pH and Impedance Evaluation of the Esophagus

History of Esophageal pH Monitoring

The first attempt to objectively detect gastroesophageal reflux (GER) was accomplished by Reichman in 1884. He lowered gelatin-coated sponges into the esophagus of patients with heartburn and showed that they contained acid when retrieved. Several decades later Aylwin found acid and pepsin in esophageal juice retrieved with a tube from a patient with esophagitis. Bernstein and Baker recognized the relationship between the presence of acid in the esophagus and symptoms of heartburn and regurgitation. They developed the acid infusion test, which is based on reproducing esophageal symptoms by the instillation of 0.1 N hydrochloric acid in the esophagus. The first in situ measurement of acid reflux in the esophagus was achieved by Tuttle and Grossman in 1958 using pH-metry equipment previously described for studies of gastric acidity. Although this approach greatly improved the detection of acid reflux, it was limited by its failure to differentiate normal subjects from abnormal subjects. Prolonged esophageal pH measurements were first described by Spencer in 1969. This technique soon became the standard method to quantify GER. Initially, the recording machines were not portable, forcing patients to remain attached to large equipment, making the procedure an inpatient system. In 1974 Johnson and DeMeester performed landmark studies in controls and GERD patients, establishing the technique and normal values for 24-hour ambulatory pH monitoring, and subsequently ambulatory pH monitoring has been widely applied in both clinical and research settings.

Indications for pH Testing

For patients with the typical symptoms of reflux, lifestyle changes of weight loss, avoidance of refluxogenic foods, and avoidance of the full recumbent position, particularly in the postprandial period, relieve symptoms. For others a therapeutic trial of acid suppressant medications, such as proton pump inhibitors (PPIs) and histamine H ₂ channel antagonists, will suffice, after excluding alternative pathologies. However, it is prudent to objectively document GER before considering invasive procedures such as antireflux surgery. Objective endoscopic evidence of GERD includes “mucosal breaks” of esophagitis in the distal esophagus, Barrett metaplasia, and the reflux-related complication of peptic esophageal stricture. In the absence of endoscopic evidence of reflux, objective evidence can be obtained by 24-hour ambulatory esophageal pH monitoring. The presence of an abnormal 24-hour pH score has been shown to be the strongest predictor of a good outcome after antireflux surgery. In addition, pH monitoring is useful in the evaluation of patients with persisting reflux symptoms despite medical or surgical therapy.

Electrochemical Properties of pH Electrodes

Esophageal pH monitoring techniques are designed to measure the intraluminal hydrogen ion concentration. The negative logarithm of the hydrogen ion concentration defines the pH value (pH = +log 1/[H ⁺ ]). The hydrogen activity can be detected by a number of different electrodes with different characteristics depending on the electrode material. The electrical potential difference, generated by a concentration gradient of hydrogen ions between two electrodes, can be extrapolated to give a pH value. Esophageal pH systems consist of glass, antimony, or ion-sensitive field effect transistor (ISFET) pH sensors and a reference electrode. The reference electrode is either external, placed on the patients' skin, or built into the catheter. A disadvantage of using external cutaneous reference electrodes is the risk of disturbed skin contact during the pH recording, which can lead to artifactual pH values. External electrodes are also associated with a risk of erroneous results as a consequence of influence of the mucosal potential difference. Based on these observations, pH catheters with an internal reference electrode are considered superior and are much more common in modern clinical practice. Glass electrodes measure the electrical potential difference across a thin glass membrane. The monocrystalline antimony electrode is a metal/metal oxide electrode that measures the corrosion potential at the hydrogen ion and antimony interface. The ISFET is a modification of the normal field effect transistor and combines in one device the sensing surface and a signal amplifier. Laboratory studies suggest that the more expensive glass electrodes are superior to monocrystalline antimony electrodes because they respond much quicker to changes in pH and have less drift and a better linear response. However, in a clinical setting, the less expensive antimony electrodes provide similar results and better patient comfort as compared with the larger glass electrodes. There is some evidence that ISFET electrodes produce the most accurate in vivo measurements of acid exposure, but they are not in widespread use.

Calibration of the pH electrodes is performed in all pH systems prior to each study, using reference buffer solutions, usually either nitrate or phthalate based. The pH value of the calibration solution varies among manufacturers, but most systems calibrate the pH sensor at room temperature to an acidic pH (range, 1.0 to 4.0) and a more neutral pH (range, 6.0 to 7.0). When the patient returns after completion of the test, the calibration should be repeated to rule out electrode failure and to allow correction for slow pH drift.

Catheter-Based pH Monitoring

The conventional catheter-based pH monitoring system principally consists of a flexible catheter, usually made from polyurethane, with one or more pH sensors and a data recorder. The catheter is passed through the nose, along the posterior wall of the pharynx, and is placed with the pH sensor in the distal esophagus 5 cm above the manometrically determined upper border of the lower esophageal sphincter (LES). It is connected to a data recorder that is carried by the patient during the study. The system samples pH data every 1 to 10 seconds, depending on the manufacturer of the catheter system. Ambulatory catheter-based pH monitoring is generally performed over a 24-hour period because a complete circadian cycle allows for determining the effect of physical activity and body positions on esophageal acid exposure, as well as allowing for an increased detection of symptoms for the calculation of symptom associations.

In general, esophageal pH monitoring is carried out while the patient is off acid-suppressant medication. Patients are normally instructed to discontinue the use of PPIs at least 7 days prior, histamine H ₂ -antagonists 5 days prior, and simple antacids 24 hours prior to the investigation. Only when the aim of the study is to measure the esophageal acid exposure that persists during treatment should acid suppressants be continued.

During the study, patients are instructed to keep a diary and to record symptoms, mealtimes, and times for supine and upright postures. Patients are often asked to avoid foods with a pH below 4, such as coffee, tea, citrus, tomato products, wine, and carbonated beverages, although the intake of these products has a rather short-lived effect on esophageal pH. Meal periods can be excluded from the analysis to avoid potential artifacts produced by acidic meal ingestion, and this may improve the clinical reliability of the test. The activity and the diet of the patients during the study should ideally be identical to that of the control population from which the normative values for esophageal acid exposure were developed. Some centers encourage the patients to eat their usual meals and may include one meal likely to precipitate their symptoms, the so-called refluxogenic or challenge meal, which often is a burger, fries, and shake at a fast-food restaurant. This challenge meal is useful because the process of esophageal pH monitoring has been shown to reduce reflux-provoking activities and patients tend to be more sedentary. In part this is related to social embarrassment and discomfort related to having the catheter coming out of the nose. When patients change their routines during pH testing, the degree of esophageal acid reflux may theoretically be underestimated, which could potentially decrease the sensitivity of the pH test. Therefore patients should be strongly encouraged to return to work and to engage in all normal daily activities. The catheter itself does not induce reflux. The test is not tolerated by all patients, and adverse symptoms may lead to interference with daily activities and eating and interruption of normal sleep, possibly leading to underestimation of reflux related to physical activity and meals and hampering the evaluation of nocturnal reflux.

Wireless pH Monitoring

Some of the limitations of the catheter-based technique have been avoided with the introduction of the catheter-free, wireless pH system (Bravo, Medtronic, Minnesota). In addition to improved patient comfort and less effect on reflux-provoking activities, the capsule-based pH system has the advantages of fixed placement of the pH electrode, minimizing the risk of slipping into the stomach and allowing for prolonged recordings. The longer duration of pH monitoring has been suggested to increase the sensitivity of reflux monitoring in identifying patients with gastroesophageal reflux. Contraindications for the use of the Bravo capsule are hemorrhagic diathesis, esophageal varices, severe esophagitis, patients with a pacemaker or a defibrillator, and pregnancy. The delivery system for the pH capsule is most commonly passed transorally after completion of an upper endoscopy and measurements of the distance between the incisors to the base of the squamocolumnar junction (SCJ). Some centers recommend that application should be performed under direct endoscopic vision and not blindly after the endoscopy. The pH capsule can also be placed transnasally based on prior manometric localization of the LES. The capsule should be positioned 6 cm above the gastroesophageal junction (GEJ) identified endoscopically or 5 cm above the manometrically determined LES.

The pH system consists of a capsule attached to the end of a catheter delivery system and a telemetry receiver ( Fig. 9.1 ). The capsule (6 × 5.5 × 25 mm ³ ) has an antimony pH electrode and a reference electrode located on the distal tip and contains an internal battery and a transmitter, all encapsulated in epoxy ( Fig. 9.2 ). The capsule has a well that fills with mucosa when suction is applied, and the device is deployed by firing a pin through the mucosa in the well. This attaches the capsule at the desired position in the esophagus. The delivery system is removed, leaving only the capsule in place in the esophagus. The capsule simultaneously measures and transmits pH data using radiotelemetry to a portable receiver worn by the patient. The receiver has two recording channels, allowing placement of up to two capsules simultaneously. The patient is instructed to remain within 6 ft (2 m) of the recorder during the study period to ensure effective telemetry signal strength. The capsule is designed to detach in 3 to 7 days and then pass through the gastrointestinal tract. There are reports of the probe remaining attached for longer periods usually without consequence but sometimes requiring endoscopic removal.

The data sampling rate at 6-second intervals of the wireless pH system is often slower than the 1- to 10-second intervals used by the catheter-based pH systems. Prior studies show that faster sampling frequencies up to 1 Hz (i.e., 1 per second) lead to detection of a greater total number of reflux events as events with shorter durations are able to be recorded, but the greater sampling frequency does not change the overall value for esophageal acid exposure.

Wireless esophageal pH monitoring is associated with fewer adverse symptoms and less interference with normal daily activities and is preferred by patients, although there are limitations associated with the wireless technique. The wireless pH capsule is associated with thoracic discomfort in 10% to 65% of the patients. The severity of chest symptoms ranges from a mild foreign body sensation to severe chest pain, although the latter is uncommon. In rare cases the pain is so severe that endoscopic removal of the capsule is necessary.

Limitations of the capsule-based pH system also include technical problems, such as premature detachment of the capsule or interruption of the radiotelemetry signal. Detachment of the pH capsule is suggested by an abrupt pH drop as the sensor dislocates into the stomach with an increasing pH reaching greater than 7 as gastric motility propels the pH capsule into the duodenum. Interruption of the pH signal can potentially be attributable to interference with other wireless systems using the same 433-MHz band or, more commonly, by the receiver being beyond the range of the signal emanating from the radio-transmitting capsule. The interruption of the recording of pH data normally constitutes only a small fraction of the total monitored time. In general, the technical limitations of early capsule detachment and interruption of the radiotelemetry signal do not significantly affect the interpretation of the recorded pH data. However, in a small proportion of patients with unsuccessful recordings, pH monitoring has to be repeated as a consequence of these technical problems.