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Refractory GERD

Introduction. GERD: Symptoms or mucosal damage due to abnormal reflux of gastric contents into esophagus Refractory GERD: GERD symptoms or esophagitis despite treatment with PPIPatients requiring more aggressive therapyPatients having other causes of S. Failure of treatment with PPI. Efficacy

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Refractory GERD

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    1. Refractory GERD Khalil HONEIN, M.D. Gastroenterology – Hôtel Dieu De France

    2. Introduction GERD: Symptoms or mucosal damage due to abnormal reflux of gastric contents into esophagus Refractory GERD: GERD symptoms or esophagitis despite treatment with PPI Patients requiring more aggressive therapy Patients having other causes of S

    3. Failure of treatment with PPI Efficacy of PPI is dose dependant Likelihood of healing esophagitis: proportional to fraction of day with intra-gastric pH above 4

    4. Factors contributing to inadequate PPI response Nocturnal Acid Breakthrough (NAB) Reduced bioavailability Effect of food and dosing interval Differences in metabolism Gastric acid hypersecretion HP status Drug resistance, slow healing

    5. Nocturnal Acid Breakthrough (NAB) May be responsible for majority of patients with refractory GERD Up to 70% of patients taking PPI twice daily will have periods of gastric pH<4 lasting for more than 1 hour(at night) Esophageal acid exposure higher in patients with GERD and correlated with severity of esophagitis Katz Po et al. Aliment Pharmacol Ther 1998;12 :1231

    6. Nocturnal Acid Breakthrough (NAB) Nocturnal acid exposure while on PPI May be reduced by H2RA and by increasing PPI dose Sometimes difficult to eliminate Ours, Am J Gastro 2003;98 :545-50

    7. Reduced Bioavailability Bioavailability of PPI influenced by environmental and manufacturing conditions For most patients, difference in bioavailability are not clinically significant Acid secretion decrease similar with lanzo or omeprazole Andersson T. Br J Pharmacol 1990; 29:557 Dammann HG. Aliment Pharmacol Ther 1997; 11:359

    8. Effect of food and dosing interval Administration 15-30 min prior to meals, particularly in refractory patients (individual variability) Brummer RJ. Dig Dis Sci 1997; 42 :2132 PPI usually given once daily and sometimes twice daily improve gastric acid suppression Kuo B. Am J Gastroent 1996; 91 :1532

    9. Differences in metabolism PPI metabolized through the CYP 2C Genetically- determined variability may ? effect on gastric acidity CYP 2C absent: 3% of Caucasian patients in more than 10% in Asians

    10. Gastric acid hypersecretion Patients with BAO > 10mEq/h may predisposed to refractory GERD Should be considered in refractory patients Collen MJ. Dig Dis Sci 1994; 39 :1434

    11. HP status Role not established in refractory patients to adequately –dosed PPI No evidence that eradication exacerbates GERD Fallone Aliment Pharm Therapy 2004;20(7) : 761-768

    12. Drug Resistance Resistance is a rare condition caused by mutations of the PP Patients can be treated by H2RA Endoscopic healing and S relief: achieved within 8 weeks Severe esophagitis take longer to heal Leite L. Gastroenterology 1995; 108:A147 Chiba N. Gastroenterology 1997;112 :1798

    13. OTHER CAUSES OF SYMPTOMS Other pathological situations Esophageal hypersensitivity Non acid reflux (Patients still S despite adequate acid supression)

    14. Other Pathological Situation IBS and dyspepsia with overlap S Atypical GERD ( cough, asthma, NCCP ) Achalasia Cancer or stricture Caustic and Infectious esophagitis NSAID ( more susceptibility to acid related E disease) Sopena. J clin Gastro 1998; 27:316 Losurdo. Gastroenterology 1999; 116: A 239

    15. Esophageal Hypersensitivity To physiologic acid reflux ( visceral hyperalgesia) Trimble KC. Dig Dis Sci 1995; 40:1098 Patients with heartburn but without endoscopic or pH evidence of GERD Acid suppressive therapy and low dose antidepressants Rodriguez Am J Gastroenterol 1999; 94:628

    16. Trimble Study Dig Dis Sci 1995; 40:1098

    17. Non Acid Reflux Mixed acid and bile refluxate (more aggressive than acid alone) DGER: in patients with gastric surgery Bilitec Test: Spectrophotometric detection of bilirubin concentration Combined pH and Bilitec > pH alone for detection of pathological reflux in refractory patients Tack J. Am J Gastro 2004; 99:981 Yumiba T. Am J Gastro 2002; 97 :1647

    18. Bilitec

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