Tobias G. Wenzl

Association of apnea and nonacid gastroesophageal reflux in infants: Investigations with the intraluminal impedance technique*

An association of apnea and gastroesophageal reflux (GER) was proposed previously. However, pH metry as the standard diagnostic tool for GER only measures acid reflux (pH < 4). It is difficult to interpret studies in infants with a presumed association between apnea and GER based on pH metry because the buffering effect of feeding may result in predominantly nonacid GER. The aim of this study was to investigate the temporal association of apnea and GER with the pH‐independent intraluminal impedance technique (IMP). Infants with recurrent regurgitation or respiratory symptoms suggestive of apnea were investigated simultaneously with IMP, pH monitoring, and polygraphy. IMP patterns, pH, oronasal flow, and chest wall movement were recorded and analyzed.

Esophageal pH monitoring and impedance measurement: a comparison of two diagnostic tests for gastroesophageal reflux.

Background pH monitoring is the standard diagnostic tool for gastroesophageal reflux in infants. However, this method does not document the reflux of all kinds of fluid from the stomach into the esophagus, but only documents acid material. The parameters that define reflux episodes by pH monitoring have been derived empirically from observations of many infants considered healthy and ill. Acid reflux is a continuum, some reflux is normal and doubt exists as to how much reflux is abnormal. In this study, one of the standardized protocols for analyzing pH recordings was evaluated and compared with simultaneously obtained intraesophageal impedance measurement (IMP), a pH-independent method of detecting bolus movement within the esophagus. Methods The esophagi of 50 infants with reflux symptoms were measured, using both standard pH probe and multiple-site impedance measurement. A standard protocol for analyzing esophageal pH records was used. The sampling rate for pH values was 15/min. Acid reflux was defined as pH less than 4.0 (threshold pH) for at least 15 seconds (minimal duration) with at least 30 seconds (latency time) between separate episodes. The software used could adjust independently or in combinations the sampling rate and these reflux criteria. Thereby it was determined whether changes in the criteria for acid reflux improved the sensitivity and predictive value of pH monitoring when compared with reflux episodes defined by IMP. Results During 318 hours of recording in 50 infants, 1,887 episodes of reflux occurred according to IMP. Only 282 (14.9%) of the IMP-determined episodes were acid reflux episodes. No alkaline reflux episodes occurred. Among the 270 pH probe–determined episodes using the standard criteria of acid reflux, only 153 (sensitivity, 54.3%; positive predictive value, 56.7%) were accompanied by unmistakable retrograde bolus movement using IMP measurements. Retrograde bolus movement did not accompany the other 117 episodes. Using a sampling rate of 15/min, a pH threshold of 4.0, a minimal duration of reflux episodes of 8 seconds, and a latency time of 60 seconds, the positive predictive value of pH probe results increased to 60.7%. Variations in the sampling rate or criteria for defining acid reflux did not significantly improve the accuracy of the pH probe results versus IMP-defined episodes. Conclusions Most reflux episodes that occur in infants are undetectable by standard pH probe monitoring. pH monitoring does not detect all reflux in the esophagus but is useful for detecting acidity in the esophagus and determining the duration of its presence. Combining pH monitoring with impedance measurement is a valuable diagnostic tool for gastroesophageal reflux in infants.

Gastroesophageal reflux and respiratory phenomena in infants: status of the intraluminal impedance technique.

BACKGROUND The coincidence of recurrent respiratory symptoms and gastroesophageal reflux (GER) is a well-known phenomenon in infants. Twenty-four-hour pH metry is the presumed gold standard of diagnostic tools for this symptom complex, but with this method, only acid (pH <4) and alkaline (pH >7) GER can be detected. Gastroesophageal reflux with an esophageal pH in the physiological range (pH 5-6.8) may represent many cases of clinically relevant GER unrecognized by pH metry. In this study the intraluminal multiple electrical impedance (IMP) procedure for complete registration of GER was compared with pH metry for its diagnostic value in the presence of respiratory symptoms. METHODS Twenty-two infants with recurrent regurgitation or pulmonary problems were investigated simultaneously with IMP, pH metry, and polygraphy during two feeding periods. Heart rate, oxygen saturation, sleep states, and oronasal flow were recorded, among other parameters. RESULTS Three hundred sixty-four occurrences of GER were detected by IMP; only 11.4% had a pH less than 4 and were therefore recognized by pH metry. Three hundred twelve (84.8%) occurrences were associated with breathing abnormalities, and 11.9% of these were detected by pH metry. Nineteen instances were accompanied by a decrease of oxygen saturation of more than 10% of the initial value. Only three (15.8%) of these had a pH less than 4. The remaining 16 reflux episodes were recognized by IMP only. After software-aided preselection, 165 instances of apnea were visually validated, 49 of which were accompanied by GER. Thirty-eight (77.6%) of these were exclusively recorded by IMP. CONCLUSIONS The use of pH metry alone cannot detect most GER incidents accompanied by respiratory symptoms and therefore does not appear to be suitable for this approach. The pH-independent IMP technique promises to be a reliable tool for presumably GER-associated respiratory symptoms.

Investigating esophageal reflux with the intraluminal impedance technique.

Various methods for using epigastric (1) and intraluminal (2,3) impedance to describe gastroesophageal motility have been reported, but have not been established as standard clinical diagnostic procedures. The aim of this article is to illustrate a new application of impedance monitoring and to review the current literature, evaluating the potential and limitations of this technique with special emphasis on the pediatric patient.

Detection of Gastroesophageal Reflux in Children Using Combined Multichannel Intraluminal Impedance and pH Measurement: Data from the German Pediatric Impedance Group

OBJECTIVE To validate the use of combined multichannel intraluminal impedance (MII)-pH (MII-pH) monitoring for detecting gastroesophageal reflux (GER) in children in daily clinical practice. STUDY DESIGN The patients were divided into 3 symptom groups based on the main indication for the procedure. MII-pH monitoring was performed in 700 children presenting with symptoms suggestive of GER, including 329 children with pulmonary symptoms, 325 with gastrointestinal symptoms, and 46 with neurologic symptoms. The MII-pH results were compared with pH monitoring alone, and retrograde bolus movements, symptom index, and symptom association probability were compared. RESULTS Overall, 270 measurements were abnormal: 101 (37%) showed abnormal MII-pH study, 49 (18%) showed only pathological pH measurements and 120 measurements (45%) had an abnormal MII recording only. Extraintestinal symptoms of GER were seen more often in younger children and were more often related to a normal pH study but an abnormal MII study. Infants had a significantly higher number of retrograde bolus movements than older children. Symptom index and symptom association probability showed moderate agreement (Cohen kappa, 0.54). CONCLUSIONS From this large systematically standardized data collection of MII-pH measurements in children, we conclude that 45% of the patients with abnormal GER would not have been recognized by 24-hour pH measurement alone. Our findings confirm that MII-pH is superior to pH monitoring alone in detecting GER.

Efficacy and Safety of Once-Daily Esomeprazole for the Treatment of Gastroesophageal Reflux Disease in Neonatal Patients

OBJECTIVE To evaluate the efficacy and safety of proton pump inhibitors in infants aged <1 year with gastroesophageal reflux disease (GERD). STUDY DESIGN In this randomized, double-blind, placebo-controlled multicenter study, neonates (premature to 1 month corrected age; n = 52) with signs and symptoms of GERD received esomeprazole 0.5 mg/kg or placebo once daily for up to 14 days. Change from baseline in the total number of GERD symptoms (from video monitoring) and GERD-related signs (from cardiorespiratory monitoring) was assessed with simultaneous esophageal pH, impedance, cardiorespiratory, and 8-hour video monitoring. RESULTS There were no significant differences between the esomeprazole and placebo groups in the percentage change from baseline in the total number of GERD-related signs and symptoms (-14.7% vs -14.1%, respectively). Mean change from baseline in total number of reflux episodes was not significantly different between esomeprazole and placebo (-7.43 vs -0.2, respectively); however, the percentage of time pH was <4.0 and the number of acidic reflux episodes >5 minutes in duration was significantly decreased with esomeprazole vs placebo (-10.7 vs 2.2 and -5.5 vs 1.0, respectively; P ≤ .0017). The number of patients with adverse events was similar between treatment groups. CONCLUSIONS Signs and symptoms of GERD traditionally attributed to acidic reflux in neonates were not significantly altered by esomeprazole treatment. Esomeprazole was well tolerated and reduced esophageal acid exposure and the number of acidic reflux events in neonates.

Effect of Gaviscon Infant on gastro-oesophageal reflux in infants assessed by combined intraluminal impedance/pH

Background: Gaviscon Infant (GI) has been recommended for gastro-oesophageal reflux (GOR) in infants. Its efficacy has not been examined with a physiologically appropriate denominator to define the degree of GOR. Aim: To investigate the influence of Gaviscon Infant on GOR in infants using combined pH and intraluminal impedance measurement. Methods: Twenty infants (mean age 163.5 days, range 34–319 days) exclusively bottle fed, with symptoms clinically suggestive of GOR, underwent 24 hour studies of intra-oesophageal 6 channel impedance and dual channel pH monitoring, during which six random administrations (3+3) of Gaviscon Infant (625 mg in 225 ml milk) or placebo (mannitol and Solvito N, 625 mg in 225 ml milk) were given in a double blind fashion. Impedance/pH reflux data were recorded and analysed blind by one observer. Results: The median number of reflux events/hour (1.58 v 1.68), acid reflux events/hour (0.26 v 0.43), minimum distal or proximal pH, total acid clearance time per hour (time with pH below pH 4), and total reflux duration per hour were not significantly different after GI than after placebo. Reflux height was marginally lower after GI (median 66.6% v 77.3% oesophageal length) compared with placebo. Conclusions: Results showed a marginal but significant difference between Gaviscon Infant and placebo in average reflux height, and raises questions regarding any perceived clinical benefit of its use.

Review article: reflux and its consequences--the laryngeal, pulmonary and oesophageal manifestations. Conference held in conjunction with the 9th International Symposium on Human Pepsin (ISHP) Kingston-upon-Hull, UK, 21-23 April 2010.

Background  Gastro‐oesophageal reflux disease (GERD) is one of the commonest diseases of Western populations, affecting 20 to 30% of adults. GERD is multifaceted and the classical oesophageal symptoms such as heartburn and regurgitation often overlap with atypical symptoms that impact upon the respiratory system and airways. This is referred to as extra‐oesophageal reflux disease (EERD), or laryngopharyngeal reflux (LPR), which manifests as chronic cough, laryngitis, hoarseness, voice disorders and asthma.

Acid and nonacid gastro-oesophageal reflux in neurologically impaired children: investigation with the multiple intraluminal impedance procedure.

Objectives: The diagnosis of gastro-oesophageal reflux (GOR) is more difficult in children with neurological impairment because symptoms are often less interpretable and frequently go undetected. The use of combined pH and multiple intraluminal impedance allows for the detection of both acid (pH < 4) and nonacid (pH > 4) GOR episodes, in addition to the height of the refluxate and the total acid and bolus clearance time in this cohort. Methods: Sixteen neurologically impaired children (9 were fed nasogastrically, 7 were fed orally) underwent 12-hour combined pH and multiple intraluminal impedance. Results: There were a total of 425 reflux episodes during the study period, of which 239 (56.2%) were nonacid. The median of reflux episodes per hour was 1.8 (range, 0.2-6.3/h). The median height of the refluxate was 1.5 channels (range, 1.1-2.9); and 71.3% of reflux episodes reached the upper oesophagus, of which 52.4% were nonacid reflux events. On average there were more GOR events (both acid and nonacid) in the children who were fed via a nasogastric tube, and the median height of refluxate was also higher in this group. However, the median acid clearance time was longer (both proximal and distal) in the children who were fed orally (28.6 s vs 16.2 s proximally; 67.9 s vs 38.3 s distally). The median acid clearance time (21.7 s proximally; 39.5 s distally) was longer when compared with bolus clearance (14.9 s). Conclusions: More than half of the reflux events in neurologically impaired children are nonacidic and would therefore go undetected by conventional pH metry. There are more reflux events in children fed nasogastrically than oral-fed children.

European pediatricians' approach to children with GER symptoms: survey of the implementation of 2009 NASPGHAN-ESPGHAN guidelines.

Objective: The aim of this study was to evaluate the current implementation of the 2009 North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition-European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines, and to assess proton pump inhibitors’ (PPIs) prescribing patterns among pediatricians from different European countries. Methods: A randomly identified sample of general pediatricians distributed across 11 European countries. They were asked to complete a case report–structured questionnaire investigating their approaches to infants, children, and adolescents with symptoms suggestive of gastroesophageal reflux. Results: A total of 567 European general pediatricians completed the study questionnaire. Only 1.8% of them showed complete adherence to the guidelines. Forty-six percent of them reported that they diagnose gastroesophageal reflux disease based on clinical symptoms irrespective of the age of the child; 39% prescribe PPIs in infants with unexplained crying and/or distressed behavior and 36% prescribe PPIs in infants with uncomplicated recurrent regurgitation and vomiting; 48% prescribed PPIs in children younger than 8 to 12 years with vomiting and heartburn, without specific testing; 45% discontinue PPI therapy abruptly rather than tapering the dose. The overall rate of pediatricians overprescribing PPIs was 82%. Conclusions: The overall results of our survey show that the majority of pediatricians are unaware of 2009 North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition-European Society for Pediatric Gastroenterology, Hepatology, and Nutrition reflux guidelines and often prescribe PPIs despite a lack of efficacy for the symptoms being treated. The overdiagnosis of gastroesophageal reflux disease places undue burden on both families and national health systems, which has not been affected by the publication of international guidelines.