Stig B Laursen: Stig B Laursen In my view, it's one of the most powerful drugs within gastroenterology. And furthermore, if you give it prior to the endoscopy, you'll double the chance that you're able to control the bleeding during the endoscopy.

Intro: Intro Welcome to the ESG podcast, Endoscopy Unplugged, Join us each month to hear the latest from European experts and where we'll discuss relevant clinical topics and provide you with tips and tricks, practical scientific evidence and pearls of wisdom to inform your endoscopy practice. So please subscribe wherever you get your podcasts and join us as we advance GI endoscopy care.

Ian Gralnek: Ian Gralnek Hello everyone and welcome to episode five of ESGE's podcast, Endoscopy Unplugged. My name is Ian Gralnek, past president of the ESGE and I am your host. Today's podcast is titled Acute Upper GI Bleeding, What to do before upper endoscopy. And my guest is Professor Stig Laursen, Department of Gastroenterology at Odense University Hospital in Odense, Denmark. Stig has a special interest in upper GI bleeding and is one of the co-authors on the ESGE's updated guideline on peptic ulcer bleeding that just came out online earlier this month. Stig, it's great to have you here. Welcome to the podcast.

Stig B Laursen: Stig B Laursen Thank you, it's a pleasure indeed and honour to be here.

Ian Gralnek: Ian Gralnek So Stig, before we actually get into this, I do want to ask you a real quick question that I think everybody would be interested in. How did you decide to pursue a career in GI endoscopy?

Stig B Laursen: Stig B Laursen Well, my father was a gastroenterologist, also liking Upper GI bleeding and ERCP, so I was looking at endoscopic videotapes in my childhood and starting doing endoscopies at 19 years. So I've liked it ever since.

Ian Gralnek: Ian Gralnek Are you practicing at the same hospital that he was? Wow, that's really cool. did not know. Yeah, I did not know that. Any of your kids into medicine?

Stig B Laursen: Stig B Laursen Not yet, not yet, they are not old enough.

Ian Gralnek: Ian Gralnek okay, so we'll see if they are smarter and maybe go into a different field. Okay, so Stig, let's get at it. So patient presents comes to the emergency department with signs and symptoms of acute upper GI bleeding. And what I mean by that is somebody who comes in with hematemesis, whether it's fresh or coffee grounds and or melena. So my question first to you really is when you see these types of patients, what's your initial evaluation of these patients in terms of hemodynamic evaluation and management, in terms of IV fluids and even what do you do about blood transfusions?

Stig B Laursen: Stig B Laursen That's an enormous great question, so to say. First, I like to keep it as simple as possible and divide patients into patients who are circulatory stable and patients with hemodynamic failure. And you can of course discuss how will you define hemodynamic instability, but to me, if patients have a systolic blood pressure below 90 and 100 millimetres of mercury and ongoing hematemesis or melena, then they have hemodynamic instability. So if we start talking about patients who are circulatory stable, it's fairly easy related to which transfusion strategy you would use. You need to know whether or not they have ischemic heart disease or not. So if we take stable patients without ischemic heart diseases, you can be guided by the haemoglobin concentration. And if it's below 7 gram per decilitre, you would normally recommend blood transfusion with the aim of a haemoglobin concentration between 7 and 9. And for patients with ischemic heart disease, we know there's an increased risk of ischemic events. And for those we would recommend giving a transfusion if the haemoglobin concentration below 8, aiming for haemoglobin concentration above 10 grams per decilitre.

Ian Gralnek: Ian Gralnek So in most patients, you're really following what's called a restrictive blood transfusion policy?

Stig B Laursen: Stig B Laursen Yeah, yeah. And the reason for that is that we have a couple of RCTs and meta-analysis showing that use of a restricted transfusion strategy is safe and associated with a low risk of transfusion related reactions. And also if you look at the Villanova study, there was a lower mortality risk among patients with recent bleeding and cirrhosis. So it seems optimal to do it that way.

Ian Gralnek: Ian Gralnek What about your use of crystalloid fluids and IVs, peripheral IVs or a central IV when these patients first come in?

Stig B Laursen: Stig B Laursen Yeah, yeah, crystals perform very good. And of course, you can discuss whether or not to use simple saline or more balanced crystal transfusions. And there's no clear evidence that perhaps in high risk patients at intensive care units, there may be a benefits of using compounds like Ringer's solution. But at our hospital for most patients, we simply use saline and then for the subgroup of patients having a they requiring a major volume of resuscitation, then we shift over and using Ringer's solutions.

Ian Gralnek: Ian Gralnek Okay, so the first thing we really need to do with these patients is to get them hemodynamically stabilized using crystalloid fluids and potentially blood transfusion. You agree with that, right? Okay. And also, would you agree that a lot of times these patients get into problems because they have other comorbidities that we're not fully dealing with prior to endoscopy? What do you think about that?

Stig B Laursen: Stig B Laursen That's a very important remark. To me, the single most important source of bleeding is peptic ulcer bleeding, accounting for around 30 to 40 % of cases, depending on your case mix. And there we have a very nice cohort study from Hong Kong showing that around 80 % of case fatalities actually are due to comorbidity, either newly developed comorbidity or worsening of existing comorbidity during hospital admissions. Therefore, it's very important in my view, when assessing these patients to have a step back and not only focusing on the bleeding, but everything that may threaten your patient's survival.

Ian Gralnek: Ian Gralnek Really, it's a really good point. Well, I think we'll sort of get back at this a little bit when we talk about the timing of endoscopy, which we'll get to a little bit later in the podcast. Any other points you want to bring up in terms of the initial patient evaluation and management?

Stig B Laursen: Stig B Laursen Yeah, we didn't talk that much about patients with hemodynamic failure, but it's important to know that they have very poor prognosis with a fivefold increased risk of mortality with a low central blood volume, a low tissue perfusion and risk of multi-organ failure. So if these patients doesn't respond to intensive resuscitation using crystallites, perhaps you want to consider using a balanced blood transfusion strategy in these patients. There's no hard evidence for that in upper GI- bleeding, but we know from studies within trauma patients requiring more than 10 units of blood within the first 24 hours that you, in those patients at least, can reduce mortality rates by using a balanced blood transfusion strategy. What you need to think of is that these patients have a massive loss, not only of red blood cells, but also platelets and coagulation factors. So that can be considered in those patients.

Ian Gralnek: Ian Gralnek Do transfusion platelets routinely?

Stig B Laursen: Stig B Laursen Yeah, in patients with severe ongoing bleeding, we use this and continuing low blood pressure that doesn't respond to crystallites, we use a combination of red blood cells, plasma and platelets in a one to one to one ratio corresponding to whole blood in order to try to stabilize them.

Ian Gralnek: Ian Gralnek Okay, let me move on to something else. What's your thoughts currently about the role of an upfront IV PPI prior to endoscopy in these types of patients?

Stig B Laursen: Stig B Laursen Well, that's a classic discussion. There are randomized controlled trials and meta-analysis indicating that you will reduce the patient's risk of needing endoscopic treatment. What's a bit strange is that the same meta-analysis did not find any difference in the rate of patients having high risk stigmata of bleeding. So I'm not really sure why that actually decreased the need for endoscopic treatment if they looked the same, whatever they found. But more importantly, there were no difference in patients' outcomes and no difference in mortality. Also, there was a recent Italian cohort study, including I believe it was more than 2,000 patients that were not able to find any association between use of pre-endoscopic PPI and need for endoscopic treatment or any other outcome.

Ian Gralnek: Ian Gralnek But do you guys still give it when these types of patients come to the emergency department?

Stig B Laursen: Stig B Laursen We senior doctors don't, but sometimes when a junior colleague sees these patients, they do it anyway. I think they want to do something good for the patients and perhaps they are not aware that they don't help the patient by doing it.

Ian Gralnek: Ian Gralnek Yeah, we actually tend to give these patients, even though I agree with everything you've said in terms of the evidence, that in terms of clinically relevant outcomes, it probably doesn't change those things. I can say that our emergency department still routinely puts these patients on an upfront IV PPI prior to endoscopy. What about risk stratification when these patients come to the emergency department? Do you have a protocol in your emergency department to risk stratify patients and if so, what do you guys use them?

Stig B Laursen: Stig B Laursen We recommend using the Glasgow Blatchford Score because it has two important aspects. First, it has a high discriminative ability to predict patients need for hospital-based intervention or death. And secondly, it has a clinical consequence, patients scoring zero or one have a very good prognosis and can be discharged from the emergency department to outpatient endoscopy within a few days.

Ian Gralnek: Ian Gralnek Are you guys actually discharging those patients who have a score of zero one?

Stig B Laursen: Stig B Laursen Yeah, yeah, we implemented it, I think it was around 12 years ago, and we have reduced the number of yearly admissions with Upper GI bleeding with 100 cases per year after implementing this. And then we have two pre-booked times slots in our endoscopic lists every week so we can discharge them to one of those time slots.

Ian Gralnek: Ian Gralnek Yeah, so that's really important that at least they understand that they're going home, but they are going to give an appointment to come back within a couple of days. And I assume you're also providing them with the knowledge that if they have any recurrent symptoms that they need to immediately come back to the emergency department for re-evaluation.

Stig B Laursen: Stig B Laursen Of course, of course.

Ian Gralnek: Ian Gralnek I was gonna ask you, have you had any negative outcomes in some of these patients who you have sent home? Because I think that oftentimes is the fear, both of gastroenterologists as well as emergency department physicians that we're gonna send these patients home even though they're very low risk that something bad could happen. What's been your experience with that? Any bad outcomes?

Stig B Laursen: Stig B Laursen No, I think we have had a case or two where we found an ulcer at the endoscopy, but there were no bad outcomes where there were cases with need for endoscopic treatment or death or anything like that.

Ian Gralnek: Ian Gralnek I think it's great that you guys have implemented that and so long ago, because I think most places have not done that, at least my experience by talking to people. I think you're ahead of the curve, so to speak. So let me change this a little bit. So a patient, comes in with acute upper GI bleeding. What do you do in those patients who you suspect may have variceal upper GI bleeding. They have some chronic liver disease history or you can tell by their appearance with stigmata of liver disease that you're worried they're actually having a variceal bleed. How do you act differently in those types of patients?

Stig B Laursen: Stig B Laursen Well, in those patients, if we believe there is a significant risk that they have a variceal bleeding, we got a very good drug that is terlipressin, which we can use prior to the endoscopic procedures. It is shown in meta analysis and a Cochrane analysis that it reduces the six weeks mortality with around 40%. So in my view, it's one of the most powerful drugs within gastroenterology. And furthermore, if you give it prior to the endoscopy, you'll double the chance that you're able to control the bleeding during the endoscopy. So I believe it's a very important drug.

Ian Gralnek: Ian Gralnek Okay, so you guys are starting terlipressin already in the emergency department. We do the same thing. We do the exact same thing. What about antibiotics? Are you giving antibiotics up front?

Stig B Laursen: Stig B Laursen No, we normally don't do it prior to the endoscopy, but await the endoscopy before doing it. You may of course argue with, in general with antibiotics, the sooner the better. But in contrast to terlipressin, use of prophylactic antibiotics prior to the endoscopy will most likely not change the outcome of the endoscopic procedure.

Ian Gralnek: Ian Gralnek Okay. We give it just because we usually give a gram of ceftriaxone, more because of we want to potentially prevent SBP or other types of infectious issues because of translocation of bacteria at the time of endoscopy.

Stig B Laursen: Stig B Laursen That makes sense.

Ian Gralnek: Ian Gralnek Can you tell me about how are you managing, anti-coagulants and anti-platelet agents? today we see many, many patients, especially older patients who are on low dose aspirin or they're coming in on a direct oral anticoagulant or even a vitamin K antagonist. What are you doing with those patients initially prior to endoscopy and in holding their medications? What's your pathway for that?

Stig B Laursen: Stig B Laursen Well, in the vast majority of patients, the main thing is just to withhold it until the endoscopy, so we know what is the patient bleeding on from and what is the bleeding related prognosis. And then there's a subgroup of patients with severe bleeding, for example, patients taking vitamin K antagonists with severe bleeding or with a very high INR. And those we consider using fresh frozen plasma or vitamin K in order to try to get the INR a bit down before the procedure. There was some data, I believe it was from the UK audit from 2007, where they showed that a high INR value was one of the strongest predictors for persistent bleeding. And there are also two RCTs showing that if you can get the INR, if it's above, think it was above 2.5, if you can get it down between 1.5 and 1.8 before the procedure, the outcome is fairly good for those patients.

Ian Gralnek: Ian Gralnek What are you doing for the patients who are on dual antiplatelet agents? We also see a lot of those patients.

Stig B Laursen: Stig B Laursen Normally we just pause it until the procedure is done and in high-risk ulcers needing endoscopic treatment we will keep it withheld for around three days and the other part will just continue it after the procedure.

Ian Gralnek: Ian Gralnek Okay, so wait, so if I understand right you're keeping them on the low dose aspirin but holding the second antiplatelet agent and then restarting it within three to five days after the endoscopy

Stig B Laursen: Stig B Laursen Yeah, exactly.

Ian Gralnek: Ian Gralnek Okay, okay, that's what we do too. At least for the dual antiplatelet agent patients, we think it's really important to keep them at least on their low dose aspirin and temporarily hold that second antiplatelet agent. So you guys are doing the same. Okay, and that's what guidelines recommend as well. So we've done all these things. We've now hemodynamically resuscitated this patient. They may or may not have gotten an upfront IV PPI. They're risk stratified. They're not zero or one on the GBS. So, you know, this patient needs to be put into the hospital. They're more severe. They probably don't have variceal bleeding. We don't think so. There's no history of liver disease here. Do you, are you, you you're getting ready to do endoscopy. Do you use a prokinetic agent prior to upper endoscopy? Do you give something like erythromycin or metaclopramide?

Stig B Laursen: Stig B Laursen We give erythromycin in very selected patients. So we would use this in patients with severe bleeding, some patients with severe bleeding at the emergency department, and patients in which we know from previous procedures that there may be a problem with gastric retention in order to increase the gastric visibility, overview of the mucosa, and decrease the need for second look endoscopy. But we do not use it in the majority of patients.

Ian Gralnek: Ian Gralnek how much do you give? What's your dosing and when do you give it before endoscopy?

Stig B Laursen: Stig B Laursen 250 milligrams of erythromycin 30 minutes to 180 minutes before the procedure.

Ian Gralnek: Ian Gralnek We do anywhere from about 30 minutes to about an hour and a half or two hours You know, there's a lot of places don't have readily available erythromycin. Then you know, the guideline that we just worked on is actually going to give a conditional recommendation for metaclopramide because there's actually some new data there that we can use metaclopramide. I personally have not used it because we usually have erythromycin. And do have any experience with metacopromide in this type of a clinical situation?

Stig B Laursen: Stig B Laursen No, no we haven't. But when looking at data it looks like you can increase the gastric visibility as well, but I don't think we found any significant difference related to the need for second look endoscopy,

Ian Gralnek: Ian Gralnek I think you're right. And the other medication people have tried, but there's very limited data, is people have given azithromycin, but I don't think that that has actually shown any type of benefit to patients in terms of increased gastric mucosal visibility and need for, or lessening the need for a follow-up endoscopy. But I agree with you, we give it to selected patients that we're very concerned that there may be residual blood and clots. We don't routinely give a prokinetic agent. One other question right before endoscopy, would do you routinely prophylactically intubate these patients? And if not, who do you intubate? I get that question a lot.

Stig B Laursen: Stig B Laursen We only perform prophylactic intubation around 5 to 10 percent of cases being the ones with severe bleeding, for example hemodynamic instability or repeated hematemesis, or patients who are not able to defend their own airways. Actually, there's I think three or four studies comparing prophylactic intubation with not performing prophylactic intubation and surprisingly they haven't been able to find any significant difference in patients' outcome. And one of the studies even indicated that there may be an increased risk of respiratory complications, but all of these studies are in high risk of confounding by severity. But there are no data indicating that it would be a benefit to routinely perform prophylactic intubation.

Ian Gralnek: Ian Gralnek We don't routinely intubate as well. We leave it, just like you said, for patients who really are having ongoing active hematemesis or even in varices patients who may be encephalopathic or people just cannot control their airway and were really worried about aspiration. let me ask you another question. Where do you routinely do these types of urgent upper endoscopies? Are you doing them? in the operating theater? Do you do them in the endoscopy unit or there are some places that even do these cases in the emergency department? What goes on at your hospital?

Stig B Laursen: Stig B Laursen Well, 90 % is done at our endoscopy unit and then the 5 to 10 % who are intubated we do at the surgical theatre.

Ian Gralnek: Ian Gralnek And do you have 24-7 emergency GI endoscopy coverage?

Stig B Laursen: Stig B Laursen Yeah, we're so lucky at our hospital that we got two dedicated endoscopic nurses trained in both upper GI- bleeding and at least one of them in ERCP as well. So we've got access to them around the clock, around the year and it makes it all very much easier actually.

Ian Gralnek: Ian Gralnek We do too. I don't know if places really realize this. I've told people this, if you don't have it, it's actually in guidelines that this is what's recommended today, is that there really should be 24 7 emergency GI endoscopy coverage with GI nurses who are trained in endoscopy and the use of endoscopic devices and tools, whether it's for GI bleeding or ERCP or foreign body removal, etc. We have that and I agree with you, we feel very lucky that we have that as a resource at our place as well. So let me get to sort of the big question, and I'm sure you get this question all the time. So when do you scope these patients? And let's first start with the patient who we're not that concerned it's gonna be a variceal bleed. What's the timing in these patients once you've hemodynamically stabilized these patients?

Stig B Laursen: Stig B Laursen Yeah. That's a tricky question. We did a national cohort study including more than 12,000 patients and we found that there was a U-shaped association between time to endoscopy and 30-day mortality. And that was also shown similar in two studies from Hong Kong. But I think there are three factors we should be aware of when discussing this. Many of the RCTs within this field are actually underpowered. Many of the cohort studies have issues with confounding bi-severity. And many of the other trials also have different case mixes. So if we look at studies that includes a high number of patients in which there were normal findings at endoscopy or low bleeding sources such as Mallort Weiss tears erosive gastritis or reflux disease, you wouldn't expect there to be any association between time to endoscopy and patient's outcome. So if we look at all of the studies from a helicopter view, so to say, you will see that there are no studies indicating any prognostic benefit for performing endoscopy within six or 12 hours from patient's presentation to hospital. On the other hand, at the end of the spectrum, if we perform endoscopy later than 24 hours, there are some cohort studies indicating that you'll have an increased risk of mortality. And to me that makes sense, because if you've got a patient who needs endoscopic treatment in order to achieve hemostasis, if you wait too long, you risk that the patient will not have the prognostic gain of the therapeutic procedure. So for the vast majority of patients, we recommend performing endoscopy from six hours to 24 hours after hospital admission.

Ian Gralnek: Ian Gralnek Yeah, that's basically where we're at. First of all, if those out there listening aren't aware of this study by Stig Laursen, it's a seminal study. I use I quote your paper all the time, show a slide of the U-shaped curve. I think it's a very good study. And to me, I've always said that the sweet spot there is probably somewhere between 12 to 24 hours, something like that, at least based upon your data.

Stig B Laursen: Stig B Laursen I fully agree, but in relation to the 12 hours, it's just you often have patients admitted around seven or eight o'clock in the morning at your unit with upper GI bleeding. And if you wait 12 hours, then it'll be around eight o'clock in the evening. You know, it's only the junior doctor being at present, the interventional radiologists have gone home hours ago and there are only one or two surgeons. So in those cases, I really like if you can just wait around six hours, you know, early afternoon, then there's a lot of experienced colleagues present, the interventional radiologists, if you're lucky to have them in your house, they are still at work and there's a lot of surgeons present. So I think it's also important to focus on doing this in daytime when everyone's awake and there's a lot of guys at work to help you.

Ian Gralnek: Ian Gralnek I agree 100%. I think if you can do these cases during the light of day, it is much better than to do it in the evening or in the middle of the night unless you're really forced to do that because you don't have those additional backup resources available to you. Listen, I think we're getting a little short on time here. First of all, Stig, you've always impressed me. You are a critical thinker. You know the literature backwards and forwards, and it's an absolute pleasure to have this discussion with you. I really appreciate that you've taken the time to be with us here on this podcast. But before I let you go, I do want to ask you something. So what do you do when you're not doing endoscopy?

Stig B Laursen: Stig B Laursen Well, I love to work with my hands, so when I'm not doing endoscopies, I like to restore old cars and some carpentry works.

Ian Gralnek: Ian Gralnek Oh really? So what kind of cars?

Stig B Laursen: Stig B Laursen Well, mostly French old cars, which nobody knows, but I've also got an old Beetle.

Ian Gralnek: Ian Gralnek Really? Wow. So you have an old, a whole old car collection?

Stig B Laursen: Stig B Laursen 8 cars.

Ian Gralnek: Ian Gralnek Really? Oh, I'd love to see them one day. I actually just sold it, but I had a 1972 MGB convertible. Yeah, it was great. It was orange in color. And my son and I restored it and I had it for a few years. But then, you know, once you restore it to me, the fun a little bit ended and I ended up selling it a few months ago, but I had a lot of fun with it. So I'd love to see your cars one day. Well, listen, I want to thank you again for being here, Stig. It was a pleasure having you. And I had a great time with you chairing the session on, upper GI bleeding at ESGE Days. And, I will come to Odense one day. I want to see those cars. Okay.

Stig B Laursen: Stig B Laursen I look forward to that. Thank you for having me on.

Ian Gralnek: Ian Gralnek It's been our pleasure. Thanks again, Stig.

Stig B Laursen: Stig B Laursen Bye.

Ian Outro: Ian Outro Thank you for listening to this episode of Endoscopy Unplugged. If you found this podcast useful, please subscribe wherever you get your podcasts. To find out more about the European Society of Gastrointestinal Endoscopy, for example, to browse our scientific publications, interact with our online learning portal, the ESGE Academy, or learn about becoming a member of ESGE, visit our website, www.esge.com. And of course, your feedback is always valuable to us. So send us your thoughts via podcast at esge.com. Thanks for listening and join us next time.