The American Journal of Gastroenterology (2007) 102, 668–685; doi:10.1111/j.1572-0241.2006.00936.x
ACG Practice Guidelines: Esophageal Reflux Testing
12Ikuo Hirano MD, Joel E Richter MD and the Practice Parameters Committee of the
*American College of Gastroenterology
11. Division of Gastroenterology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
22. Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania Correspondence: Ikuo Hirano, MD, Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, 676 North St Clair Street, Suite 1400, Chicago, Illinois 60611-2951. *The members of the Practice Parameters Committee of the American College of Gastroenterology are listed in the Appendix.
Received 26 April 2006; Accepted 28 August 2006.
Investigations and technical advances have enhanced our understanding and management of gastroesophageal reflux disease. The recognition of the prevalence and importance of patients with endoscopy-negative reflux disease as well as those refractory to proton pump inhibitor therapy have led to an increasing need for objective tests of esophageal reflux. Guidelines for esophageal reflux testing are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee and approved by the Board of Trustees. Issues regarding the utilization of conventional, catheter-based pH monitoring are discussed. Improvements in the interpretation of esophageal pH recordings through the use of symptom-reflux association analyses as well as limitations gleaned from recent studies are reviewed. The clinical utility of pH recordings in the proximal esophagus and stomach is examined. Newly introduced techniques of
duodenogastroesophageal reflux, wireless pH capsule monitoring and esophageal impedance testing are assessed and put into the context of traditional methodology. Finally, recommendations on the clinical applications of esophageal reflux testing are presented.
ACG Guidelines on the clinical applications of ambulatory esophageal pH monitoring were
1last published 10 yr ago (). Since that time, research investigations and technical
advances have enhanced our understanding of both the utility and limitations of this diagnostic modality. Studies have examined whether placement of pH probes in the pharynx, cervical esophagus, and proximal stomach yield information that alters the management of gastroesophageal reflux disease (GERD). Newer techniques for esophageal functional testing such as wireless pH capsule monitoring,
duodenogastroesophageal (formerly referred to as alkaline or bile reflux) reflux detection, and esophageal impedance testing have been introduced over the past decade and are currently available in clinical practice. A recent, prospective study compared the indications for esophageal pH monitoring in clinical practice with the indications in
2,3practice guidelines (). Less than half of the studies performed were in accordance with the recommendations. Two studies reported that pH testing resulted in a change in management in approximately 50% of investigated patients, although such changes were
4,5maintained in only half of the cohort ().
This second practice guidelines summarizes advances in GERD diagnostic testing and how they have modified the clinical management of esophageal disorders. A literature search was conducted for English-language articles dealing with functional evaluation of the esophagus from 1994 to 2006. Databases included Medline and PubMed with search terms that included esophageal pH monitoring, GERD, esophageal impedance, asthma, laryngitis, chest pain, Bilitec, and bile reflux.
WIRELESS pH MONITORING.
First introduced over 30 years ago, catheter-based esophageal pH recording remains both a widely accepted and available technique for quantifying esophageal acid exposure. The technique has been extensively examined and critically reviewed in earlier clinical
1,2guidelines (). The most significant recent technical advance in pH recording has been the incorporation of the antimony electrode into a wireless capsule that transmits pH data to an external receiver via radiofrequency telemetry (433 MHz). The current data sampling at 6-s intervals of the wireless pH capsule (Bravo system, Medtronic, Minneapolis, MN) (0.17Hz) is slower than the 4-s intervals used by the Slimline pH catheter systems (0.25Hz) (Medtronic, Minneapolis, MN) and 5-s intervals used by the Sandhill pH catheter system (0.20 Hz) (Sandhill Scientific, Highlands Ranch, CO). Prior studies have demonstrated that faster sampling frequencies up to 1 Hz lead to the detection of a greater total number of reflux events but do not change the overall acid
6exposure values (). Using the wireless pH system, the 95th percentile for distal esophageal acid exposure for control subjects was 5.3%, a value higher than values
2,7,8reported in several although not all catheter-based system studies (). The higher acid
exposure threshold reported in healthy controls using the wireless pH system may be the consequence of less restriction in daily activities or the result of a thermal calibration error that existed in the pH catheter systems. Both of these issues will now be addressed. A major advantage of the wireless pH system is patient tolerability. Nasally passed pH electrodes are both uncomfortable and conspicuous leading patients to avoid potentially
9reflux provoking stimuli such as meals and physical activity (). However, a second study
from Spain reported that patients' dietary, sleep, and tobacco use did not vary during the performance of pH studies, although 65% of patients did report diminished physical
10activity (). Wong et al. randomized 50 patients to either catheter-based or wireless pH monitoring and reported less interference with daily activity and improved overall
11satisfaction with the pH capsule (). Taking advantage of the improved patient comfort
with the wireless pH system, Pandolfino et al. demonstrated a threefold increase in acid
12exposure during physical exercise compared with nonexercise periods (). Therefore, pH
recordings using the wireless pH system improve patients' ability to perform their daily activities and thus provide a more accurate picture of their acid exposure profile as well as improve their compliance with the study.
COMPARISON OF WIRELESS pH CAPSULE AND CATHETER-BASED pH
During studies simultaneously using the wireless pH and Slimline catheter pH systems, a
13,14,15significant offset was noted in the pH values reported by the two systems (). As a
result of this offset, the Slimline system reported a median percent time pH <4 of 3.5% in a group of healthy subjects compared with 1.75% with the wireless pH system. Swallowed orange juice with pH of 3.88 measured ex vivo using a benchtop pH glass
electrode was used as a reference standard and demonstrated that the wireless pH system gave a median pH value of 3.84 compared with 3.11 for the Slimline catheter. This difference in calibration has been determined to be due to a thermal calibration correction factor error inherent to the Slimline software. This error has since been corrected. Another difference noted between the wireless pH capsule and Slimline catheter was in the detection of number of acid reflux events. The Slimline recorded a significantly greater number of events that could only partly be explained by the thermal
14correction factor error (). The difference was due to a higher detection of short reflux episodes and likely secondary to the lower sampling rate of the wireless pH compared with Slimline catheter system. It should be noted that both the wireless pH and Slimline systems miss a proportion of short reflux events due to their sampling frequencies being
6lower than the optimal frequency of 1 Hz (). Whether the short reflux episodes are
associated with symptoms and may affect the sensitivity of symptom association of pH testing with the wireless pH system is uncertain. Moreover, such short events do not alter the overall acid exposure times.
LIMITATIONS OF WIRELESS pH TESTING.
Disadvantages of the wireless pH system exist. The current capsule size does not allow for reliable nasal passage such that oral passage of the delivery catheter is necessary. Endoscopy is generally performed immediately prior to wireless pH capsule placement to determine the position of the squamocolumnar junction, thereby adding cost to the procedure. Early capsule detachment prior to 24 h is uncommon but can add additional costs for incomplete data acquisition. In one report, 12% of capsules failed to attach properly on first attempt necessitating a replacement capsule. Modifications to the catheter delivery system have since been performed by the manufacturer. A second report from two centers reported capsule detachment prior to 16 h in 3/85 subjects and
7prior to 36 h in 9/85 subjects (). Detachment that occurs during the 48-h recording
period could lead to erroneous interpretation of the acid exposure time consequent to intragastric pH recording (Fig. 1). This potential error can be minimized by manual
inspection of the pH tracing as well as querying the patient regarding the timing of loss of esophageal foreign body sensation. Finally, a single case report described a proximal
17esophageal perforation following an attempted wireless pH capsule placement ().
Serious complications including perforation have not been reported in the published
7,12,13,15,16,18,19,20,21,22,23,24,25series totaling over 850 subjects ().
Early detachment of the wireless pH capsule in a GERD patient. Note the sudden prolonged drop
in pH representing the capsule in the stomach and then the sharp rise as the capsule enters the
small intestine through the pylorus. In addition, there are two small areas indicating data loss
Full figure and legend (44K)
Additional drawbacks are minor. The validity of using the squamocolumnar junction as a reference point for the gastroesophageal junction has not been subject to the same scrutiny as the manometric positioning of the catheter-based pH electrodes. However, prior studies have demonstrated consistency of the positioning of the proximal margin of the lower esophageal sphincter (LES) 1 to 1.5 cm above the squamocolumnar junction 26(). The reliability of using other markers such as the proximal margin of the gastric folds in patients with Barrett's esophagus has not been determined. Patient discomfort from the pH capsule has been reported with many patients noting a foreign body
21,22sensation, especially with deglutition (). This is generally of little consequence with
7,11rare patients requiring early capsule removal by endoscopy secondary to discomfort ().
Manometric studies have recorded high amplitude foci of esophageal body contractions in the vicinity of the pH capsule that may account for symptoms of chest pain in some
27patients (). Inadequate data reception resulting in periods of missing data is most
commonly the result of the receiver being out of range of the capsule. Modifications to the hardware have reduced this problem and the current software automatically deletes such periods from the final analysis. Finally, failure of capsule detachment, albeit rare, can necessitate endoscopic extraction.
OPTIMAL DURATION OF pH MONITORING.
The standard duration of recording for esophageal pH testing is 24 h. With the introduction of the wireless pH system, prolonged recording periods extending beyond 24 and even 48 h are now both well tolerated and feasible. The wireless pH system routinely records for 48 h although early detachment prior to 48 h occurs in about 10% of patients 7,19(). The 48-h data could be interpreted using an average of the 2 days or only the 24-h period with the greatest acid exposure (worst day analysis). A significant increase in the sensitivity of pH testing and small decrease in specificity were evident when utilizing the worst day data compared with either the initial 24-h or overall 48-h data in comparing controls with GERD patients. Defining GERD as the presence of erosive esophagitis and an abnormal pH study as greater than 5.3% exposure time, the sensitivity of day 1 testing was 74% and specificity 90%. By using the worst day of the 2-day recording
7window, the sensitivity increased to 100% with a decrease in specificity to 85% (). A
similar increase in reflux detection was recently reported for a 2-day compared with
22single-day reflux study using the wireless pH system (). Of note, earlier catheter-based
studies examining the reproducibility of pH testing over two different study days reported
28,29concordance of between 73 and 89% (). The differences in lifestyle and dietary
factors that likely account for this variability are reduced by the prolonged recording window with the wireless pH system.
A shorter recording period utilizing the pH catheter system has been proposed as an accurate means of assessing reflux that allows for improved patient tolerance. Arora and Murray described a 3-h postprandial pH test in a series of patients with GERD and reported a sensitivity of 88% and specificity of 98% using the results of the entire 24-h
30ambulatory study as the reference standard (). Although this may be an alternative for
some patients, the wireless pH capsule circumvents many of the tolerability problems of catheter-based studies. Furthermore, the 24- to 48-h recording windows allow for assessment of supine and upright patterns of reflux as well as increased detection of
31symptoms for symptom association calculations ().
pH ELECTRODE CALIBRATION.
Calibration is performed on all pH systems prior to each study using reference buffer solutions. An analysis of 100 consecutive pH studies using posttest calibration testing of catheter-based antimony pH electrodes found drift of greater than 0.4 pH units in 5%
and a change in study interpretation in 6% of studies when the drift was factored into the
32final analysis (). Posttest calibration is currently not routinely performed for clinical studies with the wireless pH capsule due to the in vivo fixation of the capsule that does
not allow for posttest immersion into buffer solutions. Recently, a protocol involving the
13,14,19use of swallowed juice has been reported (). This method involves measuring the
pH of orange juice or a similar acidic beverage using a benchtop glass pH electrode. The juice is then swallowed and t