Narrator - Dr. Abel 00:00 Welcome to HelixTalk, an educational podcast for healthcare students and providers, covering real life clinical pearls, professional pharmacy topics and drug therapy discussions. Narrator - ? 00:11 This podcast is provided by pharmacists and faculty members at Rosalind Franklin University, College of Pharmacy. Narrator - Dr. Abel 00:17 This podcast contains general information for educational purposes only. This is not professional advice, and should not be used in lieu of obtaining advice from a qualified health care provider. Narrator - ? 00:27 And now on to the show. Dr. Sean Kane 00:31 Welcome to HelixTalk episode 185 I'm your co host, Dr. Kane, and I'm Dr. Patel, and the title of today's episode is they are late, but don't stress the new 2024 stress ulcer prophylaxis guidelines. Dr. Khyati Patel 00:44 So it seems like Dr. Kane, it's been a long time since these guidelines have been updated. So I think we're going to summarize the recommendation from the SCCM ASHP guidelines, which were recently published, and also discuss the landmark trials that kind of shaped up the recommendations for the guidelines, Dr. Sean Kane 01:02 yeah, kind of plot twist. Me, personally, as a critical care pharmacist, I'm disagreeing a little bit with the guidelines, so we'll get to that later on. But I think it's healthy to have some degree of disagreement or maybe not full alignment with guidelines, and that's why we look at the primary literature. And this is actually not common. We see European guidelines conflicting with us, guidelines all the time, or two different us guidelines not being in alignment. So we'll definitely get to that today, right? Dr. Khyati Patel 01:28 I think before we get there, though, let's kind of set the foundation for our audience to talk about, what is stress ulcer, and what is the prophylaxis that we do for stress ulcers? Dr. Sean Kane 01:38 Yeah, so kind of as the name suggests, when critically ill patients get quote unquote stressed, they have breakdown of their gastric mucosa, and they're prone to ulcerations in their gastric lining. They can either perforate, where then the stomach acid can leak out into their abdomen, or if it's right next to a blood vessel, that ulcer can actually cause a GI bleed, which is the main manifestation of a stress ulcer for a critically ill patient. And I Dr. Khyati Patel 02:03 believe this happens because there is not enough perfusion of that gastric mucosa, and something happens to the tissue. Is that right? Dr. Sean Kane 02:11 Yeah. So the term splanchnic hypoperfusion is sometimes used. So your splanchnic circulation is the blood vessels that feed a lot of your GI tract, but specifically, in this case, your stomach. And what happens is the blood flow to the cells of the stomach is not sufficient, so those cells become ischemic because they're not getting what they need. And when that happens, they don't produce the protective lining the mucosa that those cells need to not be digested by the stomach acid. What happens then is, because of this low blood flow state to the stomach, we end up with this breakdown of the gastric mucosa that ends up with the ulcerations that we talked about. Dr. Khyati Patel 02:50 And usually this happens in shock situations. So we're talking septic shock, cardiogenic shock, hypovolemic shock, or hemorrhagic shock, yeah. Dr. Sean Kane 02:59 So certainly that is the main population that the mechanism makes the most sense for. We also see it in patients that maybe it's not as obvious. So in non shock patients, like multi system trauma, patients, so significant traumas, those with traumatic brain injuries, even with an isolated brain injury, or even in people who are receiving mechanical ventilation. And those circumstances, the stress, quote, unquote, stress, is caused by the adrenal glands making a lot of epinephrine because of the that acutely stressed state. And when your body has that fight or flight response, it's shunting blood away from your stomach and your kidneys into more areas like your brain and your heart, so that shunting of blood away from the stomach through that splanchnic hypoperfusion is mediated primarily by the sympathetic nervous system, which is that stressful state that we're talking about, and Dr. Khyati Patel 03:55 particularly talking about patients who are receiving mechanical ventilation. Why is that a risk factor? And I think you said earlier, the guidelines are kind of excluding this as a risk factor, but yeah, Dr. Sean Kane 04:07 so we'll definitely talk more about this, because this is probably the hottest area of the new guideline update. But essentially, we've considered mechanical ventilation a risk factor, because people who require mechanical ventilation tend to be sicker. So it's not uncommon that when you have someone with septic shock that they need to be mechanically ventilated because they're so sick. But then two, the physiology of how a breath is given to the patient who's receiving mechanical ventilation, in itself, we think, is causing part of the problem with splanchnic hypoperfusion. The reason is that normally, when you breathe without mechanical ventilation, your diaphragm drops, and that drop in your diaphragm makes the volume of your lungs bigger. It causes a pressure drop, and then air from the outside environment goes down your mouth, through your trachea, into your lungs passively through negative pressure, so your diaphragm dropping allows air to passively move into your lungs. Yes, a mechanical ventilator works completely differently, though. So with mechanical ventilation, we don't control the patient's diaphragm. Instead, we take a tube that goes down the trachea and we push air in, so we actually add pressure to the lung, as opposed to causing negative pressure environment with the diaphragm dropping. And we think that that extra pressure in the lung that is not normal or physiologic, that that extra pressure causes a variety of problems, including low blood flow to the blood vessels that are all over the stomach. But we can also see this even with low blood flow back to the right side of the heart through the vena cava. In people who have mechanical ventilation, they don't perfuse as well because there's more pressure and more compression of these blood vessels like the inferior vena cava, or the blood vessels of the stomach that can cause this hypoperfusion state in the stomach. So that's the thought, at least historically, of why we've considered mechanical ventilation to be a risk factor for stress ulcers, Dr. Khyati Patel 05:59 and that's really nicely explained. Makes sense why patients would qualify when they are on mechanical ventilation? Well, when we talk about the phrase stress ulcer prophylaxis, is identifying these risk factors in the patient put them at a risk of stress ulcer, but then choosing a medication to help prevent that GI bleed or perforation from happening exactly. Dr. Sean Kane 06:24 And you know, for decades, this has actually been a very common misconception that being in the ICU period requires you to be receiving stress ulcer prophylaxis, which is not true. And even on top of that, any patient outside of the ICU has zero indication for stress ulcer prophylaxis, so you have to be critically ill, plus other factors to justify a stress ulcer prophylaxis. And of course, which agent to pick has been an area of controversy for a long time, and I feel like we should just mention that we're using the term stress ulcer the official term is stress related mucosal damage, or srmd. Nobody says that, but you'll see it in literature and guidelines and things like that. Dr. Khyati Patel 07:07 So I think we kind of laid out the land a little bit earlier. Dr. Kane, but it's been quite a bit since the last guideline update occurred. Right? Like, when was the last one? Dr. Sean Kane 07:18 And this is not a joke. Dr. Patel. 1999 was the last guideline update, so the old guidelines just had their 25th birthday. Unknown Speaker 07:28 Yeah, learn something from ADA. Dr. Sean Kane 07:31 So, yeah. And what's odd is that critical care in the 1990s is dramatically different than it is now. The therapies that we have now are still different than in the late 1990s you know, in 1999 we did have PPIs proton pump inhibitors like omeprazole or Nexium, but the difference is that the cost in 1999 was vastly different than the cost now, the availability, the data that we have, and as we'll talk about, we have a bunch of at least three landmark critical care trials focused on stress ulcer prophylaxis that came out in the last handful of years that have definitely changed the data that is available for this condition of stress ulcers and stress ulcer prophylaxis. Dr. Khyati Patel 08:15 So I believe the guideline is pretty succinct, and I love pico style question and answers, or the guidelines, try to answer that because it's very straightforward and easy to read. So in that helix top fashion, we're going to go over some of those recommendations, but before we even get to the guidelines, it's important that we go into that literature that you're talking about, Dr. Kane that set the tone for the guidelines. Dr. Sean Kane 08:39 Yeah. So I had a preceptor when I was a PGY two in critical care that said something to the effect of, I hate stress ulcer prophylaxis, because it's been this like minefield of bad literature and retrospective analyzes for decades. And he's not wrong. So prior to some of the landmark trials that we've had in the last handful of years, most of the literature is retrospective, observational with tons of biases and flaws, or we do have some very small randomized trials, but they're underpowered, super at high risk for bias. And then, of course, when you meta analyze low quality trials, it's not like you can just take a bunch of bad quality trials and then come up with a beautiful, reliable meta analysis, garbage in equals garbage out. So really, it wasn't until 2018 that we had a true, large, randomized, controlled trial that was actually looking at the question of who should get stress ulcer prophylaxis, and what is the benefit, the clinical benefit, what are the risks of that? And what agent should we pick? Dr. Khyati Patel 09:39 You're saying that these new literature, new studies that are out, are much more reliable than some of the meta analysis that we had from poor trials, arguably, I would Dr. Sean Kane 09:49 almost argue you should throw out all previous literature and almost exclusively focus on these three landmark trials, because the risk of bias with those older, smaller, especially observing. Trials is so different than what you benefit you get from these larger trials. Dr. Khyati Patel 10:05 So Dr. Kane, you said, you know, in 2018 it was a first publication. That's the SUP-ICU trial that looked at pantoprazole IV, 40 mg once daily, versus placebo in patients who were at risk for stress ulcers. Who were these patients? Yeah. Dr. Sean Kane 10:21 So they had kind of a checklist of potential inclusion criteria. Shock is the main one that we've talked about, being fully anticoagulated, having acute or chronic renal replacement therapy. So that would be people who already are on dialysis or people who need new dialysis because of their critical illness, mechanical ventilation, liver disease, coagulopathy, the list goes on, but those are the main ones. And really I want to focus on most people met inclusion to the trial because they were in shock and or they were mechanically ventilated. And what did they find? So they they looked at mortality, and there was no difference in mortality. And this is actually really big deal, because, again, a lot of these older, retrospective, smaller trials had this hypothesis that if you prevent a stress ulcer bleed, that there's this gigantic mortality benefit, because we observed that people who are more likely to bleed are more likely to die. So therefore, if you stop the bleed, can you prevent them from dying? And this trial showed that No. So giving stress ulcer prophylaxis did not have a mortality difference, even though we had a clinically significant difference in reducing GI bleeding events. So they called it clinically important gi bleeds, and it was about a 50% reduction. So people who got a PPI were 50% less likely to have a bleed. But preventing the bleed didn't translate to a mortality benefit, which is something that we thought we would see that we did not see in the trial. Dr. Khyati Patel 11:46 Oh, that's very interesting. And I think they also looked at a subgroup analysis in patients who were really, really sick, so the level of severity of illness was really high, and these patients had higher mortality when they received PPIs, yeah. Dr. Sean Kane 12:00 So in that subgroup, it did appear that the highest cohort of severity of illness, which is basically a score that's measured based on a bunch of different factors, that there's a signal, and I'm using signal with podcast quotations, a signal of harm, meaning that those patients, even though the drug works in terms of preventing gi bleeds, there was a signal that mortality might be a little bit higher in that cohort. And of course, there's issues with subgroup analyzes, and we'll get to it later, but this kind of raised a red flag, and you'll actually see it in the guidelines, that because of that, there was a question mark of, Well, should we still do this in that really sick patient population, even though that really sick patient population is also more likely to bleed because they're really sick, right? Dr. Khyati Patel 12:42 Well, fast forward in 2020, we had another trial. This is a clever name peptic, which looked at actually PPI versus the h2, receptor blockers. So this was not a placebo control, more of an active control trial. Again, these patients were the mechanically ventilated patients in ICU, and they were also looking at mortality and GI bleeding as the clinical outcomes, Dr. Sean Kane 13:06 yep, so same clinical outcomes. Kind of interesting. They left the route and dose of the PPI or the h2 or even the drug up to the clinicians. So it was kind of a pragmatic trial where they said, Okay, we're going to randomize you. You either get to choose a PPI of your choice, however you want to dose it, or an H2 blocker of your choice, however you want to dose it. And we'll compare the two. And they did look at mortality again. There was no difference in mortality, and what they found was that the PPIs were more effective. And we've kind of always thought that this would be the case, because we know that PPIs are more effective for GERD, we know that your stomach pH is going to be higher with a PPI versus an h2 blocker. So we had surrogate markers from other disease states that PPIs are more effective at increasing your stomach pH. So they did look at clinically important GI bleeding, and the PPI outperformed the h2 blocker by about 25% so 25% less clinically important gi bleeds if you were randomized to a PPI as opposed to an h2 blocker, all right? Dr. Khyati Patel 14:06 Dr. Kane, this study also looked at a subgroup analysis in patients who were very sick, so again, those with higher severity of illness, and found that PPI group had higher mortality. What's up with this? Dr. Sean Kane 14:19 Yeah, so this is our second quote, unquote signal of the sicker you are, maybe the PPI has some paradoxic increase in mortality, even though it's more effective at preventing gi bleeds. Couple things. One, this was a post hoc subgroup analysis, which means that they didn't plan for it, but probably on the basis of the SUP-ICU 2018 trial, they said, well, we should probably look at this and make sure it's not a thing. And then they saw it was a thing, which is not good. But the other big issue with the analysis, aside from the post hoc nature, is that this wasn't a linear relationship. And what I mean by that is that if you look at the sickest cohort, they did have a higher mortality rate versus ppi, but if you look at the second. Sickest cohort, but the third sickest cohort, it wasn't linear, where the sicker you are, the higher the mortality risk is. And you would expect that where the least sick patients up to the most sick patients, that there's a linear relationship in that risk of mortality. And we did not see that. So there are definitely concerns about mortality in this. And again, the guidelines highlight that, and to have now two trials that are big trials with a subgroup suggesting potential harm, is definitely alarming, but it isn't a slam dunk that PPIs increased mortality among the sickest patient population. Dr. Khyati Patel 15:32 Okay, so fast forward 2024 we have the REVISE trial, and unfortunately, this trial was much after the guideline cut off of April 2023, so the results of this trial were not included into the SCCM guidelines that we're about to discuss. But they also looked at pantoprazole, 40 mg IV once daily, versus placebo in patients who are mechanically ventilated. Similar outcomes were also looked at what did they find? Dr. Sean Kane 15:58 Dr. Kane, so again, we saw no difference in mortality, and we saw that PPIs did reduce the risk of clinically important GI bleeding this time by 70% instead of 50% so an even bigger benefit the population here generally was a little bit sicker than the previous studies that we've looked at. And they did look at a subgroup of that higher severity of illness, or sicker patient population, and they did not show a difference in mortality, and they specifically were designed to look at this. So now we have a third trial that specifically was designed for the subgroup that is refuting the previous two trials that hinted that there might be a signal here, I would say, based on this trial, I'm less concerned about that signal. Dr. Khyati Patel 16:38 And I think general PPI‑related ADRs were looked at, especially in this patient population, the risk of pneumonia, the C. diff. What did the study find in regards to that? Dr. Sean Kane 16:49 Yeah, so all three of these randomized control trials, and keep in mind, we're talking 1000s of patients. If you combine all three trials, there has been zero signal of PPIs increasing the risk of pneumonia and zero signal that PPIs are associated with an increased risk of C diff. So these are theoretical concerns based on observational studies of non ICU patients. So typically outpatients that take PPIs chronically, and I think it's really important at this point, I would say that this is a done deal. PPIs in critically ill patients do not give you C diff, and they do not give you pneumonia. That has now been debunked enough that I wish it would just go away. Dr. Khyati Patel 17:28 Yeah, especially, you know, keeping this patient population in mind, they're receiving it for a shorter duration of time compared to those non ICU patients. So no risk here. Dr. Sean Kane 17:38 So now that we've reviewed the three landmark trials that were at 2018 2020 and 2024 and as we mentioned, that 2024 revised study came out after the guideline had cut off their literature search. So that was not included in the guidelines, which, if you think about it like, we had 25 years of not a lot of great data, and then we had a couple years of these new landmark trials. It's great that they decided to come out with a guideline. This is gutting to think that, like, they spent all this time and effort and then this, like, really important trial came out after the fact, after they released their guidelines, Dr. Khyati Patel 18:10 they should have waited one more year. Dr. Sean Kane 18:13 So one of the areas in the new guidelines are who should receive stress ulcer prophylaxis, and they have three groups that they recommend. So they recommend those with coagulopathy. So this is intended to be patients with intrinsic coagulopathy. So it's not someone who's taking warfarin or being heparinized, but someone who has due to their critical illness, their INR and their PTT is elevated, someone who's in shock, and that shock population is most of who we're giving stress ulcer prophylaxis on. Anyway. Then the third group is chronic liver disease. And oftentimes those chronic liver disease patients will also have coagulopathies. Dr. Khyati Patel 18:49 And the guidelines actually did not recommend, though, the SUP for mechanical ventilation alone, and this is the much more debatable issue, how they're deferring from some of the patient populations in their trial we discussed, Dr. Sean Kane 19:03 yeah, so this is my area that I would disagree with the guidelines, which I think is a healthy disagreement. I'm very appreciative that after 25 years, they came up with new guideline document. But if I was to channel their rationale, their rationale is that we don't have literature firmly showing that mechanical ventilation is a risk factor for getting a stress ulcer. What I would counter to that, though, is that in the now three very large randomized control trials that we have, two of the three mandated that you were getting mechanical ventilation, and the third one that had a checklist, the SUP-ICU trial, 80% of those patients were mechanically ventilated. So of the literature we have for stress ulcer prophylaxis, almost all of the patients were getting mechanical ventilation, and granted, many of them were in shock and had other conditions to receive stressful superphylaxis. I think it's premature, though, to say that mechanical ventilation alone is not an indication for stressful superphylaxis. I think because we've done it for so long, and we have three trials that that was. Inclusion criteria, essentially, I think we just need a trial to look at whether that is a good enough risk factor or not, in lieu of having other risk factors. I think it's too premature to just say that alone is not risk factor and publish it into a guideline document. Dr. Khyati Patel 20:14 So in a practice setting, an ideal practice setting of yours, Dr. Kane, you would still consider patients with just mechanical ventilation eligible for stress ulcer prophylaxis, Dr. Sean Kane 20:24 I would, I'm sorry, I would deviate from the guidelines, and I would continue with stress ulcer prophylaxis in that COPD patient with pneumonia that doesn't have shock and doesn't have other reasons for stress ulcer prophylaxis, because the primary literature that patient would be included in those trials, and they would get a 50 to 70% reduction in getting a GI bleed using a ppi. So I think that the primary literature would still support mechanical ventilation, even though the guidelines would disagree with that. Dr. Khyati Patel 20:50 And that's a clear distinction, as you mentioned earlier. Sometimes guidelines do differ and they don't follow the literature. And so again, it's important to look at your primary literature. The guidelines are also specifically calling out this subgroup of patient who are in the neurocritical care arena or area who should receive stress ulcer prophylaxis. Again, this you know, certainty of evidence is very low compared to that low to moderate with the first three indications we just discussed here. And it's interesting that they are calling out the care setting and not the conditions. Why the patients are in that particular care Dr. Sean Kane 21:26 setting Exactly. So it's not like the first guideline recommendation was people in the ICU, but they're kind of doing that for this one. So most of the reason they called out this group is that we do have some literature specific to neuro intensive care patients or neuro critical care patients. Most of those patients, though, are traumatic brain injury TBI patients and intracranial hemorrhage or ich patients. So it's interesting that they didn't pick those people out specifically, and say among people in neuro critical care units who have TBI or ich is we recommend stressful superphylaxis. So I'm not sure why they made that decision, but that is what the guidelines currently publish, is that we have those three groups of coagulopathy, shock, chronic liver disease, and they acknowledge that there is no definition of what that means, because the original literature didn't have a definition, or it was a very heterogeneous definition. And then finally, this fourth group, with less certainty of evidence is neuro critical care patients, but we should acknowledge that's mostly TBI and ich patients, Dr. Khyati Patel 22:25 and they are at risk because, again, of the hyper secretion of that gastric acid leading to the mucosal damage. Dr. Sean Kane 22:32 Another element that the guidelines did talk about was PPIs and the risks associated with what we talked about. So the guidelines say that PPIs are very effective in preventing clinically important GI bleeding, as we mentioned, 50 to 70% risk reduction, and they say PPIs do not increase the risk of those hypothetical side effects that were mostly seen in retrospective studies. So this is again focused on pneumonia, C diff and even mortality. So they acknowledge that that is a potential concern that the subgroup, but they say that at this point, it feels like the benefits are outweighing those risks, and there is no risk of C diff and pneumonia with PPIs. Dr. Khyati Patel 23:13 And then another group to look at, Dr. Kane is these patients who are receiving enteral feeds. How does the stress ulcer guidelines or recommendations apply here? Dr. Sean Kane 23:24 So historically, there was a thought that among patients getting fed enteral feeding so they have, like, a tube going down their nose or mouth that is giving them nutrition, that the nutrition itself would be preventative for stress ulcers. What that means is that either the food itself would help with the pH of the stomach or the food would cause better perfusion to the gastric mucosa, because when you eat, you get more blood flow to your GI tract to help you digest. And really, this came from a 2018 meta analysis that suggested that enteral nutrition plus stress ulcer prophylaxis increased the risk of pneumonia, get this by 50% and it did not reduce the risk of stress ulcers. So that was a meta analysis in 2018 before we had any of this higher quality literature. Interestingly, a 2019 meta analysis where they looked at slightly different literature, found the opposite, no pneumonia risk, and that those patients being fed did decrease the risk of stress ulcers. So I just want to highlight that we have now three RCTs that have shown no pneumonia risk, and in some of these trials, there was a lot of feeding going on. So many patients did get internal nutrition. And as far as I'm aware, no subgroup has shown that the benefit was any different, or that there were any risks if patients were being fed. So at this point, the guidelines say it doesn't matter if they're being fed or not fed. You do the same thing for these patients, right? Dr. Khyati Patel 24:42 No additional risk, and they still get the benefit. All right? So I guess we answered the question of what patients or what risk factors we should be watching out for, where patients will qualify for stress ulcer prophylaxis. Now, the second question the guideline is trying to answer is, what's the best regimen? What drug? Regimen to go with. And again, we looked at, you know, H2RA blockers, PPIs versus placebo in the previous study. But let's break that down. Dr. Sean Kane 25:07 And again, this is an area that has been so hotly argued for decades. In the critical care arena, you've got people on one side that love the PPIs have better efficacy in terms of increasing the gastric pH, you have other people that are worried about h2 blockers causing cognitive impairment, especially in elderly patients, if you don't dose adjust it for renal impairment, there might be a thrombocytopenia risk, which with h2 blockers. What about the pneumonia risk and the C Diff risk with PPIs? And then we've had guidelines like the sepsis guidelines at some points recommending specific stress ulcer prophylaxis regimens when they probably should not have. So at this point, what did the guidelines say? Drum roll, you can use a PPI or an h2 blocker. And really they say PPIs are definitely more effective, and we saw that in the clinical literature, but they were concerned about the two trials that we talked about that had that subgroup analysis among the highest severity of illness, that it might increase the risk of mortality. And they acknowledge it's not a slam dunk, but they say that we're worried about it. And if you want to use an h2 blocker, because you believe in that subgroup analysis, a little bit more more power to you, as long as you recognize that the h2 blocker is going to be slightly less effective, right? Dr. Khyati Patel 26:21 And then if you're looking at patients who have the higher risk for GI bleed, so high, high GI bleed risk probably go with PPIs, because they have 50 to 70% reduction in the GI bleed. Dr. Sean Kane 26:33 And again, the revised 2024, study wasn't out at the time that these guidelines were published, which does refute that subgroup analysis. So had they had that article available to them, I don't know if they would have still recommended PPI or H2 or if they would have had a slight preference toward the PPI. Dr. Khyati Patel 26:50 Now, the question is whether we give this regimen orally versus IV. Couple of the studies we looked at, you know, provided this regimen IV, yeah, Dr. Sean Kane 26:59 and you know, this is an area that's pretty common for critical care pharmacists to focus on, especially historically, this is a cost savings measure to do IV to PO PPI conversions, because the cost of an IV PPI isn't that much, but when you have 1000s of patients within your hospital or health system receiving IV ppi, and you can switch it to something that's a 10th of the cost, you can save some money at this point, the guidelines say you can do what you want, oral or IV is fine. We basically don't have any study comparing one versus the other, so there's no evidence based way to say that you should prefer IV over Po, or po over IV. With that in mind, though, there may be a cost savings to doing oral and there are some patients that can't get oral therapy that you must do IV on. So this would be someone with an ileus, someone with profound shock, where they're not tolerating any feeding at all, people on high dose pressors, recent gi surgery, where you really can't put anything in their stomach. And obviously in those patients you must do IV, there is no option to do po Dr. Khyati Patel 28:00 and then, just to keep in mind, as we're thinking about, you know, po versus IV is that the PPI capsules can't be crushed. You could open up the granules and you can dissolve it into a liquid with a bicarb, but you can't, it can't be crushed. Dr. Sean Kane 28:15 And you would be shocked at how commonly nurses will crush the PPI. It looks crushable. Nothing bad happens when you crush it. The problem is that when the stomach acid touches the PPI molecule, it degrades it, and it doesn't work. So you risk the PPI not working at all if you do crush it. And then Dr. Khyati Patel 28:32 the question is whether Should we do a high dose PPI versus the low dose? And I'm talking bid versus once daily. Dr. Sean Kane 28:38 And you know, we see plenty of patients, even on the outpatient side, that are on very high dose twice daily PPIs. That probably shouldn't be but they are, and the guidelines say that the normal dose the daily dose. So this is esomeprazole, pantoprazole, omeprazole 40 milligrams once a day. Lansoprazole 30 milligrams once a day. You don't need the bid regimen of the PPI, Dr. Khyati Patel 29:00 and if you're using an H2RA blocker like famotidine, then you could do 40 milligrams per day. And that's usually given PO, so 20 milligrams twice daily, again, this is renally adjusted, so make sure that you are looking out for the Creatinine clearance for the patients too. So if that is below 50, then you're going to do the 20 milligram daily dose. Dr. Sean Kane 29:21 And then I think the key take home point that I would encourage everyone to recognize is that for stress listed prophylaxis, you don't do twice daily PPIs, however, and the guidelines do refer to this. If someone comes in with a ppi, you should probably give them whatever regimen they're on. So if they're already on a bid regimen, you should probably just continue that during their critical illness. If they're not on a ppi, just do daily, and if they're on some unique regimen for GERD or heartburn or whatever, as long as it's still covering your stress ulcer, indication you should continue whatever they're on. So if they're on sucralfate with ranitidine, you should still give that to them; it is still going to cover the base of their stress ulcer prophylaxis, and you're also treating whatever indication they had prior to their admission. So it's important that we're recognizing the difference between their stress ulcer indication and whatever other indications they may have. We're covering. We need to cover both bases. Dr. Khyati Patel 30:16 Yeah, but basically, if they're not on any of those regimen, we're not starting the bid PPIs, it's usually once daily. Dr. Sean Kane 30:23 Then, of course, the logical question is, if you are going to start that once daily PPI or your H2 blocker, when do you stop? Dr. Khyati Patel 30:32 This is a big, big deal when it comes to transitions of care too, because sometimes this medications are not discontinued appropriately, and then patients end up getting it, you know, on the outpatient side too. So technically, whenever the risk for stress ulcer ceases, it's appropriate to go ahead and stop this regimen, Dr. Sean Kane 30:52 or when the patient leaves the ICU. So if they were mechanically ventilated and now they're extubated, get rid of the PPI. If they were in shock on vasopressors, and now they're not in shock and they're not critically ill anymore. Get rid of the PPI. When they leave the ICU, you get rid of the PPI. And this is so incredibly common that the stress ulcer prophylaxis is not discontinued. It's continued on the floor, and then the floor person that is discharging the patient doesn't know the history of that ppi, and it just feels safer to that person to just continue it, because they didn't start it. They don't know why it was started. And then they go home on it, and then five years later, they've been on a PPI for five years, and they have zero indication. And now you have to taper it down, because their body's so used to it. You just can't cut it cold turkey, because now they would have heartburn type issues if you abruptly stop their ppi, right? Dr. Khyati Patel 31:43 And they're available as generic and, you know, better coverage. But still, it's a pill burden. It's still an added cost to the health care. And don't forget drug interactions and stuff. So, you know, look out, look out for those inappropriate therapies, and do discontinue it or de prescribe it. Dr. Sean Kane 32:00 So Dr. Patel to kind of wrap things up again, we have plenty of references in our show notes, including those three landmark trials for stress listed prophylaxis in the new 2024 guidelines. But really, this is a guideline update 25 years in the making, and this was updated by SCCM and ASHP, so kudos to them for doing that. And I would agree I really like the fairly brief format, the three question pico style format, I think, is really digestible, easy to look through and understand where the guidelines are coming from Dr. Khyati Patel 32:30 and why the older primary literature wasn't that great. But in the recent year, there's been this three landmark randomized control trial, the SUP-ICU, PEPTIC and REVISE trials that have significantly contributed towards this body of literature, although revise is not part of the guideline recommendation. Dr. Sean Kane 32:48 And then the guidelines state that the indications for stress ulcer prophylaxis are coagulopathy, shock, chronic liver disease, and then possibly being a neuro critical care patient, which typically means traumatic brain injuries and intracranial hemorrhage. They do not specifically recommend prophylaxis in mechanically ventilated patients, and we talked about that is kind of a controversial recommendation that they decided to go with. Dr. Khyati Patel 33:12 And the guidelines are equally preferring ppi and hdra blockers can be given either intravenously or orally. The important thing is that this prophylaxis should continue until a patient has the risk factor, and once those risk factors are resolved or patient leaves the ICU, they should be discontinued. Dr. Sean Kane 33:32 So Dr. Patel, I think that wraps up today's episode nicely for the listener. If you want to get on our mailing list and get an email when episodes come out, you can subscribe at HelixTalk.com We're also on x at HelixTalk, and we love the five star reviews and Apple podcasts or wherever you listen to us, so that other people are more likely to find our show. So with that, I'm Dr. Kane Dr. Khyati Patel 33:52 and I'm Dr. Patel, and as always, study hard. 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