Episode 001: Management and prevention of post-ERCP pancreatitis
Guests: Dr. Jeffrey Mosko and Dr. Paul James
SHOW NOTES
Huaqi Li
Thanks so much for tuning in to our first ever episode of Scope Notes, a Gastroenterology focused medical education podcast created by learners for learners. I’m your co-host Huaqi Li, current first year Internal Medicine resident at the University of Toronto in Canada and I am joined by my co-host Mo Bucheeri, current fifth year Gastroenterology fellow and Co-Chief resident also at the University of Toronto.
Mo Bucheeri
Hello!
Huaqi Li
Our amazing Faculty Advisor is Dr. Parul Tandon, a staff Gastroenterologist and clinician-scientist in Inflammatory Bowel Diseases at the University Health Network/Sinai Health in Toronto.
With Scope Notes you can look forward to monthly episodes covering all things GI including practice guidelines, research reviews, and special career topics. We’ll be specifically featuring prominent Gastroenterology staff from the University of Toronto and across Canada for their expert opinions. We would also like to extend a huge thank-you to the Division of Gastroenterology and Hepatology at the University of Toronto for their generous support of this podcast. With all of that being said, let’s move on to our episode.
Today we will be talking about post-ERCP complications, particularly pancreatitis, given the significant associated morbidity and mortality. We are joined by our wonderful guests, Dr. Jeffrey Mosko and Dr. Paul James who specialize in advanced endoscopy. Dr. Mosko is a Clinician in Quality and Innovation in the Division of Gastroenterology at St. Michael’s Hospital and Assistant Professor of Medicine in the Department of Medicine at the University of Toronto. Dr. James is a staff Gastroenterologist at Toronto General Hospital, Driscoll Family Digestive Health Center, and Toronto Western Hospital.
Dr. Mosko and Dr. James, welcome to the podcast, and thank you so much for joining. In terms of the first question before we get started on discussing this important topic, could you tell the audience a bit about yourselves, where you did your training, how long you've been in Toronto, and a bit about your clinical and research interests?
Dr. Mosko
Of course. So firstly, thank you so much for having me and a huge congratulations on this brand new and exciting podcast. I'm sure with you guys at the helm, it'll be a huge success and really an amazing resource for learners everywhere. So, it's an honor to be invited and be here on your first episode. So, I am a Gastroenterologist and Advanced Endoscopist at St Michael's Hospital in Toronto. I did my General Internal Medicine and GI training in Toronto, and then my Advanced Endoscopy fellowship at Beth Israel Deaconess Medical Center in Boston. I then did a Masters of Science in Quality Improvement in Patient Safety here in Toronto at the IHPME and was hired at St. Mike's at the end of 2014 so I've been in practice for just over 10 years. My clinical interests are in both luminal and advanced endoscopy including advanced resection, ESD and pancreatic biliary endoscopy, ERCP and interventional EUS. My academic focus are both research in tissue resection and pancreatic biliary endoscopy, as well as procedural innovation. So that's me, and great to be here.
Dr. James
Thank you very much for the opportunity to be here and share. So my name is Paul James, and I am currently a practicing physician and Assistant Professor at the University of Toronto, and I work at the University Health Network as the Director of the Advanced Endoscopy program. I am an advanced endoscopist. I did my Gastroenterology training at the University of Toronto, and that was following Internal Medicine training at University of Toronto. I did my therapeutic endoscopy training at the University of Calgary and started first my career at the University of Ottawa, and then came to University Health Network in 2017 and I've been there since, growing our ERCP and biliary program that includes ERCP, Spyglass, endoscopic ultrasound. My research interests include quality in endoscopy and advanced endoscopy. I also use big data to try to examine options for patients diagnosed with gastrointestinal malignancies such as pancreatic cancer, and I look at algorithms to predict outcomes such as survival and symptoms and quality of life, based on patients’ baseline characteristics and some of the treatment choices they make. In terms of endoscopy, my research has examined multiple issues, focusing first on quality in luminal endoscopy and colonoscopy, but also looking at trends in ERCP practice patterns and outcomes.
Huaqi Li
Amazing, very excited to have both of you on the podcast today. So, Dr. Mosko, could you walk us through what exactly is post-ERCP pancreatitis, and how common is it?
Dr. Mosko
Yeah, so post-ERCP pancreatitis is the nemesis of all ERCPists, it is a known complication that occurs after ERCP-one of the most common adverse events associated with the procedure, and typically presents with abdominal pain and elevated lipase after the procedure. The pathophysiology which we'll get into is multifactorial, and really the incidence varies depending on various factors, which we'll also talk about: patient-related, procedural and technique related aspects. So, the incidence is interesting. There's actually a recent meta-analysis by one of my friends and colleagues, Nauzar Forbes, out in Calgary, and he compiled 380 trials and large observational studies with more than 2 million unique patients, and he found that the incidence of post-ERCP pancreatitis was 4.6% in all-comers and 6.5% among first time patients. He broke that down further, which I think is clinically relevant, into 66% mild pancreatitis, so that's what we most commonly see, 28% moderate, 10% severe, and 1.8% fatal. So important to know that this is a potentially fatal complication. Interestingly, the incidence has remained stable over time, despite improvements in techniques, prevention and recognition.
Huaqi Li
Thank you for the great overview and some excellent datapoints as well. You mentioned the pathophysiology of post-ERCP pancreatitis. Could you delve into that a bit deeper?
Dr. Mosko
Yeah. So, the exact cause of post-ERCP pancreatitis is not completely understood, but there are likely several mechanisms that contribute, one of which is mechanical injury or pancreatic ductal trauma. So, the procedure involves cannulation of the bile duct and occasionally the pancreatic duct, where you can cause injury which can lead to transient obstruction or increased pressure within the pancreatic duct. There's also chemical injuries, so we use contrast during ERCP, which can have a toxic effect on the pancreas tissue and parenchyma. Also, sphincter of Oddi dysfunction. So, manipulation of the sphincter, and specifically the pancreatic sphincter, during cannulation can lead to spasm, causing an increase in intra-pancreatic pressure, which can result in pancreatitis as well. And then finally infection and inflammation. So, you are theoretically introducing bacteria into the pancreatic duct, which you know either from the instrumentation or from prior infection, that can trigger an inflammatory response. So, while it's unknown, lots of things that potentially can contribute.
Huaqi Li
Breaking it up into those different components is really helpful to think about, thank you. And so what kind of disease characteristics would potentially be higher risk for post-ERCP pancreatitis?
Dr. Mosko
Yeah. So great question. So, we know for a fact, and this has been very well studied and shows up in all of the guidelines, that the incidence varies widely depending on patient characteristics, procedural related factors and technical expertise. So, we sort of can break it down to within patient factors we know that young female patients have a significantly higher risk, specifically, women under 50. Patients who have had a prior episode of pancreatitis are at an increased risk, with an incidence really approaching 10% in these individuals, and then pancreatic ductal abnormalities, so conditions like pancreas divisum, known sphincter of Oddi dysfunction significantly raise the risk of developing it as well. So procedural factors, difficult cannulation, either failed or difficult attempts to cannulate the bile duct or pancreatic duct can increase the risk to up to 10 to 20% and this is Peter Cotton's old data. Sphincterotomy, so when you do a sphincterotomy, especially if the procedure is prolonged or complicated, that increases the risk, and then any pancreatic duct injection and so really the important parts here are to identify these risks in advance, to try and tailor our preventative strategies. So just to summarize: we really think of patient factors and procedure related factors as our main categories that put patients at high risk. Now, in the literature, there's a lot of different definitions of high risk, anywhere from up to two to five factors that they kind of lump together to decide whether or not someone is high risk, and a lot of the randomized control trials are quite heterogeneous in terms of how they defined high risk patients.
Huaqi Li
That’s really helpful to know that there is actually heterogeneity in the literature so maybe there is some more nuance that’s needed when interpreting studies. So, switching gears a little bit, the American Society for Gastrointestinal Endoscopy, ASGE, came out with their 2023 clinical practice guidelines. Dr. James, could you walk us through these guidelines?
Dr. James
Yes, I think it was a very, very good job by a well-recognized group, one notable colleague of mine who has been very instrumental at every part of my career and development and influence is Nauzer Forbes, who's right in the middle of the authorship. And, as I mentioned before, I did my advanced endoscopy training at the University of Calgary, and after me, Nauzer Forbes did, and he's also been a pivotal role in Canada as a young but very active and very prolific and successful investigator. Also participated in this guideline development and has his approach. And with the ASGE guideline here, what they're trying to do is simplify the review to important prophylactic interventions that can be considered. And the reason why they narrowed things early is because they wanted to be very thorough in their investigation of each topic. They did a systematic review and a meta-analysis where relevant, and it was for multiple areas, but then they also trusted a review performed by an esteemed colleague, Dr. Francis Tse at McMaster, for another topic and I think that was a smart choice. Their focus was thinking about providing pre-procedure rectal NSAIDs to help prevent post-ERCP pancreatitis. They also looked at, during the procedure, using wire guided cannulation versus contrast guided cannulation for accessing the bile duct. And a third intervention they suggested, or looked at, was at was the provision of intravenous hydration, aggressive intravenous hydration, for preventing post-ERCP pancreatitis. Another issue that they examined is the use of the insertion of pancreatic duct stents for preventing pancreatitis after an ERCP procedure. They tried to look at pancreatitis from multiple perspectives. For example, they like to look at prevention of the occurrence of post-ERCP pancreatitis. Then they also try to comment on reducing the severity of post-ERCP pancreatitis. And they did a very good review trying to examine these outcomes, then they provide some insight into whether it would be beneficial.
They did a great summary of their findings in Table 1. So, to even summarize their summary, what they basically said, or what they concluded was among unselected patients undergoing ERCP, so all-comers, minus those with significant contraindications, the ASGE recommends that pre-procedure rectal NSAIDs should be provided to prevent post-ERCP pancreatitis. And that was a strong recommendation, because, based on their systematic review and meta-analysis, there's overall an about, but it seems that way in practice as well, 50% reduction in the risk of post-ERCP pancreatitis. So, in clinical practice, rectal NSAIDs, specifically indomethacin, but an alternative that has come forward in the absence of indomethacin, or a more cost-effective in some instances, depending on your environment, diclofenac, can be provided prior to the procedure or shortly after starting intra-procedure, to prevent post-ERCP pancreatitis. During the procedure, they suggested that all patients undergoing an ERCP should have wire-guided cannulation, rather than having contrast guided cannulation. Then post-procedure, they suggest aggressive periprocedural intravenous hydration and post-procedural intravenous hydration to prevent post-ERCP pancreatitis. In the final recommendation, they note that an incredible reduction in post-ERCP pancreatitis risk of over 50% based on the studies that are available. Some questions they were not able to completely answer is, should combinations be used? And specifically, they were talking about the introduction or the use of a pancreatic duct stent. For example, how much more benefit do you get of rectal NSAIDs when a pancreatic duct is placed? Or how much more benefit you get with aggressive IV hydration, when a pancreatic duct stent is inserted. But I think what is insinuated is that when you have access to the pancreas duct, and you repeatedly have a wire going into the pancreas duct, or when a patient is a clearly high-risk person for getting post-ERCP pancreatitis, a pancreatic duct stent is going to be inserted, and they also recommend adding these maneuvers.
Huaqi Li
Thank you so much for that. That was very thorough, and we’ll get back to some of those talking points in a little bit. I wanted to ask, for the rectal NSAIDs, how did that practice first start? Why specifically are they administered rectally and why do we use indomethacin?
Dr. James
In terms of why provide a non-steroidal, anti-inflammatory medication, pathophysiologically, we can consider pancreatitis to be a cascade of mechanical and local cytokine and chemokine reactions that can lead to the inflammatory, uncontrolled event. And I tell patients, as well as residents, that when the episode of pancreatitis occurs, we're not sure how things are going to turn out. Fortunately, the majority of patients who undergo an ERCP and have post-ERCP pancreatitis have a mild course, but the mortality risk is still estimated to be around 1 in 500 and the complicated pancreatitis course can be seen in up to a third of patients. And so, we want to try and prevent this happening any way possible. And anti-inflammatory medications such as indomethacin can theoretically stop the chemokine or cytokine chain. There's been prostaglandins insinuated and other more specific chemokine-mediated pancreatitis that we believe indomethacin, or diclofenac, the non-steroidal anti-inflammatories can influence. However, we cannot absolutely be sure of why, what exactly the pathway is. Unfortunately, the cost of rectal indomethacin went up. And, they’ve actually come harder to access in Canada. Fortunately, diclofenac became available and now we’re applying that. And there have been studies examining, even head-to-head trials, examining rectal indomethacin and diclofenac, showing that at least they have an equivalent risk reduction effect on post-ERCP pancreatitis. So, we still have an affordable option.
The reason why they put in rectal indomethacin is because patients around the procedure time have to be NPO. And they need to remain NPO for at least one hour after they receive any oral or pharyngeal spray. So oral is not really an option. Intravenous could be an option, but any intravenous study looking at the issue has been generally negative. But rectal indomethacin offers an opportunity for the medication to be absorbed and be available at the time, just before or during the ERCP. I guess one question that I've asked is, how did we figure this out? How do we get to the point where rectal indomethacin was tried? Well, a lot of procedures start in the operating room and there’s anesthesia provided. It's not uncommon for after a procedure to reduce pain scores that anesthesiologists would provide per rectum, Tylenol or per rectum indomethacin. So, the practice already existed for pain reduction, so providing it rectally to prevent post-ERCP was not too novel of a concept.
Huaqi Li
Thank you so much for clarifying that, it’s really helpful to know the origin of the practice. The guidelines also talk about the different approaches of cannulation and that during an ERCP they suggest wire assisted cannulation rather than a contrast guided approach and placement of prophylactic pancreatic stents in high-risk patients. Dr. Mosko, how feasible is it to actually opt for wire-assisted cannulation and to place these prophylactic stents?
Dr. Mosko
The short answer, is, well, I'll break it down to two different parts of the question. So, part one is wire assisted cannulation. This is feasible, and this is a major difference in ERCP that has occurred over time. So, I finished my advanced endoscopy training, I'm embarrassed to say, in 2014 which makes me old, but we were already purely wire guided at that point. But historically, ERCPs were not wire guided, which makes it hard to compare very old data to data today. So, I would consider wire guided cannulation as the current standard of care, and we only inject contrast when we are absolutely out of options, or when you think you're in the duct of interest, but you really need to be as sure as you possibly can be. And there's actually another Canadian meta-analysis that showed that wire guided cannulation is far safer in terms of preventing post-ERCP pancreatitis. So, question one, definitely feasible to be wire guided, but that doesn't mean that you're not occasionally getting inadvertent contrast into the pancreatic duct, even when you're not attempting it. The prophylactic stenting is where it becomes a little more controversial, in my opinion. So, when you have a wire go inadvertently into the pancreatic duct, it's not a problem, because you either place a stent either then and there or you use your wire to facilitate cannulation and then place a stent at the end of the procedure to prevent pancreatitis. So that part is easy. The reason that we think stents work for prophylaxis is it ensures adequate drainage in the face of sort of the outflow tract edema and obstruction that we talked about before, and it reduces the potential for that intraductal hypertension that leads to consequent inflammation. So, it's when you don't get a wire into the pancreatic duct. For example, you have a patient with a common bile duct stone, and you immediately have a one touch cannulation into the bile duct. So, when both of you are advanced endoscopy fellows, you're never going to touch the PD, so you have that one shot cannulation into the bile duct. Is it worth the effort and the risk to then attempt pancreatic duct cannulation after that to place a stent? That process can be traumatic in some patients, and obviously an unsuccessful placement attempt is associated with an increased risk of pancreatitis.
The other problem is, there's some, I guess bias and exaggeration in the data about the perceived benefit of prophylactic stent placement, because some of the trials were unblinded in their design and conducted at really a small number of expert centers, so that sort of limits the generalizability to broader practice. So, should we be attempting pancreatic duct stent placement only in high-risk individuals, or only when a wire goes into the PD? So, there's actually a great study done by Joe Elmunzer from South Carolina that was in The Lancet this year. It was a multi-center randomized double blind non-inferiority study looking at rectal indomethacin alone versus a combination of indomethacin and stent placement. What they found, so they had almost 2000 participants in 20 academic centers across North America, and they found that they had a 15% post-ERCP pancreatitis risk in patients who got indomethacin alone, versus 11% in the indomethacin plus stent so that's a 32% relative risk reduction from the stent placement, and that's including a 20% failure rate of placing a stent. So, they were only able to place stents in 80%. So, how do we take that data and apply it to our practice? Well, it seems like indomethacin alone is less effective. They had a numerically higher severe acute pancreatitis rate and actually more necrotizing pancreatitis and pancreatitis deaths and stents seem to be effective in all comers and most effective in patients at high risk. So, the relative benefit of the addition of the stent was consistent across subgroups of patients in the trial. So, you really can no longer justify abandonment of prophylactic stent placement when you haven't gotten a wire into the PD. So, to me, I would say this is practice changing, because historically, I was only putting in a stent when I either inadvertently put dye in the pancreas, inadvertently got a wire in, or needed a wire to facilitate cannulation. And so, this this study, and I've spoken at Joe Elmunzer about this, and Nauzer Forbes also presented at our course about this, I think this is a game changer.
Huaqi Li
That's really exciting to hear and I think speaks to the advancements in the field so far. I’ll turn it over to Mo now for some final questions.
Mo Bucheeri
Thank you for that. Dr. Mosko, are there any major differences or different recommendations between the 2020 ESGE or European Society of Gastrointestinal Endoscopy Guidelines for ERCP related events comparing them with the ASGE 2023 ones?
Dr. Mosko
Yeah. so, thanks, Mo for the very challenging questions and forcing me to review every line of each of the guidelines, that's great. So, I would say overall, they're fairly aligned. They are a few years apart, and so they're understandably a little bit different given the some of the data that has emerged over a few years. So, I would sort of summarize the difference within the big realm of interventions for risk profile analysis in ERCP. So, number one would be hydration. So, the ASGE has a much higher emphasis on the role of hydration in preventing complications like post-ERCP pancreatitis, understandable, given the Waterfall trial and the evidence that has emerged. Both guidelines are aligned on very selective antibiotic use. ASGE really highlights avoiding unnecessary antibiotics more strongly. Historically, people were giving antibiotics for all comers in ERCP, which really has no basis anymore, and we are not recommending. Management of bleeding, both guidelines have similar recommendations, but ASGE more explicitly mentions management of larger perforations, and so really, again, people should be able to manage ERCP related perforations. ASGE introduces the concept of simulation training for improving outcomes as it relates to operator experience, where ESGE emphasizes structured certification and competency-based training. And then really for post-ERCP, pancreatitis prevention, obviously the focus of this podcast, ASGE focuses mostly on hydration and NSAIDs as primary strategies, ESGE discusses pancreatic duct stenting more frequently, but I can assure you that new iterations of both guidelines will talk about pancreatic duct stenting again.
Mo Bucheeri
Thank you for that. I noticed that they're much more aggressive in the ASGE guidelines than they were on the ESGE guidelines in 2020 so I found that interesting. Some of it you alluded to about how the guidelines changed your practice. Do you have any specific techniques or considerations to help prevent post-ERCP pancreatitis in actual practice?
Dr. Mosko
Yeah so, I would say the guidelines have not changed my practice, and the reason is that I'm very fortunate to work in an academic center and work in a, you know, center of excellence for ERCP, and we are constantly discussing techniques and data and talking about how we can do better for our patients. And so, we're, I think we're incorporating most of the data in real time into our practice before it has a way of making itself into the guidelines. So, the emerging data is definitely changing practice. I would say, by the time things get to the guidelines, we've already sort of made that change, but it's always interesting to see how a group of experts are interpreting the data.
And then, to answer your last question, I think that one of the best ways to help prevent post-ERCP pancreatitis in practice is selecting patients appropriately for ERCP, something we haven't talked about today, but is a constant back and forth that I have with referring doctors, with surgeons, in terms of who really needs an ERCP. In 2025, this should be an exclusively therapeutic procedure that's with, you know, improving MRI techniques. Really, there should be no diagnostic ERCP anymore. We need to work on improving our atraumatic and efficient procedural technique. We've talked about guidewire cannulation. We haven't talked about, but we really need to implement early alternative techniques when one thing is not working, and avoid aggressive PD injection and/or balloon dilation of the sphincter without a sphincterotomy. We have to identify high risk patients early and use evidence-based prophylactic techniques. So, pharmacoprevention with rectal NSAIDs, PD stent placement, really in all comers, but specifically in high risk patients, and then aggressive long term hydration. So important to incorporate the data, and that's sort of how we can do best for preventing post-ERCP pancreatitis in our patients. Paul, what do you do?
Dr. James
I'll say two things. One is, I think, like the people who developed this guideline, they want the adherence to be 90 plus percent, 95% but my practice pattern has been the same for you know, since I started at UHN, for example. The only thing that changed was indomethacin did not become available, and we started using diclofenac. I think one of the things that changed recently in my practice is I am more, much more likely now, to do pancreas duct stent guided cannulation instead of double wire guided cannulation. And I think it's because, when I was in training, double wire cannulation was the accepted route. And now with practice patterns, guidelines, expertise, experience, putting the PD stent seems like an obvious choice. It's actually very easy to do. The PD stand is very small French, it's very flexible. You just put it over the wire that's going to the duct, and then you push it with the same tome, so you just have the wire, put the stent on, then use the same tome. So, by the time you finish putting in the pancreas duct stent, you pull out the wire, the PD stent is deployed, and now you have a loaded tome ready to continue with cannulation into the common bile duct. So, it's a very easy and effective tool, so it's easy to apply. So no, this guideline did not change my practice. My practice was already changed based on the foundation evidence that was building that was summarized in this trial. And I think that these kind of guidelines do a great job of helping build the word and making sure that 95% of people are doing the evidence based approaches. And also, just making sure that you look at some certain details, like, what do you do in the patient who already has a pancreas duct stent? Do you save yourself the $2 and not put in diclofenac? There's no way I'm not doing that. So, I'm going to give diclofenac, you know, just to kind of add a little bit of controversy on the data. Don't think it's that controversial, but all my patients are going to get the rectal diclofenac, they’re going to get the PD stent, if I go in the PD, and they're going to get the aggressive fluid hydration if they do not have a contraindication. I'm not waiting for these other trials that are pending, because I don't think that it's going to change my practice.
Mo Bucheeri
Thank you. And, just as we wrap up, are there any barriers that may be preventing reduction in post-ERCP pancreatitis, and if so, how do you think we might be able to address them?
Dr. Mosko
It’s a difficult question. I think that determining our patient risk profile in advance is not always possible. We have very busy clinical practices and it’s sometimes hard to get a perfect history on what patients have gone through in the past and how risky the procedure really is, so I would say we need a better way of early identification of risk profiles. Giving prolonged IV fluids is not always possible. Again, I find that patients are always being rushed out of the recovery room to make space for the next patients coming through. So, making sure we adequately hydrate patients is sometimes a barrier, and then this is one of the best parts of my practice is working with trainees but it is challenging to make ERCPs atraumatic when you sometimes have a trainee early on in their training who hasn’t totally mastered all of the skills of ERCP yet. So, we need to make sure that even when we’re working with trainees we’re being as atraumatic as possible. So, risk profile, identification, IV fluids, and continued atraumatic techniques when working with trainees, those are some of the barriers to a further reduction in post-ERCP pancreatitis for me.
Dr. James
So, I think that the interventions are affordable and I think that it’s almost unanimous that providing these can reduce the risk, so I would say the barriers are, you know, every individual case has to be considered of course, just like they mention in the guideline. But in general, these are quality markers and we should hopefully find ways to measure them and provide incentives for everyone to apply them to reduce the risk in our patient populations.
Huaqi Li
Thank you so much Dr. Mosko and Dr. James for a very engaging discussion on the management and prevention of post-ERCP pancreatitis. That’s it for our episode today. Thanks so much to our listeners for tuning in and join us again next month. In the meantime, come check out our website at www.scopenotesGI.com where we’ll be posting our show notes for each episode and other resources. Follow us also on social media for the latest updates @scopenotesGI on X, formerly Twitter, and Instagram. If you have any feedback or just want to say hi, you can reach the team at scopenotesGI@gmail.com.
