INVITED ARTICLE

https://doi.org/10.5005/jp-journals-11009-0131
Annals of Pediatric Gastroenterology and Hepatology ISPGHAN
Volume 5 | Issue 2 | Year 2023

Multichannel Intraluminal Impedance with pH-metry in Children

Sakshi Karkra

Department of Paediatric Gastroenterology & Hepatology, Artemis Hospital, Gurugram, Haryana, India

Corresponding Author: Sakshi Karkra, Department of Paediatric Gastroenterology & Hepatology, Artemis Hospital, Gurugram, Haryana, India, Phone: +91 9971018789, e-mail: sakshikarkra@hotmail.com

Received on: 04 February 2023; Accepted on: 03 May 2023; Published on: 07 July 2023

ABSTRACT

Various diagnostic methods have been designed and developed over the years to discriminate between physiologic and pathologic gastroesophageal reflux. Though pH-metry has been used for years, its benefits and limitations became clearer with time and newer diagnostic techniques like wireless methods (Bravo pH capsule), pharyngeal probes, and multichannel intraluminal impedance with pH (MII-pH) to measure both acid and nonacid reflux (NAR) were introduced. Evidence indicates that MII-pH seems to be the new gold standard for the evaluation of patients with extraesophageal symptoms of suspected gastroesophageal reflux disease (GERD) or in patients with persistent symptoms despite acid suppression therapy however the lack of true pediatric normal reference values and limited therapeutic options for NAR is a major issue. The technique to perform MII-pH-metry has been described in this article.

How to cite this article: Karkra S. Multichannel Intraluminal Impedance with pH-metry in Children. Ann Pediatr Gastroenterol Hepatol 2023;5(2):27-35.

Source of support: Nil

Conflict of interest: None

Keywords: Gastroesophageal reflux disease, Impedance, Nonerosive reflux disease, Pediatric, Ph-metry, Reflux index.

Over the years, a range of diagnostic techniques has been developed to identify gastroesophageal reflux, both physiological and pathological. In 1969, the introduction of a pH electrode marked the initial step in detecting acid reflux in the distal esophagus. However, as time progressed, the advantages and limitations of this method became clearer. Subsequently, newer techniques emerged, such as wireless methods like the Bravo pH capsule, pharyngeal probes, and multichannel intraluminal impedance with pH (MII-pH), enabling the measurement of both acid and nonacid reflux. Although pH and MII-pH monitoring share similarities in indications, preparation, equipment, probe positioning, and recording conditions, the specific aspects of each technique will be addressed separately.

MULTICHANNEL INTRALUMINAL IMPEDANCE WITH PH (MII-PH)

The working principle of multichannel intraluminal impedance with pH (MII-pH) is based on the utilization of multiple sensors located in the esophagus to measure both pH changes and resistance to flow. The MII-pH system relies on the completion of a circuit between two impedance sensors through the flow of current either through the esophageal wall or the contents within the esophagus. When liquids are present, they cause a decrease in resistance or impedance, while the presence of air increases the resistance or impedance.

(MII-pH) monitoring requires a recording device, probes, software, buffer solutions, and additional tools like polysomnography or electroencephalography if necessary.
Traditionally, seven impedance sensors are placed in series along the esophagus, generating six impedance waves that correspond to each pair of adjacent sensors (Fig. 1).
(MII-pH) probes are chosen based on age or height categories—newborn (height <75 cm), pediatric (height 75–150 cm), and adult (height >150 cm). The MII-pH probe has a diameter of 2.13 mm (6.4 Fr).
The spacing between sensors varies depending on the catheter’s size. For newborns (0–2 years), the spacing is 1.5 cm, and a pH sensor is positioned in the middle of the furthest impedance channel. For pediatric patients (2–10 years) and adults (over 10 years), the electrode Spacing is 2 cm, and the pH sensor is placed at the center of the channel, Just Proximal to the distal impedance channel.
The reference electrode can either be integrated into the esophageal probe (internal reference) or placed outside the esophagus (external reference).
Before each study, the pH sensor undergoes calibration using two distinct pH buffer solutions. In the case of an external reference electrode, it should be attached to the finger, and both the finger and the sensor should be immersed in the buffer solution simultaneously. This calibration step is not necessary for internal reference probes.
The inclusion of a distal pH sensor in the catheter allows for the assessment of the acidity level of the fluid passing through it. Based on the pH value, it can classify the refluxate as acidic (<4), weakly acidic,⁴^,⁷ or nonacidic (>7). The sensors in the catheter can identify the direction of flow to distinguish reflux events from swallows. It can also determine whether the refluxate is liquid, gas, or a mixed event (Fig. 2).
The utilization of multiple sensors distributed throughout the esophagus enables precise estimation of refluxate height during MII-pH monitoring.
The MII-pH catheter has the capability to detect both acidic and nonacidic reflux (NAR), making it suitable for conducting studies with or without acid suppression therapy. However, studies conducted on adults indicate that symptom correlation may be enhanced if medications are discontinued prior to testing.
Children who receive enteral feeding through continuous or bolus regimens can be accurately evaluated only through MII-pH monitoring. This is because a significant portion of their reflux episodes are nonacidic due to the buffering effect of the feeding process.
While MII-pH monitoring provides valuable insights into reflux episodes, it does not directly determine mucosal complications such as esophagitis, stenosis, or Barrett’s esophagus. Therefore, consideration should be given to performing upper endoscopy in cases where these complications are suspected.

Fig. 1: Impedance channels, pH sensor placement, and the graphs (adopted and modified from J Pediatr 2018)

Fig. 2: Impedance tracings showing retrograde bolus flow and mixed swallow

Indications for Combined MII-pH Monitoring [(NICE, European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN), and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN)]³

These are similar to pH monitoring and are:

Infantile nonepileptic seizure-like events—Sandifer’s syndrome⁴
In cases of persistent unexplained crying despite conservative treatment.
When encountering an infant with failure to thrive who refuses to feed and no other diagnosis has been identified.
Prior to initiating acid-suppressive therapy in infants.

Unexplained respiratory symptoms, such as:

Recurrent infantile apnea or oxygen desaturations.⁵^,⁶
Idiopathic acute life-threatening events.
Recurrent aspiration pneumonia.
Chronic or recurrent cough.⁷
Chronic laryngeal disorders.⁸
Feeding disorders/dental erosions in children with neuro disability.
Esophageal surgical conditions (assessment pre and postsurgery).⁹^,¹⁰
Evaluation of preadolescent children with unreliable gastroesophageal reflux disease (GERD).¹¹
In order to evaluate the effectiveness of antireflux medications in patients who do not show a response to the treatment.
For the purpose of diagnosing rumination and aerophagia, in conjunction with manometry.
When there is persistent heartburn or epigastric pain despite being on acid suppressive treatment.
Unexplained bradycardia or cardiac arrhythmia.
Recurrent otitis media.¹²

Preparation of the Patient

Accurate interpretation of the MII-pH monitoring results requires detailed clinical information about the patient’s medical treatment and diet.
Discontinuation of histamine H2 receptor antagonists (H2 blockers) and prokinetics should be done at least 72 hours before the study. Alginates should be stopped 4 hours prior to the investigation.
If the purpose of the study is to assess esophageal acid exposure off Antacid treatment for diagnostic purposes, proton pump inhibitors (PPIs) need to be discontinued for at least 2 weeks.¹³
H2 blockers or PPIs should be continued only if the study is being conducted to evaluate their effectiveness on esophageal acid exposure and determine the appropriate dosage.
Infants should fast for at least 3 hours, while children should fast for at least 6 hours before the procedure.¹³
The presence of respiratory support, associated diseases, and the use of medications that may influence GER are not absolute contraindications, but they should be carefully considered during the analysis.

Positioning of the Probe

To ensure accurate measurements, it is advised to avoid applying the gel directly on the metallic rings and pH sensor of the catheter.
Strobel’s formula is commonly employed to determine catheter length in infants and preterm infants, using the length from the nares to the lower esophageal sphincter (LES). The formula is 0.252 multiplied by the height in centimeters, plus 5. However, alternative methods may be necessary for children over 1 meter in height as this formula may not be accurate in such cases.
Manometry, although invasive and time-consuming, is the most precise technique for localizing the LES and guiding pH probe placement. However, its use is limited due to these factors and its availability.
Prior to pH probe placement, endoscopy may be required to assess the esophagus and assist in localizing the LES.
For infants and newborns, the pH sensor should be positioned on the second vertebral body above the diaphragm. In older children, it is typically placed above the third vertebra.
Depending on the type of probe used, the pH sensor should be fixed approximately 2 (for infant type), 3 (for pediatric type), or 5 cm (for adult type) above the LES.
Confirmation of proper probe positioning should be done using fluoroscopy during a respiratory cycle to ensure accurate placement.

Monitoring Conditions and Event Recording

During the continuous 24-hour monitoring period of ambulatory MII-pH testing, patients are instructed to adhere to their regular dietary habits.
To ensure accurate recordings, it is advisable to refrain from consuming extremely hot or cold food and beverages, carbonated drinks, and acidic juices, as they can potentially interfere with the catheter’s sensitivity and compromise the precision of the measurements.
Adolescents should limit their engagement in smoking and chewing gum, as these activities can increase the frequency of swallows, potentially influencing the test outcomes. It is essential to document these habits in the provided diary.
For infants and neonates, the use of pacifiers should be kept to a minimum. If pacifiers are necessary, careful examination of the tracings is recommended to avoid misinterpretation caused by continuous swallowing.
During the procedure, it is crucial to record significant details such as the start and end times of feedings, duration of each feeding, body position (supine or upright), and any symptoms experienced by the patient. These details can be documented by utilizing the appropriate buttons on the recording device.
Furthermore, parents or caregivers are instructed to maintain a symptom diary where they can note down any relevant observations or symptoms observed in the patient.
Traditionally, ambulatory MII-pH monitoring is conducted for a continuous 24-hour period, with a minimum recommended monitoring time of 18 hours, as indicated by the ESPGHAN-NASPGHAN working group on gastroesophageal reflux.¹¹

DATA ANALYSIS

Data analysis is started with the automated software, but a manual reanalysis of the tracing (using a 3–5-minute time window) is mandatory to confirm/modify, add and/or delete reflux events.¹⁵ Meal periods are excluded from the analysis.

Definition of Reflux Episodes (Table 1)

**Table 1:** Definitions and parameters in MII-pH¹⁶
Parameters	Definition	Interpretation	Note	Reference
RI (AET)	The percent time of the entire duration of the study with esophageal pH < 4.0	>7% abnormal <3% normal 3–7% indeterminate	Applicable for pH antimony-based sensor	Vandenplas JPGN 2009
GER episodes	Total number of GER episodes with bolus reaching the two most distal impedance channels	Abnormal if >100/24 Hour Abnormal if >70/24 Hour	In infants (0–12 months) In children (>12 months)	López-Alonso Pilic 2011 Mousa 2014
Proximal GER episodes	Number of GER episodes reaching the two most proximal impedance channels	44 for acid, 57 for NAR 43 for acid, 20 for NAR (95th centile)	In infants In children	Mousa 2014
BEI	The total percent time that a bolus is present in the esophagus	2.4–2.9% 1.8–2.4% (90th–95th percentile)	In infants In children	Mousa 2014
BCT	(Mean) time (seconds) needed for the retrograde bolus to be cleared from the distal esophagus	18–20 Seconds 25–32 Seconds (90th–95th percentile)	In infants In children	Mousa 2014
IB	The mean value of impedance tracing in (an empty) esophagus	1000–1500 ohms for both distal and proximal channels (3rd percentile)	< or >6 months	Salvatore 2013
SI	Percentage of symptom episodes that are related to reflux	Positive if ≥50%	Temporal window between reflux and symptoms (2 minutes)	Wenzl 2012 Omari 2011 Rosen 2018
SAP	The statistical likelihood that the patient’s symptomsare related to GER, using Fisher exact test.	Positive if ≥95% (probability that observed association occurred by chance is <5%)
SSI	Number of reflux episodes associated with symptoms/ total number of reflux episodes × 100	Positive if >10%

RI, reflux index; AET, acid exposure time; BEI, bolus exposure index; BCT, bolus clearance time; IB, mean impedance baseline; SI, symptom index; SAP, symptom association probability; SSI, Symptom Sensitivity Index

Liquid reflux in MII-pH monitoring is characterized by a decrease in impedance of <50% from the baseline value in a minimum of two distal impedance channels. This pattern can be observed in Figure 2.
Gas reflux is identified by a rapid and substantial increase in impedance, surpassing 3000 ohms, in two or more channels, with at least one channel displaying a value exceeding 7000 ohms.
Mixed liquid/gas reflux refers to the occurrence of gas reflux immediately preceding a liquid reflux event.
Proximal reflux episodes are defined by the involvement of the uppermost impedance channels, namely channel 1 and/or channel 2, in the reflux event Table 1.¹⁶

Interpretation

The evaluation and interpretation of impedance tracings in MII-pH monitoring is a labor-intensive task that is still advised to be conducted manually, even though automated analysis software is accessible.
Manual analysis continues to be considered the benchmark for identifying a correlation between symptoms and NAR. This is especially vital in situations involving esophagitis or motility disorders such as achalasia or esophageal atresia (EA), where lower impedance baselines are observed. Solely relying on automated analysis may result in an underestimation of reflux in these cases.

There are three types of reflux episodes that can be identified in MII-pH monitoring:

pH-only events, detected solely by the pH sensor without any corresponding impedance changes.
Acid reflux events were detected by both impedance and pH sensors.
Nonacid reflux (NAR) events are only detected by the impedance sensors and include weakly acidic reflux (pH 4–7) and alkaline reflux (pH > 7).

Multichannel intraluminal impedance with pH (MII-pH) monitoring may fail to report reflux events detected by the pH probe in certain cases:

pH drops associated with swallows.
Persistent pH drops below four even after bolus clearance by impedance.
pH-only episodes that represent very distal reflux not meeting impedance criteria.
When evaluating the temporal relationship between symptoms and reflux episodes, the measurement known as symptom association probability (SAP) plays a pivotal role. To establish a time association with symptoms, the conventional practice involves examining a time interval of 2 minutes preceding and following a reflux episode.
The utilization of multiple sensors in MII-pH monitoring enables the identification of full-column or proximal reflux. This capability becomes particularly significant when assessing the impact of reflux on the airways.

Normal Values

The current challenge in MII-pH monitoring is the absence of established normal pediatric values that can effectively distinguish between physiological and pathological reflux in children.

Research findings on normal values for MII-pH monitoring in infants and children have been reported in certain studies. However, it is important to note that these studies often had limited sample sizes. Additionally, in the case of preterm infants, the presence of nasogastric (NG) tubes can potentially result in inaccurately elevated values. Consequently, further extensive research is required to establish reliable and representative normal values for MII-pH monitoring specifically in the pediatric population (Table 2).

**Table 2:** Proposed normal values of MII-pH monitoring
Reference	Age	N	MII reflux episodes (n)				BEI (%)	RI (%)
Reference	Age	N	Acid	W Acid	NAR	Total	BEI (%)	RI (%)
López-Alonso¹⁷	12 days (32 wk median)	21	18 (52)	51 (98)	0	71 (100)	0.73 (1.2)	5.59 (20.1)
Mousa et al.¹⁸	Infants	46	20 (48)	32 (67)		54 (93) [100]	1.4 (2.9)
Mutalib et al.¹⁹	Children	71	14 (55)	6 (34)		21 (71) [70]	0.6 (2.4)
Cresi et al.²⁰	Neonates	46	0.83/hour	2.17/hour		3/hour	2.03
	Infants	83	0.85/hour	1.65/hour		2.7/hour	1.5
	Children	66	1.17/hour	0.74/hour		2.09/hour	1.25
Shay et al.²¹	39 years (22–62)	60	18 (59)	9 (26)	0 (1)	30 (73)	0.5 (1.4)	1.2 (6.3)
Zerbid et al.²²	35 years (18–72)	68	22 (50)	11 (33)	3 (15)	44 (75)	0.8 (2)	1.6 (5.0)

Values are presented as median (range) or median (95th percentile)

REPORTING

Patient Baseline Information

The report should include the patient’s demographic data, relevant information on medical history (underlying diseases or previous endoscopy findings), and indication for testing.
Current medications.
Feeding and delivery methods (normal, extensively hydrolyzed, or amino acid formula).

pH Parameters

The number of only-pH reflux episodes.
The number of episodes lasting over 5 minutes.
The duration of the longest episode (in minutes).
The mean acid clearance time (in seconds).
The reflux index (RI) (%).

Impedance-based Parameters

A total number of reflux events (acid, weakly acidic, and weakly alkaline).
Number and percentage of reflux episodes reaching the most proximal impedance channels.
Total bolus exposure index (%).
Median bolus clearance time (in seconds).
Symptoms association indexes.
Adjunctive parameters like baseline impedance value.

Advantages of MII-pH

Multichannel intraluminal impedance with pH (MII-pH) monitoring exhibits significantly higher sensitivity in detecting GER episodes compared to pH monitoring alone. This holds true for both extraesophageal and esophageal symptoms associated with GER (Table 3).

**Table 3:** Association between extraesophageal symptoms and NAR
Reference	Study group	Symptom	Symptom-related NAR (%)
Wenzl et al.¹⁵	Infants and children	Breathing irregularities	78%
Rosen and Nurko²³	Children (n = 28)	Respiratory symptoms	Correlation stronger with NAR
Mousa et al.¹⁸	Infants (n = 25)	Apnea/ALTE	48% of NAR (8.2% of apnea had NAR)
Magistà et al.⁶	Preterm infants	Apnea	76%

ALTE, Acute life threatening events

The utilization of MII-pH monitoring, in the absence of acid-suppressive therapy, plays a vital role in distinguishing between nonerosive reflux disease (NERD), hypersensitive esophagus, and functional heartburn. Accurate classification of patients into these distinct subgroups holds great importance as it influences the selection of appropriate medical interventions, including PPIs or neuromodulators, as well as surgical interventions.¹¹

In symptomatic patients with negative endoscopic findings, three distinct phenotypes can be identified¹¹:

Nonerosive reflux disease (NERD): Characterized by abnormal esophageal acid exposure irrespective of symptom correlation.
Esophageal hypersensitivity: Characterized by normal esophageal acid exposure but a positive correlation between symptoms and reflux episodes.
Functional heartburn: Characterized by normal acid exposure and a negative correlation between symptoms and reflux episodes.

Multichannel intraluminal impedance with pH (MII-pH) monitoring holds the potential to provide new insights into the pathophysiology of both acid and nonacid GERD and offer new parameters, such as impedance baseline, that aid in identifying children with motility or esophageal mucosal complications.

There is conflicting data regarding the role of MII-pH monitoring in predicting the outcome of fundoplication, a surgical procedure for GERD. Further research is needed to clarify its predictive value in this context.

Current Limitations

The lack of true pediatric normal reference values.
The restricted therapeutic options, particularly for NAR episodes.

SPECIAL SCENARIOS

Newborns and Small Infants

During the initial months of life, the occurrence of GER is considered a normal physiological process.
Newborns and infants between the ages of 1 and 6 months commonly experience NAR, with cardiorespiratory (CR) events often presenting as symptoms.
Timely evaluation of GER episodes is crucial to prevent unnecessary administration of antacid medications and prolonged hospital stays.
Multichannel intraluminal impedance with pH (MII-pH) monitoring is recommended when atypical or extraesophageal GER symptoms are present and do not respond to conservative or pharmacological treatment.
The comprehensive study report should include essential details such as the infant’s chronological and gestational age, feeding method (e.g., breastfeeding, bottle feeding, and NG tube), type of milk, medications that may impact GER (e.g., caffeine, steroids, and antibiotics), number of impedance channels used for analysis, and duration of the recording.
To assess the correlation between CR events (e.g., blood oxygen saturation <80%, bradycardia with heart rate <80 beats/minute, apnea >20 seconds or >5 seconds followed by desaturation or bradycardia) and GER events, a time window of 30 seconds is recommended for accurate evaluation.²⁴
The high frequency and longer duration of GER events observed in newborns can be attributed to frequent feedings, the buffering effect of milk, and the immaturity of esophageal and gastric motility.

Patients on Enteral Feeding

Research has demonstrated that the presence of an NG tube increases postprandial reflux by approximately 70%.²⁵ This finding can be attributed to two possible explanations—firstly, the stiff tube may keep the esophagogastric junction open, allowing for increased reflux; secondly, the NG tube may interfere with esophageal clearance, leading to impaired removal of refluxed contents.

Patients on GER Treatment

Ambulatory 24-hour pH monitoring is typically conducted after discontinuing acid-suppressive therapy for a few days. This is because the test primarily detects acid reflux episodes and may not capture NAR events.

When the objective is to assess the effectiveness of therapy in patients with persistent symptoms, pH monitoring should be performed while the patient is on acid suppression. This helps evaluate the potential ineffectiveness of medications or the contribution of NAR to symptom development.

If the goal is to evaluate the frequency, severity, and pH characteristics of reflux events, pH monitoring should be conducted prior to initiating acid suppressive therapy.

In cases where MII-pH monitoring is indicated, PPIs should be gradually discontinued at least 2 weeks before the procedure.

Patients with Neurological Impairment

Impedance measurements with or without manometry give valuable information in assessing the aspiration risk by detecting altered pharyngeal swallow in cerebral palsy.²⁶

PATIENTS WITH SURGICAL CONDITIONS

Esophageal Atresia (EA)

Low baseline impedance, often associated with abnormal esophageal motility is typical of this cohort of subjects, thus manual review is advised to avoid underreporting.
According to international guidelines, all EA patients have to be treated with PPIs up to the 1st year of life or longer, due to the high prevalence of GER.

Lung Transplantation

Multichannel intraluminal impedance with pH (MII-pH) monitoring can be routinely used to diagnose motility abnormalities and abnormal acid/NAR in the evaluation of lung transplant recipients who develop a decline in forced expiratory volume in 1 second (<90% of baseline) consistent with the onset of bronchiolitis obliterans syndrome.²⁷
If GERD is confirmed, the patient should be referred for potential fundoplication.

Esophageal Achalasia

The achalasia guidelines from the Society of American Gastrointestinal and Endoscopic Surgeons have recommended that patients who undergo myotomy should also have a fundoplication Table 4.²⁸

**Table 4:** Comparison between pH monitoring and MII-pH monitoring
Parameter	pH monitoring	MII-pH monitoring
Acid reflux	Yes	Yes
NAR	No	Yes
Gas reflux	No	Yes
Reflux on PPI	+/−	Yes
Direction of reflux	No	Yes
Height of reflux	No	Yes
Proximal reflux	No	Yes
Bolus clearance	No	Yes
Cost	Cheap	Expensive
Interpretation	Easy	Difficult
Sensitivity to detect GER	Less	More
Esophageal hypersensitivity/functional heartburn	Cannot be differentiated	Can be differentiated

OTHER TECHNIQUES

Catheter-based Esophageal pH Monitoring

pH monitoring using catheter-based systems is widely utilized to assess abnormal acid exposure and establish a relationship between symptoms and acid reflux episodes. These pH probes typically include a small antimony electrode connected to a portable data logger, which records intraesophageal pH levels, symptoms, meal intake, and body position throughout the monitoring period. The criteria and definitions for pH monitoring have been discussed in the context of MII-pH. Several scoring systems, such as the DeMeester score and the Boix-Ochoa score, have been proposed, but the RI is currently considered the preferred method for reporting pH monitoring results. In children, pH monitoring has shown estimated sensitivity ranging from 83 to 100% in predicting esophagitis. However, it is important to acknowledge that the severity of reflux does not always align with the severity of symptoms experienced by the child. This highlights the need for comprehensive evaluation and consideration of other factors when interpreting pH monitoring results in pediatric patients.²⁹ A randomized controlled trial conducted to evaluate acid suppression therapy in children with pathologic reflux, utilizing pH monitoring as a diagnostic tool, reported that approximately 69–74% of patients showed symptomatic improvement when treated with acid suppression medication. These findings suggest that the results obtained from pH monitoring can effectively predict the clinical response to acid suppression therapy in pediatric patients. It highlights the value of pH probe results in guiding treatment decisions and optimizing patient management for pathologic reflux in children.³⁰

A comparison between MII-pH and catheter-based esophageal pH monitoring can be found in Table 4.

Wireless pH Monitoring

A wireless alternative to catheter-based tests called the Bravo pH system (Medtronic, Shoreview, Minneapolis, United States of America), has been developed to alleviate the discomfort experienced by patients. This system utilizes a small capsule containing an antimony electrode, which is attached to the mucosal wall of the distal esophagus during an upper gastrointestinal endoscopy. The capsule wirelessly transmits pH data to a portable receiver using radiotelemetry technology. The capsule can remain in place for a duration of 2–4 days or even longer, providing an extended monitoring period. During the placement procedure, the capsule is typically positioned 6 cm above the squamocolumnar junction in adult patients. To ensure accurate placement, confirmation is done through endoscopy, which allows visual verification. The wireless nature of the Bravo pH system eliminates the need for a nasoesophageal catheter, reducing patient discomfort and enhancing overall tolerability. It offers a convenient and reliable method for measuring pH levels in the esophagus, enabling accurate diagnosis and monitoring of GERD and related conditions.³¹ However, specific guidelines for capsule placement in children are currently lacking.

Side effects (from adult series):

Significant chest discomfort.
Early detachment of the capsule.
Perforation.
Need for endoscopic extraction of the capsule.

Because of the small case series in pediatrics, the extent of Bravo complications in children is still largely unknown.³² However, in the available studies of children older than 4 years old, pH monitoring with the Bravo capsule in comparison to the catheter-based study Showed:

The wireless Bravo pH system demonstrates superior patient tolerance in terms of appetite, activity, and overall satisfaction compared to other methods.
The primary reported complication with the Bravo system is mild chest discomfort, and no significant adverse events have been observed.
Studies with longer monitoring durations using the Bravo system have shown an improved correlation between rare symptoms and reflux episodes, enhancing diagnostic accuracy.
In a study by Croffie et al.,³³ it was found that there was no significant difference in the RI between the 1st and 2nd day of monitoring. However, the median RI recorded by the Bravo capsule was significantly higher on the 2nd day compared to the 1st day.
A series of 145 Bravo studies involving children revealed that there were significantly more long-duration reflux events and a higher RI in the upright position on the 1st day compared to the 2nd day.³⁴
Currently, there is no consensus regarding whether the interpretation of the results should be based on the 1st, 2nd day, or an average of both days, highlighting the need for further research and standardization.
The Bravo pH system provides a reasonable alternative for patients who are unable to tolerate a catheter-based system. However, its potential to become the definitive gold standard for reflux diagnosis may be limited due to the requirement for sedation during placement and the necessity to discontinue acid suppression therapy.

Proximal Esophageal pH Monitoring

Proximal esophageal pH monitoring serves a specific purpose in evaluating acid reflux in the upper region of the esophagus and its potential association with symptoms related to the oropharynx and respiratory system.
Studies employing dual-probe pH monitoring, which assesses both distal and proximal esophageal pH levels, have produced diverse outcomes concerning sensitivity, specificity, reproducibility, and the ability to predict treatment response for extraesophageal symptoms.
The clinical significance of proximal acidification in the absence of distal acidification remains uncertain and further research is needed to elucidate its implications.
In pediatric cases, challenges arise due to the limited availability of catheter sizes and the wide variation in esophageal lengths, making it difficult to consistently position the proximal sensor without compromising the placement of the distal sensor.
Furthermore, the precise pH threshold at which damage occurs in the bronchial, laryngeal, and pharyngeal tissues remains unclear. While the literature traditionally focused on a pH cutoff of 4, NAR with pH values ranging from 4 to 7 may also have a significant clinical impact on aerodigestive diseases.³⁵
Currently, the clinical advantages of proximal esophageal pH monitoring in children have not been definitively established, underscoring the need for further research to validate its utility and effectiveness.

THE FUTURE FOR MII

Based on the current body of evidence, it is evident that MII-pH monitoring has become the favored approach for assessing individuals with extraesophageal symptoms potentially associated with GERD, as well as those who continue to experience symptoms despite receiving acid suppression therapy. Nevertheless, the broader acceptance of MII-pH monitoring is impeded by two primary challenges—the labor-intensive process of interpreting study findings and the insufficient evidence demonstrating enhanced clinical outcomes compared to conventional pH monitoring techniques.

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