Brian Lacy, MD, and Brooks Cash, MD, on Constipation

In this podcast, Dr Brooks Cash joins Dr Lacy to discuss how to recognize constipation in the clinic, some potential causes of secondary constipation, and available treatments.

Brian Lacy, MD, is a professor of medicine at Mayo Clinic--Florida in Jacksonville.  Brooks D. Cash, MD, is Chief of the Division of Gastroenterology, Hepatology, and Nutrition at the University of Texas Health Science Center at Houston, and a Visiting Professor of Medicine at the University of Texas McGovern Medical School.

TRANSCRIPT

Brian Lacy, MD:
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, and I am absolutely delighted to be speaking today to Dr. Brooks Cash, professor of medicine and chief of gastroenterology, hepatology, and nutrition at the University of Texas Health Science Center in Houston, Texas.

More importantly, he's an international expert in the field of our topic here today, something that comes up routinely in GI clinics and primary care, and that of chronic constipation. Dr. Cash, welcome. Constipation is a common problem for many patients, but it comes in a variety of forms, IBS with constipation, opioid-induced constipation, and other forms as well. For our listeners today, when we start an evaluation for a patient with symptoms of constipation, what are the most common categories of constipation that we should consider?

Brooks Cash, MD:
Well, thanks, Brian. It's an absolute pleasure to be here and thank you for inviting me to talk with you today about this topic. I tend to break this up into a couple of different categories. The first division that I would recommend to the audience members is to conceptualize chronic constipation as being either primary or secondary. Now, by secondary, I mean secondary to some other cause. This could be hypothyroidism. This could be an obstructing colorectal mass. This could be other medications.

You mentioned opioids. That's the first big division. You can get clues about secondary constipation by talking to your patients, doing a complete history, a physical exam, looking at their medication lists and going through their surgical history as well. Now, most patients are going to have primary constipation. Within that category, there's three major divisions. The first and most common is what we call normal transit constipation, and that's exactly what it sounds like.

It's people who have constipation symptoms, but they have normal colon or gastrointestinal transit. The opposite of that, the rarest of the three subtypes in this primary constipation group, would be slow transit constipation. What we have termed colonic inertia in the past. These patients, obviously by the name, have delayed colonic transit or delayed gastrointestinal transits. Also, important to think about small bowel and even the stomach in these patients.

And then the third group, this is the second most common, but I think it's the least thought about would be patients who have a component of pelvic floor dysfunction. This is a number of different terms, pelvic floor dyssynergy, dyssynergic defecation, anismus. There's a number of different, very subtle features between those types of disorders, but these are disorders of the pelvic floor muscles that inhibit adequate and satisfactory defecation.

This can coexist with normal transit or slow transit constipation. But until it's discovered and dealt with, this can really inhibit our effective therapy. This is probably about 20, maybe even as high as 30% of patients with primary chronic idiopathic constipation.

Dr Lacy:
Brooks, thank you. Great overview. If we delve into this a little bit more and thinking about chronic constipation, how do you like to define this disorder? Are there specific criteria we should be using in clinic?

Dr Cash:
That's a great question, Brian, and I think there are. I use the Rome IV criteria. There's Rome Committee criteria for lots of our disorders of gut-brain interaction, functional dyspepsia, irritable bowel syndrome, which you mentioned earlier, and chronic constipation. These criteria are symptom-based criteria. They involve some chronicity and some frequency of symptoms. Patients have to have had symptoms for a certain amount of time. Typically, 3 to 6 months.

They need to have their symptoms with some relative frequency, once a week, et cetera. And then there's basically a laundry list of symptoms of chronic constipation within that categorization and patients should have at least 2 of those. These are symptoms such as a sense of incomplete evacuation, infrequent bowel movements, less than 3 per week, a sense of anal rectal obstruction, having to use manual maneuvers to facilitate defecation, excessive straining.

Those types of symptoms, and that's not the entire list, but 2 out of those features. The other category or the kind of definition that I find as very helpful is a very general definition that was put forth by the American College of Gastroenterology, which is simply dissatisfaction with defecation whereby the patient doesn't feel like they are adequately evacuating their bowels. A much less regulatory or legalistic type of definition compared to the Rome IV. I think either one of those are valuable.

The Rome IV gives you a little bit more specific idea of the symptoms that patients are experiencing. I ask patients to describe their symptoms to me rather than suggesting these symptoms. I find that that's very helpful because it allows them to put it into their own words and gives me an idea of what they're experiencing.

Dr Lacy:
That's wonderful. Brooks, I want to follow up on that just a little bit since you focus so much on symptoms, which really are this defining characteristic of chronic constipation. A lot of providers, I think, focus on stool frequency, 1 bowel per day or 1 per week as an example. But you've just mentioned some other symptoms and they seem just as valuable or just as important. Are we overlooking some patients maybe if we ask just about stool frequency?

Dr Cash:
Oh, absolutely. In fact, these other symptoms that I alluded to are probably more important. In fact, there's data that shows that when you ask patients who are self-identified as having chronic constipation, that they highlight those other more qualitative symptoms, the sense of incomplete evacuation, the sense of obstruction, straining. Those are more important to them than infrequent bowel movements.

We're taught in our training that less than 3 per week is actually abnormal, and that's been shown in population-based frequency type studies, but it's not the defining feature of chronic idiopathic constipation. I definitely encourage the audience to be very familiar with the other qualitative symptoms that patients will describe and actually go after those symptoms. In addition to the frequency or infrequency, but infrequent bowel movements does not define chronic constipation.

Dr Lacy:
Great teaching point. Thank you. Because if we just ask about stool frequency, it sounds like we'll be missing a lot of people we might be able to help. Thank you. Just thinking a little bit more, we've kind of danced around the issue or maybe I've danced around the issue about chronic constipation. What might be risk factors for developing this disorder and are there special populations maybe we should focus on who are at increased risk for having chronic constipation?

Dr Cash:
Yes, absolutely. It's traditional teaching, and there is evidence to support this, that older age, minorities, lower socioeconomic status, women, these are all risk factors for chronic idiopathic constipation. Some of that may have to do with access to medical care and social mores as well. There's also polypharmacy. Our older patients who are on more medications, they have more chronic medical conditions, whether it's neurologic conditions, diabetes, hypertension.

All of those factors come into play. You mentioned opioids as well. It's a huge population. It's an incredibly important aspect of the history to take, but those would be the major risk factors in terms of associations with chronic idiopathic constipation.

Dr Lacy:
Brooks, you're in clinic. You're taking that great history. You're looking for some of those risk factors. What about red flags or warning signs? Are there things we should be alert to that would make us think about something more serious or dangerous rather than just chronic constipation?

Dr Cash:
Yes, and, and this is really I think a lot of common sense and just good medicine. I'd take these cues from our IBS [irritable bowel syndrome] evaluations as well. If somebody's passing blood, and I actually saw clinic this morning and made the statement to a younger patient, passing blood from the rectum is never normal. That needs to be evaluated. Something along the lines of hematochezia or a bright red blood per rectum, unintentional weight loss, an abrupt onset of constipation symptoms.

This may not necessarily be chronic constipation, but somebody who has an abrupt onset of severe constipation symptoms, taking that surgical history, older females, think about ovarian cancer and other masqueraders. Always think about secondary constipation. Those are the things that should go through our minds, and we should ask those directed questions or do that directed physical exam geared towards identifying those alarm features.

And if we uncover some of those alarm features, then we need to evaluate those alarm features appropriately

Dr Lacy:
Wonderful. Brooks, we know everybody is so busy in clinic. People are being asked to do more and more. You rush in. You hear the story about constipation. What about the role of a physical exam in these patients? Does everybody really need an exam? Do they really need a rectal exam? Do you think it's going to change diagnosis or management?

Dr Cash:
We were actually talking about in this in our clinic as well. You're right. That is exactly the scenario that most of us are faced with. And then you've got the other aspect of finding a standby or a chaperone to come into the room. You should always have one in the room with you. But we really can't devalue the importance of a digital rectal examination [DRE]. That is really central to diagnosing pelvic floor dysfunction. The more rectal exams, the more expert you get at this.

The more abnormal or even normal exams that you do, the more prepared you are to feel those abnormal exams. You can get a clue for pelvic floor dysfunction when you do that examination. You can also look for things like anal fissures. That can be a reason for chronic constipation in patients. Of course, we're also doing a prostate examination, and I have actually found prostate cancer in several patients through doing DREs. It's also important to do an abdominal exam in these patients.

You want to lay hands on their belly. You want to feel... See if you can feel fecal loading. Are there any abdominal masses? Is there omental caking? You really do need to do... And it can be a very cursory, but you need to do that physical exam, especially those aspects of it.

Dr Lacy:
I'm generating this amazing list of teaching points today, Brooks. Thank you. One, I want to come to your clinic. It sounds like there's a lot going on there, but number two, for our listeners, don't underestimate the value of a rectal exam. It's not a big deal. It should be part of your exam in these patients. I too am no longer surprised by what you can uncover with that exam. So critical. What about colonoscopy?

This is a controversial area. Does everybody with constipation need a colonoscopy? That 20 year old woman with constipation symptoms for 3 years. When do we decide?

Dr Cash:
Yeah, not at all. In fact, I tend to not do colonoscopy for constipation. It's not considered an indication for colonoscopy. I actually was privileged to write the guidelines for the ASGE [American Society for Gastrointestinal Endoscopy] in terms of the role of endoscopy in chronic constipation. We were quite explicit that this is not an indication for colonoscopy. It's very low yield in a younger population. Now, obviously you have to... Again, it's common sense.

If the patient's over the age of 45 and they've never been screened for colon cancer, then use that as an opportunity to do the gold standard test for colon cancer screening and prevention, which is a colonoscopy. If there are new onset symptoms, that are alarm symptoms, then I think you could consider doing a colonoscopy in those patients. But in typical 25, 30 year old otherwise healthy patient who has no other significant medical problems, no other explanation for their symptoms, doing a colonoscopy for this particular symptom is going to be very low yield.

I tend to not do this. I keep an open mind when patients don't respond to therapy and I don't find an obvious reason for their constipation symptoms, then I may end up doing a colonoscopy. I'm more likely actually to do cross-sectional imaging before a colonoscopy in those patients

Dr Lacy:
For our listeners, Brooks is far too modest to mention the fact that he'd looked at this area specifically with several great publications looking at the role of colonoscopy in patients with IBS and constipation and, again, in a young population without warning signs found nothing different in those patients.

The yield is very, very low. Let's think about other tests. What about anorectal manometry? You were talking about these other symptoms of straining and incomplete evacuation. What's the role of anorectal manometry in a patient with chronic constipation?

Dr Cash:
I think it's got a really very important role, and I'm glad you asked about it. This is one of the tests that we use to diagnose pelvic floor dysfunction, which, again, we're trying to increase awareness. About 20 to 30% perhaps of patients with unexplained constipation suffer from this condition and it can be an overlapper. I typically will do this in patients who I've treated empirically, whether it's with over-the-counter therapies or prescription therapies or both, and they haven't responded.

Now, there is a difference of opinion between myself and other experts. It's not just me. I mean, there's kind of a diversity with regards to how early we bring this test in. Some clinicians and experts will do anorectal manometry early on in the evaluation of patients with chronic constipation. You may get that feeling from doing the digital rectal examination that may prompt you to do that. I tend to do that later on because it is the minority of patients.

Even though 25, 30% is a high percentage, it's still 6 or 7 out of 10 that aren't going to have this and that are probably going to respond to therapy. I tend to try to save those resources to the people who really are going to most benefit from it. But this is a way that we're able to measure the pressures that patients generate during defecation and look for dysfunctional pelvic floor anatomy or physiology. We also will use augmenters like balloon expulsion testing, and you can do functional MRI as well.

Some guidelines recommend a minimum of 2 of these tests to diagnose this condition. I tend to use 1, but certainly understand the data that's supporting 2. I think functional MRI in addition to this is just really escalating the cost of care. If you have the choice and you have availability to get a balloon expulsion test, cheap, easy to do, can be done at the same time as the anorectal manometry test, but very, very useful. This helps you direct patients to pelvic floor physical therapy.

Dr Lacy:
Perfect. Thank you so much. Brooks, let's shift gears now and think a little bit about treatment. Is fiber really the answer for everybody? If you don't get better on fiber, add more fiber, more fiber. Is this the best place to start?

Dr Cash:
I think it's a very reasonable place to start. Every patient's different. You have to take that history. I tend to avoid fiber in patients who complain about a lot of bloating. If that's one of their primary symptoms, fiber's probably going to make them worse. If you have a patient who let's say is a vegetarian and is ingesting a lot of crude fiber, you need to keep that in mind as well. In fact, the patient I saw just before our interview today was that type of a patient. Those kinds of things should be factored into the decision to use fiber.

When we do use fiber, we want to use soluble fiber, typically a tablespoon, and then escalate that maybe up to 2 tablespoons a day. That's about as high as I usually will go. It's not the answer for everybody, but I think it's a very reasonable first-line therapy along with maybe an osmotic over-the-counter laxative for many patients if they've not tried therapies before. By the time they get to you or me or many of our colleagues, they will have already tried these things.

I don't repeat that pattern unless I find out that they didn't take fiber adequately. And that's also not uncommon. You have to ask patients. I tried fiber. Well, how long did you do it? How much did you do? What type of fiber did you use? You'll often find, well, I ate three bowls of bran flakes a day. Well, that's not the right way of doing fiber. You can redirect them and give them a try. It's cheap. It's safe. It may be effective. It may end up causing some more symptoms, but it's certainly worth a try in most patients.

Dr Lacy:
You kind of mentioned maybe adding another agent. Let's think a little bit about osmotic agents, such as polyethylene glycol or magnesium. These are generally pretty safe and effective. Where do you place this in your treatment regimen? Do you have any tips or tricks for our listeners?

Dr Cash:
Yeah, I place these pretty high up. Again, it's for the same reasons. The guidelines for chronic constipation and even irritable bowel syndrome with constipation would echo these comments. These are cheap. They're safe. They've been reasonably well-studied, especially in the case of polyethylene glycol for chronic constipation. What they don't do is they don't seem to help patients with abdominal pain.

If you have somebody who's got overlapping or they've got really more features of irritable bowel syndrome with constipation, and the only major semantic difference there is that those patients have abdominal pain associated with their constipation, then these osmotics aren't likely, at least based on clinical trial data, to improve abdominal pain. But I do often use these. The trick that I recommend would be to do it in conjunction with fiber, and I typically do use polyethylene glycol with that approach.

I use magnesium, liquid magnesium or even pill magnesium, as an adjunctive therapy. Sometimes even as a rescue therapy for some patients. Do be cognizant of those patients with chronic renal insufficiency with regards to magnesium. The nice thing about the polyethylene glycol is it's imminently titrateable. If one cap full is too much, then have a patient titrate it down to half a cap full a day every other day. It's something that they can take control of, and I think that can sometimes be helpful as well.

You want to have them get that baseline fiber in, but they can play with the dose of the polyethylene glycol.

Dr Lacy:
In the last decade or so, a little bit longer, actually about 15 years, there's now a class of agents called secretagogues, and there are three agents approved for use, lubiprostone linaclotide, and plecanatide. Could you just briefly explain why these agents might work, how they work, and is there data to support their use?

Dr Cash:
Sure, no, there absolutely is. All three or FDA approved for chronic constipation, as well as IBS with constipation, and they work by causing secretion of fluid into the GI tract. They work slightly differently. We have two classes within the secretagogue family. Lubiprostone, also known as Amitiza, is a chloride channel activator. It opens up chloride channels in the cells that line the GI tract. That causes chloride to move into the gut. Sodium follows because the body likes to maintain homeostasis.

If you create an electrical gradient by bringing  a negative ion like chloride into the lumen, sodium, a positive ion, wants to follow. Now you've brought in sodium and chloride or salt into the gut lumen. That's an osmotic gradient. The body likes to normalize that. Water flows or fluid flows passively into the gut and gets trapped there or accumulates there. You get a distention of the gut. You solubilize stool, increase water content.

There may even be a secondary effect on peristalsis or contractions, and there may be some benefit with regards to tight junction integrity and even abdominal pain with this agent. The other two agents, linaclotide, also known as Linzess, or plecanatide, also known as Trulance, are what we call guanylate cyclase-C agonists. They bind to this enzyme called guanylate C receptor, and that causes a downstream effect of some neurotransmitters and peptides being generated, which causes more fluid to get secreted into the GI tract as well.

It's a similar mechanism of action, albeit through a different lock and key mechanism. There are some evidence that also these agents can help with abdominal pain. The difference between linaclotide and plecanatide has to do with the avidity with which they bind this receptor and the pH, whether that translates into clinical differences is not entirely clear.

None of these agents have been compared head to head, but all of them are effective therapies for some patients with chronic idiopathic constipation and IBS with constipation. That's been shown in their pivotal trials that led to them being FDA approved. They're all thought of as largely non-absorbed, so they're safe in terms of drug-drug interactions, and their major side effects, as you would imagine, are primarily diarrhea.

Dr Lacy:
Wonderful overview. Thank you. Brooks, let's take somebody in your very busy clinic who failed fiber. [Inaudible 00:21:32] They failed osmotic agents. They actually did them appropriately and failed all three secretagogues. What about a prokinetic agent such as prucalopride? How does that work and is there data to support it?

Dr Cash:
Yeah, that's another... That's our latest addition to our armamentarium. Prucalopride is a prokinetic agent, also known as Motegrity. It's a serotonin type 4 receptor agonist. Essentially it mimics serotonin. It binds to the type 4 receptor, which is localized to the GI tract. It doesn't have a significant amount of binding to other types of serotonin receptors, which is reassuring from a safety standpoint. It basically accelerates transit.

It leads to an increase in stripping or clearing waves, what we call high amplitude propagating contractions. Probably increases secretion of fluid as well and increases the strength of those contractions. There is good evidence from six randomized controlled trials, five of which showed statistically significant benefit with prucalopride versus placebo for patients with chronic constipation. I use this agent quite a bit.

I use the secretagogues quite a bit as well, because we do have a high rate of dissatisfaction or a lack of complete response to the over-the-counter therapies. I think that this agent along with secretagogues are very helpful in our patients with chronic constipation. In that scenario that you mentioned, especially if they fail this agent as well, that's when I start going and looking for pelvic floor dysfunction. I'll bring it back around to that. Don't forget about that condition, especially when patients fail multiple different therapies.

Dr Lacy:
Yeah, that's a great teaching point too, especially a younger patient failed multiple therapies, please don't forget pelvic floor dysfunction. Brooks, as we wrap up here today, you published a really nice article in the American Journal of Gastroenterology in 2020. Some of our GI listeners will know you've dedicated hundreds and hundreds and hundreds of hours over the last decade or so as associate editor. You discussed in that article myths and misconceptions about constipation. Can you highlight a few of these myths that we need to dispel?

Dr Cash:
Sure. Thank you for those kind comments. This is an article that I published with a colleague named Kyle Staller, who's at Harvard, and we basically updated a previous really landmark article by Arnie Wald, Stefan Mueller-Lissner, and Michael Kamm that was published back in 2005. I encourage you to look at both of them. I think theirs is better than ours, but ours was an update on that based on new evidence. We talked a lot about these different myths and misconceptions.

We talked about how stool frequency is not the defining criteria for chronic constipation, that IBS with constipation and chronic constipation are really incredibly distinct. They're not. We talked about the role of colonoscopy. The only things... The different types of fiber. The other myth that we really didn't address, but I would want to put out there is that myth of drinking 10, 15, 20 eight ounce glasses of water a day in terms of combating constipation.

There's a little bit of data in a geriatric, assisted care living type of scenario where that can be helpful. But for the run-of-the-mill ambulatory, otherwise healthy person with chronic idiopathic constipation, or constipation symptoms in general, drinking all that fluid really doesn't affect bowel habits. That's a big myth that really has not been I think adequately debunked. Adequate fluid intake is important. Our bodies are remarkably adept at telling us when to drink and when to hydrate.

Our osmostat that's in our brain is incredibly sensitive. When we need to drink, we drink. Now, obviously there can be some disruptions there and diabetes insipidus, et cetera. But for the most part, loading up on fluid just doesn't do much for chronic constipation. That's the last myth and misconception that I want to really highlight for the audience.

Dr Lacy:
Wonderful. Brooks, this truly has been a wonderful conversation. Thank you. Any last thoughts for our listeners?

Dr Cash:
Well, I want to just thank you for allowing me the opportunity to talk about this topic. I think the things that I would point out to the listeners are, be on the lookout for this, recognize the different subtypes of chronic constipation, recognize how common it is. Somewhere between five and 10% of the population's estimated to suffer from this. Many people suffer in silence. Ask your patients about this. The more knowledge you have about this, the more I think willing they will be to discuss these issues with you.

I think knowing how to evaluate these patients, and then more importantly, how to treat these patients is going to really lead to a much happier and healthier patient population within your clinics. Thanks again, Brian. I really enjoyed talking to you today.

Dr Lacy:
For our listeners, we've just heard from an international expert in the field of gastroenterology and constipation and functional GI disorders, Dr. Brooks Cash, professor of medicine and also associate editor of the American Journal of Gastroenterology. Thank you for tuning in today. We hope you tune in for another Gastroenterology Learning Network Podcast in the future.