Management of Refractory GERD Persistent Symptoms on PPI Twice Daily

Patients with persistent symptoms on twice-daily PPI given in ideal dosing before breakfast and before dinner are challenging. At this point we recommend reevaluating their symptoms and further testing because the symptoms might be due to persistent acid reflux, nonacid reflux, or not related to gastroesophageal reflux at all.

Patients with atypical supraesophageal symptoms (ie, laryngitis, hoarseness, chronic cough, asthma) should be treated for at least 4 to 6 months on high dose PPI before declaring their atypical GERD symptoms refractory to therapy. There is a chapter on extraesophageal manifestations of GERD. In patients with predominantly persistent nocturnal symptoms, bedtime H2RAs should be added in the attempt to control nocturnal acid breakthrough. Studies from our laboratory have indicated that up to 80% of patients receiving PPI twice daily before meals have at least 60 continuous minutes of overnight intragastric pH < 4 (nocturnal acid breakthrough) and addition of bed-

TABLE 9-2. Suggested Approach to Acid-Suppressive Therapy

Step Medical Regimen

1 Single dose PPI (AM AC)

2 Switch to another PPI

3 PPI AM plus H2RA at bedtime

4 PPI bid AC

5 PPI bid AC plus H2RA at bedtime

AC = before meals; AM = morning; bid = twice daily; H2RA = histamine-2 antagonist; PPI = proton pump inhibitor.

^Editor's Note: How long to continue successful therapy with PPIs is another question. When to taper to once per day? When to go to H2RAs? When to stop?

Author's Reply: Because GERD is a chronic disease patients with correctly diagnosed GERD should be on acid suppressive therapy indefinitely. Studies indicate that 70 to 80% of patients with healed esophageal lesions will relapse when switched to H2RAs or daily PPI therapy is discontinued. With the exception of patients with Barrett's esophagus, in whom we recommend high dose PPI twice daily with/without bedtime H2RA, we discuss with patients the possibilities of tapering down the PPI treatment, switching to H2RAs based on their symptoms.

time H2RA decreased this proportion to 32%. Despite concerns regarding tolerance to H2RAs, this combination is effective long term in many patients.

Testing patients with persistent symptoms on PPI twice daily or "maximal acid control" (ie, PPI twice daily before meals + H2RA at bedtime) will often clarify which one of the three possible causes account for the symptoms. We recommend combined multichannel intraluminal impedance and pH (MII-pH) testing on therapy as the best currently available technique in detecting gastroesophageal reflux of all types. Because combined MII-pH detects reflux by measuring changes in electrical resistance along the MII-pH probe within the esophageal lumen, it can detect both acid and nonacid reflux. Initial studies with this technique indicate that approximately 20% of patients with persistent symptoms on acid-suppressive therapy with at least twice-daily PPI have their symptoms related to continuing acid reflux. The majority traditionally present a diagnostic dilemma as to whether their symptoms are associated with nonacid reflux or not associated with any type of GERD. Combined MII-pH testing will further clarify this possible association, separating those patients with persistent symptoms due to nonacid reflux from those without temporal association between symptoms and any type of reflux. Therefore, we believe that combined MII-pH on PPI twice-daily before meals should be considered the next step in the diagnostic approach to patients not responding to PPI therapy (Figure 9-3).

In patients with documented persistent acid reflux on PPI bid ± H2RA we recommend testing for hypersecretory status (ie, serum gastrin level and possible secretin stimulation test) and recommend increasing the dose of acid suppressive medication or referral for antireflux procedures. Patients with symptomatic nonacid reflux should be offered antireflux surgery. Endoscopic antireflux procedures should be offered only in centers with experience and ade quate follow-up. There are limited pharmacologic options for nonacid reflux. To date, 7-aminobutyric acid (GABA) B-receptor agonists (ie, baclofen) have been proposed as medications to decrease the frequency of transient LES relaxations and studies indicate that baclofen decreases both acid and nonacid reflux (Vela et al, 2003). The side effect profile (dizziness, muscular weakness, fatigue) of these medications is the main limiting factor. In patients in whom symptoms cannot be associated with acid or nonacid reflux episodes, other, nonreflux, causes of their symptoms should be investigated.

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