Multichannel intraesophageal impedance with pH metry in Saudi children

Abstract

Background:

Multichannel Intraesophageal Impedance with pH (MII-pH) provides complete characterization of gastroesophageal reflux (GER). The aim of this study was to report our experience in this relatively new technique, emphasizing the challenges in the performance and interpretation of the results.

Methods:

The study was conducted at King Khalid University Hospital at King Saud University in Riyadh. A retrospective review of the medical records of children who underwent MII-pH was performed. The procedure was performed and interpreted according to the recommended methodology. The impedance catheter was introduced nasally. The use of event markers and diary were explained to the accompanying person. At the end of the recording, the data were downloaded to the software analysis system.

Results:

MII-pH was performed on 98 children, and 16 studies were excluded from analysis for technical reasons. The median age was 32 (range 2–168) months and 44 (54%) were male. The prevalence of nonacid gastroesophageal reflux (NAGER), proximal extent of GER, and postprandial NAGER were 55%, 50%, and 70%, respectively. One hundred and fifty-three symptoms were reported during the study, but only two were significant.

Conclusion:

The MII-pH was well-tolerated but the performance and interpretation were technically demanding. The main advantage was the detection of NAGER. However, the lack of normal values and the reliance on symptom association make the interpretation of the results challenging.

INTRODUCTION

The esophageal pH monitoring, which was introduced in 1969, gradually became popular as “the gold standard” for the diagnosis of gastroesophageal reflux disease (GERD) since 1980.[1,2] Pediatricians practiced pH studies and developed familiarity with the indications and limitations of the techniques worldwide, including the Kingdom of Saudi Arabia (KSA), where experience with this technology was reported for the first time in 2002.[3,4] However, one of the most important limitations of this method was the inability to detect nonacid reflux episodes that are suspected to cause symptoms. The Multichannel Intraesophageal Impedance (MII), introduced in 1991, detects refluxates based on the physical characteristics (liquid, air), regardless of the pH.[5] The combination with a pH probe (MII-pH) completed the characterization of all types of refluxates (liquid, air, acid, and nonacid) and increased the indications of this relatively new technology in children.[6,7,8] However, most of the literature on the use of MII-pH in the investigation of GERD are from Western populations. Therefore, the objective of this study was to report our experience in the performance and interpretation of the results of MII-pH in Saudi children, with emphasis on the indications and limitations in the diagnosis of GERD.

PATIENTS AND METHODS

The procedure was explained to mothers and children. Barium meal was performed in all children to exclude conditions simulating GER and to identify structural abnormalities such as hiatal hernia, that may affect the proper position of the probe.[9] All acid-controlling medications (including PPI and H2 receptor blockers) were discontinued at least two weeks before the study. We followed the recommended techniques of MII/pH.[10,11,12] Briefly, after a short fasting period (3 to 5 hours), a single-use, age-appropriate (infant/pediatric) MII/pH catheter (Sandhill Scientific, Highland Ranch, CO, USA) was used. Initially, Stroebel formula (0.252 × body length in centimeters + 5) was used to determine the probe position as recommended.[13] Subsequently, chest X-ray was used to confirm the correct position of the tip of the probe, which should be at the upper border of the second vertebral body above the diaphragm, during a full respiratory cycle.[8] In case of structural abnormalities such as hiatal hernia or corrected esophageal atresia, endoscopy was used as the most accurate method to define the probe position. After proper positioning of the probe, the catheter was fixed and connected to the exterior impedance device (Sleuth System; Sandhill Scientific, Highland Ranch, CO, USA) for signal processing and recording. Initially, the mothers were instructed in the use of the event markers indicating the meals, position, and symptoms that may occur during the study. Subsequently, an event diary form was designed and explained to mothers on how to fill it out. Normal activity and diet, except for acidic liquid or food, were advised throughout the procedure. At the completion of the procedure, the data in the events diary were uploaded in the system and the tracing generated by the software was reviewed (BioView Analysis, Sleuth System; Sandhill Scientific Highland Ranch, CO, USA), updated with the Z VU advanced G.I. diagnostic software.[14] All studies were reviewed and interpreted by the principal investigator.

The variables analyzed in this report included the demographic and clinical profile of the children, the prevalence of nonacid gastroesophageal reflux (NAGER), the proximal extent of reflux episodes, and the prevalence of NAGER in the postprandial period. Symptom association was calculated by the software using three methods. 1. The symptom index (SI), which is the percentage of symptoms associated with reflux, calculated for each channel (number of symptoms associated with reflux/number of all symptoms x100). The association is positive when SI is ≥50%.[15] 2. Symptom sensitivity index (SSI), is the percentage of reflux associated with symptoms (number of reflux episodes associated with symptoms/total number of reflux episodes x 100). The association is considered positive when the SSI value is ≥10%.[16] 3. Symptom-associated probability (SAP). SAP is determined by complex statistical analyses to determine individual symptom correlation in each 2 min window of the study. SAP values >95% indicate that the observed GERD-symptom relationship is not brought by chance.[17] Descriptive statistics (frequencies and percentages) were used to quantify the categorical variables.

Statistical analysis

Descriptive statistics (frequencies and percentages) were used to quantify the categorical variables.

Ethical approval

This study was approved by the Institutional Review Board of the College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia (no. 20/0307/IRB).

RESULTS

A total number of 98 procedures were performed as part of the investigation of GERD. The study was accepted by all mothers and tolerated by all children, except two who pulled out the catheter, which was reinserted in the same location. Sixteen studies were excluded because of malposition of the pH probe (12 too high and 4 too low probe position). These cases were detected on recording analysis before the use of X-ray confirmation of the proper position. The remaining 82 MII-pH studies, judged to be technically acceptable, were analyzed. Demographic and clinical characteristics of the children are presented in Table 1. The median age range was 32 (2–168) months, and 44 (54%) were male. The top three indications for the study were pulmonary (35%), regurgitation or vomiting (28%), and before gastrostomy (13%). Acid exposure results: median (range) included 1.2% (0.1%–22.3%), 1.3 (0.2–37) minutes, and 4.9 (0.4–183) minutes for pH reflux index, bolus clearance, and longest reflux episode, respectively. Figure 1 illustrates the pattern of acid and nonacid refluxes identified by the MII-pH, and Table 2 shows the characteristics of reflux episodes detected by the MII-pH analysis indicating a 55% prevalence of NAGER, a proximal extent of 50% of GER, and a 65% to 70% prevalence of NAGER in the 120 and first 60 minutes post-prandial periods, respectively. There were 153 symptoms recorded during the study, but the symptom association was positive in only two cases.

Table 1.

Demographic and clinical characteristics

Total number of children	82
Age, average (range) in months	32 (2-168)
Sex: no. (% male)	44 (54%)
Indications for MII-pH. no. (%):
Pulmonary disorders Regurgitation/vomiting	29 (36)
Regurgitation/vomiting	23 (28)
Before gastrostomy tube	11 (13)
Miscellaneous (ENT, ALTE, FTT, heartburn, etc.):	19 (23)

ENT: Ear Nose and Throat, ALTE: Apparent life-threatening event, FTT: Failure to thrive

Figure 1.

Reflux episodes by MII-pH. Reflux episodes are highlighted in yellow and identified by a drop of the impedance >50% of the baseline. In panel A, there is a nonacid reflux episode extending up to the third impedance channel (Z3) associated with a pH record above 4 as indicated in the pH channel. In panel B, the reflux episode extends to the fourth impedance channel (Z4) and is associated with a drop of pH below 4 (highlighted in red), indicating acid reflux

Table 2.

Characteristics of MII-pH* reflux episodes

Variables	Acid: no. (%)	Nonacid: no. (%)	Total: no. (%)
Number of refluxes	1782 (45)	2211 (55)	3993 (100)
Proximal extent to Z2*	523 (50)	528 (50)	1051 (100)
120 minutes PP†	696 (35)	1305 (65)	2001 (100)
First 60 minutes PP‡	252 (30)	579 (70)	831 (100)
Number of symptoms: 153
Significant symptom index (> 50%)		2
Symptom sensitivity index >10%		0

*MII-pH: Multi-channel Intraesophageal Impedance with pH. ^†Z2: Impedance channel 2. ^‡PP: Postprandial

DISCUSSION

The most important advantages of the MII-pH are the identification of the nonacid reflux episodes, assessment of the proximal extent, and assessment of the importance of NAGER in the post-prandial period, where all have been reported to cause symptoms.[18] In this study, the finding of 55% prevalence of NAGER is similar to other reports and could have been missed by the conventional pH studies.[18] Definition of the proximal extent of reflux episodes (acid and nonacid) is another advantage of MII-pH over the conventional acid pH methods, which might be important in the correlation of GERD with ENT and pulmonary conditions.[19,20,21] Finally, identification of the nonacid component of post-prandial GER is another important advantage that is important to define the role of nonacid GER in post-prandial symptoms.[22]

In this report, qualitative review of the study before report analysis identified technical problems and avoided false negative and false positive reports, in cases of too high and too low positions of the pH probe, respectively. Accordingly, X-ray confirmation of the pH, to minimize malposition of probe is recommended. Finally, qualitative assessment of the study is essential to exclude technical problems before generation of the numerical analysis reports.[4]

The major disadvantage of MII-pH study is the lack of normal values. Apart from neonates[23] and adults,[24] normal values for children are not available yet, although recent attempts toward the establishment of normal reference values in children have been reported.[25,26] Currently, symptom association analysis (SI, SSI, and SAP) is the only method used to establish impedance normality. However, symptom association evaluation requires accurate record of events which is usually suboptimal in children and adults. The presence of frequent symptoms during the study is not always available. In our study, there were only a few significant symptoms recorded during the study, a finding that was not surprising as most of our patients were asymptomatic before the performance of the study. As a result, the routine use of MII-pH is debatable. Nevertheless, the MII-pH study is valuable in cases with frequent symptoms and assessment of the persistence of symptoms, despite acid suppression.

CONCLUSIONS

1. MII-pH is a well-tolerated and attractive method. However, the technique is demanding and requires expensive equipment and technical expertise in the performance of the procedure in the interpretation of results.

2. X-ray confirmation of the pH probe position before recording and qualitative review of the recording before generation of the numerical report are recommended to exclude technical issues.

3. Detection of the nonacid, proximal extent, and post-prandial GER are clear advantages of the MII-pH over the conventional pH studies.

Financial support and sponsorship

The Deputyship for Research & Innovation, Ministry of Education in Saudi Arabia for funding this research. (IFKSURC-1-2012).

Conflicts of interest

There are no conflicts of interest.