver support. You know, if it's a very frail patient who can't take care of themselves, how are they going to know how much to drain, when to drain it, or when something is wrong, you're going to need someone there with them to, to make sure. And so, of course, it has to be a patient by patient uh decision. The other really common uh symptom we get is nausea and vomiting. So I think the, the thing we don't often realize is the nausea and vomiting is induced by us. Lactulose is probably one of the, the number one causes of nausea and vomiting in this population, just because it causes gas bloat. It doesn't get absorbed, it just the bacteria love it, it causes all this gas, and then they not only can they not eat, then they get more frail, sarcopenic, they fall. They get weaker, um, they get more infections, and then they get confused. So it's a vicious cycle. I think the main thing is that with hepatic encephalopathy, the treatment is not lactulose, the treatment is the bowel movements to get rid of the ammonia. And so if the patients can tolerate MiraLax, mag citrate, Senna, whatever it is, if they can come up with some kind of regimen or concoction on their own. We don't need lactulose. Lactulose just happens to work the fastest, so that if they are on the verge of getting confused, I always tell their caregivers, we'll then switch to lactulose at that point, give them a couple of doses of lactulose, make sure they have their bowel movements, and then go back to the old regimen. Um, so that usually helps treat nausea and vomiting, which is something that we actually cause. Um, the other thing that is very common in patients with cirrhosis is adrenal insufficiency. I often check all my patients with fatigue and, and, uh, hyponatremia, hyperkalemia, and nausea and vomiting for adrenal insufficiency, and I would say about 20. 5% have it, and they end up getting treated for it. But we often think all these changes are due to the liver disease. They're on diuretics. Well, that's why they have hyponatremia, hypokalemia, um, they're, they have liver disease, that's why they're fatigued, um, they have ascites, that's why they have nausea and vomiting. So just don't forget that adrenal insufficiency is very prevalent in this population as well. I also like, uh, telling patients, uh, to use ginger, if they can tolerate the taste of ginger, uh, to help with their nausea as well. The issue there is a lot of, it's, it's obviously a, um, a lot of patients can't tolerate that taste, so, uh, it's definitely an acquired taste for that, for that, uh, regards, but I always mention it, but one of the things I prescribe the most is Zyprexa. I give low dose olanzapine 2.5 mg QHS, and not only does it help, it's kind of like 24 hours of anti-emetic, but it also helps their insomnia. So once again, I always reach for the things that can help both things, uh, to two things at once. And so, uh, as we'll go later through later on, insomnia is a huge, huge issue as well. I always start with Zyprexa, because it, it also treats their nausea. The other important thing is, you know, Compazine and Zofran work well with Zyprexa. Interestingly, Compazine works better than Zyprexa, uh, based on the mechanism of action, but I usually, you know, and there's so many different, you know, there's scopolamine patches. Obviously, everything has its side effect, and you just have to talk to them about the side effects, but I usually tell patients one of two things. Either before you eat, take Zofran 30 minutes prior, along with the olanzapine that's already in the system, or maybe every 3, just every 6, every 6 hours, so 4 times a day, just schedule 4 mg of Zofran, and then for breakthrough. Take Compazine. A lot of times, you basically have to be aggressive and, and preventative. Otherwise, these patients can't take their protein shakes that we tell them to do. They can't gain weight, those types of things. Um, and obviously, treating their ascites is huge as well, because of the, the compression on the stomach. Um, so there's a lot of different things that we can do and a lot of different strategies. Reglan usually works as well. I would, I would reduce that one in half. Um, obviously, monitoring QTC for these patients as well every now and then. But, you know, patients do very well when you kind of come up with this combination. When you also incorporate some kind of standing dose as well, it usually works very, very well. And then shortness of breath. Um, so I put this picture here on the right, just to kind of show the kind of pathophysiology of, of a hepatic hydrothorax. But the reason I, I bring up hepatic hydrothorax, I personally think it's one of the most difficult things to treat. It's very different than pulmonary edema. It does not respond to diuretics. And at the same time, even though hepatic hydrothorax is due to portal hypertension, I've also seen it where We treat the portal hypertension, we do paracentesis, we do a TIPS, and yet they still have hepatic hydrothorax for whatever reason. Obviously, the etiology is you have portal hypertension, you have ascites, and then the fluid kind of gets sucked up into the pleural space from these fenestrations in the diaphragm. Um, so of course, theoretically, if you treat the source, you should, it should get better. The other issue with hepatic hydrothorax, unlike pulmonary edema, it does not cause hypoxia. So a lot of these patients with them, sure they may feel short of breath, but they never get approved for home oxygen, and that's an issue because that's a huge, huge part of their quality of life. They always feel short of breath, yeah, you know, doing a thoracentesis every now and then will help, but how often can you have a patient do it, you know, when they start to do once or twice a week, that's when you have to start thinking about a lorex, and just like a tank up, sure, it could get infected, but then we would just remove it, and as long as the patient understands the risk, then, then we can proceed with that. We do have patients with both a tank cough and a uh lorex because they can't be a TIPS candidate, and they do just fine. They're at home, they know when to drain, how much to drain, they know how to watch their sodium, they get labs when they're supposed to. Of course, if you're on hospice, labs don't matter, we just drain to your comfort level, but I'm talking about those that are not on hospice, and you're, you're just trying to treat their symptoms. The one thing that I also recommend, I do this for patients in the hospital as well, if we can find one, is a bedside fan. That pretty much has helped almost every single patient who have these symptomatic shortness of breath, but they're not hypoxic. Easy enough to get, everyone has a fan, just put it at the foot of the bed, have it point at them, and they feel much. Much, much better. Um, obviously we want to be very careful about opioids and dialytics as well. We want, we don't want to depress their, their respiratory drive as well. Um, and really, if they go to hospice, that's really the situation in which they can get all the supplemental oxygen that, that they can need, um, and that, that, that they could want. And then one that we also cause uh muscle cramps. So I'm sure you guys all get, you know, messages, phone calls about this. Obviously, a lot of time that patients have muscle cramps in the setting of liver disease are from the electrolyte changes in the setting of diuretics, but even without them, muscle cramps are actually pretty common in patients with, with liver disease. Obviously, you want to still rule out, you know, myositis, rhabdo, kidney injury, those types of things, um, and I think by now everyone has heard of the, the treatments that the home remedies that we try to do, like the sips of pickle juice. We obviously I want to be very cautious. It's very a lot of salt in the pickle juice. Uh, I had, I once had a patient who said, hey, my cramps are better after the pickle juice, but now my swelling is a lot worse. Turns out she was basically chugging, you know, glasses of pickle juice. Uh, so obviously we don't want that. We just want sips. Um, quinine has also been very beneficial in, in treating these types of muscle cramps. So we usually tell people, go buy tonic water, obviously. You don't get the, the, don't get the, the alcohol that, you know, we usually think of. It's not a gin and tonic. We, we, uh, just want the tonic water with quinine, drink that, and that will also help as well. In Europe, they use branch chain amino acids and taurine a little bit more. Um, obviously, there's taurine and, you know, supplements and energy drinks. I would not recommend they do that. So that's why I have not bolded it. But in Europe, they have different formulations and a little bit more regulated. Um, but obviously we want to check their electrolytes. We want to make sure the magnesium, potassium, and zinc are all normal. I think zinc, uh, is not checked as frequently as it should, and it can also lead to encephalopathy. So once again, more than one benefit to, to supplementing zinc. Um, of course, sometimes we have to decrease diuretics, but once again, we have options for muscle relaxants. We, we have options to also treat them. If these things don't work, it's not necessarily, OK, well, you got to deal with it. Well, we should definitely try some of the muscle relaxers, and, and, uh, they usually do work pretty well. And then the other, uh, another common one is, is pruritis. I've got this picture here of this very gritty looking powder. I think it's hot chocolate, but the, the reason I bring it up is, is I don't know how many of you guys have actually seen or tried cholestyramine, but it's disgusting. It's, it's a gritty powder, doesn't mix into anything. I, I mentioned it because, you know, pruritus due to, to, due to liver disease, you know, it's usually because of a buildup of bile acids, so it makes sense. A bile acid sequestrant, that's, that's option number one. The issue with cholestyramine is this is what it looks like, this is what it tastes. So the compliance is pretty low, and I will say we often underdose it. So we've all seen cholestyramine 1 g BID. Technically, you're supposed to go up to 16 g daily, and I don't think any patients are ever on that, and they usually say, oh, it doesn't work, it doesn't work. Well, I'm not surprised. So what I would say is, I would try, if their insurance allows it to prescribe cholestopol, which is basically the pill form of, of uh cholestyramine, and if they do do that, I would increase it. I would, I would at least go up to 4 g. BID before thinking about another agent. The most important thing with pruritus and liver disease, it should be agents added, not replaced. So the cholestyramine will always be there, and then you add, once again, I like Zoloft a lot. You start at 25 mg at nighttime because itching is usually the worst at nighttime, and then you can go up all the way up to 100 mg. I usually reevaluate every 2 weeks. And once you max out on the sertraline, you can add rifampicin, you can add naltrexone. Naltrexone usually will go up to 50 mg, for example. Naltrexone, I say, I feel like I have the least amount of compliance because it causes this like headaches, brain fogs, random GI side effects. So patients usually tolerate that, uh, the least amount. Um, and of course, Benadryl and hydroxyzine are huge. They, they can 100% use those things. It's just if they're gonna use Benadryl, once again, use it at nighttime because they're probably going to get drowsy, and at least they can sleep better at night, because a lot of these patients are up all night itching, um, and they feel miserable. Um, of course, one of the extreme treatments is plasmapheresis, and we've had multiple patients who have had suicidal ideations due to such severe. Pritis. Uh, those are the patients, of course, that, that get plasmapheresis, and they benefit from that significantly. Obviously, that's the most invasive, um, so I didn't list that here, but, but there's a lot of options, and all of these can be taken together. Rifampicin obviously has probably the most amount of interactions with other things, and I think patients are always really surprised when they get that blood red color of their body fluids. Uh, but once again, as long as you warn them, they, they can kind of look out for, and they're not very surprised. All right, and then a big one, hepatic encephalopathy and the sleep changes. Um, so, you know, what it comes down to is, it's really, it's melatonin meta meta metabolism changes, and that's what leads to these changes in the thermoregulation, and that disturbs circadian rhythms, and that's what really leads to hepatic encephalopathy. So it doesn't really matter what the ammonia level is, it doesn't matter if the ammonia is improving. You'll hear from hepatologists that we never check ammonias because if the patient is confused or the family member is telling them that they're confused, it doesn't matter if the ammonia is 25 or 50. There have been no studies that have shown that that that actually can justify the severity. Of, of, uh, hepatic encephalopathy. Really, ammonia, we only use that in the case of acute liver failure to really say if it's greater than 150, greater than 100, then there's a high risk of brain herniation, essentially, and then we start dialysis so we can get the ammonia out. In this case, then, if patients are completely ANO times 4, it doesn't matter what their ammonia is, you're gonna keep them on the same treatment. As we already kind of talked about, lactulose is not really the only treatment, it's not really that, is it? Um, and it's really associated with a lot of gas bloat, and of course, rifaximin is not always available. So I, I don't want you guys to think that, OK, we have no options, you know, you're kind of stuck with the encephalopathy, do the best you can. Any bowel regimen would work. Once again, check a zinc for these refractory uh cases, and if it's low, replete it. Um, there's also a great resource or a great uh supplement called Hepalola. It's probably the only supplement that I ever recommend. Um, it's been studied a lot in Europe, and they actually give it in hospitals and in IV formulation. I have the, the Krebs cycle here on the right, because basically what what Heplola is, it's Lornithine L aspartate. Basically, it helps get rid of more ammonia. It it prevents ammonia, um, uh, um, production essentially. So Peplola, the way that it would work is that the patient would have to go on their website, buy it. It's, it's not cheap, you know, it's $100 a bottle. And I tell people in really refractory cases, buy it, take it, see what happens. Don't buy a bunch and have a bunch just in case, but if it works, it works. And I've, I've probably say 50% of patients, it works. Um, but, but, you know, at some, some people, it ends up you kind of having to think outside the box a little bit. Um, the other thing that's important when talking about sleep disturbance is obviously you want to reinforce good sleep hygiene. So we don't want them taking their diuretics or lactulose right before they go to sleep, because they're going to be up all night. You want them to time their physical activity, their meals appropriately. Um, you, you want them to obviously avoid nocturnal awakenings as well. You want them to have, you know, like all this delirium precautions we always, you know, learn about from our neurology team, you know, want to make sure that lights are off, you know, TV is off, you know, windows are closed, all that kind of stuff. Um, and, and, and if, if that doesn't work, you know, zolpidem, melatonin can be given, hydroxyzine can be given once again, Benadryl can be given. Um, especially if they have pruritus, all of these are safe. Um, they all have been tested, so that's, that's all perfectly fine. Um, just ideally, if they can fix, you know, if there's a, a certain trigger that's lead, leading them to, to have poor sleep, that would be the ideal situation. A lot of these patients, obviously with MAS as well, who are overweight, have undiagnosed sleep apnea as well, so that's something that I've been pushing more is getting these, uh, patients, uh, sleep studies. And then we have fatigue, um, which is probably the hardest one to treat. There's different types of fatigue, you know, there's central fatigue, uh, which is basically defects in neurotransmission over time, then there's peripheral fatigue, which is more neuromuscular dysfunction that results from muscle wasting weakness like sarcopenia, and all these obviously contribute to frailty. Um, I think that this is something that probably every patient with cirrhosis complains of, and it's part of the process, unfortunately. And yeah, we usually tell people the only true treatment is a liver transplant just because it's the cirrhosis, it's the, the disturbance in the metabolism that is changing everything. But there are non-pharmalogic and pharmalogic management that we could at least suggest. They're not perfect, but, you know, energy conserving and restoring activities, you know, going through those, referring them to physical activity, it's always that kind of idea that it doesn't make sense, someone's fatigued to have them do more activity. But in liver disease patients, it does help because a lot of them are sarcopenic, and if they're not taking in a lot of protein, they need activity to rebuild that muscle mass. And so for them, really doing physical therapy is important. We have a program where we give, uh, in our transplant center, we give them Fitbits and we call them and we make sure they're getting a certain amount of steps a day. Um, obviously, it's not perfect, that's not gonna, you know, solve all the problems, but it's better than nothing. And so for patients who do have access to that, you know, those are, those are great resources to use. And then I also use uh modafinil, not so much methylphenidate, but modafinil more, um, and it, it does help for fatigue, you know, they kind of get a little burst of energy here and there for, for patients who I'm, I'm trying to have them lose weight. I put them on phentermine, and that usually helps a little bit as well. Um, but, but I would say that, you know, just dose reduce when they're very decompensated, it doesn't mean you have to stop it, um, but once again, if they have a lot of cardiac risk factors, maybe these are not the right things for them. Maybe non-pharmacological options are better for them, but once again, there, there aren't a lot of, a lot of options. And then I think this is the last one I'm gonna go through here, and probably the one that's least talked about, but, uh, obviously, as you can see based on those numbers, they're very prevalent in this population. Um, it all once again happens, it all happens because of all of the hormonal imbalances in the setting of cirrhosis. You could be the most compensated cirrhotic, but still have really bad sexual dysfunction, and it is awkward to talk about, it's awkward to ask about, you know, especially if caregivers are there, um, and so it's, it's, it's tough, and it gets underaddressed. But I do want to mention that we often do this as well. We nowadays, like I, I mentioned before, we're putting everyone on Coreg, because Coreg is, you know, all the data showing Coreg is much better for secondary bleeding prophylaxis, primary bleeding prophylaxis as well, uh, when it comes to non-selective beta blockers. Well, guess what, it can cause sexual dysfunction, it can cause fatigue. Um, so obviously, if we can't stop it or we stop it and it persists, then there are medications that are safe. Tadalafil is very, very safe. There's more studies in tadalafil than sildenafil. I usually start low, 2.5 mg, go up to 10 mg if needed over time. Um, if not, then I'll try sildenafil. Sildenafil is obviously very safe. It's actually what we use in very high doses for our, uh, portal pulmonary hypertension patients who are extremely sick, uh, with portal hypertension. They tolerate 20 mg TID per day, you know, and so it's, obviously, you know, talking to them about if they have cardiac disease, yeah, obviously, they're not the ones to give it to, um, but, you know, making sure they know what to look out for lightheadedness, dizziness, those types of things, telling them when to take it, um, adjusting their medications as needed, um, you know, and, and making sure they're not drinking, for example, if they have other comorbid conditions that are, that are contributing, obviously treating those things as well. So, so, basically, um, all in all, um. The whole point of saying this is, you know, these are, these medications are obviously all familiar to you guys. It's just usually we give them in cirrhotics at lower doses and we titrate them slowly. Usually, we, I recheck every 2-ish weeks. If, if that dose is not working, I go up. Obviously, just like any patients, these patients are susceptible to side effects. So I, you know, as long as you discuss these side effects with the patient and their caregivers, know what to look out for. And just have them reach out, you know, if, if they come up, then you can always make an adjustment at that point. A lot of these medications can certainly be given together. I always reach for those that can treat more than one thing, uh, so that it helps them in more than one facet in their life, um, because I do think that, you know, although transplant, yes, it's great if we can get there. Majority of patients are not transplant candidates. They're not sick enough or they're too sick. Regardless, all of these patients have symptoms in one way, shape, or the other. Um, so I don't have a lot of other time, but I, I, I'm just gonna give a brief, just kind of summary of this program that I started. Um, so it's only inpatient right now at, at Big Barnes. Uh, it's called Supportive Care and hepatology. It's only myself. So right now, what I'm doing is I'm just seeing inpatients with this high symptom burden. Um, what I basically wanted to show, um, is, are these interventions that we just talked about. So, so I spend basically an hour with these patients. I, um, Uh, do these surveys. I do the Edmonton symptoms scale. I just focus on treating their symptoms, whatever it may be. And what we saw is just within that same admission, they had a significant improvement. Now, what we don't have right now is an outpatient, you know, plan for this. The hope is, is that once this inpatient program continues to build and grow, we'll be able to expand it to the outpatient setting. And this is where I think you guys would also be very much involved is what. Where there would be just a specific clinic for kind of palliative hepatology where we're just talking about symptoms. Uh, of course, other things could be addressed as well, but these things like nausea, uh, pain, all those things can be addressed. And even though, you know, we had a 40% improvement in the pain, not a single patient got an opioid. So I, I, I actually thought that was very, very cool. Um, same thing with the surveys that looked at more subjective things. You know, do they actually understand their diagnoses? Do they actually have a goals of care outlined? Do they have a plan, um, and do they feel understood? Everything improved after we had these discussions, we give them those papers, um, we talk about what their diagnosis is, what their prognosis is, what their treatment options are, and that really does help with compliance as well. It does help with caregiver burden as well, um, and so patients really, really felt a benefit to that. Um, and outcomes, you know, that we've seen so far are everything, you know, some we do transition to hospice care, some are very hesitant about transplant, and they say actually, after talking about it, we don't want to move forward with it, or some, it's the opposite. So really, in the end, all of these are, are, are appropriate outcomes, it's essentially. Uh, so, hopefully, you're going to be hearing more about this in the future. Um, but, um, that's kind of all I have. Um, always happy to, to, you know, chat about, uh, patients and, and whatnot, you know, kind of co-manage as, as best as possible. I think this is a huge unmet need. Um, obviously, we're getting More and more patients with chronic liver disease, they are surviving longer too, so we're getting older patients with, uh, uh, chronic liver disease as well. And so I, I, I just want to kind of share that there are options for these, these patients, and, uh, there's a lot we can do for them. So, uh, I appreciate your guys' attention and uh thank you for being here. Created by Presenters Bhooma Aravamuthan, MD, DPhil Pediatric Neurology, Neurology View full profile
