Activity Transcript

Joel J. Heidelbaugh, MD, FAAFP, FACG: Hi, I'm Dr Joel Heidelbaugh. I'm a clinical professor in the Department of Family Medicine at the University of Michigan Medical School in Ann Arbor, Michigan, and welcome to this program titled, “Practice Pearls for Managing Opioid-Induced Constipation.” Joining me today is my colleague, Dr Leah Sera, program co-director in graduate studies in medical cannabis science and therapeutics, and associate professor in the Department of Practice, Sciences, and Health Outcomes Research at the University of Maryland School of Pharmacy. Welcome, Leah.

Leah Sera, PharmD, MA, BCPS: Thank you.

Dr Heidelbaugh: We're going to be engaging in what's called a quickfire discussion today focusing on the management of opioid-induced constipation (OIC). There will be a topic that is introduced, and within the bounds of about a minute or 2 minutes, Dr Sera and I are going to quickly go through some really important pearls and questions that need to be considered when we're taking care of these patients.

What do we already know about OIC? We know it's a major adverse event associated with the use of opioids. We know that it's been reported to develop in approximately 40% to even 80% of patients taking opioids, and it can be especially problematic with prolonged or long-term use of opioid therapy, generally defined as therapy lasting longer than 3 months. So, what's the problem? Well, there are multiple problems, and one of them is the failure to ask about patient's bowel habits. Another problem ends up being both in the inpatient and outpatient settings we encounter OIC frequently, and patients are sometimes admitted for a further workup of chronic constipation and can spend days in the inpatient setting for, as we call, clean out. What's important here is not only the treatment of OIC, but certainly strategies toward appropriate prevention.

Dr Sera, before we discuss the management of OIC, can you briefly explain how opioids actually cause constipation?

Dr Sera: Sure. Well, we know that opioids alleviate pain by activating mu opioid receptors in the central nervous system. However, opioids also stimulate mu opioid receptors in the enteric nervous system in the gut, and this causes reduced gastric emptying and increased intestinal water absorption and sphincter tone, and essentially this means that the movement of contents through the gastrointestinal (GI) tract is slowed, and because the contents of the gut are spending more time in the GI tract, more water is being absorbed, leading to harder, drier stools, plus increased sphincter tone can make it harder to have a bowel movement. And unlike other side effects with opioids, typically patients don't become tolerant to the effects of constipation. As long as they're taking opioids, they'll usually continue to experience these effects, and that's different from other opioid side effects like somnolence or nausea.

Now, the Rome IV criteria categorizes disorders of chronic constipation into 4 subtypes including OIC. Dr Heidelbaugh, can you review what these diagnostic criteria are?

Dr Heidelbaugh: Sure, and I think going forward it's important that practitioners are aware of these criteria because it's going to not only aid in diagnosis but appropriate treatment paradigms. So, for the diagnostic criteria of OIC, we're looking for new or worsening symptoms of constipation when initiating, changing, or increasing opioid therapy that needs to include 2 or more of the following conditions, and that's straining during more than about 25% of defecation, lumpy or hard stools as measured on the Bristol Stool Form Scale category 1 or 2 and more than a quarter of defecations. The third would be a sensation of incomplete evacuation of more than a quarter of defecations, sensation of anorectal obstruction or blockage of more than a quarter of defecations, any manual maneuvers to facilitate more than a quarter of the defecations, including digital evacuation or pelvic floor support, and the last one is fewer than 3 spontaneous bowel movements per week. The second major criterion category really has to do with loose stools being rarely present without the use of laxatives.

Dr Sera: Recently, the American Gastroenterological Association (AGA) issued guidelines for managing OIC. What are their recommendations for the initial management of OIC?

Dr Heidelbaugh: Sure, and I think these are important guidelines for everyone to review, especially for those of us in primary care, and these guidelines actually start with some very simple provisions, initially ensuring that the indication for opioid therapy is appropriate, and understanding our scope of practice, and how we may or may not engage with chronic pain management. It's always appropriate to ensure the indication is not only appropriate but being closely monitored. The second important tenet is really nonpharmacologic measures and that's increasing fluid and fiber intake as well as physical activity. Now, fluid and fiber intake can help to a point, but ultimately there is some good evidence behind physical activity in terms of increasing spontaneous bowel movements, and then the last point is to evaluate the patient's opioid regimen and to always consider adjunctive analgesic agents or other options that may facilitate dosage reduction of the opioid therapy.

Dr Sera, if nonpharmacologic measures don't work, and it's been determined that the patient must continue to take the opioid medications for the treatment of chronic pain, what do you consider next?

Dr Sera: Well, there is a strong AGA recommendation for over-the-counter (OTC) laxatives. They are inexpensive. They're easily accessible and readily available, and they're generally well tolerated by patients, and so the panel favors the use of a combination of at least 2 different types of laxatives, so laxatives with different mechanisms of action, and utilizing a scheduled use of laxatives, not just as-needed, PRN laxatives before moving to an alternative therapy for OIC, and an example of such a regimen would be something like daily use of an osmotic laxative in combination with a stimulant laxative at least 2 to 3 times a week.

Dr Heidelbaugh: Absolutely, and I think that's very important for us to understand. What are the recommended traditional laxatives for OIC, and what are their mechanisms of action?

Dr Sera: There are several different classes of OTC laxatives. First, there are osmotic laxatives. These are compounds that draw water into the intestinal lumen, and what that does is it softens the stool, and it causes bowel distension stimulating peristalsis. Patients with renal insufficiency may be more likely to experience some electrolyte imbalances with some of these preparations, so that's one thing to consider. Another class of laxatives are stimulant laxatives. These stimulate peristalsis directly by acting on intestinal smooth muscle. That also increases the water content by altering intestinal fluid and electrolyte secretion. Some things to consider here are that they can be dangerous if patients have an intestinal obstruction, so they shouldn't be used if the patient has acute or undiagnosed abdominal pain. Next, there are stool softeners. These act by lowering surface tension, allowing water and fat to penetrate and soften stool, and then finally, there is mineral oil, which lubricates the lining of the gut to facilitate defecation. Now, many of these medications are available as both oral and rectal formulations, with the oral formulations generally having an onset of action of a few hours to a few days, and the rectal formulations having a much faster onset of action usually within minutes.

Dr Heidelbaugh: Great. And what about bulk forming agents? Would those be helpful for this patient population?

Dr Sera: That's a great question. It's very common for patients with constipation to pick up bulk forming agents like psyllium at the pharmacy. These work by increasing fecal bulk, distending the colon, and stimulating peristalsis. However, they shouldn't be used in OIC. They won't work because opioids prevent peristalsis of fiber increased bulk. They can cause distension, and they can increase the risk of obstruction, which worsens OIC.

Are there any key studies that have evaluated the use of these traditional laxatives recommended by the AGA in the treatment of OIC?

Dr Heidelbaugh: There are, and the AGA guideline took into consideration many of these studies and their recommendations. Starting with the Friedman study in 1997, which was a randomized controlled clinical trial, it looked at the use of osmotic laxatives, polyethylene glycol (PEG) and lactulose vs placebo, and ultimately what the study found was there was a significant improvement in stool consistency and frequency with both of the laxatives vs the placebo, but no significant differences between PEG and the lactulose regimens, and I think that's important to know. Fast-forward about a decade to 2006, you look at the Twycross R.G. and colleagues study. This was an open-label trial. They looked at the efficacy of stimulant laxative sodium picosulfate, and ultimately, they found that about 75% of patients in the laxative treatment group experienced a satisfactory bowel movement.

About 6 years later in 2012, another open-label study done by Wirz S. and colleagues compared sodium picosulfate, PEG, and lactulose, and they found that all 3 agents resulted in improvement in symptomatic constipation, but PEG and sodium picosulfate were more efficacious than the lactulose.

In summary, again, the AGA guidelines on OIC really did a deep dive into the current literature, and these particular studies that we've just highlighted I think did a great job at giving recommendations on common OTC laxatives and laxative preparations. I think what's important here is to understand the take-home points. Dr Sera just mentioned the issue with fiber. Fiber does not always mean more bowel movements, and sometimes it can also cause complications. And I think in summary for these particular trials, when they took a look at osmotic laxatives, PEG, lactulose, sodium picosulfate, and compared them with placebo, the reality is that all of them can improve constipation, and most of them are more efficacious than the lactulose.

Dr Sera: With all of the options that you just talked about, lots of different potentially effective options, how do you choose a treatment plan for a given patient?

Dr Heidelbaugh: Sure. Well, I think as most of us know in primary care, I think these visits can really be a great opportunity for educating patients. It needs to start with learning what a patient has tried, what's worked, what has not worked, and just working through exactly what we just taught, talking about mechanisms of actions and when these medications might be most efficacious for an individual patient. What are your thoughts?

Dr Sera: I agree. I think that telling patients what to expect and starting when patients are ideally started on opioids, so that they're aware that this is an expected side effect, and then talking about the treatment plan, so that they can be a part of it and understand why we're making the decisions about one laxative over another, I think is important. How do you handle that kind of shared decision making when you're talking to a patient?

Dr Heidelbaugh: Sure. Well, again, I try to find out what might have worked and what might not have worked. I'll also ask if a patient has had any adverse effects to anything that they may have tried. As you pointed out before, I think it's about specific education, but I think it's also about understanding a patient's specific symptoms. You also made a really important point before that I think can't go understated, and that is to get at this early. That comes in with counseling, but for shared decision making, coming up with a regimen that's going to work best for the patient early on in the treatment, so that they're not getting behind.

Dr Sera: Absolutely.

Dr Heidelbaugh: So, when do you consider prescription laxatives in these patients?

Dr Sera: I think it's important to try lifestyle modifications, diet changes, as we've discussed before, and different OTC laxatives before we consider prescription products, and one thing that providers should ensure, as we kind of touched on a little bit ago, is that patients are using laxatives from multiple classes, so we're getting at this from different mechanisms of action, and that the doses are appropriately titrated before we determine that a specific medication or class of medications is ineffective, and again, before we turn to expensive prescription treatments for OIC.

Dr Heidelbaugh: Is it common for healthcare team members to not address the topic of OIC unless a patient or caregiver reports constipation symptoms? I know pharmacists play a very important role in speaking to these patients by proactively inquiring about the development of OIC, but specifically, do you have any tips or strategies for how to counsel patients and bring this to the forefront of the discussion?

Dr Sera: Absolutely. I think that it should be on the pharmacist's mind or the provider's mind when you see a patient who is on opioids, and from a pharmacist's standpoint or a community pharmacist's standpoint, if you see a new prescription for an opioid, ideally, you're counseling the patient at the outset on the likelihood of constipation or the risk of OIC and making recommendations. Now, ideally, patients who are starting opioids will also be starting on laxatives at the same time. We've already mentioned a few times that OIC is a predictable side effect. We know it's likely to happen, so treating it prophylactically can prevent it from becoming a problem in the first place, so that they don't have to visit you in the hospital for a clean out. Prevention really is key here.

Dr Heidelbaugh: Absolutely agree not only for patients to bring it to our attention, but for us and our care teams to bring it to the attention of the patients and the caregivers. Like you said, these 2 issues need to go hand in hand really to prevent bad outcomes, but also to prevent hospitalizations.

Dr Sera: We've both talked about the importance of counseling patients about constipation, but sometimes providers may not know what to ask or how to start that conversation. Some patients may be embarrassed to talk about their bowel movements; are there any tools that can help providers ask patients or start this conversation about OIC?

Dr Heidelbaugh: Sure. I think there are several. I think good medicine at the beginning of every visit, and certainly medication review and medication reconciliation go hand in hand with talking about potential adverse effects. So obviously reviewing that at every encounter and every visit I think is important. One tool I'll commonly use, and it's easy to access because most of us will have a smartphone, or smart tool, or even a computer where we're seeing patients is it's easy enough to pull up the Bristol Stool Scale. I think it's interactive. It makes sense for everyone, and reluctant patients who may not want to talk about their bowel habits can be easily engaged with a schematic like this where they can easily point out, "Yes, this is common for me," or where they live on that stool scale. Have you found any tools that help you and help your practice?

Dr Sera: I think that there are certain tools, as you said, like the Bristol Stool Scale, but I've also found that just being matter of fact and upfront about asking patients about their bowel movements usually is pretty effective, and sometimes even especially if you're maybe a new practitioner or you haven't had this opportunity to talk to patients, just sort of practicing asking these questions can help you feel more comfortable bringing these topics up. And as long as you, the provider, are comfortable, the patient is going to be comfortable too, because you're there to help them.

Dr Heidelbaugh: Well, thank you very much, Dr Sera. This was a very robust discussion, and just to highlight a few takeaway points, one would be it's certainly imperative to have this dialogue with patients on chronic opioids, understanding that constipation is a frequent and, as you said, often expected side effect. It's imperative to have that discussion and ask about bowel habits on a regular basis. Two, it's about patient education to find out if they're using any products or what their strategies are for adequate bowel movements, coupled with talking about what options are available OTC and how these various medications work. Certainly, lifestyle factors, appropriate diet, appropriate hydration, and appropriate exercise are also important. And then the final key takeaway would be really just to understand that there are prescription medications available for refractory cases, and this is a great opportunity to engage with the AGA guidelines. This is also a great opportunity to engage with our greater team network.

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This transcript has not been copyedited.