Update on GI medication management Megan Butler, M.D. Pediatric Gastroenterology Duke University Objectives • Discuss common GI diseases in children • Reflux • EoE • Constipation • Functional GI disorders • Review pharmacologic and non-pharmacologic treatment for GI disorders in children • Understand adverse events associated with GI medications Reflux “Name’s Reflux. Medical condition or super power, you decide.” -Reflux ©Disney-Pixar Reflux • Gastroesophageal Reflux • Reflux ≠ Reflux • Kids are NOT just little adults • Reflux in kids can be physiologic or pathologic • 80% of babies regurgitate in the first month of life • ~10% at 1yo • Need to distinguish • Important to rule out other reasons for symptoms Reflux • Definitions • GER • Passage of gastric contents into the esophagus with or without regurgitation and vomiting • GERD • When GER leads to symptoms that affect daily functioning and/or complications • Refractory GERD • GERD not responding to optimal treatment after 8 weeks • Look for “alarm signs” Reflux - DDxs • Gastrointestinal Obstruction • Cardiac • Pyloric stenosis, Malrotation with • Heart failure, vascular ring, autonomic volvulus, Intussusception, Hirschsprung dysfunction disease, Antral/duodenal web, Incarcerated hernia, Superior mesenteric • Other GI disorders artery syndrome • Achalasia, gastroparesis, gastroenteritis, peptic ulcers, eosinophilic esophagitis, • Neurologic food allergy/intolerance, inflammatory • Hydrocephalus, Subdural hematoma, bowel disease, pancreatitis, appendicitis Intracranial hemorrhage, Intracranial mass • Infectious • Sepsis/meningitis, UTI, upper/lower • Metabolic airway infection, otitis media, hepatitis • Galactosemia, hereditary fructose intolerance, urea cycle defects, amino • Other and organic acidemias, fatty acid • Pediatric condition falsification/factitious oxidation disorders, metabolic acidosis, disorder by proxy, child neglect or abuse, congenital adrenal hyperplasia/adrenal self-induced vomiting, cyclic vomiting crisis syndrome, rumination syndrome • Toxic • Lead poisoning, other toxins Alarm signs • Weight loss • Macro/microcephaly • Lethargy • Persistent forceful vomiting • Fever • Nocturnal vomiting • Excessive irritability/pain • Bilious vomiting • Dysuria • Hematemesis • Onset >6 months or increasing >12- • Chronic diarrhea 18 months of age • Rectal bleeding • Bulging fontanel/rapidly increasing • Abdominal distention head size • Seizures Clinical management algorithms • Etiologies can differ by age • Treatment algorithms differ by age • 2018 NASPGHAN clinical guidelines • Infants < 6 months • Infants and children ≥6 months Reflux - DDxs • Gastrointestinal Obstruction • Cardiac • Pyloric stenosis, Malrotation with • Heart failure, vascular ring, autonomic volvulus, Intussusception, Hirschsprung dysfunction disease, Antral/duodenal web, Incarcerated hernia, Superior mesenteric • Other GI disorders artery syndrome • Achalasia, gastroparesis, gastroenteritis, peptic ulcers, eosinophilic esophagitis, • Neurologic food allergy/intolerance, inflammatory • Hydrocephalus, Subdural hematoma, bowel disease, pancreatitis, appendicitis Intracranial hemorrhage, Intracranial mass • Infectious • Sepsis/meningitis, UTI, upper/lower • Metabolic airway infection, otitis media, hepatitis • Galactosemia, hereditary fructose intolerance, urea cycle defects, amino • Other and organic acidemias, fatty acid • Pediatric condition falsification/factitious oxidation disorders, metabolic acidosis, disorder by proxy, child neglect or abuse, congenital adrenal hyperplasia/adrenal self-induced vomiting, cyclic vomiting crisis syndrome, rumination syndrome • Toxic • Lead poisoning, other toxins Infant with H&P Yes Alarm sign? Appropriate testing suspected GERD No Avoid overfeeding Thicken feeds Education 1st Not improved? 2-4 week trial protein hydrolysate or AA Improved? Discuss protein formula, or cow’s milk reintroduction at follow up elimination (EBF) Formula/elimination trial 2nd Not improved Medications 3rd line Consider 4-8 week trial of Pediatric GI referral acid suppression, wean if sxs improve Adapted from Rosen et al, 2018 Child with suspected H&P Yes Alarm sign? Appropriate testing GERD No Lifestyle and dietary Improved? st Continue management 1 line education Not improved Acid suppression x 4-8 Improved? nd Attempt wean 2 line weeks Not improved Symptoms recur with weaning Pediatric GI referral Adapted from Rosen et al, 2018 GERD management • Non pharmacologic • Thickened feedings • Modification of feeding volumes/intervals • Discuss overfeeding! • Infants: Milk elimination, extensively hydrolyzed formula, AA formulas • Children: discuss excessive body weight, foods that may exacerbate reflux (tomato, spicy, chocolate, citrus, peppermint) • No evidence: • Massage therapy, hypnotherapy, homeopathy, acupuncture, herbal medicine, dietary supplementation, pre- and pro-biotics Medications for GERD • Histamine-2 Receptor Antagonist • Proton pump inhibitor • Prokinetics • Antacids Histamine-2 Receptor Antagonist • Ranitidine • Tachyphylaxis • 5-10 mg/kg/day (max 300mg) • Many drug interactions • Cimetidine • cytochrome P450 • 30-40 mg/kg/day (max 800mg) • Interfere with absorption • Nizatidine • Inhibit Renal excretion • 10-20 mg/kg/day (max 300mg) • CNS • Famotidine • Confusion • 1 mg/kg/day (max 40mg) • Headache • depression • Hematologic • thrombocytopenia • CV • Related to IV administration Proton Pump Inhibitors • Omeprazole • Changes in gastric mucosa • 1-4 mg/kg/day (max 40 mg) • ↑risk of GI and respiratory infxns • Lansoprazole • Vit B12 def • 2 mg/kg/day infants (max 30 mg) • ↓Mg • Esomeprazole • 10 mg/day (< 20kg) • ↑risk of fractures • 20 mg/day (>20 kg) • Rebound hyperacidity • Pantoprazole • ↑gastric microbiota • 1-2 mg/kg/day (max 40 mg) • headache • ?CV • ?renal • ?neuro Prokinetics • Metoclopramide • AE: Neurologic • Extrapyramidal, dyskinesia, dystonia, seizures, hypertonia, tremor • AE: Cardiac • Shock, hypotension, cardiac arrest, tachycardia, bradycardia, hypertension, cardiorespiratory arrest, circulatory collapse • tachyphylaxis • Domperidone • NOT FDA approved in US • AE: Cardiac toxicity • Baclofen • AE: Muscle weakness, somnolence, muscle weakness, nausea, paresthesia Miscellaneous medications • Antacids and aglinates • Neutralize acid • Sodium/potassium bicarbonate, or Al, Mg or Ca salts • Mg alginate, sodium alginate, Ca carbonate, Al hydroxide • Unclear benefit • AE: milk alkali syndrome (↑Ca, alkalosis, renal failure), ↑serum Al • Sucralfate • Site protective agent • AE: Al toxicity, intraluminal drug binding, drug interactions • Bethanechol • Cholinergic used for urinary retention • AE: flushing, hypotension, tachycardia, colic, bronchoconstriction… When to use medicines for GERD? • Erosive esophagitis PPI 1st line • Crying/distress in infants • Regurgitation in infants • Children with symptomatic GERD (heartburn, etc) 4-8 wks H2RAs or PPI • Extraesophageal sxs (cough, asthma, wheezing) • Other medications? Rosen et al. 2018 Eosinophilic Esophagitis • Chronic condition • Immune mediated • 1 in 10,000 people • Clinically can be very similar to GERD Eosinophilic Esophagitis • Often mistaken for GERD • Vomiting, regurgitation, chest pain, dysphagia, food impactions • Needs EGD to differentiate • > 15 eos/HPF in ≥ 1 biopsy specimen • Management • Non-pharmacologic • Elimination diet • Pharmacologic • Steroids (topical and systemic) • Response to therapy • EGD!! Eosinophilic esophagitis Uptodategastro.wordpress.com University of Chicago EoE non-pharmacologic management • Multi-disciplinary approach • GI • A/I • RD • PCP • Elimination diet • 4 food/6 food • Milk, wheat, egg, soy • +/- nuts and seafood • Intact protein elimination • AA formula • May need feeding tube (NG/GT) EoE medications • Swallowed, topical corticosteroids • OVB • Budesonide slurry Nothing to eat/drink x 20 mins • Fluticasone • PPI? • AE: thrush, incorrect administration, steroid SE • Systemic steroids • Rarely required • AE: many Constipation • Common in children • 3% PCP visits • 25% Pediatric GI visits ©2019 the Awkward Store Constipation • Infrequent and/or painful bowel movements • fecal incontinence • abdominal pain • Can significantly impact quality of life and health care costs • Vast majority of children no underlying medical disease found Rome III diagnostic criteria • Need ≥ 2 in absence of organic pathology: • ≤ 2 bowel movements in the toilet per week • 1 episode fecal incontinence per week • History of excessive stool retention or retentive posturing • History of painful or hard bowel movements • Presence of large fecal mass in rectum • History or large diameter stools that may obstruct the toilet • Developmental age <4y sxs present at least 1 month • DA ≥4y, sxs present at least 2 months Hymen et al 2006 and Rasquin et al 2006 Constipation DDxs • Celiac • Anal achalasia • Hypothyroid • Colonic inertia • Electrolyte abnormalities • Anorectal malformations • Dietary protein allergy • Pelvic mass • Medications/toxins • Spinal cord anomalies • Vitamin D intoxication • Abnormal abdominal musculature • Botulism • Pseudoobstruction • Cystic fibrosis • Multiple endocrine neoplasia type • Hirschsprung disease 2B • Behavioral/anxiety Alarm signs • Onset <1 mo • Perianal fistula • Passage of meconium >48 hours • Abnormal position of anus • Family h/o HD • Absent anal or cremasteric reflex • Ribbon stools • Decreased LE strength/tone/reflex • Blood in stools (absence of anal • Tuft of hair on spine fissure) • Sacral dimple • FTT • Gluteal cleft deviation • Bilious emesis • Extreme