NEGATIVE ENDOSCOPY, What is the Diagnosis and Treatment?
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1 NEGATIVE ENDOSCOPY, PPI REFRACTORY REFLUX: What is the Diagnosis and Treatment? Michael F. Vaezi, MD, PhD, MSc, FACG Professor of Medicine Clinical Director Division of Gastroenterology, Hepatology and Nutrition Vanderbilt University Medical Center STEP DOWN PPI - BID PPI s - q day H2RA s - BID H2RA s-q day Antacids Life Style Modification 1
2 ACID SUPPRESSION H2RA Cimetidine (Tagament) 400 mg BID Ranitidine (Zantac) 150 mg BID DR Famotidine (Pepcid) 20 mg BID Nizatidine (Axid) PPI s Omeprazole (Prilosec) 20 mg QD Lansoprazole (Prevacid) 30 mg QD Rabeprazole (Aciphex) 20 mg QD Pantoprazole (Protonix) 40 mg QD Esomeprazole (Nexium) 150 mg BID 40 mg QD IR Omeprazole + bicarb (Zegerid) 40 mg QD DDR Dexlansoprazole (Dexilant) 60 mg QD 2
3 META-ANALYSIS ENDOSCOPIC HEALING WITH PPI'S % Total healed PPI H 2 RA Placebo 7635 patients Grade II-IV 85% 52% 28% Weeks Chiba Earnest et al. AJG Gastroenterology - November, Suppl., 1997; : GERD Symptoms Esophagitis Barrett s 3
4 Response to Acid-Suppressive Therapy Moayyedi et al Gastroenterology 2004; 127: Refractory GERD Poor response to bid PPI 4
5 Refractory Reflux Symptoms Compliance Dosing ZE PPI resistance NAB Inadequate Acid Suppression Regurgitation Bile Non-acid Non-acid Reflux Refractory Symptoms NOT Reflux Related Rumination Aerophagia Motility disorder (achalasia) Functional DGE EoE Vaezi, AJG 2004 Rumination Rare Often confused with GERD Persistent regurgitation of ingested food Remastication and swallow No nausea Does not respond to PPI 5
6 RUMINATION: MII-EM Tutuian and Castell. CJG 2004; 2: Aerophagia Belching (up to 20 / min) Excessive air swallow Gastric Subpragastric Often confused with GERD Poor response to PPI 6
7 Air Swallow Impedance-manometry Bredenoord et al Gut 2004; 53: Air Swallow Gastric Supra-gastric Bredenoord et al Gut 2004; 53:
8 mmhg Achalasia Seconds Pharynx Cm 35 Stomach EoE 8
9 ph monitoring in symptomatic patients on PPI therapy 30 % Distal Total Time ph < Upper limit of normal (69%) (93%) (70%) (99%) QD BID TYPICAL GERD (n = 135) QD BID ATYPICAL GERD (n = 115) Vaezi. Am J Gastroenterol 2005;100: Compliance Aliment. Pharmacol ther : pts with persistent GERD 54% not dosed appropriately 39% qhs ppi use 4% prn The gallup Organization % pts reported qhs ppi use 9
10 Impedance-pH Antegrade Bolus Movement 10
11 Retrograde Bolus Movement Impedance-pH in GERD Refractory to PPI BID Symptomatic pts (N=144) Abnl Non-acid reflux (37%) Inadequate Acid Supp (Distal acid > 1.6%) (11%) Normal (52%) Mainie et al. Gut 2006; 55:
12 Abnormal Impedance ON therapy = Abnormal ph OFF therapy Pts Refractory Sx on BID PPI Impedance 64% Normal Abnormal 36% N=25 N=14 Stop PPI 93% Wireless ph Normal Abnormal Pritchett and Vaezi, CGH 2009 Post-Fundoplication Predictor of Response: HB/Regurg; Abnormal ph; Hiatal hernia NOT IMPEDANCE -HB/Acid +HB/-acid -HB/+acid +HB/acid Francis and Vaezi, Laryngoscope
13 SI/SAP Depend on Degree of Reflux Symptom S + R + S - R + Reflux S + R - S - R - - S + S - R + R - N Slaughter and Vaezi, CGH 2011 OTHER THERAPIES More PPI s over the counter Additional PPI enantiomers Rb Rabeprazole? PPI + other agents TLESR inhibitors Baclofen mglur5 antagonist??pcabs/cck2-receptor antagonists Sensory inhibition** 13
14 Suspected LPR Patients N=72 Responders N=47 BID PPI 4-months Surgery (Fundoplication) Non-responders N=25 - Abnormal baseline ph - Normal ph on BID PPI - Continued signs/symptoms Continued BID PPI N=10 N=15 Surgery Does not Improve Symptom month response % Surgery Group 7% Medical Group Swoger and Vaezi, CGH
15 Refractory Reflux Symptoms Compliance Dosing ZE PPI resistance NAB Inadequate Acid Suppression Regurgitation Bile Non-acid Non-acid Reflux Refractory Symptoms NOT Reflux Related Rumination Aerophagia Motility disorder (achalasia) Functional DGE EoE Vaezi, AJG 2004 Algorithm Change PPI s GERD Alarm Sx s EGD PPI qd (bid) 1 2 months MII/pH Impedance/pH Symptoms Symptoms monitoring available persist improve (on Therapy) bloating positive???????? negative early satiety Empiric therapy Titrate Pain modulators CAUTION Off tx testing: EGD/pH Surgery Carafate (TCA, SSRI s, Trazedone) Gastroparesis Diet Low bulk/fat Promotility motilin/reglan 15
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