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The pathophysiologic role of acid in GERD has been well established in studies in both animals and humans [7]. Until recently, measuring GER was based solely upon esophageal pH monitoring, which bases detection of reflux of acidic material into the esophagus on changes in hydrogen ion concentration (i.e. drops in esophageal pH to below 4.0) [8]. In a number of patients, reflux symptoms persist despite treatment with medications that decrease gastric acid secretion; recent studies have shown that these symptoms can be caused by reflux having pH greater than 4 (i.e. nonacid reflux or weakly acidic reflux) [9]. In fact, when the contents of the stomach are buffered (in the post‐prandial period or during treatment with potent acid‐suppressing medications like proton‐pump inhibitors), a significant proportion of GER is nonacid and therefore not accurately detectable by conventional pH recording [10–13]. This is highlighted by the fact that the likelihood of a positive pH test in acid‐suppressed patients is indeed very low [14]. This limitation of pH‐metry has created the need for a method that can accurately measure nonacid reflux.

Figure 9.9 Example of rumination on HRIM. Length of the esophagus is shown along the y‐axis, with the distal end of the y‐axis representing catheter position within the stomach. Pressures > 30 mmHg are circled in black. Low impedance, indicative of fluid, is shown in purple. Time is shown along the x‐axis. A rise in intragastric pressure is highlighted by an arrow, which is subsequently followed by movement of liquid from the stomach to the esophagus, as represented by the movement of purple and highlighted by the arrow.

Source: Courtesy of Dr. David Katzka.

Several techniques have been considered in the past for the study of nonacid or alkaline reflux, including aspiration, scintigraphy, ambulatory pH monitoring, and bilirubin monitoring (Bilitec) [15–19], all of which have certain limitations. Aspiration studies allow for only short analysis periods, and the accuracy of enzymatic determination of the contents of the aspirates has been questioned [18, 20]. Scintigraphic studies are expensive, involve radiation exposure, and are usually limited to short monitoring periods [16]. During ambulatory pH monitoring, a pH of 7 or greater has been used as the definition of “alkaline” reflux, but increased saliva production or bicarbonate secreted by esophageal submucosal glands confounds measurements by increasing esophageal pH in the absence of reflux [21]. Some authors propose that reflux can be detected by pH‐metry even when intraesophageal pH remains greater than 4.0 through measurement of pH decreases of greater than 1 unit [22]. However, ingestion of acidic foods can mimic reflux by provoking pH drops of greater than 1 unit [23]; furthermore, pH‐metry is unable to detect nonacid reflux that occurs in the absence of pH changes or with small pH changes (<1 unit) [9]. Monitoring with the Bilitec probe is based on the presence of bilirubin and is therefore incapable of measuring bile‐free nonacid reflux. Additionally, bilirubin monitoring requires a special diet to avoid false‐positive readings [18].

MII–pH represents an important advance in GER testing because it enables accurate detection of GER at all pH levels: impedance detects retrograde bolus movement (i.e. reflux), while pH measurement establishes the acidity of the reflux episode (acid if pH < 4.0; nonacid otherwise). The technique has been validated fluoroscopically and manometrically to detect bolus movement in the esophagus, both in the oral and aboral direction [24], thus allowing measurement of and distinction between swallows and reflux. As discussed earlier, a catheter with multiple pairs of impedance electrodes can record impedance changes in response to movement of intraesophageal material in either antegrade or retrograde direction. As shown in Figure 9.3, this means that a swallow can be clearly distinguished from reflux, i.e. retrograde movement of gastric contents into the esophagus. Because MII records retrograde flow of gastric contents into the esophagus in a pH‐independent fashion, combining the technique with pH‐metry enables detection of acid as well as nonacid reflux. Some authors classify reflux with a pH above 4.0 as either weakly acidic (pH ≥ 4 but <7) or weakly alkaline (pH ≥ 7). In this chapter, nonacid reflux refers to any reflux with a pH of 4 or greater.

Table 9.2 Normative data for reflux using combined impedance‐pH monitoring.

Study	n	Number of reflux episodes: upper limit of normal*
Total	Acid	Nonacid
United States (Shay et al. [27])	60	73	59	27
France–Belgium (Zerbib et al. [28])	72	75	50	48

^* Upper limit of normal for the number of reflux episodes was based on the 95th percentile for the healthy volunteers in each study.

Because of its ability to measure GER at all pH levels, MII–pH monitoring has emerged as a useful diagnostic and research tool, particularly in patients with ongoing symptoms despite acid suppression [12]. Additionally, MII–pH provides very meticulous characterization of the reflux episode, including determination of the composition (gas, liquid, mixed), proximal extent (height reached), velocity, and clearance time [9]. Based on the very detailed information that MII–pH monitoring provides, a recently convened panel of experts concluded that it is the most sensitive tool for measuring GER [25]. Assessment of reflux with MII–pH has been found to be reproducible [26], and normal values for ambulatory 24‐h MII–pH monitoring obtained by independent multicenter studies are similar (Table 9.2) [27, 28].