All right, our last speaker for this morning's session is Dr. Chris Thompson from the Brigham. He's director of endoscopy, co-director of the Wait Center, and our faculty with the longest disclosure list, but he's obviously familiar with a lot of different tools from different companies, and he's going to talk about managing adverse events of ERCP. Thank you. Good to be here, good to see everyone. My disclosures. So, agenda. I think I want to cover kind of briefly the best ways to avoid complications as well as management strategies when they do occur, and this is one quote that kind of comes to mind and what I'd like, if you take anything away from this talk, this is probably the main thing, right? Have an appropriate indication, and this is from a surgeon in London, still alive. There are some patients that you can't help, but there are none that you can't hurt, right? And I think that really speaks volumes, honestly. Peter Cotton also said patients who need ERCP least are the most likely to develop complications. I think this is kind of at the heart of everything I'm talking about, so just keep that in mind. And starting with some kind of oldie but a goodie, Peter Cotton, 2010 here, he looked back through various lawsuits and found that pancreatitis was the most common diagnosis in these lawsuits, and 50% of them, there were six deaths in that series of 59 lawsuits as well. An inadequate indication was the most common issue in those lawsuits, it was problematic. Inadequate consent was the most common secondary issue. And a follow-up with an additional 20 lawsuits, poor indication and communication was indicated to be a major issue, and ERCP volume by provider also had come up. Things to keep in mind with lawsuits. To prevent these, it's good to ensure that the indication is appropriate. ERCP is not a first-line diagnostic procedure, we all are aware of that now, but keep it in mind. Have a low threshold for EUS, MRCP, prior to ERCP. And a thorough documentation of the consent process is important. Good patient and family communication before and after the procedure, and it's also important to have adequate training to maintain case volume. There's higher potential for serious complication than any other standard advanced procedure. Now we have other procedures, you know, like poems and bariatric procedures and other things that are coming about now, therapeutic EUS, but among our, and I think that we don't have large enough volumes necessarily to exactly know what complications are, especially as people are on their learning curves and whatnot, but as far as standard, you know, more common procedures, ERCP is certainly the one with the highest adverse event rate. There's two types, broadly speaking. General ones, medication reactions, oxygen desaturation, cardiopulmonary events, et cetera, and there's also selective ones. Those are the ones I'm going to be focusing on. These are specific to pancreatobiliary instrumentation. Here's a list, pancreatitis, bleeding, cholangitis, perforation, contrast reaction, and those are the ones I'm focusing on, and infection was already nicely covered by Doug, and we'll limit it to these, so pancreatitis. This is the most serious and most frequent serious complication, ranging from 3% to 8%, as high as 25% in some series, if you go way back to the literature. There's all sorts of factors that are related to this, mechanical, hydrostatic, chemical, allergic, enzymatic, thermal injury, and 0.4% are severe, as defined there. Risk factors are additive. Throughout each one of these, we'll talk about the different risk factors. You have physician risk factors, and this is operator experience or lack thereof. Patient risk factors, which we have listed here, prior, posterior pancreatitis, probably the most important. Also, suspected SOD, female gender, normal bilirubin, absence of chronic pancreatitis, and age there. Then there's also procedural risk factors, so difficult cannulation, PD injection, if you're doing a pancreatic doxyphankterotomy, SOD manometry, pre-cut, complicated access certainly contributes, minor pillow work, and balloon sphincteroplasty and epileptomy. Prevention here, judicious use of ERCP has already been mentioned, wire-guided cannulation, avoid PD cannulation and injection, limit cannulation time, prophylactic stenting, rectal endomethysin, and aggressive hydration. Now, there's a few older studies I'm going to show you, because we've been thinking these things for a long time, and we've only recently got a really nice grade document that has kind of confirmed it, but this is some of the older literature that really led us to think this over the past many years. So, this was a Cochrane meta-analysis of 12 RCTs over 3,400 patients, and it was looking at wire-guided cannulation versus contrast, and the group with wire-guided cannulation at 3.7% rate of posterior pancreatitis, and the conventional group at 7.2%. So, clearly, better success rate in cannulation as well as lower PEP rates. Then we had a meta-analysis that was looking at the use of pancreatic duct stents, and this was, you know, there's several of these. There's three different meta-analyses that all agreed that stents were favorable, and there's still some issues with that, you know, regarding, you know, what type of stent to use, what size stent, is it a pigtail, is it an internal flange, etc., but clearly, stents were favorable. Limitations here is that you can sometimes have trouble placing a PD stent, and so how hard do you want to try to get that stent in, and we don't have great answers for this. This can require repeat endoscopy. It may increase the cost of the procedure, and there's a lack of expert agreement on the methods, as I said. And then moving on to IV fluids and the methasin, this was a randomized trial, 48 subjects in each one of these arms, and you have saline plus placebo, saline plus endomethasin, lactated ringers and placebo, and lactated ringers plus endomethasin, and you can see that the—oops, I was going to have a transition there. I'm trying to go backwards. I'm at the bottom button. Perfect, thank you. So, much better. So, the difference between saline and placebo versus lactated ringers and endomethasin was significant, and the others weren't quite significant. So, that's kind of the background and where we came from on this. Now, there's a great guideline from the AHG led by Buxbaum that really goes through this more methodologically. They actually use great methodology, so this is looking at a high level of evidence that's confirming kind of all the things we thought all those years, right? And they went through the various questions. They had five major clinical questions that they looked at. They looked at in unselected patients undergoing ERCP, should rectal insets be given? In high-risk patients, should they be given? In unselected patients undergoing ERCP, is wire-guided cannulation preferred to contrast injections? So, the same things that we've kind of suspected. High-risk patients undergoing ERCP, should pancreatic duct stents be placed? And then unselected patients undergoing ERCP, what about aggressive fluid resuscitation? Basically, they went through a very good rigor, and I've kind of pulled out and reworded these a little bit because great methodology can be kind of strange there, but this is the summary. The take-home message is from the document. AHG recommends that unselected and high-risk patients should be given PERI procedural rectal insets to prevent PEP. It's a strong recommendation with moderate quality of evidence. They suggest wire-guided cannulation over contrast-guided cannulation to minimize the risk of PEP in unselected patients undergoing ERCP. It's conditional with moderate quality. It recommends that PD stent placement to reduce the risk of PEP in patients undergoing deep access as well as ampulectomy, and that's a strong recommendation with moderate quality of evidence. It also recommends that PD stent placement in high-risk groups, including patients with difficult cannulation history of sphincterotomy, and that is a conditional recommendation, and recommends aggressive PERI procedural and post-procedural intravenous hydration. So that is post-treatment pancreatitis. Moving on to bleeding, this was a case that I was involved in as a fellow, and it still kind of is horrifying to see this, but this was a patient who had a liver transplant, and they were having some issues with blood loss, and the surgeons really wanted us to do this ERCP and see if we could place a metal stent to tamponade the thing and see if there was hemobilia, kind of, if we could treat it that way. So you can see there's lots of clots in there. And so clearly, this is something that I would not be doing in my current practice, I think, but we were able to gain cannulation, deep cannulation here, and then we do a sphincterotomy, and we'll do some sweeps. You know, you're thinking about vascular anomalies, obviously, in this situation with a prior liver transplant as well. And so I've never quite seen bleeding like this. It's going to get worse. There it is. Yeah, right? And the patient lived because, you know, we were doing this in an operating room ready to go if this had happened, so it was nice that they lived. Really be cautious in dealing with these patients, right? That can happen. So you don't want to do a sphincterotomy and sweep out blood clots necessarily, right? You can maybe get in and stealthily open a fully covered metal stent to try to tamponade some kind of lower level bleeding, but you have to be careful with this. So incidence of ERCP-related bleeding, 0.3% to 2%. Etiology, sphincterotomy, biliary and pancreatic duct injury, as you can see there, splenic injury, hepatic injury, et cetera. Certainly patients with prior hepatobiliary surgery are at higher risk. Classifications in the literature can be by timing. Most of these are delayed, 50% to 70%, or severity-based, and that's really kind of when you're looking at the literature, how it really breaks down. And cotton had described as mild, moderate, and severe based on blood transfusions. So, you know, less than three grams per deciliter drop in hemoglobin is going to be mild. Less than four unit blood transfusions, less than or equal to four unit blood transfusions, moderate, and then greater than that. Severe, ASCE guideline classified it a bit differently with moderate requiring blood transfusion or IR intervention, and severe is a prolonged hospital stay greater than 10 days, a day in the ICU, or surgical intervention. So there's five independent risk factors, really, when you think about post-ERCP bleeding. Physician-related ones, again, related to case volume and experience. Patient-related coagulopathy, active cholangitis, and anticoagulation therapy, then three days after. And then procedure-related, which is occurrence of any bleeding during the procedure. And this is from, actually, an article in Gut that came out in 2021, and it's ESGE and British Society of Gastroenterology kind of put this together, looking at how you manage anticoagulation. There's an ASCE document, I think the most recent update on that was probably 2017, so it's due for something soon, I believe. So you can see here, we have the two categories. Whenever you're looking at this, you have low-risk and high-risk patients. I'm just including high-risk here. So if you're not doing a sphincterotomy, that can be considered low-risk, and you wouldn't be doing these modifications. But this is, in my mind, kind of the best guideline right now, if you're looking at how to manage these patients. And you have warfarin on the left, and you'll see there that you can hold it for five days in low-risk patients. And if it's higher-risk patients, you still do it five days, but you're going to be using low-molecular weight heparin. Then you have your DOACs. And these actually, it's kind of a complicated rubric, but in general, you take the last dose three days before the procedure. And then into your anti-platelet therapies, again, you have low-risk conditions and high-risk conditions. And generally, these, you're looking at seven days, or you're going to have to talk to the surgeon or the cardiologist about how to best manage those patients. So more work to come on these, but it looks like we're going to be kind of learning a lot more in the near future, because this new guideline, I think, will be coming out soon. All right, so what about prevention? So blended current is definitely better than cure cutting. A pure cutting current for sphincterotomy. Balloon sphincteroplasty might be associated with a decreased risk of bleeding. However, you have increased risk of PEP, so you have to be careful with that. Maybe a small release sphincterotomy, and that's another way to go. A prophylactic injection of hypertonic saline and epinephrine proximal to the papilla has also been shown to be helpful in select patients. So management, obviously IV fluid resuscitation. Treat it pretty much like a regular GI bleed. And reversal of coagulopathy when possible. Endoscopically, again, injecting diluepinephrine can be helpful, or spraying it. Balloon tamponade, questionable, but sometimes you can use that for certain situations. Thermal therapy certainly can be used. You want to avoid the pancreatic duct orifice in those situations. Clips, difficult to get them down. Some smaller clips are effective, but fully covered metal stents are probably the way to go for a lot of these patients. Hemostatic agents. Puristat has been used in these cases. Anecdotally, quite decently. You can see through it. You don't obscure a vision like you do with other hemostatic agents. And no studies really have specifically addressed combination therapy right now. Moving on to cholangitis. See here, we're removing a stent, and there we go. So that's kind of gross. The person was really sick, and just on pulling that stent out, they immediately looked better. So, you know, something that can happen as a result of us doing procedures and the stents getting occluded, we've manipulated the duct, now there's androbes to worry about, is something to think about. So, incidence of cholangitis, 0.5 to 3 percent of cases. Significant risk factors are listed here. Combined percutaneous endoscopic procedures, stenting of malignant strictures, and failed drainage, you get little pockets of contrast that you don't drain properly and that can certainly put the patient at risk. Risk is highest in patients with incomplete biliary drainage. Prior history of liver transplant as well. So how to avoid and manage this, MRCP is a road map, is really a great way to do this. You want to find the area you're interested in, get the wire into that segment before injecting any contrast. So that's really one of the best measures to minimize kind of retained islands of contrast that lead to infection. Meticulous drainage of all segments that do get contrast in them. A wire cannulation with aspiration of bile. So if you have a patient with known cholangitis already, rather than making a bad situation worse, you want to either aspirate that contrast out and replace with less, or get in, do a sphincterotomy and sweep some of it out or just sweep some of it out before proceeding. And remove all stone fragments or place a stent if you have a question about clearance. Proper stent selection is also important to minimize migration and antibiotic prophylaxis before ERCP in patients who've had liver transplant, it's very important. So really no new guidance on this from the ASGE. We have this one from some time ago, 2015 I think it was, but ASGE recommends antibiotics before and after ERCP in all patients presenting with cholangitis, of course, that's pretty clear. They recommend antibiotics before ERCP in patients who have post-liver transplant and coverage should include enterogram negatives as well as anaerobes if there's been prior instrumentation. And moving on to perforation. So incidence of perforation during ERCP is about between 0.08 to 1.6 percent. It's likely underreported. Some series have shown 13 to 29 percent incidence in retropyritoneal error on CT scans one day after sphincterotomy. Mortality, if this does occur, ranges from 3 to 23 percent in the literature. Numerous causes of perforations, sphincterotomy, balloon dilation, wire trauma, placement, positioning of the endoscope, and many different ways of classifying this as well. Location-based, mechanism of perforation, time, or acuity of illness, and classification has impacted management in the literature. I think one of the better ways of doing this is a stat for classification. This is what we use at our hospital. This really focuses a little bit on everything, but the site's primary here. So type one is a duodenal wall perforation, and that's usually due to passage of the scope itself. Type two is perianpular perforation and medial wall, and that's usually done by the sphincterotome. Type three is a bile duct or pancreatic duct injuries caused by instrumentation, and type four is a diminutive retropyritoneal perforation. You get retropyritoneal error there, and you just don't really see where the defect is. So this is various other systems. As you see there, the stat for systems on the left, and basically, I think I have a better slide on this coming up, but you can use this actually to guide therapy. So we'll get back to that, I think. So signs and symptoms, obviously perforation, C90-RCP, you're going to know it's there. Epigastric pain, flank pain, back or shoulder pain should kind of make you concerned about this. Subcutaneous epizema, fever, tachycardia, tachycardia is the most common sign of leak after surgery. We also see it here, and you can also get signs of peritonitis within four to six hours, and surgery within 12 hours. And here, basically, you just see the time of presentation. So less than one hour is in the majority of cases, followed by one to two, and the vast majority are identified by three hours. Again, risk factors, patient-related risk factors, suspected SOD at the time of procedure, female, sex, older patient age, and surgically altered anatomy. Procedure-related factors, difficult cannulation, intramural injection of contrast, long duration of procedure, sphincterotomy, pre-cut papillotomy, biliary stricture dilation, and less experienced operators. So this is a systematic review that assess the relationship of the STAP for classification to successful conservative management and surgical outcomes. They had screened 250 studies, and 12 were included. You can see the breakdown here. Fifty-eight percent were type 2, and then we have 18 percent type 1, and then the less less of the 3 and 4. So that's how it breaks down. And you can see the total number of perforations, 305. Fifty-four type 1s, most type 2s are 177, type 3 and type 4 listed below. So if you look at this area on each one of these boxes, this shows you the patients that were attempted to be managed with non-operative management, so 7, so 13 percent, and then you can see that 42.8 percent failed with type 1. Moving on to type 2, you can see 84 percent underwent non-operative management, and failure rate was 28.9 percent. Type 3 is basically 11 percent failure rate, and there was no failure rate for type 4. So as you kind of go down that classification, non-operative management becomes more effective. So I'm just saying that when an OSPI fails, the other thing to note here is that surgical intervention should be pretty rapid, because there are rather high mortality rates if you delay this beyond 24 hours. So general management of perforations, you want to switch to CO2 right away. If you're not already using it, give IV antibiotics that they haven't been given. Determine the type of perforation, if you can, right there during the procedure, and proceed with endoscopic therapy if indicated, and that's specific to the type of perforation. So post-procedure, you want to make an NPO, continue IV antibiotics, consider an NG tube. Pre-abdominal examinations, of course, routine labs, abdominal imaging with oral contrast can be helpful. Consider early drainage or surgery for a clinical deterioration, repeat contrast study recommended prior to resuming any diet. So for type 1, this is a duodenal wall perforation. This traditionally has been managed with immediate surgery. If you see it, however, now we have better ways of closing things. So depending on your skill set and comfort, you might want to take that on. So atrogenic perforations have a lower risk of bacterial contamination, and the patients are in a fasted state, so you're less likely to get any food debris out there. Several reports have shown this can be treated successfully. So in these situations, again, IV antibiotics, CO2, consider changing to general anesthesia if you're under MAC or conscious sedation. Clear the area of any fluid or debris, and then consider changing endoscopes and doing an abdominal decompression before trying to close this thing. Some places now have perforation teams. They're very effective at helping in these situations. It's a systematic review, 726 patients, 24 were included, and three of these were prospective. So kind of not the best data, but there's several series in here. And this showed that basically of these 466 acute perforations, 89% were managed endoscopically. And this is not focusing on ERCP, but it's showing you that perforations can be managed endoscopically with various techniques, whether it's endoclips or over-the-scope clips or metal stents. This is a case I published in GIE probably a decade ago now, or eight years ago. It's a big perforation with fat coming in. This happened during an ERCP in the Lothrid anatomy case. So it was clean. So the first thing we do is we go out in the abdomen. You look around and make sure there's not any contaminants out there that escaped that you weren't aware of that could cause problems, because they'd have to go to surgery. Additionally, if there's bleeding out in the abdomen, you'd probably have to go to surgery. And placing an angiocath there, varus needles are good as well. And we find some momentum, and if it's tacked down too much, you can free it up a little bit. But in this situation, it moved quite nicely back to the perforation. And then we're going to suture that into sort of an endoscopic grand patch, right? We're going to suture that into the area of the perforation. And you can do this with a running suture. You can see we grabbed a bit of the momentum as we're suturing across this. And the patient did very well. So you can manage these. The main thing is just control the pneumoperitoneum that you've got all the time in the world. If you're under anesthesia and you're using CO2, it's not a big deal to do this, right? Basically, you've got to control that with an angiocath or with a varus needle. And a little water valve on top of that is an open syringe with some fluid in it. You take all the time you want to close this. So again, we explored the abdomen, made sure there's nothing that would be a contraindication of endoscopic closure like bleeding or debris. We control the pneumoperitoneum. You consider a mental patch and then close the defect either with X-TAC, suturing devices, whatever you've got. Type 1, this is a stent-induced aluminum perforation, so a different type of type 1. So you're still perforating through the duodenum. It's kind of oftentimes this is more chronic and sometimes it's walled off. So if it's walled off, it's less of a concern, right? You can get out there and remove it and not worry about it too much. And you can see this with either plastic or metal stents. So if there's no peritonitis and it isn't walled off, you can still consider endoscopic closure. I'd probably put a wire alongside the stent, pull the stent just so you don't lose the hole because you can lose it pretty easily and then clip the defect. If there are peritoneal findings, that should go to surgery most certainly. If there's a fluid collection and there's not peritoneal findings, it's a little more iffy in what you do. Probably still go to surgery, honestly, but you can manage those endoscopically in select cases. Type 2. So if the perforation is suspected during the procedure, again, switch to CO2, give IV antibiotics, inject a small amount of contrast, try to see where it's coming from, so maybe place a stent across it. Basically, you want to avoid this by limiting the length of the cutting wire and the contact with tissue. Just using the end of that cutting wire during your sphincterotomy, you're less likely to have this happen and also perform stepwise cutting. Blended currents also help with that as well. Optimal management really is kind of dependent on different elements. If it's huge, you might not be able to place, if your sphincterotomy or balloon dilation is quite large, you might not be able to place a fully covered metal stent. In that case, you might have to go with a clip or other nasobiliary drainage, et cetera. But in general, if it's a reasonable sized sphincterotomy, a fully covered metal stent is probably the way to go. So for type 2, basically, there's several series that are shown that's effective, result 100%, small series, so you can't really rely on that too much. Type 3. This is typically due to guide wire puncturing biliary radicals, et cetera, and most of these do heal spontaneously, definitely doesn't hurt to have a stent in place, and basically follow them clinically, fairly straightforward. What about patients that you have a delayed diagnosis with? Well, in the absence of contrast material extravasation on fluoroscopy, ARCP perforation from, well, I think that delayed diagnosis here is something where you have to do a multidisciplinary approach. Definitely get imaging studies and look for the amount of gas that's on those CT scans. There's going to be a decent amount typically, and that does not necessarily portend a bad diagnosis, especially if you're using air. If you're using CO2, I think that you could expect less, and if you see a lot out there on CO2, that's something where you might want to follow them more closely. Contrast studies are not perfect. We know this from leak management as well. A lot of times, even with contrast with the CT scan, you're not going to see that perforation, so it doesn't mean it's not there. You have to follow them clinically, track their progress, and multidisciplinary team is important. Last topic, contrast reaction. Reactions to contrast material are idiosyncratic and can range from a rash to anaphylaxis. Adverse reactions to contrast are rare during ARCP. We really very seldom see this. There's a prospective study of 601 patients undergoing ARCP, including a subset of patients with history of intravenous and shellfish allergies that were severe, and none of these patients had a reaction to full-strength contrast. There's basically a lack of any evidence supporting pre-medication, so it's not something that's recommended. In conclusion, ARCP is the highest risk, commonly performed therapeutic procedure, again, not diagnostic. Things to consider to minimize and manage adverse events include proper indication and patient selection. That's very critical. From a pre-procedure standpoint, you want to prepare properly for this. You want to do imaging, get a roadmap for what you're working on, consider modifying anticoagulation, and consider antibiotics. Interprocedural decision-making is also very important. You want to make sure you use efficient cannulation technique, optimal techniques, wire-guided cannulation. Complete drainage of any contrast you put in endomethacin and intravenous flutas are important to minimize post-UHP pancreatitis, as well as pancreatic duct stents. Finally, identify AEs early and be proactive. You don't want to kind of just hope you don't have an adverse event. You really have to dig in there, look to make sure you don't have one, prove it to yourself you don't have one, otherwise treat it and do what you can to treat it and follow these patients very closely, and then again, very important to have very close follow-up and communication with the patient and family. Thank you.

ERCP

adverse events

preventive measures

complications management

multidisciplinary approach

prophylactic stenting

endoscopic techniques