Acid suppressive therapy:
Antacids are enteral agents that can be used to directly buffer gastric juice and, thereby, provide rapid symptom relief. Alginate and sucralfate are surface-protective agents that bind to gastric mucosa to decrease symptoms and promote mucosal healing. According to the 2009 NASPGHAN Guidelines, antacids and surface-protective agents may be used to decrease symptoms of GERD and promote healing of nonerosive esophagitis. However, neither is recommended as long-term therapy for pediatric GERD, in particular because their safety and efficacy in children have not been adequately determined. The safety of absorbable agents that contain aluminum is of specific concern. Indeed, studies have shown that prolonged treatment with aluminum-containing antacids can increase plasma aluminum levels in infants, in turn increasing risks of osteopenia, microcytic anemia, and neurotoxicity. Sucralfate also contains aluminum and may not be safe for long-term use in children. Some pediatric gastroenterologists suggest using a 0.5 ml/kg dose of sucralfate for infants. Remind parents or guardians that sucralfate should be mixed with water, not formula, to be effective.
H2RAs decrease acid secretion by inhibiting histamine-2 receptors on gastric parietal cells. Studies of gastric pH in infants have shown more than 40% reduction in gastric acidity in infants receiving twice-daily dosing of H2RAs and more than 90% reduction in infants receiving doses three times a day. Pharmacokinetic studies of H2RAs in children are numerous and suggest that appropriate doses can increase gastric pH within a few hours of administration and for clinically significant periods (4–6 hours). Randomized, controlled trials in pediatric populations have also shown that H2RAs are more effective than placebo for healing esophagitis and providing symptom relief. Adverse effects of H2RAs are rare but can include irritability, headache, somnolence, and in some cases, liver disease and gynecomastia.
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In addition, H2RA use is associated with tachyphylaxis in as soon as 6 weeks and may represent a drawback to long-term use.
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If patients and/or parents report that symptoms persist, especially after a 2-week trial of a medication, reevaluate and consider changing to or adding a different GERD pharmacological treatment strategy. For example, an infant whose symptoms have not improved after 2 weeks of H2RA therapy may be given a trial of PPI therapy.
PPIs inhibit acid secretion by blocking Na+,K+-ATPase, aptly known as the “proton pump,” or the final common pathway of parietal cell acid secretion. PPIs are accepted as superior antisecretory agents to H2RAs for two reasons; first they are able to maintain intragastric pH at or above 4 for longer periods, and second, because of their unique ability to inhibit meal-induced acid secretion. PPIs can be used with excellent acid suppressive effects for indefinite periods and are not associated with tachyphylaxis. Drawbacks to PPI use in children include side effects of headache, diarrhea, constipation, and nausea seen in up to 14% of children. PPIs have not been approved for use in North America in infants. In addition, PPI use and resulting gastric achlorhydria in adults and in small cohorts of children retrospective studies have demonstrated an association with an increased incidence of community-acquired infections, alteration in intestinal bacterial flora, and deficiencies of vitamin B12. Nevertheless, the number of PPI prescriptions written for infants continues to increase. Accordingly, the 2009 Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of NASPGHAN and ESPGHAN state that risks of PPI therapy in infants may outweigh perceived benefits, which have not been substantiated by placebo-controlled trials.
Promotility agents should ideally enhance esophageal peristalsis and accelerate gastric emptying, while decreasing the number and duration of transient lower esophageal sphincter relaxations. There are no medications available that specifically target transient lower esophageal sphincter relaxations, although this relaxation is recognized to be the most important pathophysiologic mechanism of reflux. To date, the effectiveness of commercially available promotility agents in children is unproven and not recommended for routine use. In addition, a number of promotility agents may have common, serious side effects such as cardiac arrhythmias and central nervous system complications. Putnam et al (1992)1 reported that parkinsonian reactions and tardive dyskinesia may occur in up to 30% of patients taking metoclopramide and may be irreversible. The FDA released a black box warning in February 2009 stating that it is not recommended for prolonged (>2 months) use except in rare cases. (Link to FDA web site) The 2009 Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of NASPGHAN and ESPGHAN recommend against routine use of any available promotility agents to treat pediatric GERD.
1Putnam PE, Orenstein SR, Wessel HB. Tardive dyskinesia associated with use of metoclopramide in a child. J Pediatr. 1992 Dec;121(6):983–985.