GERD: How to Manage Treatment Failures John Fang MD University of Utah Introduction GERD: condition of reflux of stomach contents causes troublesome symptoms and/complications Refractory GERD: poor response (<50% improvement) in chief complaint after 12 weeks BID PPI ~ 30% (10-40%) have incomplete response to PPI s Either esophageal or extra-esophageal esophageal symptoms Most common presentations to GI s 1
Gallup Study GERD Relief Products Refractory GERD Causes GERD Insufficient acid suppression Poor Compliance Insufficient duration Genetic variation Non-acid reflux Esophageal hypersensitivity Not GERD NUD Rumination Aerophagia Achalasia EoE 2
Definitions NERD: patients without any mucosal break at endoscopy and abnormal oesophageal acid exposure at 24-h oesophageal ph monitoring. Acid hypersensitive esophagus: patients without any mucosal break at endoscopy, normal oesophageal acid exposure and positive symptom-reflux association analysis (SI>50%, SAP>95%). Functional heartburn: patients with heartburn refractory to PPIs, without any mucosal break at endoscopy, normal esophageal acid exposure and negative symptom reflux association analysis (symptom index <50%, symptom association probability <95%) at 24-h oesophageal ph monitoring. Algorithm for NERD and Functional HB 3
Refractory GERD: Diagnostic Tests EGD in Refractory GERD 4
ph testing: on or off meds Off PPI s On PPI s Does patient have GERD at all? Classifies NERD, hypersensitive, functional 48 hour study increased yields If normal excludes GERD as cause ph/impedance little added value off meds Does not address why patient has continuing symptoms on meds Is reflux present on meds? Low yield ph alone vs. ph/impedance Establish symptom correlation (SI,SAP) Exclude any GER as cause of persistent symptoms Normal 63-90% No outcome data Cannot exclude baseline reflux 5
Likelihood of abnormal ph on PPI Am J Gastro 2005 100, 283 289 Combined multichannel intraluminal impedance ph monitoring Measure 24 acid reflux Measure reflux episodes Acid Non-acid: weakly acid, alkaline Symptom correlation SAP, SI Problems Availability Interpretation Outcome data 6
Combined multichannel intraluminal impedance ph monitoring Symptom Reflux Correlation Symptom Association Probability Symptom Index Probability of positive association between reflux and symptoms Divide into 2-min segments and determine if reflux and/or symptom occurred Positive > 95% % symptom events that are temporally related to a reflux episode # reflux-related symptom events/total # symptom events] 100% Positive > 50% 7
Increased yield of ph/ impedance in refractory GERD Clini Gastro and Hep 2009;7:743 748 Benefit of ph/impedance on PPI 50-60% do not have symptoms a/w non-acid reflux (weakly acid, alkaline) 30-40% have symptoms a/w non-acid reflux 10% have symptoms a/w acid reflux Am J Gastroenterol 2006;101:1956 1963 Am J Gastroenterol 2008;103:2446-53 Gut 2006;55:1398e402 8
Diagnostic Evaluation Maximize acid suppression EGD Test for acid reflux: ph off PPI MII/pH on PPI Symptom correlation: SAP Symptom Index Treatment Medical Acid Suppression Dosing: 15-30 min before breakfast + dinner qhs: H2RA s vs. Immediate release PPI Baclofen Inhibit TLESRs Side effects Visceral analgesics TCA s Trazadone SSRI s-citolopram Fundoplication 9
Therapy for Nocturnal Acid Breakthrough Pro NAB occurs 50-70% on PPI BID qhs H2RA s reduces NAB Con Tolerance to H2RA s? Immediate release PPI No symptom correlation with NAB J Clin Gastroenterol 2008;42:676 679 Diseases of the Esophagus (2005) 18, 370 373 Baclofen efficacy in patients with symptoms and DGER refractory to PPI s 16 pt s persistent symptoms on PPI s Baclofen 20 mg TID Bilitec/pH performed on PPI and PPI+Baclofen Severity score 10.3 (1.7) ) 5.8 (1.3) p<0.01 Gut 2003;52:1397 1402 10
MII/pH to select patients with persistent GER for fundoplication Prospective database 200 pt s ph/mii for persistent GER 19 under lap Nissan 18 abnl MII, 1 normal by SI 94% asymptomatic/markedly improved Retrospective case series British Journal of Surgery 2006;93:1483 1487 Putting it all Together Gut 2012;61:1340-1354 11
Conclusion Partial or incomplete response to BID PPI after 12 weeks EGD performed but low yield Combined ph/impedance test on PPI likely most useful May need ph off PPI to establish baseline GERD Most common result is control of GER Search for another cause refractory symptoms Treat for visceral hyperalgesia Treatment for refractory reflux Medical: Baclofen, NAB rx Careful selection for anti-reflux surgery 12