Gastroesophageal Reflux Disease Lecture for Students

Gastroesophageal Reflux Disease Lecture for Students

1. What have you heard about GERD? Truths Behind Your Questions

2. Gird for GERD What is it? What is its natural course? How is it recognized from infancy to adolescence? Are there solutions to the problem? J Pediatr Gastroenterol Nutr 2018;66

3. 3 Scenarios First Scenario: 6 week old baby boy presenting to the clinic for frequent “vomiting” starting at 1 month of age Second Scenario: 7 year-old girl with cerebral palsy admitted for recurrent pneumonias Third scenario 14 year-old girl consulting for frequent episodes of chest tightness associated with epigastric pain Possible GER or GERD

4. Is GERD different from GER?

5. GER vs. GERD GER GERD GER that leads to troublesome symptoms affecting daily functioning and/or complications Passage of gastric contents into the esophagus with or without vomiting or regurgitation 2009 NASPAGHAN and ESPGHAN consensus statements. Arch Pediatr 2010;17

6. Problems with definition in pediatrics exist Actual clinical practice terms often interchanged Symptoms age-specific and variable Excessive crying, fussiness, back-arching, irritability in infants “heart burn” in adolescents What are “troublesome symptoms”? Dilemma overshadowed by n eed to standardize

7. Spectrum Innocent ; physiologic Life-threatening GER GERD

8. How likely will I see these c hildren in the clinic?

9. infancy 70% of happy, healthy, thriving infants at 3-7 mos. with GER Decreases after 7-8 mos. Resolves by 12 -15 mos teen ≈ 5% of adolescents report symptoms of heartburn, epigastric pain or regurgitation Martin Aj , et al. Pediatrics 2002;109 Nelson SP, et al. Arch Pediatr Adolesc Med 1997; 151 Nelson SP, et al. Arch Pediatr Adolesc Med 2000; 154 Davidson GP and Omari TI. Curr Gastroenterol Rep 2001; 3

10. Are there clues that will make you suspect that the child has GERD?

11. Symptoms (to be asked from parent/patient) General Discomfort/irritability Failure to thrive Feeding refusal Dystonic neck posturing ( Sandifer syndrome) GI Hematemesis Dysphagia/odynophagia In older child: Recurrent regurgitation ± vomiting Heartburn/chest pain Epigastric pain Airway Wheezing Cough Hoarseness Stridor Signs (to be looked for by M.D.) General Dental erosion Anemia GI Esophagitis Esophageal stricture Barrett esophagus Airway Apnea spells Asthma Recurrent pneumonia associated with aspiration Recurrent otitis media

12. Important points in history and PE Help to distinguish GER from GERD Identify complications of GERD Help exclude more worrisome disorders requiring further work-ups

13. For infants (0-12 months) with frequent regurgitation and/or vomiting History and PE enough to clinch diagnosis History: Age of onset Thorough feeding/dietary Hx Pattern of regurge /vomiting/spitting Family medical Hx Environmental triggers Growth trajectory Management given Warning signs Physiologic GER seldom before 1 week or after 6 months of age

14. For children (12 mos. – 18 yrs.) with frequent regurgitation and/or vomiting Persistence of symptoms beyond 12months calls for alternative diagnosis other than GER Recommended: seek consult with pediatric gastroenterologist

15. Red Flags

16. Aside form history and PE is there a need to work-up the child ?

17. Diagnostic Evaluation for GERD Intervention Locally Available Can diagnose GERD? Usefulness Barium contrast studies No Exclusion of anatomic abnormalities Ultrasound No Exclusion of anatomic abnormalities Esophago -gastro- duodenoscopy No Assessment of complications of GERD if underlying mucosal disease suspected and prior to intensifying therapy Scintigraphy No Indicated when GERD symptoms not responding to standard therapies & other diagnoses / triggers like delayed gastric emptying considered

18. Diagnostic Evaluation for GERD Intervention Not Locally Available Recommended for diagnosis of GERD? Usefulness Manometry No Only when motility disorder suspected Salivary pepsin No Debatable usefulness; lack of standards 24-hour pH monitoring No Consider only if pH multichannel intraluminal impedance (pH-MII) is not available to: Correlate persistent troublesome symptoms of acid reflux Clarify role of acid reflux in esophagitis and other S/ Sx of GERD Determine efficacy of acid suppression therapy pH-MII No if used alone Consider only to : Correlate persistent troublesome symptoms with acid and non-acid GER events Determine efficacy of acid suppression therapy Differentiate non-erosive reflux disease, hypersensitive esophagus and functional heartburn in those with normal endoscopy

19. 24-hour pH monitoring pH-MII

20. Diagnostic Evaluation for GERD: Proton Pump Inhibitor (PPI) Test Based on hypothesis: if symptoms respond to PPIs they are therefore GERD-related  Test NOT recommended for INFANTS  Recommended for older children : 4 to 8 week trial of PPIs for typical symptoms ( heartburn, retrosternal or epigastric pain) Greatest symptomatic relief in first 2-4 weeks Can be shortened if clinical suspicion for reflux is low or concerns for side effects high

21. Can we use non-pharmacologic treatment safely and effectively?

22. Non-pharmacologic treatments investigated Use of thickeners Reduced feeding volume Elimination of cow’s milk Positioning therapy Patient/parental education Alternative medicine

23. Usefulness of non-pharmacologic treatments for GERD Intervention Usefulness Comments Thickened feeds ✔ Cereal -based or commercial thickeners Reduce vomiting and visible regurgitation Increase the number of days without regurgitation Reduce symptoms like crying and irritability Reduction in feeding volume ✔ Modify feeding volumes and frequency according to age and weight to avoid overfeeding Cow’s milk protein elimination ✔ 2-4 week trial of extensively hydrolyzed protein formula Certain infants with CMPA experience GER-or GERD-related symptoms so worthwhile to give trial for formula-fed infants Done if optimal non-pharmacologic treatment fails

24. Usefulness of non-pharmacologic treatments Intervention Usefulness Comments Positional therapy ✗ (for sleeping infants) ✔ (in older children) Head elevation, lateral/prone position: r isk of SIDS and other safety issues Head elevation or left lateral position Alternative medicine ✗ No role : massage; lifestyle/complementary interventions like prebiotics/ probiotics, herbal medicines Patient/parental education ✔ Inform excessive body weight associated with GERD Patient/parental education & support should be part of treatment

25. What pharmacologic treatments are effective and safe?

26. Usefulness of pharmacologic treatments for GERD Intervention Usefulness ? Comments Antacids ✗ Absence of compelling evidences With safety issues Alginates ✗ Domperidone ✗ Metoclopromide ✗ Other prokinetics (erythromycin, bethanecol ) ✗ Proton pump inhibitors ✔ As first line treatment for reflux – related erosive esophagitis; typical GERD symptoms in older children H2 receptor antagonists ✔ If PPIs not available or contraindicated for reflux-related erosive esophagitis; typical GERD symptoms in older children

27. Rational use of PPIs and H2RAs in GERD For healthy infants use of H2RA or PPI: not recommended if crying/distress as presenting symptoms not recommended for treatment of visible regurgitation For older children : 4 to 8- week course recommended for treatment of typical symptoms (heartburn, retrosternal or epigastric pain) of GERD evaluation of treatment efficacy and exclusion of alternative causes if not responding to the 4-8 week course

28. Rational use of PPIs and H2RAs in GERD For both infants and children Not recommended for extra-esophageal symptoms (cough, wheezing, asthma) except if typical GERD symptoms (+) and/or (+) diagnostic test suggestive of GERD Regular assessment of long-term need for acid suppression due to possible side effects In general PPIs more effective than H2RAs; H2RAs shown to develop tachyphylaxis

29. K + H + Acid secretion Proton pump inhibitor _ Histamine PGE2 Ach Gastrin ECL Gs Ac G1 ATP Cyclic AMP Protein kinase H2RA antagonist Misoprostol Gastrin Ach Vagus Vessel _ _ ATPase Ca 2+ Ca 2+ Ach = Acetylcholine PGE2= Prostaglandin E2 ECL= Enterochormaffin like cell Gastric A c id Secretion APICAL SURFACE

30. Do all PPIs work the same ?

31. Differences and similarities All share the same basic structure and mode of action Characteristics Comparability Oral bioavailabity Lansoprazole and Esomeprazole (85-95%) > than rabeprazole (52%) Omeprazole higher but after multiple doses Time to reach peak effectiveness Omeprazole (30 min) > Lansoprazole , Dexlansoprazole , Esomeprazole (1-2 hours > Pantoprazole, Rabeprazole Half-life Omeprazole, Esomeprazole (3 hours) > Lansoprazole , Dexlansoprazole , Pantoprazole , Rabeprazole (1-2 hours) Time of best intake Dexlansoprazole can be taken with or without food vs. the others ( before breakfast) https://www.goodrx.com/blog/compare-popular-proton-pump-inhibitors-acid-reflux-gerd-treatments / Accessed May 25, 2021

32. In addition … GI Issues Dexlansoprazole less abdominal complaints (diarrhea, abdominal distention) Winner! Alternative to pills or capsules Lansoprazole as easily dissolving pleasant tasting fully dispersible tablet; Esomeprazole in powder formulation Safe to use in pregnancy All as Class B by US FDA (no potential fetal toxicity from animal studies) except Omeprazole and Rabeprazole https://www.goodrx.com/blog/compare-popular-proton-pump-inhibitors-acid-reflux-gerd-treatments/ Accessed May 25, 2021

33. Recommended Pediatric Dosages Drug Pediatric Dose Histamine-2 Receptor Antagonists Ranitidine 5-10 mg/kg/d Cimetidine 30-40 mg/kg/d Nizatidine 10-20 mg/kg/d Famotidine 1 mg/kg/d Proton pump inhibitors Omeprazole 1-4 mg/kg/d Lansoprazole 2 mg/kg/d Esomeprazole 10 mg/d (weight < 20 kg) or 20 mg/d (weight > 20 kg) Pantoprazole 1 -2 mg/kg/d Dexlansoprazole 30 mg od for > 12 years

34. Possible Side Effects of Long-term (≥ 6 months) PPI use Few data in children Increased lower respiratory tract infections in infants Prolonged use (2.5 years) resulted in reduced bone mineralization, moderate hypergastrinemia , enterochromaffin -like cell hyperplasia Risk factor for community-acquired pneumonia, gastroenteritis, candidemia , NEC in preterms Rybak A, et al. Int J Mol Sci 2017;18

35. What are the consequences of pediatric GERD ?

36. GERD Outcomes Persistence of abnormal esophageal histology after 1 year despite improvement in symptomatology of reflux esophagitiis (Orenstein SR, et al Am J Gastroenterol 2006;101) Childhood GERD a risk factor for GERD in adolescents and young adults (El- Serag HB, et al. Am J Gastroenterol 2004; 99) Almost 80% experienced at least monthly heartburn and/or acid regurgitation Almost 1/3 taking anti-secretory or PPI Adults with GERD more likely to have experienced childhood GER ( Waring JP, et al. JPGN 2002; 35)

37. Scenario 1: 6 week old baby boy presenting to the clinic for frequent “vomiting” starting at 1 month of age

38. Infant with suspicion of GERD History and PE Presence of alarm signs Tailor testing or address alarm signs & refer appropriately Avoid overfeeding Thicken feeds Continue breastfeeding Continue management Consider 2-4 wks of protein hydrolysate or AA-based formula If breastfed: maternal elimination of cow’s milk Continue management & discuss milk protein reintroduction on ff -up Referral to Pediatric GI Consider 4-8 wk trial of acid suppression then wean if symptoms improve Revisit differential dx; consider testing &/or short medication trial No further treatment Yes No Improved Not improved Improved Not improved Improved Referral Successful weaning Sx not improved or Recur Algorithm 1. Management o f symptomatic infant

39. Scenario 2: 14 year-old girl consulting for frequent episodes of chest tightness associated with epigastric pain

40. Child with typical symptoms of GERD History and PE Presence of alarm signs Lifestyle and dietary education Acid suppression for 4-8 weeks Refer to Pediatric GI Tailor testing to address alarm signs and refer appropriately Continue management Continue for a total of 4-8 weeks and then attempt to wean Yes No Improved Not improved Improved Not improved Symptoms recur with weaning Algorithm 2. Diagnosis and therapy for typical reflux symptoms in older child

41. KEY TAKEAWAY MESSAGES Reflux symptoms fairly common in pediatrics Terms GER and GERD have specific definitions Natural course points to possible persistence so early treatment should be addressed History and PE can clinch the diagnosis in majority of cases Additional work-ups needed for those with alarm signs and refractory to treatment

42. KEY TAKEAWAY MESSAGES Non-pharmacologic and pharmacologic treatments available for infants and older children Those presenting with typical GERD symptoms need a trial of PPI which works as both diagnostic and therapeutic intervention Not all PPIs are the same and should be tailored to individual needs Diagnostic and therapeutic algorithms are available and useful tools in general clinical practice