With gastroesophageal reflux disease affecting 40% of the U.S. population every month, primary care providers need a straightforward plan for initiating therapy, as well as an up-to-date understanding of causes and treatment complications. In this video, gastroenterologist Priya Kathpalia, MD, shares her wisdom on dosing PPIs effectively, tapering the drugs, using adjunct meds and responding to patients’ worries. Learn when to screen for Barrett’s and when to refer.
Uh, so, this is a topic near and dear to my heart, GERD, the prevalence and management, and of course, we could, uh, talk about this for hours, but we'll try to, uh, limit it to about 45 minutes, so we have plenty of time for questions. So, just wanted to start with uh understanding the prevalence of GERD in the United States, and we know we're all seeing more and more of this uh in our clinic, and it's certainly increased over the years. So, studies show anywhere from 20 to 30% of the population in the US um has some degree of GERD at least weekly. And a lot of that heterogeneity in, in the GERD prevalence really lies in which questionnaire is being used and what population, uh, what is the threshold and duration of symptoms required to be classified as GEERD. And, uh, you know, some studies that, uh, list numbers as high as 30% were actually, uh, from survey-based studies that were done at the Houston VA Medical Center, and, uh, whereas the kind of the lower rates are from Olmstead County in Minnesota, predominantly white population, um, so that just kind of accounts for some of the differences in GERD prevalence depending on the regions in the United States. So outpatient visits for GERD, uh, the National Ambulatory Medical Care Survey, this was granted 20 years ago, said that GERD-related visits at that time to PCPs was up by 46%. Non-related, non-related GERD visits was up by 6%. Now, PPIs, as we know, have really revolutionized GERD treatment, but still about 30% failed to completely respond to at least daily therapy. And so not surprisingly, the number one reason for an outpatient GI referral, uh, is in fact, uh, refractory GERD these days. Now, the classic symptoms of GERD, as you all know, are, uh, heartburn and, uh, acid regurgitation. Patients will often describe a burning feeling in their retrosternal area. Symptoms often occur postprandially, particularly after large fatty meals or ingestion of spicy foods, and the supine position may exacerbate some of these symptoms as well. But the truth is there's really no clear standard for the diagnosis of GERD. And that's part of the issue. Um, you know, the Diamond study, and this was a UK study that was done evaluating patients who presented to family practice providers with upper GI symptoms. And based on endoscopy or pH testing, about 2/3 of them had GERD. Based on solely symptoms, about 50% had GERD. The other thing to keep in mind, as you all know, is that it's, there's also a lot of overlap with GEERD and other GI conditions. So, patients may have GERD and some dysphagia or chest pain and water rush, um, or burping and hiccups. Uh, and so, uh, we also need to recognize that they could have GERD with another condition. They could have functional dyspepsia. They could have eosinophilic esophagitis. They could have a motility disorder, which can really pose, you know, significant significant management dilemmas and we'll be um discussing further uh over the course of this talk. Now, the most predominant mechanism of GERD, it is the defective barrier of the lower esophageal sphincter. And uh the most common mechanism are TLESRs or transient lower esophageal sphincter relaxation. Now, patients who have a hiatal hernia are also predisposed to GERD because, um, you know, the acid is, uh, should be in the stomach and now we're exposing the esophagus, uh, which is not, uh, uh, used to that degree of acid exposure um to now a much larger, um, kind of burden. In addition, uh, increased, uh, pressure, intraabdominal pressure, intraabdominal girth in patients with obesity, pregnancy, uh, and then, um, those with delayed gastric emptying, this can also, uh, all impact the lower esophageal sphincter. Now, certainly, this can be further impacted by patients who have decreased esophageal clearance, whether they have a disorder like phalagia or even a minor motility disorder such as ineffective motility. And finally, uh, patients can also have decreased intrathoracic pressure, particularly those with COPD, um, those who have more of a chronic cough presentation, uh, patients who are professional singers, we see many of those have kind of more likely to have GERD. So, how do we manage these patients? And certainly, there's a lot of variability and um this is just, you know, one algorithm. Um, but the initial treatment when we see patients with heartburn or regurgitation, um, even before uh they come to the gastroenterologist, they're seeing your, you know, the primary care provider and the PPI or an H2 blocker is started. And I would highly recommend that, you know, you go straight to the PPI and start at least the dosage of 40 mg daily. So, um, the over the counter 20 mg dosage, uh, for two weeks is just not adequate and we're not actually, um, you know, Getting to the heart of the problem. And so patients often have recurrence of symptoms with the lower dosage or, um, you know, they're refractory, but they actually haven't tried the higher dosage. Um, so the initial treatment in my mind is really the PPI, uh, uh, you know, omeprazole, for example, 40 mg daily. Uh, and then if, if they have a good initial response and they're symptom-free, uh, then, you know, you wanna try to get to the lowest effective dose, and ideally, you wanna get them off the medication entirely. And, um, you know, we'll talk about side effects. Shortly, but I think that the big issue is that so many different providers are prescribing PPIs and they don't often give the patients an endpoint. And so it's really important to communicate with the patient how long they need to be on the medication. What should they do with the medication once they've been on it for, you know, 8 weeks? Um, should they stop it cold turkey? No, right? They should taper it because they can get some rebound acid reflux. And so it's really important to counsel them through that process. Now, it's also important to recommend, uh, screening for Barrett's esophagus, particularly, uh, Caucasian men over age 50 who are obese or smokers or who have long long-term symptoms. We really need to think about. um, screening them for Barrett's at least one time. And, you know, I won't have them necessarily make a special trip to the endoscopy unit just for this. I'll try to coordinate with an upcoming colonoscopy and recommend an endoscopy at that time just to help minimize their sedation. Now, what about the patients who don't respond to uh PPIs? Well, um, you know, I had mentioned starting omeprazole 40 mg daily for 8 weeks. And so, uh, you can certainly go up to twice a day if there's no benefit. Um, you could, um, add, uh, an H2 blocker as well either at nighttime or, um, you know, if they're on an H2 blocker and not a PPI certainly switch them to a PPI at that time. Um, and if they have a, a good response, then I, I think you can then go to tapering them slowly, um, after, uh, an adequate trial. Uh, however, if they don't have a good response, this is certainly what I would consider refractory GERD that would warrant, uh, an, uh, a, a referral to GI. So, uh, once they come and see us, uh, if they've had the adequate PPI trial, we'll want to probably consider doing, uh, an endoscopy just to make sure that we understand their anatomy. Do they have a hiatal hernia? Do they have any signs of Barrett's esophagus? Um, do they have any peptic strictures or narrowing as a result of long-standing kind of poorly controlled GERD? And then, uh, if the endoscopy is unrevealing, I would go next to, um, considering, uh, formal ambulatory PH monitoring. And generally, we would do this off of PPI therapy cause we wanna understand their baseline level of reflux. Uh, but the pH testing is also particularly important in understanding how their symptoms correlate with, uh, reflux. And so every time patients have symptoms, they'll push a button and we would be able to understand whether or not their symptoms are correlating to reflux. There are patients who have reflux and functional dyspepsia, as I had mentioned earlier, and there are patients who have just functional symptoms, but it's really mimicking reflux, and so that may be part of the reason why they're not responding to PPI therapy. Um, Now, certainly, if patients have any alarm symptoms, uh, even at the onset of, of, of treating them, I would send them to GI at that moment. So, what are some of these alarm symptoms? Uh, certainly, if they have any dysphagia or dinophagia, you wanna send them to us. Uh, obviously, if there's any signs of GI bleed, uh, if they have, uh, iron deficiency anemia. without another clear cause, unintentional weight loss, family history of any upper GI malignancies, um, feel free to send them sooner than later and we'd probably consider endoscopy even before, uh, Or concurrently while trialing the medication. Now, some indications for long-term PPI therapy. Um, certainly, if they have a history of erosive esophagitis on a prior endoscopy, so somebody who has reflux esophagitis, LA grade C or D, you might see in the reports, that's an indication where they should probably be on PPIs long term. Uh, and or consider more definitive therapies like a fundoplication, for example. And then Barrett's esophagus, uh, all the literature suggests that patients should be on at least once daily low-dose PPI, uh, as PPIs tend to be the one thing that can help prevent further progression of Barrett's to esophageal adenos CA. I should also add on this list, uh, the, kind of a separate topic, eosinophilic esophagitis is another reason, uh, for patients to be on long-term PPI therapy, and, uh, some degree of kind of chronic suppressive PPI therapy is necessary in that population. Now I know you can't really read this slide and um I put this up here on purpose to show you, yes, there's a lot of side effects of PPI therapy that have been reported and patients will always ask us about this, understandably worried. Uh, there were studies that came out 5 to 10 years ago showing risk of heart disease and dementia and kidney disease, uh, with PPI use, but, um, none of that was proven on subsequent studies. These studies really looked at, uh, patients, uh, who had comorbidities and who were on a PPI, but we really don't know what came first in this population. Um, the chicken or the egg. And so, I, I really caution when we're interpreting those studies that we should reassure our patients that those side effects, uh, are highly, highly unlikely. What I will say are the side effects that I always tell my patients to think about are, uh, you know, acid is protective on the GI tract and so we're suppressing acid, we are making you more prone to diarrhea or infectious illnesses of the gut. And so the studies that suggest Tested, uh, increased risk of C. diff and, uh, SIB or small intestinal bacterial overgrowth. I think those are, are real side effects that we see in our clinical practice and, and need to be dealt with on a case by case basis, but it's generally very rare, yeah. The other thing is, is that, um, certainly, uh, the medications can impair calcium absorption, and magnesium absorption, and, uh, you know, we need to be cognizant of their bone health, particularly, uh if it's a postmenopausal woman who's at Risk of osteoporosis or already has osteoporosis. Uh, we, we need to just make sure we have a clear indication for PPI therapy in them and that we have again, a, a well-defined, uh, a defined understanding of how long we're gonna keep them on the medication. That being said, none of our GI guidelines say that, um, primary care providers or gastroenterologists should be checking calcium and vitamin D and magnesium levels because patients are on PPIs. Certainly, if it's, um, you know, part of their, their other healthcare maintenance, that's a different issue, but for PPIs alone, uh, there is no need for routine, um, checking of, of these, uh, electrolytes. Now, I want to also emphasize that in addition to medications, dietary and lifestyle modifications can be particularly important and complementary to the medications. So telling patients to elevate the head of the bed, the upper back, getting a wedge pillow, uh, can be particularly helpful. Of course, telling them to stop smoking, avoid, uh, sleeping until at least 3 hours after the last meal. Eating smaller, more frequent meals throughout the day as opposed to three large meals, kind of grazing will give the stomach a little bit more time to empty. Um, weight loss, uh, even, uh, if a patient is not obese and they're just overweight, uh, it, it can be beneficial to lose even 5 or 10 pounds again to minimize pressure, uh, on the lower esophageal sphincter. And then, you know, patients often ask me about what dietary modifications they should consider doing, and I, I always caution them that uh uh they're gonna find various GERD diets on the internet, and if they look at those, they might not eat anything because at at least, um, you know, one thing that they're eating daily has been implicated in this. Um, but I tell them, you know, be familiar with foods that might trigger your symptoms. Keep a food diary. Certainly, you guys know the common culprits, chocolate, alcohol, peppermint, caffeine, greasy foods, spicy foods, tomatoes, citrus, basically all the good stuff. And so I tell them, you know, everything in moderation. Now, there are certainly uh adjunct therapies for GEERD and uh we talked briefly about uh H2 blockers, particularly, uh, those that are taken at bedtime can be helpful. Um, prokinetic agents, there's, uh, metoclopramide, uh, you know, we have to be cautious about that because of, uh, the black box warning of tardive dyskinesia. So I really reserve giving Patients metoclopramide and unless they're uh on uh unless they have documented uh gastroparesis. But there's a lot of emerging data for procaloride, uh, which is a medication that, um, has been approved for constipation, uh, but, uh, has also been, uh, more recently found to be effective for patients with gastroparesis as well. Um. Uh, procalopride is a 5-HT agonist, and, uh, it has been shown to improve gastric emptying and reduce esophageal acid exposure in patients with GERD. And finally, uh, sucralfate, uh, can be, um, I missed, uh, baclofen actually. That's a GABAB agonist, and it can reduce the TLESRs. Uh, I find this medication is, uh, again, can be used together with PPI therapy, but on itself, uh, uh, on its own is not particularly effective. And then sucralfate or Carafate is something else to consider. Uh, it's a mucosal protective agent. Uh, it might be beneficial in patients who we think have more bile reflux or non-acid reflux, and, uh, pH testing can help distinguish that acid from non-acid reflux. Now, I wanted to show a little bit of data about what is the prevalence of GERD across ages, and there's certainly a lot of conflicting data on this. In a meta-analysis of 19 studies reporting GERD prevalence according to various ages, um, the prevalence in those over age 50, uh, was 17% compared to 14% in those under age 50. And uh there was an odds ratio of 1.32 in these two groups, and, uh, you know, I think it's important to recognize that there was significant heterogeneity among the groups. What is clear though, is that advancing age is more strongly associated with complications from GEERD. And so between 2003 and 2006, hospital discharges were looked at with a primary GERD related diagnosis, and they uh found that about half a million uh hospital discharges compared to 14.5 million uh where GERERD was the kind of this listed as a secondary diagnosis. Now, uh, the highest rate of GERD-related complications, particularly of, uh, adenocarcinoma, is, uh, as well as, you know, hiatal hernias and esophageal strictures tend to peak in this, uh, 65 to 84 age group. And is there a difference in the prevalence of GERD across races? Heartburn occurs at least weekly in the black population in this study was about 27% compared to 23.5% in white participants, and then uh 23.7% of other races, though the prevalence was not statistically significant amongst the three racial groups. And while the prevalence of GERD is not variable among the races, the severity of GERD is certainly distinct. And here we can see the prevalence rates of erosive esophagitis stratified by weekly GERD symptoms, with severe erosive esophagitis being characterized as those having LA class B or higher esophagitis. And, uh, regardless of whether their presenting symptom was heartburn or regurgitation, white participants tended to have a greater proportion of erosive esophagitis uh than the, the black participants. And so as the prevalence of GERD is increasing, so are the downstream consequences of GERD, including Barrett's esophagus. This is a study actually done at Kaiser in Northern California, looking at the prevalence of Barrett's esophagus, based on diagnosis, electronic diagnosis, sorry, dating back to 1994, when the diagnosis was first recorded in their system. And we can see that the, the prevalence of diagnosed ferrett's rose steadily throughout the study interval, and ultimately reached 131 per 1,000,000 member years in in 2006. I'm sure it's even higher now. And the prevalence in 2006 among non-Hispanic whites was twofold higher than among Hispanic whites. And fivefold higher in uh than among blacks and Asians. And so with rising rates of Barrett's esophagus, not surprisingly, we're also seeing an increased incidence of esophageal adenocarcinoma. Which is now the 8th leading cause of cancer in the United States. The CER database shows rising trends of oesophageal adeno, particularly in the male population, and it's thought to be the fastest growing malignancy among males. Though, uh, reassuringly, it seems like, uh, perhaps, uh, we're reaching a plateau, and it's likely due to the more widespread use of PPIs in the last decade. And I know there's a lot of concern, as I mentioned before about the side effects, uh, and I could probably do a, you know, a whole talk on the side effects of PPIs, um, but I think again, it's important to, to remember this data and uh try to reassure patients that if there's a clear indication for PPI use such as Barrett's esophagus, that they should remain on the drug. And so, why the rise in in GEERD and associated complications? Well, um, certainly, uh, it's because it might be because of our aging population. Uh, with aging, we know that there's, uh, decreased esophageal peristalsis, and there may be, uh, increase in the number of TLESRs, and there may be additional, you know, anatomic disruption to this esophagogastric junction. There's also some question about the decreasing prevalence of H. pylori. There's some debate that H. pylori can prevent, uh, or, or can H. pylori patients actually develop atrophy in the gastric body and decreased acid secretion as a result, particularly in those with the CAGA strain. So perhaps we're just better looking for, uh, better at looking for H. pylori, and, uh, by treating them, we're maybe making their GERD a little bit worse. We also know that tobacco use is weakly associated with GERD. There's been a lot of longitudinal studies showing that those with decreased tobacco smoking, um, those who decreased tobacco smoking were 3 times more likely to have reductions in symptoms of heartburn and reduction. And then, finally, we need to think about the obesity epidemic in America. And we know, as I mentioned before, that uh obese people have increased intraabdominal pressure that can further displace the lower esophageal sphincter and increase the gastroesophageal gradient. In addition, it may simply be to their, uh, due to the dietary intake or dietary indiscretions that may, uh, directly be making them more prone to acid reflux as well. Now I wanted to spend a little bit more time discussing GERD as it relates to the obesity epidemic. It was estimated in 2016 that nearly 40% of the US's population was considered obese. This is a really nice study that uh looks at the association between uh BMI and the risk of frequent symptoms for GERD, and they looked at multivariate odds ratios based on 2300 women who had GERD symptoms at least once a week. Compared to 3900 without symptoms. And the two groups were adjusted for age, smoking status, their activity levels over the course of the day, their daily caloric intake, their intake of alcohol, coffee, tea, and chocolate, um. Use of postmenopausal hormonal therapy, anti-hypertensive or asthma medications, and then the presence or absence of diabetes. And not surprisingly, we see a dose-dependent relationship between increasing BMI and the frequency of reflux symptoms. Those with increased waist circumference, central adipocity are much more likely to have GERD, and in part again due to the increased pressure on the lower esophageal sphincter, studies have actually shown that patients, uh, these patients in particular, have increased reflux episodes on PH studies, increased esophageal acid exposure time, and an increased number of TLESRs, the predominant mechanism implicated in GEERD. Reassuringly, studies suggest that by reducing their BMI by just 3.5 points, they can actually decrease their GERD symptoms more than 2-fold. And so it's really clear that uh obesity and GERD are highly intertwined. So in a motivated patient who's not trying to be on PPIs, long-term weight loss can have a huge impact on their symptoms. So, I'll end with this slide on my approach to GERD treatment. I think we'll have a little bit of extra time for questions. Uh, if patients have no alarm symptoms, put them on at least a daily dose of PPI for 8 weeks, omeprazole 40 mg daily. And they're not considered refractory unless they don't respond to the 8 weeks of therapy. If they have improved improvement, taper them off. And when I taper patients, uh, certainly there's so many different ways to do it. But if they're on, uh, BID dosing, I go to daily for 1 week, I go to daily every other day for a week, and then I have them stop it. So it's a relatively rapid taper over, you know, a course of 2 or 3 weeks. And then, when they're tapering, I always tell them, I warn them, you may get rebound reflux. Don't go back on the medication. Consider using an H2 blocker, uh, in place of the PPI, uh, on the days you feel you have more symptoms. I also counsel them that, uh, if they feel the need to go back on the PPI therapy, I'd, I'd love to know about it, uh, and try to understand what happened, uh, when they were tapering, what, what their symptom burden was. Um. I, I really try to convince them that H2 blockers work well on demand as a pill in pocket when uh they, they have breakthrough symptoms as they're tapering, uh, or even, you know, A random day that they're gonna be eating a larger meal or have an extra glass of wine, perhaps taking an H2 blocker on those days, uh, may be beneficial. Now, if they have no improvement after, uh, uh, the standard dosing of PPI for 8 weeks, I would refer them for an endoscopy and further evaluation. And if the endoscopy is normal, and I should caution by saying patients, sometimes we need to remind them that just because you have a normal endoscopy doesn't mean that you don't have GERD. It just means you don't have any complications from GERD or any structural abnormalities that might predispose you to GERD. But a normal endoscopy doesn't mean you don't have GERD. And I may consider doing a pH test on them off of therapy, and this is a 24 hour pH test done with impedance. So we um we get data for not only acid but non-accid reflux as well. Now if you're thinking about doing pH testing, I would just refer them uh to GI for sure, and, um, we can have the discussion with them. If the pH test is positive for acid reflux, then, uh, we do want to ensure appropriate use of the PPI. I should mention, you know, we always tell them take it 30 minutes before breakfast, take it 30 minutes before dinner. The timing makes a huge impact. If it's a patient who has been on PPI trials in the past and is hesitant uh to go back on them, perhaps going straight to pH testing is not an unreasonable approach in those patients. Uh, if, uh, they are on the right dose of PPI and, uh, despite taking it properly, they're still having breakthrough symptoms, that's when I'll tend to add a famotidine 40 mg nightly or consider one of those adjunct therapies that we discussed, uh, like baclofen or Carafate, uh, or a prokinetic agent. Now, patients who are having breakthrough reflux despite PPI therapy, those are the patients who I consider for fundoplication. And, uh, this could be a whole separate talk on its own, but patients, uh, who respond the best to fundoplication are the ones who respond to PPI therapy. And so, we have to remind them that, of that as well, that, uh, I will never send a patient for a fundoplication unless they're, uh, unless they They're responding to PPI therapy, uh, or they're responding to PPI therapy, but despite that, they're having reflux, reflux above the PPI, and that's highly unlikely unless they have a huge hiatal hernia or they've had some prior, you know, they have a gastric sleeve, uh, that might predispose them to increased reflux. And there's various types of fundoplication. There's, there's surgical fundoplication, and now at UCSF we're also doing, uh, an endoscopic fundoplication called TIFF or transoral incisionless fundoplication. And uh it's important to recognize that the endoscopic approach only works for patients who have hernias that are less than 2 centimeters. So doing an endoscopy and, and confirming the size of the hernia, uh, in real time is particularly important. Before considering fundoplication, patients not only have to have a documented pH study that shows increased reflux, but it's also part of the stages, the surgical criteria that, uh, esophageal manometry needs to be done as well, uh, to understand or confirm that there is no underlying esophageal dysmotility. So the last thing you want to do is wrap the bottom of the esophagus if they have an underlying motility disorder. Now, if patients have uh non-acid reflux on a pH test, they're not, not likely to respond to PPI therapy, and we should consider treatment of bile reflux, often with Carafate in these patients. I don't recommend just throwing Carafate at them if they're not responding to PPIs though. I think I would really do it in a stepwise approach and, and get the objective data so we know how to treat them in the future should their symptoms recur. And then if a pH test is negative, so they, their baseline level of esophageal acid exposure is normal, uh, and, and they have poor symptom correlation, meaning every time they push a button when they had a symptom, it didn't really correlate to an acid reflux event. In those patients, I would consider the use of neuromodulators. Uh, my go to tends to be something like nortriptyline, uh, though other medications such as Buspar can help with gastric accommodation and fundic relaxation and can, uh, also, uh, improve, uh, symptoms in these patients. I, uh, always counsel them, you know, they're, when they're looking up these medications on Google, they, they get nervous because they see these are medications used for depression and anxiety, and I swear I'm having reflux. Um, so I'll go over the pH test with them. I'll Show them the actual report. We'll discuss it in detail, and I'll explain to them about the gut-brain connection and that, uh, they, they may simply have hyperactive nerves in the esophagus and the stomach that are mimicking reflux when in fact it's not. Patients can also have a combination of things. Perhaps they have true acid reflux, but beyond that, there is a functional component. And so neuromodulators can also be combined with PPI therapies as well.
