Reviews for Primary Care - Fall 2007 - (Page 59) GERD Symptoms on Antisecretory Therapy PPIs who complained of continued heartburn had abnormal esophageal acid exposure.30 These results support the results of a report documenting a small number of patients with continued heartburn who responded to even higher doses of antisecretory therapy.31 These same groups reported few patients with abnormal esophageal acid exposure and little response to an increase in antisecretory therapy in patients with extraesophageal GERD symptoms. A review of our own database ( 400 studies on twice-daily PPI) supports these data. Patients with heartburn and regurgitation are more likely to have continued acid reflux compared to extraesophageal symptoms. In further support of a small but potential treatable number with continued acid exposure on high-dose PPI are preliminary results of studies evaluating the efficacy of combined impedance/pH studies in work-up of “refractory patients.” Two have found that just under 10% will have symptoms associated with continued acid reflux.32,33 A body of literature has documented continued esophageal acid exposure (particularly at night) in patients with Barrett’s esophagus, despite treatment with twice-daily PPI. Several studies reveal that a substantial number will have abnormal esophageal reflux despite being asymptomatic.34-36 Although there are no definitive data available that support treating this continued asymptomatic reflux, accumulating intermediate marker data and a retrospective case review showing a decrease in dysplasia in patients on PPIs compared to those on H2RAs or no therapy37 lead me further toward strongly supporting aggressive anti-secretory treatment of these patients. No definitive studies have documented continued reflux as the cause of refractory strictures; however, there are studies showing incomplete response to 40 mg omeprazole38,39 and most of us have seen a refractory stricture that responded to higher doses of PPI or antireflux surgery. The recent availability of multichannel intraluminal impedance monitoring has made it possible to detect reflux events in which the esophageal pH does not drop to less than 4. This so-called non-acid (weakly acidic) reflux appears to be associated with some symptoms, although definitive outcome studies remain to be performed. Early results support that if any symptom is likely to be “truly” associated with a non-acid reflux event it is regurgitation, with heartburn the second most likely.32 Again, extraesophageal symptoms appear less likely to be associated. (See further discussion below.) Thus the optimal approach to the patient with symptoms suspected due to GERD who is still symptomatic on twice-daily PPI is to perform a thorough and careful evaluation to determine if reflux is responsible. This often involves multiple interventions including determining whether the patient had GERD in the first place. In our practice, the evaluation includes a careful history of PPI compliance and dose timing. Despite continued teaching of the importance of dosing PPIs before a meal, this is often ignored. When omeprazole-IR is prescribed, many completely disregard meal timing. Whereas bedtime administration of this drug is reasonable it is not clear that it can be taken any time of day. I do not advocate the empiric use of H2RA at bedtime, or addition of a prokinetic agent unless nocturnal reflux and/or erosive esophagitis has been documented. As such in this patient, a nighttime dose of an H2RA would be acceptable. In my experience the overall likelihood of success is low when H2RA is used empirically, and a prolonged pH study is likely more valuable. We perform endoscopy if one has not been done or carefully reported. This is, granted, of low yield from the standpoint of finding erosive esophagitis, but may document the presence of Barrett’s, a rare but other structural cause for symptoms (large hernia, ulcer), and allow for accurate placement of a telemetry pH capsule. In addition there is the still to be defined value of a negative endoscopy for the patient and indeed the treating physician. Barium studies are rarely performed for symptoms suspected to be due to GERD. The exception is the patient in whom careful questioning reveals that heartburn has little or no relationship to meals and the presence of dysphagia, in which case we would suspect achalasia. Thus, the cornerstone of evaluation of these patients is prolonged pH (reflux) monitoring. This is the only way to document the presence or absence of continued reflux, the association of reflux with symptoms, and adequacy of PPI therapy in acid control. Because almost every patient has been on at least one PPI and on at least twice-daily therapy (many on H2RA at bedtime), we most often perform studies on therapy to determine if the continued symptoms are due to reflux. In many more cases we later also perform a study off therapy to determine if the original suspicion of GERD can be supported. If we perform a study off therapy we discontinue PPIs for at least 7 days although 10 days is ideal because 1 study has shown some efficacy in pH control for esomeprazole for 10 days after discontinuing the drug.40 Our offtherapy studies are almost exclusively done using 48-hour telemetry capsule monitoring (Bravo™; Medtronic, Inc, Minneapolis, MN). The technology is more patient (and physician) friendly and offers the additional 24-hour (or longer) monitoring period.41 The most difficult decision concerns the most VOL. 1 NO. 1 2007 REVIEWS FOR PRIMARY CARE 59
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