When PPIs Don't Do the Trick, What Next?

Educational Objectives

The goal of this program is to improve the management of refractory symptoms of gastroesophageal reflux disease (GERD). After hearing and assimilating this program, the clinician will be better able to:

1. Evaluate symptoms of GERD refractory to therapy with proton pump inhibitors.

2. Effectively treat refractory symptoms of GERD.

Summary

Efficacy of proton pump inhibitors (PPIs) in management of symptoms of gastroesophageal reflux disease (GERD): regurgitation — recent study of 31 randomized controlled trials (RCTs) of PPIs for GERD found none used regurgitation as inclusion criteria or primary outcome; 55% to 60% of patients had resolution of heartburn; therapeutic gain for regurgitation ≈20%; chest pain — response to PPIs ranges from 0% to 50%; supralaryngeal symptoms — studies show PPIs provide no benefit

Etiology of GERD: hiatal hernia can predispose patient to reflux but most cases due to transient relaxation of lower esophageal sphincter; occasionally may be due to diminished esophageal clearance, excess acid production, gastric outlet obstruction, or gastroparesis; etiology of refractory GERD also likely includes element of hypersensitivity in esophagus

Differential diagnosis of refractory symptoms: regurgitation — esophageal stasis (eg, from achalasia); chest pain — cardiac, musculoskeletal, or somatization disorder; eosinophilic esophagitis; supralaryngeal symptoms — postnasal drip; tumor; tobacco use; asthma; chronic bronchitis

Evaluation of refractory symptoms: upper endoscopy — possible findings include erosive esophagitis (unlikely), eosinophilic esophagitis, hiatal hernia, and Barrett syndrome; however, recent study showed symptoms refractory to PPI associated with lower likelihood of Barrett syndrome compared to patients with responsive GERD or no symptoms of GERD; incidence of esophageal adenocarcinoma low in patients with GERD; recent American College of Physicians guidelines recommend screening for esophageal adenocarcinoma only in men age >50 yr with symptoms of GERD for ≥5 yr and additional risk factors; University of Michigan prediction tool for Barrett syndrome available at http://mberet.umms.med.umich.edu/; upper endoscopy has little diagnostic yield and need not be repeated; barium esophagraphy — sensitivity for spontaneous reflux ≈40%; provocative maneuvers (eg, Valsalva) increase sensitivity but decrease specificity; value in identifying achalasia; ambulatory pH monitoring — pH recorded across time (pH <4 considered acid); patient keeps diary of symptoms; diagnostic yield fairly low in patients who have not responded to PPI; multichannel intraluminal impedance (MII)-pH monitoring new technique that can assess reflux of acidic and nonacidic contents of esophagus

Treatment of refractory symptoms of GERD: lifestyle modification — if patient has nocturnal symptoms, head of bed should be elevated and patient should not eat for ≥3 hr before lying down; if problems noticed when consuming specific foods, these should be avoided; make sure timing of medications correct (PPIs work best when taken 30-45 min before breakfast [and dinner if taken twice daily]); further reduction of acid — increase of PPI from once to twice daily associated with significant decrease in abnormal reflux in patients with typical or extra-esophageal symptoms

Nocturnal acid breakthrough: gastric acid breakthrough while on PPI (drug loses effect while patient sleeping; can result in some esophageal reflux); responds to histamine (H)2 blockers but patient can develop tachyphylaxis; if patient has nocturnal symptoms despite taking PPI twice daily, addition of ranitidine 300 mg at bedtime may help

Sucralfate (Carafate): no RCT of adding sucralfate to PPI; RCT (Herrera et al, 1990) of adding it to H2 blocker found some improvement in symptoms and esophagitis, but no difference in complete endoscopic resolution of erosive esophagitis; effectiveness unclear in patient on PPI; associated with many side effects; best to avoid

Fundoplication: RCT of fundoplication compared to ranitidine 150 mg twice daily found procedure has good short- and long-term results for improving erosive esophagitis; however, after 10 yr follow-up, ≈62% of surgery patients on some form of medical therapy; potential side effects include gas bloat syndrome and dysphagia; no RCTs of fundoplication in nonresponders to PPI

Baclofen: γ-aminobutyric acid agonist; used to block reflux due to relaxation of lower esophageal sphincter; number of short-term RCTs of baclofen for GERD show decrease in reflux events and symptoms; however, drug associated with side effect of drowsiness; off-label indication

Neuromodulation: little data for hypersensitive esophagus; older RCT of imipramine vs clonidine and placebo in patients with noncardiac chest pain showed improvement in symptoms with tricyclic antidepressant; physiologic studies of patients on selective serotonin reuptake inhibitor (SSRI) show use of drug decreases esophageal sensitivity to balloon distension and acid perfusion

Proposed treatment algorithm: assess patient adherence, categorize symptoms, and determine whether any alarm features (eg, weight loss, dysphagia) present that require endoscopy; if not, increase PPI to twice daily dosing and initiate lifestyle modifications; if symptoms do not resolve, do one-time upper endoscopy, esophageal manometry, and MII-pH monitoring on PPI twice daily; if tests show persistent gastric reflux — make sure patient adhering to PPI therapy; consider gastrinoma, gastroparesis, or gastric outlet obstruction; increase dose of PPI; if pH negative but ongoing reflux by impedance — again, consider gastroparesis; can offer baclofen or fundoplication; if no or little pH or reflux by impedance (but good correlation between amount of reflux and symptoms) — consider neuromodulation with tricyclic antidepressant or SSRI; if results normal — consider other etiology

 

Readings

Suggested Reading

Dandapani M, Stoffel EM: Clinical management of families with hereditary colorectal cancer syndromes. Semin Colon Rectal Surg 2011 Jun 1;22(2):100-104; Gala M, Chung DC: Hereditary colon cancer syndromes. Semin Oncol 2011 Aug;38(4):490-9; Gatta L et al: Meta-analysis: the efficacy of proton pump inhibitors for laryngeal symptoms attributed to gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2007 Feb 15;25(4):385-92; Guarinos C et al: Serrated polyposis syndrome: molecular, pathological and clinical aspects. World J Gastroenterol 2012 May 28;18(20):2452-61; Hampel H et al: Feasibility of screening for Lynch syndrome among patients with colorectal cancer. J Clin Oncol 2008 Dec 10;26(35):5783-8; Herrera JL et al: Sucralfate used as adjunctive therapy in patients with severe erosive peptic esophagitis resulting from gastroesophageal reflux. Am J Gastroenterol 1990 Oct;85(10):1335-8; Hila A et al: Combined multichannel intraluminal impedance and pH esophageal testing compared to pH alone for diagnosing both acid and weakly acidic gastroesophageal reflux. Clin Gastroenterol Hepatol 2007 Feb;5(2):172-7; Jasperson KW et al: Hereditary and familial colon cancer. Gastroenterology 2010 Jun;138(6):2044-58; Kahrilas PJ et al: Management of the patient with incomplete response to PPI therapy. Best Pract Res Clin Gastroenterol 2013 Jun;27(3):401-14; Kahrilas PJ et al: Response of regurgitation to proton pump inhibitor therapy in clinical trials of gastroesophageal reflux disease. Am J Gastroenterol 2011 Aug;106(8):1419-25; Kalady MF: Surgical management of hereditary nonpolyposis colorectal cancer. Adv Surg 2011;45:265-74; Koh PK et al: Familial colorectal cancer type X: polyp burden and cancer risk stratification via a family history score. ANZ J Surg 2011 Jul-Aug;81(7-8):537-42; Lindor NM et al: Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X. JAMA 2005 Apr 27;293(16):1979-85; Lynch HT et al: Hereditary colorectal cancer syndromes: molecular genetics, genetic counseling, diagnosis and management. Fam Cancer 2008;7(1):27-39; Nason KS et al: Gastroesophageal reflux disease symptom severity, proton pump inhibitor use, and esophageal carcinogenesis. Arch Surg 2011 Jul;146(7):851-8; Palles C et al: Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat Genet 2013 Feb;45(2):136-44; Rubenstein JH et al: Esophageal adenocarcinoma incidence in individuals with gastroesophageal reflux: synthesis and estimates from population studies. Am J Gastroenterol 2011 Feb;106(2):254-60; Rubenstein JH et al: Prediction of Barrett’s esophagus among men. Am J Gastroenterol 2013 Mar;108(3):353-62; Shaheen NJ et al: Upper endoscopy for gastroesophageal reflux disease: best practice advice from the clinical guidelines committee of the American College of Physicians. Ann Intern Med 2012 Dec 4;157(11):808-16; Sifrim D, Zerbib F: Diagnosis and management of patients with reflux symptoms refractory to proton pump inhibitors. Gut 2012 Sep;61(9):1340-54; Sturgeon D et al: Increasing Lynch syndrome identification through establishment of a hereditary colorectal cancer registry. Dis Colon Rectum 2013 Mar;56(3):308-14.

Disclosures

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the faculty and planning committee reported nothing to disclose. In this lecture, Dr. Rubenstein presents information that is related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Rubenstein spoke at the Department of Internal Medicine Spring Review, presented May 10-11, 2013, in Ann Arbor, MI. and presented by the University of Michigan Health System. For information about upcoming CME events presented by the University of Michigan Health System, please visit their website at www.med.umich.edu. The Audio-Digest Foundation thanks Dr. Rubenstein and the University of Michigan Health System for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

IM604702

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

More Details - Certification & Accreditation