Brian Lacy, MD, and Jay Pasricha, MD, on Chronic Nausea and Vomiting: Part 1

In the first of a 2-part podcast, Brian Lacy, MD, and Jay Pasricha, MD, Maryland, discuss the diagnosis and management of chronic nausea and vomiting.

Brian Lacy, MD, is a professor of medicine at the Mayo Clinic in Jacksonville, Florida. Jay Pasricha, MD, is a professor of medicine and director of the Johns Hopkins Center for Neurogastroenterology in Baltimore, Maryland.

TRANSCRIPT:

Dr. Brian Lacy:  Welcome to this Gastroenterology Learning Network Podcast. My name is Brian Lacy. I'm a professor of medicine at the Mayo Clinic in Jacksonville, Florida.

I am absolutely delighted today to be speaking with Dr. Jay Pasricha, professor of medicine in the Division of Gastroenterology and Hepatology at Johns Hopkins University in Baltimore, Maryland.

He is a world-known expert in gastroparesis and nausea and vomiting, and our topic today is something that affects every GI provider and really every medical provider, regardless of specialty, and that's of chronic nausea and vomiting.

Jay, thank you so much for joining this podcast today. Let's begin simply by setting the stage for our listeners. How common is chronic nausea and vomiting?

Dr. Jay Pasricha:  Thank you, Brian. That's a good question. There aren't any easy answers to that. Intuitively, we know it's very common. Perhaps those gastroenterologists, particularly at tertiary medical centers, who may be biased because we see a skewed portion of the population.

If you look at the few surveys that have been done of a large community, then the prevalence of chronic nausea and/or vomiting defined as duration of 3 months or more is probably close to 10% which is a large number.

That's, of course, a mixed bag because as you know, there are many, many causes of nausea. If nausea persists for more than 3 months, it's a real medical problem.

Dr. Lacy:  Ten percent is a lot of people. Think about 30 million US adult Americans.

Jay, you kind of touched on that right now. For those of us who routinely see these patients, we understand how persistent symptoms of nausea and vomiting can affect them. Can you let our listeners know how it really affects these patients on a personal level?

Dr. Pasricha:  I think there's probably no human being that has not experienced an acute bout of nausea and vomiting. We all know that desperate feeling when the nausea hits its peak and you're just about to upchuck. It is like no other sensation. Your mind shuts down, your body goes numb, all you can focus is on the heaving. Then, miraculously in most cases, you throw up. It can last for a while, but usually there is this sweet, intense relief because you've now experienced what it's like to be on the dark side with that nausea and suddenly it's gone.

Now imagine you're a patient where that nausea persists. There is no relief in the offing. All you have to deal with is live with that sensation. Sometimes it's intense, sometimes it's not so intense, but it never goes away. That's with chronic nausea.

People say, "Well, chronic pain is a problem." I can tell you compared to chronic pain, chronic nausea may be even more debilitating, because there's something that it does to your mind that really takes the fight out of you. So it is perhaps one of the most extreme examples of human suffering.

Dr. Lacy:  Jay, that's such a nice description. And I think it's a reminder for all of us who see these patients to be so empathetic for these patients with these daily symptoms, so thank you.

You kind of touched on this early on already, but a key differentiating point in the evaluation of nausea and vomiting is distinguishing acute nausea and vomiting from chronic. Why is that so important and what time cutoff do you like to use?

Dr. Pasricha:  I think the time cutoff is arbitrary, right? It all depends on what the patient finds a nuisance. Most patients will take a day or 2 of nausea in their stride. They won't like it, but they'll take it.

After a couple of days of nausea, it's not like a nagging small pain. Nausea is something that is difficult to ignore at a certain level. So most people, after a few days of nausea, are going to seek some help for it. They may help themselves—for instance, there's a new medication that they started. They'll call up the doctor and say I'm getting nausea that's very difficult for me to handle. A lot of times, it is medication-induced, at least in the short term. That can fix that.

But often, if you have persistent nausea, it's something that usually goes hand-in-hand with other symptoms, whether they are GI origin or even central nervous system in origin, like a headache or a migraine. These are some of the features that really make a patient seek medical attention. For me, that's more important than the exact duration.

Like I said, when we do epidemiological studies, people like to use cutoff. Typically for almost anything, including pain or change in bowel movements, we use a 3-month cutoff. I don't think that's that particularly helpful in individual cases.

Dr. Lacy:  That's a good point. Maybe we should focus more on the impact and how it affects patients rather than some arbitrary numbers you pointed out.

Jay, the etiology of chronic nausea and vomiting is so diverse. You could probably wax poetic for the next couple of hours. But for our listeners here today, could you identify some of the major causes that you'd think about?

Dr. Pasricha:  As gastroenterologists, we naturally focus on GI causes of nausea. Most off, we'd think about focusing on the upper GI tract, particularly the stomach. Now, there are certainly esophageal causes of nausea, if you have severe reflux esophagitis, that can cause nausea. But most often, people start thinking about a disorder of the stomach.

Now, if you've ruled out obvious lesions, like an ulcer, then it comes down to consideration of a modality issue. This is where things start to get tricky.

I said upper GI, but clearly, the wiring of the gut is so crossed that you could potentially get nausea from almost any disorder anywhere in the GI tract, from your rectum...You can have patients who present with even obstructive defecation and they'll have nausea.

But assuming that you've ruled out some obvious factors, the patient is not obstipated, there's no history of intestinal obstruction, and you've ruled out issued like an ulcer, then it really comes down to consideration of, does this patient have a gastric motility problem? Then of course, like I said, that's where things start getting a little tricky.

Dr. Lacy:  Yeah, and that in itself is such a big topic. As you're alluding to, whether that's delayed gastric emptying with gastroparesis, or functional dyspepsia, or cyclic vomiting syndrome, or cannabinoid hyperemesis syndrome, all these things factor in together, don't they?

Dr. Pasricha:  Yes. I think 20 years ago or more, cyclic vomiting, or CVS as it is called, was not something in the lexicon of most adult gastroenterologists, although pediatric gastroenterologists have been dealing with it for quite some time.

But it was thought not to occur in adults, and now, of course, we know it's well-established both in terms of an idiopathic problem, but more recently, with a cannabinoid hyperemesis syndrome being brought to attention, a lot of people are thinking about that, rightfully.

What I want to point out about the cannabinoids is just the classical presentation is cyclic vomiting syndrome. But long-term use of cannabinoids can, by itself, slow down gastric motility. As patients present with chronic GI symptoms, that includes chronic and not simply episodic or periodic nausea.

Those are still, I would say, not the majority of patients that we'd see. The majority of patients that we see will have other evidence of gastric dysfunction. I always ask for that, so you always ask for early satiety, fullness, postprandial distress, pain, bloating, distension. These are hallmarks of a stomach that's not doing its job.

And that's a clue that the nausea is tied into the stomach. In the absence of any one of those symptoms, the cause of nausea then becomes a little more elusive.

Dr. Lacy:  Great teaching point. Jay, you've spent so much of your career thinking about these patients with these really bothersome symptoms. You're a great diagnostician. When you think about somebody with chronic nausea and vomiting, how do you like to begin the evaluation? What tests are required in all patients, or is there really no validated diagnostic algorithm?

Dr. Pasricha:  For most GI motility problems, the single most important component of the diagnostic evaluation is the history. If I didn't have any objective tests, I'd be fairly comfortable in about 90% of the patients with a good history. And a good history always begins at the beginning.

It's important for me to establish the premorbid conditions. If nausea begins abruptly—and I can tell you, a lot of my patients come to me and can recall the exact day that it began, even if it was 10 years ago—that's a clue that there was a trigger. And if there's a trigger, then there is a substrate on which that trigger produced this effect. Typically, it may be some kind of genetic predisposition. It goes back to a 2-hit hypothesis. But take a history. You really delve into what other symptoms that could be referable in either a gastric or a generalized GI dysmotility.

Again, assuming there are no red flags and there's no inclination of ulcers that are obvious, no tumors, then you start thinking about in classical teaching, at least whether this patient has gastroparesis or not. Right? That's how we've been taught, that’s still in the textbooks, and for a long time, I was following the same pattern. Except when you start seeing the numbers of patients that I have, you realize that a large portion of those patients have normal gastric emptying, yet their symptoms are indistinguishable. Twenty years ago, if I was to take a bet, based on history, I'd say, "Yes, this patient for sure has gastroparesis," and about 5 times out of 10, or perhaps with more, I'd be wrong, that their emptying would be normal.

That was part of one of the tracks that I undertook in terms of my investigations. What's really going on with this? What does gastric emptying really mean? And what is its relationship to nausea?

Dr. Lacy:  So Jay, couple of great teaching points. One is that all chronic nausea and vomiting is not gastroparesis and so keep your blinders off. Also, I like the way you started, meaning let the patients tell their story. I oftentimes begin my exam with that, "Tell me your story. When did symptoms start?" You get so much valuable information, don't you?

Dr. Pasricha:  Yeah.

Dr. Lacy:  Just thinking about testing a little bit, tet's take a patient who came in with maybe a several-year history of chronic nausea and vomiting, and their endoscopy or 2 endoscopies have been normal, and their gastric emptying scan is normal, and their small bowel follow-through is normal, and this is not pancreatitis or liver disease.

Do you feel a need to go on to other second or third layer of testing? Or do you just feel comfortable at that point, saying this is chronic nausea and vomiting and just treating?

Dr. Pasricha:  Yes, if you do a comprehensive evaluation, and your tests are negative, and the patient has classical symptoms of gastric dysmotility, apart from the nausea, early satiety, fullness, etc., I'm pretty comfortable treating it.

The question that you alluding to is, what you call it, and how you treat it? I'm not a big fan of nomenclature for the sake of nomenclature. It's important to have nomenclature because it's a way to conveniently study a certain group of patients. But for a long time, these patients who look and talk and have an illness that's just like gastroparesis but have normal gastric emptying have been called various monikers. I used to call them first gastroparesis-like syndrome because it's obvious, then as part of the NIH-funded consortium that I'm part of, we started using the term CUNV, chronic unexplained nausea and vomiting. We did that because people who used to submit papers who say what are you calling them, what do you think they're in.

But it is always part of our intention to figure out what is the relationship. If this looks, acts, feels like gastroparesis, what is, in fact, distinguishing it from gastroparesis? Is it just that they have a normal emptying? How reliable is that normal emptying, or how reliable is gastric emptying to begin with? Do they actually have other similar features that you can be more confident about apart from their symptoms?

This was a 10-plus year odyssey , if not more, that culminated in this paper that we published where we showed, yes, so let's forget what we came up with arbitrarily a CUNV or gastroparesis-like syndrome, let's use the wrong criteria to classify.

As it turns out, obviously, either gastroparesis or this other syndrome meets all the criteria for functional dyspepsia or spandrel distress type. But that is neither here nor there. That's just another name. What does that really mean?

We went a couple of steps further. First we showed very, very broad similarity in terms of the baseline presentation, as well as outcomes after one rate improvement with the same baseline severity.

But we did one more thing, and we repeated the gastric emptying after 48 weeks for about a year and found roughly 40% of patients with abnormal gastric emptying at baseline had normalized at 48 weeks, and conversely, about the same percentage who had normal emptying at one year, had delayed emptying. In the meantime, nothing else had changed. The symptoms remained the same.

Finally, we took a subset of these patients and were able to obtain full-thickness biopsies of their stomachs. We showed that at a pathological level, they had the same features as we had previously shown with gastroparesis, i.e., loss of interstitial cells of Cajal and an aberrant macrophage profile.

So pathologically, they're similar, clinically, their outcomes are similar, and gastric emptying is labile. You can't really use it reliably to classify patients into one or the other bucket. So we don’t know where we are, what our peers are going to make of this, but my own personal thinking is, let's start making this distinction.

These are all patients who have a relatively similar neuromuscular disorder of the stomach. Let's start thinking about this very differently, because if you label them as functional dyspepsia, I can tell you it's very, very frustrating for the patients because they’re given the impression, at least intentionally or not, that this is not real, it's by definition, not organic. Therefore, it must be in their mind, and they're tired of hearing it.

It's also a reason why the pharma world has ignored these patients, because there is no label to go.

But I think as we go forward, and these boundaries sort of break down, we realize that we're actually dealing with a large portion of the population, 10% of population that has a real pathologically definable disease of the stomach. I'm hoping that a lot of pharma will get interested and we're seeing some of that happen.

I'm also hoping that gastroenterologists will not, subconsciously at least, put different weights on the severity of the symptoms depending on whether you have delayed gastric emptying. They're just equally severe, they're equally debilitating, quality of life impact is just as bad.

We should be embracing these patients, just like we do with other disorders that we know are organic. Just because we have a paucity of medications doesn't mean that we shouldn't give them the attention and empathy that they deserve.

Dr. Lacy:  Absolutely. For our listeners, if you do your PubMed, search, and lookup Dr. Pasricha. Go to the top, look at one of these most recent articles. You've been such an important leader in this NIH consortium. There's fascinating data in his last publication, so please, for our listeners, take a look at that.

As you pointed out, there are distinct changes in the enteric nervous system and macrophages, so we're learning a lot about these patients.

In our next podcast, Dr Jay Pasricha and I will continue our conversation on chronic nausea and vomiting with a discussion of medications, both over-the-counter and prescription, and other possible treatments for this condition.