Abstract

Symptoms suggesting unexplained arousals from sleep resulting in complaints of insomnia or daytime sleepiness may well have nocturnal gastroesophageal reflux (GER) as an underlying contributing factor. In addition, nocturnal GER may be the cause of exacerbations from bronchial asthma and repeated pulmonary infections as a result of pulmonary aspiration of refluxed gastric contents. For most clinical circumstances, 24-hour ambulatory pH studies with careful documentation of the sleeping interval are suitable and allow a reasonable assessment of waking GER and sleep-related GER, as well as acid contact time (ACT) during the total interval and the sleep interval. When patients present with unexplained extraesophageal symptoms, such as chronic cough, uncontrolled nocturnal wheezing, or repeated pulmonary aspiration, dual pH monitoring can provide unique data concerning the role of GER in the pathogenesis of these symptoms. Impedance monitoring of the esophagus now allows the assessment of nonacidic reflux and the proximal migration of refluxant to the level of the upper esophageal sphincter. In the majority of instances, ambulatory studies provide adequate information for clinical management. In certain circumstances, however, more precise information may be needed concerning specific responses to reflux or infused acid, necessitating a complete polysomnographic evaluation.

Gastroesophageal reflux (GER) is a common problem associated with considerable morbidity.¹ Studies have shown the highest incidence of esophagitis, as well as the most severe complications (erosion and stricture), to be associated with recumbent reflux that occurs during sleep, a situation permitting prolonged acid mucosal contact.^2,3 This is presumably the result not only of an incompetent lower esophageal sphincter (LES) but also of an inability to effectively clear the refluxed material. Poor clearance of acid from the esophagus and subsequent acid neutralization have been documented to be impaired during sleep.^4,5

GER may be viewed as consisting of two components: the retrograde flow of gastric contents through the antireflux barrier at the esophagogastric junction and the return of the acid gastric juice to the stomach and subsequent neutralization of the distal esophagus to a pH of 4 (i.e., esophageal acid clearing). The critical parameter in determining the extent of GER, and its potential damage to the esophageal mucosa, is the percentage of time the esophagus is exposed to a pH lower than 4. In view of the previous research documenting the importance of sleep-related GER in the pathogenesis of reflux esophagitis, it is important to determine the percentage of acid contact time (ACT) at night, as well as during the day.

Postprandial reflux has been shown to be physiologic, and when confined to the postprandial interval, it is considered benign.⁶ In determining the clinical significance of GER, it is important to assess the 24-hour pattern (see Chapter 127). Twenty-four-hour patterns of GER can be evaluated with commercially available devices. Two types of pH studies are described here: ambulatory pH studies in which sleep monitoring does not occur and in-laboratory pH studies that include simultaneous pH monitoring with polysomnography (PSG). More recent developments include techniques that allow the assessment of both acidic and nonacidic reflux via impedance measurement.

Ambulatory pH Monitoring

Ambulatory esophageal pH monitoring can be accomplished by using commercially available pH probes and portable data-acquisition devices. The techniques are similar to those in Holter monitoring; the patient is intubated with either a glass- or antimony-tipped pH electrode, the output of which is attached to a small recorder (3.5-inch wide × 7.25-inch long × 1-inch deep) that recorder patient wears either at the waist with a belt or across the shoulder with a shoulder strap.

Our laboratory specifically conducted a validation study of one of these units, which included simultaneous monitoring of input to the computer system and polygraphic tracing of the pH. Although this was not an ambulatory study, because the patient had to be tethered to a recording device, there was excellent agreement between the computer-detected reflux events and those detected by visual inspection from the paper tracing.⁷

The decision to use antimony or glass electrodes depends on a variety of factors; each has advantages and disadvantages. The glass electrode is somewhat more accurate and linear across a large pH range, whereas the antimony electrode is somewhat more durable. From a clinical standpoint, there is little difference between the two with regard to the accuracy of data collected. These commercially available devices have internal calibration techniques that should be performed before every intubation.

For the best readings, the pH probe is placed 5 cm above the proximal border of the manometrically determined LES. The LES must be determined manometrically, which can be somewhat inconvenient because it can require two separate intubations (the first to determine the LES location and the second to insert the pH probe). However, a pH probe has been developed to allow the site of the LES to be determined and the pH probe to be placed with a single intubation.

Data have shown that an approximation of the ideal site can be accomplished by using pH determinations only. This method requires placing the pH probe distally until a clearly acidic (approximately 1.5 to 2.5) pH is established (indicating that the pH probe is in the stomach) and then slowly withdrawing the probe until the pH rises to approximately 4. At that point, the pH probe is most likely out of the stomach and in the esophagogastric junction. The probe is then withdrawn 5 to 7 cm above this level and affixed at that point. Although not as accurate as the manometric method of determination, for clinical purposes this is an acceptable placement method. It should be recognized, however, that this method has been shown to be most problematic with regard to accuracy in patients who actually have substantial GER and most accurate in normal volunteers.⁸ Thus, whenever feasible, the manometric method should be used to locate the LES for accurate pH probe placement.

With the increasing clinical interest in establishing GER as the cause of a variety of extraesophageal symptoms such as bronchial asthma, chronic cough, laryngopharyngitis, and pulmonary aspiration, dual pH probe monitoring has become substantially more popular. It entails monitoring at least two sites in the esophagus: one at the standard site in the distal esophagus (placed as described earlier) and one in the more proximal esophagus. The exact location in the more proximal esophagus varies from the midesophagus to the pharynx, and there is little in the way of currently accepted standard as to the proximal probe placement. Studies have shown that proximal esophageal and pharyngeal acid exposure effectively discriminates persons with posterior laryngitis.⁹ A study by Jacob and colleagues¹⁰ has shown that supine (primarily during sleep) proximal acid exposure best discriminates patients with laryngeal symptoms from those with reflux esophagitis and normal persons.¹⁰ These data suggest that some proximal acid exposure has clinically significant correlates.

Dual pH probe monitoring assumes additional clinical significance in reviewing data from Koufman, who has shown in an animal model that even minute amounts of acid exposure can create cancerous lesions in the larynx.¹¹ In addition, numerous studies have shown that patients with aerodigestive symptoms such as chronic cough and pulmonary aspiration have greater proximal esophageal and pharyngeal acid exposure.^10,12,13 Although much work needs to be done to assess the importance of, and specific parameters relating to, proximal esophageal acid exposure in the pathogenesis of extraesophageal symptoms of reflux, it is clear that the trend is moving increasingly toward use of dual pH monitoring.

Once the intubation has been accomplished, the patient is instructed concerning the operation of the data-acquisition system. Patients may be given special dietary instructions to avoid acidic foods; however, our preference is not to have the patient adopt a special diet. GER and heartburn are both significantly affected by dietary intake; therefore a more accurate clinical picture of the frequency and severity of GER can be obtained if patients eat their usual meals. The patient completes a log to document significant events. The patient is instructed to indicate the start and end time of meals, time of going to sleep and waking up, time of taking medication, and time of occurrence of clinical symptoms. The patient is instructed to return to the laboratory approximately 24 hours from the time of departure.

On returning to the laboratory, the patient is extubated and the data are downloaded into a computer system that analyzes a variety of reflux parameters over the total recording interval. These parameters include number of reflux episodes, average duration of the reflux episodes, longest reflux episode, percentage of ACT, and a summary of these events according to upright (primarily waking) and supine (primarily sleeping) postures. The computer printout summarizes the timing of meals, sleep, and clinical symptoms as well. This information allows one to determine the relationship of symptoms to episodes of GER.

A technique for monitoring pH via wireless telemetry is also now available. The Medtronic Bravo pH monitoring system is approved in the United States. This pH system involves attaching a radiotelemetry pH capsule to the mucosal wall of the esophagus using a prepackaged assembly that incorporates both a delivery system and the pH capsule. The capsule is oblong (6 × 5.5 × 25 mm) and contains a well (4 mm in diameter by 3.5 mm deep) for delivery, antimony pH electrode and reference electrode, and an internal battery and transmitter. The pH capsule sends a data signal to the external receiver via radiofrequency telemetry. Using endoscopic measurement, the pH probe is positioned 6 cm above the squamocolumnar junction, which approximates the placement method targeting a position 5 cm proximal to the upper margin of LES that is typically used in conventional pH recordings.¹⁴ The wireless pH monitoring system has demonstrated usefulness by successfully recording up to 2 days in 89% of all enrolled subjects.¹⁵ The Bravo system has been shown to have minimal impact on daily acidity and diet. It is a viable option for patients who are unwilling or unable to undergo conventional pH studies using a transnasally placed pH electrode and who will be undergoing endoscopy or part of an evaluation for acid reflux disease.

The power of the wireless pH recording system in distinguishing esophagitis patients from controls has been demonstrated to be comparable with previous results using a conventional pH monitoring system.^15–17 In fact, the discriminative power of the wireless pH study is comparable using data from the first 24-hour recording, but the sensitivity is more improved using data from the worse day of the 48-hour recording. It takes advantage of the observation that esophageal acid exposure can exhibit day-to-day variability.¹⁸ The comparable ability of the wireless pH system was also observed in discriminating endoscopy negative gastroesophageal reflux disease (GERD) from controls. However, in this patient population, there was no significant improvement in sensitivity or specificity using data from the worse day of the 48-hour recording.¹⁵ This is likely due to the fact that excessive acid exposure is one of the several pathophysiologic factors contributing to nonerosive GERD (NERD) in which hypersensitivity to acid reflux and symptoms can occur without pathologic acid reflux.¹⁹ Although more work is needed related to analyzing symptoms, the wireless pH monitoring system using 48-hour recording may be particularly beneficial in the diagnosis of NERD by increasing the possibility of documenting the association between symptoms and reflux over a longer duration of recording.

Multichannel intraluminal impedance (MII) has been introduced as a new technique to study esophageal motility, and the reflux of gastric contents (acidic and nonacidic) based on differences in conductivity to alternating current of intraluminal content.²⁰ Impedance is the average electric resistance between two adjacent electrodes and is measured using a specialized catheter with a 2.1-mm diameter consisting of a series of cylindrical electrodes that make up measuring segments, each 2 cm long, corresponding to one recording channel. The impedance between the two electrodes is inversely proportion to the electrical conductivity and the cross-sectional area of the material through which the current must travel. If a highly conductive bolus arrives at the measuring segment (saliva), impedance will decrease, and the opposite occurs with a resistive bolus (air). Additionally, increasing the luminal diameter (arrival of bolus into the measuring segment) results in an impedance drop, whereas a luminal narrowing (contraction wave) causes an impedance increase. Studies have indicated that MII can be used as a discriminative test of esophageal function evaluating bolus transport.²¹ It has been shown that combining MII with esophageal manometry (MII-EM) allows simultaneous measurement of intraesophageal pressure and bolus movement.²² These data suggest that MII-EM is a more sensitive tool in assessing esophageal function compared to standard manometry because impedance can distinguish different bolus transit pattern.

The use of MII allows determination of the direction of bolus movement within the esophagus. Progression of impedance changes from distal to proximal indicates retrograde bolus movement as found in GER. It allows prolonged monitoring and detection of bolus volume presence independent of the chemical (pH) composition, as well as the proximal migration of the refluxant. In combined MII-pH, the pH sensor is used to define whether the refluxant is acid or nonacid based on predefined criteria. Combined manometry pH impedance has been used to study the patterns of gas and liquid reflux in adults or patients with GERD.^23–25 Using this approach in subjects in the sitting position, Sifrim and colleagues have shown that patients with reflux disease had more acid reflux, less nonacid reflux, and higher proportion of pure liquid reflux compared with healthy subjects.^24–25

Intraluminal impedance is able to detect small volumes of liquid reflux of more neutral pH that are not detected by the traditional pH sensor. Combined impedance with pH monitoring allows the detection of most reflux episodes: very acid (pH <4), moderately acid (pH 4 to 6), and nonacid (pH 6 to 7). A pH drop below 4 usually indicates acidic GER. All other reflux events could be categorized as nonacidic reflux. The pathophysiologic relevance of nonacidic reflux in GERD is still unknown, but previous data suggest that it does not play a role in the development of esophageal mucosal damage because of no difference in the patterns of nonacidic reflux between patients with reflux disease and healthy controls.²⁶ However, it might be more important as a cause of persistent symptoms in patients taking acid-suppressant therapy²⁷ or in patients with endoscopy-negative reflux disease. The nonacidic reflux episodes in the most proximal impedance segment have been shown to be less than that of traditional acid reflux episodes both in patients with reflux disease and controls, suggesting a smaller volume of liquid refluxant.²⁸