![Page 1: Refractory Gastroesophageal Reflux Disease (GERD ... GERD...Pathophysiology of GERD Locke GR, Fett SL, Zinsmeister AR et al. Gastroenterology 1997, 112: 1448-56 Nebel OT, Fornes MF,](https://reader035.vdocuments.mx/reader035/viewer/2022062402/5f082fd97e708231d420c563/html5/thumbnails/1.jpg)
Refractory Gastroesophageal Reflux Disease (GERD) Symptoms:
Diagnosis and Management Nina S. George, DO
Fellow, PGY-6 Division of Gastroenterology/Hepatology
Case Western Reserve University/Metrohealth Medical Center September 6th, 2015
![Page 2: Refractory Gastroesophageal Reflux Disease (GERD ... GERD...Pathophysiology of GERD Locke GR, Fett SL, Zinsmeister AR et al. Gastroenterology 1997, 112: 1448-56 Nebel OT, Fornes MF,](https://reader035.vdocuments.mx/reader035/viewer/2022062402/5f082fd97e708231d420c563/html5/thumbnails/2.jpg)
Objectives
• Review the classification of GERD and proposed mechanisms for refractory GERD
• Understand the diagnostic approaches for refractory GERD
• Discuss the management for refractory GERD
![Page 3: Refractory Gastroesophageal Reflux Disease (GERD ... GERD...Pathophysiology of GERD Locke GR, Fett SL, Zinsmeister AR et al. Gastroenterology 1997, 112: 1448-56 Nebel OT, Fornes MF,](https://reader035.vdocuments.mx/reader035/viewer/2022062402/5f082fd97e708231d420c563/html5/thumbnails/3.jpg)
![Page 4: Refractory Gastroesophageal Reflux Disease (GERD ... GERD...Pathophysiology of GERD Locke GR, Fett SL, Zinsmeister AR et al. Gastroenterology 1997, 112: 1448-56 Nebel OT, Fornes MF,](https://reader035.vdocuments.mx/reader035/viewer/2022062402/5f082fd97e708231d420c563/html5/thumbnails/4.jpg)
Peery AF, Dellon ES, Lund J et al. Gastroenterol 2012: 143(5): 1179-1187
![Page 5: Refractory Gastroesophageal Reflux Disease (GERD ... GERD...Pathophysiology of GERD Locke GR, Fett SL, Zinsmeister AR et al. Gastroenterology 1997, 112: 1448-56 Nebel OT, Fornes MF,](https://reader035.vdocuments.mx/reader035/viewer/2022062402/5f082fd97e708231d420c563/html5/thumbnails/5.jpg)
Vakil N, Zaten SVV, Kahrilas P. AJG 2006; 101:1900-20
![Page 6: Refractory Gastroesophageal Reflux Disease (GERD ... GERD...Pathophysiology of GERD Locke GR, Fett SL, Zinsmeister AR et al. Gastroenterology 1997, 112: 1448-56 Nebel OT, Fornes MF,](https://reader035.vdocuments.mx/reader035/viewer/2022062402/5f082fd97e708231d420c563/html5/thumbnails/6.jpg)
Pathophysiology of GERD
Locke GR, Fett SL, Zinsmeister AR et al. Gastroenterology 1997, 112: 1448-56 Nebel OT, Fornes MF, Castell DO. Am J Digest Dis 1976; 21: 953-6 El-Serag H, Becher A, Jones R. APT 2010; 32: 720-37 Castell DO. Practical Gastroenteroly 2004
![Page 7: Refractory Gastroesophageal Reflux Disease (GERD ... GERD...Pathophysiology of GERD Locke GR, Fett SL, Zinsmeister AR et al. Gastroenterology 1997, 112: 1448-56 Nebel OT, Fornes MF,](https://reader035.vdocuments.mx/reader035/viewer/2022062402/5f082fd97e708231d420c563/html5/thumbnails/7.jpg)
Dickman R, Maradey-Romero C, R Fass. JNM 2015: 21(3): 309-19
Erosive Esophagitis (EE)
Barrett’s esophagus
Phenotypes of GERD
Non Erosive Reflux Disease (NERD)
![Page 8: Refractory Gastroesophageal Reflux Disease (GERD ... GERD...Pathophysiology of GERD Locke GR, Fett SL, Zinsmeister AR et al. Gastroenterology 1997, 112: 1448-56 Nebel OT, Fornes MF,](https://reader035.vdocuments.mx/reader035/viewer/2022062402/5f082fd97e708231d420c563/html5/thumbnails/8.jpg)
Refractory GERD Symptoms
• Up to 45% of patients have partial/non response to PPI therapy
• Ongoing reflux symptoms or endoscopic evidence of esophagitis despite treatment with proton pump inhibitor (PPI)* for 8 weeks
• Acid Regurgitation is predominant symptom
• Increased healthcare costs, impaired quality of life
Fass R, Sifrim D. Gut 2009: 58; 295-309 El-Serag H, Becher A, Jones R. APT 2010; 32: 720-37
![Page 9: Refractory Gastroesophageal Reflux Disease (GERD ... GERD...Pathophysiology of GERD Locke GR, Fett SL, Zinsmeister AR et al. Gastroenterology 1997, 112: 1448-56 Nebel OT, Fornes MF,](https://reader035.vdocuments.mx/reader035/viewer/2022062402/5f082fd97e708231d420c563/html5/thumbnails/9.jpg)
PPI Failure Rates in GERD
• Non-Erosive Reflux Disease: 40-50%
• Erosive Esophagitis: 25-40%
• Barrett’s Esophagus: 20%
Dickman R, Maradey-Romero C, R Fass. JNM 2015: 21(3): 309-19
![Page 10: Refractory Gastroesophageal Reflux Disease (GERD ... GERD...Pathophysiology of GERD Locke GR, Fett SL, Zinsmeister AR et al. Gastroenterology 1997, 112: 1448-56 Nebel OT, Fornes MF,](https://reader035.vdocuments.mx/reader035/viewer/2022062402/5f082fd97e708231d420c563/html5/thumbnails/10.jpg)
Fass R, Sifrim D. Gut 2009; 58: 295-309
2000 Gallop Study of Consumers use of Stomach Relief Products
![Page 11: Refractory Gastroesophageal Reflux Disease (GERD ... GERD...Pathophysiology of GERD Locke GR, Fett SL, Zinsmeister AR et al. Gastroenterology 1997, 112: 1448-56 Nebel OT, Fornes MF,](https://reader035.vdocuments.mx/reader035/viewer/2022062402/5f082fd97e708231d420c563/html5/thumbnails/11.jpg)
Mechanisms for Refractory GERD
Fass and Sifrim. Gut 2009; 58: 295-309 Cicala M, Emerenzian iS, Guarino MP et al. WJG 201`3; 19: 6529-35 Barrison AF, Jarboe LA, Weinberg BM et al. AJM 2011; 111:469-73
55% at 1 month, 30% at 6 months Improper advice by 70% of primary care, 20% GI
? Cost effectiveness of esophageal bx
• Nocturnal reflux
![Page 12: Refractory Gastroesophageal Reflux Disease (GERD ... GERD...Pathophysiology of GERD Locke GR, Fett SL, Zinsmeister AR et al. Gastroenterology 1997, 112: 1448-56 Nebel OT, Fornes MF,](https://reader035.vdocuments.mx/reader035/viewer/2022062402/5f082fd97e708231d420c563/html5/thumbnails/12.jpg)
Initial Management in PPI failure
• Evaluate for proper compliance & lifestyle modifications
• Consider switching to different PPI or empiric trial of double dose PPI
• Initiate diagnostic workup
– Esophagogastroduodenoscopy (EGD)
– pH +/- impedance testing
Hershcovici T, Fass R. Disease of the Esophagus 2013; 26: 27-36
![Page 13: Refractory Gastroesophageal Reflux Disease (GERD ... GERD...Pathophysiology of GERD Locke GR, Fett SL, Zinsmeister AR et al. Gastroenterology 1997, 112: 1448-56 Nebel OT, Fornes MF,](https://reader035.vdocuments.mx/reader035/viewer/2022062402/5f082fd97e708231d420c563/html5/thumbnails/13.jpg)
Carlson DA, JE Pandolfino. Gastroenterol Clin N Am 2014: 43; 89-104
![Page 14: Refractory Gastroesophageal Reflux Disease (GERD ... GERD...Pathophysiology of GERD Locke GR, Fett SL, Zinsmeister AR et al. Gastroenterology 1997, 112: 1448-56 Nebel OT, Fornes MF,](https://reader035.vdocuments.mx/reader035/viewer/2022062402/5f082fd97e708231d420c563/html5/thumbnails/14.jpg)
pH/Impedance Testing
• Measures difference in electrical conductivity across a pair of electrodes within esophageal lumen – Composition (air, liquid, mixed) – Direction/extent (anterograde or retrograde) – Velocity and clearance time
• Concomitant pH testing – pH < 4: acidic – pH 4-7: weakly acidic – pH > 7: weakly alkaline
![Page 15: Refractory Gastroesophageal Reflux Disease (GERD ... GERD...Pathophysiology of GERD Locke GR, Fett SL, Zinsmeister AR et al. Gastroenterology 1997, 112: 1448-56 Nebel OT, Fornes MF,](https://reader035.vdocuments.mx/reader035/viewer/2022062402/5f082fd97e708231d420c563/html5/thumbnails/15.jpg)
Type of reflux events on vs off PPI
Boeckxstaens GE, Smouth A. APT 2010; 32: 334-343
![Page 16: Refractory Gastroesophageal Reflux Disease (GERD ... GERD...Pathophysiology of GERD Locke GR, Fett SL, Zinsmeister AR et al. Gastroenterology 1997, 112: 1448-56 Nebel OT, Fornes MF,](https://reader035.vdocuments.mx/reader035/viewer/2022062402/5f082fd97e708231d420c563/html5/thumbnails/16.jpg)
Symptom correlation and reflux events
Boeckxstaens GE, Smouth A. APT 2010; 32: 334-343
![Page 17: Refractory Gastroesophageal Reflux Disease (GERD ... GERD...Pathophysiology of GERD Locke GR, Fett SL, Zinsmeister AR et al. Gastroenterology 1997, 112: 1448-56 Nebel OT, Fornes MF,](https://reader035.vdocuments.mx/reader035/viewer/2022062402/5f082fd97e708231d420c563/html5/thumbnails/17.jpg)
Management Options for Refractory GERD Symptoms
![Page 18: Refractory Gastroesophageal Reflux Disease (GERD ... GERD...Pathophysiology of GERD Locke GR, Fett SL, Zinsmeister AR et al. Gastroenterology 1997, 112: 1448-56 Nebel OT, Fornes MF,](https://reader035.vdocuments.mx/reader035/viewer/2022062402/5f082fd97e708231d420c563/html5/thumbnails/18.jpg)
TLESR inhibitor
Baclofen (ɣ-aminobutryic acid type B receptor agonist)
• Pharmacologic effects
– 40-60% decrease in TLESR rate
– 43% decrease in reflux episodes
– Increased LES basal tone
– Accelerate gastric emptying
• Side effects: dizziness, somnolence, weakness, trembling
Fass R, Sifrim D. Gut 2009; 58: 295-309
![Page 19: Refractory Gastroesophageal Reflux Disease (GERD ... GERD...Pathophysiology of GERD Locke GR, Fett SL, Zinsmeister AR et al. Gastroenterology 1997, 112: 1448-56 Nebel OT, Fornes MF,](https://reader035.vdocuments.mx/reader035/viewer/2022062402/5f082fd97e708231d420c563/html5/thumbnails/19.jpg)
Visceral Pain modulators
• Most studies conducted in noncardiac chest pain patients
• Selective Serotonin Receptor Inhibitor (SSRI)
– Citalopram 20mg, once daily
• Serotonin Reuptake Inhibitors (SNRI)
• Tricyclic Antidepressants (TCA)
• Trazadone
Hershcovici T, Fass R. Trends in Pharmacological Sciences. 2011; 32(4): 258-64 Ates FA, Vaezi MF. Current Treatment Options in Gastroenterology 2014; 12: 18-33
![Page 20: Refractory Gastroesophageal Reflux Disease (GERD ... GERD...Pathophysiology of GERD Locke GR, Fett SL, Zinsmeister AR et al. Gastroenterology 1997, 112: 1448-56 Nebel OT, Fornes MF,](https://reader035.vdocuments.mx/reader035/viewer/2022062402/5f082fd97e708231d420c563/html5/thumbnails/20.jpg)
Anti-Reflux Surgery
• Decrease number of reflux episodes, regardless of content
• Prior PPI response predicts post surgical symptom resolution
• Satisfaction rates up to 87% postop
Hershcovici T, Fass R. Trends in Pharmacological Sciences. 2011; 32(4): 258-64 Ates FA, Vaezi MF. Current Treatment Options in Gastroenterology 2014; 12: 18-33
![Page 21: Refractory Gastroesophageal Reflux Disease (GERD ... GERD...Pathophysiology of GERD Locke GR, Fett SL, Zinsmeister AR et al. Gastroenterology 1997, 112: 1448-56 Nebel OT, Fornes MF,](https://reader035.vdocuments.mx/reader035/viewer/2022062402/5f082fd97e708231d420c563/html5/thumbnails/21.jpg)
Stretta
• Radiofrequency energy
• Decrease reflux events & esophageal acid sensitivity
• Normalized GERD-HRQL scores at mean 20 month follow-up
• Improved esophageal acid exposure time and De-Meester scores
Wendling MR, Melvin SM. Current Surgical Therapy 11ed. 2014
![Page 22: Refractory Gastroesophageal Reflux Disease (GERD ... GERD...Pathophysiology of GERD Locke GR, Fett SL, Zinsmeister AR et al. Gastroenterology 1997, 112: 1448-56 Nebel OT, Fornes MF,](https://reader035.vdocuments.mx/reader035/viewer/2022062402/5f082fd97e708231d420c563/html5/thumbnails/22.jpg)
Hershcovici T, Fass R. Diseases of the Esophagus 2013; 26: 27-36
![Page 23: Refractory Gastroesophageal Reflux Disease (GERD ... GERD...Pathophysiology of GERD Locke GR, Fett SL, Zinsmeister AR et al. Gastroenterology 1997, 112: 1448-56 Nebel OT, Fornes MF,](https://reader035.vdocuments.mx/reader035/viewer/2022062402/5f082fd97e708231d420c563/html5/thumbnails/23.jpg)
Summary
• Refractory GERD is a spectrum of clinical symptoms suggestive of heartburn/acid regurgitation despite PPI therapy
• Most patients with refractory GERD on PPI therapy do not have residual acid reflux
• Further evaluation with pH/impedance testing should be considered
• Management of refractory GERD symptoms is patient centered