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Three Part Question

In [children with gastroesophageal reflux] does [treatment with a proton pump inhibitor] [decrease symptoms, increase gastric pH, and improve endoscopic findings]?

Clinical Scenario

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 percentile, but weight is below 5th percentile for age. A barium swallow reveals significant gastro-oesophageal reflux to the pharynx. A gastroscopic examination with biopsy reveals moderate esophagitis without eosinophilia. You wonder if a proton pump inhibitor will be an effective treatment.

Search Strategy

Pubmed 1966-present
"treatment of gastroesophageal reflux in children" LIMIT to ages 0-18, English language AND human subjects

Search Outcome

1039 articles - 7 relevant

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Gunasekaran TS and Hassall EG, 1993, Canada	15 children (0.8 – 17 years) with oesophagitis and failed H2 blocker and prokinetic therapy; 4 with fundoplication. Omeprazole (0.7-3.3mg/kg/day) for 5.5-26 months. Dose titrated upward against 24 degrees EpHM	Case Series	Clinical	Follow-up:3 months reduction in symptoms 75%. 6 months reduced symptoms all	No controls 8 neurologically impaired children and 1 with CF. Gastroscopy at 6 months only done on patients with endoscopic evidence of esophagitis at first follow up
			Oesophageal pH monitoring (OpHM)	Before treatment pH<4 for 11-88% of time. After treatment normal pH (<4 for < 6% of time)
			Gastroscopy	6 months: 9/15 had gastroscopy and all 9 improved
Cucchiara S et al, 1993, Italy	32 children (6months to 13 years) with severe reflux oesophagitis and failed ranitidine and cisapride; Patients randomized to high dose ranitidine (20mg/kg/day) or omeprazole (40mg/day/1.73m2) for 8 weeks	RCT	Gastroscopy (Histology)	Reduction in Histologic Score (p<0.01) Omep: 8(6-10) to 2(0-6)Ranit: 8(8-10) to 2(2-6)	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 anti-reflux surgery
			OpHM	Reduction in OpHM reflux time. Omep: 129 (84-217) to 44.6 (0.16-128) Ran: 207 (66-306) to 58.4 (32-128)
			Clinical	Both regimen effective; reduction in Clinical Score (p<0.01) Omep: 24 (15-33) to 9 (0-18) Ran: 19.5 (12-33) to 9 (6-12)
Karjoo M and Kane R, 1995, USA	153 children (6-18 years) with >3 weeks of epigastric pain had OGD; 129 (84%) with oesophagitis were given high dose ranitidine (4mg/kg/dose BID-TID for 4 weeks); 38 (30%) non-responsive to ranitidine were given omeprazole (20mg/day) for 8 weeks	Case Series (prospective)	Gastroscopy	91/129 (70%) responded to ranitidine. 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
Kato S et al, 1996, Japan	13 Cases (3 -18 years) with oesophagitis and/or ulcer; failed cimetidine or famotidine. Omeprazole 0.6mg/kg/day. 9 controls; 5 without GI disease. 4 with ulcers treated with cimetidine or famotidine	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 pre-treatment pH studies No treatment for patients with H pylori; 7/12(58%) relapsed
			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)
De Giacomo C et al, 1997, Italy	10 children (25-109 months) with abnormal GOR and severe esophagitis, failed prokinetic, H2blocker or antacid therapy	Case Series	Gastroscopy/Histology/OpHM	Reduction, No difference in histologic scores, reduced score GOR (%, no., no.>5min., and longest GOR)	No controls. 4 (40%) with significant comorbidities, 6 (60%) relapse after therapy, 3 required anti-reflux surgery
			Clinical	Reduction in Symptoms all (0<0.05) reduced score all
Alliet P et al, 1998, Belgium	12 children (2.9 +/- 0.9 months); oesophagitis and failed cimetidine, positioning, cisapride, or Gaviscon therapy. Omeprazole 0.5mg/kg/day for 6 weeks	Case Series	Clinical	Reduction in symptoms 10/12 (83%)	No controls One-year follow-up 83% asymptomatic
			OpHM during Rx	reduction in intragastric acidity (No p values)
			Gastroscopy Biopsy	9 (75%) had completely normal mucosa; 3 (25%) improved. 8 (67%) completely healed; 4 (33.%) improved
Hassal E et al, 2000, Canada, Australia, Germany, Sweden, UK, Denmark	57 children (1-16years) with erosive oesophagitis and pathologic acid reflux (pH <4 for >6% of the time). Treatment began at 0.7mg/kg/day and increased by 0.7mg/kg/day q 5-14 days to a max of 3.5mg/kg/day if pathologic reflux was still present. Treatment continued for 3 months after healing dose was determined.	Case Series (prospective)	Clinical	Reduction in symptoms 53 (93%)	21 (37%) neurologically impaired; 7 (12%) repaired esophageal atresia No treatment for patients with H pylori No long-term follow-up
			Gastroscopy	Healed 54 (98%). Median healing time 102 days

Comment(s)

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 comordities 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%. This higher relapse rates in the studies by Kato et al and DeGiacomo 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 "optimized medical management" in children. It is our opinion that in most circumstances, a trial of the new optimized medical therapy should be considered before antireflux surgery."

Clinical Bottom Line

When children with gastroesophageal 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 esophageal atresia, and neurological impairment.

Level of Evidence

Level 2 - Studies considered were neither 1 or 3.

References

1. Gunasekaran TS, Hassall EG. Efficacy and safety of omeprazole for severe gastroesophageal reflux in children. J Pediatr 1993;123(1):148-54.
2. Cucchiara S, Minella R, Iervolino C, et al. Omeprazole and high dose ranitidine in the treatment of refractory reflux oesophagitis. Arch Dis Child 1993;69(6):655-9.
3. Karjoo M, Kane R. Omeprazole treatment of children with peptic esophagitis refractory to ranitidine therapy. Arch Pediatr Adolesc Med 1995;149(3):267-71.
4. Kato S, Ebina K, Fujii K, et al. Effect of omeprazole in the treatment of refractory acid-related diseases in childhood: endoscopic healing and twenty-four-hour intragastric acidity. J Pediatr 1996;128(3):415-21.
5. De Giacomo C, Bawa P, Franceschi M, et al. Omeprazole for severe reflux esophagitis in children. J Pediatr Gastroenterol Nutr 1997;24(5):528-32.
6. Alliet P, Raes M, Bruneel E, et al. Omeprazole in infants with cimetidine-resistant peptic esophagitis. J Pediatr 1998;132(2):352-4.
7. Hassall E, Israel D, Shepherd R, et al. Omeprazole for treatment of chronic erosive esophagitis in children: a multicenter study of efficacy, safety, tolerability and dose requirements. International Pediatric Omeprazole Study Group. J Pediatr 2000;137(6):800-7.