Gut Check: Kyle Staller, MD, on Refractory Constipation
The newest Gut Check podcast features Drs Brian Lacy and Kyle Staller discussing the types, causes, and treatments for both occasional and chronic constipation.
Brian Lacy, MD, is a professor of medicine at Mayo Clinic-Florida in Jacksonville, Florida. Kyle Staller, MD, is director of the Gastrointestinal Motility Laboratory at Massachusetts General Hospital in Boston.
TRANSCRIPT:
Dr Lacy:
Welcome to Gut Check, 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 am absolutely delighted to be speaking today to Dr. Kyle Staller, associate professor of medicine and director of the Gastrointestinal Motility Lab at Massachusetts General Hospital in Boston, Massachusetts. Our topic today is one that is of great interest to providers of every specialty—refractory constipation. So Dr. Stoller, thank you for joining this podcast today. Let's begin simply in order to set the stage for our listeners. How common are symptoms of constipation?
Dr Staller:
Well, first, thank you so much for having me. It's an honor to be here. And to answer your question, I mean constipation is super common. It's one of the most common reasons why people come to a gastroenterologist. It's a common reason for people to show up in the emergency room in primary care and elsewhere. And generally we expect chronic constipation to affect about 8 to 12% of the population. So this is something we're all going to see.
Dr Lacy:
So speaking of constipation, a lot of clinicians categorize constipation into either occasional or chronic in nature, and as you mentioned, chronic. Why is this even important?
Dr Staller:
Well, I think it's important to realize that chronic constipation, which really has a specific definition laid out by the Rome Foundation, the Rome group, is that chronic symptoms of constipation, the type of symptoms that all of us are very familiar with that have started at least six months ago, have been occurring for at least three months. These are the kind of symptoms, these are the kind of patients that often show up to see people like yourself and me. These are people who've been chronically affected and a lot of the literature, a lot of the drugs, medications, even devices, are really geared or targeted toward this group. On the other hand, occasional constipation. This is really something that's been around forever in the sense that so many people have experienced it and their first encounter with it is when they walk down the pharmacy hall or the aisle and find something that they're looking for to treat their symptoms. Recently there's been some consensus documents that have come up that define this and really define it as sort of the usual constipation symptoms without any alarm symptoms. So things like blood weight loss, et cetera, that really are bad enough that you're going to seek care and that might be going to a gastroenterologist, but it might be just walking down the aisle of your local pharmacy and picking something out to try and get you feeling better.
Dr Lacy:
And you're right, that aisle is a long aisle in your pharmacy highlighting how common and how burdensome this problem is. We're talking about constipation in a big global sense, but for our listeners who may not see these patients every day or may not suffer from constipation, what are some of the most common causes of chronic constipation?
Dr Staller:
I think for many patients that we see on the gastroenterology side, the most common cause is we don't know, right? It's chronic idiopathic constipation or CIC where there's probably some innate neuromuscular dysfunction in the way that the GI tract, the colon specifically moves things from one end to the other. But things that are often overlooked are chronic medical conditions. For example, neurologic disorders, endocrine disorders that may change the way the gut work. And then something that is really often missed is iatrogenic so many times where prescribing people, medications, opioids for pain, calcium channel blockers for high blood pressure, even antacids, right? Calcium-based antacids can be quite constipating. And so many patients don't realize that the constipation they're experiencing is actually because we're treating something else.
Dr Lacy:
Such a good point. Always remember to look at the medication list and dig through the chart a little bit and ask about supplements and other things. So we know, Kyle, that a lot of patients with chronic constipation respond to fiber supplements or over the counter agents or prescription medications, but there's definitely a group of patients who seem to have refractory symptoms of constipation. And when you think about refractory constipation, how common of a problem is this and is this more of a diagnostic issue in terms of the refractory symptoms or is this more of a treatment failure issue?
Dr Staller:
It's a great question. And in terms of how common it is, we don't know. And one of the reasons is how do we define refractory constipation, right? This is very variable. The AGA in conjunction, and we're part of this group, is issuing a clinical practice update on refractory constipation, and we defined refractory constipation as infrequent or unsatisfactory bowel habits with or without abdominal pain, despite an adequate trial of lifestyle, dietary, medical, and or pelvic floor biofeedback therapy in adults who meet criteria for chronic constipation—hose are those criteria that I mentioned before—or IBS with constipation. So these patients are out there, but to answer the second part of your question in terms of how do we really define it or what are the things that are driving this part of it, I think is one of the most important things is perception, right?
What do we mean by refractory, right? Is this a patient who has a partial response to treatment or someone who has no response to treatment at all? Is this someone who has not really tried multiple treatments, and there are multiple over the counter FDA-approved treatments. Device treatments? Is it someone who has failed to evaluate some other cause of constipation, for example, a rectal evacuation disorder or pelvic floor dysfunction? And finally, I think one of the most important things is what do they mean by their constipated? I think it's important to kind of give normalizing data to our patients to know that what is a normal frequency of bowel movements anywhere from 3 times a day to 3 times a week and normal consistency using the Bristol stool scale, which is really a surrogate marker of colonic transit, is normally in the middle between a Bristol type 2 and a Bristol type 6, but really between 3 and 5, all clustering around that perfectly normal stool, which is sort of that smooth soft snake-like projection. So I think kind of defining what a patient means by being unsatisfied or dissatisfied and then doing a reality check to make sure that that fits in with what we think medically is someone who is constipated or not. Then kind of doing some additional diagnostics potentially to figure out if this refractory constipation is really something like pelvic floor dysfunction that has not been yet recognized.
Dr Lacy:
Wow. So many amazing teaching points there for our listeners, you may want to just rewind a little bit, listen to that again because there's so much buried in there, which is just great. And Kyle, looking forward to that nice clinical practice update, that CPU, which will shed light on this topic. So this is a perfect segue. You kind of mentioned symptoms and testing. So how do you ensure that an accurate diagnosis has been made for refractory constipation? Is specialized testing necessary for these patients?
Dr Staller:
I think specialized testing is necessary and while the colonic transit test, and you can do that in a variety of ways—either with radio pick markers and an x-ray or some soon to be available wireless motility capsules of a variety of form—those can be very helpful. But one of the biggest drivers of patients that I see that are refractory are people who have not had a pelvic floor disorder or rectal evacuation disorder excluded. So in that case, people with anal rectal, who undergo anal rectal manometry, about 40% of them are going to have dyssynergic defecation or impaired defecation. Why is that important? Well, when that happens, it's difficult to get stool out, right? It's difficult to defecate and that probably causes a reflexive slowing of the colon and thus people become progressively more constipated. So despite patients trying lots of different medications, sometimes the problem is not that they're missing a certain type of medication, but they really would benefit from pelvic floor or biofeedback or physical therapy to correct a defecation disorder.
Dr Lacy:
So great teaching point, a group of patients who are frequently overlooked, persistent symptoms, failing medications. Think about the pelvic floor and thinking again about some of these patients with refractory constipation and refractory to the number either over-the-counter agents or prescription medications, why do you think they're refractory? Do you think it's a drug resistant state or is there a receptor issue or what do you think is going on?
Dr Staller:
Well, I think at the end of the day that chronic constipation is probably a heterogeneous condition, which means although many people are idiopathic, right, we've excluded the medications, we've excluded a medical problem, and now we've excluded let's say pelvic floor dysfunction. Many patients, their colon just doesn't work well. And it may be for different reasons and unfortunately, fortunately we have, I should say fortunately, we have a lot of FDA-approved treatments out there. Unfortunately, none of them have been compared head to head. And so one patient may respond to a certain mechanism as with a certain drug like a secretagogue, another one may respond to a different mechanism like a prokinetic, other patients may respond to over the counter therapies. So sometimes it's a little bit of a trial and error process to find the right mechanism of action for the right patient. And unfortunately, symptoms really don't serve as a good guide.
In fact, I would just reiterate for the listeners that in symptoms of pelvic floor dysfunction, right, you'd think straining, a sense of incomplete evacuation, feeling a sense of anal rectal blockage, would tell you oh, I need to think about pelvic floor dysfunction. In fact, those are just common symptoms that people who are constipated experience. So even those types of symptoms don't tell us who's who. And so again, getting back to the pharmacotherapy, the medical treatments, a lot of times this is just something where we have to do trial and error, sometimes maybe even combinations of medications to find the right medication for the right patient.
Dr Lacy:
Kyle, wonderful. Thank you. I like all of that and I think especially the teaching point about symptoms really don't predict what's going on and also probably don't really predict response to therapy. So let's take that patient who you see, and you've kind of alluded to this, but let's just tease it down a little bit. You see them and they've tried the over-the-counter agents of fiber and osmotic agents such as polyethylene glycol or magnesium. You mentioned the big categories of drugs like secretagogues, but could you just list the 4 or 5 prescription therapies that you might employ for some of these patients with persistent symptoms?
Dr Staller:
Yeah, I think many patients will see a secretagogue as one of the first prescription agents. They are sort of some of the agents that have been around the longest. Lubiprostone was one of the first drugs that was approved for chronic idiopathic constipation followed by Linaclotide ide. And then the so-called retainagogue, which is tenapanor, which is really approved only for IBS-C. But many of us may use these drugs interchangeably for both conditions because it's really a spectrum of disease and patients may fall into one one day and one the other, then the other category. So all those drugs essentially in one way or another allow more ions to stay in the lumen of the GI tract that draws water in. That creates secondary peristalsis. On the other hand, we have prokinetics; right now the only one on the US market is prucalopride and prucalopride directly stimulates the mechanisms of peristalsis that cause contractions.
And so we like to wax poetic about mechanisms and think about these various agents. But as you alluded to, and as I said before, we don't really know which one is going to work for which patient. And even within the secretagogue, for example, category, we have linaclotide and lactide, which in some ways have similar mechanisms of action. I've certainly seen many cases where a patient will respond to one and not another. I do tend to switch from one agent to another mechanism of action if one is not working. But I'm not afraid to go back even to a similar mechanism of action because I just know patients are so variable.
Dr Lacy:
Yeah, it would be nice to say if you're 40 and you're this weight and you have this symptom, you're going to respond to drug A but not B, but we're not quite there yet. So shifting gears a little bit, sacral nerve stimulation is used to treat some patients with fecal incontinence with some benefits. Many patients ask, is there any role for sacral nerve stimulation in the treatment of refractory constipation?
Dr Staller:
There was some sort of smaller data pilot data that suggested there would be a role in. The idea is that sacral nerve stimulation, either by modulating the autonomic nervous system or by other sort of handwaving type mechanisms might improve constipation. But unfortunately when subjected to more rigorous trials and then when we really look, there was a Cochrane analysis that really looked at this overall, it doesn't seem to have a significant benefit over placebo and mechanistically, we don't actually see a change in transit time either, let alone symptoms or quality of life. So I think sacral nerve stimulation, where it certainly has a role in urinary, in fecal incontinence, does not seem to have a role in chronic constipation.
Dr Lacy:
Right? Let's not use things that don't work. We know some patients use enemas routinely for constipation and pelvic floor issues, but also some providers use what are called antegrade enemas, place a little irrigating device in the cecum in the beginning of the colon and then irrigate the colon from the proximal beginning of the colon to the end of the colon. What about this? Is there a role for this type of treatment in patients with refractory constipation?
Dr Staller:
Yeah, I'm glad you asked about it, Brian, because I think this is an interesting evolution of my own career. I know as a new attending, I was really enthusiastic about using this type of device to really prevent people from undergoing colectomy for constipation. And so I worked with some pediatric GI folks, pediatric surgeons, to start doing this in an adult population at our facility. And although we were initially hopeful, we ended up finding that adults and kids are not the same. So just as a background kids, actually, this has been used in pediatrics for a long time and has been very successful for some kids and avoids colectomy and major surgery in adults. What we found is that although in some ways it would delay the eventual colectomy for patients who truly needed them, many times we were flushing large amounts of some type of laxative, maybe polyethylene glycol, water, mineral oil, you name it into the colon, and then it would just sit there and these patients wouldn't still have satisfactory bowel habits.
And at the same time, the colon is not the stomach. So putting a gastrostomy tube, we all know how well that works, but putting a cecostomy or some sort of hole in the right colon often leads to abdominal pain, abdominal wall pain, and then leakage. And unfortunately this is leakage of stool, which of course is very distressing to patients. So what we found is although we have a few patients who are very enthusiastic users of their antegrade enemas and their cecostomy tubes, many patients ultimately went on to find that they were not effective and ended up having a completion surgery and either an ileostomy or a colectomy with an ileal rectal anastomosis. So I think if anything, it buys us time, especially maybe where we're a little bit concerned that doing a more extreme surgery may not be the answer, but it's not the panacea that I had initially hoped and I've moved away from it to be honest.
Dr Lacy:
Thank you. Very helpful. And a nice point too about that we can't compare data from the pediatric population to a 40 or 50-year-old. So the vibrating capsule is a new device that has been shown to improve symptoms of constipation in some patients. How does this capsule work, and is this a viable treatment option for these patients with refractory symptoms?
Dr Staller:
The idea with the vibrating capsule is just as it sounds, a capsule that vibrates at a certain frequency and certain timing to correspond with certain circadian rhythms of the GI tract. And so the patient takes it for 5 out of 7 days a week, they swallow a capsule, they do not have to retrieve it, so they just use a new one for each time and then it vibrates. And the idea is that the mechanical vibration would stimulate these circadian rhythms. And in a large phase 3 trial, it was found that this was effective in improving the amount of what we call complete spontaneous bowel movements. This is one of the endpoints that we often hear about in constipation, where someone has a bowel movement without any help and they feel completely empty after that bowel movement or a complete evacuation.
And so what they did find is that this worked in an 8-week trial. It led to an improved number of complete spontaneous bowel movements. I would say that this is a new tool in our arsenal. I think some of the issues that I would think about is one, insurance coverage is not, I would say is absent. Patients are paying out of the pocket for most part; two, because this is a device and not a drug, the level of data required for approval is less than pharmacotherapy. And so what that means is this was an 8-week trial as opposed to a 12-week trial, which we've seen for all the medications. And the outcome is a little bit less strict as well. That's not to say that it may not work as well as any medications. I would just say we don't have the level of evidence to say that it works as well as any of them. But that old caveat that I mentioned before is that different device slash drug for different people may work. And so now we have yet another option for our patients, which is a good thing. But now we have even more confusion about which one is going to be best for which patient, which unfortunately none of us know yet.
Dr Lacy:
Wait a minute, Kyle, you're supposed to be helping to educate and elucidate us. Not making it more confusing! But you're right. And again, you made the point earlier, there are no head-to-head comparisons. So it seems like a reasonable option for patients, but we don't have head-to-head data comparing it to other medications.
So speaking about medications, you probably see a lot of the same patients I do. When patients come in, they have persistent symptoms, refractory symptoms, they've tried multiple medications for their constipation symptoms, but still are struggling and they ask about surgery. So what's the role for surgery in patients with refractory constipation and how do you choose the patient who is most likely to benefit from this?
Dr Staller:
Yeah, this is an area that's really fascinating to me because the literature is really rife with examples of patients who have not done well after surgery for constipation. And we know that, for example, that there are a lot of perioperative complications. We know that patients have a lot of small bowel obstruction. There was actually a data series using I believe, Medicare data that showed that many patients who underwent surgery for constipation actually had an increased rate of health care utilization after surgery compared to before surgery. So clearly not every patient is benefiting from surgery, but there is really a subset that I'm sure you've seen, Brian, and I know I've seen as well, who do really well with surgery. So how do we pick them out?
Well, I think there's kind of a stepwise approach that we think about it. One, we think about all of what we talked about before, which is patients really should have tried and failed all of the available over the counter and FDA-approved prescription agents for constipation that they can get ahold of. Two, we need to make sure that they have ruled out pelvic floor dysfunction, dyssynergic defecation, and if it's there, to have it treated. And then three, we really want to confirm that they have slow transit constipation because constipation is heterogeneous and what surgery is going to do, it's going to remove the colon and it's going to make people have more frequent bowel movements. But if the problem, for example, primarily was bloating or abdominal pain and not infrequent or hard stools, then that patient may not benefit from surgery.
Now, after we've gotten through that first layer where we say they have slow transit constipation, we've done all the specialized testing that we need to, now we want to say, are there abnormalities elsewhere in the GI tract? And I always say, when the colon goes down, so goes the rest, which means it's not uncommon to have small bowel dysmotility or dysmotility in patients who have very severe colonic dysmotility. And you can imagine if their small bowel symptoms are still there, if we take out the colon, then we've just subjected them to a major surgery, but we haven't necessarily fixed the problem. And then finally, we know that there is a high level of psychiatric psychological comorbidity, including things like sexual abuse and trauma, in patients who have slow transit constipation. So even though physiologically we know these patients have slow transit, it's probably also true that these patients have complex psychosocial factors that play as well. And so if these issues have not been addressed, then we are more likely to see failure in these patients who undergo surgery.
So there really are a lot of considerations, and I almost think of our evaluation for someone getting surgery for constipation, like an evaluation of a patient who's getting an organ transplant. We need them to jump through the hoops because we know that this is a surgery that doesn't work for everyone, and we want to make sure that this is really a multidisciplinary discussion among GI, colorectal surgery, pelvic floor physical therapists, and even psychology. And we have all our patients see a psychologist before they go to surgery to make sure we send the right person to the operating room.
Dr Lacy:
Kyle, so many amazing teaching points. There are 6 major topics. Thank you for going through that so carefully. And I think if I were to summarize that great explanation from you, I would just say approach these patients carefully, logically, and thoughtfully.
So Kyle, this really has been a wonderful discussion. Thank you so very much looking forward to that great CPU publication. Thanks for spearheading that. Any last comments for our listeners?
Dr Staller:
No, I would say that one, thanks so much for having me. But two, when it comes to surgery, I think it's the patients that are often demanding the most care may be the ones that are the least good candidates, right? The least appropriate candidates for surgery. So be very cautious.
Dr Lacy:
Wonderful. Great. So Kyle, again, thank you for lending your expertise on this important topic to our listeners on Apple and Spotify and other streaming networks. I'm Brian Lacy, a professor of medicine at the Mayo Clinic in Jacksonville, Florida. You have been listening to GutCheck, a podcast from the Gastroenterology Learning Network. Our guest today was Dr. Kyle Staller. I hope you found this just as enjoyable as I did, and I look forward to having you join us for future GutCheck podcasts. Stay well.
