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CEimpact Podcast
New Stress Ulcer Prophylaxis Guidelines Have Monumental Changes
The Society of Critical Care Medicine just released their first set of updated stress ulcer prophylaxis (SUP) guidelines since 1999 that include groundbreaking changes. We also discuss evidence on proton pump inhibitor (PPI) use for SUP that impacts ICU practice.
The GameChanger
New guidelines for use of PPIs for stress ulcer prophylaxis will have a significant impact on ICU practice.
Guest
Geoff Wall, PharmD, BCPS, FCCP, BCGP
Professor of Pharmacy Practice, Drake University
Internal Medicine/Critical Care, UnityPoint Health
Matthew Trump, DO, FACP, FCCP
Pulmonologist
The Iowa Clinic
Reference
Guidelines
Paper
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CPE Information
Learning Objectives
Upon successful completion of this knowledge-based activity, participants should be able to:
1. Describe the new Stress Ulcer Prophylaxis (SUP) guidelines from the Society of Critical Care Medicine (SCCM), including identifying patients at risk.
2. Discuss the use of Proton Pump Inhibitors (PPI) and Histamine-2 Receptor Antagonists (H2RA) for Stress Ulcer Prophylaxis (SUP).
0.05 CEU/0.5 Hr
UAN: 0107-0000-24-247-H01-P
Initial release date: 08/26/2024
Expiration date: 08/26/2025
Additional CPE details can be found here.
Hey, ce Plan members From CE Impact. This is Game Changers. Today, I'm joined by our resident pharmacist expert, dr Geoff Wall and Dr Matt Trump. Welcome, gentlemen. Dr Trump, can you tell us a little bit about your practice and how you work with Geoff?
Speaker 2:Yeah, so I'm a practicing pulmonary and critical care physician. I've been at it for over 10 years now and I mostly work with Dr Wall at Methodist in Des Moines and we make rounds in the ICU. Geoff my right hand, my right hand man, so to say, and he's with us all the time he's. He and I are both working with residents and the nursing staff and respiratory therapists to help take care of critically ill patients in the ICU and we're always looking to advance practice and find the best ways to take care of patients in the ICU. We always talk about and I emphasize to my residents that there's no magic bullet, so to say, in the ICU. It's good critical care medicine, it's good evidence-based medicine.
Speaker 2:So we try to practice sound, evidence-based medicine. What we do and we know it works in the ICU, we know it doesn't work and we know that there's a lot of study that has guided us on this. So that's what we do. We got a big tertiary referral center for the state. We take care of people all throughout the state and surrounding areas too in the Midwest, the state and surrounding areas too in the Midwest. So we're, I think, I think, I. I'd love to say that we're really proud that of what we do and all the service we provide for for this region of the country. So it's an honor to work with Geoff and I've known him since I was in medical school and he just blows me away every day. So thanks for having me.
Speaker 1:Thank you man, awesome, yeah, Same, he blows us away as well. Love it so fun to work with you, and it's great to work with you today too, matt. Okay, so today we are talking about stress ulcer prophylaxis guidelines, and I just want to get this straight, because we talked about a lot of guidelines on the show and often we say, oh, they haven't been updated for five years or 10 years. Can you believe that? And often we say, oh, they haven't been updated for five years or 10 years. Can you believe that? Well, in this case, is it true that these guidelines haven't been updated since 1999?
Speaker 1:So 25 years it has been, and I know both of you are going to talk about why that is, so tell me why that is.
Speaker 3:Yeah, yeah. Yeah, you're right, Jen, it's been an unbelievable 25 years no-transcript to kind of trickle in about, you know, stress ulcer prophylaxis and how to approach it. There really hasn't been a lot of high level data, so it's been retrospective studies. They've been small, you know it. Just I don't think there's been really enough to kind of trigger getting a bunch of people together to do this and I think finally they're kind of reached a threshold point where the Society of Critical Care Medicine said, okay, yes, we finally have enough.
Speaker 3:Relatively seen this, I think in his practice as well is that how we approach critical care patients in certain areas is really changing. One of them is enteral feeding. You know, when I came out of school, you know when the dinosaurs roamed the earth, you know we waited and waited and waited to start enteral feeding on patients. You know. So someone had, you know, was intubated, had septic shock. We wouldn't start feeding till they ate 10, 12, you know, assuming they still stayed sick, and you know that's not a good thing. People need to eat. And so you know the evidence had been clear that earlier feeding helped a wide variety of different disease states in the ICU, and we've also since learned that enteral feeding is also a really good protection against stress ulcers. So you know. So you know, practice has also been evolving during this period as well. So I think that's why SECM finally decided yeah, you know, it's time to come up with new guidelines to kind of reflect what's going on. And there's some big changes here.
Speaker 3:One I'm not going to lie, it's going to take some time to wrap my head around, so we'll talk about that in a second. So these guidelines were just published in the August issue of Critical Care Medicine and we've got a link in the show notes for you guys. This was a formal convening of a group of experts, in fact led by Rob McLaren, who I've known for years. He's one of the gods of pharmacy and critical care medicine in New York's UCSF group. He's a real nice guy. He led this group.
Speaker 3:And how they did it is pretty much how they do most guidelines. They use the great approach. They use PICO questions to try and answer. They did do their own meta-analyses and systematic reviews, which a lot of society groups do but not all do. So that's kind of nice where they all you know they didn't rely on previous data. They literally took all the studies they could find and did their own meta-analysis and systematic review to kind of you know guide what their recommendations are going to be. And you know they have a number of questions they wanted to answer. In fact there's 13 questions and I'm not going to read every single one of them, but there are ones they wanted to kind of talk about.
Speaker 3:They do mention that, even with the improved evidence base that we're dealing with again, this is just not an area where a ton of randomized control trials have been done. So the level of evidence is mostly low to moderate, you know, but that's how it's been for 30 years and I don't see that changing anytime soon. So I you know, keep in mind that that. You know this is evidence based and it's the best evidence we have, but it's certainly not the strongest evidence you could possibly get on this. But it's just. This is not an area of medicine where you're going to get a lot of funding from drug companies, for example, to do large RCTs. So it's basically up to smaller groups or smaller hospitals to kind of pull this off. So that's kind of a little background.
Speaker 3:So turning to the guidelines themselves, again, you know 13 recommendation statements, the first I think most important one is the big shift in suggesting which patients are at risk for clinically relevant bleeding. And they do talk in the guidelines that there is, you know, a difference between people who have clinically relevant bleeding compared to people who have overt bleeding or covert bleeding, excuse me. So you know there are patients where you know, yes, if you do, you know EGDs on them or you, you know, do you know daily YX tools or something along those lines? Yes, you may see that there, there's some blood there, but that's not usually considered clinically relevant. You know, clinically relevant bleeding is usually where you need to give blood to the patient, where the patient becomes hemodynamically unstable. You know things along those lines and of course, that's what we're really trying to prevent.
Speaker 3:And you know, for those who are not in the world of critical care, you may ask yourself well, you know why. Why do people get ulcers at all in the ICU? And it's because the physiologic stress involved with most diseases in the unit has been shown to basically increase gastric acid production and actually break down the protective barriers, the mucus layers and stuff like that. That happens in patients normally right, so that protects you from having ulcers. All that breaks down in patients who are critically ill and so that's why patients you know have this and the incidence of stresscers has gone down again, probably because we have been feeding patients earlier. But that's kind of by the by.
Speaker 3:So the big and I think I think one of the big ones is that for 25 years now, since the 1999 guidelines came came out, one of the biggest known the recommended risk factors for considering stress ulcer prophylaxis was patients who were mechanically ventilated over 48 hours. That is no longer considered a risk factor for developing stress ulcers and that is going to really take me a long time to get my head around because it's what I've been recommending for years and years and years. They actually say that there are four disease states that put patients at risk for clinically relevant bleeding. It is shock and it's any type of shock. Obviously septic shock is probably the most common when we deal with the ICU, but any type of shock chronic liver disease and then known coagulopathies and that does not mean patients who are on warfarin or DOACs, that means people who have like an innate coagulopathy and then neurocritical care patients. So they actually note that those are the four classes of patients who have the highest risk of clinically relevant stress ulcers and upper GI bleeding from stress ulcers. Again, huge change. That means I'm probably going to be stopping stress ulcer prophylaxis in patients, for example, who have respiratory failure on the vent but don't have any of these other things. And you know, matt, I'm sure we'll talk about and we'll probably talk together about how we are going to implement this and some of the educational. You know what we're going to have to get done to kind of get this implemented basically. So that's the first big and probably the most important recommendation they mentioned. They suggest that you know, big surprise we should administer enteral feeding as early as possible and that, in addition to all its other benefits, that it does reduce the risk of stress-related upper GI bleeding. Again they recommend that patients that at risk and again bleeding, again they recommend that patients at risk and again it's these four types of patients do be considered for stress ulcer prophylaxis and that even if they're internally fed, that they do suggest stress ulcer prophylaxis. So again, that's been some area of debate is do you even need to give pharmacologic agents for stress ulcer prophylaxis? In patients who are being fed entrally, they do recommend that, again, if they have one of these four risk categories, that even if you're feeding them entrally, you probably should go ahead and start stress ulcer prophylaxis. But if they are at low risk, they suggest not using stress ulcer prophylaxis again, especially if they're being internally fed. So again, huge, huge change.
Speaker 3:As far as other recommendations, they kind of say, and again the study that we're going to talk about here in a minute may upend this, but they actually suggest either proton pump inhibitors or H receptor antagonists. They say either is reasonable. I'm old enough to remember back when some clinicians recommended sucralfate for prevention of stress ulcers, the theory that it caused less bacterial translocation. I think that there's been enough randomized control trials that have suggested that's actually not a thing and that actual anti-separatory agents like PPIs or H2s they actually seem to do a better job at preventing stress ulcers. So that's kind of out and either of these is reasonable. They give this a fairly low level of recommendation and again, I think it's because this is before.
Speaker 3:The study we're going to talk about just came out. They noted that you know, the problems with proton pump inhibitors has always been a theoretical increase in development of pneumonia or C, diff and colitis, as well as some retrospective studies suggesting that patients who got proton pump inhibitors for stress ulcer prophylaxis in the ICU actually had increased mortality, even though they didn't make a lot of sense from kind of a biological plausible thing. So I think that with these guidelines they kind of, you know, were not very keen on making a recommendation of one over the other. H2 blockers, of course, do have the risk of thrombocytopenia, which, god knows, I've seen over the years. As well as that, it can cause an increased risk of delirium, like all histamine blockers can.
Speaker 3:So they say it doesn't matter whether you give stress ulcer prophylaxis, po or IV. I think that's think that's reassuring to pharmacists all over the country who's one of the things they always do is automatically switch patients who are, for example, on IV pantoprazole over to around. In my world we use a lot of the dissolvable tablets of lanceoprazole, but other places do other things. They note that the lowest dose possible of drugs should be used and so, for example, you know, 40 milligrams a day of pantoprazole, 20 milligrams BID of famotidine in someone with normal renal function, and that it should be discontinued as soon as that risk factor is no longer present. Now, of course, the only one that's really probably going to affect is shock patients, right? Because if you have chronic liver disease, you're always going to have chronic liver disease right.
Speaker 3:So it's mostly going to be shock and I suppose you know if patients are improving in neurocritical care patients, you should stop therapy. They also again when the patient gets discharged from the ICU, that therapy should be stopped unless they have another indication for anti-secratory agents. We have had studies now for over 10 years that suggest that a lot of patients who get started on these medications in the ICU go to the floor on them and actually go home on them for no real reason.
Speaker 3:So that's something that we need to be kind of vigilant about it and protect and watch against again just for no other reason for polypharmacy issues and stuff like that. So now, of course, a lot of patients already are on anti-secratory agents, particularly proton pump inhibitors, and so a question I sometimes get asked is okay. Well, you know, we've extubated the patient back when we thought intubation was a big risk factor. Should I continue their proton pump inhibitor? And my answer has always been well, if they were on a proton pump inhibitor on the outside.
Speaker 3:yeah, we probably should continue it on the inside, though it was probably for GERD. That's what most people are on proton pump inhibitors for. The final recommendation basically says something similar that you know if somebody's no longer at risk, you have to just basically consider the benefits and risks of continuing the antiretroviral radiation. So in a nutshell.
Speaker 3:That's kind of the guidelines. Again, you know we've got a link to the guidelines in the show notes. You can kind of take a look at them yourselves. But I think the real, real big one, the one that is absolutely going to change my practice, is that mechanical ventilation is no longer a risk factor. So that's just huge. So, matt, what do you think? You know I try and think about you know how are we going to implement this at our ICU? I suspect I'll probably be talking to your partners and probably trying to get everyone together, maybe shoot them an email about this. But yeah, it's pretty big. So what do you think, matt?
Speaker 2:Yeah, so this is really a game changer, right? Yes, exactly.
Speaker 3:Yeah, no, you're right.
Speaker 2:No, this was a surprise. I, when I wrote my notes after reading this, I put an exclamation point next to it. This is a total practice changer in what we do in the ICU. I mean, it's one of those measures we always want to make sure we have and that we don't miss. And so to see this sort of change happen with mechanically ventilated patients you know that it's not a risk factor for stress ulcers it is surprising. But I also think that the authors are to be commended for doing this.
Speaker 2:You know it's the Society of Critical Care Medicine has in the last year, published a number of guidelines. They've done a number of meta-analyses to help really give us some guidance on what to do. And we know that when we follow the evidence and we kind of follow guidelines, that patients get cared for better. And we know that there's risks, albeit minor and probably theoretical, about drugs. But there's always a risk and benefits to any therapy that we use. And if something's not going to help somebody and potentially put them in harm's way for other problems to develop, then we shouldn't do it. So or we should think about the why we do it and we shouldn't just do it Cause that's what we've always done so.
Speaker 2:Um, you know this is huge, but I I have a hard time thinking this is going to be accepted. But I don't know what the buzz has been. Um, you know, and the other concern that we see is the regulatory side of things. You know in what CMS and other regulatory bodies are going to look at, and when they measure quality with patients, they tend to take several years to change their recommendations. So there's a lot of concerns, a lot of different ends with this. But you know it's, it's surprising, but I'm glad that they did it. And you know we're always open to change and to do things better for our patients. So it changes. I mean this is going to be trying to turn around a ship in the ocean. I mean this is going to be huge. It's not going to be an easy thing just to stop doing so. We've got to change the way we think, but that's why we're doing it.
Speaker 2:So that's why we do these things.
Speaker 3:So we've got to change the way we think, but that's why we're doing it. So that's why we do these things. And you know, here, you know, in our hospital, of course, you know, like most hospitals in the country, have, you know, order sets attached to the electronic medical records. You know, I think you know, once we kind of disseminate this information among your partners and, I think, among the residents, I think, yeah, that'll be the next step is, you know, do we remove that? You know, you know, automatic checkbox, the mechanical ventilation order set, do we, you know, say, well, you know you can do this, but consider these risks, other risk factors. Yeah, I mean, I think that's going to be, that's going to play a role in that. You're absolutely right.
Speaker 3:The Joint Commission, cms, are always behind, you know. You know way behind often sometimes with are always behind, you know, you know, way behind often sometimes with with what guideline recommendations are. And yeah, I'd hate to see you know our hospital, other hospitals, you know, get dinged by by some of these regulatory ages. Well, you know, you know you stopped using. You know, you know, protonics in your, in your mechanically ventilated patients and unfortunately, it's been my experience, they experience that showing these regulatory bodies. But these are the new guidelines, this is what it shows. They don't care, right. I mean they you know. Well, I'm sorry, but this is our measure, this is our metric, and you didn't meet it. So you know, we don't really care why you didn't meet it, you just didn't meet it. So I think, yeah, I think that's something that we're really going to have to take a look as well as well.
Speaker 3:Turning to you know, you know which agent. You know, have you ever had a preference? I don't think you have and I don't think any of your partners really have. I think we went, I think we went kind of you know, all proton pump inhibitors in the early 2000s. And then I think, as there was some evidence, like I just talked about, where there may be harms, and I think you know certainly the pendulum scene, at least in our system, the pendulum kind of swung back more to H2 blockers. But what's kind of been your personal preference, if any?
Speaker 2:Ooh, that's a loaded question. Yes, it is. So I actually prefer PPIs and part of it's delivery. We can easily give Lansoprazole enterically, part of it's delivery. We can easily give Lansoprazole enterically, and I find delirium more problematic in the intensive care unit and with the critically ill patient, and I have much more patients at risk for that, I feel.
Speaker 2:And so if there's anything that I can do to try to avoid that and that includes not give a medication that has been known to link to that with the histamine blocker that I tend to try to avoid it, and I think that the data and we'll talk about it in the next study too in general I think the authors note this in the guidelines is that for reducing upper GI bleeds from stress ulcers, that PPI has probably got a little better data from their recent study, from their meta-analysis, and so I think that just supports my practice and what I do, and I've seen it both ways. When I trained in fellowship, I had attendings that had different preferences too, and that was based on what the guidelines and the evidence were at the time. So I typically prefer PPIs, and if we can give it enterically with Lansoprasol, I tend to prefer that, and that way, we don't have to worry about the excess volume and it's pretty easily to administer.
Speaker 3:So that's what I prefer, and I think that's reasonable and I was glad to see that that you know they didn't prefer IV over PO in this case, as you know, in fact, yesterday on rounds you were talking about the fact that you know we tend to fluid overload. You know, patients, just because they get so much piggybacks, so much, you know, continuous drips on stuff, that it's it's very, very easy to push these patients into fluid overload and so, yeah, anything we can do, even if it's a hundred mils less a day, that's a hundred mils less a day, you know. So I, I, I think that's that's kind of good too. And again, you know, uh, I remember a study that came out in the mid 2015s and again it was a retrospective study that you know suggested that oral therapy may actually be superior as far as proton pump inhibitors. And you know, I'm not sure, you know, I ever really jumped up and down on that, but I, you know, that kind of made me feel good that you know, it really doesn't matter which way you go. So I was kind of glad to see that. I completely agree with you. That you know, I think that you know that safety balance between oh, we're going to cause C diff versus oh, we're going to, you know, cause delirium, you know, I think, I think has has really kind of kept people on the fence, and so that's a terrific segue into our, our, our next topic.
Speaker 3:So, interestingly, just as this set of guidelines was was released, and I'm I'm I'm sure Rob and his and his group just went you've got to be kidding me, because the Lord only knows how long they've been working on these guidelines, right? I mean, I have no doubt it took them months, maybe even a year plus, to actually get everybody together, have them, review the data, get to people who are expert in meta-analysis to do the stuff, sit down and and, and you know, do multiple online meetings to figure this out. You're super proud. You come out with this, you know, state-of-the-art, uh set of guidelines and then two weeks later, the Wing and Journal of Medicine publishes a paper. That makes you go. You've got to be kidding me, so, but it is what it is, you know, and that's and that's how evidence-based medicine goes.
Speaker 3:So in the July 4th 2024 issue of New England Journal, a paper was published on stress osoprophylaxis during invasive mechanical ventilation, and the study was called the revised study. So you know, again, this study was done. It was a multicenter, randomized study, done not in the United States, but also a wide variety of other countries Brazil, pakistan, saudi Arabia, et cetera, et cetera. Like all critical care studies you know you need to have, almost always has to be a multicenter study to get the number of patients. You need to show a significant difference. The authors point out just we've been talking about is that you?
Speaker 3:know proton pump inhibitors, as Dr Trump pointed out do over H2 blockers probably have added benefit in preventing significant upper GI bleeds.
Speaker 3:But small studies have suggested that there might be an increased risk of pneumonia, increased risk of C diff, and that there again has been a signal for actually increased mortality in patients who receive proton pump inhibitors for stress ulcer prophylaxis in the ICU. So that's where the revised study came out. It's, again, probably the only randomized control trial we're ever going to see on this would be my guess, and they, you know, tried to answer the question. You know, first of all, do proton pump inhibitors in fact prevent stress ulcers? I think we've kind of known for a while it does, but they were going to do this large study, so why not? But I think, much more importantly, and I think they talk about this, this was more of a, even more of a safety study. They really wanted to see, you know. You know, in a randomized control study, are these risks that we've talked about, you know, actually real or are they residual issues? So in this study, the patients were over 18 years of age, they underwent mechanical ventilation. So right, there you're like. Well, hold it a second. We just said mechanical ventilation isn't a risk factor.
Speaker 3:Well, I'm sure when they started this study they weren't aware of what the guidelines were going to be.
Speaker 3:So you know, these people did receive mechanical ventilation that was continued to be continued it wasn't like a 24 hour and then be extubated.
Speaker 3:They had to be initiated to be in the study at least 72 hours before randomization and that if they had received more than one daily dose equivalent of acid suppression in the ICU or if acid suppression was specifically indicated or contraindicated. So I think that's another key issue with the study was that if you were already on a proton pump inhibitor coming into the study, you weren't included under most circumstances. There were some exceptions to that, but you basically weren't included as far as the study is concerned. They then randomized patients one-to-one to receive either intravenous pantoprazole or placebo. They did stratify by trial center and pre-hospital receipt of acid suppression. So again, you know, even though they tried not to get people in, I think they basically found that that was almost impossible to do, since so many patients are on acid suppression therapy on the outside, the placebo and protonics were exactly the same and I, you know, I've seen enough IV protonics to know you really couldn't tell the difference if they're not labeled.
Speaker 3:So that was pretty easy to do it was administered by nursing staff in a blinded manner for up to 90 days Hopefully I didn't happen too often or until discontinuation of mechanical ventilation. The occurrence of a pre-specified clinical indication or contraindication to proton pump inhibitors or death whichever came first.
Speaker 3:So you know there's that. They then collected all sorts of data to kind of stratify patients and basically compare them and look for confounders and stuff like that. The primary efficacy outcome was clinically important upper gastrointestinal bleeding, which they defined again as something that required either blood or some other therapeutic intervention in the ICU, hemodynamic compromise or readmission to the ICU during the index hospital stay for up to 90 days after randomization. So they then had two trained physicians who were unaware of the trial group assignments and they're the ones who looked at bleeding events and said, yes, this is, you know, related distress ulcers and stuff like that. Secondary outcomes the primary safety outcome first was death at any cause at 90 days, because again they wanted to see if this signal for increased mortality was actually real or not. They also looked again at C diff infection, incidences of pneumonia, incidences of renal replacement therapy, hospital mortality and other things like that. They also had tertiary outcomes, which was the total number of units of red blood cell transfusions, creatinine levels, duration of mechanical ventilation and length of stay in the ICU and in the hospital. Hospital Statistical analysis they estimated they'd need about 5,000 patients to provide the trial of 85% power to detect a absolute difference in 1.5% in the incidence of upper GI bleeds.
Speaker 3:So again, keep in mind that the study was powered to look at that and less powered to look at the safety outcomes. So just something to kind of keep in mind. They did again try to account for things like how sick patients were coming into the hospital, their Apache 2 scores, did again, uh, um, try to account for things like how sick patients were coming into the hospital, uh, their Apache two scores. And again, for, for those who don't practice in critical care, apache two is basically a, a, um, standardized way to to take a look at different comorbidities and laboratory values to, um, uh, look at risk of death, uh, particularly from septic shock, but from other things along those along those lines as well death, particularly from septic shock, but from other things along those along those lines as well. And then of course they did all sorts of, you know, regression analyses or things along those lines to kind of match patients for all these different, different issues as far as the results of the study.
Speaker 3:Taking a look at the patients themselves, average age was 58. Apache score was 21. And 24 is usually the breakpoint at which mortality really spikes, particularly in septic shock. So these were sick patients.
Speaker 3:These were patients who were in with overdoses or something like that. They were pretty sick. Majority male, about 61 percent between the two. Vast majority were MICU patients. So patients in for medical reasons, and leading the list was respiratory issues. Big surprise there, those sepsis. Neurologic issues were pretty high as well. Again, they tried to keep patients who were not on pre-hospital acid suppression and they managed to do that in 76% of patients. So that was pretty good. And then the rest the vast majority of the rest were on proton pump inhibitors prior to admission.
Speaker 3:They did look at glucocorticoid administration for greater than one week before randomization and that was the same between the two. Don't know why they did that, because the evidence is actually pretty clear that steroids by themselves do not increase the risk of GI bleed and that's been kind of studied into the ground. But they did that anyway. 100% of patients were on mechanical ventilation, 70% of them were on vasopressors and 6% were on some sort of renal replacement therapy. So again, these were sick patients, right as far as the outcome was concerned, when they took a look at that, that pertonics or placebo was administered for a median of five days and the range was three to 10, and there wasn't a lot of switching between things, so I think that was important as well. Looking again at clinically important upper GI bleeds, clinically important upper GI bleeds occurred in 1% of the patients receiving pantobrasol and 3.5% of patients who received placebo. So an absolute risk difference of 2.5, which was well, and 3.5% of patients who received placebo. So an absolute risk difference of 2.5, which was well within their power and, of course, was statistically significant. Again, that may not seem like a large number but again, when you take a look at the wide variety of patients admitted to the ICU, that is clinically significant as well as statistically significant as well.
Speaker 3:So, and then when they looked at, you know, different patients across different outcomes, whether they had sepsis or not, whether they were on renal replacement therapy or not, whether their creatinine was high, et cetera, et cetera, et cetera. Those numbers were, you know, held, held firm pretty much across all the subgroups. The big outcome was was patients who required a transfusion of at least two units of blood, but there was other ones as well, but that was the thing that was the highest among the groups. And then you know, again, I was actually more interested in the safety analysis and what they basically find was there was no difference between safety outcomes between pantoprazole placebo group.
Speaker 3:Ventilator associated pneumonia was virtually identical 23%, which in our world is a pretty high number nowadays. There was no significant difference in C diff infection and there was no difference in all cause or in-hospital mortality between the two. So at least in this group there was no signal or no evidence to suggest that there was significant harm associated with proton pump inhibitors compared to placebo, and in fact all-cause mortality was about 20% in both groups. And then everything else again didn't show a significant difference, except things like the need for more than two nuspector blood cells. There was no difference in hospital stay, there was no difference in ICU stay, et cetera, et cetera.
Speaker 3:So what this study kind of really shows is that I think proton pump inhibitors are very effective at preventing clinically relevant upper GI bleeding, not just covert bleeding. And more to me, much more importantly, there is no signal, no evidence at all that proton pump inhibitors are associated with any of the bad stuff that we've previously thought of. So really I think this positions proton pump inhibitors as the treatment of choice for stress ulcer prophylaxis, even given the fact that again, the reason for stress ulcer prophylaxis in this group is no longer considered a major reason. The only other real thing I was kind of concerned about this study that they don't really talk about at all was enteral feeding, and again, we've said multiple times now that enteral feeding is associated with a decreased risk of stress ulcer prophylaxis, and I did some digging into the supplemental materials as well and they don't really talk about that at all, which kind of surprised me. You would think that'd be something they'd definitely want to talk about.
Speaker 3:So you know I think you know, this study basically, in my opinion, kind of shows that we probably should be using proton pump inhibitors as the major treatment. So, matt, again, what's your take on all this?
Speaker 2:Yeah, so this was fascinating Large randomized trial, which is really what we want to see. You know multi centers and it looks like they carried out over a number of years. So you know, again, the authors are committed to doing this degree of work to get us this information. And you know, I just think, stepping back and looking at the evidence just in general and the methods, you know, anytime we do a randomized control trial, that's really what we see and that's kind of our highest level of evidence and and as good as and as helpful as meta-analyses can be, they really take a look at the big picture. But that, you know, it's these randomized trials I think, that give us a lot more details and can help kind of guide our practice on the ground.
Speaker 2:I think meta-analysis are really high level and they can kind of give us some ideas and and thoughts and things, but but with the randomized trials they really kind of get. I think they help with the nuance of the conversation. Right, and I think that's what we see in this study, is that there is a nuance. So, absolutely, ppis help, okay, with patients on ventilators to reduce stress, ulcer and bleeding, and it'd be interesting if they rer-ran their numbers, if their thoughts on mechanical ventilation being a risk factor would be different, because there was obviously a therapeutic benefit here.
Speaker 2:The other things about the baseline characteristics of the group that I thought were noteworthy is that 70% of the patients were in shock and on pressers, so that's still a lot of patients that are that are still going to need to be on mechanical ventilation and needing some sort of stress ulcer prophylaxis. You look at people who are probably coagulopathic and and have some of these other conditions and you might be taken up to to, you know, another five to six, maybe 7% of patients are going to need in general, and I think what it depth, I think what it helps me understand too is, you know, the patient that comes in with an overdose, who's on a ventilator, who doesn't have a lot of risk factors, um, or maybe, like a patient with a COPD exacerbation, for example, not in shock, just needs to let some time to have their vent, you know, let some time to have their um, their lungs get better, or just kind of a straightforward, which there's no real thing of that in the ICU, right?
Speaker 2:But a little more straightforward vent patient probably doesn't need it. Okay, you know, and and I think that that helps I think that helps with some more um, just kind of the nuance of the of the situation, and then we don't have to expose them to a drug that they don't need. Of the situation, then we don't have to expose them to a drug that they don't need. And you know, that's what I think and that's what I gleaned from it. You know, you read the guidelines at first and you say, okay, well, I'm not going to use them on vent patients anymore. But then you read this study and you're like, okay, well, no, my practice might change a little bit, but probably not too much, because most of these patients are going to have these issues when they're receiving mechanical ventilation.
Speaker 3:Yeah, it'd be interesting to say and I would if I were the investigators you've got the data. I mean, now that these guidelines are out, why not run a post hoc analysis just on the shock patients or just on the patients? I mean they have the data. Why not run that information?
Speaker 2:Yeah, I think I would be floored if these guys don't do that, cause you know you know, yeah, you know, you publish a great paper like this and they, they're, they're going to have the opportunity to go back and publish three or four more studies. Exactly, exactly.
Speaker 3:Correct, so are you. So I think you know you had already said proton pump inhibitors were probably your, your, your stress holes or prophylaxis agent of choice, this kind of cements that you think.
Speaker 2:Yeah, I think so. I think you know if we're going to do it and they have an indication for it. This is compelling enough evidence to say, yeah, we should probably use a PPI. Obviously, they didn't do a head-to-head study right with H2 blockers, and we know that's probably not going to happen. But this is enough, and I think of enough of a difference and enough of a sample size and and and you know, enough of a of a meaningful difference, that that it's going to make it that that's going to be my choice.
Speaker 3:So yeah, I agree. That's probably what I'm recommending from now on too.
Speaker 2:Without any detriments, you know, without concerns. And that was the other. I think things that I can glean from this study is the concerns for C, diff and venal associated pneumonias that that have been brought about through other studies. We didn't see that risk increase in this trial and and I think the power of the study is is enough. That helps me feel more comfortable that that's, that's the right way to go.
Speaker 3:I agree so so, yeah, I, you know, I think, I think you know in totality, you know, yeah, these, these two documents, I think are, are, are really going to, are really going to drive forward, I think, some, some big changes in the ICU and certainly how I'm going to start recommending stuff. Though, again, before Matt starts to panic, not before I contact all your partners and say, why are you doing this? You know so, yeah, so I will, I will be sure to, to, to, to, to send out an email to all your partners and say, okay, this is why we're doing this now, sort of thing. But but, yeah, I think you know, yeah, I, this is, this is going to be a change and and you know, you know you're right, change is always hard, especially for ingrained things in the unit, but we've done it many times before. I think probably the most recent one is the lactated ringers versus normal saline thing.
Speaker 3:You know what I mean. That was a huge, huge shift in how we did fluid resuscitation. Now, really, two or three or four years after the fact I don't think I've it's been a long time since I've seen normal saline use, so it could happen. But you're right, it just takes time.
Speaker 2:So any last minute thoughts, you know, if you apply to a patient. It was funny. We had this talk on rounds the other day. We had a patient who was on a ventilator for a while, kind of sick, but never really had any other of the risk factors and we hadn't started them on a PPI yet. It was just one of those things that that we hadn't thought about and the pharmacist brought it up.
Speaker 2:Hey, you know, we should probably do this and now it, you know, with that patient in particular, we probably didn't need to, and so I think that's, you know, just a good time to pause and it, you know, that's why we have pharmacists with us rounding, that's why we have the discussion to, to to highlight opportunities for improvement and better ways to care for the patient. But now we have a different way to discuss that, so it's great. I mean, I, we always love changes and new things and, um, yeah, I guess the last thing I this is probably um anticlimactic, but I was fascinated by the fact that in this study, um, 70% of the subjects were not on PPIs coming into this, and I think that goes and says a lot to the differences in the way medicine is in different parts of the world.
Speaker 2:Whereas the US. I don't know what it's like, but I'm guessing it's probably coming into the ICU. We have at least probably half or more.
Speaker 3:Right, at least yeah. I mean again most of these patients have multiple core morbidities and they're all going to mean again this isn't a healthy 30 year old guy walking around. He may not be on a proton pump inhibitor. These are all patients with multiple morbidities, exactly.
Speaker 2:So you know there may be some unanswered questions with that down the road. That's just hypothesis generating, just you know, one of a small little piece on the end. But yeah, these are great studies and great work by the authors and you know it's it's a lot of fun to talk about when it can impact our practice.
Speaker 3:So that's where we're at, jen. What do you?
Speaker 2:think.
Speaker 1:Well, I thank you both for this discussion today. We've run a little long but I was like that's okay, cause we there's so much here. I really appreciate the call out for transitioning, you know, new guidelines into practice, and I think that's a challenge that so many healthcare providers face is, you know there's these measures and standards and you know things that you're guided on from an administrative perspective, but then there's the practice and there's the patient nuances and the guidelines that come out quickly. You know, in this case, of course, we talked about 25 years, but now that they're out, it's like okay, now we have to change this, because now you've read it and you know. So when you see that patient, you're like, okay, this is what I should do.
Speaker 1:But then you know joint commission is saying do this, or a measure that's going to be two years lag, you know, down the road. So I think those are some of the challenges and you know I think Dr Trump, you talked a little bit about you know regulatory and legal. You know there's all of that that plays in and so it's not just a guideline change, it's all the other pieces. So it's a big picture and you know getting everybody on board and making those formulary changes and you know everything. So I just appreciated that call out because it's not just clinical. There's a lot of things that play into health care these days. So yeah, appreciate it.
Speaker 1:Well, thank you so much. Thank you Dr Trump, thank you Dr Wall and, as always, if you are a CE plan member, be sure to claim your credit by logging into CEimpactcom, and we appreciate you being with us. Have a great week and keep learning. We'll talk to you next week.
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