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Original Articles: Gastroenterology

Accuracy and Tolerability of the Bravo Catheter-free pH Capsule in Patients Between the Ages of 4 and 18 Years

Croffie, Joseph M*; Fitzgerald, Joseph F*; Molleston, Jean P*; Gupta, Sandeep K*; Corkins, Mark R*; Pfefferkorn, Marian D*; Lim, Joel R*; Steiner, Steven J*; Dadzie, Steven K

Author Information
Journal of Pediatric Gastroenterology and Nutrition: November 2007 - Volume 45 - Issue 5 - p 559-563
doi: 10.1097/MPG.0b013e3180dc9349
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Abstract

INTRODUCTION

Ambulatory extended esophageal pH monitoring is considered the gold standard test for establishing the presence of abnormal gastroesophageal reflux in children. This is performed by placing an esophageal catheter through the nose and advancing it to a manometrically determined fluoroscopically guided or precalculated distance above the lower esophageal sphincter. The presence of the catheter in the nose is often associated with morbidity. Older children are uncomfortable, may not eat well, and may not carry out their usual activities in the presence of the catheter. Younger children may be irritable, may refuse to eat, and often require restraints to prevent them from pulling the catheter out. The test may therefore not be truly representative of the normal daily life in these patients, particularly when usual activity or eating is curtailed, and may result in false-negative results.

The Bravo pH system (Medtronic, Shoreview, MN) consists of a small capsule containing a radiotransmitter, an internal battery, and an antimony pH electrode. It is attached to the mucosal wall of the distal esophagus so that no tube protrudes from the nose. The capsule monitors pH and transmits data to a pager-sized device that may be worn on the patient's belt or placed next to the patient. The capsule detaches after several days and is expelled from the body in the stool.

Studies in adults suggest that data obtained from the Bravo system are comparable to data obtained with the conventional nasal catheter, but the Bravo system is better tolerated (1–4). Bothwell and colleagues (5) have reported safe placement of the Bravo capsule in the upper esophagus in children as young as 3 months of age with upper airway symptoms suspected to be caused by gastroesophageal reflux disease, and 2 recent studies reported in abstract form (6,7) concluded that the Bravo system is safe and has a sensitivity of 100% and a specificity of 83.3% in diagnosing pediatric gastroesophageal reflux disease. There are no reports comparing esophageal pH results obtained simultaneously with the Bravo capsule and the regular pH catheter in children; neither are there reports comparing the tolerability of the Bravo capsule with that of the pH catheter in children.

The primary aims of this study were to determine the accuracy and tolerability of the Bravo pH capsule compared with a standard pH catheter in children between the ages of 4 and 18 years. A secondary aim was to determine safety with regard to placement of the Bravo capsule in patients in this age group. The study was approved by the Indiana University/Purdue University at Indianapolis and Clarian Health Partners institutional review boards. Written informed consent was obtained from a parent or legal guardian before enrollment. Assent was obtained from children 7 years of age and older.

PATIENTS AND METHODS

Patient Selection

Subjects between the ages of 4 and 18 years and weighing at least 30 lb who were undergoing esophagogastroduodenoscopy and esophageal pH testing for symptoms suggestive of gastroesophageal reflux during the period of study were recruited to participate in the study. The lower age and weight limits of 4 years and 30 lb were arbitrarily selected to satisfy concerns expressed by our institutional review boards about using the Bravo capsule in younger children. Thirty pounds is approximately the 10th to the 25th percentile for a 4-year-old child.

Exclusion Criteria

Children younger than 4 years of age or weighing <30 lb were excluded from the study, as were those with anatomic abnormalities of the esophagus precluding placement of the pH catheter or deployment of the Bravo capsule. Patients were also excluded if they had a history of a surgical procedure of the esophagus, stomach, or duodenum; history of coagulopathy or bleeding diathesis; presence of esophageal varices; or significant medical illness (ie, serious illness or hospitalization, significant mental impairment).

The patients were divided into 3 groups based on age. Group 1 consisted of patients 4 to 6 years of age, group 2 consisted of patients 7 to 10 years of age, and group 3 consisted of patients older than 10 years of age. The age groups were selected to roughly represent preschool age, grade school age, and adolescence. The patients in each age group were randomized to 1 of 3 subgroups with use of a computer-generated random number table. Each subject in subgroup A received a Bravo capsule and a standard pH catheter simultaneously, those in subgroup B received a Bravo capsule alone, and those in subgroup C received a conventional pH catheter alone.

Probe Placement

For placement of the catheter, the distance from the nostril to the esophagogastric junction was determined according to the Strobel formula (8). The catheter was advanced through the nostril and positioned with its tip at 87% of this distance. This was done at the end of the esophagogastroduodenoscopy procedure. The catheter position was verified with a chest radiograph to ensure that the tip was appropriately positioned above the gastroesophageal junction. The Bravo capsule was attached to the esophageal mucosal wall using an accompanying delivery system that enables the physician to deploy a pin to tack the capsule to the mucosa. After identifying the z-line at the esophagogastric junction during endoscopy and noting its distance from the incisors on the endoscope, the endoscope was withdrawn. The prepackaged delivery system and capsule were then introduced into the esophagus to position the pH electrode at the distal end of the capsule at 87% of the endoscopically predetermined distance from the incisors to the z-line. The endoscope was reintroduced to verify capsule attachment.

Esophageal pH data were collected with the conventional catheter over a period of 24 hours, which is the storage capacity of the catheter's data storage device. Esophageal pH data from the Bravo capsule were collected over a period of 48 hours, which is the storage capacity of the Bravo's data storage device. A chest radiograph was obtained on day 14 to verify detachment of the capsule.

Monitoring

A daily log was maintained and turned in when the data storage device was returned. Parents or older children were instructed to record any adverse events. They were specifically asked to record any vomiting that was more than the patient's usual symptoms (if vomiting was a presenting symptom), and throat pain, chest pain, or esophageal discomfort. Parents or older children were also instructed to rank activity level, appetite, and overall satisfaction with the test on a Likert scale with rankings from 1 to 5, with 1 being not active, having no appetite, or being very dissatisfied with the test; and 5 being very active, having very good appetite, or being very satisfied with the test.

Number of Subjects Required for the Study

Assuming an SE of 5% for the reflux index (9), ≥9 subjects were needed in each group to detect a 10% difference in the reflux index obtained with the Bravo capsule versus the nasal catheter at a power of 0.95 and α value of 0.05. To detect a 50% difference in tolerability, ≥6 patients were needed from each age group in subgroups B and C. It was therefore proposed to study 10 patients in each age group for subgroup A and 6 patients in each age group for subgroups B and C. A total of 66 patients were therefore needed for this study.

Analysis

Comparison of pH data collected simultaneously by the pH catheter and the Bravo capsule was done for patients in subgroup A. A comparison of the tolerability of the 2 methods of study was done between subgroups B and C. Mann-Whitney U test was used to determine differences between the reflux indices (percent of the investigation time that the esophageal pH is <4) obtained by the Bravo and the nasal catheter in subgroup A patients. A Student t test was used to detect any differences in tolerability between subjects in subgroups B and C, and the Fisher exact test was used to compare frequencies of adverse events between the 2 groups. P ≤ 0.05 was considered significant. Statistical analysis was performed using commercially available Minitab software (version 14; Minitab, State College, PA).

RESULTS

A total of 66 patients were enrolled in the study; mean age was 9.4 years (range, 4–16.5 years). Thirty-two (48%) were male. Indications for endoscopy and pH monitoring included persistent epigastric or substernal pain, persistent vomiting, heartburn, chronic nocturnal cough or wheezing, persistent throat clearance, and dental abnormalities suspected to be caused by gastroesophageal reflux. The pH catheter and/or capsule were successfully placed in all of the patients. In 1 patient randomized to receive the catheter, pH data was recorded for <18 hours, and this patient was excluded from analysis, as was another patient randomized to receive the catheter who failed to turn in a diary. In 1 patient randomized to receive the Bravo capsule and catheter, the Bravo recording stopped after 24 hours. A second patient also randomized to receive the Bravo capsule and catheter pulled out the catheter and refused to have it reinserted. These 2 patients were excluded from analysis. Premature detachment of the capsule was suspected in another patient randomized to receive the Bravo capsule and catheter based on the pH recorded by the 2 devices simultaneously. Review of the Bravo pH tracing from this patient revealed a sudden decrease from normal pH toward the end of the first 24 hours to a pH of approximately 2 for a 3-hour period, followed by a sudden increase to a pH >6. The catheter recorded normal pH the entire time. We believed these findings were consistent with premature detachment of the capsule. This patient was also excluded from analysis. Therefore, 3 patients from subgroup A (catheter and Bravo capsule) and 2 patients from subgroup C (catheter alone) were excluded from analysis. In the rest of the patients, the pH tracings from the catheter and the capsule were of excellent quality. A chest radiograph obtained on day 14 in patients randomized to receive the capsule revealed that all of the capsules had detached and no capsule was found in the esophagus.

Tolerability

Six of 18 patients (33%) randomized to receive the Bravo capsule reported vomiting more than usual during the study, compared with 3 of 16 (19%) randomized to receive the catheter (P = 0.25). Seven of 18 patients in the Bravo capsule group (39%) reported chest pain, compared with 1 of 16 patients in the catheter arm (6%; P = 0.02). Eight of 18 patients who received the Bravo capsule (44%) reported throat pain, compared with 15 of 16 who received the catheter (94%; P = 0.001). Seven of 18 patients who received the Bravo capsule (39%) reported esophageal discomfort, compared with 11 of 16 who received the catheter (69%; P = 0.06). On a scale of 1 to 5, with 5 being best, Bravo capsule recipients ranked their appetite an average of 3.54, compared with a ranking of 2.72 by the catheter recipients (P = 0.029). Activity was ranked an average of 3.66 by the Bravo capsule recipients and 2.33 by the catheter recipients (P = 0.001). Overall satisfaction was ranked at 4.31 by Bravo capsule recipients and 3.11 by catheter recipients (P = 0.003). Patients randomized to receive both the capsule and catheter completed 2 questionnaires, 1 for each day of study. In these patients, appetite, activity, and satisfaction scores increased from means of 2.68, 2.26, and 3.08 to means of 3.50, 3.52, and 4.23, respectively (P = 0.019, P = 0.0003, and P = 0.013) after the catheter was removed. We assumed that the improvement in the scores on day 2 was a result of removal of the catheter, although we cannot say with certainty that the scores on day 1 reflect discomfort with the catheter alone because the patients had both devices in the esophagus during that time period.

Esophageal pH Data

There were no statistically significant differences between the pH data obtained with the catheter on day 1 and the Bravo capsule on day 1, the catheter on day 1 and the Bravo on day 2, or the catheter on day 1 and the combined day 1 and day 2 of the Bravo capsule in the age groups individually; however, there were significant differences between pH data obtained by the catheter on day 1 and day 2 of the Bravo capsule and between the catheter on day 1 and the combined days 1 and 2 of the Bravo capsule when all of the age groups are combined (Table 1).

T1-7
TABLE 1:
Comparison of mean reflux indexes between the Bravo capsule and conventional catheter

One patient in the >10-year age group had normal reflux indices of 1.5 and 1.6 recorded by the capsule and catheter, respectively, on day 1 but an abnormal reflux index of 6.2 recorded by the capsule on day 2. Another patient in the 7 to 10–year age group had abnormal reflux indices (8.2 and 6) recorded by the Bravo capsule on days 1 and 2 but a normal reflux index (3.2) recorded by the catheter on day 1.

DISCUSSION

To our knowledge this is the first study comparing the accuracy and tolerability of the Bravo capsule with the conventional pH catheter in children. We successfully placed the Bravo pH capsule in 48 children 4 to 16 years of age. In adults, the Bravo capsule is placed 6 cm above the squamocolumnar junction. This distance was selected by researchers based on the understanding that the proximal border of the high-pressure zone, representing the lower esophageal sphincter (LES), is 1 to 1.5 cm proximal to the squamocolumnar junction. They believed placement of the capsule 6 cm above the squamocolumnar junction would approximate the conventional placement of pH probes 5 cm proximal to the upper margin of the LES (2). The position of the high-pressure zone of the LES relative to the squamocolumnar junction may vary with age or height in the pediatric patient and may not be a fixed 1 to 1.5 cm as in adults. For this reason, we chose to position the pH electrode of the Bravo capsule 87% of the length of the esophagus, measured from the incisors to the upper border of the squamocolumnar junction during the endoscopy. This is similar to placement of the conventional pH probe according to the Strobel formula, and correlates with the traditional 5 cm in adults, which is approximately 13% of the length of the typical adult esophagus of 45 cm. An advantage of the Bravo capsule is that it is physically attached to the esophageal mucosa and therefore it maintains a constant position relative to the z-line and is not likely to slide into the stomach, as can occur with the catheter.

In patients tested with the Bravo capsule, 48-hour recordings were obtained in all but 1 patient in whom the recording stopped after 24 hours, and premature detachment was suspected in 1 patient. A chest radiograph obtained on day 14 confirmed detachment of all capsules. As in adult studies (2,3,10), the Bravo capsule was better tolerated than the traditional pH catheter. Patients randomized to receive the Bravo reported better appetite, less impairment of activity, and a better overall satisfaction level than their counterparts randomized to receive the traditional catheter (P = 0.029, P = 0.001, and P = 0.003, respectively). Patients randomized to receive the capsule reported more chest pain than their counterparts randomized to receive the catheter (39% vs 6%), but chest pain was severe enough to call a physician in only 1 patient who was treated with acetaminophen and codeine and completed the study with no further complaints. No patient requested removal of the capsule. The reason for chest pain is not clear, but similar observations have been made in adults (2,3,10,11). Interestingly, 6 of the 7 patients who reported chest pain were ≥7 years of age. It has been suggested that this chest pain may be related to abnormal visceral nociception (11). Throat pain was the most common complaint reported by the catheter recipients (94% vs 44%). The reason for this is believed to be irritation from the catheter as it traversed the pharynx.

We compared reflux indices obtained with the Bravo capsule on days 1 and 2 individually and the average of the 2 days combined, with the reflux index obtained simultaneously with the catheter on day 1 for the patients who received both devices. There was no statistically significant difference between median reflux indices obtained by the catheter and the capsule for the individual age groups. When all of the age groups were combined, there was no significant difference between the median reflux indices obtained on day 1 by the catheter and the capsule (P = 0.0665), but there was a significant difference between the median reflux index recorded by the catheter on day 1 and the median reflux index recorded by the Bravo capsule on day 2 (P = 0.0075), as well as the median combined reflux index (days 1 and 2) recorded by the capsule (P = 0.0107). Similar results have been reported in adults (2,10,11). The higher mean reflux index noted on day 2 may have reflected increased activity and, therefore, likely more gastroesophageal reflux in patients 1 day after anesthesia for endoscopy; however, it may also reflect day-to-day variability in esophageal acid exposure, as has been reported previously (12). Although the reflux index was consistently higher on day 2 than on day 1, the difference did not mean a normal study finding on day 1 and an abnormal study finding on day 2 for most patients. In fact, a discordant value of a reflux index that was normal on one day and pathological the next was observed in only 1 patient. However, the advantage of the Bravo capsule is in being able to extend the test beyond 24 hours so that pathological day-to-day variability can be detected.

Some limitations of this study must be acknowledged. Ideally, esophageal manometry to identify the location of the LES before placement of the esophageal pH catheter is desired. In children, this is usually not possible and the Strobel formula for estimating esophageal length has often been used to estimate where to place the catheter. This equation has limitations, however. Although we verified placement of all of the catheters by radiography and adjusted the position as necessary, we cannot be absolutely certain that all of the catheters remained at the desired location above the LES, and this could have affected the results of the study, particularly in patients who had simultaneous studies, if the catheter tip was not close enough to the Bravo capsule. The inability to record esophageal pH for longer than 24 hours with the Bravo capsule and catheter simultaneously makes it difficult to determine whether patients would have adapted to the presence of the catheter and tolerated it as well as they did the Bravo capsule. Finally, the Likert scale used for monitoring activity, appetite, and satisfaction has not been validated previously.

In conclusion, the Bravo pH capsule was safe, reliable, and better tolerated than the conventional pH catheter by children ranging in age from 4 to 16 years. As in adult studies, the most common complaint was chest pain, which did not require any intervention in most patients, and, as in adult studies, the ability to perform an extended study with the Bravo capsule may increase the ability to detect abnormal acid exposure in children with pathological gastroesophageal reflux who may exhibit day-to-day variability in esophageal acid exposure.

Acknowledgements

The authors thank Gail Waltz, RN, Debbie Horn, RN, and Sue Lee, BS, for their diligent work in the performance of this study, and Vicki Haviland-Wilhite for her excellent administrative support.

REFERENCES

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Keywords:

Bravo capsule; Esophageal pH test; Gastroesophageal reflux; Wireless esophageal pH testing

© 2007 Lippincott Williams & Wilkins, Inc.