GASTROESOPHAGEAL REFLUX & REFLUX ESOPHAGITIS


I. Pathophysiology

  1. Predisposing factors
  1. Low basal LES tone
  2. Inappropriate LES relaxation
  3. Impaired esophageal peristalsis and acid clearance
  4. Hiatal hernia
  5. Gastric hypersecretion
  6. Impaired gastric emptying
  1. Reflux esophagitis can result from prolonged or severe GERD; can lead to stricture formation and Barrett's esophagus (columnar metaplasia of esophageal epithelium)
  2. Barrett's Esophagus is considered a precursor to esophageal adenocarcinoma, the risk for which is increased in people with GERD

II. Nonpharmacologic approaches

  1. Postural methods
  2. Weight loss
  3. Smoking cessation
  4. Dietary modifications (avoid fat, caffeine, mint; small not big meals)
  5. Avoid drugs that lower LES tone: (EtOH, theophylline, Ca-blockers, anticholinergics, beta-agonists, alpha-agonists)
  6. Surgery--Nissen fundoplication
    1. Involves wrapping the gastric fundus around lower end of esophagus and suturing in place, increasing pressure on lower esophagus
    2. Ass'd with better control of sx compared with Omeprazole 20mg/d in one randomized trial, BUT no sig. diff. in sx if pts on omeprazole allowed to increase dose to 40-60mg/d as needed (J. Am. Coll. Surg. 192:172, 2001--Med. Lett.)
    3. Ass'd with less use of antireflux meds at 10-13y f/u but no diff. in overall symptom rate in a randomized trial of surgery vs. meds in 247 pts with complicated GERD (JAMA 285:2376, 2001--JW)
    4. Laparoscopic technique ass'd with shorter hospital stays but higher incidence of postoperative dysphagia in one randomized trial (Lancet 355:170, 2000--Med. Lett.)
    5. In a study in 554 pts with GERD rseponsive to PPIs randomized to esomeprazole (20mg/d, could increase to 40mg/d) vs. laparoscopic antireflex surgery, the 5y remission rate was sig. higher in the esomeparole group (92% vs. 85%) ("Laparoscopic antireflux surgery vs. esomeprazole treatment for chronic GERD" ("LOTUS") trial; JAMA 305:1969, 2011-JW)
  7. Polymer injection at GE junction (Enteryx)
    1. Associated with sig. better symptom control c/w sham surgery over 3y in a randomized study in 64 pts with PPI-dependent GERD (68% completely off PPIs at 3mos as opposed to 41% in sham surgery group) (Study presented by Dr. Jacques Deviere at Digestive Disease Week, reported in Family Practice News 7/15/2005)
  8. Endoluminal gastric plication ("Endocinch")
    1. Done via endoscopy
    2. Associated with high initial relief rates but high (about 80%) incidence of treatment failure at 18mos in one uncontrolled prospective study (Gut 54:752, 2005--abst)
    3. Not associated with significantly different outcomes from sham surgery in two small randomized trials (Studies presented by Dr. Per-Ola Park and Dr. Matthijs Schwartz at Digestive Disease Week, reported in Family Practice News 7/15/05).
  9. Endoscopic RF energy to GE junction
    1. 64 pts w/GERD requiring daily meds but no ulcerative esophagitis randomized to endoscopic RF energy to GE junction vs. a sham endoscopic procedure.  At 6mos, active-tx pts were sig. more likely to be without daily heartburn (61% vs. 33%) and have substantially improved GERD-related quality-of-life scores (61% vs. 30%) (Gastorent. 125:668, 2003--JW)

III. Medications for GERD & Reflux esophagitis

  1. Antacids
  1. No good evidence as of 1992 (Arch Int Med 152:717, 1992) for symptomatic or endoscopic improvement
  2. Short duration of action and lack of effect on nocturnal acid exposure make them poorly suited for frequent sx or esophagitis
  3. In pts with renal insufficiency may cause mypermagnesemia, hyperaluminemia, osteomalacia over long-term
  1. H2-antagonists--See link for doses
  1. Relieve sx and promote healing of esophagitis
  2. Nocturnal dose more associated with reduction of esophagitis complications even though may not add to relief of sx
  3. Divided doses associated with better outcome than single daily dose
  4. Probably safe with continuous use for years
  1. Proton-Pump Inhibitors--Probably more effective than H2-blockers; see link for doses
    1. Omeprazole 20-60 QD better healing of mod-to-severe esophagitis than H2-blockers or metoclopramide
    2. Better symptomatic response rate w/Omeprazole, both for initial and maintenance (12mo) therapy than H2-blockers for GERD with only mild esophagitis in one trial of 446 pts randomized to omeprazole 20mg QD vs. ranitidine 300mg BID (Am. J. Gastroent. 94:931, 1999--JW)
    3. 677 pts w/GERD randomized to Omeprazole 20mg QD, Omeprazole 10mg QD, or Ranitidine 150mg QD for 2wks initial tx (longer if necessary) then repeat courses PRN for relapses. % asmptomatic after 2wks was 55% in omeprazole 20mg group, 40% in omeprazole 10mg gorup, and 26% in ranitidine group. However, need for repeat intermittent tx or maintenance tx was not sig. diff. in the 3 groups (BMJ 318:502, 1999--UW Pharm Letter)
    4. In a trial of 34 pts with frequent heartburn randomized to 5-day courses of five oral proton-pump inhibitors (esomeprazole 40mg/d, lansoprazole 30mg/d, omeprazole 20mg/d, pantoprazole 40mg/d, or rabeprazole 20mg/d), all of whom underwent 24h intragastric pH monitoring at day 5, the mean % of time with intragastric pH > 4.0 was sig. higher for esomeprazole (58%) vs. any of the others (42%-51%) (Am. J. Gastroent. 98:2616, 2003--JW)
    5. In a study in 162 pts 28d-12mos old with symptoms consistent with GERD (no diagnostic confirmation was performed) not responsive to nonpharmagologic tx, randomized to lansoprazole vs. placebo x 4wks, there was no sig. diff. in incidence of (50% or greater reduction in feeding-related crying) or various secondary outcomes, though treatment group had sig. more adverse events, including lower respiratory tract infections (12% vs. 2%) (J. Peds. 154:514, 2009-JW)
  1. Prokinetic agents--Enhance LES pressure, increase esophageal contractions, accelerate gastric emptying
    1. Bethanechol 25 QID as good endoscopic healing as cimetidine
    2. Metoclopramide 10 QID relieves sx-can cause dyskinesias if used in long term (30% of pts get some CNS side effects)
    3. Cisapride--Ass'd with sig. QT prolongation; removed from US market 2000
  1. Sucralfate
    1. May promote healing as well as H2-blockers; less data
    2. In pts with renal insufficiency may raise Aluminum levels and lower PO4 levels
  2. Baclofen
    1. Baclofen 5mg PO TID titrated to 20mg PO TID was associated with significant decreases in symptoms in an uncontrolled study of 16 patients with symptomatic GERD refractory to proton-pump inhibitor therapy (Gut 52:1397, 2003--abst)

VIII. Combination therapy

  1. H2-blocker and prokinetic agents-little data as of 1992, but may be promising, e.g. cisapride + cimetidine
  2. Sucralfate and H2-blockers-seems not to add to healing rates

IX. Refractory cases-High-dose H2-blockers (e.g. ranitidine 300 QID) may improve healing rates from esophagitis

X. Maintenance therapy

  1. For those who get frequent relapses after discontinuation of tx
  2. H2-blockers for maintenance rx, e.g. ranitidine 150-300/d, generally disppointing
  3. Omeprazole 20/d (after achieving healing with 40/d) achieves relapse rates of 25% at 1y and 34% at 2y; better than ranitidine in one head-head study
  4. Lansoprazole for maintenance therapy: 173 pts with endoscopically proven healing of erosive esophagitis after 2mo of acid-suppressive therapy randomized to lansoprazole 15mg QD or 30mg QD or placebo; sig. better healing and sx reduction at 1mo and 1yr with either dose of lansoprazole (no sig. diff. between different doses) (Ann. Int. Med 124:859, 1996-JW)
  5. If no endoscopically proven esophagitis, maintenance rx to just control sx, e.g. lifestyle modification + PRN antacids, may be appropriate

XI. GERD in Infants

  1. Diagnosis: Sx (regurgitation, possibly cough) and esophageal pH monitoring
  2. Treatment
    1. Thickened feeds (apparently effective per Craig WR, Hanlon-Dearman A, Sinclair C, Taback S, Moffatt M. Metoclopramide, thickened feedings, and positioning for gastro-oesophageal reflux in children under two years. The Cochrane Database of Systematic Reviews 2004, Issue 3. Art. No.: CD003502. DOI: 10.1002/14651858.CD003502.pub2)
    2. Metoclopramide (also apparently effective; ibid.)
    3. Elevation of head of crib when infant supine (no good evidence as of 2004; ibid.)