Drs Brian Lacy and Linda Nguyen on Updates to the ACG Guideline for Gastroparesis

In this episode of Gut Check, guest Linda Nguyen, MD, and host Brian Lacy, MD, talk about recent updates to the American College of Gastroenterology guideline on diagnosing and managing gastroparesis.

Brian Lacy, MD, is a professor of medicine at Mayo Clinic-Florida in Jacksonville, Florida. Linda Nguyen, MD, is a clinical professor of medicine in gastroenterology and hepatology at Stanford University in Palo Alto, California.

TRANSCRIPT:

Speaker 1:

Any views and opinions expressed are those of the authors and/or participants and do not necessarily reflect the views, policy or position of the Gastroenterology Learning Network or HMP Global, its employees and affiliates.

Brian Lacy:

Welcome to GutCheck, a podcast from the Gastroenterology Learning Network. My name is Brian Lacy. I'm a professor of medicine at the Mayo Clinic in Jacksonville, Florida, and I'm absolutely delighted to be speaking today with Dr. Linda Nguyen, clinical professor of medicine at Stanford University in Palo Alto, California. Dr. Nguyen is an expert in the field of motility disorders, especially that of gastroparesis, and is one of the authors of the recently published American College of Gastroenterology guideline on gastroparesis, published in late 2022 in the American Journal of Gastroenterology. Dr. Nguyen, welcome. What a delight to have you here. Let's begin really simply; why an ACG or American College of Gastroenterology guideline on gastroparesis?

Dr. Linda Nguyen:

Well, Dr. Lacy, first of all, thank you for having me on. I think the importance of it is that the last ACG guideline for gastroparesis was in 2013, so we felt that it was time to update the guidelines with the acknowledgement that unfortunately, in that almost decade or so, there hasn't been any new FDA approved therapy, so we have to interpret these guidelines with a little grain of salt that there are no new therapies on the market.

Brian Lacy:

Wonderful. Linda, how was this guideline put together?

Dr. Linda Nguyen:

Well, we started with PICO. We created a PICO question. We felt that the questions needed to be clinically relevant, so we stayed within the clinical relevance and came up with questions that we thought would be interesting or important for clinicians out there. Then the team of authors, we reviewed it and then made some edits and then our librarians went and did a literature search. We then reviewed the literature. Essentially there were 2 reviewers for each of the articles, and we paired it down to relevant articles that were then graded by our grade experts, and then using those, we developed the recommendation.

Brian Lacy:

Wonderful. Just to clarify, for some of people who may not be quite as involved in research as you are, Linda, the PICO stands for population, intervention, comparator, and outcome, and then you mentioned the grade recommendations, which we think are really the best way to develop guidelines. It's a very strong way, and this guideline has a total of 20 recommendations. One focuses on controlling blood sugar to prevent a worsening of gastroparesis, and 4 focus on diagnostic testing, and 15 focus on management. Let's start simply with a question about the diagnosis of gastroparesis. What are the three key components to help make an accurate diagnosis of gastroparesis?

Dr. Linda Nguyen:

I think first you have to have symptoms. If someone's asymptomatic, you don't want to make the diagnosis of gastroparesis. They do have to have delayed gastric emptying, meaning that there has to be a valid test, that diagnosis of slow emptying, and then a normal endoscopy to rule out presence of a mechanical obstruction. You don't want to diagnose someone with gastroparesis who has an obstructing gastric ulcer.

Brian Lacy:

Yeah. Such a great teaching point. It's really that triad of symptoms and a normal endoscopy and then delayed stomach emptying by some validated test. That's a perfect segue. If someone has symptoms of nausea and vomiting and maybe some upper abdominal pain or discomfort, and the endoscopy, as you've mentioned is normal, there's no evidence of a mechanical or anatomic issue to cause these symptoms, what's the best way to diagnose a delay in stomach empty? Is it a 4-hour solid meal test or is a breath test a reasonable alternative?

Dr. Linda Nguyen:

I think the 4-hour gastric emptying test or scintigraphy is at this moment we consider the gold standard. The challenge there is it's not available everywhere. I think the breath test is a reasonable alternative, much better than doing a 90-minute gastric emptying test or a liquid gastric emptying test or any other varieties I've seen coming through my office either do a 4-hour solid gastric emptying test or don't waste time, energy, money doing it. Then if you don't have access to that, then the breath test is a nice alternative.

Brian Lacy:

Yeah. For our clinical listeners here today and for our patients who listen in, really 2 great clinical pearls there for clinical care, meaning if you do the gastric emptying scan, make sure it's a 4-hour scan, not 90 minutes or 120 minutes, and it has to be a solid meal, not a liquid meal. Linda, that's great in terms of diagnosis. Now, in terms of management, let's start very simply, what's the role of diet?

Dr. Linda Nguyen:

Yeah. I think that it's the mainstay and is the first-line therapy, and I typically tell patients to eat a small particle diet. This is based on a study by Allison where they compared the small particle versus our more traditional gastroparesis diet, which is the low fat, low fiber diet, which if you think about that low fat, low fiber diet, it's not very healthy. With small particles, you can still get the fiber in as long as it is... I think of it as partially digested by a blender, cooking, et cetera.

Brian Lacy:

Yes, and your point about the fiber is such a good point too, because so many people on this super low fiber diet become very constipated and that can add more symptoms or exacerbate symptoms, so that's a good point. Thinking about managing symptoms of gastroparesis, which can be difficult because of the multiple symptoms, what's your approach? Do you focus on the predominant symptom? Do we choose nausea or vomiting or pain, or do you always start with the one that you kind of pointed out early on, the one FDA approved medication to treat gastroparesis, which is metoclopramide?

Dr. Linda Nguyen:

Yeah. I look at 4 things when I talk to patients and discuss therapies. First, is the predominant symptom, as you mentioned, whether it's nausea, vomiting, pain, bloating. The other one is the severity of the symptoms. How severe are the symptoms in terms of impacting the patient's quality of life? Not so much the severity of the delay in emptying, but the severity of the symptoms and the impact on the patients. The third thing are the comorbid conditions. Patients with gastroparesis often will experience disordered sleep, constipation, irritable bowel, migraines, fibromyalgia, postural orthostatic tachycardia syndrome. I take all those comorbidities into account when I think about recommendations of therapies. Then the final one is really the patient and their preferences. Do they want medications? Do they want more natural therapies? What have they tried before and what are they currently on? Those are all 4 factors that I take into account. I don't follow a single algorithm. It's much more personalized.

Brian Lacy:

I like that your patients are lucky to have you. This really personalized approach, identifying the predominant symptom and the most bothersome symptom, identifying what's affecting their quality of life and then really personalizing their therapy. That's wonderful. Linda, thinking a little bit more about metoclopramide, many patients and providers are concerned about using metoclopramide. For listeners who don't know this field as well, that's also called Reglan, as you know. Do you think these concerns about metoclopramide are justified? Should we be using this medication?

Dr. Linda Nguyen:

The risk of tardive dyskinesia is real with metoclopramide, although I think the risk is lower than we thought. We used to think it was between 1 and 10% or even studies up to 15%, but in looking at some of the databases, it's probably less than 0.1%. There are people who have greater risk factors, so people who are taking other psychotropic medications, women, elderly, renal insufficiency, diabetics. My approach is using the lowest effective amount and then if they can, use it as needed or have drug holidays. The drug holiday is not evidence-based, but this is more Linda-comfort-based to say having holidays decreases the risk, but mostly just educating the patients about what to look out for.

Brian Lacy:

All right. I would say maybe not evidence-based, but also based on 25 years of clinical experience, sounds pretty good to me. Some providers like to use prokinetic agents, and these are medications as we know that accelerate gastrointestinal transit and may help some symptoms of gastroparesis. Prucalopride, a 5-HT4 agonist, acting in a serotonin type 4 receptor, has been used to treat symptoms of chronic constipation. We know it's FDA-approved to treat chronic constipation. Although its use would be off-label, what about the use of prucalopride for symptoms of gastroparesis?

Dr. Linda Nguyen:

Yeah. I did use prucalopride for gastroparesis and there was a small study done in Europe that looked at 2 milligrams of prucalopride in patients with idiopathic gastroparesis and it found that it accelerated gastric emptying and improved symptoms. Now, when you use it off-label, it's hard to get it covered and it can be very expensive, but keep in mind that 40 to 50... actually in our series was 60%, 40 to 60% of patients with gastroparesis may also experience constipation. If I have a patient who has both gastroparesis and constipation, then I absolutely will use the prucalopride.

Brian Lacy:

Wonderful. Circling back just a little bit to the nausea and vomiting, which is oftentimes a predominant symptom or symptoms in these patients, and we know that nausea and vomiting can be very difficult to treat. Clinicians are so busy. We all love algorithms. If someone has persistent symptoms of nausea and vomiting and they've failed a reasonable trial of metoclopramide, do you have an algorithm for our listeners or is there always something you jump to as number 2 or number 3 in your treatment algorithm?

Dr. Linda Nguyen:

Yeah. I used to not have an algorithm. We did a survey years ago, or we conducted a survey years ago of patients with nausea and vomiting and listed every neuromodulator that we've ever used and asked them to rank how they felt the efficacy was for them. This was really a patient perception type of study. What floated to the top in terms of therapies that patients felt were most effective were promethazine, ondansetron, and then cannabis.

For my patients, I'll use promethazine, ondansetron, and as you know, Brian, promethazine, the downside of it has to do with the sedation, so it's hard to work and be on promethazine. I do use ondansetron. If they fail that, then I'll use some of the antihistamines, like diphenhydramine. I borrow from our pediatricians who use a lot of cyproheptadine and we use it for cyclic vomiting syndrome, so I'll use something like that for patients, especially if they're underweight or they have insomnia. Promethazine is great for weight... not promethazine. Cyproheptadine is great for weight and for sleep. Then borrowing from our chemotherapy-induced nausea and vomiting, mirtazapine, olanzapine. Those are kind of the 3 buckets that I look at afterwards.

Brian Lacy:

Wonderful. Again, this is part of your art of personalizing the therapy to that patient, monitoring side effects and probably using some things in combination, a concept of augmentation therapy. Shifting gears a little bit, let's say that patients have some persistent symptoms, maybe nausea and vomiting, despite your best efforts. You've tried medication 2, 3, 4, 5. Some providers inject the pylorus with botulinum toxin, Botox. Preliminary data over 20 years ago looked kind of promising, but in retrospect, the data really wasn't that great. Do you recommend Botox injection of pylorus or should we discourage it's use?

Dr. Linda Nguyen:

I think there's emerging data going back to the personalization, that there are a subset of patients who would benefit from botulinum toxin or pyloric intervention, and those are the ones with decreased distensibility of the pylorus. I think of it in terms of symptoms because doing pyloric endoFLIP is not available to everybody. It's more of a volume problem. If they have more bloating and a more regurgitating fullness and they have more severe delayed gastric emptying, those are the patients that I think are more likely to respond to the botulinum toxin as opposed to nausea. I think nausea is so complex that it's not necessarily an emptying problem. I don't necessarily use Botox for symptoms of nausea.

Brian Lacy:

Yeah. I like the way you tease that out quite a bit because nausea is so complex and so many things can cause nausea. Just a simple Botox injection may not improve that at all. Gastric electrical stimulation, it's been the treatment of gastroparesis for quite some time. It's a huge topic. We could spend the next hour talking about just gastric electrical stimulation, but if you had to choose a group of patients who are most likely to respond to that, who would you choose?

Dr. Linda Nguyen:

It would be the nausea patients. Gastric electrical stimulation I think works on the sensory or the vagal afferent parts of it, which I think helps with nausea. The studies have shown that patients with predominant nausea symptoms do better than the pain-predominant symptoms for gastric electrical stimulation.

Brian Lacy:

Wonderful. You're right. The GI tract is a sensory organ, isn't it? Right. 90% of those nerves in the GI tract are sensory in nature and nausea may be part of that. As we start to wind down here, Linda, there's been a lot of excitement in the field about a technique called G-POEM, gastric peroral endoscopic myotomy. For our listeners who may not be familiar with this, this is where during endoscopy, an incision, a small incision is made in the pylorus to open it up to allow food to empty better. What's the data to support this endoscopic technique? Is this something we should do for all of our gastroparesis patients? Is this standard of care now or is just for a select few?

Dr. Linda Nguyen:

I would say this would be for the select few; just because we can cut, we shouldn't necessarily cut everybody. The whole, because you can do it, you shouldn't. The data is emerging. It is quite promising. There was a G-POEM versus SHAM and crossover study that was done in Europe that showed that it did decrease symptoms and accelerated gastric emptying. Then in the SHAM group that crossed over, they also had a similar response. Very promising, but the question is, who would respond to these therapies? We've seen that once you cut, it's permanent. We can't go back. There was actually a really nice study that was done looking prospectively in terms of who were the responders to G-POEM. What they found was that the patients who had the more severe symptoms of satiety, bloating, minimal or milder symptoms of nausea in more severe delayed gastric empty, so 4-hour gastric retention was over 50%, they were more likely to respond. Kind of similar to what I was talking about with the botulinum toxin group. It's sort of the volume patients.

Brian Lacy:

I like that, and I like that approach. Again, personalize your patient. We have lots of treatment options out there. One size does not fit all. Linda, this has been a wonderful conversation. I've learned so much. I know our listeners have learned so much. Any last thoughts for our listeners?

Dr. Linda Nguyen:

Yeah. I think gastroparesis is challenging for patients and clinicians treating patients because there aren't any FDA approved therapies beyond the metoclopramide. The one thing I would leave with is keep trying. Don't give up on patients. Augmentation is absolutely necessary, especially with the more severe symptoms, but don't forget as you augment to go back and think about stopping things that are not working so that patients aren't on 20 different medications when they come in, but just to keep trying.

Brian Lacy:

Yeah. Wonderful, and with such a great last teaching point, don't forget to keep looking at that medication list and maybe we can wean people off. Linda, again, thank you. To our listeners on Apple, Spotify, and other streaming networks, I'm Brian Lacy, Professor of Medicine at the Mayo Clinic in Jacksonville, Florida. You've been listening to GutCheck, a podcast from the Gastroenterology Learning Network. Our guest today was Dr. Linda Nguyen, Clinical Professor of Medicine at Stanford University in Palo Alto, California. I hope all of our listeners found this just as enjoyable as I did, and I look forward to having you join us again on GutCheck for future podcasts. Stay well.