Gut Check: Acute Pancreatitis with Drs Brian Lacy and Timothy Gardner

Dr Brian Lacy welcomes Dr Timothy Gardner from Dartmouth-Hitchcock Medical Center to discuss the diagnosis and treatment of acute pancreatitis.

Brian Lacy, MD, is a professor of medicine at Mayo Clinic-Florida in Jacksonville, Florida. Timothy Gardner, MD, is professor of medicine and director of Pancreatic Disorders at Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire.

TRANSCRIPT:

Welcome to Gut Check, a podcast from the Gastroenterology Learning Network. My name is Brian Lacey. I'm a professor of medicine at the Mayo Clinic in Jacksonville, Florida, and I'm absolutely delighted to be speaking today with Dr. Timothy Gardner, professor of medicine in the division of gastroenterology and hepatology at the Geisel of School of Medicine at Dartmouth in Hanover, New Hampshire. Dr. Gardner, as you know, is a nationally recognized expert in the field of pancreatitis. He has authored many of the key guidelines on the evaluation and treatment of both acute and chronic pancreatitis, including the key guidelines published in Gastroenterology in 2018. He has published practice-changing articles on ERCP-induced pancreatitis and the use of TPAIT— total pancreatectomy and auto-islet transplant—for the treatment of chronic pancreatitis. He's a sought-after lecturer, both nationally and internationally, on all topics related to pancreas. And in addition, Dr. Gardner is the GI Fellowship director at Dartmouth. Today though, with all these things going on, we're going to focus on the topic of acute pancreatitis. So Dr. Gardner, welcome. What a delight to have you here today. For our listeners, not quite as comfortable with the topic as you are. Let's begin simply. How common is acute pancreatitis?

Dr Gardner:

Well, thanks Brian, and really honored to be here talking to you. Great question. Surprisingly, acute pancreatitis is much more common than most people think. In fact, it's the second most common reason why patients are hospitalized for a gastrointestinal illness in the United States. So we think anywhere between 400 to 500,000 admissions to the United States annually, and that's just hospital admissions.

Dr Lacy:

Wow. A lot more than I think people would think. So this is certainly an important topic and I'm glad we're addressing it today. And so what are the cardinal symptoms of acute pancreatitis? Is there any one symptom that easily distinguishes or differentiates acute pancreatitis from gastroparesis as an example, or biliary colic or pyelonephritis?

Dr Gardner:

Well, the classic symptom of acute pancreatitis is pain. So the classic symptom would be epigastric pain usually radiating to the back, and that is something that occurs in about 90% of patients. Not everyone, but about 90% of patients will have pain. Again, epigastric boring to the back. The other thing to remember about acute pancreatitis is that it's extraordinarily painful. In general, this is not a subtle pain attack, and almost every woman who's ever been in labor, who I've taken care of who's had acute pancreatitis says they would much rather go through labor than one attack of acute pancreatitis. That's the severity of the pain we're talking about. And that's probably a way that one can distinguish this type of pain for other types of pain, both the severity of the pain and the location of the pain.

Dr Lacy:

And I like your description of kind of boring pain to the back, which too distinguishes it. So that's very helpful. So what about some of the most common causes of acute pancreatitis? Many of us were taught it was just alcohol or gallstones or elevated triglycerides. Is that still true or are medications playing more of a role and do you think genetics might even play a role?

Dr Gardner:

That's a great question. So by far and away, the 2 most common reasons people get acute pancreatitis in the United States—adults in the United States—is alcohol and gallstone. And it varies a little bit, but we do think that gallstones accompany, excuse me, gallstones is about 50% of the patients who get acute pancreatitis and alcohol between 35 and 40%, depends a little bit on the region where you live. But with the increasing obesity epidemic, we know that more patients are getting gallstones and microlithiasis, which is associated with gallstones. So at this point, we know that gallstone disease appears to be the most common reason with alcohol a close second. So that includes about 80 to 85% of all patients with acute pancreatitis.

But your question's a great one about what other causes. So some of the other less frequent causes: triglycerides, especially in young people, so very, very triglyceride levels, over 1000, usually are in those patients who get hypertriglyceride-induced pancreatitis.

Medications are always a common reason. The classic ones we talk about are medications like furosemide, ACE inhibitors, some of the HIV medications, estrogens. Those are the kind of classic medications that cause it, although just about any medication can cause acute pancreatitis, including some of our new GLP-1 drugs that we have available.

Now genetics is a great question. So as I was training 20 to 25 years ago in medical school, especially in pediatric patients, the thought was that pediatric patients got acute pancreatitis mainly because of viral disease. And we know that now that's changed. We have a much better understanding of genetics as a cause of acute pancreatitis. So certainly in children and much more in adults now we're seeing genetic causes as an underlying reason for acute pancreatitis. So it's just something to think about as well as in children, the increasing obesity, we're seeing a lot more microglia in that population in gallstones as well.

Dr Lacy:

Tim, that's wonderful. And I like your nice teaching point about triglyceride levels, because it's not 200 or 300, it's 1000, 1500, 3000. That's very helpful for our listeners. And thinking about the best way to diagnose pancreatitis, you've already mentioned this cardinal symptom of kind of boring pain, but is it that symptom alone and maybe other symptoms plus blood work? Or is imaging always required?

Dr Gardner:

It's a great question. We actually have a classification called the Atlanta classification, and that's what we use to help diagnose acute pancreatitis. And what you need per the Atlanta classification to have acute pancreatitis is 2 out of the following 3 criteria to make that diagnosis. So one, you need the classic abdominal pain symptoms, and we already covered those two. You need elevated serum amylase and or lipase levels greater than 3 times the upper limit of normal. So to make the diagnosis of pancreatitis, you need generally a lab value that tells you that. As far as the third criteria, that's cross-sectional imaging demonstrating pancreatitis. So if you have those first two, then you don't need to do a CAT scan or imaging to make the diagnosis. However, if you don't have those first 2 and you still suspect the diagnosis, then that's when you'd go ahead and get a CAT scan or MRI to make the diagnosis.

The important teaching point I think with this is that there are patients who have acute pancreatitis who don't have elevations in their amylase and lipase. So they may have a classic symptom, they may have normal lab values, and then you're still concerned that they may have this diagnosis. You get a CT scan and you see it on the CT scan. So again, teaching point is that patients can have acute pancreatitis without elevations in their amylase or lipase.

Dr Lacy:

Wonderful. That's good to remember that, not with a normal value to discard that diagnosis too early. So Tim, we're going to talk about treatment in just a minute, and this will play a little bit into our treatment, but I want to think a little bit and learn a little bit more about the natural history of acute pancreatitis in this inflammatory insult. Is this something we can just observe and treat with tincture of time or do we need to characterize patients as kind of early phase pancreatitis or late phase pancreatitis to guide them to the direct therapy? And along with that, what percentage of patients develop complications from acute pancreatitis such as a pseudocyst or chronic pancreatitis?

Dr Gardner:

Yeah, it's a really important question, Brian. So when someone has acute pancreatitis, what we really try to prognosticate within the first 24 hours that they're in the hospital is the severity of the pancreatitis. So we have 3 different categories—mild, moderate, and severe. And mild pancreatitis is that pancreatitis, which is generally going to resolve without complications within a week or so. And 80% of patients who get acute pancreatitis have mild pancreatitis. And those—we're going to talk about treatment in a little bit, I'm sure—but mild pancreatitis generally just goes away on its own with a tincture of time and some supportive care.

What we worry about in the moderate and severe pancreatitis are complications including organ failure, fluid collections, venous thrombosis, and really, death. And we know that about one out of every 20 patients with acute pancreatitis dies. So it's something that we really need to pay attention to and prognosticate and how we do that in the emergency room really is to look at if they in fact have evidence of organ failure, if their creatinine's elevated, if they're hypotensive, if there's any sort of cardiac abnormalities like elevated troponins, et cetera. Those are the things we kind of pay attention to, and we follow their course much more carefully.

So again, most patients who come in are going to have a very mild pancreatitis. Again, it doesn't feel mild to the patient, but most of the time they're going to do just fine with supportive care. But it's that 20% of folks who develop moderate or severe pancreatitis based on whether or not they have organ failure or local complications such as food collections that we really want to pay attention to.

Dr Lacy:

Tim and I like that point a lot too, that we shouldn't underestimate how severe this can be with a mortality rate in some of these patients approaching 5%, which is pretty scary. We need to take this very seriously. So you've done a lot of really neat cutting edge research into the treatment of acute pancreatitis with aggressive volume resuscitation, and really what's the physiology behind that and how should a provider do this? Is it normal saline? Is that the fluid of choice? Is it lactated ringers, and is there any new data in the field about fluid resuscitation and acute pancreatitis?

Dr Gardner:

Yeah, so for many years, one of the criticisms of how we took care of patients with acute pancreatitis was that they were under-resuscitated, that we simply were not giving patients enough fluid when they came into the hospital. So for the last 2 decades or so, we've really been pushing on this, we need to hydrate, hydrate, hydrate very, very aggressively, and that can by aggressive, that can be anywhere from 200 ccs an hour to up to 500 ccs an hour of aggressive resuscitation for patients really titrated to their BUN levels and how much urine volume they're making. So this was really an emphasis. The other point of emphasis was that we found that normal saline really was not the best way to resuscitate patients. And we found that lactated ringers solution was really the better way to resuscitate patients having to do with the pH of lactated ringers and what it supplies.

So over the last 2 decades, we said very, very aggressive resuscitation. Really, really need to push it, and you have to use lactated ringers.

I think an answer to your question about is there any new data, well, last fall there was a huge study that came out called the Waterfall Study in the New England Journal of Medicine, which looked at this issue of aggressive fluid resuscitation, which they described as 3 ccs per kilogram per hour versus a more moderate approach, which was 1.5 ccs per kilogram per hour. And using lactated ringers in both groups in patients with predicted severe pancreatitis. And they looked at important outcomes like complications from fluid resuscitation. And what they found was that patients who had a more moderated approach, who were on that 1.5 CCS per hour approach for the first several hours they were in the hospital, did much better.

So these patients did much better. And the reason was because a lot of these patients developed complications related to over-resuscitation, so they ended up with abdominal compartment syndrome, they ended up with pleural effusions, et cetera. So what we're doing now is we're moderating our approach a little bit with fluids. So rather than really, really hammering people, the goal here is to go 1.5 ccs an hour for about the first 24 hours. And really, we know that the total volume of fluid in the first 24 hours based on this Waterfall study from the New England Journal showed that patients who got less fluid, patients who got 6 and a half liters in their first 24 hours in the moderate group versus about 9 liters in the aggressive group actually did better. So it's a slower rate of infusion and a lesser volume, and patients seem to be doing better.

Dr Lacy:

Okay, an important study, and again, showing how science slowly evolves, but a couple of key teaching points: fluids are important, lactate ringers is better, and this more moderate approach is really the best right now.

Tim, there's been a lot of controversy about when to start feeding a patient. I know that probably many of our listeners were told in the past, you wait a week or even longer because you want to kind of “rest the pancreas.” But then some guidelines that shorten that maybe 3 days or 5 days, now there's even new data that may be earlier feeding better. Where do we stand right now?

Dr Gardner:

So the data has shown that the sooner we get patients to eat the better. So if that means a patient comes in with acute pancreatitis and they're able to tolerate eating a low-fat diet, then that's great to do from the moment they arrive. And the reason behind that is probably due to the fact that in using the gut, we know this helps prevent bacterial translocation if the gut is fed. So we really want to avoid bacterial translocation because, especially in patients with necrotic pancreatitis, this can lead to infected necrosis. So it's okay for patients to feed. Now, of course, you have to make sure that they're not vomiting, they're not nausea, you worry about aspiration. But if a patient can tolerate a low-fat diet from the beginning, you want to feed them as soon as they arrive.

Dr Lacy:

Tim, as usual, you kind of beat me to the punch. And I had another question for you, but I want to just jump ahead a bit because you mentioned this concept of epithelial barriers and bacterial translocation, and we know that acute pancreatitis is an acute inflammatory event, and this may change epithelial barriers and maybe increase intestinal permeability. So as a logical consequence, a lot of providers say, well, let's use the antibiotics, right? So where do we stand now? Should everybody get antibiotics? Should only the most severe, should nobody get antibiotics?

Dr Gardner:

Really at this point, we're not recommending antibiotics for anyone with acute pancreatitis. Remember, pancreatitis is an inflammatory event. So patients are going to have an elevated white blood cell, they're going to have a fever, and it can be very tempting to put patients on antibiotics. But we know from well-designed clinical trial that antibiotics generally don't help, and they can actually probably cause some harm in that it can predispose patients to getting intra-abdominal fungal infections if they're on antibiotics unnecessarily. So, although it can be really tempting to want to give antibiotics for acute pancreatitis, we really recommend they don't, unless of course they have a documented infection, or in fact, you're concerned about something concomitantly like cholangitis, you'd want to give antibiotics for something like that. But in general for acute pancreatitis, no antibiotics.

Dr Lacy:

Alright, so let's remember one of our true said “first, do no harm” and antibiotics can actually hurt people, so let's not use them routinely and only with specific reasons.

So you mentioned too that acute pancreatitis is an inflammatory event, and I know you probably get to ask this all the time when you give a lecture nationally or internationally. So if it's an acute event, why don't we just give steroids right at the start? Can't that help people?

Dr Gardner:

Yeah, I wish we could. In fact, we have given every iteration of steroid and well-designed clinical studies over the last several decades. And unfortunately, steroids don't help. Steroids don't help, and for all the reasons that they can be harmful, we see those harms. And just to take the point a bit further, Brian, is that we don't have a medication, a pharmacologic therapy that is designed to stop acute pancreatitis. Many, many have been tried. Many, many have failed. There's multiple trials ongoing now for various medications to help with acute pancreatitis, but at this point, we just don't have that specific medication that can shut down that inflammatory response. Although again, as I said, there's multiple trials ongoing, looking at lots of different medications using lots of different mechanisms for this disease.

Dr Lacy:

Most likely, it seems like once that inflammatory cascade begins kind of the horses out of the barn, and we're always a step behind, aren't we? So Tim, what's the role of surgeons for patients with pancreatitis? When do we ask for a surgical consult? Should everybody see a surgeon at the start? And certainly, what about those patients, as you mentioned with gallstone pancreatitis, should they have surgery during the hospital stay or do we wait until they've recovered?

Dr Gardner:

It's a great question. So in general, Brian, what we try to do is keep surgeons away from patients with acute pancreatitis, with the exception of one real important reason. And that's in patients who have documented gallstone pancreatitis. We know that we really want them to have their gallbladder out before they leave the hospital. So in those patients who, again, need a cholecystectomy, what we don't want to do is get them through their hospitalization, send them home, because we know that patients have a high instance of complications from gallstones—recurrent pancreatitis, cholangitis, et cetera— if they don't get their gallbladder out before they leave. Other than that, in general, we really try to keep surgeons away. The teaching decades ago of surgery needed for patients with infected necrosis, that's gone. We generally really try to keep the surgeons away, even for infected necrosis, we can really generally treat them supportively through it.

Dr Lacy:

Yeah. Again, another great example of how this whole paradigm has shifted in the last 2 decades. So Tim, we've covered a huge amount of material here today. Any last thoughts for our listeners?

Dr Gardner:

Not really. I just want to thank our listeners for listening to the podcast, and Brian, I really appreciate you having me on.

Dr Lacy:

Okay. Well, Tim, again, thank you so very much. We know how incredibly busy you are. We appreciate you taking time out for this podcast today. To our listeners on Apple, Spotify, and other streaming networks, I'm Brian Lacy, a professor of medicine at the Mayo Clinic in Jacksonville, Florida, and you've had this wonderful opportunity to listen to Gut Check, a podcast from the GI Learning Network. And our guest today was Dr. Timothy Gardner, professor of medicine at the Geisel School of Medicine in Hanover, New Hampshire. I hope you found this episode just as enjoyable as I did, and I look forward to having you join us in the future for future Gut Check podcasts. Stay well. I.