Nocturnal acid breakthrough in children with reflux esophagitis taking proton pump inhibitors

OBJECTIVES: We aimed to determine if nocturnal acid breakthrough occurs in children receiving proton pump inhibitors for reflux esophagitis, and to compare the healing of esophagitis in children with nocturnal acid breakthrough receiving proton pump inhibitors +/- ranitidine. METHODS: This is a prospective, double-blind study. Endoscopic and histologic esophagitis were scored 0-4 and 0-3, respectively. Patients were treated with a proton pump inhibitor twice daily and esophagogastric pH monitoring was performed at week 3. Patients with nocturnal acid breakthrough were randomized. One group received ranitidine and the other received placebo at bedtime in addition to proton pump inhibitor therapy. Endoscopy was performed on all patients (with pH monitoring on patients with nocturnal acid breakthrough) during the 17th week of therapy. RESULTS: We enrolled 18 patients, ages 1 to 13 years (mean = 10.3 years). Mean baseline endoscopic and histologic scores were 3.1 +/- 1.4 and 1.8 +/- 0.7, respectively. Mean dose of proton pump inhibitor was 1.3 mg/kg +/- 0.6. Nocturnal acid breakthrough was documented in 16/18 (89%) patients. Seven patients received ranitidine and 9 received placebo. The reflux index improved: mean of 14.3 at baseline, 2.0 at week 3 (P = 0.0001), and 5.1 at week 17 (P = 0.09). Nocturnal acid breakthrough persisted in 9/12 (75%) patients, 3 of whom received ranitidine at bedtime. Esophagitis improved in all patients following therapy: mean endoscopy and histology scores were 1.6 +/- 1.8 (P = 0.0020) and 0.8 +/- 0.9 (P = 0.0013), respectively. Symptoms significantly improved from a mean score of 2.0 at baseline to 0.4 at week 17 (P = 0.0001). CONCLUSIONS: Nocturnal acid breakthrough is common in pediatric patients treated with proton pump inhibitors. Reflux index remains normal in spite of nocturnal acid breakthrough. Symptoms and esophagitis continued to improve during therapy in spite of nocturnal acid breakthrough. There appears to be no additional benefit to supplementation with ranitidine at bedtime.     

Pharmacologic efficacy of sodium alginate suspension on gastro-esophageal reflux in infants and children

Eighty-three children presenting with symptomatic gastro-esophageal reflux (GER) (48 males, 35 females, aged 15 days to 57 months (mean = 7 months) were assessed by pH monitoring. All showed acid pathological GER on the 3 hours post-prandial esophageal pH measurement (% of time at pH less than 4 greater than 4.2) and all had a second pH measurement within the following 3 hours after intake of a single (5 ml) dose of sodium alginate (AGS). AGS administration was followed by a highly significant reduction (p less than 0.00001) of all pH measurement variables: a) Percentage of time spent at pH less than 4 returned to normal with a mean 11.7% to 4.8%; that is a 52.5% improvement (median); b) Total number of reflux reduced on average from 8.9 to 5.0: that is a 35% improvement (median); c) Mean duration of reflux reduced on average for 4 to 2 min; that is a 60% improvement (median). In 76 patients hourly monitoring of % of time spent at pH less than 4 shows that hourly improvement persists.     

Esophageal motor activity in children with gastro-esophageal reflux disease and esophagitis

OBJECTIVE: To evaluate esophageal body motor contractions occurring during esophageal reflux in pediatric patients with gastro-esophageal reflux disease (GERD). METHODS: Patients referred for the evaluation of GERD who were evaluated with combined 24-hour pH probe and esophageal manometry test (MP24) were included. Patients were separated into the following groups: Group C -- normal pH probe and normal EGD; Group 1 -- abnormal pH probe and normal EGD; and Group 2 -- abnormal pH probe and EGD with histologic esophagitis. Esophageal motor function during reflux episodes was analyzed. RESULTS: Twenty-five patients were included. All had a normal stationary esophageal manometry. Patients in Groups 1 and 2 had significantly more gastroesophageal reflux by pH probe than Group C (P < 0.01). During the MP24, patients in Group 1 and 2 had significantly fewer contractions per minute pre-, during, and post-GER (P < 0.05). There were significant differences in the number of isolated and prolonged contractions (>7 sec) during prolonged GERD episodes >5 minutes (P < 0.05). CONCLUSION: Children with GERD have a decreased number and abnormal esophageal body contractions with esophageal reflux. This suggests that children with GERD with and without esophagitis have impaired esophageal body acid clearance.     

Long-term outcome and need of re-operation in gastro-esophageal reflux surgery in children

Background

Fundoplication is considered a mainstay in the treatment of gastro-esophageal reflux. However, the literature reports significant recurrences and limited data on long-term outcome.

Aims

To evaluate our long-term outcomes of antireflux surgery in children and to assess the results of redo surgery.

Methods

We retrospectively analyzed all patients who underwent Nissen fundoplication in 8 consecutive years. Reiterative surgery was indicated only in case of symptoms and anatomical alterations. A follow-up study was carried out to analyzed outcome and patients’ Visick score assessed parents’ perspective.

Results

Overall 162 children were included for 179 procedures in total. Median age at first intervention was 43 months. Comorbidities were 119 (73 %), particularly neurological impairments (73 %). Redo surgery is equal to 14 % (25/179). Comorbidities were risk factors to Nissen failure (p = 0.04), especially children suffering neurological impairment with seizures (p = 0.034). Follow-up datasets were obtained for 111/162 = 69 % (median time: 51 months). Parents’ perspectives were excellent or good in 85 %.

Conclusions

A significant positive impact of redo Nissen intervention on the patient’s outcome was highlighted; antireflux surgery is useful and advantageous in children and their caregivers. Children with neurological impairment affected by seizures represent significant risk factors.

     

Extensively hydrolyzed protein formula reduces acid gastro-esophageal reflux in symptomatic preterm infants

Background

Gastro-esophageal reflux (GER) is diagnosed frequently in preterm infants. Pharmacological treatment of GER has some potential side effects. Conservative treatment of GER should be the first-line approach and should include body positioning and diet modifications.Formula-fed preterm infants experience frequently symptoms of feeding intolerance. Hydrolyzed protein formula (HPF) is often used in these infants due to their effects on gastrointestinal motility.

Aims

To investigate the role of an extensively HPF (eHPF) on GER indexes in formula-fed preterm infants with symptoms of both GER and feeding intolerance.

Study design

Randomized crossover trial

Subjects

Preterm infants (gestational age ≤ 33 weeks) with symptoms of feeding intolerance (large gastric residuals, abdominal distension and constipation) and GER (frequent regurgitations and/or postprandial desaturations).

Outcome measures

GER indexes detected by 24-h combined multichannel intraluminal impedance and pH monitoring. GER indexes detected after 4 feeds of an eHPF were compared to those detected after 4 feeds of a standard preterm formula (SPF) by Wilcoxon signed ranks test. A p < 0.05 was considered statistically significant.

Results

eHPF significantly reduced the number of GERs detected by pH monitoring (p = 0.036) and also the reflux index (p = 0.044) compared to SPF. No differences in impedance bolus exposure indexes nor in GER height were detected.

Conclusions

The use of an eHPF should be evaluated for reducing esophageal acid exposure in preterm infants with feeding intolerance and symptoms of GER. Future research should focus on the evaluation of an eHPF adequate for preterm infants in improving clinical symptoms of GER.     

Role of surgical treatment of gastro-esophageal reflux in children with severe asthma]

The relationship between gastro-esophageal reflux (GER) and asthma, and the role of treatment of this disorder in severe asthma cases remain ill-defined. Using esophageal pH monitoring, pathological GER was demonstrated in 57 of 139 children with severe asthma. Among these 57 patients medical treatment of GER lessened the respiratory symptoms in 24 and was without effect in 33. In the latter group, asthma was improved in 29 with surgical treatment of the GER, the results being less satisfactory in those patients without GER digestive symptoms. Our results suggest that there is a place for treatment of GER in selected children with severe asthma. Esophageal pH monitoring appears useful to detect pathological GER and to determine which patients may benefit from surgical treatment.     

小儿胃酸反流与反流性食管炎的关系

目的探讨胃酸反流与小儿反流性食管炎（RE）发病的关系。方法对180例以呕吐为主要临床表现的患儿进行食管动态pH监测和胃镜检查,观察本组病例中RE、非食管炎（NE）、非糜烂性反流病（NERD）及其反流情况。RE分级参照《全国反流性食管炎研讨会》制定的内镜分级标准。结果180例息儿中诊断为RE的有65例（36．1％）,其中Ⅰ、Ⅱ、Ⅲ级分别有37例、19例和9例;诊断为NE的有115例。RE组病理性胃食管反流（GER）检出率为58．5％（38／65）,NE组为42．6％（49／115）,差异有统计学意义（r=4．179,P〈0．05）。RE组各项酸反流指标均大于NE组,除反流次数和反流〉5min的次数外,差异均有统计学意义（P〈0．05）。Ⅰ、Ⅱ级RE患儿之间各项酸反流指标的差异均无统计学意义;Ⅲ级RE患儿的各项酸反流指标均大于Ⅰ级和Ⅱ级,但除Boix-Ochoa综合评分外差异均无统计学意义。180例患儿中病理性GER有87例（占48．3％）,其中38例为Iu巳。49例为非糜烂性反流病（NERD）,两组间各项酸反流指标的差异无统计学意义（P均〉0．05）。结论胃酸反流在小儿RE的发病中起着重要的作用,但并不是惟一的致病因素;酸反流的程度与RE的严重性之间并无严格的对应关系;酸反流并不都会引起RE。要加强对有反流症状患儿的内镜检杏。     

Overview of pediatric gastroesophageal reflux disease and proton pump inhibitor therapy

Symptoms of gastroesophageal reflux disease (GERD) are prevalent in children of all ages. Despite limited clinical data, proton pump inhibitors (PPIs) are frequently prescribed in pediatric patients. Studies are needed to determine the natural history of GERD, to assess its impact on the quality of life of affected children, and to identify risk groups in infancy and childhood. There is a critical need to evaluate PPI efficacy and safety in infants and children.     

The surgical treatment of gastro-esophageal reflux in neonates and infants

Gastro-esophageal reflux (GER) is a physiological process characterized by the involuntary passage of gastric contents into the lower esophagus not induced by noxious stimuli. It represents a common condition in preterm infants and may occur in healthy neonates. The phenomenon is only considered as GER disease when it causes the patient to be symptomatic or results in pathological complications. Fundoplication is recommended in symptomatic neonates and infants with GER that does not respond to medical treatment. The presence of respiratory symptoms related to GER is the primary indication for fundoplication in this selected population. The Nissen fundoplication is the antireflux procedure of choice and the experience concerning other procedures, including laparoscopic techniques, is limited in this age group. The best results are achieved in newborn infants with isolated GER, as the recurrence rate of GER in infants with associated anomalies is high. Further studies are necessary to evaluate the benefit of laparoscopic fundoplication in this age group.     

Pharmacologic control of gastro-esophageal reflux in infants with cisapride

Autonomic receptors in the upper gastro-intestinal tract permit pharmacologic manipulation of esophageal and gastric function. A new non-anti-dopaminergic, non-cholinergic, prokinetic agent, cisapride, was evaluated to determine it's efficacy in controlling gastro-esophageal reflux (GER) in infancy. Forty infants, mean age 6.5 months, were studied and their response to therapy determined by continuous measurement of lower esophageal pH over a 36-hour period. Five parameters were assessed in the erect, supine, and prone positions, both before and during short-term cisapride therapy. The drug was effective in reducing GER in 86% of the infants studied. Those infants who had a poor overall response to therapy could be identified retrospectively by the lack of improvement in esophageal acid clearance and frequency of reflux episodes; anatomic abnormalities were present in the majority of this subgroup. Cisapride is considered to be effective in the short-term treatment of primary GER of infancy, and a more prolonged assessment is indicated. Offprint requests to: H. Rode     

Bile and acid reflux in the pathogenesis of reflux oesophagitis in children

Aim:   The aim of this study was to investigate the role of bile and acid reflux in the pathogenesis of reflux oesophagitis (RE) in children.
Methods:   A total of 44 patients aged 5–17 years with gastro-oesophageal reflux symptoms were enrolled. Simultaneous 24-h oesophageal Bilitec 2000 (Medtronic Instruments, Minneapolis, MN, USA) bilirubin monitoring and pH monitoring, in biopsy of oesophageal mucosa by gastro-endoscopy, were performed in all patients.
Results:   According to the diagnostic criteria of pathological acid reflux and pathological bile reflux, 10 of 44 cases (22.7%) had acid reflux, 10 (22.7%) had isolated bile reflux, 16 (36.4%) had mixed acid and bile reflux, and the other eight (18.2%) had no reflux. Significant difference was observed in the ratio of different patterns of reflux between the RE group (26 cases) and the non-erosive reflux disease (NERD) group (18 cases) (χ² = 9.096, P  < 0.01). All the parameters of acid reflux in the RE group were higher significantly than that in the NERD group ( P  < 0.05 or P  < 0.01). A total of 20 out of 26 cases (76.9%) with RE had oesophageal acid reflux as against six out of 18 cases (33.3%) in patients with NERD ( P  < 0.01). The difference of each parameter of bile reflux had not reached significance between the two groups.
Conclusions:   Mixed reflux is the predominant form of reflux in the causation of oesophageal mucosal injury in children. Isolated bile reflux also plays a role in the development of RE, although only in patients without acid reflux.     

儿童非糜烂性反流病与反流性食管炎症状及酸反流比较

目的比较非糜烂性反流病（NERD）与反流性食管炎（RE）临床症状及食管酸暴露特点。方法将127例胃食管反流病（GERD）患儿根据内镜检查结果分为NERD组和RE组,分别对两组的临床症状及食管24hpH值监测结果进行比较。结果127例中NERD79例（62.2%）,RE48例（37.8%）,RE组Ⅰ、Ⅱ、Ⅲ级分别为34、10和4例。NERD组和RE组pH监测阳性者分别为51例（64.6%）和30例（62.5%）,两组阳性率差异无统计学意义（χ^2=0.05,P〉0.05）。NERD组呕吐/反食、腹痛及食管外症状的发生率较RE组高,差异有统计学意义（P〈0.05）,而反酸、烧心/胸骨后痛的发生率两组差异无统计学意义（P〉0.05）。RE组总反流次数及pH值〈4的百分比显著高于NERD组（P〈0.05）;pH值监测阳性的RE组各项酸反流指标均大于pH监测阳性的NERD组,差异均有统计学意义（P〈0.05）;Ⅰ级、Ⅱ级和Ⅲ级RE患儿之间的各项pH监测指标差异无统计学意义（P〉0.05）。结论儿童NERD患者的不典型反流症状和食管外症状发生率更高。GERD的发生与胃酸反流密切相关,酸暴露持续时间延长及反流频率增加可能是导致RE的重要因素,酸反流量与RE的严重程度无明确关系。     

Efficacy and safety measurements of proton pump inhibitors in infants and children

The design of studies to evaluate the efficacy of acid-lowering drugs in children differs significantly from study designs in adult populations. Efficacy measurements may be less extensive than those used in adult studies because of limitations that exist secondary to concerns for patient safety, parental and institutional review board acceptance of efficacy end points, and existing standards of care within the pediatric gastroenterology community. Study designs involving patients who would routinely receive acid-lowering therapy have been successfully used to characterize the pharmacokinetics and pharmacodynamics of acid-lowering therapies (H2 receptor antagonists) and have led to pediatric labeling for these drugs. This approach may likewise be used in the study of newer acid-lowering agents, such as proton pump inhibitors.     

Correlation between gastric acid secretion and severity of acid reflux in children

The purpose of our study was to systematically evaluate gastric acid output in children with long-lasting gastro-esophageal reflux (GER) in order to assess its mechanism and the need for anti-acid treatment. The investigation was carried out in 20 males and 10 females, aged 7.5 +/- 3.8 years, with prolonged (>15 months) clinical manifestations of GER. All underwent routine ambulatory 24-h esophageal pH-monitoring and measurement of gastric acid secretion including gastric basal (BAO) (micromol/kg/h), maximal (MAO) and peak acid outputs (PAO) after pentagastrin (6 microg/kg sec) stimulation. Children with heartburn or abdominal pain underwent upper fiber-endoscopy. In group A (moderate GER, n=12), patients had a normal reflux index (pH<4 below 5.2% of total recording time) despite abnormal Euler and Byrne scoring (median 57, 95% confidence interval 53.5-73.4). In group B (severe GER, n=18, among whom 5 were with grade III esophagitis), reflux index was >5.2%. When considering all children, esophageal pH (%) was significantly correlated with MAO and PAO, r=0.33, p=0.05 and r=0.37, p=0.04, respectively. Children of group B exhibited significantly higher BAO (75, 53.96-137.81), MAO (468, 394.1-671.3) and PAO (617, 518.8-782.3) than those of group A, BAO (27, 10.8-38.5), MAO (266, 243.2-348.2) and PAO (387, 322.5-452.7), p<0.05). The five children of group B with severe esophagitis exhibited significantly higher BAO, MAO and PAO than the other 13 children from the same group and those of group A, p<0.05. Children with long-lasting and severe GER hyper-secrete gastric acid. Individual variations in gastric acid secretion probably account for variations in gastric acid inhibitor requirements. Anti-secretory treatment is justified in children with long-lasting GER and high pH-metric reflux index.     

小儿食管裂孔疝时的酸反流分析

目的 了解小儿食管裂孔疝（ＨＨ）时的酸反流情况及不同类型疝的酸反流特点。方法对３５例经钡餐造影诊的ＨＨ患儿作２４ｈ食管下端ＰＨ值监测,其中滑动型１８例,食管旁型８例、混合型９例,１６例健康儿作为对照组。结果 ＨＨ患儿各项反流指标明显大于对照组,差异有显著性,以Ｂｏｉｘ－Ｏｃｈｏａ综合评分为标准,３５例ＨＨ患儿中３３例为病理性胃酸反流,占９４％;另２例为重量性反流,其中１例为食管旁型,１例为混合型。