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An 18 month old boy with cerebral palsy is brought to your office because of “spitting up” after feeds. It has been a problem for the past several months, but is progressively worsening and now occurs after every meal and even at night. He was breast fed for 12 months and has slight developmental delay. Height and head circumference are between 25–50th centile, but weight is below 5th centile for age. A barium swallow reveals significant gastro-oesophageal reflux to the pharynx. A gastroscopic examination with biopsy reveals moderate oesophagitis without eosinophilia. You wonder if a proton pump inhibitor will be an effective treatment.
Structured clinical question
In children with gastro-oesophageal reflux [patients] does treatment with a proton pump inhibitor [intervention] decrease symptoms, increase gastric pH, and improve endoscopic findings [outcome]?
Search strategy and outcome
Pubmed: “treatment of gastroesophageal reflux in children”—limited to ages 0–18, English language, and human subjects.
1966–present: 1039 articles, seven relevant. See table 2.
There is adequate and consistent evidence that the proton pump inhibitor omeprazole is effective in the treatment of gastroesophageal reflux in children. In the five studies that addressed clinical outcomes, all patients had improvement in their symptoms. All of the studies addressed endoscopic outcomes and all patients had improvement in their findings after treatment. Six of the seven studies included patients who had failed other treatment modalities. Four of the five studies which looked at oesophageal pH showed an increase with treatment, which is indicative of decreased acid production. In the three studies that included children with significant comorbidities such as oesophageal atresia, neurological impairment, and cystic fibrosis, omeprazole was effective. In the four studies that had long term follow up, the relapse rates ranged from 17% to 60%. The higher relapse rates in the studies by Kato et al and De Giacomo et al could be attributed to the fact that there were more patients with comorbid conditions and untreated H pylori infections, respectively. Based on these results, clinicians may want to consider Hassall et al's advice that “the high degree of efficacy and safety of omeprazole defines a new standard for `optimised medical management' in children. It is our opinion that in most circumstances, a trial of the new optimised medical therapy should be considered before antireflux surgery”.
▸ CLINICAL BOTTOM LINE
When children with gastro-oesophageal reflux fail first line therapy, omeprazole is an effective second line choice. It may also be effective treatment in children with comorbid conditions such as cystic fibrosis, repaired oesophageal atresia, and neurological impairment.
Citation Study group Study type (level of evidence) Outcome Key result Comments
Cucchiara et al (1993) 32 children (6 months to 13 years) with severe reflux oesophagitis and failed ranitidine and cisapride. Patients randomised to high dose ranitidine (20 mg/kg/day) or omeprazole (40 mg/day/1.73m2) for 8 weeks RCT Clinical Both regimens effective. Decreased clinical score (p<0.01) Omep: 24 (15–33) to 9 (0–18) Ran: 19.5 (12–33) to 9 (6–12) Double blind RCT; 7 (22%) drop out; 6 month follow up. High relapse rate after treatment; 5/13 (38%) ranitidine and 7/12 (58%) omeprazole patients were still symptomatic, 2 required antireflux surgery Oesophageal pH monitoring (OpHM) Decreased OpHM reflux time Omep: 129 (84–217) to 44.6 (0.16–128) Ran: 207 (66–306) to 58.4 (32–128) Gastroscopy (histology) Decreased histologic score (p<0.01) Omep: 8 (6–10) to 2(0–6) Ranit: 8 (8–10) to 2(2–6) Kato et al (1996) 13 cases (3–18 years) with oesophagitis and/or ulcer; failed cimetidine or famotidine. Omeprazole 0.6 mg/kg/day Case-control Gastroscopy Benefit in biopsy (healing rate): 2 weeks 46%; 4 weeks 85%; 6 weeks 92%; 8 weeks 92% Criteria for healing not clear (biopsy results not reported); No controls No pretreatment pH studies; No treatment for patients with H pylori; 7/12(58%) relapsed. 9 controls; 5 without GI disease, 4 with ulcers treated with cimetidine or famotidine Gastric-pHM Mean gastric pH Controls: 2.1 (1.8–2.5) Omep: 5.2 (3.0–6.6) (p=0.005) Cim/Fam: 3.1 (1.9–3.8) (p=0.05) Gunasekaran et al (1993) 15 children (0.8–17 years) with oesophagitis and failed H2 blocker and prokinetic therapy; 4 with fundoplication Case series Clinical Follow up:3 months: decreased symptoms 75% 6 months: decreased symptoms all No controls; 8 neurologically impaired children and 1 with CF. Gastroscopy at 6 months only done on patients with endoscopic evidence of oesophagitis at first follow up Omeprazole (0.7–3.3 mg/kg/day) for 5.5–26 months. Dose titrated upward against 24° EpHM Gastroscopy 6 months: 9/15 had gastroscopy and all 9 improved OpHM Before treatment pH<4 for 11–88% of time. After treatment normal pH (<4 for < 6% of time) De Giacomo et al (1997) 10 children (25–109 months) with abnormal GOR and severe oesophagitis, failed prokinetic, H2 blocker or antacid therapy Case series Clinical Decreased symptoms all (p<0.05) Decreased score all No controls; 4 (40%) with significant comorbidities; 6 (60%) relapse after therapy; 3 required antireflux surgery Gastroscopy Histology OpHM No difference in histologic scores Decreased GOR (%, no., no. >5 min., and longest GOR) Alliet et al (1998) 12 children (2.9 ± 0.9 months); oesophagitis and failed cimetidine, positioning, cisapride, or Gaviscon therapy. Omeprazole 0.5 mg/kg/day for 6 weeks Case series Clinical Decreased symptoms 10/12 (83%) No controls. One year follow up 83% asymptomatic Gastroscopy Biopsy 9 (75%) had completely normal mucosa; 3 (25%) improved 8 (67%) completely healed; 4 (33.%) improved OpHM during Rx Decreased intragastric acidity (no p values) Hassall et al (2000) 57 children (1–16years) with erosive oesophagitis and pathologic acid reflux (pH <4 for >6% of the time). Treatment began at 0.7 mg/kg/day and increased by 0.7 mg/kg/day q 5–14 days to a max of 3.5 mg/kg/day if pathologic reflux was still present. Treatment continued for 3 months after healing dose was determined Case series (prospective) Clinical Decreased symptoms: 53 (93%) 21 (37%) neurologically impaired; 7 (12%) repaired oesophageal atresia. No treatment for patients with H pylori No long term follow up Gastroscopy Healed: 54 (98%). Median healing time 102 days Karjoo et al (1995) 153 children (6–18 years) with >3 weeks of epigastric pain had OGD; 129 (84%) with oesophagitis were given high dose ranitidine (4 mg/kg/dose BID-TID for 4 weeks); 38 (30%) non-responsive to ranitidine were given omeprazole (20 mg/day) for 8 weeks Case series (prospective) Gastroscopy 91/129 (70%) responded to ranitidin;e 38/129 (30%) non-responsive to ranitidine; 33/38 (87%) responded to omeprazole (p<0.05); 5 (4%) failed both treatments (3 had Nissen fundoplications) Degree of oesophagitis on gastroscopy predictive of response to ranitidine (90% of patients with grade 1 respond). No long term follow up