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Esophageal Ph-Impedance Monitoring in Children: Position Paper On Digestive and Liver Disease 51 (2019) 1522–1536 Contents lists available at ScienceDirect Digestive and Liver Disease journal homepage: www.elsevier.com/locate/dld Position Paper Esophageal pH-impedance monitoring in children: position paper on indications, methodology and interpretation by the SIGENP working group a,b,∗ c,d e f Paolo Quitadamo , Renato Tambucci , Valentina Mancini , Fernanda Cristofori , g h f i Mariella Baldassarre , Licia Pensabene , Ruggiero Francavilla , Giovanni Di Nardo , c j j k b Tamara Caldaro , Paolo Rossi , Saverio Mallardo , Elena Maggiora , Annamaria Staiano , k l m Francesco Cresi , Silvia Salvatore , Osvaldo Borrelli a Department of Pediatrics, A.O.R.N. Santobono-Pausilipon, Naples, Italy b Department of Translational Medical Science,“Federico II”, University of Naples, Italy c Digestive Endoscopy and Surgery Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy d Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy e Department of Pediatrics and Neonatology, Saronno Hospital, Saronno, Italy f Department of Pediatrics, Giovanni XXIII Hospital, Aldo MoroUniversity of Bari, Bari, Italy g Department of Biomedical Science and Human Oncology-neonatology and Nicu section, University “Aldo Moro”, Bari, Italy h Department of Medical and Surgical Sciences, Pediatric Unit, University “Magna Graecia” of Catanzaro, Catanzaro, Italy i NESMOS Department, School of Medicine and Psychology, Sapienza University of Rome, Sant’Andrea University Hospital, Rome, Italy j Department of Pediatrics, Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Rome, Italy k Neonatology and Neonatal Intensive Care Unit, Department of Public Health and Pediatrics, University of Turin, Turin, Italy l ¨ Pediatric Department, Ospedale F. Del Ponte¨, University of Insubria, Varese, Italy m Division of Neurogastroenterology and Motility, Department of Paediatric Gastroenterology, UCL Institute ofChild Health and Great OrmondStreet Hospital, London, UK a r t i c l e i n f o a b s t r a c t Article history: Multichannel intraluminal impedance pH (MII-pH) monitoring currently represents the gold standard Received 15 May 2019 diagnostic technique for the detection of gastro-esophageal reflux (GER), since it allows to quantify and Accepted 20 July 2019 characterize all reflux events and their possible relation with symptoms. Over the last ten years, thanks Available online 13 September 2019 to its strengths and along with the publication of several clinical studies, its worldwide use has gradually increased, particularly in infants and children. Nevertheless, factors such as the limited pediatric reference Keywords: values and limited therapeutic options still weaken its current clinical impact. Through an up-to-date Gastro-esophageal reflux review of the available scientific evidence, our aim was to produce a position paper on behalf of the pH-impedance Children working group on neurogastroenterology and acid-related disorders of the Italian Society of Pediatric Infants Gastroenterology, Hepatology and Nutrition (SIGENP) on MII-pH monitoring technique, indications and interpretation in pediatric age, in order to standardise its use and to help clinicians in the diagnostic approach to children with GER symptoms. © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. 1. Introduction the detection of gastro-esophageal reflux (GER), since it allows to quantify and characterize all reflux events and their possible rela- Multichannel intraluminal impedance pH (MII-pH) monitoring tion with symptoms [1]. MII-pH monitoring provides an accurate currently represents the gold standard diagnostic technique for assessment of the number of both acid and non acid GER episodes, the acid esophageal exposure percent time, the height and com- position of the refluxate (liquid, gas, or mixed contents). It also recognizes swallows from reflux episodes, measures the bolus and On behalf of the working group on Neurogastroenterology and Acid-related Dis- acid clearance time, and assesses the temporal association between orders of the Italian Society for Pediatric Gastroenterology, Epatology, and Nutrition reflux episodes and symptoms occurring during the study period. (SIGENP) ∗ Over the last ten years, thanks to its strengths and along with the Corresponding author at: Department of Pediatrics, A.O.R.N. Santobono- Pausilipon, Via Mario Fiore 6, 80100 Naples, Italy. E-mail address: [email protected] (P. Quitadamo). https://doi.org/10.1016/j.dld.2019.07.016 1590-8658/© 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. P. Quitadamo et al. / Digestive and Liver Disease 51 (2019) 1522–1536 1523 Fig. 1. Change of impedance in 2 channels: the figure shows a reflux episode, followed by a return of impedance to the baseline. publication of several clinical studies its worldwide use has gradu- 2. Technical and methodological aspects ally increased, particularly in infants and children. Although MII-pH monitoring provides a great amount of MII-pH monitoring was first described by Silny et al. in 1991 esophageal data, yet the limited reference and normative val- for the study of esophageal motility, providing information on the ues, the lack of therapeutic choices for non acid GER and the presence of esophageal bolus movements and type of esophageal cost of the device and catheters currently reduce its clinical content (solids, liquids, gas) by changes in intraluminal electri- impact. cal conductivity [2]. The basic component of MII technology is The aim of the current paper is to present an updated summary an impedance circuit, including an alternating current generator of MII-pH monitoring technique, indications, and interpretation (located in the recording device) and multiple metal rings placed in pediatric age to help clinicians in the diagnostic approach to across a catheter, which acts as an electrical isolator. The electri- children with GER disease. Therefore, an exhaustive search for eli- cal circuit is closed by electrical charges in the esophageal mucosa gible studies was performed in MEDLINE (via PubMed), EMBASE surrounding the catheter. and Cochrane Library databases. The following headings were The test is based on the measurement of impedance (changes used: “pH monitoring technique”, “gastroesophageal reflux”, “mul- in resistance to electrical current in a circuit), which is inversely tichannel intraluminal impedance (MII) pH monitoring technique”. correlated to the ionic concentration of luminal content. A liquid Proper Boolean operators “AND” “OR” were also included to be bolus with a high ionic content (e.g. swallows, refluxate) has a high as comprehensive as possible. English language restriction was conductivity and therefore a low impedance measure, whilst in the applied while geographical restrictions were not. All relevant arti- presence of air the content of ions is low, resulting in a poor conduc- cles detected were further scrutinized for additional references tivity and hence a high impedance. At rest, in an empty esophagus, which did not appear in the initial search. Search limits were set the conductivity and the so called baseline impedance are stable, for studies on human subjects published between January 1990 and ranging between 2000 and 4000 ohm. When a liquid bolus enters December 2018. When the scientific evidence was lacking, the rec- the esophagus, the impedance rapidly drops and remains low as comendations were formulated according to the authors’ personal long as the bolus lies between the 2 electrodes, then raises and experience. returns to the baseline values once the bolus has passed (Fig. 1). 1524 P. Quitadamo et al. / Digestive and Liver Disease 51 (2019) 1522–1536 Fig. 2. Reflux episode followed by a swallow. In the presence of a gas bolus, a typical impedance spike above impedance channels, as every channel is created by two consec- 5000 ohm is observed. utive rings/sensors. Various age (height)-appropriate impedance The presence of multiple channels on the same catheter allows catheters are available: infant (height <75 cm), pediatric (height the measurement of sequential transitory impedance changes >75 cm and <150 cm), and adult (height >150 cm) type. The probes (drop or rise) involving consecutive channels, determines the direc- differ for the spacing between the impedance rings and the posi- tion of bolus flow, and hence allows to discriminate between tion of the pH sensor. In infant catheters, the space between two antegrade flow (swallow) from retrograde movement from the electrodes is 1.5 cm, whist in pediatric and adult catheters the dis- stomach (reflux) as well as the esophageal location (height) of the tance is 2 cm due to the increased esophageal length. Combined refluxate. Combining MII with pH monitoring enables the identifi- MII-pH and (simplified) manometry catheters have been devel- cation and classification of acidic (pH < 4), weakly acidic (pH 4–7) oped and may provide important additional information in selected and weakly alkaline (pH > 7) episodes (Fig. 2). patients (e.g. children with chronic cough or candidates to anti- reflux surgery). 3. The recording device 5. pH electrodes Many ambulatory and stationary devices from different brands are now available and used in children of all ages. Portable ambu- MII-pH catheters include 1 or 2 pH electrodes (for proximal latory devices are very small and allow recording during normal and distal esophagus, esophageal
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