All right, good morning, good morning everybody. Good to, I want to echo the point made by Richard earlier that it's great to be back in person after three long years to SCCM, good to see some familiar faces here as well as some new ones. And this will be, I guess, an appropriate topic to have right before lunchtime, because we're talking about constipation and preventative bowel regimens. And as a pharmacist, and hopefully most if not all of the pharmacists in the room can attest to this, bowel prevention and healthy gut motility is a team-based effort, but often our pharmacists on the team, whether on rounds or throughout the rest of the day on our follow-ups, we play a really important role in ensuring that the appropriate patients have bowel regimens on board. But at the same time, the focus of this session, and I do not have any conflicts to disclose, the focus of this session will be more on those, like the philosophical question of should every patient in the ICU be put on a preventative bowel regimen? Or are there more direct criteria that indicate who should have a bowel regimen? And we know for sure, despite these medicines being the most, or among the most commonly prescribed in our ICU patients, we know they have a role in opioid-related constipation, so we're going to chuck that out the window for the next 15 minutes and try to take more of that holistic approach of outside of opioid-related constipation, is there a role for preventative bowel regimens? And just as a summary here, most of the folks in the room should have a very good understanding of these classes, pharmacologic classes of bowel regimens medications. They run the gamut of how they work and their mechanisms of action, both from softening the stool to stimulating or through osmosis of electrolyte movement through the GI tract, helping to expel feces and other fecal matter from our patients' bodies, and that they have a very important role in promoting a healthy overall ICU patient. And we can also try to target our bowel prevention efforts based on what type of effect we want to see. So we know, we're looking first at the bottom row here, that if we want to have more of an immediate effect within one to six hours, it is going to produce a more watery consistency to the stool because we are expelling those contents and a lot of water that goes with the electrolytes using our stimulant and osmotic diuretics, I'm sorry, our osmotic agents. And if we want a little bit more of a semi-solid or a formed consistency to the stool, we'll have to allow more time for those electrolytes and water movement to change in the bowel, and that will be with also our stimulants, but some of our bulk and emollient laxatives. And now kind of putting this into perspective of the case for bowel regimens, this table here on your slides shows a logistic regression for some significant predictors of bowel movements from a study published in 2006, and showing that significant predictors were, as we know, patients having, or as we would expect, patients with stimulant or osmotic laxative use, those patients were most likely to have a bowel movement within a period of time, as well as morphine equivalents. If patients who were on opioids, if those opioid doses were converted to morphine equivalents, the higher amount of morphine equivalents per hour, per day, that is going to decrease the likelihood of a bowel movement, unless if a patient is on a preventative bowel regimen. So again, we know the evidence for opioid-related constipation, and we're going to chuck that out the window, but what is the overall recommendation, and should we change our practice? Okay, based on this study alone, there can be an argument that we should provide regular stimulant or osmotic laxative use to our ICU patients, but again, trying to separate whether that's due to the opioid nature or the high opioid use in our ICUs, or is it an overall non-opioid-related fact? In the case for bowel regimens, this is often considered a lower priority concern, if we're thinking about the acuity of items and conditions that we have to treat and manage in the ICU in the average patient. More often than not, bowel care is going to be a little bit on the middle to lower end of the spectrum of what we need to prioritize. But we do know that there are adverse consequences associated with patients not having regular bowel movements and then developing constipation. So just to highlight a few examples, no bowel regimen, this can lead to our patients developing abdominal pain and distension, vomiting, dehydration, altered mental status, of course constipation, and in the worst cases, obstruction and perforation of the gut. And this can lead, looking just at constipation, to our patients experiencing feeding intolerance, higher time on the mechanical ventilators, delirium due to this confusion about not having regular bowel movements may be related to not eating on a normal schedule and the other interventions that are happening in the ICU, which can increase our ICU and hospital length of stay. And several factors that contribute to the development of constipation in the ICU are listed here on this slide. We won't go over all of them, but they shouldn't be surprising to anyone in the room. Obviously a previous history of a GI condition or obstruction, perforation, constipation. Use of chronic laxatives can also develop or cause our patients to develop constipation in an acute care setting. Certain bowel conditions, dehydration. The immobility that is often seen in our ICU patients, especially earlier on in their care as we're trying to stabilize them. And the one that I'm sure surprises nobody here, medications. And several medications that have been implicated, the big green box at the top showing our opioid analgesics as the most likely causative agents for constipation in the ICU and outside of the ICU. But some other ones to highlight to make sure we don't forget the potential for bowel conditions or adverse bowel effects in some of our patients in the ICU include anticholinergics, due to slowing down that cholinergic drive to keep GI motility going. Antacids and iron that can directly influence and cause constipation. Kaexolate because of its resin and cation exchange mechanism can lead to constipation and we don't use it in those patients who have already an existing obstruction or risk for obstruction. Diuretics due to loss of water and certain key electrolytes. And our neuromuscular blocking agents because they are paralytic agents, including within the gut. So now I want to switch gears a little bit. And this is where the talk is going to take a little bit of a philosophical turn. Because interestingly enough, when trying to prepare for this session, I was looking at that evidence outside of the opioid world, the opioid-induced constipation world. And trying to see what evidence exists for general bowel prep or bowel prevention regimens. And most of the published literature comes from our nursing colleagues, especially this group led by Serena Knowles out of Australia. And the first study that we're highlighting here from 2015 is a pre-post-survey-based study of nurses and physicians within three different ICUs in this health system. And the three ICUs were a cardiothoracic ICU, a more medical-surgical ICU, and then a private ICU that had predominantly more surgical patients. So each of them have their own, you would think, increased indication to have patients put on bowel prevention regimens, especially because many of those patients are post-operative. And these teams within the different ICUs were collaborative in nature. So it was, of course, our perceptions of our nursing and physician colleagues, but also pharmacy and nutrition were involved in the development of the survey that was issued to the nurses and physicians. And the survey was a targeted, multi-step process that was assessed to develop implementation of these bowel management protocols into practice across these three ICUs. So the teams across the three ICUs were issued the survey. And the survey, as you can see, was pretty extensive and looked at several different domains focused on the behavioral aspect of how bowel management protocols are perceived. And interestingly, this survey was developed and validated using the theory of planned behavior that more or less tries to put across that a behavior has to be, for you to influence behavior, you have to understand the motivations and the perceptions of the individuals toward that behavior, and then try to assess the controllability, or how much control an individual perceives they have over the outcome that they're trying to achieve. So in this case, bowel management, how important is it perceived by the physicians and nurses, how important of a behavior it is relative to everything else happening in these patients, and how much control, based on the understanding they have of the medications and which patients need bowel management medications, how much control do the physicians and nurses feel they have to put the proper patients on these medications and promote healthy bowel movements among the patients. And what they found was that despite a significant increase in the overall knowledge of the medications that can induce constipation and which medications can be prescribed to try to prevent or manage constipation and general overall bowel management itself, there wasn't a corresponding significant change in behavioral intentions across the three ICUs. So although there was this increased knowledge and awareness of what medications can produce constipation, how we can treat constipation or prevent constipation, there wasn't that corresponding effect seen in the behavioral intention to change practice across the three ICUs, which is interesting. And then here we have the same group of researchers from those same sites in Australia, but a bit of an earlier publication. And this publication was what influenced the one that we just focused on about the intentions and the behavioral intention. This initial study looked at what were these ICUs' actual outcomes related to bowel management protocols. Another retrospective chart review, so not the highest level of evidence, but across those same three ICUs and looking at different outcomes related to a bowel management protocol being implemented across the three ICUs. Roughly the same period of time, 2007 through 2008, and I just highlighted some baseline characteristics here from the pre- and post-group. Really the only significant difference at baseline was a slightly higher Apache 2 score in the pre-group than the post, but this can be taken with a grain of salt. The other characteristics were fairly similar at baseline. And the results from this original study on the outcomes of the bowel management protocols are summarized here in this table. I'll draw your attention to the fact that none of these really were statistically significant. Again, so our outcomes of how many patients were, or the proportion of patients who were constipated three days versus four days from the start of being put on the bowel management protocol was not significantly different. The patients who were constipated for the duration of their ICU stay, not significantly different after the implementation of the protocols. How many episodes of constipation or episodes of diarrhea as the consequence of concern we have from overdoing it on these medications. So unfortunately, this protocol did not significantly change practice in terms of outcomes related to patient care and promoting healthy bowel movements. And this influenced the study that we focused on before because it was implied that perhaps because bowel care is perceived to be a lower acuity concern or a lower priority concern, maybe that's why this very interprofessional targeted protocol that they developed, maybe that was why it didn't have the effects that they wanted or they expected to see. And just looking a little bit further here, the bowel assessment documentation and compliance with the different elements of the bowel management protocol. Also nothing significantly different pre versus post. So although there was a protocol to guide prescribers and the nursing to administer these medications, there wasn't a significant change pre versus post in administration or assessment of patients or administration of the medications. And then finally, one of the more recent pieces of evidence we have, and certainly a lot higher basis of evidence, is a systematic review and meta-analysis from 2017 of ICU bowel management protocols overall. And the studies that were included in this meta-analysis were four listed here in chronological order, and most of them in Europe, but some in Asia and one in South America. And you can see the bowel regimens on the far right column that were used. Although there was some difference, site to site, the overarching agent that was used in all of these bowel regimens was lactulose, either monotherapy or compared to a polyethylene glycol and saline control. And the patients were also fairly similar across these four different studies across the world, most of them being medical surgical with being intubated for at least 24 hours and having fairly moderate, you know, Apache 2 severity scores. And what this meta-analysis found is threefold. Look at the top panel first. This forest plot of their primary outcome of constipation when the bowel management protocol was implemented, not statistically significant in the first, or across the four studies for constipation. I know the confidence interval just slightly crosses one, but technically not statistically significant, and similarly for incidence of feeding intolerance or duration of mechanical ventilation, not statistically significant. With a bowel management protocol than it was without. Some of the secondary outcomes of the meta-analysis, first one being ICU length of stay and the bottom panel reflecting ICU mortality, also not significantly different. So we're kind of left with a what if here. It seems that although the evidence we have is predominantly not high-quality evidence because it is based on retrospective and survey-based approaches, it is kind of showing us that having a bowel management protocol in your ICU is not always a guarantee to positively impact clinical outcomes of these patients, having healthy bowel movements and not over-experiencing diarrhea. As a consequence, but that from a behavioral standpoint as well, our own members of our ICU interprofessional team, the protocol is not really changing behaviors as you would expect that they should by the fact of them being protocolized actions. So some implications for the future, not all of the patients that were reflected in the studies that we looked at here were non-opioid-related constipation, so there's always that elephant in the room of can you extrapolate this or take these results and remove the opioid-induced constipation influence from it, where we do know that there is a benefit. The medications themselves were not directly assessed or compared head-to-head, except for that meta-analysis that did predominantly all have lactulose in each of the four included studies. But we also don't really know is it a consequence of what medications are in your bowel management protocol, are you just using stimulants and not a softening component that we know works better for certain cases like the opioid-induced constipation patient. We need to soften the feces and then stimulate the removal of the bowel matter from the patients. Potential for more interprofessional collaboration as well, the Australian studies really highlighted even though the results were not what they were expecting or what we may have expected them to be, they did highlight the importance of interprofessional collaboration, having all of the professions in the ICU develop the protocol in tandem and then implement it in tandem, and the need to assess full clinical outcomes again. What is the real impact when we look at one medication versus another or one regimen versus another in different types of patients outside of the opioid constipation world? And something else that's not on the slides here, a fairly recent development is the FDA clearance in August 2022 of these capsules that are called Vibrant, under the brand name Vibrant, that are non-drug bowel management treatments, I almost said medication like out of a habit. They're not medication-based at all, it's a vibrating capsule that when you activate it in the little chamber that it comes with, the patient takes it and it's over the course of a few hours, it helps to start, it starts vibrating in the patient's gut. So as the capsule moves through the gut, it'll vibrate and those vibrations help to sync up the gut and help the patient get back in touch with their biological clock, their gut's biological clock. So that's another aspect of if we are concerned about medication-related side effects, will future practice change toward us not needing to always give medications and we can rely on certain treatments that are not drug-based at all and also have very low incidence of side effects like diarrhea and help our patients get back onto a healthier schedule as it were for their bowel, their bowel management. So still more to come and we don't unfortunately have a full answer yet, but some food for thought including from the behavioral standpoint of how our practices and perceptions can affect constipation management in the ICU. Thank you for your time.

constipation

preventative bowel regimens

ICU

pharmacists

bowel management protocols