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.
So this is a topic near and dear to my heart guard the prevalence and management. And of course we could talk about this for hours but we'll try to limit it to about 45 minutes. So we have plenty of time for questions. So I just wanted to start with understanding the prevalence of guard in the United States and we know we're all seeing more and more of this 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 has some degree of guard at least weekly and a lot of the heterogeneity and in the GERD prevalence really lies. And which questionnaire is being used and what population? What is the threshold and duration of symptoms required to be classified as GERD? And you know some studies that list numbers as high as 30% were actually uh from survey based studies that were done at the Houston be a medical center. And whereas the kind of the lower rates are from Olmstead County in Minnesota predominantly white population. So that just kind of accounts for some of the differences in prevalence depending on the regions in the United States. So outpatient visits for guard. The National ambulatory Medical Care survey. This was granted 20 years ago said that good related visits at that time to PC PS was up by 46% Non related or non-related. Good visits was up by 6%. Now P. P. I. S. 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 is in fact refractory GERD these days. Now the classic symptoms of GERD as you all know, our heartburn and acid regurgitation, patients will often describe a burning feeling in their retro sternal area, symptoms often occur postprandial lee, 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 two thirds of them had guard 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 GERD and other gi conditions. So patients may have garnered and some dysplasia or chest pain and water brush or burping and hiccups. And so uh we also need to recognize that they could have gourd 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 will be um discussing further over the course of this talk. Now the most predominant mechanism of good is the defective barrier of the lower esophageal sphincter. And uh the most common mechanism R. T. L. E. S. R. S. Or transient lower esophageal sphincter relaxations. Now patients who have a high it'll hernia are also predisposed to guard because you know the acid is should be in the stomach and now we're exposing the esophagus which is not used to that degree of acid exposure to now a much larger um kind of burden. In addition uh increased pressure, intra abdominal pressure, intra abdominal girth and patients with obesity pregnancy. Uh and then um those with delayed gastric empty. This can also 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 in Malaysia or even a minor motility disorder such as ineffective motility. And finally patients can also have decreased intra thoracic pressure particularly those with COPD. Um those who have more of a chronic cough presentation patients who are professional singers. We see many of those have kind of more likely to have guard. So how do we manage these patients? And certainly there's a lot of variability and this is just you know one algorithm. But the initial treatment when we see patients with heartburn and regurgitation even before they come to the gastroenterologist there same year, you know the primary care provider and the P. P. I. Or an H. Two blocker is started and I would highly recommend that you know you go straight to the P. P. I. And start at least the dosage of 40 mg daily. So um the over the counter 20 mg dosage 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. So the initial treatment in my mind is really the PP. I. Uh you know not resolved for example 40 mg daily. And then if if they have a good initial response and they're symptom free uh then you know you want to try to get to the lowest effective dose and ideally want to 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 P. P. I. S. And we 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 eight 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 caucasian men over age 50 who are obese or smokers or who have long term long term symptoms. We really need to think about screening them for barrettes 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 P. P. I. S. Well um you know I had mentioned starting on that resolved 40 mg daily for eight weeks. And so you can certainly go up to twice a day if there's no benefit. Um You could um Add an H. two blocker as well either at nighttime or um you know if they're on an H. Two blocker and not a P. P. I certainly switch them to a P. P. I. At that time. Um And if they have a good response then I think you can then go to tapering them slowly after uh an adequate trial. However if they don't have a good response this is certainly what I would consider. Refract record that would warrant a referral to G. I. So once they come and see us if they've had the adequate PPE. I trial Will want to probably consider doing uh an endoscopy just to make sure that we understand their anatomy. Do they have a high it'll hernia. Do they have any signs of barrett's esophagus? Do they have any peptic strictures or narrowing as a result of long standing kind of poorly controlled guard? And then uh if the endoscopy is unrevealing, I would go next to considering formal ambulatory ph monitoring and generally we would do this off of PP. I. Therapy because we want to understand their baseline level of reflux. But the ph testing is also particularly important in understanding how their symptoms correlate correlate with 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 PP. I. Therapy. Um Now certainly if patients have any alarm symptoms even at the onset of of treating them, I would send them to G. I. At that moment. So what are some of these alarm symptoms? Certainly if they have any dysplasia or dino aphasia you want to send them to us? Obviously if there's any signs of G. I bleed. If they have iron deficiency anemia without another clear cause unintentional weight loss of 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 currently while trialing the medication Now, some indications for long term PP. I. Therapy. Um Certainly if they have a history of erosive esophagitis on a prior endoscopy. So somebody who has reflux esophagitis, L. A. Grade C. Or D. You might see in the reports. That's an indication where they should probably be on PP eyes long term and or consider more definitive therapies. Like a fund application for example. And then barrett's esophagus. All the literature suggests that patients should be on at least once daily low dose PP. I. As P. P. I. S. Tend to be the one thing that can help prevent further progression of barrett's to esophageal ADN O. C. A. I should also add on this list. Uh the kind of a separate topic. Eosinophilic esophagitis is another reason for patients to be on long term PP. I. Therapy and uh some degree of kind of chronic suppressive PP. I. 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 PP. I. 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 with PP. I. Use, but none of that was proven on subsequent studies. These studies really looked at patients who had comorbidities and who were on A P. P. I. But we really don't know what came first in this population, the chicken or the egg. And so I really caution when we're interpreting those studies that we should reassure our patients that those side effects are highly highly unlikely. What I will say are the side effects that I always tell my patients to think about our uh you know, acid is protective on the G. I. Tract. And so if we're suppressing acid we are making you more prone to diarrhea or infectious illnesses of the gut. And so the studies that suggested increased risk of C. Diff and uh cibo or small intestinal bacterial overgrowth. I think those 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. Yet the other thing is is that certainly the medications can impair calcium absorption and magnesium absorption. And uh you know, we need to be cognizant of their bone health, particularly if it's a postmenopausal woman who's at risk of osteoporosis are already has osteoporosis. We need to just make sure we have a clear indication for PP. I. Therapy in them. And that we have again, a well defined a defiant understanding of how long we're going to keep them on the medication. That being said none of our G. I. Guidelines say that um primary care providers or gastroenterologist should be checking calcium and vitamin D. And magnesium levels because patients are on P. P. I. S. Certainly if it's um you know part of their their other health care maintenance, that's a different issue. But for PPS alone there is no need for routine um checking of of these 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 can be particularly helpful of course telling them to stop smoking, avoid uh sleeping until at least three 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. Even if a patient is not obese and there Just overweight, it can be beneficial to lose even five or £10 again to minimize pressure on the lower esophageal sphincter. And then you know, patients often asked me about what dietary modifications they should consider doing. And I always caution them that they're going to find various their diets on the internet. And if they look at those that might not eat anything because at least you know one thing that they're eating daily has been implicated in this. 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, tomato, citrusy, basically all the good stuff. And so I tell them, you know everything in moderation. Now. There are certainly adjunct therapies for guard and we talked briefly about H2 blockers, particularly those that are taken at bedtime can be helpful. Um pro-Kinetic agents. There's medical provide, you know, we have to be cautious about that because of the black box warning of tardive dyskinesia. So I really reserved giving patients medical provider unless there uh on unless they have documented gastro paralysis. But there's a lot of emerging data for Pre Kala Pride which is a medication that has been approved for constipation but has also been more recently found to be effective for patients with gastro paralysis as well. Um Pre Kala Pride is a five HT agonist and it has been shown to improve gastric empty and reduces salvageable asset exposure and patients with GERD. And finally uh so cruel fate can be um I must back often actually that's a Gabba b agonist and it can reduce the T. L. E. S. R. S. I find this medication is can be used together with PP. I. Therapy but on itself on its own is not particularly effective. And then so cruel fate or cara fate is something else to consider. It's a mucosal protective agent. It might be beneficial in patients who we think have more bile reflux or non acid reflux. And ph testing can help distinguish that asset 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 I was 17% compared to 14% in those under age 50. And 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 guard. And so between 2003 and 2000 and six, hospital discharges were looked at with a primary GERD related diagnosis and they found that about half a million uh Hospital discharges compared to 14.5 million where guard was kind of this listed as a secondary diagnosis. Now, the highest rate of good related complications, particularly of adenocarcinoma is uh as well as, you know, Heidel 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 uh the black population in this study was about 27% compared to 23.5% in white participants and then 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 erosion of esophagitis stratified by weekly GERD symptoms with severe rows of esophagitis being characterized as those having L. A. Class B. Or higher esophagitis. And uh regardless of whether they're presenting symptom was heartburn or regurgitation, white participants tended to have a greater proportion of erosive esophagitis than 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 northern California. Looking at the prevalence of barrett's esophagus based on electric diagnoses, electronic diagnoses, sorry, dating back to 1994 when the diagnosis was first recorded in their system and we can see that the prevalence of diagnosed ferrets rose steadily throughout the study interval and ultimately reached 131 for 100,000 member years in in 2000 and six, I'm sure it's even higher now and the prevalence in 2000 and six among non hispanic whites was two fold higher than among hispanic whites and 5-fold 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 seer database shows rising trends of esophageal add no particularly in the male population and it's got to be the fastest growing malignancy among males. Though reassuringly it seems like perhaps we're reaching a plateau and it's likely due to the more widespread use of P. P. I. S. In the last decade. And I know there's a lot of concern as I mentioned before about the side effects. And I could probably do a you know a whole talk on the side effects of P. P. I. S. But I think again it's important too to remember this data and try to reassure patients that if there is a clear indication for PP. I use such as barrett's esophagus that they should remain on the drug. And so why the rise in in GERD and associated complications? Well um certainly uh it's because it might be because of our aging population with aging. We know that there's uh decreased esophageal peristalsis. And there may be an increase in the number of T. L. E. S. R. S. And there may be additional you know an atomic disruption to this esophageal gastric junction. There's also some question about the decreasing prevalence of H. Pylori. There's some debate that H. Pylori can prevent. Uh can H. Pylori patients actually developed atrophy in the gastric body and decreased assets secretion as a result, particularly in those with the cog A strain. So perhaps we just better looking for better at looking for H. Pylori and by treating them or maybe making their good a little bit worse. We also know that tobacco use is weekly associated with good. There's been a lot of longitudinal studies showing that those with decreased tobacco smoking. Um So there are those who decreased tobacco smoking were three times more likely to have reductions and 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 obese people have increased intra abdominal pressure that can further displaced the lower esophageal sphincter and increase the gastroesophageal gradient. In addition it may simply be too there due to the dietary intake or dietary indiscretions that may directly be making them more probe 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 is estimated in 2016 that nearly 40% of US population was considered obese. This is a really nice study that looks at the association between B. M. I. And the risk of frequent symptoms regard. And they looked at multi various 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, antihypertensive or asthma medications and then the presence or absence of diabetes. And not surprisingly, we see a dose dependent relationship between increasing B. M. I. And the frequency of reflux symptoms. Those with increased waist circumference central at capacity are much more likely to have guard and in part again due to the increased pressure on the lower esophageal sphincter. Studies have actually shown that patients, these patients in particular have increased reflux episodes on ph studies increased esophageal acid exposure time and an increased number of T. L. E. S. R. S. The predominant mechanism implicated incurred reassuringly. Studies suggests that by reducing their B. M. I. By just 3.5 points they can actually decrease their GERD symptoms more than twofold. And so it's really clear that obesity and GERD are highly intertwined. So in a motivated patient who's not trying to be on P. P. I. S. Long term weight loss can have a huge impact on their symptoms. So I'll end with this slide on my approach to good 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 P. P. I. For eight weeks will not resolve 40 mg daily and they're not considered refractory unless They don't respond to the eight weeks of therapy. If they have improved improvement, taper them off and when I taper patients, certainly there's so many different ways to do it. But if they're on B. I. D. Dozing, I go to daily for a 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, of course of two or 3 weeks and then when they're tapering, I always tell them, I warned them you may get rebound reflux. Don't go back on the medication, consider using an H. Two blocker in place of the P. P. I. On the days you feel you have more symptoms. I also council them that if they feel the need to go back on the PP. I. Therapy, I'd love to know about it uh and try to understand what happened when they were tapering what what they're symptom burden was. Um I really try to convince them that H2 blockers work well on demand as a pill in pocket when they have breakthrough symptoms as they're tapering, or even you know. A random day that they're going to be eating a larger meal or have an extra glass of wine. Perhaps taking an H2 blocker on those days may be beneficial. Now if they have no improvement after uh the standard dose ng of P. P. I. For eight 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 good. It just means you don't have any compliment complications from GERD or any structural abnormalities that might predispose you to gird. But a normal endoscopy doesn't mean you don't have good. 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 we get data for not only acid but not acid reflux as well. Now, if you're thinking about doing ph testing I would just refer them to G. I. For sure and we can have the discussion with them. If the ph test is positive for acid reflux, then we do want to ensure appropriate use of the PP. I. 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 T. P. I. Trials in the past and is hesitant to go back on them perhaps going straight to ph testing is not an unreasonable approach in those patients, uh if they are on the right dose of P. P. I. And despite taking it properly, they're still having breakthrough symptoms. That's when I'll tend to add promoted in 40 mg nightly or consider one of those adjunct therapies that we discussed black back often or cara fate or a pro kinetic agent. Now, patients who are having breakthrough reflux despite PP. I. Therapy. Those are the patients who I consider for fund application and uh this could be a whole separate talk on its own. But patients who respond the best to fund application are the ones who respond to PP. I. Therapy. And so we have to remind them that of that as well, that I will never send a patient for a fund application unless they're unless they're responding to PP. I. Therapy or they're responding to PP. I. Therapy. But despite that they're having reflux reflux above the P. P. I. And that's highly unlikely unless they have a huge hospital hernia or they've had some prior, you know, they have a gastric sleeve that might predispose them to increase reflux. And there's various types of funding application. There's there's surgical fund application and now UCSF we're also doing an endoscopic fund application called tiff or trans oral incision list fund application. And it's important to recognize that the endoscopic approach only works for patients who have hernias that are less than 2cm. So doing an endoscopy and and confirming the size of the hernia in real time is particularly important before considering fund application patients not only have to have documented ph study that shows increased reflux, but it's also part of the stage, is the surgical criteria that uh it's official manama tree needs to be done as well to understand or confirm that there is no underlying esophageal this motility, because 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 PP. I therapy and we should consider treatment of bile reflux often with cara feet in these patients. I don't recommend just throwing tariff ate at them. If they're not responding to PPS though, I think I would really do it in a stepwise approach 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 about esophageal acid exposure is normal, uh and and they have four 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 neural modulators. My go to tends to be something like nor tripped. Elaine though other medications such as bus fire can help with gastric accommodation and funding relaxation and can also improve symptoms in these patients. I always council them. You know, they're when they're looking up these medications on google, they get nervous because they see these are medications used for depression and anxiety and I swear I'm having reflux and 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 they may simply have hyperactive nerves in the esophagus and the stomach that are mimicking reflex 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 neuro modulators can also be combined with PP. I. Therapies as well. Mm hmm.
