Cabrera, José; Davis, Miriam; Horn, Debbie; Pfefferkorn, Marian; Croffie, Joseph M.
Division of Pediatric Gastroenterology, Hepatology and Nutrition, Indiana University School of Medicine, Indianapolis, IN.
Address correspondence and reprint requests to Jose Cabrera, MD, 702 Barnhill Dr, ROC Room 4210, Indianapolis, IN 46202 (e-mail: email@example.com).
Received 23 November, 2010
Accepted 18 April, 2011
The authors report no conflicts of interest.
Aim: The aim of the present study was to report the global experience with placement, complication rate, and recording of esophageal pH using the BRAVO capsule at our institution.
Patients and Methods: We recorded the rate of any technical problems and complications during placement in all of the patients (ages 4–22 years) who received this device during a 2-year period. All of the patients undergoing esophagogastroduodenoscopy with the placement of BRAVO pH capsule were included in this analysis. We also examined the pH data recorded on days 1 and 2 for significant day-to-day variability during 2 days of pH monitoring.
Results: Two hundred eighty-nine BRAVO pH probes were placed from January 1, 2006 to December 31, 2008. At least 1 day of data was obtained in 278 patients (96.2%). Two days of data were obtained in 274 patients (94.8%). Of all of the reported complications, 1% occurred before deployment of the capsule, 4% occurred during deployment of the capsule, and 9% occurred after successful deployment of the capsule. One patient experienced a superficial esophageal tear that was associated with failure of the capsule to release from the delivery system. No patient requested removal of the capsule and all of the capsules detached within 14 days. In 9.12% of our patients, reflux index was normal on day 1 and abnormal on day 2. There was no statistically significant difference between reflux index recorded on day 1 versus day 2 (P = 0.686).
Conclusions: The BRAVO pH capsule is easy to place, safe, and well tolerated by children. Performing a 48-hour study detected abnormal reflux in an additional 9% of our patients.
Esophageal pH monitoring of the distal esophagus is the standard for diagnosis of acidic gastroesophageal reflux disease (GERD). The BRAVO pH system (Given Imaging Inc, Yokeam, Israel) consists of a small capsule containing a radio transmitter, an internal battery, and an antimony pH electrode. This device is attached to the distal esophageal wall and transmits pH data via radiotelemetry, thus eliminating the need for a traditional pH probe in which a pH electrode is attached to a transnasal catheter. The BRAVO wireless pH capsule therefore enables 48- or 96-hour pH monitoring without the discomfort of a nasally placed catheter. The capsule monitors pH and transmits data to a pager-sized device carried by the patient. The capsule detaches after several days with the natural sloughing of the esophageal mucosa and it is then expelled in the stool.
Our institution (an academic pediatric medical center) has previously reported that data obtained from this device are comparable with the nasally placed catheter in pH monitoring and the device is safe and better tolerated (1). Adult studies also suggest that data obtained from the BRAVO system are comparable with data obtained with the conventional nasal catheter, but the BRAVO system is better tolerated (2–6). Investigators have reported safe placement of the BRAVO capsule in the upper esophagus in children as young as 3 months of age (7). Although studies in both adults and children suggest that placement of the BRAVO system is safe (no adverse events), tolerable, and has minimal effect on daily activity of patients (1,8–12), anecdotal experiences of esophageal injury during placement of this device by some pediatric gastroenterologists may make others hesitant to attempt placement of the BRAVO system in their pediatric patients with suspected gastroesophageal reflux disease.
The primary aim of the present study was to report the complication encountered during placement and the variability of the pH data collected with the BRAVO system in 289 patients during the course of 2 years. Our institution is a tertiary medical center with 10 attending pediatric gastroenterologists and up to 5 fellows. The present study was approved by the Indiana University/Purdue University at Indianapolis and Clarian Health Partners institutional review boards.
PATIENTS AND METHODS
We prospectively documented any technical problems and complications encountered in all of the patients undergoing esophagogastroduodenoscopy with placement of the BRAVO pH capsule at our institution for any indication from January 1, 2006 to December 31, 2008. We kept strict records during this time, including any adverse events or technical problems encountered during placement of the capsule, and pH data (reflux index [RI]) collected using the device. As we previously reported at our institution (1), we place the BRAVO capsule in children who are at least 4 years old and weigh at least 30 lb. We do not place this device in children with a history of esophageal surgery (eg, tracheoesophageal fistula repair, Nissen fundoplication), with a documented anatomic abnormality (eg, esophageal stricture), or with a history of coagulopathy or a bleeding diathesis.
BRAVO Capsule Placement
The BRAVO device was attached to the esophageal mucosa using an accompanying delivery system. The device was calibrated with stock acidic and neutral solutions before endoscopy. General anesthesia, administered by a pediatric anesthesiologist with continuous cardiopulmonary monitoring, was used for sedation during endoscopy and capsule placement. 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. A prepackaged catheter assembly (Given Imaging, Yokneam, Israel), including the pH capsule and a delivery system, was introduced transorally under direct endoscopic vision through the pharynx into the esophagus. The catheter was advanced 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 capsule was attached to the mucosa of the esophagus using a freestanding custom-built external vacuum device (positioned close to the patient at the bedside) that maintained suction (560 mmHg) for 30 to 45 seconds and suctioned mucosa into a small well on the capsule. A deploying pin on the delivery system was then engaged, which fastened the capsule to the esophageal mucosa. The endoscope was reintroduced to verify capsule attachment. Distal esophageal pH data from the BRAVO capsule were collected during a period of 2 days. The BRAVO capsule has a pH sampling rate of 6 seconds, has a transmission frequency of 12 seconds, and records pH values to 1 decimal point (eg, pH 6.7). A daily log was maintained by the patients/parents and submitted when the data storage device was returned. Parents or older children were instructed to record any adverse events. An abdominal radiograph was obtained to verify successful detachment of the capsule 14 days after placement unless the device had been seen in the stool before the 14th day after placement.
We reviewed all of the technical problems and any associated complications recorded during placement of the BRAVO pH probes. We also compared the pH data recorded on days 1 and 2 for significant day-to-day variability in the RI using standard Student t test calculations.
A total of 289 BRAVO pH probes were placed from January 1, 2006 to December 31, 2008. The ages of the patients ranged from 4 to 22 years old (Table 1). The oldest patient was a severely impaired young man with cerebral palsy. One hundred forty-five (50.2%) of the patients were men. The indications for the pH study in our patients are summarized in Table 2. The most common indication was epigastric abdominal pain (59.9%). At least 1 day of data was obtained in 278 patients (96.2%). Two days of data were obtained in 274 patients (94.8%).
Tables 3 to 5 summarize the complications reported during the course of the 2-year period. In 1 patient, the capsule was not successfully deployed at initial placement and a small nonbleeding mucosal tear was noted in the distal esophagus in the area where the capsule appeared to have attached to the esophagus. In this patient, it is believed that the capsule did not release from the delivery system, causing the superficial tear when the delivery system was withdrawn from the esophagus (Fig. 1). In another patient, 1 capsule would not record after attachment, necessitating the use of a second capsule after safely removing and retrieving the first capsule with a cold polypectomy snare.
There were 4 premature detachments (1.38%) of the capsule before the conclusion of the second day of the study. Figure 2 illustrates an example of pH data from a prematurely detached capsule. One capsule detached before the end of day 1, and 3 capsules (1.04%) detached before the end of day 2. For the 1 study that resulted in premature detachment before the end of day 1, the patient vomited the capsule after <2 hours of placement. For the 3 studies that resulted in premature detachment before the end of day 2, we obtained at least 24 hours of pH monitoring, which provided adequate data for interpretation.
In 10 patients (3.46%), the device stopped recording before the end of the first day (including 1 patient with premature detachment of the capsule and 1 patient in which the capsule failed to record any data). For these studies, we obtained <24 hours of pH monitoring, which did not provide adequate data for clinical interpretation and diagnosis. In 15 patients (5.19%), the device stopped recording before the end of the second day. In 12 of these studies (80%), we obtained at least 24 hours of pH monitoring, which provided adequate data for interpretation. No patient requested removal of the capsule and all of the capsules were detached within 14 days.
There was no statistically significant difference between RI recorded on day 1 and RI recorded on day 2 (P = 0.686). For our patient population, we considered the upper limit of normal for RI to be 6% (13,14). There was discordance in the RI recorded between day 1 and day 2 in 58 (21.17%) of the patients who completed 2 days of recordings. The RI was normal on day 1 and abnormal on day 2 in 25 (9.12%) of those patients. These findings are summarized in Table 6.
To our knowledge, this is the largest reported cohort of pediatric patients having undergone placement of the BRAVO pH capsule. One study of 50 pediatric patients younger than 6 years old reported that patients had minimal discomfort during the procedure and sustained no major procedural complications (12). Another study, with a cohort of 50 pediatric patients (average age of 13 years), reported no adverse events during placement of the BRAVO capsule, while demonstrating that the data collected from the device changed clinical management in 88% of patients (9).
As noted in Table 5, most complications in our patients occurred after successful deployment of the capsule. We noted 2 common types of complications: premature detachment of the capsule from the esophageal wall and premature cessation of data recording. The most common procedural complication in our study, therefore, was failure of the device to record for the 2 days of intended data acquisition. This occurred in 8.65% of our patients; however, in these 25 patients (summarized in Table 4), we were able to obtain at least 24 hours of pH data from 15 patients (60%), which provided adequate data for interpretation. In a smaller pediatric cohort, investigators reported that in placing of 62 BRAVO pH probes, there were only 3 technical problems; in 1 child, there was a failure of communication between the receiver and the capsule, whereas in 2 other children, there was a problem with fastening the capsule, requiring 3 capsules in 1 patient (8). In our experience, 4 patients (1.38%) experienced premature detachment of the capsule, with 1 of these patients vomiting the capsule within hours of placement.
In our study, there was 1 relatively serious complication related to placement of the capsule (Fig. 1). A 15-year-old patient sustained a small distal esophageal mucosal tear when the capsule failed to release from the delivery system after attachment to the esophagus. She had no long-term consequences from this procedure and responded well to topical therapy with sucralfate. Following this complication, we learned that such a complication can be prevented with an alternative maneuver to disengage the capsule from the delivery system. After successful attachment of the capsule to the esophagus, there should be no resistance felt during withdrawal of the delivery system. The presence of any resistance would indicate that the capsule was attached to the esophagus and also likely remained connected to the delivery system. In this situation, depressing the 2 blue tabs on the handle of the delivery system (Fig. 3) followed by twisting the handle in a counterclockwise direction will disengage the capsule from the delivery system. Using this maneuver, we have not experienced any further esophageal injuries during placement of the BRAVO capsule. Given Imaging will soon introduce a new delivery system, which may decrease the likelihood of this complication occurring.
The RI is a classic calculation used during interpretation of pH studies. The RI is the percentage of the total time of study that the esophageal pH is <4. In our analysis of the pH data obtained during the present study, we detected no statistically significant difference in the RI obtained on day 1 compared with day 2 (P = 0.686); however, in 21.17% of our patients, there was a discordance between the RI on day 1 and day 2, such that 1 of these days revealed normal data, whereas the other was abnormal (RI >6%). Approximately 9% of our patients who completed 2 days of pH recording had a normal RI on day 1 but an abnormal RI on day 2. Thus, by continuing the pH monitoring in our patients with GERD symptoms through 2 days rather than 1 day, we were able to diagnose abnormal esophageal pH in an additional 9.12% of our patients. This may have considerable clinical significance in children undergoing wireless pH monitoring. Other adult studies suggest similar findings with extended (>24 hours) wireless esophageal pH monitoring (15,16).
In conclusion, our experience with the BRAVO pH capsule in this large cohort of pediatric patients revealed that this device was easy to place, safe, and well tolerated by our patients between 4 and 22 years old. The most common complication was premature termination of data recording as seen in 8.65% of our patients. By performing 2 days of pH monitoring, we detected abnormal reflux in an additional 9.12% of our patients. Our study confirms what other investigators have observed regarding the BRAVO pH probe in adults with GERD symptoms. This wireless probe provides a tolerable yet minimally invasive modality to objectively measure reflux symptoms (15,17–20). Furthermore, when compared with the standard 24-hour transnasal distal esophageal pH catheter in pediatric patients, this wireless device has the added benefit of not interfering with the lifestyle or physical activity of the patient (10).
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